Publications

BACKGROUND AND PURPOSE: Chondrosarcoma is a rare bone malignancy with a poor response to systemic therapy in advanced stages. European-level epidemiological data remain scarce. This study aimed to characterise patient demographics, treatments and survival using real-world data to inform regulatory decisions about the feasibility and design of new trials for the systemic treatment of chondrosarcoma. Patient/material and methods: This cohort study, part of the DARWIN EU® initiative, analysed data from six healthcare databases in Finland, France, the Netherlands, Spain and the UK. Patients diagnosed with chondrosarcoma between 2010 and 2022 were identified. Standardised analyses were performed within a federated network using the Observational Medical Outcomes Partnership (OMOP) Common Data Model. RESULTS: A total of 2,498 chondrosarcoma patient records were identified, covering at least 2,356 unique patients. Median age at diagnosis was 52-55 years, with a balanced sex distribution. Surgical treatment was the most common intervention, recorded in 15.2% to 88.9% of patients, depending on the database. Fewer than 5% received systemic anticancer therapy, and radiotherapy was reported in fewer than 7%. The 10-year overall survival (OS) ranged from 58% (95% confidence interval [CI]: 43-78) to 80% (95% CI: 78-82), with restricted mean survival between 7.4 and 8.7 years. In the Netherlands, patients with late-stage, metastatic or high-grade disease showed significantly poorer outcomes. INTERPRETATION: This study demonstrates the feasibility of using real-world data across Europe to describe chondrosarcoma patients. Most had early-stage, low-grade disease amenable to surgery, with limited use of systemic therapies. Survival was generally favourable, except in advanced disease. Clinical trials remain difficult due to the rarity of advanced chondrosarcoma and the lack of standards.

@article{RN508,
   author = {Barchuk, A. and Barboza, C. and Politi, J. and Raventós, B. and Prinsen, P. and Evers, J. and Ho, V. K. and Van de Sande, M. A. and Fey, E. and Porkka, K. and Hammais, A. and Wahlfors, T. and Nieminen, T. and Lehtonen, T. and Delmestri, A. and Verdy, G. and Griffier, R. and De Burgos-González, A. and Llorente-Garcia, A. and Justo-Astorgano, C. and Macia-Martinez, M. A. and Tenhunen, O. and Schiel, A. and Pacurariu, A. and Brennan, R. and Williams, R. and Verhamme, K. and Duarte Salles, T.},
   title = {Characteristics, treatment and survival of patients with chondrosarcoma in five European countries: a DARWIN EU® cohort study},
   journal = {Acta Oncol},
   volume = {65},
   pages = {193-200},
   note = {1651-226x
Barchuk, Anton
Orcid: 0000-0002-4629-3326
Barboza, Cesar
Orcid: 0009-0002-4453-3071
Politi, Julieta
Orcid: 0000-0001-7315-034x
Raventós, Berta
Orcid: 0000-0002-4668-2970
Prinsen, Peter
Orcid: 0000-0002-0444-4579
Evers, Jelle
Orcid: 0000-0003-0525-9786
Ho, Vincent Ky
Orcid: 0000-0001-7065-928x
Van de Sande, Michiel Aj
Orcid: 0000-0002-9156-7656
Fey, Eric
Orcid: 0009-0005-7847-7479
Porkka, Kimmo
Orcid: 0000-0003-4112-5902
Hammais, Anna
Wahlfors, Tiina
Orcid: 0000-0002-3910-796x
Nieminen, Tuomo
Orcid: 0000-0002-6901-2208
Lehtonen, Toni
Orcid: 0000-0003-2089-2299
Delmestri, Antonella
Orcid: 0000-0003-0388-3403
Verdy, Guillaume
Orcid: 0000-0002-0745-0034
Griffier, Romain
Orcid: 0000-0002-1096-137x
De Burgos-González, Airam
Orcid: 0000-0002-4928-0491
Llorente-Garcia, Ana
Justo-Astorgano, Cristina
Macia-Martinez, Miguel-Angel
Orcid: 0000-0002-1471-4376
Tenhunen, Olli
Orcid: 0009-0009-0802-1619
Schiel, Anja
Orcid: 0000-0002-1258-4731
Pacurariu, Alexandra
Orcid: 0000-0002-2217-0540
Brennan, Ross
Williams, Ross
Orcid: 0000-0001-7723-417x
Verhamme, Katia
Orcid: 0000-0001-8162-4904
Duarte Salles, Talita
Orcid: 0000-0002-8274-0357
Journal Article
Sweden
2026/03/11
Acta Oncol. 2026 Mar 10;65:193-200. doi: 10.2340/1651-226X.2026.45117.},
   abstract = {BACKGROUND AND PURPOSE: Chondrosarcoma is a rare bone malignancy with a poor response to systemic therapy in advanced stages. European-level epidemiological data remain scarce. This study aimed to characterise patient demographics, treatments and survival using real-world data to inform regulatory decisions about the feasibility and design of new trials for the systemic treatment of chondrosarcoma. Patient/material and methods: This cohort study, part of the DARWIN EU® initiative, analysed data from six healthcare databases in Finland, France, the Netherlands, Spain and the UK. Patients diagnosed with chondrosarcoma between 2010 and 2022 were identified. Standardised analyses were performed within a federated network using the Observational Medical Outcomes Partnership (OMOP) Common Data Model. RESULTS: A total of 2,498 chondrosarcoma patient records were identified, covering at least 2,356 unique patients. Median age at diagnosis was 52-55 years, with a balanced sex distribution. Surgical treatment was the most common intervention, recorded in 15.2% to 88.9% of patients, depending on the database. Fewer than 5% received systemic anticancer therapy, and radiotherapy was reported in fewer than 7%. The 10-year overall survival (OS) ranged from 58% (95% confidence interval [CI]: 43-78) to 80% (95% CI: 78-82), with restricted mean survival between 7.4 and 8.7 years. In the Netherlands, patients with late-stage, metastatic or high-grade disease showed significantly poorer outcomes. INTERPRETATION: This study demonstrates the feasibility of using real-world data across Europe to describe chondrosarcoma patients. Most had early-stage, low-grade disease amenable to surgery, with limited use of systemic therapies. Survival was generally favourable, except in advanced disease. Clinical trials remain difficult due to the rarity of advanced chondrosarcoma and the lack of standards.},
   keywords = {Humans
*Chondrosarcoma/therapy/mortality/pathology/epidemiology
Male
Female
*Bone Neoplasms/therapy/mortality/pathology/epidemiology
Middle Aged
Europe/epidemiology
Cohort Studies
Aged
Adult
Young Adult
Aged, 80 and over
Adolescent
Survival Rate},
   ISSN = {0284-186x},
   DOI = {10.2340/1651-226x.2026.45117},
   year = {2026},
   type = {Journal Article}
}

OBJECTIVE: Macrolides are used in patients with chronic respiratory conditions to prevent exacerbations. However, due to their QT interval prolonging effect, an electrocardiogram (ECG) assessment prior to long-term treatment is recommended. The objective was to evaluate the incidence of macrolides use (azithromycin, clarithromycin, erythromycin) in individuals with asthma, chronic obstructive pulmonary disease (COPD), asthma-COPD overlap (ACO), and to assess the frequency of ECGs performed prior to long-term macrolide prescribing. METHODS: We utilized data from the Dutch Integrated Primary Care Information (IPCI) database and Spanish Information System for Research in Primary Care (SIDIAP), between 2006 and 2022. The study population consisted of individuals diagnosed with asthma, COPD, and ACO with ≥365 days follow-up after diagnosis. Incidence was analyzed by type of macrolide, database, year, and prescribing-duration (short-, medium-, long-term [

@article{RN506,
   author = {Pera, V. and Lepouttre, H. and Barboza, C. and Palomar-Cros, A. and López-Sánchez, I. and Duarte-Salles, T. and Rijnbeek, P. R. and Verhamme, K. M. C.},
   title = {Macrolide prescribing and preemptive electrocardiograms in asthma, COPD, ACO, and general population: a drug-utilization study},
   journal = {J Asthma},
   volume = {63},
   number = {2},
   pages = {249-262},
   note = {1532-4303
Pera, Victor
Orcid: 0000-0002-0786-4712
Lepouttre, Heleen
Barboza, Cesar
Orcid: 0009-0002-4453-3071
Palomar-Cros, Anna
Orcid: 0000-0001-8151-9290
López-Sánchez, Irene
Orcid: 0009-0001-5658-8945
Duarte-Salles, Talita
Orcid: 0000-0002-8274-0357
Rijnbeek, Peter R
Orcid: 0000-0003-0621-1979
Verhamme, Katia M C
Orcid: 0000-0001-8162-4904
Journal Article
England
2025/11/18
J Asthma. 2026 Feb;63(2):249-262. doi: 10.1080/02770903.2025.2589788. Epub 2025 Dec 1.},
   abstract = {OBJECTIVE: Macrolides are used in patients with chronic respiratory conditions to prevent exacerbations. However, due to their QT interval prolonging effect, an electrocardiogram (ECG) assessment prior to long-term treatment is recommended. The objective was to evaluate the incidence of macrolides use (azithromycin, clarithromycin, erythromycin) in individuals with asthma, chronic obstructive pulmonary disease (COPD), asthma-COPD overlap (ACO), and to assess the frequency of ECGs performed prior to long-term macrolide prescribing. METHODS: We utilized data from the Dutch Integrated Primary Care Information (IPCI) database and Spanish Information System for Research in Primary Care (SIDIAP), between 2006 and 2022. The study population consisted of individuals diagnosed with asthma, COPD, and ACO with ≥365 days follow-up after diagnosis. Incidence was analyzed by type of macrolide, database, year, and prescribing-duration (short-, medium-, long-term [<30, 30-179, ≥180 days]). RESULTS: SIDIAP included 224,783 individuals with asthma, 167,524 with COPD, and 34,475 with ACO, while IPCI included 66,383 with asthma, 26,805 with COPD, and 7250 with ACO. The incidence of short-term use per 100,000 person-years (PYs) was 3500-6700 for azithromycin, 1300-2100 for clarithromycin and 200-300 for erythromycin. The incidence of medium- and long-term use was less than <1100/100,000 PYs. Incidence rates were higher in SIDIAP, females, and 60-79 year-olds. Medium- and long-term use was 2- to 4-fold higher in COPD and ACO than asthma, and increased over time. Database-registered ECGs were found in less than 1% of long-term macrolide users. CONCLUSIONS: Long-term macrolide users were on the rise among COPD- and ACO individuals; however, ECG monitoring was rare, raising concerns given guideline recommendations.},
   keywords = {Humans
*Asthma/drug therapy
Female
Male
*Pulmonary Disease, Chronic Obstructive/drug therapy
Middle Aged
*Macrolides/therapeutic use/adverse effects/administration & dosage
*Electrocardiography/statistics & numerical data
Aged
Adult
*Anti-Bacterial Agents/therapeutic use/adverse effects
Erythromycin/therapeutic use
Clarithromycin/therapeutic use
Netherlands
*Practice Patterns, Physicians'/statistics & numerical data
Young Adult
Aco
Copd
Macrolides
asthma
electrocardiogram
prescriptions},
   ISSN = {0277-0903},
   DOI = {10.1080/02770903.2025.2589788},
   year = {2026},
   type = {Journal Article}
}

BACKGROUND: An increase in the use of medications for Attention-Deficit Hyperactivity Disorder (ADHD) has been reported globally. This study aims to estimate the trends of ADHD medications use among children and adults across Europe from 2010 to 2023. METHODS: We conducted a population-level observational study using electronic health records from five European countries: Belgium, Germany, the Netherlands, Spain, and the UK. We estimated the prevalence and incidence of methylphenidate, dexamphetamine, lisdexamfetamine, atomoxetine and guanfacine use among individuals aged 3 years and older. We used the proportion of patients covered to measure treatment adherence. All analyses were reported by country and stratified by age group and sex. FINDINGS: The prevalence of ADHD medication use increased across all five countries during the study period. Between 2010 and 2023, prevalence rose more than threefold in the UK (from 0.12% to 0.39%) and more than doubled in the Netherlands (from 0.67% to 1.56%). Adult use increased substantially in all countries, particularly among females. In the UK, prevalence among adults aged over 25 increased from 0.01% in 2010 to approximately 0.20% in 2023, representing a more than twenty-fold increase in females and fifteen-fold in males. Although ADHD medication use remained higher among males, the sex gap in treatment narrowed over time and with increasing age. After 1-year of medication initiation, 14.9%, 16.0%, 43.9%, and 30.8% of participants were covered by treatment in Germany, the Netherlands, Spain, and the UK respectively. Among initiators, the prevalence of psychiatric conditions and prior use of psycholeptic medications was higher in females and in older age groups. INTERPRETATION: Over 14 years, ADHD medication prevalence increased across Europe, with varying incidence trends by country, age, and sex. Understanding the utilisation of ADHD medications can provide useful information in monitoring use, as well as for anticipation and planning to minimise potential shortages. FUNDING: European Medicines Agency.

@article{RN507,
   author = {Li, X. and Guo, Y. and Giuliodori Picco, A. and Palomar-Cros, A. and Delmestri, A. and Man, W. Y. and Kaczmarczyk, I. and Brash, J. T. and Verhamme, K. and Mosseveld, M. and Duarte-Salles, T. and Prieto-Alhambra, D. and Burn, E.},
   title = {Trends in use of Attention-Deficit Hyperactivity Disorder medications among children and adults in five European countries, 2010 to 2023: a population-based observational study},
   journal = {Lancet Reg Health Eur},
   volume = {61},
   pages = {101556},
   note = {2666-7762
Li, Xintong
Guo, Yuchen
Giuliodori Picco, Agustina
Palomar-Cros, Anna
Delmestri, Antonella
Man, Wai Yi
Kaczmarczyk, Isabella
Brash, James T
Verhamme, Katia
Mosseveld, Mees
Duarte-Salles, Talita
Prieto-Alhambra, Daniel
Burn, Edward
Journal Article
England
2026/02/09
Lancet Reg Health Eur. 2026 Jan 21;61:101556. doi: 10.1016/j.lanepe.2025.101556. eCollection 2026 Feb.},
   abstract = {BACKGROUND: An increase in the use of medications for Attention-Deficit Hyperactivity Disorder (ADHD) has been reported globally. This study aims to estimate the trends of ADHD medications use among children and adults across Europe from 2010 to 2023. METHODS: We conducted a population-level observational study using electronic health records from five European countries: Belgium, Germany, the Netherlands, Spain, and the UK. We estimated the prevalence and incidence of methylphenidate, dexamphetamine, lisdexamfetamine, atomoxetine and guanfacine use among individuals aged 3 years and older. We used the proportion of patients covered to measure treatment adherence. All analyses were reported by country and stratified by age group and sex. FINDINGS: The prevalence of ADHD medication use increased across all five countries during the study period. Between 2010 and 2023, prevalence rose more than threefold in the UK (from 0.12% to 0.39%) and more than doubled in the Netherlands (from 0.67% to 1.56%). Adult use increased substantially in all countries, particularly among females. In the UK, prevalence among adults aged over 25 increased from 0.01% in 2010 to approximately 0.20% in 2023, representing a more than twenty-fold increase in females and fifteen-fold in males. Although ADHD medication use remained higher among males, the sex gap in treatment narrowed over time and with increasing age. After 1-year of medication initiation, 14.9%, 16.0%, 43.9%, and 30.8% of participants were covered by treatment in Germany, the Netherlands, Spain, and the UK respectively. Among initiators, the prevalence of psychiatric conditions and prior use of psycholeptic medications was higher in females and in older age groups. INTERPRETATION: Over 14 years, ADHD medication prevalence increased across Europe, with varying incidence trends by country, age, and sex. Understanding the utilisation of ADHD medications can provide useful information in monitoring use, as well as for anticipation and planning to minimise potential shortages. FUNDING: European Medicines Agency.},
   keywords = {Adhd
Electronic health records
Observational study
Pharmacotherapy
Real-world evidence
Stimulants},
   ISSN = {2666-7762},
   DOI = {10.1016/j.lanepe.2025.101556},
   year = {2026},
   type = {Journal Article}
}

BACKGROUND: Real-world data (RWD) are increasingly used in health research and regulatory decision-making to assess the effectiveness, safety, and value of interventions in routine care. However, the heterogeneity of European health care systems, data capture methods, coding standards, and governance structures poses challenges for generating robust and reproducible real-world evidence. The European Health Data & Evidence Network (EHDEN) was established to address these challenges by building a large-scale federated data infrastructure that harmonizes RWD across Europe. OBJECTIVE: This study aims to describe the composition and characteristics of the databases harmonized within EHDEN as of September 2024. We seek to provide transparency regarding the types of RWD available and their potential to support collaborative research and regulatory use. METHODS: EHDEN recruited data partners through structured open calls. Selected data partners received funding and technical support to harmonize their data to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM), with assistance from certified small-to-medium enterprises trained through the EHDEN Academy. Each data source underwent an extract-transform-load process and data quality assessment using the data quality dashboard. Metadata-including country, care setting, capture method, and population criteria-were compiled in the publicly accessible EHDEN Portal. RESULTS: As of September 1, 2024, the EHDEN Portal includes 210 harmonized data sources from 30 countries. The highest representation comes from Italy (13%), Great Britain (12.5%), and Spain (11.5%). The mean number of persons per data source is 2,147,161, with a median of 457,664 individuals. Regarding care setting, 46.7% (n=98) of data sources reflect data exclusively from secondary care, 42.4% (n=89) from mixed care settings (both primary and secondary), and 11% (n=23) from primary care only. In terms of population inclusion criteria, 55.7% (n=117) of data sources include individuals based on health care encounters, 32.9% (n=69) through disease-specific data collection, and 11.4% (n=24) via population-based sources. Data capture methods also vary, with electronic health records (EHRs) being the most common. A total of 74.7% (n=157) of data sources use EHRs, and more than half of those (n=85) rely on EHRs as their sole method of data collection. Laboratory data are used in 29.5% (n=62) of data sources, although only one relies exclusively on laboratory data. Most laboratory-based data sources combine this method with other forms of data capture. CONCLUSIONS: EHDEN is the largest federated health data network in Europe, enabling standardized, General Data Protection Regulation-compliant analysis of RWD across diverse care settings and populations. This descriptive summary of the network's data sources enhances transparency and supports broader efforts to scale federated research. These findings demonstrate EHDEN's potential to enable collaborative studies and generate trusted evidence for public health and regulatory purposes.

@article{RN501,
   author = {Blacketer, C. and Schuemie, M. J. and Moinat, M. and Voss, E. A. and Camprubi, M. and Rijnbeek, P. R. and Ryan, P. B.},
   title = {Advancing Real-World Evidence Through a Federated Health Data Network (EHDEN): Descriptive Study},
   journal = {J Med Internet Res},
   volume = {27},
   pages = {e74119},
   note = {1438-8871
Blacketer, Clair
Orcid: 0000-0003-2570-2124
Schuemie, Martijn J
Orcid: 0000-0002-0817-5361
Moinat, Maxim
Orcid: 0000-0001-8473-2433
Voss, Erica A
Orcid: 0000-0002-0651-0613
Camprubi, Montse
Orcid: 0009-0008-3512-0666
Rijnbeek, Peter R
Orcid: 0000-0003-0621-1979
Ryan, Patrick B
Orcid: 0000-0002-9727-2138
Journal Article
Canada
2025/08/08
J Med Internet Res. 2025 Aug 7;27:e74119. doi: 10.2196/74119.},
   abstract = {BACKGROUND: Real-world data (RWD) are increasingly used in health research and regulatory decision-making to assess the effectiveness, safety, and value of interventions in routine care. However, the heterogeneity of European health care systems, data capture methods, coding standards, and governance structures poses challenges for generating robust and reproducible real-world evidence. The European Health Data & Evidence Network (EHDEN) was established to address these challenges by building a large-scale federated data infrastructure that harmonizes RWD across Europe. OBJECTIVE: This study aims to describe the composition and characteristics of the databases harmonized within EHDEN as of September 2024. We seek to provide transparency regarding the types of RWD available and their potential to support collaborative research and regulatory use. METHODS: EHDEN recruited data partners through structured open calls. Selected data partners received funding and technical support to harmonize their data to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM), with assistance from certified small-to-medium enterprises trained through the EHDEN Academy. Each data source underwent an extract-transform-load process and data quality assessment using the data quality dashboard. Metadata-including country, care setting, capture method, and population criteria-were compiled in the publicly accessible EHDEN Portal. RESULTS: As of September 1, 2024, the EHDEN Portal includes 210 harmonized data sources from 30 countries. The highest representation comes from Italy (13%), Great Britain (12.5%), and Spain (11.5%). The mean number of persons per data source is 2,147,161, with a median of 457,664 individuals. Regarding care setting, 46.7% (n=98) of data sources reflect data exclusively from secondary care, 42.4% (n=89) from mixed care settings (both primary and secondary), and 11% (n=23) from primary care only. In terms of population inclusion criteria, 55.7% (n=117) of data sources include individuals based on health care encounters, 32.9% (n=69) through disease-specific data collection, and 11.4% (n=24) via population-based sources. Data capture methods also vary, with electronic health records (EHRs) being the most common. A total of 74.7% (n=157) of data sources use EHRs, and more than half of those (n=85) rely on EHRs as their sole method of data collection. Laboratory data are used in 29.5% (n=62) of data sources, although only one relies exclusively on laboratory data. Most laboratory-based data sources combine this method with other forms of data capture. CONCLUSIONS: EHDEN is the largest federated health data network in Europe, enabling standardized, General Data Protection Regulation-compliant analysis of RWD across diverse care settings and populations. This descriptive summary of the network's data sources enhances transparency and supports broader efforts to scale federated research. These findings demonstrate EHDEN's potential to enable collaborative studies and generate trusted evidence for public health and regulatory purposes.},
   keywords = {Humans
Europe
*Databases, Factual
data governance
data quality
electronic health records
epidemiology
health informatics
real-world data
registries},
   ISSN = {1439-4456 (Print)
1438-8871},
   DOI = {10.2196/74119},
   year = {2025},
   type = {Journal Article}
}

Federated network studies allow data to remain locally while the research is conducted through the sharing of analytical code and aggregated results across different health care settings and countries. A large number of databases have been mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), boosting the use of analytical pipelines for standardized observational research within this open science framework. Transparency, reproducibility, and robustness of results have positioned federated analyses using the OMOP CDM within the European Health Data and Evidence Network (EHDEN) as an essential tool for generating large-scale evidence.We conducted large-scale federated analyses involving 52 databases from 19 countries using the OMOP CDM. In this State-of-the-Art/Best Practice article, we aimed to share key lessons and strategies for conducting such complex, large multidatabase analyses.Meticulous planning, establishing a strong community of collaborators, efficient communication channels, standardized analytics, and strategic division of responsibilities are essential. We highlight the benefits of network engagement, cross-fertilization of ideas, and shared learning. Further key elements contributing to the study's success included an inclusive, incremental implementation of the analytical code, timely engagement of data partners, and community webinars to discuss and interpret study findings.We received predominantly positive feedback from data custodians about their participation, and included input for further improvements for future large-scale federated network studies from this shared learning experience.

@article{RN505,
   author = {Burkard, T. and Camprubi, M. and Prieto-Alhambra, D. and Rijnbeek, P. and Pineda-Moncusi, M.},
   title = {Best Practices to Design, Plan, and Execute Large-Scale Federated Analyses-Key Learnings and Suggestions from a Study Comprising 52 Databases},
   journal = {Appl Clin Inform},
   volume = {16},
   number = {5},
   pages = {1507-1517},
   note = {1869-0327
Burkard, Theresa
Camprubi, Montse
Prieto-Alhambra, Daniel
Rijnbeek, Peter
Pineda-Moncusi, Marta
Journal Article
Germany
2025/09/27
Appl Clin Inform. 2025 Oct;16(5):1507-1517. doi: 10.1055/a-2710-4226. Epub 2025 Sep 26.},
   abstract = {Federated network studies allow data to remain locally while the research is conducted through the sharing of analytical code and aggregated results across different health care settings and countries. A large number of databases have been mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), boosting the use of analytical pipelines for standardized observational research within this open science framework. Transparency, reproducibility, and robustness of results have positioned federated analyses using the OMOP CDM within the European Health Data and Evidence Network (EHDEN) as an essential tool for generating large-scale evidence.We conducted large-scale federated analyses involving 52 databases from 19 countries using the OMOP CDM. In this State-of-the-Art/Best Practice article, we aimed to share key lessons and strategies for conducting such complex, large multidatabase analyses.Meticulous planning, establishing a strong community of collaborators, efficient communication channels, standardized analytics, and strategic division of responsibilities are essential. We highlight the benefits of network engagement, cross-fertilization of ideas, and shared learning. Further key elements contributing to the study's success included an inclusive, incremental implementation of the analytical code, timely engagement of data partners, and community webinars to discuss and interpret study findings.We received predominantly positive feedback from data custodians about their participation, and included input for further improvements for future large-scale federated network studies from this shared learning experience.},
   keywords = {*Databases, Factual
Federated Learning},
   ISSN = {1869-0327},
   DOI = {10.1055/a-2710-4226},
   year = {2025},
   type = {Journal Article}
}

BACKGROUND: Drug shortages can negatively impact patient care. We aimed to estimate the incidence and prevalence of use of medicines with shortages announced by the European Medicines Agency between January, 2013, and September, 2023, and to characterise the users of these drugs. METHODS: In this multinational network cohort study, we used routinely collected data from 52 databases across 18 European countries and the USA covering primary care, secondary care, health insurance claims, and disease registries. We included all participants with a minimum of 365 days of medical history between 2010 and 2024. We estimated annual incidence rates and period prevalence of use of medicines with a reported shortage (n=16), and their key alternatives (n=41). A reduction of 33% or more in incidence or prevalence after the shortage announcement was considered confirmation of a shortage. Additionally, we analysed changes in utilisation in terms of age, sex, indication, duration, and dosage. FINDINGS: Eight drugs had a 33% or higher reduction in incidence and nine drugs had a 33% or higher reduction in prevalence. Varenicline and amoxicillin (alone or combined with clavulanate) were the medicines affected in the highest number of countries and databases. Additionally, we observed changes in the indication of alteplase (pulmonary embolism indication increased in hospitals in Finland and Germany during the shortage period) and sarilumab (rheumatoid arthritis indication decreased in databases in the UK, Spain, Finland, and Sweden); and among incident users of sarilumab, a decrease in the cumulative dose was observed in databases in the Netherlands (from 84 mg in 2020 to 28 mg in 2023) and a reduction in treatment duration was observed in databases in Finland (from 104 days in 2020 to 1 day in 2022) and Belgium (from 71 days in 2020 to 30 days in 2022). INTERPRETATION: This study highlighted changes in incidence and prevalence of use of medicines after shortage announcements, and changes observed in patient care in terms of the indication, duration, or prescribed dose of medicines. Our findings showed that some reductions in use were observed across Europe and the USA, and others differed across countries. More research is needed to reduce the effects of drug shortages globally. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking.

@article{RN498,
   author = {Pineda-Moncusí, M. and Rekkas, A. and Martínez Pérez, Á and Leis, A. and Lopez Gomez, C. and Fey, E. and Bruninx, E. and Maljković, F. and Sánchez-Sáez, F. and Rodeiro-Boliart, J. and Zsuzsa Kiss, L. and Franz, M. and Mayer, M. A. and Eleangovan, N. and Pulido, P. P. and Natsiavas, P. and Şen, S. and Cooper, S. and Reisberg, S. and Manlik, K. and Price, D. B. and Moscetti, L. and Merkelbach, M. and Tadrous, M. and Rappoport, N. and Claire, R. and Garcia-Torrens, S. and Prieto-Alhambra, D. and Rijnbeek, P. R. and Burkard, T.},
   title = {Changes in use and utilisation patterns of drugs with reported shortages between 2010 and 2024 in Europe and North America: a network cohort study},
   journal = {Lancet Public Health},
   volume = {10},
   number = {10},
   pages = {e835-e847},
   note = {2468-2667
Pineda-Moncusí, Marta
Rekkas, Alexandros
Martínez Pérez, Álvaro
Leis, Angela
Lopez Gomez, Carlos
Fey, Eric
Bruninx, Erwin
Maljković, Filip
Sánchez-Sáez, Francisco
Rodeiro-Boliart, Jordi
Zsuzsa Kiss, Loretta
Franz, Michael
Mayer, Miguel-Angel
Eleangovan, Neva
Pulido, Pau Pericàs
Natsiavas, Pantelis
Şen, Selçuk
Cooper, Steven
Reisberg, Sulev
Manlik, Katrin
Price, David Brendan
Moscetti, Luca
Merkelbach, Manon
Tadrous, Mina
Rappoport, Nadav
Claire, Ravinder
Garcia-Torrens, Salvador
Prieto-Alhambra, Daniel
Rijnbeek, Peter R
Burkard, Theresa
Drug Shortages EHDEN Study Group
Journal Article
England
2025/09/25
Lancet Public Health. 2025 Oct;10(10):e835-e847. doi: 10.1016/S2468-2667(25)00194-X.},
   abstract = {BACKGROUND: Drug shortages can negatively impact patient care. We aimed to estimate the incidence and prevalence of use of medicines with shortages announced by the European Medicines Agency between January, 2013, and September, 2023, and to characterise the users of these drugs. METHODS: In this multinational network cohort study, we used routinely collected data from 52 databases across 18 European countries and the USA covering primary care, secondary care, health insurance claims, and disease registries. We included all participants with a minimum of 365 days of medical history between 2010 and 2024. We estimated annual incidence rates and period prevalence of use of medicines with a reported shortage (n=16), and their key alternatives (n=41). A reduction of 33% or more in incidence or prevalence after the shortage announcement was considered confirmation of a shortage. Additionally, we analysed changes in utilisation in terms of age, sex, indication, duration, and dosage. FINDINGS: Eight drugs had a 33% or higher reduction in incidence and nine drugs had a 33% or higher reduction in prevalence. Varenicline and amoxicillin (alone or combined with clavulanate) were the medicines affected in the highest number of countries and databases. Additionally, we observed changes in the indication of alteplase (pulmonary embolism indication increased in hospitals in Finland and Germany during the shortage period) and sarilumab (rheumatoid arthritis indication decreased in databases in the UK, Spain, Finland, and Sweden); and among incident users of sarilumab, a decrease in the cumulative dose was observed in databases in the Netherlands (from 84 mg in 2020 to 28 mg in 2023) and a reduction in treatment duration was observed in databases in Finland (from 104 days in 2020 to 1 day in 2022) and Belgium (from 71 days in 2020 to 30 days in 2022). INTERPRETATION: This study highlighted changes in incidence and prevalence of use of medicines after shortage announcements, and changes observed in patient care in terms of the indication, duration, or prescribed dose of medicines. Our findings showed that some reductions in use were observed across Europe and the USA, and others differed across countries. More research is needed to reduce the effects of drug shortages globally. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking.},
   keywords = {Humans
Europe
Cohort Studies
Male
Female
Middle Aged
North America
Aged
Adult
Pharmaceutical Preparations/supply & distribution
*Drug Utilization/statistics & numerical data/trends
Young Adult},
   DOI = {10.1016/s2468-2667(25)00194-x},
   year = {2025},
   type = {Journal Article}
}

OBJECTIVE: Polypharmacy is the use of multiple drugs. Many definitions have been established for polypharmacy, often cross-sectionally, despite it naturally changing over time. In this study, we aimed to identify clusters of older people with distinct polypharmacy trajectories over time and associated mortality risks. We then characterised the identified clusters and assessed their generalisability in two external databases. METHODS: Data were extracted from three primary care databases: the UK Clinical Practice Research Datalink (CPRD) GOLD, CPRD Aurum and the Dutch Integrated Primary Care Information (IPCI). People aged ≥65 on 1 January 2015 were included. Polypharmacy, defined as the cumulative number of prescribed ingredients, was calculated at baseline and at the end of each subsequent follow-up year (2015-19). We applied joint latent class modelling, which divides the population into clusters with different trajectories and associated mortality risks. The model was trained in GOLD and validated in Aurum and IPCI. RESULTS: Four clusters were identified and characterised based on polypharmacy baseline and rate of progression: low-steady, intermediate-slow/increasing, intermediate-fast/increasing and high-decreasing. The high-decreasing cluster had the highest average baseline polypharmacy (intercept = 23.4) and prevalence of non-cancer chronic comorbidities, whilst the intermediate-fast/increasing had the steepest polypharmacy rate of progression per year (slope = 6.4), highest baseline and cumulative incidence of cancer, and worst survival outcome. Good validation was found in Aurum and IPCI. CONCLUSION: High baseline levels and increasing levels of polypharmacy were associated with an increased mortality risk in older people. The clusters identified in this study were externally validated in two European databases, confirming their robustness and generalisability.

@article{RN500,
   author = {Elhussein, L. and Williams, R. D. and Man, W. Y. and Burn, E. and Delmestri, A. and Strauss, V. Y. and Prieto-Alhambra, D.},
   title = {Longitudinal trajectories of polypharmacy in older people, and their association with the risk of mortality: a joint latent class model analysis of real-world data from the UK and the Netherlands},
   journal = {Age Ageing},
   volume = {54},
   number = {8},
   note = {1468-2834
Elhussein, Leena
Williams, Ross D
Orcid: 0000-0001-7723-417x
Man, Wai Yi
Burn, Edward
Orcid: 0000-0002-9286-1128
Delmestri, Antonella
Strauss, Victoria Y
Prieto-Alhambra, Daniel
Orcid: 0000-0002-3950-6346
European Health Data and Evidence Network (EHDEN)/
Journal Article
England
2025/08/22
Age Ageing. 2025 Aug 1;54(8):afaf233. doi: 10.1093/ageing/afaf233.},
   abstract = {OBJECTIVE: Polypharmacy is the use of multiple drugs. Many definitions have been established for polypharmacy, often cross-sectionally, despite it naturally changing over time. In this study, we aimed to identify clusters of older people with distinct polypharmacy trajectories over time and associated mortality risks. We then characterised the identified clusters and assessed their generalisability in two external databases. METHODS: Data were extracted from three primary care databases: the UK Clinical Practice Research Datalink (CPRD) GOLD, CPRD Aurum and the Dutch Integrated Primary Care Information (IPCI). People aged ≥65 on 1 January 2015 were included. Polypharmacy, defined as the cumulative number of prescribed ingredients, was calculated at baseline and at the end of each subsequent follow-up year (2015-19). We applied joint latent class modelling, which divides the population into clusters with different trajectories and associated mortality risks. The model was trained in GOLD and validated in Aurum and IPCI. RESULTS: Four clusters were identified and characterised based on polypharmacy baseline and rate of progression: low-steady, intermediate-slow/increasing, intermediate-fast/increasing and high-decreasing. The high-decreasing cluster had the highest average baseline polypharmacy (intercept = 23.4) and prevalence of non-cancer chronic comorbidities, whilst the intermediate-fast/increasing had the steepest polypharmacy rate of progression per year (slope = 6.4), highest baseline and cumulative incidence of cancer, and worst survival outcome. Good validation was found in Aurum and IPCI. CONCLUSION: High baseline levels and increasing levels of polypharmacy were associated with an increased mortality risk in older people. The clusters identified in this study were externally validated in two European databases, confirming their robustness and generalisability.},
   keywords = {Humans
*Polypharmacy
Aged
United Kingdom/epidemiology
Netherlands/epidemiology
Female
Male
Latent Class Analysis
Aged, 80 and over
Risk Factors
Risk Assessment
Databases, Factual
*Mortality/trends
Age Factors
Time Factors
Longitudinal Studies
joint latent class models
longitudinal
mortality
older people
polypharmacy},
   ISSN = {0002-0729 (Print)
0002-0729},
   DOI = {10.1093/ageing/afaf233},
   year = {2025},
   type = {Journal Article}
}

BACKGROUND: Valproate-containing medicines (VPA) are first-line treatments for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in the use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration, and indication in new VPA users. METHODS: We conducted a multi-national population-based cohort study using primary care records from the Netherlands, Spain, and the UK (IPCI, SIDIAP, CPRD GOLD), primary and outpatient specialist care records from Germany and Belgium (IQVIA DA Germany, IQVIA LPD Belgium), and hospital records from Finland (ACI VARHA), all mapped to the OMOP Common data model. All women present in the databases aged ≥ 12 and ≤ 55 years on the 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation, were included. RESULTS: A total of 2 948 860 (CPRD GOLD), 718 835 (IPCI), 2 494 052 (SIDIAP), 157 361 (ACI VARHA), 218 250 (IQVIA LPD Belgium); and 5 152 752 (IQVIA DA Germany) women were included. Among those, 6416, 1241, 10 398, 1447, 945, and 4002 started treatments with VPA, respectively. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while the prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40 and 43 years. Anxiety and depressive disorder were frequent comorbidities, and the use of hormonal contraceptives we were able to capture was low. Average treatment duration varied substantially across databases. CONCLUSION: Incidences and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilization, supporting the regulatory agencies in their decision-making and improving patient safety across Europe.

@article{RN504,
   author = {Bellas, L. and Català, M. and Burn, E. and Guo, Y. and Du, M. and Verhamme, K. and Fridgeirsson, E. and Duarte-Salles, T. and Kauko, T. and Kronqvist, E. and Brash, J. T. and Seager, S. and Prieto-Alhambra, D. and Jödicke, A. M. and Prats-Uribe, A.},
   title = {Secular Trends in the Use of Valproate-Containing Medicines in Women of Childbearing Age in Europe: A Multinational DARWIN EU Network Study},
   journal = {Pharmacoepidemiol Drug Saf},
   volume = {34},
   number = {10},
   pages = {e70232},
   note = {1099-1557
Bellas, Lucía
Orcid: 0000-0001-8255-9841
Català, Martí
Burn, Edward
Guo, Yuchen
Du, Mike
Verhamme, Katia
Fridgeirsson, Egil
Duarte-Salles, Talita
Kauko, Tommi
Kronqvist, Eeva
Brash, James T
Seager, Sarah
Prieto-Alhambra, Daniel
Jödicke, Annika M
Prats-Uribe, Albert
Darwin eu/
Journal Article
Multicenter Study
England
2025/10/16
Pharmacoepidemiol Drug Saf. 2025 Oct;34(10):e70232. doi: 10.1002/pds.70232.},
   abstract = {BACKGROUND: Valproate-containing medicines (VPA) are first-line treatments for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in the use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration, and indication in new VPA users. METHODS: We conducted a multi-national population-based cohort study using primary care records from the Netherlands, Spain, and the UK (IPCI, SIDIAP, CPRD GOLD), primary and outpatient specialist care records from Germany and Belgium (IQVIA DA Germany, IQVIA LPD Belgium), and hospital records from Finland (ACI VARHA), all mapped to the OMOP Common data model. All women present in the databases aged ≥ 12 and ≤ 55 years on the 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation, were included. RESULTS: A total of 2 948 860 (CPRD GOLD), 718 835 (IPCI), 2 494 052 (SIDIAP), 157 361 (ACI VARHA), 218 250 (IQVIA LPD Belgium); and 5 152 752 (IQVIA DA Germany) women were included. Among those, 6416, 1241, 10 398, 1447, 945, and 4002 started treatments with VPA, respectively. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while the prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40 and 43 years. Anxiety and depressive disorder were frequent comorbidities, and the use of hormonal contraceptives we were able to capture was low. Average treatment duration varied substantially across databases. CONCLUSION: Incidences and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilization, supporting the regulatory agencies in their decision-making and improving patient safety across Europe.},
   keywords = {Humans
Female
*Valproic Acid/administration & dosage/adverse effects
Adult
*Anticonvulsants/administration & dosage/adverse effects
Young Adult
Adolescent
Europe/epidemiology
Middle Aged
Cohort Studies
*Epilepsy/drug therapy
Databases, Factual
Child
antiepileptic drugs
drug utilization
network study
pharmacoepidemiology},
   ISSN = {1053-8569 (Print)
1053-8569},
   DOI = {10.1002/pds.70232},
   year = {2025},
   type = {Journal Article}
}

BACKGROUND: In patients with uncontrolled asthma treated with medium dose inhaled corticosteroid/long-acting β(2)-agonist (ICS/LABA), the Global Initiative for Asthma (GINA) recommends to increase to high-dose ICS/LABA or to start therapy consisting of medium-dose ICS/LABA+LAMA (long-acting muscarinic antagonist). Adding LAMA on top of high-dose ICS/LABA is not recommended for Step 4 asthma patients, yet it is used in the real world. Patient characteristics influencing treatment step-up are unknown. The objectives of the present study were to identify determinants of step-up option (high-dose ICS/LABA, medium-dose ICS/LABA+LAMA, high-dose ICS/LABA+LAMA) in patients with moderate to severe asthma. METHODS: A retrospective cohort study using three primary care databases (IPCI, HSD, CPRD GOLD) and one prescription database (Aarhus) included asthma patients with step-up after ≥3 months use of medium-dose ICS/LABA, from January 2010 to April 2020. Characteristics of patients were described, and determinants of choice for medium-dose ICS/LABA+LAMA or high dose ICS/LABA were investigated. RESULTS: 492 639 adults with asthma and ≥1 year of database history were identified and 25 558 were eligible for analysis. 6126 patients stepped-up to medium-dose ICS/LABA+LAMA and 18 947 patients stepped-up to high-dose ICS/LABA. Determinants for step-up to medium-dose ICS/LABA+LAMA were higher age and presence of COPD whereas history of atopy lowered this choice. Other covariates were differentially associated with specific treatment step-up depending on the databases. CONCLUSION: In uncontrolled asthma patients on medium-dose ICS/LABA, treatment step-up with add-on LAMA was more likely than step-up to high-dose ICS/LABA in older patients, current smokers, with a history of asthma exacerbations and concomitant diagnosis of COPD.

@article{RN499,
   author = {Jeannetot, D. and de Ridder, M. and Mosseveld, M. and Pedersen, L. and Lapi, F. and Marconi, E. and Tan, E. H. and Delmestri, A. and Prieto-Alhambra, D. and Van Der Deijl, M. and Brusselle, G. and Verhamme, K.},
   title = {Treatment choice for adult patients with moderate-to-severe asthma: the TAILOR study},
   journal = {ERJ Open Res},
   volume = {11},
   number = {3},
   note = {2312-0541
Jeannetot, Daniel
Orcid: 0000-0001-8797-0883
de Ridder, Maria
Mosseveld, Mees
Orcid: 0000-0001-9301-8565
Pedersen, Lars
Lapi, Francesco
Marconi, Ettore
Tan, Eng Hooi
Orcid: 0000-0003-4470-2736
Delmestri, Antonella
Orcid: 0000-0003-0388-3403
Prieto-Alhambra, Daniel
Van Der Deijl, Marielle
Brusselle, Guy
Orcid: 0000-0001-7021-8505
Verhamme, Katia
Orcid: 0000-0001-8162-4904
Journal Article
England
2025/07/01
ERJ Open Res. 2025 Jun 30;11(3):00869-2024. doi: 10.1183/23120541.00869-2024. eCollection 2025 May.},
   abstract = {BACKGROUND: In patients with uncontrolled asthma treated with medium dose inhaled corticosteroid/long-acting β(2)-agonist (ICS/LABA), the Global Initiative for Asthma (GINA) recommends to increase to high-dose ICS/LABA or to start therapy consisting of medium-dose ICS/LABA+LAMA (long-acting muscarinic antagonist). Adding LAMA on top of high-dose ICS/LABA is not recommended for Step 4 asthma patients, yet it is used in the real world. Patient characteristics influencing treatment step-up are unknown. The objectives of the present study were to identify determinants of step-up option (high-dose ICS/LABA, medium-dose ICS/LABA+LAMA, high-dose ICS/LABA+LAMA) in patients with moderate to severe asthma. METHODS: A retrospective cohort study using three primary care databases (IPCI, HSD, CPRD GOLD) and one prescription database (Aarhus) included asthma patients with step-up after ≥3 months use of medium-dose ICS/LABA, from January 2010 to April 2020. Characteristics of patients were described, and determinants of choice for medium-dose ICS/LABA+LAMA or high dose ICS/LABA were investigated. RESULTS: 492 639 adults with asthma and ≥1 year of database history were identified and 25 558 were eligible for analysis. 6126 patients stepped-up to medium-dose ICS/LABA+LAMA and 18 947 patients stepped-up to high-dose ICS/LABA. Determinants for step-up to medium-dose ICS/LABA+LAMA were higher age and presence of COPD whereas history of atopy lowered this choice. Other covariates were differentially associated with specific treatment step-up depending on the databases. CONCLUSION: In uncontrolled asthma patients on medium-dose ICS/LABA, treatment step-up with add-on LAMA was more likely than step-up to high-dose ICS/LABA in older patients, current smokers, with a history of asthma exacerbations and concomitant diagnosis of COPD.},
   ISSN = {2312-0541 (Print)
2312-0541},
   DOI = {10.1183/23120541.00869-2024},
   year = {2025},
   type = {Journal Article}
}

BACKGROUND: The opioid crisis has been a serious public health challenge in North America for decades, despite numerous efforts to mitigate its devastating consequences. As concerns grow about a similar situation developing in Europe, we evaluated the trends in opioid use and characterized prescribing indications across seven European countries. METHODS: We conducted a multinational cohort study using electronic health records from various healthcare settings: primary care [Clinical Practice Research Datalink (CPRD) GOLD (United Kingdom), Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP, Spain), and Integrated Primary Care Information Project (IPCI, the Netherlands)]; primary and outpatient specialist care [IQVIA Disease Analyzer (DA) Germany and IQVIA Longitudinal Patient Database (LPD) Belgium]; hospital care [Clinical Data Warehouse of Bordeaux University Hospital (CHUBX, France)]; and the Estonian Biobank (EBB). All data were mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). All people registered in a contributing database for ≥365 days between 2012 and 2022 were included. Annual period prevalence and incidence rates of opioid prescriptions were estimated, and long-term trends were quantified as the percent change from 2012 to 2019. New opioid users were characterized, including potential prescribing indications. RESULTS: Between 2012 and 2019, the incidence of opioid prescriptions in primary care decreased by -50·7% (CPRD GOLD) and -2·0% (SIDIAP), while it increased in EBB (+52·8%) and CHUBX (+25·3%) data. The incidence of codeine and tramadol use decreased in most databases. However, the prevalence of oxycodone, morphine, and fentanyl increased. Opioid use was highest among older age groups, and the majority of prescriptions were for oral formulations. Respiratory and pain-related conditions were the most common indications for new opioid users in outpatient settings. CONCLUSION: Despite a decrease in new opioid prescriptions in many European countries, the prevalence of opioid use remained largely stable over the last decade. More data are needed to monitor evolving opioid prescription patterns in Europe, particularly in the post-pandemic era.

@article{RN502,
   author = {Xie, J. and Du, M. and Guo, Y. and Barboza, C. and Brash, J. T. and Delmestri, A. and Duarte-Salles, T. and Gratton, J. and Griffier, R. and Kolde, R. and Man, W. Y. and Mercadé-Besora, N. and Oja, M. and Seager, S. and Verhamme, K. and Vojinovic, D. and Burn, E. and Prieto-Alhambra, D. and Català, M. and Jödicke, A. M.},
   title = {Trends in prescription opioid use in Europe: A DARWIN EU(®) multinational cohort study including seven European countries},
   journal = {Front Pharmacol},
   volume = {16},
   pages = {1608051},
   note = {1663-9812
Xie, Junqing
Du, Mike
Guo, Yuchen
Barboza, Cesar
Brash, James T
Delmestri, Antonella
Duarte-Salles, Talita
Gratton, Jasmine
Griffier, Romain
Kolde, Raivo
Man, Wai Yi
Mercadé-Besora, Núria
Oja, Marek
Seager, Sarah
Verhamme, Katia
Vojinovic, Dina
Burn, Edward
Prieto-Alhambra, Daniel
Català, Martí
Jödicke, Annika M
Journal Article
Switzerland
2025/09/03
Front Pharmacol. 2025 Aug 18;16:1608051. doi: 10.3389/fphar.2025.1608051. eCollection 2025.},
   abstract = {BACKGROUND: The opioid crisis has been a serious public health challenge in North America for decades, despite numerous efforts to mitigate its devastating consequences. As concerns grow about a similar situation developing in Europe, we evaluated the trends in opioid use and characterized prescribing indications across seven European countries. METHODS: We conducted a multinational cohort study using electronic health records from various healthcare settings: primary care [Clinical Practice Research Datalink (CPRD) GOLD (United Kingdom), Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAP, Spain), and Integrated Primary Care Information Project (IPCI, the Netherlands)]; primary and outpatient specialist care [IQVIA Disease Analyzer (DA) Germany and IQVIA Longitudinal Patient Database (LPD) Belgium]; hospital care [Clinical Data Warehouse of Bordeaux University Hospital (CHUBX, France)]; and the Estonian Biobank (EBB). All data were mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). All people registered in a contributing database for ≥365 days between 2012 and 2022 were included. Annual period prevalence and incidence rates of opioid prescriptions were estimated, and long-term trends were quantified as the percent change from 2012 to 2019. New opioid users were characterized, including potential prescribing indications. RESULTS: Between 2012 and 2019, the incidence of opioid prescriptions in primary care decreased by -50·7% (CPRD GOLD) and -2·0% (SIDIAP), while it increased in EBB (+52·8%) and CHUBX (+25·3%) data. The incidence of codeine and tramadol use decreased in most databases. However, the prevalence of oxycodone, morphine, and fentanyl increased. Opioid use was highest among older age groups, and the majority of prescriptions were for oral formulations. Respiratory and pain-related conditions were the most common indications for new opioid users in outpatient settings. CONCLUSION: Despite a decrease in new opioid prescriptions in many European countries, the prevalence of opioid use remained largely stable over the last decade. More data are needed to monitor evolving opioid prescription patterns in Europe, particularly in the post-pandemic era.},
   keywords = {common data model
electronic health records
opioids
real-world data
trends multinational},
   ISSN = {1663-9812 (Print)
1663-9812},
   DOI = {10.3389/fphar.2025.1608051},
   year = {2025},
   type = {Journal Article}
}

BACKGROUND: The SCORE2 model is a derived risk prediction model that estimates the CVE risk. Originally developed with population-based cohort data, this model is also intended to be used in routine primary care to calculate the risk of first-onset CVE and guide treatment decisions. AIM: In this study, we followed adult patients in the Netherlands who visited their general practitioner (GP) and underwent a CVE risk assessment at their GP office. The aim was to relate the results of the SCORE2 model to the observed risk of a first CVE during follow-up. METHODS: A retrospective cohort study was conducted of 205,548 patients, analyzing factors including age, sex, smoking status, diabetes, total and HDL cholesterol, and mean systolic blood pressure. The performance of the SCORE2 model was assessed using observed-to-expected (O/E) risk ratios, calibration plots, and C-statistics. Analyses were stratified by sex, age groups (< 50 and ≥ 50 years), and low and moderate risk country categories. MAIN RESULTS: Results indicated a mean observed 10-year risk of 10.1%, notably higher than the model-predicted risk of 6.2%. The O/E ratio in females and men was 1.54 and 1.68 respectively.The mean observed 10-year CVE was in the age groups < 50 years and ≥ 50 years 6.9% and 11%, respectively. (O/E ratio: 1.78 vs. 1.62).Consequently, approximately 35% of patients potentially missed preventive treatments due to SCORE2's underestimation. CONCLUSION: These findings suggest the SCORE2 model may underestimate CVE risk in primary care, highlighting the need for calibration in this setting. Overview of the Study on Cardiovascular Risk Prediction Background: The SCORE2 model is used by doctors to predict the risk of cardiovascular events (such as heart attacks and strokes) over the next 10 years. It considers factors like age, sex, blood pressure, smoking, diabetes, and cholesterol levels. PURPOSE: This study looked at how well the SCORE2 model works for patients visiting their general practitioner (GP) for a heart health check. The researchers wanted to see if the predicted risks matched the actual risks observed over time. METHODS: The study included adults aged 40-69 in the Netherlands who had their first heart health check with their GP. The researchers used the SCORE2 model to estimate each person's risk and then tracked their health during follow-up to see who had a cardiovascular event. RESULTS: The study included 205,548 patients with an average age of 58. The SCORE2 model predicted a 6.2% risk of heart attacks or strokes over 10 years, but the actual observed risk was higher at 10.1%. This means the model underestimated the risk for many patients. CONCLUSION: The SCORE2 model underestimates the risk of heart attacks and strokes in this selected group of patients. As a result, since treatment is based on the estimated risk, many patients might not receive the treatment they need based on this model alone. eng

@article{RN503,
   author = {Voorbrood, V. M. I. and Bohnen, A. M. and Bosman, A. P. and Rijnbeek, P. R. and Rizopoulos, D. and Bindels, P. J. E.},
   title = {Underestimation of Cardiovascular Risk by the SCORE2 Model in Primary Care: A Call for Recalibration},
   journal = {Eur J Prev Cardiol},
   note = {2047-4881
Voorbrood, V M I
Orcid: 0000-0002-8636-2533
Bohnen, A M
Orcid: 0000-0002-6645-9100
Bosman, A P
Orcid: 0009-0001-4334-7392
Rijnbeek, P R
Orcid: 0000-0003-0621-1979
Rizopoulos, D
Orcid: 0000-0001-9397-0900
Bindels, P J E
Orcid: 0000-0001-5941-4820
Journal Article
England
2025/04/27
Eur J Prev Cardiol. 2025 Apr 27:zwaf253. doi: 10.1093/eurjpc/zwaf253.},
   abstract = {BACKGROUND: The SCORE2 model is a derived risk prediction model that estimates the CVE risk. Originally developed with population-based cohort data, this model is also intended to be used in routine primary care to calculate the risk of first-onset CVE and guide treatment decisions. AIM: In this study, we followed adult patients in the Netherlands who visited their general practitioner (GP) and underwent a CVE risk assessment at their GP office. The aim was to relate the results of the SCORE2 model to the observed risk of a first CVE during follow-up. METHODS: A retrospective cohort study was conducted of 205,548 patients, analyzing factors including age, sex, smoking status, diabetes, total and HDL cholesterol, and mean systolic blood pressure. The performance of the SCORE2 model was assessed using observed-to-expected (O/E) risk ratios, calibration plots, and C-statistics. Analyses were stratified by sex, age groups (< 50 and ≥ 50 years), and low and moderate risk country categories. MAIN RESULTS: Results indicated a mean observed 10-year risk of 10.1%, notably higher than the model-predicted risk of 6.2%. The O/E ratio in females and men was 1.54 and 1.68 respectively.The mean observed 10-year CVE was in the age groups < 50 years and ≥ 50 years 6.9% and 11%, respectively. (O/E ratio: 1.78 vs. 1.62).Consequently, approximately 35% of patients potentially missed preventive treatments due to SCORE2's underestimation. CONCLUSION: These findings suggest the SCORE2 model may underestimate CVE risk in primary care, highlighting the need for calibration in this setting.
Overview of the Study on Cardiovascular Risk Prediction Background: The SCORE2 model is used by doctors to predict the risk of cardiovascular events (such as heart attacks and strokes) over the next 10 years. It considers factors like age, sex, blood pressure, smoking, diabetes, and cholesterol levels. PURPOSE: This study looked at how well the SCORE2 model works for patients visiting their general practitioner (GP) for a heart health check. The researchers wanted to see if the predicted risks matched the actual risks observed over time. METHODS: The study included adults aged 40-69 in the Netherlands who had their first heart health check with their GP. The researchers used the SCORE2 model to estimate each person's risk and then tracked their health during follow-up to see who had a cardiovascular event. RESULTS: The study included 205,548 patients with an average age of 58. The SCORE2 model predicted a 6.2% risk of heart attacks or strokes over 10 years, but the actual observed risk was higher at 10.1%. This means the model underestimated the risk for many patients. CONCLUSION: The SCORE2 model underestimates the risk of heart attacks and strokes in this selected group of patients. As a result, since treatment is based on the estimated risk, many patients might not receive the treatment they need based on this model alone.
eng},
   keywords = {Primary Prevention
Risk of Cardiovascular Disease
Score2},
   ISSN = {2047-4873},
   DOI = {10.1093/eurjpc/zwaf253},
   year = {2025},
   type = {Journal Article}
}

BACKGROUND: Electronic health records (EHRs) consist of both structured data (eg, diagnostic codes) and unstructured data (eg, clinical notes). It is commonly believed that unstructured clinical narratives provide more comprehensive information. However, this assumption lacks large-scale validation and direct validation methods. OBJECTIVE: This study aims to quantitatively compare the information in structured and unstructured EHR data and directly validate whether unstructured data offers more extensive information across a patient population. METHODS: We analyzed both structured and unstructured data from patient records and visits in a large Dutch primary care EHR database between January 2021 and January 2024. Clinical concepts were identified from free-text notes using an extraction framework tailored for Dutch and compared with concepts from structured data. Concept embeddings were generated to measure semantic similarity between structured and extracted concepts through cosine similarity. A similarity threshold was systematically determined via annotated matches and minimized weighted Gini impurity. We then quantified the concept overlap between structured and unstructured data across various concept domains and patient populations. RESULTS: In a population of 1.8 million patients, only 13% of extracted concepts from patient records and 7% from individual visits had similar structured counterparts. Conversely, 42% of structured concepts in records and 25% in visits had similar matches in unstructured data. Condition concepts had the highest overlap, followed by measurements and drug concepts. Subpopulation visits, such as those with chronic conditions or psychological disorders, showed different proportions of data overlap, indicating varied reliance on structured versus unstructured data across clinical contexts. CONCLUSIONS: Our study demonstrates the feasibility of quantifying the information difference between structured and unstructured data, showing that the unstructured data provides important additional information in the studied database and populations. The annotated concept matches are made publicly available for the clinical natural language processing community. Despite some limitations, our proposed methodology proves versatile, and its application can lead to more robust and insightful observational clinical research.

@article{RN410,
   author = {Seinen, T. M. and Kors, J. A. and van Mulligen, E. M. and Rijnbeek, P. R.},
   title = {Using Structured Codes and Free-Text Notes to Measure Information Complementarity in Electronic Health Records: Feasibility and Validation Study},
   journal = {J Med Internet Res},
   volume = {27},
   pages = {e66910},
   note = {1438-8871 Seinen, Tom M Orcid: 0000-0001-5369-8260 Kors, Jan A Orcid: 0000-0002-4929-026x van Mulligen, Erik M Orcid: 0000-0003-1377-9386 Rijnbeek, Peter R Orcid: 0000-0003-0621-1979 Journal Article Validation Study Canada 2025/02/13 23:03 J Med Internet Res. 2025 Feb 13;27:e66910. doi: 10.2196/66910.},
   abstract = {BACKGROUND: Electronic health records (EHRs) consist of both structured data (eg, diagnostic codes) and unstructured data (eg, clinical notes). It is commonly believed that unstructured clinical narratives provide more comprehensive information. However, this assumption lacks large-scale validation and direct validation methods. OBJECTIVE: This study aims to quantitatively compare the information in structured and unstructured EHR data and directly validate whether unstructured data offers more extensive information across a patient population. METHODS: We analyzed both structured and unstructured data from patient records and visits in a large Dutch primary care EHR database between January 2021 and January 2024. Clinical concepts were identified from free-text notes using an extraction framework tailored for Dutch and compared with concepts from structured data. Concept embeddings were generated to measure semantic similarity between structured and extracted concepts through cosine similarity. A similarity threshold was systematically determined via annotated matches and minimized weighted Gini impurity. We then quantified the concept overlap between structured and unstructured data across various concept domains and patient populations. RESULTS: In a population of 1.8 million patients, only 13% of extracted concepts from patient records and 7% from individual visits had similar structured counterparts. Conversely, 42% of structured concepts in records and 25% in visits had similar matches in unstructured data. Condition concepts had the highest overlap, followed by measurements and drug concepts. Subpopulation visits, such as those with chronic conditions or psychological disorders, showed different proportions of data overlap, indicating varied reliance on structured versus unstructured data across clinical contexts. CONCLUSIONS: Our study demonstrates the feasibility of quantifying the information difference between structured and unstructured data, showing that the unstructured data provides important additional information in the studied database and populations. The annotated concept matches are made publicly available for the clinical natural language processing community. Despite some limitations, our proposed methodology proves versatile, and its application can lead to more robust and insightful observational clinical research.},
   keywords = {*Electronic Health Records
Humans
Feasibility Studies
Netherlands
Ehr
clinical concept extraction
clinical concept similarity
code
data
electronic health records
electronic record
framework
free-text
information
machine learning
named entity recognition
natural language processing
patient records
structured data
text mining
unstructured data
word embeddings ,
ISSN = 1439-4456 (Print)
1438-8871 ,
DOI = 10.2196/66910},
   year = {2025},
   type = {Journal Article}
}

BACKGROUND: In the adult population, about 50% have hypertension, a risk factor for cardiovascular disease and subsequent premature death. Little is known about the quality of the methods used to diagnose hypertension in primary care. OBJECTIVES: The objective was to assess the frequency of use of recognized methods to establish a diagnosis of hypertension, and specifically for OBPM, whether three distinct measurements were taken, and how correctly the blood pressure levels were interpreted. METHODS: A retrospective population-based cohort study using electronic medical records of patients aged between 40 and 70 years, who visited their general practitioner (GP) with a new-onset of hypertension in the years 2012, 2016, 2019, and 2020. A visual chart review of the electronic medical records was used to assess the methods employed to diagnose hypertension in a random sample of 500 patients. The blood pressure measurement method was considered complete if three or more valid office blood pressure measurements (OBPM) were performed, or home-based blood pressure measurements (HBPM), the office- based 30-minute method (OBP30), or 24-hour ambulatory blood pressure measurements (24 H-ABPM) were used. RESULTS: In all study years, OBPM was the most frequently used method to diagnose new-onset hypertension in patients. The OBP-30 method was used in 0.4% (2012), 4.2% (2016), 10.6% (2019), and 9.8% (2020) of patients respectively, 24 H-ABPM in 16.0%, 22.2%, 17.2%, and 19.0% of patients and HBPM measurements in 5.4%, 8.4%, 7.6%, and 7.8% of patients, respectively. A diagnosis of hypertension based on only one or two office measurements occurred in 85.2% (2012), 87.9% (2016), 94.4% (2019), and 96.8% (2020) of all patients with OBPM. In cases of incomplete measurement and incorrect interpretation, medication was still started in 64% of cases in 2012, 56% (2016), 60% (2019), and 73% (2020). CONCLUSION: OBPM is still the most often used method to diagnose hypertension in primary care. The diagnosis was often incomplete or misinterpreted using incorrect cut-off levels. A small improvement occurred between 2012 and 2016 but no further progress was seen in 2019 or 2020. If hypertension is inappropriately diagnosed, it may result in under treatment or in prolonged, unnecessary treatment of patients. There is room for improvement in the general practice setting.

@article{RN481,
   author = {Voorbrood, V. M. I. and de Schepper, E. I. T. and Bohnen, A. M. and Ruiterkamp, M. F. E. and Rijnbeek, P. R. and Bindels, P. J. E.},
   title = {Blood pressure measurements for diagnosing hypertension in primary care: room for improvement},
   journal = {BMC Prim Care},
   volume = {25},
   number = {1},
   pages = {6},
   note = {2731-4553 Voorbrood, Vincent M I Orcid: 0000-0002-8636-2533 de Schepper, Evelien I T Orcid: 0000-0002-1896-6343 Bohnen, Arthur M Orcid: 0000-0002-6645-9100 Ruiterkamp, Marit F E Orcid: 0000-0001-6165-0582 Rijnbeek, Peter R Orcid: 0000-0003-0621-1979 Bindels, Patrick J E Orcid: 0000-0001-5941-4820 Journal Article England 2024/01/03 BMC Prim Care. 2024 Jan 2;25(1):6. doi: 10.1186/s12875-023-02241-z.},
   abstract = {BACKGROUND: In the adult population, about 50% have hypertension, a risk factor for cardiovascular disease and subsequent premature death. Little is known about the quality of the methods used to diagnose hypertension in primary care. OBJECTIVES: The objective was to assess the frequency of use of recognized methods to establish a diagnosis of hypertension, and specifically for OBPM, whether three distinct measurements were taken, and how correctly the blood pressure levels were interpreted. METHODS: A retrospective population-based cohort study using electronic medical records of patients aged between 40 and 70 years, who visited their general practitioner (GP) with a new-onset of hypertension in the years 2012, 2016, 2019, and 2020. A visual chart review of the electronic medical records was used to assess the methods employed to diagnose hypertension in a random sample of 500 patients. The blood pressure measurement method was considered complete if three or more valid office blood pressure measurements (OBPM) were performed, or home-based blood pressure measurements (HBPM), the office- based 30-minute method (OBP30), or 24-hour ambulatory blood pressure measurements (24 H-ABPM) were used. RESULTS: In all study years, OBPM was the most frequently used method to diagnose new-onset hypertension in patients. The OBP-30 method was used in 0.4% (2012), 4.2% (2016), 10.6% (2019), and 9.8% (2020) of patients respectively, 24 H-ABPM in 16.0%, 22.2%, 17.2%, and 19.0% of patients and HBPM measurements in 5.4%, 8.4%, 7.6%, and 7.8% of patients, respectively. A diagnosis of hypertension based on only one or two office measurements occurred in 85.2% (2012), 87.9% (2016), 94.4% (2019), and 96.8% (2020) of all patients with OBPM. In cases of incomplete measurement and incorrect interpretation, medication was still started in 64% of cases in 2012, 56% (2016), 60% (2019), and 73% (2020). CONCLUSION: OBPM is still the most often used method to diagnose hypertension in primary care. The diagnosis was often incomplete or misinterpreted using incorrect cut-off levels. A small improvement occurred between 2012 and 2016 but no further progress was seen in 2019 or 2020. If hypertension is inappropriately diagnosed, it may result in under treatment or in prolonged, unnecessary treatment of patients. There is room for improvement in the general practice setting.},
   keywords = {Adult
Humans
Middle Aged
Aged
Blood Pressure
*Blood Pressure Monitoring, Ambulatory/methods
Retrospective Studies
Cohort Studies
*Hypertension/diagnosis
Primary Health Care
Diagnosis of Hypertension
Hypertension
Primary care},
   ISSN = {2731-4553},
   DOI = {10.1186/s12875-023-02241-z},
   year = {2024},
   type = {Journal Article}
}

PURPOSE: We aimed to develop a standardized method to calculate daily dose (i.e., the amount of drug a patient was exposed to per day) of any drug on a global scale using only drug information of typical observational data in the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) and a single reference table from Observational Health Data Sciences And Informatics (OHDSI). MATERIALS AND METHODS: The OMOP DRUG_STRENGTH reference table contains information on the strength or concentration of drugs, whereas the OMOP DRUG_EXPOSURE table contains information on patients' drug prescriptions or dispensations/claims. Based on DRUG_EXPOSURE data from the primary care databases Clinical Practice Research Datalink GOLD (United Kingdom) and Integrated Primary Care Information (IPCI, The Netherlands) and healthcare claims from PharMetrics® Plus for Academics (USA), we developed four formulas to calculate daily dose given different DRUG_STRENGTH reference table information. We tested the dose formulas by comparing the calculated median daily dose to the World Health Organization (WHO) Defined Daily Dose (DDD) for six different ingredients in those three databases and additional four international databases representing a variety of healthcare settings: MAITT (Estonia, healthcare claims and discharge summaries), IQVIA Disease Analyzer Germany (outpatient data), IQVIA Longitudinal Patient Database Belgium (outpatient data), and IMASIS Parc Salut (Spain, hospital data). Finally, in each database, we assessed the proportion of drug records for which daily dose calculations were possible using the suggested formulas. RESULTS: Applying the dose formulas, we obtained median daily doses that generally matched the WHO DDD definitions. Our dose formulas were applicable to >85% of drug records in all but one of the assessed databases. CONCLUSION: We have established and implemented a standardized daily dose calculation in OMOP CDM providing reliable and reproducible results.

@article{RN278,
   author = {Burkard, T. and López-Güell, K. and Gorbachev, A. and Bellas, L. and Jödicke, A. M. and Burn, E. and de Ridder, M. and Mosseveld, M. and Gratton, J. and Seager, S. and Vojinovic, D. and Mayer, M. A. and Ramírez-Anguita, J. M. and Machín, A. L. and Oja, M. and Kolde, R. and Bonadt, K. and Prieto-Alhambra, D. and Reich, C. and Català, M.},
   title = {Calculating daily dose in the Observational Medical Outcomes Partnership Common Data Model},
   journal = {Pharmacoepidemiol Drug Saf},
   volume = {33},
   number = {6},
   pages = {e5809},
   note = {1099-1557 Burkard, Theresa Orcid: 0000-0003-1313-4473 López-Güell, Kim Gorbachev, Artem Bellas, Lucía Jödicke, Annika M Burn, Edward de Ridder, Maria Mosseveld, Mees Gratton, Jasmine Seager, Sarah Vojinovic, Dina Mayer, Miguel Angel Ramírez-Anguita, Juan Manuel Machín, Angela Leis Oja, Marek Kolde, Raivo Bonadt, Klaus Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Reich, Chistian Català, Martí EMA/2021/08/TDA/Darwin EU/ Ehden/ Journal Article Research Support, Non-U.S. Gov't England 2024/05/22 Pharmacoepidemiol Drug Saf. 2024 Jun;33(6):e5809. doi: 10.1002/pds.5809.},
   abstract = {PURPOSE: We aimed to develop a standardized method to calculate daily dose (i.e., the amount of drug a patient was exposed to per day) of any drug on a global scale using only drug information of typical observational data in the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) and a single reference table from Observational Health Data Sciences And Informatics (OHDSI). MATERIALS AND METHODS: The OMOP DRUG_STRENGTH reference table contains information on the strength or concentration of drugs, whereas the OMOP DRUG_EXPOSURE table contains information on patients' drug prescriptions or dispensations/claims. Based on DRUG_EXPOSURE data from the primary care databases Clinical Practice Research Datalink GOLD (United Kingdom) and Integrated Primary Care Information (IPCI, The Netherlands) and healthcare claims from PharMetrics® Plus for Academics (USA), we developed four formulas to calculate daily dose given different DRUG_STRENGTH reference table information. We tested the dose formulas by comparing the calculated median daily dose to the World Health Organization (WHO) Defined Daily Dose (DDD) for six different ingredients in those three databases and additional four international databases representing a variety of healthcare settings: MAITT (Estonia, healthcare claims and discharge summaries), IQVIA Disease Analyzer Germany (outpatient data), IQVIA Longitudinal Patient Database Belgium (outpatient data), and IMASIS Parc Salut (Spain, hospital data). Finally, in each database, we assessed the proportion of drug records for which daily dose calculations were possible using the suggested formulas. RESULTS: Applying the dose formulas, we obtained median daily doses that generally matched the WHO DDD definitions. Our dose formulas were applicable to >85% of drug records in all but one of the assessed databases. CONCLUSION: We have established and implemented a standardized daily dose calculation in OMOP CDM providing reliable and reproducible results.},
   keywords = {Humans
*Databases, Factual/statistics & numerical data
United Kingdom
Drug Dosage Calculations
Netherlands
Primary Health Care
Pharmacoepidemiology/methods
World Health Organization
Omop
Who ddd
common data model
dose},
   ISSN = {1053-8569},
   DOI = {10.1002/pds.5809},
   year = {2024},
   type = {Journal Article}
}

BACKGROUND: A prediction model can be a useful tool to quantify the risk of a patient developing dementia in the next years and take risk-factor-targeted intervention. Numerous dementia prediction models have been developed, but few have been externally validated, likely limiting their clinical uptake. In our previous work, we had limited success in externally validating some of these existing models due to inadequate reporting. As a result, we are compelled to develop and externally validate novel models to predict dementia in the general population across a network of observational databases. We assess regularization methods to obtain parsimonious models that are of lower complexity and easier to implement. METHODS: Logistic regression models were developed across a network of five observational databases with electronic health records (EHRs) and claims data to predict 5-year dementia risk in persons aged 55-84. The regularization methods L1 and Broken Adaptive Ridge (BAR) as well as three candidate predictor sets to optimize prediction performance were assessed. The predictor sets include a baseline set using only age and sex, a full set including all available candidate predictors, and a phenotype set which includes a limited number of clinically relevant predictors. RESULTS: BAR can be used for variable selection, outperforming L1 when a parsimonious model is desired. Adding candidate predictors for disease diagnosis and drug exposure generally improves the performance of baseline models using only age and sex. While a model trained on German EHR data saw an increase in AUROC from 0.74 to 0.83 with additional predictors, a model trained on US EHR data showed only minimal improvement from 0.79 to 0.81 AUROC. Nevertheless, the latter model developed using BAR regularization on the clinically relevant predictor set was ultimately chosen as best performing model as it demonstrated more consistent external validation performance and improved calibration. CONCLUSIONS: We developed and externally validated patient-level models to predict dementia. Our results show that although dementia prediction is highly driven by demographic age, adding predictors based on condition diagnoses and drug exposures further improves prediction performance. BAR regularization outperforms L1 regularization to yield the most parsimonious yet still well-performing prediction model for dementia.

@article{RN334,
   author = {John, L. H. and Fridgeirsson, E. A. and Kors, J. A. and Reps, J. M. and Williams, R. D. and Ryan, P. B. and Rijnbeek, P. R.},
   title = {Development and validation of a patient-level model to predict dementia across a network of observational databases},
   journal = {BMC Med},
   volume = {22},
   number = {1},
   pages = {308},
   note = {1741-7015 John, Luis H Fridgeirsson, Egill A Kors, Jan A Reps, Jenna M Williams, Ross D Ryan, Patrick B Rijnbeek, Peter R Journal Article Research Support, Non-U.S. Gov't Validation Study England 2024/07/30 BMC Med. 2024 Jul 29;22(1):308. doi: 10.1186/s12916-024-03530-9.},
   abstract = {BACKGROUND: A prediction model can be a useful tool to quantify the risk of a patient developing dementia in the next years and take risk-factor-targeted intervention. Numerous dementia prediction models have been developed, but few have been externally validated, likely limiting their clinical uptake. In our previous work, we had limited success in externally validating some of these existing models due to inadequate reporting. As a result, we are compelled to develop and externally validate novel models to predict dementia in the general population across a network of observational databases. We assess regularization methods to obtain parsimonious models that are of lower complexity and easier to implement. METHODS: Logistic regression models were developed across a network of five observational databases with electronic health records (EHRs) and claims data to predict 5-year dementia risk in persons aged 55-84. The regularization methods L1 and Broken Adaptive Ridge (BAR) as well as three candidate predictor sets to optimize prediction performance were assessed. The predictor sets include a baseline set using only age and sex, a full set including all available candidate predictors, and a phenotype set which includes a limited number of clinically relevant predictors. RESULTS: BAR can be used for variable selection, outperforming L1 when a parsimonious model is desired. Adding candidate predictors for disease diagnosis and drug exposure generally improves the performance of baseline models using only age and sex. While a model trained on German EHR data saw an increase in AUROC from 0.74 to 0.83 with additional predictors, a model trained on US EHR data showed only minimal improvement from 0.79 to 0.81 AUROC. Nevertheless, the latter model developed using BAR regularization on the clinically relevant predictor set was ultimately chosen as best performing model as it demonstrated more consistent external validation performance and improved calibration. CONCLUSIONS: We developed and externally validated patient-level models to predict dementia. Our results show that although dementia prediction is highly driven by demographic age, adding predictors based on condition diagnoses and drug exposures further improves prediction performance. BAR regularization outperforms L1 regularization to yield the most parsimonious yet still well-performing prediction model for dementia.},
   keywords = {Humans
*Dementia/diagnosis/epidemiology
Aged
Female
Male
Aged, 80 and over
Middle Aged
*Databases, Factual
Electronic Health Records
Risk Assessment/methods
Risk Factors
Dementia prediction
External validation
Logistic regression model
Observational data},
   ISSN = {1741-7015},
   DOI = {10.1186/s12916-024-03530-9},
   year = {2024},
   type = {Journal Article}
}

BACKGROUND: The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations. METHODS: A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses. FINDINGS: 3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8-5.1) per 100 person-years to 103.9 (95% CI 103.2-104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3-1.9) to 14.3 (95% CI 14.1-14.6)), abdominal pain (from 0.3 (95% CI 0.1-0.5) to 9.9 (95% CI 9.7-10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4-0.9) to 13.3 (95% CI 13.1-13.6)), cough (from 0.3 (95% CI 0.2-0.5) to 9.1 (95% CI 8.9-9.3)), and anxiety (from 0.8 (95% CI 0.6-1.2) to 11.4 (95% CI 11.2-11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008-0.2) to 1.7 (95% CI 1.6-1.8)), pins and needles (from 0.05 (95% CI 0.03-0.0.9) to 1.5 (95% CI 1.4-1.6)), memory issues (from 0.03 (95% CI 0.02-0.06) to 0.8 (95% CI 0.7-0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004-0.01) to 0.6 (95% CI 0.4-0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03-0.04) to 0.7 (95% CI 0.6-0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1-2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7-3.9); anxiety, 2.3 (1.4-3.8); allergy, 2.1 (1.7-2.8) and sleep disorders, 2.1 (1.5-2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3-2.8). INTERPRETATION: Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO- isted symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets. FUNDING: This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).

@article{RN493,
   author = {Xie, J. and López-Güell, K. and Dedman, D. and Duarte-Salles, T. and Kolde, R. and López-Blasco, R. and Martínez, Á and Mercier, G. and Abellan, A. and Arinze, J. T. and Cuccu, Z. and Delmestri, A. and Delseny, D. and Khalid, S. and Kim, C. and Kim, J. W. and Kostka, K. and Loste, C. and Mateu, L. and Mayer, M. A. and Meléndez-Cardiel, J. and Mercadé-Besora, N. and Mosseveld, M. and Nishimura, A. and Nordeng, H. M. E. and Oyinlola, J. O. and Pérez-Crespo, L. and Pineda-Moncusí, M. and Ramírez-Anguita, J. M. and Trinh, N. T. H. and Uusküla, A. and Valdivieso, B. and Burkard, T. and Burn, E. and Català, M. and Prieto-Alhambra, D. and Paredes, R. and Jödicke, A. M.},
   title = {Incidence of post-acute COVID-19 symptoms across healthcare settings in seven countries: an international retrospective cohort study using routinely-collected data},
   journal = {EClinicalMedicine},
   volume = {77},
   pages = {102903},
   note = {2589-5370 Xie, Junqing López-Güell, Kim Dedman, Daniel Duarte-Salles, Talita Kolde, Raivo López-Blasco, Raúl Martínez, Álvaro Mercier, Gregoire Abellan, Alicia Arinze, Johnmary T Cuccu, Zara Delmestri, Antonella Delseny, Dominique Khalid, Sara Kim, Chungsoo Kim, Ji-Woo Kostka, Kristin Loste, Cora Mateu, Lourdes Mayer, Miguel A Meléndez-Cardiel, Jaime Mercadé-Besora, Núria Mosseveld, Mees Nishimura, Akihito Nordeng, Hedvig M E Oyinlola, Jessie O Pérez-Crespo, Laura Pineda-Moncusí, Marta Ramírez-Anguita, Juan Manuel Trinh, Nhung T H Uusküla, Anneli Valdivieso, Bernardo Burkard, Theresa Burn, Edward Català, Martí Prieto-Alhambra, Daniel Paredes, Roger Jödicke, Annika M Journal Article England 2024/11/18 EClinicalMedicine. 2024 Oct 30;77:102903. doi: 10.1016/j.eclinm.2024.102903. eCollection 2024 Nov.},
   abstract = {BACKGROUND: The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations. METHODS: A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses. FINDINGS: 3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8-5.1) per 100 person-years to 103.9 (95% CI 103.2-104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3-1.9) to 14.3 (95% CI 14.1-14.6)), abdominal pain (from 0.3 (95% CI 0.1-0.5) to 9.9 (95% CI 9.7-10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4-0.9) to 13.3 (95% CI 13.1-13.6)), cough (from 0.3 (95% CI 0.2-0.5) to 9.1 (95% CI 8.9-9.3)), and anxiety (from 0.8 (95% CI 0.6-1.2) to 11.4 (95% CI 11.2-11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008-0.2) to 1.7 (95% CI 1.6-1.8)), pins and needles (from 0.05 (95% CI 0.03-0.0.9) to 1.5 (95% CI 1.4-1.6)), memory issues (from 0.03 (95% CI 0.02-0.06) to 0.8 (95% CI 0.7-0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004-0.01) to 0.6 (95% CI 0.4-0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03-0.04) to 0.7 (95% CI 0.6-0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1-2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7-3.9); anxiety, 2.3 (1.4-3.8); allergy, 2.1 (1.7-2.8) and sleep disorders, 2.1 (1.5-2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3-2.8). INTERPRETATION: Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO- isted symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets. FUNDING: This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).},
   keywords = {Epidemiology
Incidence of post-acute COVID-19 symptoms
International cohort study
Post-acute COVID-19 condition
Real world data},
   ISSN = {2589-5370},
   DOI = {10.1016/j.eclinm.2024.102903},
   year = {2024},
   type = {Journal Article}
}

BACKGROUND: There is a lack of knowledge on how patients with asthma or chronic obstructive pulmonary disease (COPD) are globally treated in the real world, especially with regard to the initial pharmacological treatment of newly diagnosed patients and the different treatment trajectories. This knowledge is important to monitor and improve clinical practice. METHODS: This retrospective cohort study aims to characterise treatments using data from four claims (drug dispensing) and four electronic health record (EHR; drug prescriptions) databases across six countries and three continents, encompassing 1.3 million patients with asthma or COPD. We analysed treatment trajectories at drug class level from first diagnosis and visualised these in sunburst plots. RESULTS: In four countries (USA, UK, Spain and the Netherlands), most adults with asthma initiate treatment with short-acting ß2 agonists monotherapy (20.8%-47.4% of first-line treatments). For COPD, the most frequent first-line treatment varies by country. The largest percentages of untreated patients (for asthma and COPD) were found in claims databases (14.5%-33.2% for asthma and 27.0%-52.2% for COPD) from the USA as compared with EHR databases (6.9%-15.2% for asthma and 4.4%-17.5% for COPD) from European countries. The treatment trajectories showed step-up as well as step-down in treatments. CONCLUSION: Real-world data from claims and EHRs indicate that first-line treatments of asthma and COPD vary widely across countries. We found evidence of a stepwise approach in the pharmacological treatment of asthma and COPD, suggesting that treatments may be tailored to patients' needs.

@article{RN359,
   author = {Markus, A. F. and Rijnbeek, P. R. and Kors, J. A. and Burn, E. and Duarte-Salles, T. and Haug, M. and Kim, C. and Kolde, R. and Lee, Y. and Park, H. S. and Park, R. W. and Prieto-Alhambra, D. and Reyes, C. and Krishnan, J. A. and Brusselle, G. G. and Verhamme, K. M.},
   title = {Real-world treatment trajectories of adults with newly diagnosed asthma or COPD},
   journal = {BMJ Open Respir Res},
   volume = {11},
   number = {1},
   note = {2052-4439 Markus, Aniek F Orcid: 0000-0001-5779-4794 Rijnbeek, Peter R Orcid: 0000-0003-0621-1979 Kors, Jan A Burn, Edward Orcid: 0000-0002-9286-1128 Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 Haug, Markus Orcid: 0000-0003-0935-3307 Kim, Chungsoo Orcid: 0000-0003-1802-1777 Kolde, Raivo Orcid: 0000-0003-2886-6298 Lee, Youngsoo Orcid: 0000-0001-8918-9353 Park, Hae-Sim Orcid: 0000-0003-2614-0303 Park, Rae Woong Orcid: 0000-0003-4989-3287 Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Reyes, Carlen Orcid: 0000-0001-8486-3265 Krishnan, Jerry A Orcid: 0000-0001-5525-4778 Brusselle, Guy G Orcid: 0000-0001-7021-8505 Verhamme, Katia Mc Orcid: 0000-0001-8162-4904 Journal Article Research Support, Non-U.S. Gov't England 2024/02/28 BMJ Open Respir Res. 2024 Feb 27;11(1):e002127. doi: 10.1136/bmjresp-2023-002127.},
   abstract = {BACKGROUND: There is a lack of knowledge on how patients with asthma or chronic obstructive pulmonary disease (COPD) are globally treated in the real world, especially with regard to the initial pharmacological treatment of newly diagnosed patients and the different treatment trajectories. This knowledge is important to monitor and improve clinical practice. METHODS: This retrospective cohort study aims to characterise treatments using data from four claims (drug dispensing) and four electronic health record (EHR; drug prescriptions) databases across six countries and three continents, encompassing 1.3 million patients with asthma or COPD. We analysed treatment trajectories at drug class level from first diagnosis and visualised these in sunburst plots. RESULTS: In four countries (USA, UK, Spain and the Netherlands), most adults with asthma initiate treatment with short-acting ß2 agonists monotherapy (20.8%-47.4% of first-line treatments). For COPD, the most frequent first-line treatment varies by country. The largest percentages of untreated patients (for asthma and COPD) were found in claims databases (14.5%-33.2% for asthma and 27.0%-52.2% for COPD) from the USA as compared with EHR databases (6.9%-15.2% for asthma and 4.4%-17.5% for COPD) from European countries. The treatment trajectories showed step-up as well as step-down in treatments. CONCLUSION: Real-world data from claims and EHRs indicate that first-line treatments of asthma and COPD vary widely across countries. We found evidence of a stepwise approach in the pharmacological treatment of asthma and COPD, suggesting that treatments may be tailored to patients' needs.},
   keywords = {Adult
Humans
Retrospective Studies
Administration, Inhalation
Bronchodilator Agents/therapeutic use
Adrenergic beta-2 Receptor Agonists/therapeutic use
Adrenal Cortex Hormones/therapeutic use
*Pulmonary Disease, Chronic Obstructive/diagnosis/drug therapy/epidemiology
*Asthma/diagnosis/drug therapy/epidemiology
Asthma Pharmacology
COPD Pharmacology},
   ISSN = {2052-4439},
   DOI = {10.1136/bmjresp-2023-002127},
   year = {2024},
   type = {Journal Article}
}

PURPOSE: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. PATIENTS AND METHODS: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE. RESULTS: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US. CONCLUSION: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.

@article{RN356,
   author = {Lo Re Iii, V. and Cocoros, N. M. and Hubbard, R. A. and Dutcher, S. K. and Newcomb, C. W. and Connolly, J. G. and Perez-Vilar, S. and Carbonari, D. M. and Kempner, M. E. and Hernández-Muñoz, J. J. and Petrone, A. B. and Pishko, A. M. and Rogers Driscoll, M. E. and Brash, J. T. and Burnett, S. and Cohet, C. and Dahl, M. and DeFor, T. A. and Delmestri, A. and Djibo, D. A. and Duarte-Salles, T. and Harrington, L. B. and Kampman, M. and Kuntz, J. L. and Kurz, X. and Mercadé-Besora, N. and Pawloski, P. A. and Rijnbeek, P. R. and Seager, S. and Steiner, C. A. and Verhamme, K. and Wu, F. and Zhou, Y. and Burn, E. and Paterson, J. M. and Prieto-Alhambra, D.},
   title = {Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19: A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States},
   journal = {Clin Epidemiol},
   volume = {16},
   pages = {71-89},
   note = {1179-1349 Lo Re Iii, Vincent Orcid: 0000-0001-7955-0600 Cocoros, Noelle M Orcid: 0000-0001-7090-2761 Hubbard, Rebecca A Orcid: 0000-0003-0879-0994 Dutcher, Sarah K Orcid: 0000-0003-0574-2890 Newcomb, Craig W Connolly, John G Orcid: 0000-0003-1916-557x Perez-Vilar, Silvia Orcid: 0000-0003-1272-1502 Carbonari, Dena M Orcid: 0000-0003-0310-270x Kempner, Maria E Hernández-Muñoz, José J Orcid: 0000-0002-2553-3159 Petrone, Andrew B Orcid: 0000-0001-8413-6236 Pishko, Allyson M Orcid: 0000-0001-9997-454x Rogers Driscoll, Meighan E Orcid: 0000-0003-1371-9658 Brash, James T Burnett, Sean Cohet, Catherine Orcid: 0000-0002-0022-7251 Dahl, Matthew DeFor, Terese A Delmestri, Antonella Orcid: 0000-0003-0388-3403 Djibo, Djeneba Audrey Orcid: 0000-0003-3378-0691 Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 Harrington, Laura B Orcid: 0000-0001-5951-8291 Kampman, Melissa Kuntz, Jennifer L Orcid: 0000-0002-0017-6853 Kurz, Xavier Orcid: 0000-0002-9838-7754 Mercadé-Besora, Núria Orcid: 0009-0006-7948-3747 Pawloski, Pamala A Orcid: 0000-0002-1005-5764 Rijnbeek, Peter R Orcid: 0000-0003-0621-1979 Seager, Sarah Steiner, Claudia A Verhamme, Katia Orcid: 0000-0001-8162-4904 Wu, Fangyun Zhou, Yunping Burn, Edward Orcid: 0000-0002-9286-1128 Paterson, J Michael Orcid: 0000-0001-5995-1714 Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Journal Article New Zealand 2024/02/15 Clin Epidemiol. 2024 Feb 10;16:71-89. doi: 10.2147/CLEP.S448980. eCollection 2024.},
   abstract = {PURPOSE: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. PATIENTS AND METHODS: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE. RESULTS: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US. CONCLUSION: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.},
   keywords = {Covid-19
ischemic stroke
myocardial infarction
thromboembolism
venous thromboembolism},
   ISSN = {1179-1349 (Print) 1179-1349},
   DOI = {10.2147/clep.S448980},
   year = {2024},
   type = {Journal Article}
}

PURPOSE: The generation of representative disease phenotypes is important for ensuring the reliability of the findings of observational studies. The aim of this manuscript is to outline a reproducible framework for reliable and traceable phenotype generation based on real world data for use in the Data Analysis and Real-World Interrogation Network (DARWIN EU). We illustrate the use of this framework by generating phenotypes for two diseases: pancreatic cancer and systemic lupus erythematosus (SLE). METHODS: The phenotyping process involves a 14-steps process based on a standard operating procedure co-created by the DARWIN EU Coordination Centre in collaboration with the European Medicines Agency. A number of bespoke R packages were utilised to generate and review codelists for two phenotypes based on real world data mapped to the OMOP Common Data Model. RESULTS: Codelists were generated for both pancreatic cancer and SLE, and cohorts were generated in six OMOP-mapped databases. Diagnostic checks were performed, which showed these cohorts had broadly similar incidence and prevalence figures to previously published literature, despite significant inter-database variability. Co-occurrent symptoms, conditions, and medication use were in keeping with pre-specified clinical descriptions based on previous knowledge. CONCLUSIONS: Our detailed phenotyping process makes use of bespoke tools and allows for comprehensive codelist generation and review, as well as large-scale exploration of the characteristics of the resulting cohorts. Wider use of structured and reproducible phenotyping methods will be important in ensuring the reliability of observational studies for regulatory purposes.

@article{RN297,
   author = {Dernie, F. and Corby, G. and Robinson, A. and Bezer, J. and Mercade-Besora, N. and Griffier, R. and Verdy, G. and Leis, A. and Ramirez-Anguita, J. M. and Mayer, M. A. and Brash, J. T. and Seager, S. and Parry, R. and Jodicke, A. and Duarte-Salles, T. and Rijnbeek, P. R. and Verhamme, K. and Pacurariu, A. and Morales, D. and Pinheiro, L. and Prieto-Alhambra, D. and Prats-Uribe, A.},
   title = {Standardised and Reproducible Phenotyping Using Distributed Analytics and Tools in the Data Analysis and Real World Interrogation Network (DARWIN EU)},
   journal = {Pharmacoepidemiol Drug Saf},
   volume = {33},
   number = {11},
   pages = {e70042},
   note = {1099-1557 Dernie, Francesco Corby, George Robinson, Abigail Bezer, James Mercade-Besora, Nuria Griffier, Romain Verdy, Guillaume Leis, Angela Ramirez-Anguita, Juan Manuel Mayer, Miguel A Brash, James T Seager, Sarah Parry, Rowan Jodicke, Annika Duarte-Salles, Talita Rijnbeek, Peter R Verhamme, Katia Pacurariu, Alexandra Morales, Daniel Orcid: 0000-0002-0063-8069 Pinheiro, Luis Orcid: 0000-0002-6253-7175 Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Prats-Uribe, Albert NIHR Oxford Biomedical Research Centre/ European Medicines Agency/ Journal Article Research Support, Non-U.S. Gov't England 2024/11/13 Pharmacoepidemiol Drug Saf. 2024 Nov;33(11):e70042. doi: 10.1002/pds.70042.},
   abstract = {PURPOSE: The generation of representative disease phenotypes is important for ensuring the reliability of the findings of observational studies. The aim of this manuscript is to outline a reproducible framework for reliable and traceable phenotype generation based on real world data for use in the Data Analysis and Real-World Interrogation Network (DARWIN EU). We illustrate the use of this framework by generating phenotypes for two diseases: pancreatic cancer and systemic lupus erythematosus (SLE). METHODS: The phenotyping process involves a 14-steps process based on a standard operating procedure co-created by the DARWIN EU Coordination Centre in collaboration with the European Medicines Agency. A number of bespoke R packages were utilised to generate and review codelists for two phenotypes based on real world data mapped to the OMOP Common Data Model. RESULTS: Codelists were generated for both pancreatic cancer and SLE, and cohorts were generated in six OMOP-mapped databases. Diagnostic checks were performed, which showed these cohorts had broadly similar incidence and prevalence figures to previously published literature, despite significant inter-database variability. Co-occurrent symptoms, conditions, and medication use were in keeping with pre-specified clinical descriptions based on previous knowledge. CONCLUSIONS: Our detailed phenotyping process makes use of bespoke tools and allows for comprehensive codelist generation and review, as well as large-scale exploration of the characteristics of the resulting cohorts. Wider use of structured and reproducible phenotyping methods will be important in ensuring the reliability of observational studies for regulatory purposes.},
   keywords = {Humans
*Phenotype
*Pancreatic Neoplasms/epidemiology/diagnosis
*Lupus Erythematosus, Systemic/epidemiology/diagnosis
Reproducibility of Results
*Databases, Factual/statistics & numerical data/standards
Data Analysis
Observational Studies as Topic/methods
pancreatic cancer
phenotyping
systemic lupus erythematosus},
   ISSN = {1053-8569},
   DOI = {10.1002/pds.70042},
   year = {2024},
   type = {Journal Article}
}

BACKGROUND: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. SETTING: Primary care data (country/database) from the UK/CPRD-GOLD (2007-20), Spain/SIDIAP (2010-20) and the Netherlands/IPCI (2008-20), standardised to a common data model. METHODS: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). RESULTS: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI.In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891-32,862)) to 2010 (17,793 (17,083-18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021-25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199-52,855)) to 2020 (14,571 (14,109-15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967-29,031)) to 2020 (4763 (4176-5409)). Subjects aged ≥65-79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. CONCLUSIONS: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.

@article{RN399,
   author = {Reyes, C. and Newby, D. and Raventós, B. and Verhamme, K. and Mosseveld, M. and Prieto-Alhambra, D. and Burn, E. and Duarte-Salles, T.},
   title = {Trends of use and characterisation of anti-dementia drugs users: a large multinational-network population-based study},
   journal = {Age Ageing},
   volume = {53},
   number = {5},
   note = {1468-2834 Reyes, Carlen Orcid: 0000-0001-8486-3265 Newby, Danielle Raventós, Berta Verhamme, Katia Mosseveld, Mees Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Burn, Edward Duarte-Salles, Talita Real World Epidemiology/ Agency for Management of University and research/ Journal Article Multicenter Study Research Support, Non-U.S. Gov't England 2024/05/24 Age Ageing. 2024 May 1;53(5):afae106. doi: 10.1093/ageing/afae106.},
   abstract = {BACKGROUND: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. SETTING: Primary care data (country/database) from the UK/CPRD-GOLD (2007-20), Spain/SIDIAP (2010-20) and the Netherlands/IPCI (2008-20), standardised to a common data model. METHODS: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). RESULTS: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI.In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891-32,862)) to 2010 (17,793 (17,083-18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021-25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199-52,855)) to 2020 (14,571 (14,109-15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967-29,031)) to 2020 (4763 (4176-5409)). Subjects aged ≥65-79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. CONCLUSIONS: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.},
   keywords = {Humans
Male
Female
*Dementia/drug therapy/epidemiology
Aged
Aged, 80 and over
Middle Aged
Netherlands/epidemiology
Databases, Factual
Time Factors
Nootropic Agents/therapeutic use
Spain/epidemiology
United Kingdom/epidemiology
Practice Patterns, Physicians'/trends
Age Factors
Drug Utilization/trends/statistics & numerical data
cohort studies
dementia
drug utilization studies
older people},
   ISSN = {0002-0729 (Print) 0002-0729},
   DOI = {10.1093/ageing/afae106},
   year = {2024},
   type = {Journal Article}
}

OBJECTIVE: Observational studies using electronic health record (EHR) databases often face challenges due to unspecific clinical codes that can obscure detailed medical information, hindering precise data analysis. In this study, we aimed to assess the feasibility of refining these unspecific condition codes into more specific codes in a Dutch general practitioner (GP) EHR database by leveraging the available clinical free text. METHODS: We utilized three approaches for text classification-search queries, semi-supervised learning, and supervised learning-to improve the specificity of ten unspecific International Classification of Primary Care (ICPC-1) codes. Two text representations and three machine learning algorithms were evaluated for the (semi-)supervised models. Additionally, we measured the improvement achieved by the refinement process on all code occurrences in the database. RESULTS: The classification models performed well for most codes. In general, no single classification approach consistently outperformed the others. However, there were variations in the relative performance of the classification approaches within each code and in the use of different text representations and machine learning algorithms. Class imbalance and limited training data affected the performance of the (semi-)supervised models, yet the simple search queries remained particularly effective. Ultimately, the developed models improved the specificity of over half of all the unspecific code occurrences in the database. CONCLUSIONS: Our findings show the feasibility of using information from clinical text to improve the specificity of unspecific condition codes in observational healthcare databases, even with a limited range of machine-learning techniques and modest annotated training sets. Future work could investigate transfer learning, integration of structured data, alternative semi-supervised methods, and validation of models across healthcare settings. The improved level of detail enriches the interpretation of medical information and can benefit observational research and patient care.

@article{RN409,
   author = {Seinen, T. M. and Kors, J. A. and van Mulligen, E. M. and Fridgeirsson, E. A. and Verhamme, K. M. and Rijnbeek, P. R.},
   title = {Using clinical text to refine unspecific condition codes in Dutch general practitioner EHR data},
   journal = {Int J Med Inform},
   volume = {189},
   pages = {105506},
   note = {1872-8243 Seinen, Tom M Kors, Jan A van Mulligen, Erik M Fridgeirsson, Egill A Verhamme, Katia Mc Rijnbeek, Peter R Journal Article Ireland 2024/06/01 Int J Med Inform. 2024 Sep;189:105506. doi: 10.1016/j.ijmedinf.2024.105506. Epub 2024 May 29.},
   abstract = {OBJECTIVE: Observational studies using electronic health record (EHR) databases often face challenges due to unspecific clinical codes that can obscure detailed medical information, hindering precise data analysis. In this study, we aimed to assess the feasibility of refining these unspecific condition codes into more specific codes in a Dutch general practitioner (GP) EHR database by leveraging the available clinical free text. METHODS: We utilized three approaches for text classification-search queries, semi-supervised learning, and supervised learning-to improve the specificity of ten unspecific International Classification of Primary Care (ICPC-1) codes. Two text representations and three machine learning algorithms were evaluated for the (semi-)supervised models. Additionally, we measured the improvement achieved by the refinement process on all code occurrences in the database. RESULTS: The classification models performed well for most codes. In general, no single classification approach consistently outperformed the others. However, there were variations in the relative performance of the classification approaches within each code and in the use of different text representations and machine learning algorithms. Class imbalance and limited training data affected the performance of the (semi-)supervised models, yet the simple search queries remained particularly effective. Ultimately, the developed models improved the specificity of over half of all the unspecific code occurrences in the database. CONCLUSIONS: Our findings show the feasibility of using information from clinical text to improve the specificity of unspecific condition codes in observational healthcare databases, even with a limited range of machine-learning techniques and modest annotated training sets. Future work could investigate transfer learning, integration of structured data, alternative semi-supervised methods, and validation of models across healthcare settings. The improved level of detail enriches the interpretation of medical information and can benefit observational research and patient care.},
   keywords = {*Electronic Health Records/statistics & numerical data
Humans
Netherlands
*General Practitioners
Machine Learning
Algorithms
Clinical Coding/standards/methods
Databases, Factual
Primary Health Care
Natural Language Processing
Electronic Health Record
Text Mining},
   ISSN = {1386-5056},
   DOI = {10.1016/j.ijmedinf.2024.105506},
   year = {2024},
   type = {Journal Article}
}

Background: Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US. Methods: We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01/2017-11/2020), and a vaccinated cohort of people followed for 28 days after a dose of any COVID-19 vaccine recorded from 12/2020 onwards). Results: Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use. Conclusion: TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.

@article{RN360,
   author = {Markus, A. F. and Strauss, V. Y. and Burn, E. and Li, X. and Delmestri, A. and Reich, C. and Yin, C. and Mayer, M. A. and Ramírez-Anguita, J. M. and Marti, E. and Verhamme, K. M. C. and Rijnbeek, P. R. and Prieto-Alhambra, D. and Jödicke, A. M.},
   title = {Characterising the treatment of thromboembolic events after COVID-19 vaccination in 4 European countries and the US: An international network cohort study},
   journal = {Front Pharmacol},
   volume = {14},
   pages = {1118203},
   note = {1663-9812 Markus, Aniek F Strauss, Victoria Y Burn, Edward Li, Xintong Delmestri, Antonella Reich, Christian Yin, Can Mayer, Miguel A Ramírez-Anguita, Juan-Manuel Marti, Edelmira Verhamme, Katia M C Rijnbeek, Peter R Prieto-Alhambra, Daniel Jödicke, Annika M Journal Article Switzerland 2023/04/11 Front Pharmacol. 2023 Mar 24;14:1118203. doi: 10.3389/fphar.2023.1118203. eCollection 2023.},
   abstract = {Background: Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US. Methods: We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01/2017-11/2020), and a vaccinated cohort of people followed for 28 days after a dose of any COVID-19 vaccine recorded from 12/2020 onwards). Results: Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use. Conclusion: TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.},
   keywords = {Covid-19
anticoagulation
drug utilization
epidemiology
thromboembolic events
treatment pathways
vaccination ,
ISSN = 1663-9812 (Print) 1663-9812 ,
DOI = 10.3389/fphar.2023.1118203},
   year = {2023},
   type = {Journal Article}
}

Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma.Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions.Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients.Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients.[Box: see text]Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .

@article{RN369,
   author = {Morales, D. R. and Ostropolets, A. and Lai, L. and Sena, A. and Duvall, S. and Suchard, M. and Verhamme, K. and Rjinbeek, P. and Posada, J. and Ahmed, W. and Alshammary, T. and Alghoul, H. and Alser, O. and Areia, C. and Blacketer, C. and Burn, E. and Casajust, P. and You, S. C. and Dawoud, D. and Golozar, A. and Gong, M. and Jonnagaddala, J. and Lynch, K. and Matheny, M. and Minty, E. and Nyberg, F. and Uribe, A. and Recalde, M. and Reich, C. and Scheumie, M. and Shah, K. and Shah, N. and Schilling, L. and Vizcaya, D. and Zhang, L. and Hripcsak, G. and Ryan, P. and Prieto-Alhambra, D. and Durate-Salles, T. and Kostka, K.},
   title = {Characteristics and outcomes of COVID-19 patients with and without asthma from the United States, South Korea, and Europe},
   journal = {J Asthma},
   volume = {60},
   number = {1},
   pages = {76-86},
   note = {1532-4303 Morales, Daniel R Orcid: 0000-0002-0063-8069 Ostropolets, Anna Lai, Lana Sena, Anthony Duvall, Scott Suchard, Marc Orcid: 0000-0001-9818-479x Verhamme, Katia Orcid: 0000-0001-8162-4904 Rjinbeek, Peter Posada, Joe Ahmed, Waheed Alshammary, Thamer Orcid: 0000-0002-5630-2468 Alghoul, Heba Alser, Osaid Areia, Carlos Blacketer, Clair Burn, Edward Casajust, Paula You, Seng Chan Dawoud, Dalia Golozar, Asieh Gong, Menchung Jonnagaddala, Jitendra Lynch, Kristine Matheny, Michael Minty, Evan Nyberg, Fredrik Uribe, Albert Recalde, Martina Reich, Christian Scheumie, Martijn Shah, Karishma Shah, Nigam Schilling, Lisa Vizcaya, David Zhang, Lin Hripcsak, George Ryan, Patrick Prieto-Alhambra, Daniel Durate-Salles, Talita Kostka, Kristin 214588/Z/18/Z/WT_/Wellcome Trust/United Kingdom Journal Article Research Support, Non-U.S. Gov't England 2022/01/12 J Asthma. 2023 Jan;60(1):76-86. doi: 10.1080/02770903.2021.2025392. Epub 2022 Feb 11.},
   abstract = {Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma.Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions.Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients.Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients.[Box: see text]Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .},
   keywords = {Humans
United States/epidemiology
*COVID-19/epidemiology
*Asthma/epidemiology
SARS-CoV-2
Comorbidity
*Diabetes Mellitus/epidemiology
Hospitalization
Asthma
Covid-19
epidemiology ,
ISSN = 0277-0903 ,
DOI = 10.1080/02770903.2021.2025392},
   year = {2023},
   type = {Journal Article}
}

BACKGROUND: Comorbidities are common in patients with osteoarthritis (OA). This study aimed to determine the association of a wide range of previously diagnosed comorbidities in adults with newly diagnosed OA compared with matched controls without OA. METHODS: A case-control study was conducted. The data were derived from an electronic health record database that contains the medical records of patients from general practices throughout the Netherlands. Incident OA cases were defined as patients with one or more diagnostic codes recorded in their medical records that correspond to knee, hip, or other/peripheral OA. Additionally, the first OA code had to be recorded between January 1, 2006, and December 31, 2019. The date of cases' first OA diagnosis was defined as the index date. Cases were matched (by age, sex, and general practice) to up to 4 controls without a recorded OA diagnosis. Odds ratios were derived for each 58 comorbidities separately by dividing the comorbidity prevalence of cases by that of their matched controls at the index date. RESULTS: 80,099 incident OA patients were identified of whom 79,937 (99.8%) were successfully matched with 318,206 controls. OA cases had higher odds for 42 of the 58 studied comorbidities compared with matched controls. Musculoskeletal diseases and obesity showed large associations with incident OA. CONCLUSIONS: Most of the comorbidities under study had higher odds in patients with incident OA at the index date. While previously known associations were confirmed in this study, some associations were not described earlier.

@article{RN338,
   author = {Kamps, A. and Runhaar, J. and de Ridder, M. A. J. and de Wilde, M. and van der Lei, J. and Zhang, W. and Prieto-Alhambra, D. and Englund, M. and de Schepper, E. I. T. and Bierma-Zeinstra, S. M. A.},
   title = {Comorbidity in incident osteoarthritis cases and matched controls using electronic health record data},
   journal = {Arthritis Res Ther},
   volume = {25},
   number = {1},
   pages = {114},
   note = {1478-6362 Kamps, Anne Orcid: 0000-0002-8998-6501 Runhaar, Jos de Ridder, Maria A J de Wilde, Marcel van der Lei, Johan Zhang, Weiya Prieto-Alhambra, Daniel Englund, Martin de Schepper, Evelien I T Bierma-Zeinstra, Sita M A Journal Article Research Support, Non-U.S. Gov't England 2023/07/05 Arthritis Res Ther. 2023 Jul 4;25(1):114. doi: 10.1186/s13075-023-03086-8.},
   abstract = {BACKGROUND: Comorbidities are common in patients with osteoarthritis (OA). This study aimed to determine the association of a wide range of previously diagnosed comorbidities in adults with newly diagnosed OA compared with matched controls without OA. METHODS: A case-control study was conducted. The data were derived from an electronic health record database that contains the medical records of patients from general practices throughout the Netherlands. Incident OA cases were defined as patients with one or more diagnostic codes recorded in their medical records that correspond to knee, hip, or other/peripheral OA. Additionally, the first OA code had to be recorded between January 1, 2006, and December 31, 2019. The date of cases' first OA diagnosis was defined as the index date. Cases were matched (by age, sex, and general practice) to up to 4 controls without a recorded OA diagnosis. Odds ratios were derived for each 58 comorbidities separately by dividing the comorbidity prevalence of cases by that of their matched controls at the index date. RESULTS: 80,099 incident OA patients were identified of whom 79,937 (99.8%) were successfully matched with 318,206 controls. OA cases had higher odds for 42 of the 58 studied comorbidities compared with matched controls. Musculoskeletal diseases and obesity showed large associations with incident OA. CONCLUSIONS: Most of the comorbidities under study had higher odds in patients with incident OA at the index date. While previously known associations were confirmed in this study, some associations were not described earlier.},
   keywords = {Adult
Humans
Electronic Health Records
Case-Control Studies
*Osteoarthritis/epidemiology/diagnosis
Comorbidity
Obesity/epidemiology
*Osteoarthritis, Knee/diagnosis
*Osteoarthritis, Hip/epidemiology
Epidemiology
Osteoarthritis
Primary Care ,
ISSN = 1478-6354 (Print) 1478-6354 ,
DOI = 10.1186/s13075-023-03086-8},
   year = {2023},
   type = {Journal Article}
}

BACKGROUND: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. METHODS: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. FINDINGS: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. INTERPRETATION: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. FUNDING: None.

@article{RN486,
   author = {Voss, E. A. and Shoaibi, A. and Yin Hui Lai, L. and Blacketer, C. and Alshammari, T. and Makadia, R. and Haynes, K. and Sena, A. G. and Rao, G. and van Sandijk, S. and Fraboulet, C. and Boyer, L. and Le Carrour, T. and Horban, S. and Morales, D. R. and Martínez Roldán, J. and Ramírez-Anguita, J. M. and Mayer, M. A. and de Wilde, M. and John, L. H. and Duarte-Salles, T. and Roel, E. and Pistillo, A. and Kolde, R. and Maljković, F. and Denaxas, S. and Papez, V. and Kahn, M. G. and Natarajan, K. and Reich, C. and Secora, A. and Minty, E. P. and Shah, N. H. and Posada, J. D. and Garcia Morales, M. T. and Bosca, D. and Cadenas Juanino, H. and Diaz Holgado, A. and Pedrera Jiménez, M. and Serrano Balazote, P. and García Barrio, N. and Şen, S. and Üresin, A. Y. and Erdogan, B. and Belmans, L. and Byttebier, G. and Malbrain, Mlng and Dedman, D. J. and Cuccu, Z. and Vashisht, R. and Butte, A. J. and Patel, A. and Dahm, L. and Han, C. and Bu, F. and Arshad, F. and Ostropolets, A. and Nyberg, F. and Hripcsak, G. and Suchard, M. A. and Prieto-Alhambra, D. and Rijnbeek, P. R. and Schuemie, M. J. and Ryan, P. B.},
   title = {Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study},
   journal = {EClinicalMedicine},
   volume = {58},
   pages = {101932},
   note = {2589-5370 Voss, Erica A Shoaibi, Azza Yin Hui Lai, Lana Blacketer, Clair Alshammari, Thamir Makadia, Rupa Haynes, Kevin Sena, Anthony G Rao, Gowtham van Sandijk, Sebastiaan Fraboulet, Clement Boyer, Laurent Le Carrour, Tanguy Horban, Scott Morales, Daniel R Martínez Roldán, Jordi Ramírez-Anguita, Juan Manuel Mayer, Miguel A de Wilde, Marcel John, Luis H Duarte-Salles, Talita Roel, Elena Pistillo, Andrea Kolde, Raivo Maljković, Filip Denaxas, Spiros Papez, Vaclav Kahn, Michael G Natarajan, Karthik Reich, Christian Secora, Alex Minty, Evan P Shah, Nigam H Posada, Jose D Garcia Morales, Maria Teresa Bosca, Diego Cadenas Juanino, Honorio Diaz Holgado, Antonio Pedrera Jiménez, Miguel Serrano Balazote, Pablo García Barrio, Noelia Şen, Selçuk Üresin, Ali Yağız Erdogan, Baris Belmans, Luc Byttebier, Geert Malbrain, Manu L N G Dedman, Daniel J Cuccu, Zara Vashisht, Rohit Butte, Atul J Patel, Ayan Dahm, Lisa Han, Cora Bu, Fan Arshad, Faaizah Ostropolets, Anna Nyberg, Fredrik Hripcsak, George Suchard, Marc A Prieto-Alhambra, Dani Rijnbeek, Peter R Schuemie, Martijn J Ryan, Patrick B Journal Article England 2023/04/11 EClinicalMedicine. 2023 Apr;58:101932. doi: 10.1016/j.eclinm.2023.101932. Epub 2023 Apr 4.},
   abstract = {BACKGROUND: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. METHODS: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. FINDINGS: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. INTERPRETATION: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. FUNDING: None.},
   keywords = {Adverse events of special interest
Covid-19
Omop cdm
Observational research ,
ISSN = 2589-5370 ,
DOI = 10.1016/j.eclinm.2023.101932},
   year = {2023},
   type = {Journal Article}
}

BACKGROUND: Recognising acute appendicitis in children presenting with acute abdominal pain in primary care is challenging. General practitioners (GPs) may benefit from a clinical prediction rule. OBJECTIVES: To develop and validate a clinical prediction rule for acute appendicitis in children presenting with acute abdominal pain in primary care. METHODS: In a historical cohort study data was retrieved from GP electronic health records included in the Integrated Primary Care Information database. We assigned children aged 4-18 years presenting with acute abdominal pain (≤ 7 days) to development (2010-2012) and validation (2013-2016) cohorts, using acute appendicitis within six weeks as the outcome. Multiple logistic regression was used to develop a prediction model based on predictors with > 50% data availability derived from existing rules for secondary care. We performed internal and external temporal validation and derived a point score to stratify risk of appendicitis into three groups, i.e. low-risk, medium-risk and high-risk. RESULTS: The development and validation cohorts included 2,041 and 3,650 children, of whom 95 (4.6%) and 195 (5.3%) had acute appendicitis. The model included male sex, pain duration ( 48 h), nausea/vomiting, elevated temperature (≥ 37.3 °C), abnormal bowel sounds, right lower quadrant tenderness, and peritoneal irritation. Internal and temporal validation showed good discrimination (C-statistics: 0.93 and 0.90, respectively) and excellent calibration. In the three groups, the risks of acute appendicitis were 0.5%, 7.5%, and 41%. CONCLUSION: Combined with further testing in the medium-risk group, the prediction rule could improve clinical decision making and outcomes.

@article{RN274,
   author = {Blok, G. and Burger, H. and van der Lei, J. and Berger, M. and Holtman, G.},
   title = {Development and validation of a clinical prediction rule for acute appendicitis in children in primary care},
   journal = {Eur J Gen Pract},
   volume = {29},
   number = {1},
   pages = {2233053},
   note = {1751-1402 Blok, Guus Orcid: 0000-0003-1654-6844 Burger, Huib Orcid: 0000-0001-6484-0349 van der Lei, Johan Orcid: 0000-0002-9203-3410 Berger, Marjolein Orcid: 0000-0001-6774-5961 Holtman, Gea Orcid: 0000-0001-6579-767x Journal Article England 2023/08/14 Eur J Gen Pract. 2023 Dec;29(1):2233053. doi: 10.1080/13814788.2023.2233053.},
   abstract = {BACKGROUND: Recognising acute appendicitis in children presenting with acute abdominal pain in primary care is challenging. General practitioners (GPs) may benefit from a clinical prediction rule. OBJECTIVES: To develop and validate a clinical prediction rule for acute appendicitis in children presenting with acute abdominal pain in primary care. METHODS: In a historical cohort study data was retrieved from GP electronic health records included in the Integrated Primary Care Information database. We assigned children aged 4-18 years presenting with acute abdominal pain (≤ 7 days) to development (2010-2012) and validation (2013-2016) cohorts, using acute appendicitis within six weeks as the outcome. Multiple logistic regression was used to develop a prediction model based on predictors with > 50% data availability derived from existing rules for secondary care. We performed internal and external temporal validation and derived a point score to stratify risk of appendicitis into three groups, i.e. low-risk, medium-risk and high-risk. RESULTS: The development and validation cohorts included 2,041 and 3,650 children, of whom 95 (4.6%) and 195 (5.3%) had acute appendicitis. The model included male sex, pain duration (<24, 24-48, > 48 h), nausea/vomiting, elevated temperature (≥ 37.3 °C), abnormal bowel sounds, right lower quadrant tenderness, and peritoneal irritation. Internal and temporal validation showed good discrimination (C-statistics: 0.93 and 0.90, respectively) and excellent calibration. In the three groups, the risks of acute appendicitis were 0.5%, 7.5%, and 41%. CONCLUSION: Combined with further testing in the medium-risk group, the prediction rule could improve clinical decision making and outcomes.},
   keywords = {Humans
Male
Child
*Clinical Decision Rules
Cohort Studies
*Appendicitis/diagnosis
Abdominal Pain/diagnosis/etiology
Acute Disease
Primary Health Care
Appendicitis
abdominal pain
clinical prediction rule ,
ISSN = 1381-4788 (Print) 1381-4788 ,
DOI = 10.1080/13814788.2023.2233053},
   year = {2023},
   type = {Journal Article}
}

INTRODUCTION: Ranitidine, a histamine H(2)-receptor antagonist (H(2)RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives. OBJECTIVES: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications. METHODS: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H(2)RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H(2)RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders). RESULTS: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18-74 years. Ranitidine was the most commonly prescribed H(2)RA in the pre-referral period (September 2017-August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3-3.8/1000 PY was observed in the referral period (September 2019-March 2020), eventually dropping to 0.0-0.4/1000 PY in the post-referral period (April 2020-March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time. CONCLUSIONS: Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs.

@article{RN260,
   author = {Arinze, J. T. and de Ridder, M. A. J. and Vojinovic, D. and van Ballegooijen, H. and Markov, E. and Duarte-Salles, T. and Rijnbeek, P. and Verhamme, K. M. C.},
   title = {Drug Utilisation Patterns of Alternatives to Ranitidine-Containing Medicines in Patients Treated with Ranitidine: A Network Analysis of Data from Six European National Databases},
   journal = {Drug Saf},
   volume = {46},
   number = {12},
   pages = {1353-1362},
   note = {1179-1942 Arinze, Johnmary T Orcid: 0000-0002-4981-6823 de Ridder, Maria A J Vojinovic, Dina van Ballegooijen, Hanne Markov, Emanuil Duarte-Salles, Talita Rijnbeek, Peter Verhamme, Katia M C Journal Article New Zealand 2023/11/01 Drug Saf. 2023 Dec;46(12):1353-1362. doi: 10.1007/s40264-023-01354-9. Epub 2023 Oct 31.},
   abstract = {INTRODUCTION: Ranitidine, a histamine H(2)-receptor antagonist (H(2)RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives. OBJECTIVES: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications. METHODS: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H(2)RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H(2)RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders). RESULTS: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18-74 years. Ranitidine was the most commonly prescribed H(2)RA in the pre-referral period (September 2017-August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3-3.8/1000 PY was observed in the referral period (September 2019-March 2020), eventually dropping to 0.0-0.4/1000 PY in the post-referral period (April 2020-March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time. CONCLUSIONS: Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs.},
   keywords = {Humans
Female
Male
*Ranitidine/adverse effects
Retrospective Studies
Cohort Studies
*Histamine H2 Antagonists/adverse effects
Proton Pump Inhibitors/adverse effects
Drug Utilization ,
ISSN = 0114-5916 (Print) 0114-5916 ,
DOI = 10.1007/s40264-023-01354-9},
   year = {2023},
   type = {Journal Article}
}

We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. PURPOSE: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. METHODS: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. RESULTS: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52-73% at 6 months to 29-53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50-66% at 6 months and decreased to 30-44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40-73% and decreased to 25-59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50-85% (6 month), 30-63% (12 month) and with teriparatide 40-75% (6 month) decreasing to 21-54% (12 month). Switching occurred most frequently in the alendronate group (2.8-5.8%) and in the teriparatide group (7.1-14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. CONCLUSION: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare.

@article{RN432,
   author = {Tan, E. H. and Robinson, D. E. and Jödicke, A. M. and Mosseveld, M. and Bødkergaard, K. and Reyes, C. and Moayyeri, A. and Voss, A. and Marconi, E. and Lapi, F. and Reinold, J. and Verhamme, K. M. C. and Pedersen, L. and Braitmaier, M. and de Wilde, M. and Ruiz, M. F. and Aragón, M. and Bosco-Levy, P. and Lassalle, R. and Prieto-Alhambra, D. and Sanchez-Santos, M. T.},
   title = {Drug utilization analysis of osteoporosis medications in seven European electronic health databases},
   journal = {Osteoporos Int},
   volume = {34},
   number = {10},
   pages = {1771-1781},
   note = {1433-2965 Tan, Eng Hooi Robinson, Danielle E Jödicke, Annika M Mosseveld, Mees Bødkergaard, Katrine Reyes, Carlen Moayyeri, Alireza Voss, Annemarie Marconi, Ettore Lapi, Francesco Reinold, Jonas Verhamme, Katia M C Pedersen, Lars Braitmaier, Malte de Wilde, Marcel Ruiz, Marc Far Aragón, María Bosco-Levy, Pauline Lassalle, Regis Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Sanchez-Santos, Maria T Journal Article England 2023/07/12 Osteoporos Int. 2023 Oct;34(10):1771-1781. doi: 10.1007/s00198-023-06837-0. Epub 2023 Jul 12.},
   abstract = {We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. PURPOSE: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. METHODS: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. RESULTS: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52-73% at 6 months to 29-53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50-66% at 6 months and decreased to 30-44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40-73% and decreased to 25-59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50-85% (6 month), 30-63% (12 month) and with teriparatide 40-75% (6 month) decreasing to 21-54% (12 month). Switching occurred most frequently in the alendronate group (2.8-5.8%) and in the teriparatide group (7.1-14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. CONCLUSION: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare.},
   keywords = {Adult
Humans
Female
Male
Alendronate/therapeutic use
*Bone Density Conservation Agents/therapeutic use
Teriparatide/therapeutic use
Denosumab/therapeutic use
Cohort Studies
Selective Estrogen Receptor Modulators
*Osteoporosis/drug therapy
Diphosphonates/therapeutic use
Drug Utilization
Electronics
*Osteoporosis, Postmenopausal/drug therapy
Anabolic drug
Anti-resorptive drug
Osteoporosis
Persistence
Switching ,
ISSN = 0937-941X (Print) 0937-941x ,
DOI = 10.1007/s00198-023-06837-0},
   year = {2023},
   type = {Journal Article}
}

OBJECTIVE: Health data standardized to a common data model (CDM) simplifies and facilitates research. This study examines the factors that make standardizing observational health data to the Observational Medical Outcomes Partnership (OMOP) CDM successful. MATERIALS AND METHODS: Twenty-five data partners (DPs) from 11 countries received funding from the European Health Data Evidence Network (EHDEN) to standardize their data. Three surveys, DataQualityDashboard results, and statistics from the conversion process were analyzed qualitatively and quantitatively. Our measures of success were the total number of days to transform source data into the OMOP CDM and participation in network research. RESULTS: The health data converted to CDM represented more than 133 million patients. 100%, 88%, and 84% of DPs took Surveys 1, 2, and 3. The median duration of the 6 key extract, transform, and load (ETL) processes ranged from 4 to 115 days. Of the 25 DPs, 21 DPs were considered applicable for analysis of which 52% standardized their data on time, and 48% participated in an international collaborative study. DISCUSSION: This study shows that the consistent workflow used by EHDEN proves appropriate to support the successful standardization of observational data across Europe. Over the 25 successful transformations, we confirmed that getting the right people for the ETL is critical and vocabulary mapping requires specific expertise and support of tools. Additionally, we learned that teams that proactively prepared for data governance issues were able to avoid considerable delays improving their ability to finish on time. CONCLUSION: This study provides guidance for future DPs to standardize to the OMOP CDM and participate in distributed networks. We demonstrate that the Observational Health Data Sciences and Informatics community must continue to evaluate and provide guidance and support for what ultimately develops the backbone of how community members generate evidence.

@article{RN485,
   author = {Voss, E. A. and Blacketer, C. and van Sandijk, S. and Moinat, M. and Kallfelz, M. and van Speybroeck, M. and Prieto-Alhambra, D. and Schuemie, M. J. and Rijnbeek, P. R.},
   title = {European Health Data & Evidence Network-learnings from building out a standardized international health data network},
   journal = {J Am Med Inform Assoc},
   volume = {31},
   number = {1},
   pages = {209-219},
   note = {1527-974x Voss, Erica A Orcid: 0000-0002-0651-0613 Blacketer, Clair Orcid: 0000-0003-2570-2124 van Sandijk, Sebastiaan Moinat, Maxim Kallfelz, Michael van Speybroeck, Michel Prieto-Alhambra, Daniel Schuemie, Martijn J Rijnbeek, Peter R Journal Article Observational Study England 2023/11/12 J Am Med Inform Assoc. 2023 Dec 22;31(1):209-219. doi: 10.1093/jamia/ocad214.},
   abstract = {OBJECTIVE: Health data standardized to a common data model (CDM) simplifies and facilitates research. This study examines the factors that make standardizing observational health data to the Observational Medical Outcomes Partnership (OMOP) CDM successful. MATERIALS AND METHODS: Twenty-five data partners (DPs) from 11 countries received funding from the European Health Data Evidence Network (EHDEN) to standardize their data. Three surveys, DataQualityDashboard results, and statistics from the conversion process were analyzed qualitatively and quantitatively. Our measures of success were the total number of days to transform source data into the OMOP CDM and participation in network research. RESULTS: The health data converted to CDM represented more than 133 million patients. 100%, 88%, and 84% of DPs took Surveys 1, 2, and 3. The median duration of the 6 key extract, transform, and load (ETL) processes ranged from 4 to 115 days. Of the 25 DPs, 21 DPs were considered applicable for analysis of which 52% standardized their data on time, and 48% participated in an international collaborative study. DISCUSSION: This study shows that the consistent workflow used by EHDEN proves appropriate to support the successful standardization of observational data across Europe. Over the 25 successful transformations, we confirmed that getting the right people for the ETL is critical and vocabulary mapping requires specific expertise and support of tools. Additionally, we learned that teams that proactively prepared for data governance issues were able to avoid considerable delays improving their ability to finish on time. CONCLUSION: This study provides guidance for future DPs to standardize to the OMOP CDM and participate in distributed networks. We demonstrate that the Observational Health Data Sciences and Informatics community must continue to evaluate and provide guidance and support for what ultimately develops the backbone of how community members generate evidence.},
   keywords = {Humans
*Global Health
Databases, Factual
Europe
*Medicine
Electronic Health Records
OMOP common data model
data standardization
observational data ,
ISSN = 1067-5027 (Print) 1067-5027 ,
DOI = 10.1093/jamia/ocad214},
   year = {2023},
   type = {Journal Article}
}

OBJECTIVE: Developing accurate phenotype definitions is critical in obtaining reliable and reproducible background rates in safety research. This study aims to illustrate the differences in background incidence rates by comparing definitions for a given outcome. MATERIALS AND METHODS: We used 16 data sources to systematically generate and evaluate outcomes for 13 adverse events and their overall background rates. We examined the effect of different modifications (inpatient setting, standardization of code set, and code set changes) to the computable phenotype on background incidence rates. RESULTS: Rate ratios (RRs) of the incidence rates from each computable phenotype definition varied across outcomes, with inpatient restriction showing the highest variation from 1 to 11.93. Standardization of code set RRs ranges from 1 to 1.64, and code set changes range from 1 to 2.52. DISCUSSION: The modification that has the highest impact is requiring inpatient place of service, leading to at least a 2-fold higher incidence rate in the base definition. Standardization showed almost no change when using source code variations. The strength of the effect in the inpatient restriction is highly dependent on the outcome. Changing definitions from broad to narrow showed the most variability by age/gender/database across phenotypes and less than a 2-fold increase in rate compared to the base definition. CONCLUSION: Characterization of outcomes across a network of databases yields insights into sensitivity and specificity trade-offs when definitions are altered. Outcomes should be thoroughly evaluated prior to use for background rates for their plausibility for use across a global network.

@article{RN357,
   author = {Makadia, R. and Shoaibi, A. and Rao, G. A. and Ostropolets, A. and Rijnbeek, P. R. and Voss, E. A. and Duarte-Salles, T. and Ramírez-Anguita, J. M. and Mayer, M. A. and Maljković, F. and Denaxas, S. and Nyberg, F. and Papez, V. and Sena, A. G. and Alshammari, T. M. and Lai, L. Y. H. and Haynes, K. and Suchard, M. A. and Hripcsak, G. and Ryan, P. B.},
   title = {Evaluating the impact of alternative phenotype definitions on incidence rates across a global data network},
   journal = {JAMIA Open},
   volume = {6},
   number = {4},
   pages = {ooad096},
   note = {2574-2531 Makadia, Rupa Shoaibi, Azza Rao, Gowtham A Ostropolets, Anna Orcid: 0000-0002-0847-6682 Rijnbeek, Peter R Voss, Erica A Orcid: 0000-0002-0651-0613 Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 Ramírez-Anguita, Juan Manuel Mayer, Miguel A Maljković, Filip Denaxas, Spiros Orcid: 0000-0001-9612-7791 Nyberg, Fredrik Orcid: 0000-0003-0892-5668 Papez, Vaclav Orcid: 0000-0002-2123-7993 Sena, Anthony G Orcid: 0000-0001-8630-5347 Alshammari, Thamir M Lai, Lana Y H Haynes, Kevin Suchard, Marc A Orcid: 0000-0001-9818-479x Hripcsak, George Ryan, Patrick B Journal Article United States 2023/11/29 JAMIA Open. 2023 Nov 21;6(4):ooad096. doi: 10.1093/jamiaopen/ooad096. eCollection 2023 Dec.},
   abstract = {OBJECTIVE: Developing accurate phenotype definitions is critical in obtaining reliable and reproducible background rates in safety research. This study aims to illustrate the differences in background incidence rates by comparing definitions for a given outcome. MATERIALS AND METHODS: We used 16 data sources to systematically generate and evaluate outcomes for 13 adverse events and their overall background rates. We examined the effect of different modifications (inpatient setting, standardization of code set, and code set changes) to the computable phenotype on background incidence rates. RESULTS: Rate ratios (RRs) of the incidence rates from each computable phenotype definition varied across outcomes, with inpatient restriction showing the highest variation from 1 to 11.93. Standardization of code set RRs ranges from 1 to 1.64, and code set changes range from 1 to 2.52. DISCUSSION: The modification that has the highest impact is requiring inpatient place of service, leading to at least a 2-fold higher incidence rate in the base definition. Standardization showed almost no change when using source code variations. The strength of the effect in the inpatient restriction is highly dependent on the outcome. Changing definitions from broad to narrow showed the most variability by age/gender/database across phenotypes and less than a 2-fold increase in rate compared to the base definition. CONCLUSION: Characterization of outcomes across a network of databases yields insights into sensitivity and specificity trade-offs when definitions are altered. Outcomes should be thoroughly evaluated prior to use for background rates for their plausibility for use across a global network.},
   keywords = {algorithms
electronic health record
incidence study
phenotype ,
ISSN = 2574-2531 ,
DOI = 10.1093/jamiaopen/ooad096},
   year = {2023},
   type = {Journal Article}
}

OBJECTIVE: Developing accurate phenotype definitions is critical in obtaining reliable and reproducible background rates in safety research. This study aims to illustrate the differences in background incidence rates by comparing definitions for a given outcome. MATERIALS AND METHODS: We used 16 data sources to systematically generate and evaluate outcomes for 13 adverse events and their overall background rates. We examined the effect of different modifications (inpatient setting, standardization of code set, and code set changes) to the computable phenotype on background incidence rates. RESULTS: Rate ratios (RRs) of the incidence rates from each computable phenotype definition varied across outcomes, with inpatient restriction showing the highest variation from 1 to 11.93. Standardization of code set RRs ranges from 1 to 1.64, and code set changes range from 1 to 2.52. DISCUSSION: The modification that has the highest impact is requiring inpatient place of service, leading to at least a 2-fold higher incidence rate in the base definition. Standardization showed almost no change when using source code variations. The strength of the effect in the inpatient restriction is highly dependent on the outcome. Changing definitions from broad to narrow showed the most variability by age/gender/database across phenotypes and less than a 2-fold increase in rate compared to the base definition. CONCLUSION: Characterization of outcomes across a network of databases yields insights into sensitivity and specificity trade-offs when definitions are altered. Outcomes should be thoroughly evaluated prior to use for background rates for their plausibility for use across a global network.

@article{RN358,
   author = {Makadia, R. and Shoaibi, A. and Rao, G. A. and Ostropolets, A. and Rijnbeek, P. R. and Voss, E. A. and Duarte-Salles, T. and Ramírez-Anguita, J. M. and Mayer, M. A. and Maljković, F. and Denaxas, S. and Nyberg, F. and Papez, V. and Sena, A. G. and Alshammari, T. M. and Lai, L. Y. H. and Haynes, K. and Suchard, M. A. and Hripcsak, G. and Ryan, P. B.},
   title = {Evaluating the impact of alternative phenotype definitions on incidence rates across a global data network},
   journal = {JAMIA Open},
   volume = {6},
   number = {4},
   pages = {ooad096},
   note = {2574-2531 Makadia, Rupa Shoaibi, Azza Rao, Gowtham A Ostropolets, Anna Orcid: 0000-0002-0847-6682 Rijnbeek, Peter R Voss, Erica A Orcid: 0000-0002-0651-0613 Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 Ramírez-Anguita, Juan Manuel Mayer, Miguel A Maljković, Filip Denaxas, Spiros Orcid: 0000-0001-9612-7791 Nyberg, Fredrik Orcid: 0000-0003-0892-5668 Papez, Vaclav Orcid: 0000-0002-2123-7993 Sena, Anthony G Orcid: 0000-0001-8630-5347 Alshammari, Thamir M Lai, Lana Y H Haynes, Kevin Suchard, Marc A Orcid: 0000-0001-9818-479x Hripcsak, George Ryan, Patrick B MC_PC_20030/MRC_/Medical Research Council/United Kingdom MC_PC_20051/MRC_/Medical Research Council/United Kingdom MC_PC_20059/MRC_/Medical Research Council/United Kingdom Journal Article United States 2023/11/29 JAMIA Open. 2023 Nov 21;6(4):ooad096. doi: 10.1093/jamiaopen/ooad096. eCollection 2023 Dec.},
   abstract = {OBJECTIVE: Developing accurate phenotype definitions is critical in obtaining reliable and reproducible background rates in safety research. This study aims to illustrate the differences in background incidence rates by comparing definitions for a given outcome. MATERIALS AND METHODS: We used 16 data sources to systematically generate and evaluate outcomes for 13 adverse events and their overall background rates. We examined the effect of different modifications (inpatient setting, standardization of code set, and code set changes) to the computable phenotype on background incidence rates. RESULTS: Rate ratios (RRs) of the incidence rates from each computable phenotype definition varied across outcomes, with inpatient restriction showing the highest variation from 1 to 11.93. Standardization of code set RRs ranges from 1 to 1.64, and code set changes range from 1 to 2.52. DISCUSSION: The modification that has the highest impact is requiring inpatient place of service, leading to at least a 2-fold higher incidence rate in the base definition. Standardization showed almost no change when using source code variations. The strength of the effect in the inpatient restriction is highly dependent on the outcome. Changing definitions from broad to narrow showed the most variability by age/gender/database across phenotypes and less than a 2-fold increase in rate compared to the base definition. CONCLUSION: Characterization of outcomes across a network of databases yields insights into sensitivity and specificity trade-offs when definitions are altered. Outcomes should be thoroughly evaluated prior to use for background rates for their plausibility for use across a global network.},
   keywords = {algorithms
electronic health record
incidence study
phenotype},
   ISSN = {2574-2531},
   DOI = {10.1093/jamiaopen/ooad096},
   year = {2023},
   type = {Journal Article}
}

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

@article{RN413,
   author = {Sing, C. W. and Lin, T. C. and Bartholomew, S. and Bell, J. S. and Bennett, C. and Beyene, K. and Bosco-Levy, P. and Bradbury, B. D. and Chan, A. H. Y. and Chandran, M. and Cooper, C. and de Ridder, M. and Doyon, C. Y. and Droz-Perroteau, C. and Ganesan, G. and Hartikainen, S. and Ilomaki, J. and Jeong, H. E. and Kiel, D. P. and Kubota, K. and Lai, E. C. and Lange, J. L. and Lewiecki, E. M. and Lin, J. and Liu, J. and Maskell, J. and de Abreu, M. M. and O'Kelly, J. and Ooba, N. and Pedersen, A. B. and Prats-Uribe, A. and Prieto-Alhambra, D. and Qin, S. X. and Shin, J. Y. and Sørensen, H. T. and Tan, K. B. and Thomas, T. and Tolppanen, A. M. and Verhamme, K. M. C. and Wang, G. H. and Watcharathanakij, S. and Wood, S. J. and Cheung, C. L. and Wong, I. C. K.},
   title = {Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality},
   journal = {J Bone Miner Res},
   volume = {38},
   number = {8},
   pages = {1064-1075},
   note = {1523-4681 Sing, Chor-Wing Orcid: 0000-0002-2180-3676 Lin, Tzu-Chieh Bartholomew, Sharon Bell, J Simon Bennett, Corina Beyene, Kebede Bosco-Levy, Pauline Bradbury, Brian D Chan, Amy Hai Yan Chandran, Manju Cooper, Cyrus Orcid: 0000-0003-3510-0709 de Ridder, Maria Doyon, Caroline Y Droz-Perroteau, Cécile Ganesan, Ganga Hartikainen, Sirpa Ilomaki, Jenni Jeong, Han Eol Kiel, Douglas P Orcid: 0000-0001-8474-0310 Kubota, Kiyoshi Lai, Edward Chia-Cheng Lange, Jeff L Lewiecki, E Michael Orcid: 0000-0003-2026-9587 Lin, Julian Liu, Jiannong Maskell, Joe de Abreu, Mirhelen Mendes O'Kelly, James Ooba, Nobuhiro Pedersen, Alma B Orcid: 0000-0002-3288-9401 Prats-Uribe, Albert Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Qin, Simon Xiwen Shin, Ju-Young Orcid: 0000-0002-2791-1037 Sørensen, Henrik T Tan, Kelvin Bryan Thomas, Tracy Tolppanen, Anna-Maija Verhamme, Katia M C Wang, Grace Hsin-Min Watcharathanakij, Sawaeng Wood, Stephen J Cheung, Ching-Lung Orcid: 0000-0002-6233-9144 Wong, Ian C K Journal Article Research Support, Non-U.S. Gov't United States 2023/04/29 J Bone Miner Res. 2023 Aug;38(8):1064-1075. doi: 10.1002/jbmr.4821. Epub 2023 May 29.},
   abstract = {In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).},
   keywords = {Male
Female
Humans
Middle Aged
Aged
Incidence
*Hip Fractures/drug therapy/epidemiology
*Osteoporosis/drug therapy
*Osteoporotic Fractures/epidemiology
Diphosphonates/therapeutic use
Epidemiology
Fracture prevention
Hip fracture
Mortality
Osteoporosis ,
ISSN = 0884-0431 ,
DOI = 10.1002/jbmr.4821},
   year = {2023},
   type = {Journal Article}
}

OBJECTIVE: To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA). DESIGN: A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9% confidence intervals (CI). RESULTS: The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR

@article{RN339,
   author = {Kamps, A. and Runhaar, J. and de Ridder, M. A. J. and de Wilde, M. and van der Lei, J. and Zhang, W. and Prieto-Alhambra, D. and Englund, M. and de Schepper, E. I. T. and Bierma-Zeinstra, S. M. A.},
   title = {Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the Netherlands},
   journal = {Osteoarthritis Cartilage},
   volume = {31},
   number = {4},
   pages = {519-528},
   note = {1522-9653 Kamps, A Runhaar, J de Ridder, M A J de Wilde, M van der Lei, J Zhang, W Prieto-Alhambra, D Englund, M de Schepper, E I T Bierma-Zeinstra, S M A Journal Article Research Support, Non-U.S. Gov't England 2022/12/18 Osteoarthritis Cartilage. 2023 Apr;31(4):519-528. doi: 10.1016/j.joca.2022.12.003. Epub 2022 Dec 15.},
   abstract = {OBJECTIVE: To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA). DESIGN: A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9% confidence intervals (CI). RESULTS: The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR < 1 was found, other comorbidities showed no association with exposure to knee OA. For 26 comorbidities, exposure to hip OA showed a HR larger than 1. The largest were found for polymyalgia rheumatica 1.81 (1.41-2.32) and fibromyalgia 1.70 (1.10-2.63). All other comorbidities showed no associations with hip OA. CONCLUSION: This study showed that many comorbidities were diagnosed more often in patients with knee or hip OA. This suggests that the management of OA should consider the risk of other long-term-conditions.},
   keywords = {Adult
Humans
Cohort Studies
*Osteoarthritis, Hip/diagnosis/epidemiology
*Fibromyalgia/diagnosis/epidemiology
Netherlands/epidemiology
*Osteoarthritis, Knee/diagnosis/epidemiology
Comorbidity
Electronic health record (EHR)
Osteoarthritis
Primary care ,
ISSN = 1063-4584 ,
DOI = 10.1016/j.joca.2022.12.003},
   year = {2023},
   type = {Journal Article}
}

INTRODUCTION: Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals. OBJECTIVE: The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process. METHODS: Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals. RESULTS: Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15-60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development. CONCLUSIONS: Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost-benefit of integrating these analyses at this stage of signal management requires further research.

@article{RN316,
   author = {Gauffin, O. and Brand, J. S. and Vidlin, S. H. and Sartori, D. and Asikainen, S. and Català, M. and Chalabi, E. and Dedman, D. and Danilovic, A. and Duarte-Salles, T. and García Morales, M. T. and Hiltunen, S. and Jödicke, A. M. and Lazarevic, M. and Mayer, M. A. and Miladinovic, J. and Mitchell, J. and Pistillo, A. and Ramírez-Anguita, J. M. and Reyes, C. and Rudolph, A. and Sandberg, L. and Savage, R. and Schuemie, M. and Spasic, D. and Trinh, N. T. H. and Veljkovic, N. and Vujovic, A. and de Wilde, M. and Zekarias, A. and Rijnbeek, P. and Ryan, P. and Prieto-Alhambra, D. and Norén, G. N.},
   title = {Supporting Pharmacovigilance Signal Validation and Prioritization with Analyses of Routinely Collected Health Data: Lessons Learned from an EHDEN Network Study},
   journal = {Drug Saf},
   volume = {46},
   number = {12},
   pages = {1335-1352},
   note = {1179-1942 Gauffin, Oskar Orcid: 0000-0003-1593-356x Brand, Judith S Orcid: 0000-0002-3720-1274 Vidlin, Sara Hedfors Orcid: 0000-0003-1619-3751 Sartori, Daniele Orcid: 0000-0003-3634-0317 Asikainen, Suvi Català, Martí Chalabi, Etir Dedman, Daniel Danilovic, Ana Duarte-Salles, Talita García Morales, Maria Teresa Hiltunen, Saara Jödicke, Annika M Lazarevic, Milan Mayer, Miguel A Miladinovic, Jelena Mitchell, Joseph Pistillo, Andrea Ramírez-Anguita, Juan Manuel Reyes, Carlen Rudolph, Annette Sandberg, Lovisa Savage, Ruth Schuemie, Martijn Spasic, Dimitrije Trinh, Nhung T H Veljkovic, Nevena Vujovic, Ankica de Wilde, Marcel Zekarias, Alem Rijnbeek, Peter Ryan, Patrick Prieto-Alhambra, Daniel Norén, G Niklas Orcid: 0000-0002-4595-230x No 806968/Innovative Medicines Initiative (IMI)/ Journal Article New Zealand 2023/10/07 Drug Saf. 2023 Dec;46(12):1335-1352. doi: 10.1007/s40264-023-01353-w. Epub 2023 Oct 7.},
   abstract = {INTRODUCTION: Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals. OBJECTIVE: The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process. METHODS: Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals. RESULTS: Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15-60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development. CONCLUSIONS: Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost-benefit of integrating these analyses at this stage of signal management requires further research.},
   keywords = {Humans
*Pharmacovigilance
Adverse Drug Reaction Reporting Systems
*Drug-Related Side Effects and Adverse Reactions/epidemiology
Databases, Factual
Netherlands ,
ISSN = 0114-5916 (Print) 0114-5916 ,
DOI = 10.1007/s40264-023-01353-w},
   year = {2023},
   type = {Journal Article}
}

INTRODUCTION: Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals. OBJECTIVE: The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process. METHODS: Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals. RESULTS: Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15-60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development. CONCLUSIONS: Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost-benefit of integrating these analyses at this stage of signal management requires further research.

@article{RN317,
   author = {Gauffin, O. and Brand, J. S. and Vidlin, S. H. and Sartori, D. and Asikainen, S. and Català, M. and Chalabi, E. and Dedman, D. and Danilovic, A. and Duarte-Salles, T. and García Morales, M. T. and Hiltunen, S. and Jödicke, A. M. and Lazarevic, M. and Mayer, M. A. and Miladinovic, J. and Mitchell, J. and Pistillo, A. and Ramírez-Anguita, J. M. and Reyes, C. and Rudolph, A. and Sandberg, L. and Savage, R. and Schuemie, M. and Spasic, D. and Trinh, N. T. H. and Veljkovic, N. and Vujovic, A. and de Wilde, M. and Zekarias, A. and Rijnbeek, P. and Ryan, P. and Prieto-Alhambra, D. and Norén, G. N.},
   title = {Supporting Pharmacovigilance Signal Validation and Prioritization with Analyses of Routinely Collected Health Data: Lessons Learned from an EHDEN Network Study},
   journal = {Drug Saf},
   volume = {46},
   number = {12},
   pages = {1335-1352},
   note = {1179-1942 Gauffin, Oskar Orcid: 0000-0003-1593-356x Brand, Judith S Orcid: 0000-0002-3720-1274 Vidlin, Sara Hedfors Orcid: 0000-0003-1619-3751 Sartori, Daniele Orcid: 0000-0003-3634-0317 Asikainen, Suvi Català, Martí Chalabi, Etir Dedman, Daniel Danilovic, Ana Duarte-Salles, Talita García Morales, Maria Teresa Hiltunen, Saara Jödicke, Annika M Lazarevic, Milan Mayer, Miguel A Miladinovic, Jelena Mitchell, Joseph Pistillo, Andrea Ramírez-Anguita, Juan Manuel Reyes, Carlen Rudolph, Annette Sandberg, Lovisa Savage, Ruth Schuemie, Martijn Spasic, Dimitrije Trinh, Nhung T H Veljkovic, Nevena Vujovic, Ankica de Wilde, Marcel Zekarias, Alem Rijnbeek, Peter Ryan, Patrick Prieto-Alhambra, Daniel Norén, G Niklas Orcid: 0000-0002-4595-230x No 806968/Innovative Medicines Initiative (IMI)/ Journal Article New Zealand 2023/10/07 Drug Saf. 2023 Dec;46(12):1335-1352. doi: 10.1007/s40264-023-01353-w. Epub 2023 Oct 7.},
   abstract = {INTRODUCTION: Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals. OBJECTIVE: The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process. METHODS: Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals. RESULTS: Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15-60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development. CONCLUSIONS: Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost-benefit of integrating these analyses at this stage of signal management requires further research.},
   keywords = {Humans
*Pharmacovigilance
Adverse Drug Reaction Reporting Systems
*Drug-Related Side Effects and Adverse Reactions/epidemiology
Databases, Factual
Netherlands},
   ISSN = {0114-5916 (Print) 0114-5916},
   DOI = {10.1007/s40264-023-01353-w},
   year = {2023},
   type = {Journal Article}
}

OBJECTIVE: This work aims to explore the value of Dutch unstructured data, in combination with structured data, for the development of prognostic prediction models in a general practitioner (GP) setting. MATERIALS AND METHODS: We trained and validated prediction models for 4 common clinical prediction problems using various sparse text representations, common prediction algorithms, and observational GP electronic health record (EHR) data. We trained and validated 84 models internally and externally on data from different EHR systems. RESULTS: On average, over all the different text representations and prediction algorithms, models only using text data performed better or similar to models using structured data alone in 2 prediction tasks. Additionally, in these 2 tasks, the combination of structured and text data outperformed models using structured or text data alone. No large performance differences were found between the different text representations and prediction algorithms. DISCUSSION: Our findings indicate that the use of unstructured data alone can result in well-performing prediction models for some clinical prediction problems. Furthermore, the performance improvement achieved by combining structured and text data highlights the added value. Additionally, we demonstrate the significance of clinical natural language processing research in languages other than English and the possibility of validating text-based prediction models across various EHR systems. CONCLUSION: Our study highlights the potential benefits of incorporating unstructured data in clinical prediction models in a GP setting. Although the added value of unstructured data may vary depending on the specific prediction task, our findings suggest that it has the potential to enhance patient care.

@article{RN408,
   author = {Seinen, T. M. and Kors, J. A. and van Mulligen, E. M. and Fridgeirsson, E. and Rijnbeek, P. R.},
   title = {The added value of text from Dutch general practitioner notes in predictive modeling},
   journal = {J Am Med Inform Assoc},
   volume = {30},
   number = {12},
   pages = {1973-1984},
   note = {1527-974x Seinen, Tom M Orcid: 0000-0001-5369-8260 Kors, Jan A van Mulligen, Erik M Fridgeirsson, Egill Rijnbeek, Peter R European Health Data & Evidence Network/ 806968/Innovative Medicines Initiative 2 Joint Undertaking/ European Union's Horizon 2020/ Journal Article England 2023/08/17 J Am Med Inform Assoc. 2023 Nov 17;30(12):1973-1984. doi: 10.1093/jamia/ocad160.},
   abstract = {OBJECTIVE: This work aims to explore the value of Dutch unstructured data, in combination with structured data, for the development of prognostic prediction models in a general practitioner (GP) setting. MATERIALS AND METHODS: We trained and validated prediction models for 4 common clinical prediction problems using various sparse text representations, common prediction algorithms, and observational GP electronic health record (EHR) data. We trained and validated 84 models internally and externally on data from different EHR systems. RESULTS: On average, over all the different text representations and prediction algorithms, models only using text data performed better or similar to models using structured data alone in 2 prediction tasks. Additionally, in these 2 tasks, the combination of structured and text data outperformed models using structured or text data alone. No large performance differences were found between the different text representations and prediction algorithms. DISCUSSION: Our findings indicate that the use of unstructured data alone can result in well-performing prediction models for some clinical prediction problems. Furthermore, the performance improvement achieved by combining structured and text data highlights the added value. Additionally, we demonstrate the significance of clinical natural language processing research in languages other than English and the possibility of validating text-based prediction models across various EHR systems. CONCLUSION: Our study highlights the potential benefits of incorporating unstructured data in clinical prediction models in a GP setting. Although the added value of unstructured data may vary depending on the specific prediction task, our findings suggest that it has the potential to enhance patient care.},
   keywords = {Humans
*General Practitioners
Electronic Health Records
Language
Algorithms
Software
Natural Language Processing
clinical prediction model
machine learning
prognostic prediction ,
ISSN = 1067-5027 (Print) 1067-5027 ,
DOI = 10.1093/jamia/ocad160},
   year = {2023},
   type = {Journal Article}
}

BACKGROUND: The diagnostic value of C-reactive protein (CRP) for appendicitis in children has not been evaluated in primary care. As biochemical responses and differential diagnoses vary with age, separate evaluation in children and adults is needed. OBJECTIVES: To determine whether adding CRP to symptoms and signs improves the diagnosis of appendicitis in children with acute abdominal pain in primary care. METHODS: A retrospective cohort study in Dutch general practice. Data was collected from the Integrated Primary Care Information database between 2010 and 2016. We included children aged 4-18 years, with no history of appendicitis, presenting with acute abdominal pain, and having a CRP test. Initial CRP levels were related to the specialist's diagnosis of appendicitis, and the test's characteristics were calculated for multiple cut-offs. The value of adding CRP to signs and symptoms was analysed by logistic regression. RESULTS: We identified 1076 eligible children, among whom 203 were referred for specialist evaluation and 70 had appendicitis. The sensitivity and specificity of a CRP cut-off ≥10 mg/L were 0.87 (95%CI, 0.77-0.94) and 0.77 (95%CI, 0.74-0.79), respectively. When symptoms lasted > 48 h, this sensitivity increased to 1.00. Positive predictive values for CRP alone were low (0.18-0.38) for all cut-off values (6-100 mg/L). Adding CRP increased the area under the curve from 0.82 (95%CI, 0.78-0.87) to 0.88 (95%CI, 0.84-0.91), and decision curve analysis confirmed that its addition provided the highest net benefit. CONCLUSION: CRP adds value to history and physical examination when diagnosing appendicitis in children presenting acute abdominal pain in primary care. Appendicitis is least likely if the CRP value is < 10 mg/L and symptoms have been present for > 48 h.

@article{RN275,
   author = {Blok, Gcgh and Nikkels, E. D. and van der Lei, J. and Berger, M. Y. and Holtman, G. A.},
   title = {Added value of CRP to clinical features when assessing appendicitis in children},
   journal = {Eur J Gen Pract},
   volume = {28},
   number = {1},
   pages = {95-101},
   note = {1751-1402 Blok, Guus C G H Orcid: 0000-0003-1654-6844 Nikkels, Eelke D van der Lei, Johan Orcid: 0000-0002-9203-3410 Berger, Marjolein Y Orcid: 0000-0001-9906-3666 Holtman, Gea A Orcid: 0000-0001-6579-767x Journal Article England 2022/05/11 Eur J Gen Pract. 2022 Dec;28(1):95-101. doi: 10.1080/13814788.2022.2067142.},
   abstract = {BACKGROUND: The diagnostic value of C-reactive protein (CRP) for appendicitis in children has not been evaluated in primary care. As biochemical responses and differential diagnoses vary with age, separate evaluation in children and adults is needed. OBJECTIVES: To determine whether adding CRP to symptoms and signs improves the diagnosis of appendicitis in children with acute abdominal pain in primary care. METHODS: A retrospective cohort study in Dutch general practice. Data was collected from the Integrated Primary Care Information database between 2010 and 2016. We included children aged 4-18 years, with no history of appendicitis, presenting with acute abdominal pain, and having a CRP test. Initial CRP levels were related to the specialist's diagnosis of appendicitis, and the test's characteristics were calculated for multiple cut-offs. The value of adding CRP to signs and symptoms was analysed by logistic regression. RESULTS: We identified 1076 eligible children, among whom 203 were referred for specialist evaluation and 70 had appendicitis. The sensitivity and specificity of a CRP cut-off ≥10 mg/L were 0.87 (95%CI, 0.77-0.94) and 0.77 (95%CI, 0.74-0.79), respectively. When symptoms lasted > 48 h, this sensitivity increased to 1.00. Positive predictive values for CRP alone were low (0.18-0.38) for all cut-off values (6-100 mg/L). Adding CRP increased the area under the curve from 0.82 (95%CI, 0.78-0.87) to 0.88 (95%CI, 0.84-0.91), and decision curve analysis confirmed that its addition provided the highest net benefit. CONCLUSION: CRP adds value to history and physical examination when diagnosing appendicitis in children presenting acute abdominal pain in primary care. Appendicitis is least likely if the CRP value is < 10 mg/L and symptoms have been present for > 48 h.},
   keywords = {Abdominal Pain/diagnosis/etiology
Acute Disease
Adolescent
*Appendicitis/diagnosis
*C-Reactive Protein/analysis
Child
Child, Preschool
Humans
Leukocyte Count
Retrospective Studies
Sensitivity and Specificity
C-reactive protein
Primary health care
abdominal pain
appendicitis
point-of-care testing ,
ISSN = 1381-4788 (Print) 1381-4788 ,
DOI = 10.1080/13814788.2022.2067142},
   year = {2022},
   type = {Journal Article}
}

@article{RN280,
   author = {Burn, E. and Li, X. and Kostka, K. and Stewart, H. M. and Reich, C. and Seager, S. and Duarte-Salles, T. and Fernandez-Bertolin, S. and Aragón, M. and Reyes, C. and Martinez-Hernandez, E. and Marti, E. and Delmestri, A. and Verhamme, K. and Rijnbeek, P. and Horban, S. and Morales, D. R. and Prieto-Alhambra, D.},
   title = {Background rates of five thrombosis with thrombocytopenia syndromes of special interest for COVID-19 vaccine safety surveillance: Incidence between 2017 and 2019 and patient profiles from 38.6 million people in six European countries},
   journal = {Pharmacoepidemiol Drug Saf},
   volume = {31},
   number = {5},
   pages = {495-510},
   note = {1099-1557 Burn, Edward Orcid: 0000-0002-9286-1128 Li, Xintong Orcid: 0000-0002-6872-5804 Kostka, Kristin Orcid: 0000-0003-2595-8736 Stewart, Henry Morgan Reich, Christian Orcid: 0000-0002-3641-055x Seager, Sarah Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 Fernandez-Bertolin, Sergio Orcid: 0000-0002-0029-6564 Aragón, María Reyes, Carlen Martinez-Hernandez, Eugenia Orcid: 0000-0002-8317-7068 Marti, Edelmira Orcid: 0000-0002-5678-2916 Delmestri, Antonella Orcid: 0000-0003-0388-3403 Verhamme, Katia Orcid: 0000-0001-8162-4904 Rijnbeek, Peter Orcid: 0000-0003-0621-1979 Horban, Scott Morales, Daniel R Orcid: 0000-0002-0063-8069 Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Journal Article Research Support, Non-U.S. Gov't England 2022/02/23 Pharmacoepidemiol Drug Saf. 2022 May;31(5):495-510. doi: 10.1002/pds.5419. Epub 2022 Feb 27.},
   keywords = {*COVID-19/epidemiology/prevention & control
COVID-19 Vaccines/adverse effects
Humans
Incidence
Syndrome
*Thrombocytopenia/chemically induced/epidemiology
*Thrombosis/epidemiology
Covid-19
post vaccine
thrombosis-thrombocytopenia syndromes (TTS)
vaccine ,
ISSN = 1053-8569 (Print) 1053-8569 ,
DOI = 10.1002/pds.5419},
   year = {2022},
   type = {Journal Article}
}

BACKGROUND AND OBJECTIVES: Although there is evidence of disruption in acute cerebrovascular and cardiovascular care during the coronavirus disease 2019 (COVID-19) pandemic, its downstream effect in primary care is less clear. We investigated how the pandemic affected utilization of cerebrovascular and cardiovascular care in general practices (GPs) and determined changes in GP-recorded diagnoses of selected cerebrovascular and cardiovascular outcomes. METHODS: From electronic health records of 166,929 primary care patients aged 30 or over within the Rotterdam region, the Netherlands, we extracted the number of consultations related to cerebrovascular and cardiovascular care, and first diagnoses of selected cerebrovascular and cardiovascular risk factors (hypertension, diabetes, lipid disorders), conditions, and events (angina, atrial fibrillation, TIA, myocardial infarction, stroke). We quantified changes in those outcomes during the first COVID-19 wave (March-May 2020) and thereafter (June-December 2020) by comparing them to the same period in 2016-2019. We also estimated the number of potentially missed diagnoses for each outcome. RESULTS: The number of GP consultations related to cerebrovascular and cardiovascular care declined by 38% (0.62, 95% confidence interval 0.56-0.68) during the first wave, as compared to expected counts based on prepandemic levels. Substantial declines in the number of new diagnoses were observed for cerebrovascular events: 37% for TIA (0.63, 0.41-0.96) and 29% for stroke (0.71, 0.59-0.84), while no significant changes were observed for cardiovascular events (myocardial infarction [0.91, 0.74-1.14], angina [0.77, 0.48-1.25]). The counts across individual diagnoses recovered following June 2020, but the number of GP consultations related to cerebrovascular and cardiovascular care remained lower than expected throughout the June to December period (0.93, 0.88-0.98). DISCUSSION: While new diagnoses of acute cardiovascular events remained stable during the COVID-19 pandemic, diagnoses of cerebrovascular events declined substantially compared to prepandemic levels, possibly due to incorrect perception of risk by patients. These findings emphasize the need to improve symptom recognition of cerebrovascular events among the general public and to encourage urgent presentation despite any physical distancing measures.

@article{RN467,
   author = {Velek, P. and Splinter, M. J. and Ikram, M. K. and Ikram, M. A. and Leening, M. J. G. and van der Lei, J. and Olde Hartman, T. and Peters, L. L. and Tange, H. and Rutten, F. H. and van Weert, H. and Wolters, F. J. and Bindels, P. J. E. and Licher, S. and de Schepper, E. I. T.},
   title = {Changes in the Diagnosis of Stroke and Cardiovascular Conditions in Primary Care During the First 2 COVID-19 Waves in the Netherlands},
   journal = {Neurology},
   volume = {98},
   number = {6},
   pages = {e564-e572},
   note = {1526-632x Velek, Premysl Splinter, Marije J Ikram, M Kamran Ikram, M Arfan Leening, Maarten J G Orcid: 0000-0002-4143-4839 van der Lei, Johan Olde Hartman, Tim Peters, Lilian L Tange, Huibert Rutten, Frans H van Weert, Henk Orcid: 0000-0001-6370-4724 Wolters, Frank J Orcid: 0000-0003-2226-4050 Bindels, Patrick J E Licher, Silvan de Schepper, Evelien I T Journal Article Research Support, Non-U.S. Gov't United States 2021/12/31 Neurology. 2022 Feb 8;98(6):e564-e572. doi: 10.1212/WNL.0000000000013145. Epub 2021 Dec 29.},
   abstract = {BACKGROUND AND OBJECTIVES: Although there is evidence of disruption in acute cerebrovascular and cardiovascular care during the coronavirus disease 2019 (COVID-19) pandemic, its downstream effect in primary care is less clear. We investigated how the pandemic affected utilization of cerebrovascular and cardiovascular care in general practices (GPs) and determined changes in GP-recorded diagnoses of selected cerebrovascular and cardiovascular outcomes. METHODS: From electronic health records of 166,929 primary care patients aged 30 or over within the Rotterdam region, the Netherlands, we extracted the number of consultations related to cerebrovascular and cardiovascular care, and first diagnoses of selected cerebrovascular and cardiovascular risk factors (hypertension, diabetes, lipid disorders), conditions, and events (angina, atrial fibrillation, TIA, myocardial infarction, stroke). We quantified changes in those outcomes during the first COVID-19 wave (March-May 2020) and thereafter (June-December 2020) by comparing them to the same period in 2016-2019. We also estimated the number of potentially missed diagnoses for each outcome. RESULTS: The number of GP consultations related to cerebrovascular and cardiovascular care declined by 38% (0.62, 95% confidence interval 0.56-0.68) during the first wave, as compared to expected counts based on prepandemic levels. Substantial declines in the number of new diagnoses were observed for cerebrovascular events: 37% for TIA (0.63, 0.41-0.96) and 29% for stroke (0.71, 0.59-0.84), while no significant changes were observed for cardiovascular events (myocardial infarction [0.91, 0.74-1.14], angina [0.77, 0.48-1.25]). The counts across individual diagnoses recovered following June 2020, but the number of GP consultations related to cerebrovascular and cardiovascular care remained lower than expected throughout the June to December period (0.93, 0.88-0.98). DISCUSSION: While new diagnoses of acute cardiovascular events remained stable during the COVID-19 pandemic, diagnoses of cerebrovascular events declined substantially compared to prepandemic levels, possibly due to incorrect perception of risk by patients. These findings emphasize the need to improve symptom recognition of cerebrovascular events among the general public and to encourage urgent presentation despite any physical distancing measures.},
   keywords = {Adult
*COVID-19/epidemiology
*Cardiovascular Diseases/diagnosis
Humans
Netherlands/epidemiology
Pandemics
*Primary Health Care/statistics & numerical data
*Stroke/diagnosis ,
ISSN = 0028-3878 (Print) 0028-3878 ,
DOI = 10.1212/wnl.0000000000013145},
   year = {2022},
   type = {Journal Article}
}

Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients. Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.

@article{RN370,
   author = {Moreno-Martos, D. and Verhamme, K. and Ostropolets, A. and Kostka, K. and Duarte-Sales, T. and Prieto-Alhambra, D. and Alshammari, T. M. and Alghoul, H. and Ahmed, W. U. and Blacketer, C. and DuVall, S. and Lai, L. and Matheny, M. and Nyberg, F. and Posada, J. and Rijnbeek, P. and Spotnitz, M. and Sena, A. and Shah, N. and Suchard, M. and Chan You, S. and Hripcsak, G. and Ryan, P. and Morales, D.},
   title = {Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe},
   journal = {Wellcome Open Res},
   volume = {7},
   pages = {22},
   note = {2398-502x Moreno-Martos, David Orcid: 0000-0002-8652-6235 Verhamme, Katia Ostropolets, Anna Orcid: 0000-0002-0847-6682 Kostka, Kristin Duarte-Sales, Talita Prieto-Alhambra, Daniel Alshammari, Thamir M Alghoul, Heba Orcid: 0000-0001-8234-5843 Ahmed, Waheed-Ul-Rahman Blacketer, Clair DuVall, Scott Lai, Lana Matheny, Michael Nyberg, Fredrik Orcid: 0000-0003-0892-5668 Posada, Jose Orcid: 0000-0003-3864-0241 Rijnbeek, Peter Spotnitz, Matthew Orcid: 0000-0003-2869-0237 Sena, Anthony Shah, Nigam Suchard, Marc Orcid: 0000-0001-9818-479x Chan You, Seng Orcid: 0000-0002-5052-6399 Hripcsak, George Ryan, Patrick Morales, Daniel Orcid: 0000-0002-0063-8069 Journal Article England 2023/03/01 Wellcome Open Res. 2022 Mar 24;7:22. doi: 10.12688/wellcomeopenres.17403.2. eCollection 2022.},
   abstract = {Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.},
   keywords = {Copd
Covid
SARS-CoV-2
coronavirus
epidemiology. ,
ISSN = 2398-502X (Print) 2398-502x ,
DOI = 10.12688/wellcomeopenres.17403.2},
   year = {2022},
   type = {Journal Article}
}

BACKGROUND: Asthma can occur at any age but the differences in patient characteristics between childhood-, adult-, and late-onset asthma are not well understood. OBJECTIVE: To investigate differences in patients' characteristics by age at asthma onset. METHODS: From 5 European electronic databases, we created a cohort encompassing adult patients with doctor-diagnosed asthma in 2008 to 2013. Patients were categorized based on their age at asthma onset: childhood-onset (age at onset < 18 y), adult-onset (age at onset 18-40 y), and late-onset asthma (age at onset ≥ 40 y). Comorbidities were assessed at study entry. For each characteristic and comorbidity, odds ratios and age- and sex-adjusted odds ratios (OR(adj)) comparing asthma-onset categories were estimated per database and combined in a meta-analysis using a random effect model. RESULTS: In total, 586,436 adult asthma patients were included, 81,691 had childhood-onset, 218,184 adult-onset, and 286,561 late-onset asthma. Overall, 7.3% had severe asthma. Subjects with adult-onset compared with childhood-asthma had higher risks for overweight/obesity (OR(adj) 1.4; 95% CI 1.1-1.8) and lower risks for atopic disorders (OR(adj) 0.8; 95% CI 0.7-0.95). Patients with late-onset compared with adult-onset asthma had higher risks for nasal polyposis (OR(adj) 1.8; 95% CI 1.2-2.6), overweight/obesity (OR(adj) 1.3; 95% CI 1.2-1.4), gastroesophageal reflux disease (OR(adj) 1.4; 95% CI 1.2-1.7), and diabetes (OR(adj) 2.3; 95% CI 1.8-2.9). A significant association between late-onset asthma and uncontrolled asthma was observed (OR(adj) 2.8; 95% CI 1.7-4.5). CONCLUSIONS: This international study demonstrates clear differences in comorbidities between childhood-, adult-, and late-onset asthma phenotypes in adults. Furthermore, patients with late-onset asthma had more frequent uncontrolled asthma.

@article{RN264,
   author = {Baan, E. J. and de Roos, E. W. and Engelkes, M. and de Ridder, M. and Pedersen, L. and Berencsi, K. and Prieto-Alhambra, D. and Lapi, F. and Van Dyke, M. K. and Rijnbeek, P. and Brusselle, G. G. and Verhamme, K. M. C.},
   title = {Characterization of Asthma by Age of Onset: A Multi-Database Cohort Study},
   journal = {J Allergy Clin Immunol Pract},
   volume = {10},
   number = {7},
   pages = {1825-1834.e8},
   note = {2213-2201 Baan, Esmé J de Roos, Emmely W Engelkes, Marjolein de Ridder, Maria Pedersen, Lars Berencsi, Klara Prieto-Alhambra, Dani Lapi, Francesco Van Dyke, Melissa K Rijnbeek, Peter Brusselle, Guy G Verhamme, Katia M C Journal Article Meta-Analysis Research Support, Non-U.S. Gov't United States 2022/04/11 J Allergy Clin Immunol Pract. 2022 Jul;10(7):1825-1834.e8. doi: 10.1016/j.jaip.2022.03.019. Epub 2022 Apr 8.},
   abstract = {BACKGROUND: Asthma can occur at any age but the differences in patient characteristics between childhood-, adult-, and late-onset asthma are not well understood. OBJECTIVE: To investigate differences in patients' characteristics by age at asthma onset. METHODS: From 5 European electronic databases, we created a cohort encompassing adult patients with doctor-diagnosed asthma in 2008 to 2013. Patients were categorized based on their age at asthma onset: childhood-onset (age at onset < 18 y), adult-onset (age at onset 18-40 y), and late-onset asthma (age at onset ≥ 40 y). Comorbidities were assessed at study entry. For each characteristic and comorbidity, odds ratios and age- and sex-adjusted odds ratios (OR(adj)) comparing asthma-onset categories were estimated per database and combined in a meta-analysis using a random effect model. RESULTS: In total, 586,436 adult asthma patients were included, 81,691 had childhood-onset, 218,184 adult-onset, and 286,561 late-onset asthma. Overall, 7.3% had severe asthma. Subjects with adult-onset compared with childhood-asthma had higher risks for overweight/obesity (OR(adj) 1.4; 95% CI 1.1-1.8) and lower risks for atopic disorders (OR(adj) 0.8; 95% CI 0.7-0.95). Patients with late-onset compared with adult-onset asthma had higher risks for nasal polyposis (OR(adj) 1.8; 95% CI 1.2-2.6), overweight/obesity (OR(adj) 1.3; 95% CI 1.2-1.4), gastroesophageal reflux disease (OR(adj) 1.4; 95% CI 1.2-1.7), and diabetes (OR(adj) 2.3; 95% CI 1.8-2.9). A significant association between late-onset asthma and uncontrolled asthma was observed (OR(adj) 2.8; 95% CI 1.7-4.5). CONCLUSIONS: This international study demonstrates clear differences in comorbidities between childhood-, adult-, and late-onset asthma phenotypes in adults. Furthermore, patients with late-onset asthma had more frequent uncontrolled asthma.},
   keywords = {Age of Onset
*Asthma/epidemiology
Child
Cohort Studies
Humans
Obesity
*Overweight
Adults
Age at onset
Asthma
Comorbidity
Epidemiology
Exacerbations
General population ,
DOI = 10.1016/j.jaip.2022.03.019},
   year = {2022},
   type = {Journal Article}
}

OBJECTIVE: To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines. DESIGN: International network cohort study. SETTING: Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US. PARTICIPANTS: Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021. MAIN OUTCOME MEASURES: Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses. RESULTS: Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2. CONCLUSIONS: In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.

@article{RN353,
   author = {Li, X. and Burn, E. and Duarte-Salles, T. and Yin, C. and Reich, C. and Delmestri, A. and Verhamme, K. and Rijnbeek, P. and Suchard, M. A. and Li, K. and Mosseveld, M. and John, L. H. and Mayer, M. A. and Ramirez-Anguita, J. M. and Cohet, C. and Strauss, V. and Prieto-Alhambra, D.},
   title = {Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different covid-19 vaccines: international network cohort study from five European countries and the US},
   journal = {Bmj},
   volume = {379},
   pages = {e071594},
   note = {1756-1833 Li, Xintong Orcid: 0000-0002-6872-5804 Burn, Edward Orcid: 0000-0002-9286-1128 Duarte-Salles, Talita Yin, Can Reich, Christian Delmestri, Antonella Verhamme, Katia Rijnbeek, Peter Suchard, Marc A Li, Kelly Mosseveld, Mees John, Luis H Mayer, Miguel-Angel Ramirez-Anguita, Juan-Manuel Cohet, Catherine Strauss, Victoria Prieto-Alhambra, Daniel Journal Article Meta-Analysis England 2022/10/27 BMJ. 2022 Oct 26;379:e071594. doi: 10.1136/bmj-2022-071594.},
   abstract = {OBJECTIVE: To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines. DESIGN: International network cohort study. SETTING: Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US. PARTICIPANTS: Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021. MAIN OUTCOME MEASURES: Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses. RESULTS: Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2. CONCLUSIONS: In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.},
   keywords = {Adolescent
Adult
Humans
Ad26COVS1/adverse effects
BNT162 Vaccine/adverse effects
Cohort Studies
COVID-19/epidemiology/prevention & control
*COVID-19 Vaccines/adverse effects
*Thrombocytopenia/epidemiology
*Thromboembolism/epidemiology
*Thrombosis/epidemiology
Venous Thrombosis/epidemiology ,
ISSN = 0959-8138 (Print) 0959-8138 ,
DOI = 10.1136/bmj-2022-071594},
   year = {2022},
   type = {Journal Article}
}

@article{RN296,
   author = {de Ridder, M. A. J. and de Wilde, M. and de Ben, C. and Leyba, A. R. and Mosseveld, B. M. T. and Verhamme, K. M. C. and van der Lei, J. and Rijnbeek, P. R.},
   title = {Data Resource Profile: The Integrated Primary Care Information (IPCI) database, The Netherlands},
   journal = {Int J Epidemiol},
   volume = {51},
   number = {6},
   pages = {e314-e323},
   note = {1464-3685 de Ridder, Maria A J Orcid: 0000-0002-6555-2741 de Wilde, Marcel de Ben, Christina Leyba, Armando R Mosseveld, Bartholomeus M T Verhamme, Katia M C van der Lei, Johan Rijnbeek, Peter R Journal Article Research Support, Non-U.S. Gov't England 2022/02/20 Int J Epidemiol. 2022 Dec 13;51(6):e314-e323. doi: 10.1093/ije/dyac026.},
   keywords = {Humans
Netherlands/epidemiology
Databases, Factual
*Primary Health Care ,
ISSN = 0300-5771 (Print) 0300-5771 ,
DOI = 10.1093/ije/dyac026},
   year = {2022},
   type = {Journal Article}
}

BACKGROUND: Identification of rheumatoid arthritis (RA) patients at high risk of adverse health outcomes remains a major challenge. We aimed to develop and validate prediction models for a variety of adverse health outcomes in RA patients initiating first-line methotrexate (MTX) monotherapy. METHODS: Data from 15 claims and electronic health record databases across 9 countries were used. Models were developed and internally validated on Optum® De-identified Clinformatics® Data Mart Database using L1-regularized logistic regression to estimate the risk of adverse health outcomes within 3 months (leukopenia, pancytopenia, infection), 2 years (myocardial infarction (MI) and stroke), and 5 years (cancers [colorectal, breast, uterine] after treatment initiation. Candidate predictors included demographic variables and past medical history. Models were externally validated on all other databases. Performance was assessed using the area under the receiver operator characteristic curve (AUC) and calibration plots. FINDINGS: Models were developed and internally validated on 21,547 RA patients and externally validated on 131,928 RA patients. Models for serious infection (AUC: internal 0.74, external ranging from 0.62 to 0.83), MI (AUC: internal 0.76, external ranging from 0.56 to 0.82), and stroke (AUC: internal 0.77, external ranging from 0.63 to 0.95), showed good discrimination and adequate calibration. Models for the other outcomes showed modest internal discrimination (AUC < 0.65) and were not externally validated. INTERPRETATION: We developed and validated prediction models for a variety of adverse health outcomes in RA patients initiating first-line MTX monotherapy. Final models for serious infection, MI, and stroke demonstrated good performance across multiple databases and can be studied for clinical use. FUNDING: This activity under the European Health Data & Evidence Network (EHDEN) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.

@article{RN494,
   author = {Yang, C. and Williams, R. D. and Swerdel, J. N. and Almeida, J. R. and Brouwer, E. S. and Burn, E. and Carmona, L. and Chatzidionysiou, K. and Duarte-Salles, T. and Fakhouri, W. and Hottgenroth, A. and Jani, M. and Kolde, R. and Kors, J. A. and Kullamaa, L. and Lane, J. and Marinier, K. and Michel, A. and Stewart, H. M. and Prats-Uribe, A. and Reisberg, S. and Sena, A. G. and Torre, C. O. and Verhamme, K. and Vizcaya, D. and Weaver, J. and Ryan, P. and Prieto-Alhambra, D. and Rijnbeek, P. R.},
   title = {Development and external validation of prediction models for adverse health outcomes in rheumatoid arthritis: A multinational real-world cohort analysis},
   journal = {Semin Arthritis Rheum},
   volume = {56},
   pages = {152050},
   note = {1532-866x Yang, Cynthia Williams, Ross D Swerdel, Joel N Almeida, João Rafael Brouwer, Emily S Burn, Edward Carmona, Loreto Chatzidionysiou, Katerina Duarte-Salles, Talita Fakhouri, Walid Hottgenroth, Antje Jani, Meghna Kolde, Raivo Kors, Jan A Kullamaa, Lembe Lane, Jennifer Marinier, Karine Michel, Alexander Stewart, Henry Morgan Prats-Uribe, Albert Reisberg, Sulev Sena, Anthony G Torre, Carmen O Verhamme, Katia Vizcaya, David Weaver, James Ryan, Patrick Prieto-Alhambra, Daniel Rijnbeek, Peter R 21605/VAC_/Versus Arthritis/United Kingdom DH_/Department of Health/United Kingdom Journal Article Research Support, Non-U.S. Gov't United States 2022/06/22 Semin Arthritis Rheum. 2022 Oct;56:152050. doi: 10.1016/j.semarthrit.2022.152050. Epub 2022 Jun 15.},
   abstract = {BACKGROUND: Identification of rheumatoid arthritis (RA) patients at high risk of adverse health outcomes remains a major challenge. We aimed to develop and validate prediction models for a variety of adverse health outcomes in RA patients initiating first-line methotrexate (MTX) monotherapy. METHODS: Data from 15 claims and electronic health record databases across 9 countries were used. Models were developed and internally validated on Optum® De-identified Clinformatics® Data Mart Database using L1-regularized logistic regression to estimate the risk of adverse health outcomes within 3 months (leukopenia, pancytopenia, infection), 2 years (myocardial infarction (MI) and stroke), and 5 years (cancers [colorectal, breast, uterine] after treatment initiation. Candidate predictors included demographic variables and past medical history. Models were externally validated on all other databases. Performance was assessed using the area under the receiver operator characteristic curve (AUC) and calibration plots. FINDINGS: Models were developed and internally validated on 21,547 RA patients and externally validated on 131,928 RA patients. Models for serious infection (AUC: internal 0.74, external ranging from 0.62 to 0.83), MI (AUC: internal 0.76, external ranging from 0.56 to 0.82), and stroke (AUC: internal 0.77, external ranging from 0.63 to 0.95), showed good discrimination and adequate calibration. Models for the other outcomes showed modest internal discrimination (AUC < 0.65) and were not externally validated. INTERPRETATION: We developed and validated prediction models for a variety of adverse health outcomes in RA patients initiating first-line MTX monotherapy. Final models for serious infection, MI, and stroke demonstrated good performance across multiple databases and can be studied for clinical use. FUNDING: This activity under the European Health Data & Evidence Network (EHDEN) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.},
   keywords = {*Antirheumatic Agents/therapeutic use
*Arthritis, Rheumatoid/drug therapy
Cohort Studies
Humans
Methotrexate/therapeutic use
Outcome Assessment, Health Care
*Stroke/etiology
Cardiovascular diseases
Infections
Methotrexate
Prediction models
Rheumatoid arthritis ,
ISSN = 0049-0172 ,
DOI = 10.1016/j.semarthrit.2022.152050},
   year = {2022},
   type = {Journal Article}
}

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare but disabling disorder that often requires long-term immunomodulatory treatment. Background incidence rates and prevalence and risk factors for developing CIDP are still poorly defined. In the current study, we used a longitudinal population-based cohort study in The Netherlands to assess these rates and demographic factors and comorbidity associated with CIDP. We determined the incidence rate and prevalence of CIDP between 2008 and 2017 and the occurrence of potential risk factors in a retrospective Dutch cohort study using the Integrated Primary Care Information (IPCI) database. Cases were defined as CIDP if the diagnosis of CIDP was described in the electronic medical file. In a source population of 928 030 persons with a contributing follow-up of 3 525 686 person-years, we identified 65 patients diagnosed with CIDP. The overall incidence rate was 0.68 per 100 000 person-years (95% CI 0.45-0.99). The overall prevalence was 7.00 per 100 000 individuals (95% CI 5.41-8.93). The overall incidence rate was higher in men compared to woman (IRR 3.00, 95% CI 1.27-7.11), and higher in elderly of 50 years or older compared with people

@article{RN277,
   author = {Broers, M. C. and de Wilde, M. and Lingsma, H. F. and van der Lei, J. and Verhamme, K. M. C. and Jacobs, B. C.},
   title = {Epidemiology of chronic inflammatory demyelinating polyradiculoneuropathy in The Netherlands},
   journal = {J Peripher Nerv Syst},
   volume = {27},
   number = {3},
   pages = {182-188},
   note = {1529-8027 Broers, Merel C Orcid: 0000-0002-7770-8475 de Wilde, Marcel Lingsma, Hester F van der Lei, Johan Verhamme, Katia M C Jacobs, Bart C Case Reports Research Support, Non-U.S. Gov't United States 2022/05/15 J Peripher Nerv Syst. 2022 Sep;27(3):182-188. doi: 10.1111/jns.12502. Epub 2022 May 29.},
   abstract = {Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare but disabling disorder that often requires long-term immunomodulatory treatment. Background incidence rates and prevalence and risk factors for developing CIDP are still poorly defined. In the current study, we used a longitudinal population-based cohort study in The Netherlands to assess these rates and demographic factors and comorbidity associated with CIDP. We determined the incidence rate and prevalence of CIDP between 2008 and 2017 and the occurrence of potential risk factors in a retrospective Dutch cohort study using the Integrated Primary Care Information (IPCI) database. Cases were defined as CIDP if the diagnosis of CIDP was described in the electronic medical file. In a source population of 928 030 persons with a contributing follow-up of 3 525 686 person-years, we identified 65 patients diagnosed with CIDP. The overall incidence rate was 0.68 per 100 000 person-years (95% CI 0.45-0.99). The overall prevalence was 7.00 per 100 000 individuals (95% CI 5.41-8.93). The overall incidence rate was higher in men compared to woman (IRR 3.00, 95% CI 1.27-7.11), and higher in elderly of 50 years or older compared with people <50 years of age (IRR 17 95% CI 4-73). Twenty percent of CIDP cases had DM and 9% a co-existing other auto-immune disease. These background rates are important to monitor changes in the frequency of CIDP following infectious disease outbreaks, identify potential risk factors, and to estimate the social and economic burden of CIDP.},
   keywords = {Aged
Cohort Studies
Female
Humans
Incidence
Male
Netherlands/epidemiology
*Polyradiculoneuropathy, Chronic Inflammatory
Demyelinating/diagnosis/epidemiology
Retrospective Studies
Cidp
chronic inflammatory demyelinating polyradiculoneuropathy
epidemiology
prevalence ,
ISSN = 1085-9489 (Print) 1085-9489 ,
DOI = 10.1111/jns.12502},
   year = {2022},
   type = {Journal Article}
}

OBJECTIVE: To determine the incidence and prevalence of hip osteoarthritis (OA) in electronic health records (EHRs) of Dutch general practices by using narrative and codified data. METHOD: A retrospective cohort study was conducted using the Integrated Primary Care Information database. An algorithm was developed to identify patients with narratively diagnosed hip OA in addition to patients with codified hip OA. Incidence and prevalence estimates among people aged ≥30 were assessed from 2008 to 2019. The association of comorbidities with codified hip OA diagnosis was analysed using multivariable logistic regression. RESULTS: Using the hip OA narrative data algorithm (positive predicted value = 72%) in addition to codified hip OA showed a prevalence of 1.76-1.95 times higher and increased from 4.03% in 2008 to 7.34% in 2019. The incidence was 1.83-2.41 times higher and increased from 6.83 to 7.78 per 1000 person-years from 2008 to 2019. Among codified hip OA patients, 39.4% had a previous record of narratively diagnosed hip OA, on average approximately 1.93 years earlier. Hip OA patients with a previous record of spinal OA, knee OA, hypertension, and hyperlipidaemia were more likely to be recorded with a hip OA code. CONCLUSION: This study using Dutch EHRs showed that epidemiological estimates of hip OA are likely to be an underestimation. Using our algorithm, narrative data can be added to codified data for more realistic epidemiological estimates based on routine healthcare data. However, developing a valid algorithm remains a challenge, possibly due to the diagnostic complexity of hip pain in general practice.

@article{RN261,
   author = {Arslan, I. G. and Damen, J. and de Wilde, M. and van den Driest, J. J. and Bindels, P. J. E. and van der Lei, J. and Bierma-Zeinstra, S. M. A. and Schiphof, D.},
   title = {Estimating incidence and prevalence of hip osteoarthritis using electronic health records: a population-based cohort study},
   journal = {Osteoarthritis Cartilage},
   volume = {30},
   number = {6},
   pages = {843-851},
   note = {1522-9653 Arslan, I G Damen, J de Wilde, M van den Driest, J J Bindels, P J E van der Lei, J Bierma-Zeinstra, S M A Schiphof, D Journal Article England 2022/03/22 Osteoarthritis Cartilage. 2022 Jun;30(6):843-851. doi: 10.1016/j.joca.2022.03.001. Epub 2022 Mar 18.},
   abstract = {OBJECTIVE: To determine the incidence and prevalence of hip osteoarthritis (OA) in electronic health records (EHRs) of Dutch general practices by using narrative and codified data. METHOD: A retrospective cohort study was conducted using the Integrated Primary Care Information database. An algorithm was developed to identify patients with narratively diagnosed hip OA in addition to patients with codified hip OA. Incidence and prevalence estimates among people aged ≥30 were assessed from 2008 to 2019. The association of comorbidities with codified hip OA diagnosis was analysed using multivariable logistic regression. RESULTS: Using the hip OA narrative data algorithm (positive predicted value = 72%) in addition to codified hip OA showed a prevalence of 1.76-1.95 times higher and increased from 4.03% in 2008 to 7.34% in 2019. The incidence was 1.83-2.41 times higher and increased from 6.83 to 7.78 per 1000 person-years from 2008 to 2019. Among codified hip OA patients, 39.4% had a previous record of narratively diagnosed hip OA, on average approximately 1.93 years earlier. Hip OA patients with a previous record of spinal OA, knee OA, hypertension, and hyperlipidaemia were more likely to be recorded with a hip OA code. CONCLUSION: This study using Dutch EHRs showed that epidemiological estimates of hip OA are likely to be an underestimation. Using our algorithm, narrative data can be added to codified data for more realistic epidemiological estimates based on routine healthcare data. However, developing a valid algorithm remains a challenge, possibly due to the diagnostic complexity of hip pain in general practice.},
   keywords = {Cohort Studies
Electronic Health Records
Humans
Incidence
*Osteoarthritis, Hip
*Osteoarthritis, Knee
Prevalence
Retrospective Studies
Epidemiology
Hip osteoarthritis ,
ISSN = 1063-4584 ,
DOI = 10.1016/j.joca.2022.03.001},
   year = {2022},
   type = {Journal Article}
}

OBJECTIVE: We introduce and review the concept of a study-a-thon as a catalyst for open science in medicine, utilizing harmonized real world, observation health data, tools, skills, and methods to conduct network studies, generating insights for those wishing to use study-a-thons for future research. MATERIALS AND METHODS: A series of historical study-a-thons since 2017 to present were reviewed for thematic insights as to the opportunity to accelerate the research method to conduct studies across therapeutic areas. Review of publications and experience of the authors generated insights to illustrate the conduct of study-a-thons, key learning, and direction for those wishing to conduct future such study-a-thons. RESULTS: A review of six study-a-thons have provided insights into their scientific impact, and 13 areas of insights for those wishing to conduct future study-a-thons. Defining aspects of the study-a-thon method for rapid, collaborative research through network studies reinforce the need to clear scientific rationale, tools, skills, and methods being collaboratively to conduct a focused study. Well-characterized preparatory, execution and postevent phases, coalescing skills, experience, data, clinical input (ensuring representative clinical context to the research query), and well-defined, logical steps in conducting research via the study-a-thon method are critical. CONCLUSIONS: A study-a-thon is a focused multiday research event generating reliable evidence on a specific medical topic across different countries and health systems. In a study-a-thon, a multidisciplinary team collaborate to create an accelerated contribution to scientific evidence and clinical practice. It critically accelerates the research process, without inhibiting the quality of the research output and evidence generation, through a reproducible process.

@article{RN327,
   author = {Hughes, N. and Rijnbeek, P. R. and van Bochove, K. and Duarte-Salles, T. and Steinbeisser, C. and Vizcaya, D. and Prieto-Alhambra, D. and Ryan, P.},
   title = {Evaluating a novel approach to stimulate open science collaborations: a case series of study-a-thon events within the OHDSI and European IMI communities},
   journal = {JAMIA Open},
   volume = {5},
   number = {4},
   pages = {ooac100},
   note = {2574-2531 Hughes, N Orcid: 0000-0002-1168-0537 Rijnbeek, P R van Bochove, K Duarte-Salles, T Orcid: 0000-0002-8274-0357 Steinbeisser, C Vizcaya, D Prieto-Alhambra, D Ryan, P Journal Article United States 2022/11/22 JAMIA Open. 2022 Nov 17;5(4):ooac100. doi: 10.1093/jamiaopen/ooac100. eCollection 2022 Dec.},
   abstract = {OBJECTIVE: We introduce and review the concept of a study-a-thon as a catalyst for open science in medicine, utilizing harmonized real world, observation health data, tools, skills, and methods to conduct network studies, generating insights for those wishing to use study-a-thons for future research. MATERIALS AND METHODS: A series of historical study-a-thons since 2017 to present were reviewed for thematic insights as to the opportunity to accelerate the research method to conduct studies across therapeutic areas. Review of publications and experience of the authors generated insights to illustrate the conduct of study-a-thons, key learning, and direction for those wishing to conduct future such study-a-thons. RESULTS: A review of six study-a-thons have provided insights into their scientific impact, and 13 areas of insights for those wishing to conduct future study-a-thons. Defining aspects of the study-a-thon method for rapid, collaborative research through network studies reinforce the need to clear scientific rationale, tools, skills, and methods being collaboratively to conduct a focused study. Well-characterized preparatory, execution and postevent phases, coalescing skills, experience, data, clinical input (ensuring representative clinical context to the research query), and well-defined, logical steps in conducting research via the study-a-thon method are critical. CONCLUSIONS: A study-a-thon is a focused multiday research event generating reliable evidence on a specific medical topic across different countries and health systems. In a study-a-thon, a multidisciplinary team collaborate to create an accelerated contribution to scientific evidence and clinical practice. It critically accelerates the research process, without inhibiting the quality of the research output and evidence generation, through a reproducible process.},
   keywords = {clinical research
data sciences
epidemiology
observational research
research process ,
ISSN = 2574-2531 ,
DOI = 10.1093/jamiaopen/ooac100},
   year = {2022},
   type = {Journal Article}
}

BACKGROUND: Many dementia prediction models have been developed, but only few have been externally validated, which hinders clinical uptake and may pose a risk if models are applied to actual patients regardless. Externally validating an existing prediction model is a difficult task, where we mostly rely on the completeness of model reporting in a published article. In this study, we aim to externally validate existing dementia prediction models. To that end, we define model reporting criteria, review published studies, and externally validate three well reported models using routinely collected health data from administrative claims and electronic health records. METHODS: We identified dementia prediction models that were developed between 2011 and 2020 and assessed if they could be externally validated given a set of model criteria. In addition, we externally validated three of these models (Walters' Dementia Risk Score, Mehta's RxDx-Dementia Risk Index, and Nori's ADRD dementia prediction model) on a network of six observational health databases from the United States, United Kingdom, Germany and the Netherlands, including the original development databases of the models. RESULTS: We reviewed 59 dementia prediction models. All models reported the prediction method, development database, and target and outcome definitions. Less frequently reported by these 59 prediction models were predictor definitions (52 models) including the time window in which a predictor is assessed (21 models), predictor coefficients (20 models), and the time-at-risk (42 models). The validation of the model by Walters (development c-statistic: 0.84) showed moderate transportability (0.67-0.76 c-statistic). The Mehta model (development c-statistic: 0.81) transported well to some of the external databases (0.69-0.79 c-statistic). The Nori model (development AUROC: 0.69) transported well (0.62-0.68 AUROC) but performed modestly overall. Recalibration showed improvements for the Walters and Nori models, while recalibration could not be assessed for the Mehta model due to unreported baseline hazard. CONCLUSION: We observed that reporting is mostly insufficient to fully externally validate published dementia prediction models, and therefore, it is uncertain how well these models would work in other clinical settings. We emphasize the importance of following established guidelines for reporting clinical prediction models. We recommend that reporting should be more explicit and have external validation in mind if the model is meant to be applied in different settings.

@article{RN335,
   author = {John, L. H. and Kors, J. A. and Fridgeirsson, E. A. and Reps, J. M. and Rijnbeek, P. R.},
   title = {External validation of existing dementia prediction models on observational health data},
   journal = {BMC Med Res Methodol},
   volume = {22},
   number = {1},
   pages = {311},
   note = {1471-2288 John, Luis H Kors, Jan A Fridgeirsson, Egill A Reps, Jenna M Rijnbeek, Peter R Journal Article Research Support, Non-U.S. Gov't Review England 2022/12/06 BMC Med Res Methodol. 2022 Dec 5;22(1):311. doi: 10.1186/s12874-022-01793-5.},
   abstract = {BACKGROUND: Many dementia prediction models have been developed, but only few have been externally validated, which hinders clinical uptake and may pose a risk if models are applied to actual patients regardless. Externally validating an existing prediction model is a difficult task, where we mostly rely on the completeness of model reporting in a published article. In this study, we aim to externally validate existing dementia prediction models. To that end, we define model reporting criteria, review published studies, and externally validate three well reported models using routinely collected health data from administrative claims and electronic health records. METHODS: We identified dementia prediction models that were developed between 2011 and 2020 and assessed if they could be externally validated given a set of model criteria. In addition, we externally validated three of these models (Walters' Dementia Risk Score, Mehta's RxDx-Dementia Risk Index, and Nori's ADRD dementia prediction model) on a network of six observational health databases from the United States, United Kingdom, Germany and the Netherlands, including the original development databases of the models. RESULTS: We reviewed 59 dementia prediction models. All models reported the prediction method, development database, and target and outcome definitions. Less frequently reported by these 59 prediction models were predictor definitions (52 models) including the time window in which a predictor is assessed (21 models), predictor coefficients (20 models), and the time-at-risk (42 models). The validation of the model by Walters (development c-statistic: 0.84) showed moderate transportability (0.67-0.76 c-statistic). The Mehta model (development c-statistic: 0.81) transported well to some of the external databases (0.69-0.79 c-statistic). The Nori model (development AUROC: 0.69) transported well (0.62-0.68 AUROC) but performed modestly overall. Recalibration showed improvements for the Walters and Nori models, while recalibration could not be assessed for the Mehta model due to unreported baseline hazard. CONCLUSION: We observed that reporting is mostly insufficient to fully externally validate published dementia prediction models, and therefore, it is uncertain how well these models would work in other clinical settings. We emphasize the importance of following established guidelines for reporting clinical prediction models. We recommend that reporting should be more explicit and have external validation in mind if the model is meant to be applied in different settings.},
   keywords = {Humans
United Kingdom
Risk Factors
*Dementia/diagnosis/epidemiology
Netherlands/epidemiology
Germany
Prognosis
Alzheimer
Dementia
External validation
Patient-level prediction
Prognostic model
Transportability ,
ISSN = 1471-2288 ,
DOI = 10.1186/s12874-022-01793-5},
   year = {2022},
   type = {Journal Article}
}

OBJECTIVES: Methylphenidate is a 'prescription only' drug against attention disorders which is increasingly used by adults. We investigated whether methylphenidate in adults was associated with an increased risk of psychiatric events such as depression, and suicide attempt and overall mortality. DESIGN: A population-based matched cohort design. SETTING: The Integrated Primary Care Information system, a general practitioners (GP) database in the Netherlands with a source population of 2.5 million inhabitants. PARTICIPANTS: During the study period between 1 June 1996 and 1 January 2018, 8905 adults started methylphenidate and were matched to 10 non-users on sex, age, GP practice and ad prescription date. The total study population consisted of 97 198 participants. MAIN OUTCOME MEASURES: Serious psychiatric events such as depression and suicide attempts, and overall mortality. ANALYSES: Risks of development of each event during the use of methylphenidate were expressed as HR with 95% CI, adjusted for relevant confounders with methylphenidate as a time-dependent determinant. Additional adjustment was performed for the intervention ('intention-to-treat'). RESULTS: Although during follow-up, the unadjusted risks of depression and suicide attempt were strongly increased in users, depression and psychosis became non-significant after adjustment for alcohol-abuse and substance-abuse and psychiatric disease in the medical history and after adjustment for 'intention-to-treat'. However, the risk of suicide attempts remained significantly increased after full adjustment (HR 2.0; 95% CI 1.1 to 3.6), and was highest in women and in participants within the age-group of 18-40 years. The unadjusted risk of overall mortality was strongly increased, but this lowered to a significant 30% risk increase (HR 1.3; 95% CI 1.1 to 1.6) after full adjustment. CONCLUSION: There is an increased risk of suicide attempts in adults up to 40 years of age after starting methylphenidate and this risk should be carefully considered before prescribing to this group.

@article{RN419,
   author = {Stricker, B. and Cheung, K. and Verhamme, K.},
   title = {General practice database on mortality in adults on methylphenidate: cohort study},
   journal = {BMJ Open},
   volume = {12},
   number = {8},
   pages = {e057303},
   note = {2044-6055 Stricker, Bruno Orcid: 0000-0003-3713-9762 Cheung, Kiki Verhamme, Katia Orcid: 0000-0001-8162-4904 Journal Article Research Support, Non-U.S. Gov't England 2022/08/27 BMJ Open. 2022 Aug 26;12(8):e057303. doi: 10.1136/bmjopen-2021-057303.},
   abstract = {OBJECTIVES: Methylphenidate is a 'prescription only' drug against attention disorders which is increasingly used by adults. We investigated whether methylphenidate in adults was associated with an increased risk of psychiatric events such as depression, and suicide attempt and overall mortality. DESIGN: A population-based matched cohort design. SETTING: The Integrated Primary Care Information system, a general practitioners (GP) database in the Netherlands with a source population of 2.5 million inhabitants. PARTICIPANTS: During the study period between 1 June 1996 and 1 January 2018, 8905 adults started methylphenidate and were matched to 10 non-users on sex, age, GP practice and ad prescription date. The total study population consisted of 97 198 participants. MAIN OUTCOME MEASURES: Serious psychiatric events such as depression and suicide attempts, and overall mortality. ANALYSES: Risks of development of each event during the use of methylphenidate were expressed as HR with 95% CI, adjusted for relevant confounders with methylphenidate as a time-dependent determinant. Additional adjustment was performed for the intervention ('intention-to-treat'). RESULTS: Although during follow-up, the unadjusted risks of depression and suicide attempt were strongly increased in users, depression and psychosis became non-significant after adjustment for alcohol-abuse and substance-abuse and psychiatric disease in the medical history and after adjustment for 'intention-to-treat'. However, the risk of suicide attempts remained significantly increased after full adjustment (HR 2.0; 95% CI 1.1 to 3.6), and was highest in women and in participants within the age-group of 18-40 years. The unadjusted risk of overall mortality was strongly increased, but this lowered to a significant 30% risk increase (HR 1.3; 95% CI 1.1 to 1.6) after full adjustment. CONCLUSION: There is an increased risk of suicide attempts in adults up to 40 years of age after starting methylphenidate and this risk should be carefully considered before prescribing to this group.},
   keywords = {Adolescent
Adult
*Attention Deficit Disorder with Hyperactivity
Cohort Studies
Female
*General Practice
Humans
*Methylphenidate
Suicide, Attempted
Young Adult
adverse events
epidemiology
suicide & self-harm ,
ISSN = 2044-6055 ,
DOI = 10.1136/bmjopen-2021-057303},
   year = {2022},
   type = {Journal Article}
}

OBJECTIVE: To determine the incidence and prevalence of knee osteoarthritis (OA) using codified and narrative data from general practices throughout The Netherlands. METHODS: This retrospective cohort study was conducted using the Integrated Primary Care Information database. Patients with codified knee OA were selected, and an algorithm was developed to identify patients with narratively diagnosed knee OA only. Point prevalence proportions and incidence rates among people age ≥30 years were assessed from 2008 to 2019. The association of comorbidities with codified knee OA was analyzed using multivariable logistic regression. RESULTS: The positive predicted value of narratively diagnosed knee OA only was 94.0% (95% confidence interval [95% CI] 87.4-100%) and for codified knee OA 96.0% (95% CI 90.6-100%). Including narrative data in addition to codified data resulted in a prevalence 1.83-2.01 times higher (over the study years); prevalence increased from 5.8% to 11.8% between 2008 and 2019. The incidence rate was 1.93-2.28 times higher and increased from 9.98 per 1,000 person-years to 13.8 per 1,000 person-years between 2008 and 2019. Among patients with codified knee OA, 39.4% were previously diagnosed narratively with knee OA, on average 3 years earlier. Comorbidities influenced the likelihood of being recorded with codified knee OA. CONCLUSION: Our study of a Dutch primary care database showed that current incidence and prevalence estimates based on codified data alone from electronic health records are underestimated. Narrative data can be incorporated in addition to codified data to identify knee OA patients more accurately.

@article{RN262,
   author = {Arslan, I. G. and Damen, J. and de Wilde, M. and van den Driest, J. J. and Bindels, P. J. E. and van der Lei, J. and Schiphof, D. and Bierma-Zeinstra, S. M. A.},
   title = {Incidence and Prevalence of Knee Osteoarthritis Using Codified and Narrative Data From Electronic Health Records: A Population-Based Study},
   journal = {Arthritis Care Res (Hoboken)},
   volume = {74},
   number = {6},
   pages = {937-944},
   note = {2151-4658 Arslan, Ilgin G Orcid: 0000-0003-2046-6177 Damen, Jurgen de Wilde, Marcel van den Driest, Jacoline J Orcid: 0000-0001-9206-5431 Bindels, Patrick J E van der Lei, Johan Schiphof, Dieuwke Bierma-Zeinstra, Sita M A Journal Article United States 2022/01/19 Arthritis Care Res (Hoboken). 2022 Jun;74(6):937-944. doi: 10.1002/acr.24861. Epub 2022 Apr 9.},
   abstract = {OBJECTIVE: To determine the incidence and prevalence of knee osteoarthritis (OA) using codified and narrative data from general practices throughout The Netherlands. METHODS: This retrospective cohort study was conducted using the Integrated Primary Care Information database. Patients with codified knee OA were selected, and an algorithm was developed to identify patients with narratively diagnosed knee OA only. Point prevalence proportions and incidence rates among people age ≥30 years were assessed from 2008 to 2019. The association of comorbidities with codified knee OA was analyzed using multivariable logistic regression. RESULTS: The positive predicted value of narratively diagnosed knee OA only was 94.0% (95% confidence interval [95% CI] 87.4-100%) and for codified knee OA 96.0% (95% CI 90.6-100%). Including narrative data in addition to codified data resulted in a prevalence 1.83-2.01 times higher (over the study years); prevalence increased from 5.8% to 11.8% between 2008 and 2019. The incidence rate was 1.93-2.28 times higher and increased from 9.98 per 1,000 person-years to 13.8 per 1,000 person-years between 2008 and 2019. Among patients with codified knee OA, 39.4% were previously diagnosed narratively with knee OA, on average ~3 years earlier. Comorbidities influenced the likelihood of being recorded with codified knee OA. CONCLUSION: Our study of a Dutch primary care database showed that current incidence and prevalence estimates based on codified data alone from electronic health records are underestimated. Narrative data can be incorporated in addition to codified data to identify knee OA patients more accurately.},
   keywords = {Adult
Electronic Health Records
Humans
Incidence
*Osteoarthritis, Hip/diagnosis
*Osteoarthritis, Knee/diagnosis/epidemiology/etiology
Prevalence
Retrospective Studies ,
ISSN = 2151-464X (Print) 2151-464x ,
DOI = 10.1002/acr.24861},
   year = {2022},
   type = {Journal Article}
}

PURPOSE: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. PATIENTS AND METHODS: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services. RESULTS: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed. CONCLUSION: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.

@article{RN347,
   author = {Kostka, K. and Duarte-Salles, T. and Prats-Uribe, A. and Sena, A. G. and Pistillo, A. and Khalid, S. and Lai, L. Y. H. and Golozar, A. and Alshammari, T. M. and Dawoud, D. M. and Nyberg, F. and Wilcox, A. B. and Andryc, A. and Williams, A. and Ostropolets, A. and Areia, C. and Jung, C. Y. and Harle, C. A. and Reich, C. G. and Blacketer, C. and Morales, D. R. and Dorr, D. A. and Burn, E. and Roel, E. and Tan, E. H. and Minty, E. and DeFalco, F. and de Maeztu, G. and Lipori, G. and Alghoul, H. and Zhu, H. and Thomas, J. A. and Bian, J. and Park, J. and Martínez Roldán, J. and Posada, J. D. and Banda, J. M. and Horcajada, J. P. and Kohler, J. and Shah, K. and Natarajan, K. and Lynch, K. E. and Liu, L. and Schilling, L. M. and Recalde, M. and Spotnitz, M. and Gong, M. and Matheny, M. E. and Valveny, N. and Weiskopf, N. G. and Shah, N. and Alser, O. and Casajust, P. and Park, R. W. and Schuff, R. and Seager, S. and DuVall, S. L. and You, S. C. and Song, S. and Fernández-Bertolín, S. and Fortin, S. and Magoc, T. and Falconer, T. and Subbian, V. and Huser, V. and Ahmed, W. U. and Carter, W. and Guan, Y. and Galvan, Y. and He, X. and Rijnbeek, P. R. and Hripcsak, G. and Ryan, P. B. and Suchard, M. A. and Prieto-Alhambra, D.},
   title = {Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS},
   journal = {Clin Epidemiol},
   volume = {14},
   pages = {369-384},
   note = {1179-1349 Kostka, Kristin Orcid: 0000-0003-2595-8736 Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 Prats-Uribe, Albert Orcid: 0000-0003-1202-9153 Sena, Anthony G Pistillo, Andrea Orcid: 0000-0002-4467-0220 Khalid, Sara Lai, Lana Y H Golozar, Asieh Alshammari, Thamir M Orcid: 0000-0002-5630-2468 Dawoud, Dalia M Nyberg, Fredrik Orcid: 0000-0003-0892-5668 Wilcox, Adam B Andryc, Alan Orcid: 0000-0002-2663-2298 Williams, Andrew Ostropolets, Anna Areia, Carlos Jung, Chi Young Harle, Christopher A Reich, Christian G Orcid: 0000-0002-3641-055x Blacketer, Clair Morales, Daniel R Dorr, David A Burn, Edward Orcid: 0000-0002-9286-1128 Roel, Elena Tan, Eng Hooi Minty, Evan DeFalco, Frank de Maeztu, Gabriel Lipori, Gigi Alghoul, Hiba Orcid: 0000-0001-8234-5843 Zhu, Hong Thomas, Jason A Bian, Jiang Park, Jimyung Orcid: 0000-0002-6998-2546 Martínez Roldán, Jordi Posada, Jose D Banda, Juan M Orcid: 0000-0001-8499-824x Horcajada, Juan P Orcid: 0000-0001-9873-5459 Kohler, Julianna Shah, Karishma Natarajan, Karthik Orcid: 0000-0002-9066-9431 Lynch, Kristine E Liu, Li Orcid: 0000-0002-5265-4159 Schilling, Lisa M Recalde, Martina Spotnitz, Matthew Gong, Mengchun Matheny, Michael E Valveny, Neus Orcid: 0000-0003-1105-5018 Weiskopf, Nicole G Shah, Nigam Alser, Osaid Casajust, Paula Orcid: 0000-0003-2733-5436 Park, Rae Woong Schuff, Robert Seager, Sarah DuVall, Scott L Orcid: 0000-0002-4898-3865 You, Seng Chan Song, Seokyoung Orcid: 0000-0002-5653-7005 Fernández-Bertolín, Sergio Fortin, Stephen Magoc, Tanja Orcid: 0000-0001-8213-2266 Falconer, Thomas Orcid: 0000-0001-6904-1394 Subbian, Vignesh Huser, Vojtech Ahmed, Waheed-Ul-Rahman Orcid: 0000-0003-0880-0355 Carter, William Orcid: 0000-0001-5346-3453 Guan, Yin Galvan, Yankuic He, Xing Rijnbeek, Peter R Hripcsak, George Ryan, Patrick B Suchard, Marc A Orcid: 0000-0001-9818-479x Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 INV-016201/GATES/Bill & Melinda Gates Foundation/United States INV-016910/GATES/Bill & Melinda Gates Foundation/United States R01 LM006910/LM/NLM NIH HHS/United States UL1 TR002369/TR/NCATS NIH HHS/United States INV-016284/GATES/Bill & Melinda Gates Foundation/United States INV-019257/GATES/Bill & Melinda Gates Foundation/United States Journal Article New Zealand 2022/03/30 Clin Epidemiol. 2022 Mar 22;14:369-384. doi: 10.2147/CLEP.S323292. eCollection 2022.},
   abstract = {PURPOSE: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. PATIENTS AND METHODS: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services. RESULTS: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed. CONCLUSION: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.},
   keywords = {Ohdsi
Omop cdm
descriptive epidemiology
open science
real world data
real world evidence ,
ISSN = 1179-1349 (Print) 1179-1349 ,
DOI = 10.2147/clep.S323292},
   year = {2022},
   type = {Journal Article}
}

BACKGROUND: There are few data on the incidence of thrombosis among COVID-19 cases, with most research concentrated on hospitalised patients. We aimed to estimate the incidence of venous thromboembolism, arterial thromboembolism, and death among COVID-19 cases and to assess the impact of these events on the risks of hospitalisation and death. METHODS: We conducted a distributed network cohort study using primary care records from the Netherlands, Italy, Spain, and the UK, and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed up from the date of a diagnosis of COVID-19 or positive RT-PCR test for SARS-CoV-2 (index date) for 90 days. The primary study outcomes were venous thromboembolic events, arterial thromboembolic events, and death, all over the 90 days from the index date. We estimated cumulative incidences for the study outcomes. Multistate models were used to calculate adjusted hazard ratios (HRs) for the association between venous thromboembolism or arterial thromboembolism occurrence and risks of hospitalisation or COVID-19 fatality. FINDINGS: Overall, 909 473 COVID-19 cases and 32 329 patients hospitalised with COVID-19 on or after Sept 1, 2020, were studied. The latest index dates across the databases ranged from Jan 30, 2021, to July 31, 2021. Cumulative 90-day incidence of venous thromboembolism ranged from 0·2% to 0·8% among COVID-19 cases, and up to 4·5% for those hospitalised. For arterial thromboembolism, estimates ranged from 0·1% to 0·8% among COVID-19 cases, increasing to 3·1% among those hospitalised. Case fatality ranged from 1·1% to 2·0% among patients with COVID-19, rising to 14·6% for hospitalised patients. The occurrence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of death (adjusted HRs 4·42 [3·07-6·36] for those not hospitalised and 1·63 [1·39-1·90] for those hospitalised), as was the occurrence of arterial thromboembolism (3·16 [2·65-3·75] and 1·93 [1·57-2·37]). INTERPRETATION: Risks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency. FUNDING: European Medicines Agency.

@article{RN279,
   author = {Burn, E. and Duarte-Salles, T. and Fernandez-Bertolin, S. and Reyes, C. and Kostka, K. and Delmestri, A. and Rijnbeek, P. and Verhamme, K. and Prieto-Alhambra, D.},
   title = {Venous or arterial thrombosis and deaths among COVID-19 cases: a European network cohort study},
   journal = {Lancet Infect Dis},
   volume = {22},
   number = {8},
   pages = {1142-1152},
   note = {1474-4457 Burn, Edward Duarte-Salles, Talita Fernandez-Bertolin, Sergio Reyes, Carlen Kostka, Kristin Delmestri, Antonella Rijnbeek, Peter Verhamme, Katia Prieto-Alhambra, Daniel Journal Article Research Support, Non-U.S. Gov't United States 2022/05/17 Lancet Infect Dis. 2022 Aug;22(8):1142-1152. doi: 10.1016/S1473-3099(22)00223-7. Epub 2022 May 13.},
   abstract = {BACKGROUND: There are few data on the incidence of thrombosis among COVID-19 cases, with most research concentrated on hospitalised patients. We aimed to estimate the incidence of venous thromboembolism, arterial thromboembolism, and death among COVID-19 cases and to assess the impact of these events on the risks of hospitalisation and death. METHODS: We conducted a distributed network cohort study using primary care records from the Netherlands, Italy, Spain, and the UK, and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed up from the date of a diagnosis of COVID-19 or positive RT-PCR test for SARS-CoV-2 (index date) for 90 days. The primary study outcomes were venous thromboembolic events, arterial thromboembolic events, and death, all over the 90 days from the index date. We estimated cumulative incidences for the study outcomes. Multistate models were used to calculate adjusted hazard ratios (HRs) for the association between venous thromboembolism or arterial thromboembolism occurrence and risks of hospitalisation or COVID-19 fatality. FINDINGS: Overall, 909 473 COVID-19 cases and 32 329 patients hospitalised with COVID-19 on or after Sept 1, 2020, were studied. The latest index dates across the databases ranged from Jan 30, 2021, to July 31, 2021. Cumulative 90-day incidence of venous thromboembolism ranged from 0·2% to 0·8% among COVID-19 cases, and up to 4·5% for those hospitalised. For arterial thromboembolism, estimates ranged from 0·1% to 0·8% among COVID-19 cases, increasing to 3·1% among those hospitalised. Case fatality ranged from 1·1% to 2·0% among patients with COVID-19, rising to 14·6% for hospitalised patients. The occurrence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of death (adjusted HRs 4·42 [3·07-6·36] for those not hospitalised and 1·63 [1·39-1·90] for those hospitalised), as was the occurrence of arterial thromboembolism (3·16 [2·65-3·75] and 1·93 [1·57-2·37]). INTERPRETATION: Risks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency. FUNDING: European Medicines Agency.},
   keywords = {*COVID-19/epidemiology
Cohort Studies
Humans
Male
SARS-CoV-2
*Venous Thromboembolism/complications/epidemiology
*Venous Thrombosis/complications ,
ISSN = 1473-3099 (Print) 1473-3099 ,
DOI = 10.1016/s1473-3099(22)00223-7},
   year = {2022},
   type = {Journal Article}
}

OBJECTIVES: There are signs that antidepressants and anticonvulsants are being prescribed more often for OA patients, despite limited evidence. Our objectives were to examine prescription rates and time trends for antidepressants and anticonvulsants in OA patients, to assess the percentage of long-term prescriptions, and to determine patient characteristics associated with antidepressant or anticonvulsant prescription. METHODS: A population-based cohort study was conducted using the Integrated Primary Care Information database. First, episodic and prevalent prescription rates for antidepressants (amitriptyline, nortriptyline and duloxetine) and anticonvulsants (gabapentinoids) in OA patients were calculated for the period 2008-17. Logistic regression was used to assess which patient characteristics were associated with prescriptions. RESULTS: In total, 164 292 OA patients were included. The prescription rates of amitriptyline, gabapentin and pregabalin increased over time. The increase in prescription rates for pregabalin was most pronounced. Episodic prescription rate increased from 7.1 to 13.9 per 1000 person-years between 2008 and 2017. Amitriptyline was prescribed most (15.1 episodic prescriptions per 1000 person-years in 2017). Prescription rates of nortriptyline and duloxetine remained stable at 3.0 and 2.0 episodic prescriptions per 1000 person-years, respectively. For ≤3% of patients with incident OA, medication was prescribed long-term (≥3 months). In general, all medication was prescribed more frequently for older patients (except duloxetine), women, patients with OA in ≥2 joints, patients with spinal OA and patients with musculoskeletal disorders. CONCLUSION: Prescription rates of amitriptyline, gabapentin and pregabalin increased over time. Since there is little evidence to support prescription in OA, caution is necessary when prescribing.

@article{RN446,
   author = {van den Driest, J. J. and Schiphof, D. and de Wilde, M. and Bindels, P. J. E. and van der Lei, J. and Bierma-Zeinstra, S. M. A.},
   title = {Antidepressant and anticonvulsant prescription rates in patients with osteoarthritis: a population-based cohort study},
   journal = {Rheumatology (Oxford)},
   volume = {60},
   number = {5},
   pages = {2206-2216},
   note = {1462-0332 van den Driest, Jacoline J Schiphof, Dieuwke de Wilde, Marcel Bindels, Patrick J E van der Lei, Johan Bierma-Zeinstra, Sita M A Journal Article Research Support, Non-U.S. Gov't England 2020/11/12 Rheumatology (Oxford). 2021 May 14;60(5):2206-2216. doi: 10.1093/rheumatology/keaa544.},
   abstract = {OBJECTIVES: There are signs that antidepressants and anticonvulsants are being prescribed more often for OA patients, despite limited evidence. Our objectives were to examine prescription rates and time trends for antidepressants and anticonvulsants in OA patients, to assess the percentage of long-term prescriptions, and to determine patient characteristics associated with antidepressant or anticonvulsant prescription. METHODS: A population-based cohort study was conducted using the Integrated Primary Care Information database. First, episodic and prevalent prescription rates for antidepressants (amitriptyline, nortriptyline and duloxetine) and anticonvulsants (gabapentinoids) in OA patients were calculated for the period 2008-17. Logistic regression was used to assess which patient characteristics were associated with prescriptions. RESULTS: In total, 164 292 OA patients were included. The prescription rates of amitriptyline, gabapentin and pregabalin increased over time. The increase in prescription rates for pregabalin was most pronounced. Episodic prescription rate increased from 7.1 to 13.9 per 1000 person-years between 2008 and 2017. Amitriptyline was prescribed most (15.1 episodic prescriptions per 1000 person-years in 2017). Prescription rates of nortriptyline and duloxetine remained stable at 3.0 and 2.0 episodic prescriptions per 1000 person-years, respectively. For ≤3% of patients with incident OA, medication was prescribed long-term (≥3 months). In general, all medication was prescribed more frequently for older patients (except duloxetine), women, patients with OA in ≥2 joints, patients with spinal OA and patients with musculoskeletal disorders. CONCLUSION: Prescription rates of amitriptyline, gabapentin and pregabalin increased over time. Since there is little evidence to support prescription in OA, caution is necessary when prescribing.},
   keywords = {Aged
Analgesics/therapeutic use
Anticonvulsants/*therapeutic use
Antidepressive Agents/*therapeutic use
Depressive Disorder/*drug therapy
*Drug Prescriptions
Female
Gabapentin/therapeutic use
Humans
Male
Middle Aged
Osteoarthritis/*drug therapy
Practice Patterns, Physicians'/*statistics & numerical data
Pregabalin/therapeutic use
analgesics
anticonvulsants
antidepressants
gabapentinoids
osteoarthritis
pain ,
ISSN = 1462-0324 (Print) 1462-0324 ,
DOI = 10.1093/rheumatology/keaa544},
   year = {2021},
   type = {Journal Article}
}

BACKGROUND: General practitioners (GPs) face a diagnostic challenge when assessing acute abdominal pain in children. However, no information is available on the current diagnostic process or the diagnostic accuracy of history and physical examination in primary care settings. OBJECTIVE: To describe the diagnostic process for acute abdominal pain among children in primary care, focusing on appendicitis, and to assess the diagnostic accuracy of individual clinical features. METHODS: A retrospective cohort study in Dutch primary care, using the Integrated Primary Care Information database. Children aged 4-18 years were included if they had no history of appendicitis and presented with acute abdominal pain during 2010-2016. We evaluated GP management and the diagnostic accuracy of clinical features for appendicitis. Pre- and post-test probabilities were calculated for each clinical feature and compared with the probability of appendicitis after GP assessment. RESULTS: Out of 5691 children, 944 (16.6%) were referred and 291 (5.1%) had appendicitis, of whom 55 (18.9%) were initially misdiagnosed. The pre-test probability (i.e. of appendicitis in evaluated children) varied from 3% (rigidity) to 28% (migratory pain). Concerning post-test probabilities, positive values for rebound pain (32.1%) and guarding (35.8%) and the negative value for right lower quadrant tenderness (0.6%) were superior to overall GP assessment (29.6% and 1.1%, respectively). CONCLUSIONS: GP assessment will miss almost one-fifth of children with appendicitis at their first presentation, and about two-third of GP referrals will be negative. The presence of specific signs can increase or decrease the likelihood of appendicitis, emphasising the importance of a physical examination. It can be difficult for general practitioners (GPs) to assess acute abdominal pain in children because they must decide whether it is a common minor problem or an uncommon serious problem. However, unlike their hospital counterparts, GPs must often rely on only the history and examination. We, therefore, wanted to gain a better understanding of how GPs assess abdominal pain and the accuracy of the different parts of their assessment. To do this, we looked back at clinical records for children who presented to a GP with acute abdominal pain between 2010 and 2016. The effect of examination on the probability of detecting appendicitis was calculated for several clinical features, and these were compared with the probability of appendicitis after a full GP assessment. Approximately 1 in 20 of the included children was diagnosed with appendicitis, one in five were initially misdiagnosed, and one in four were ultimately referred to the hospital. We show that some signs and symptoms were not particularly useful for assessment, but when they were, signs detected by the GP examining the patient were more useful than symptoms reported by patients or parents. We recommend that GPs provide safety netting advice and examine the abdomen. eng

@article{RN276,
   author = {Blok, Gcgh and Veenstra, L. M. M. and van der Lei, J. and Berger, M. Y. and Holtman, G. A.},
   title = {Appendicitis in children with acute abdominal pain in primary care, a retrospective cohort study},
   journal = {Fam Pract},
   volume = {38},
   number = {6},
   pages = {758-765},
   note = {1460-2229 Blok, Guus C G H Orcid: 0000-0003-1654-6844 Veenstra, Laura M M van der Lei, Johan Berger, Marjolein Y Holtman, Gea A Journal Article England 2021/07/20 Fam Pract. 2021 Nov 24;38(6):758-765. doi: 10.1093/fampra/cmab039.},
   abstract = {BACKGROUND: General practitioners (GPs) face a diagnostic challenge when assessing acute abdominal pain in children. However, no information is available on the current diagnostic process or the diagnostic accuracy of history and physical examination in primary care settings. OBJECTIVE: To describe the diagnostic process for acute abdominal pain among children in primary care, focusing on appendicitis, and to assess the diagnostic accuracy of individual clinical features. METHODS: A retrospective cohort study in Dutch primary care, using the Integrated Primary Care Information database. Children aged 4-18 years were included if they had no history of appendicitis and presented with acute abdominal pain during 2010-2016. We evaluated GP management and the diagnostic accuracy of clinical features for appendicitis. Pre- and post-test probabilities were calculated for each clinical feature and compared with the probability of appendicitis after GP assessment. RESULTS: Out of 5691 children, 944 (16.6%) were referred and 291 (5.1%) had appendicitis, of whom 55 (18.9%) were initially misdiagnosed. The pre-test probability (i.e. of appendicitis in evaluated children) varied from 3% (rigidity) to 28% (migratory pain). Concerning post-test probabilities, positive values for rebound pain (32.1%) and guarding (35.8%) and the negative value for right lower quadrant tenderness (0.6%) were superior to overall GP assessment (29.6% and 1.1%, respectively). CONCLUSIONS: GP assessment will miss almost one-fifth of children with appendicitis at their first presentation, and about two-third of GP referrals will be negative. The presence of specific signs can increase or decrease the likelihood of appendicitis, emphasising the importance of a physical examination. It can be difficult for general practitioners (GPs) to assess acute abdominal pain in children because they must decide whether it is a common minor problem or an uncommon serious problem. However, unlike their hospital counterparts, GPs must often rely on only the history and examination. We, therefore, wanted to gain a better understanding of how GPs assess abdominal pain and the accuracy of the different parts of their assessment. To do this, we looked back at clinical records for children who presented to a GP with acute abdominal pain between 2010 and 2016. The effect of examination on the probability of detecting appendicitis was calculated for several clinical features, and these were compared with the probability of appendicitis after a full GP assessment. Approximately 1 in 20 of the included children was diagnosed with appendicitis, one in five were initially misdiagnosed, and one in four were ultimately referred to the hospital. We show that some signs and symptoms were not particularly useful for assessment, but when they were, signs detected by the GP examining the patient were more useful than symptoms reported by patients or parents. We recommend that GPs provide safety netting advice and examine the abdomen. eng},
   keywords = {Abdominal Pain/etiology
*Appendicitis/complications/diagnosis
Child
Humans
Physical Examination
Primary Health Care
Retrospective Studies
Appendicitis
Diagnosis
electronic health records
observational study ,
ISSN = 0263-2136 ,
DOI = 10.1093/fampra/cmab039},
   year = {2021},
   type = {Journal Article}
}

OBJECTIVE: To quantify the background incidence rates of 15 prespecified adverse events of special interest (AESIs) associated with covid-19 vaccines. DESIGN: Multinational network cohort study. SETTING: Electronic health records and health claims data from eight countries: Australia, France, Germany, Japan, the Netherlands, Spain, the United Kingdom, and the United States, mapped to a common data model. PARTICIPANTS: 126 661 070 people observed for at least 365 days before 1 January 2017, 2018, or 2019 from 13 databases. MAIN OUTCOME MEASURES: Events of interests were 15 prespecified AESIs (non-haemorrhagic and haemorrhagic stroke, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, anaphylaxis, Bell's palsy, myocarditis or pericarditis, narcolepsy, appendicitis, immune thrombocytopenia, disseminated intravascular coagulation, encephalomyelitis (including acute disseminated encephalomyelitis), Guillain-Barré syndrome, and transverse myelitis). Incidence rates of AESIs were stratified by age, sex, and database. Rates were pooled across databases using random effects meta-analyses and classified according to the frequency categories of the Council for International Organizations of Medical Sciences. RESULTS: Background rates varied greatly between databases. Deep vein thrombosis ranged from 387 (95% confidence interval 370 to 404) per 100 000 person years in UK CPRD GOLD data to 1443 (1416 to 1470) per 100 000 person years in US IBM MarketScan Multi-State Medicaid data among women aged 65 to 74 years. Some AESIs increased with age. For example, myocardial infarction rates in men increased from 28 (27 to 29) per 100 000 person years among those aged 18-34 years to 1400 (1374 to 1427) per 100 000 person years in those older than 85 years in US Optum electronic health record data. Other AESIs were more common in young people. For example, rates of anaphylaxis among boys and men were 78 (75 to 80) per 100 000 person years in those aged 6-17 years and 8 (6 to 10) per 100 000 person years in those older than 85 years in Optum electronic health record data. Meta-analytic estimates of AESI rates were classified according to age and sex. CONCLUSION: This study found large variations in the observed rates of AESIs by age group and sex, showing the need for stratification or standardisation before using background rates for safety surveillance. Considerable population level heterogeneity in AESI rates was found between databases.

@article{RN355,
   author = {Li, X. and Ostropolets, A. and Makadia, R. and Shoaibi, A. and Rao, G. and Sena, A. G. and Martinez-Hernandez, E. and Delmestri, A. and Verhamme, K. and Rijnbeek, P. R. and Duarte-Salles, T. and Suchard, M. A. and Ryan, P. B. and Hripcsak, G. and Prieto-Alhambra, D.},
   title = {Characterising the background incidence rates of adverse events of special interest for covid-19 vaccines in eight countries: multinational network cohort study},
   journal = {Bmj},
   volume = {373},
   pages = {n1435},
   note = {1756-1833 Li, Xintong Orcid: 0000-0002-6872-5804 Ostropolets, Anna Makadia, Rupa Shoaibi, Azza Rao, Gowtham Sena, Anthony G Orcid: 0000-0001-8630-5347 Martinez-Hernandez, Eugenia Orcid: 0000-0002-8317-7068 Delmestri, Antonella Verhamme, Katia Rijnbeek, Peter R Duarte-Salles, Talita Suchard, Marc A Ryan, Patrick B Hripcsak, George Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 R01 LM006910/LM/NLM NIH HHS/United States Journal Article England 2022/06/22 BMJ. 2021 Jun 14;373:n1435. doi: 10.1136/bmj.n1435.},
   abstract = {OBJECTIVE: To quantify the background incidence rates of 15 prespecified adverse events of special interest (AESIs) associated with covid-19 vaccines. DESIGN: Multinational network cohort study. SETTING: Electronic health records and health claims data from eight countries: Australia, France, Germany, Japan, the Netherlands, Spain, the United Kingdom, and the United States, mapped to a common data model. PARTICIPANTS: 126 661 070 people observed for at least 365 days before 1 January 2017, 2018, or 2019 from 13 databases. MAIN OUTCOME MEASURES: Events of interests were 15 prespecified AESIs (non-haemorrhagic and haemorrhagic stroke, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, anaphylaxis, Bell's palsy, myocarditis or pericarditis, narcolepsy, appendicitis, immune thrombocytopenia, disseminated intravascular coagulation, encephalomyelitis (including acute disseminated encephalomyelitis), Guillain-Barré syndrome, and transverse myelitis). Incidence rates of AESIs were stratified by age, sex, and database. Rates were pooled across databases using random effects meta-analyses and classified according to the frequency categories of the Council for International Organizations of Medical Sciences. RESULTS: Background rates varied greatly between databases. Deep vein thrombosis ranged from 387 (95% confidence interval 370 to 404) per 100 000 person years in UK CPRD GOLD data to 1443 (1416 to 1470) per 100 000 person years in US IBM MarketScan Multi-State Medicaid data among women aged 65 to 74 years. Some AESIs increased with age. For example, myocardial infarction rates in men increased from 28 (27 to 29) per 100 000 person years among those aged 18-34 years to 1400 (1374 to 1427) per 100 000 person years in those older than 85 years in US Optum electronic health record data. Other AESIs were more common in young people. For example, rates of anaphylaxis among boys and men were 78 (75 to 80) per 100 000 person years in those aged 6-17 years and 8 (6 to 10) per 100 000 person years in those older than 85 years in Optum electronic health record data. Meta-analytic estimates of AESI rates were classified according to age and sex. CONCLUSION: This study found large variations in the observed rates of AESIs by age group and sex, showing the need for stratification or standardisation before using background rates for safety surveillance. Considerable population level heterogeneity in AESI rates was found between databases.},
   keywords = {Adolescent
*Anaphylaxis
*COVID-19/epidemiology/prevention & control
COVID-19 Vaccines/adverse effects
Cohort Studies
Female
Humans
Incidence
Male
United States/epidemiology
*Venous Thrombosis ,
ISSN = 0959-8138 (Print) 0959-8138 ,
DOI = 10.1136/bmj.n1435},
   year = {2021},
   type = {Journal Article}
}

OBJECTIVE: To characterise patients with and without prevalent hypertension and COVID-19 and to assess adverse outcomes in both inpatients and outpatients. DESIGN AND SETTING: This is a retrospective cohort study using 15 healthcare databases (primary and secondary electronic healthcare records, insurance and national claims data) from the USA, Europe and South Korea, standardised to the Observational Medical Outcomes Partnership common data model. Data were gathered from 1 March to 31 October 2020. PARTICIPANTS: Two non-mutually exclusive cohorts were defined: (1) individuals diagnosed with COVID-19 (diagnosed cohort) and (2) individuals hospitalised with COVID-19 (hospitalised cohort), and stratified by hypertension status. Follow-up was from COVID-19 diagnosis/hospitalisation to death, end of the study period or 30 days. OUTCOMES: Demographics, comorbidities and 30-day outcomes (hospitalisation and death for the 'diagnosed' cohort and adverse events and death for the 'hospitalised' cohort) were reported. RESULTS: We identified 2 851 035 diagnosed and 563 708 hospitalised patients with COVID-19. Hypertension was more prevalent in the latter (ranging across databases from 17.4% (95% CI 17.2 to 17.6) to 61.4% (95% CI 61.0 to 61.8) and from 25.6% (95% CI 24.6 to 26.6) to 85.9% (95% CI 85.2 to 86.6)). Patients in both cohorts with hypertension were predominantly >50 years old and female. Patients with hypertension were frequently diagnosed with obesity, heart disease, dyslipidaemia and diabetes. Compared with patients without hypertension, patients with hypertension in the COVID-19 diagnosed cohort had more hospitalisations (ranging from 1.3% (95% CI 0.4 to 2.2) to 41.1% (95% CI 39.5 to 42.7) vs from 1.4% (95% CI 0.9 to 1.9) to 15.9% (95% CI 14.9 to 16.9)) and increased mortality (ranging from 0.3% (95% CI 0.1 to 0.5) to 18.5% (95% CI 15.7 to 21.3) vs from 0.2% (95% CI 0.2 to 0.2) to 11.8% (95% CI 10.8 to 12.8)). Patients in the COVID-19 hospitalised cohort with hypertension were more likely to have acute respiratory distress syndrome (ranging from 0.1% (95% CI 0.0 to 0.2) to 65.6% (95% CI 62.5 to 68.7) vs from 0.1% (95% CI 0.0 to 0.2) to 54.7% (95% CI 50.5 to 58.9)), arrhythmia (ranging from 0.5% (95% CI 0.3 to 0.7) to 45.8% (95% CI 42.6 to 49.0) vs from 0.4% (95% CI 0.3 to 0.5) to 36.8% (95% CI 32.7 to 40.9)) and increased mortality (ranging from 1.8% (95% CI 0.4 to 3.2) to 25.1% (95% CI 23.0 to 27.2) vs from 0.7% (95% CI 0.5 to 0.9) to 10.9% (95% CI 10.4 to 11.4)) than patients without hypertension. CONCLUSIONS: COVID-19 patients with hypertension were more likely to suffer severe outcomes, hospitalisations and deaths compared with those without hypertension.

@article{RN400,
   author = {Reyes, C. and Pistillo, A. and Fernández-Bertolín, S. and Recalde, M. and Roel, E. and Puente, D. and Sena, A. G. and Blacketer, C. and Lai, L. and Alshammari, T. M. and Ahmed, W. U. and Alser, O. and Alghoul, H. and Areia, C. and Dawoud, D. and Prats-Uribe, A. and Valveny, N. and de Maeztu, G. and Sorlí Redó, L. and Martinez Roldan, J. and Lopez Montesinos, I. and Schilling, L. M. and Golozar, A. and Reich, C. and Posada, J. D. and Shah, N. and You, S. C. and Lynch, K. E. and DuVall, S. L. and Matheny, M. E. and Nyberg, F. and Ostropolets, A. and Hripcsak, G. and Rijnbeek, P. R. and Suchard, M. A. and Ryan, P. and Kostka, K. and Duarte-Salles, T.},
   title = {Characteristics and outcomes of patients with COVID-19 with and without prevalent hypertension: a multinational cohort study},
   journal = {BMJ Open},
   volume = {11},
   number = {12},
   pages = {e057632},
   note = {2044-6055 Reyes, Carlen Orcid: 0000-0001-8486-3265 Pistillo, Andrea Fernández-Bertolín, Sergio Recalde, Martina Roel, Elena Puente, Diana Sena, Anthony G Blacketer, Clair Lai, Lana Alshammari, Thamir M Ahmed, Waheed-Ui-Rahman Alser, Osaid Orcid: 0000-0001-6743-803x Alghoul, Heba Orcid: 0000-0001-8234-5843 Areia, Carlos Orcid: 0000-0002-4668-7069 Dawoud, Dalia Prats-Uribe, Albert Orcid: 0000-0003-1202-9153 Valveny, Neus de Maeztu, Gabriel Sorlí Redó, Luisa Martinez Roldan, Jordi Lopez Montesinos, Inmaculada Schilling, Lisa M Golozar, Asieh Reich, Christian Posada, Jose D Shah, Nigam You, Seng Chan Lynch, Kristine E DuVall, Scott L Matheny, Michael E Nyberg, Fredrik Ostropolets, Anna Hripcsak, George Rijnbeek, Peter R Orcid: 0000-0003-0621-1979 Suchard, Marc A Ryan, Patrick Kostka, Kristin Orcid: 0000-0003-2595-8736 Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 R01 LM006910/LM/NLM NIH HHS/United States Journal Article Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2021/12/24 BMJ Open. 2021 Dec 22;11(12):e057632. doi: 10.1136/bmjopen-2021-057632.},
   abstract = {OBJECTIVE: To characterise patients with and without prevalent hypertension and COVID-19 and to assess adverse outcomes in both inpatients and outpatients. DESIGN AND SETTING: This is a retrospective cohort study using 15 healthcare databases (primary and secondary electronic healthcare records, insurance and national claims data) from the USA, Europe and South Korea, standardised to the Observational Medical Outcomes Partnership common data model. Data were gathered from 1 March to 31 October 2020. PARTICIPANTS: Two non-mutually exclusive cohorts were defined: (1) individuals diagnosed with COVID-19 (diagnosed cohort) and (2) individuals hospitalised with COVID-19 (hospitalised cohort), and stratified by hypertension status. Follow-up was from COVID-19 diagnosis/hospitalisation to death, end of the study period or 30 days. OUTCOMES: Demographics, comorbidities and 30-day outcomes (hospitalisation and death for the 'diagnosed' cohort and adverse events and death for the 'hospitalised' cohort) were reported. RESULTS: We identified 2 851 035 diagnosed and 563 708 hospitalised patients with COVID-19. Hypertension was more prevalent in the latter (ranging across databases from 17.4% (95% CI 17.2 to 17.6) to 61.4% (95% CI 61.0 to 61.8) and from 25.6% (95% CI 24.6 to 26.6) to 85.9% (95% CI 85.2 to 86.6)). Patients in both cohorts with hypertension were predominantly >50 years old and female. Patients with hypertension were frequently diagnosed with obesity, heart disease, dyslipidaemia and diabetes. Compared with patients without hypertension, patients with hypertension in the COVID-19 diagnosed cohort had more hospitalisations (ranging from 1.3% (95% CI 0.4 to 2.2) to 41.1% (95% CI 39.5 to 42.7) vs from 1.4% (95% CI 0.9 to 1.9) to 15.9% (95% CI 14.9 to 16.9)) and increased mortality (ranging from 0.3% (95% CI 0.1 to 0.5) to 18.5% (95% CI 15.7 to 21.3) vs from 0.2% (95% CI 0.2 to 0.2) to 11.8% (95% CI 10.8 to 12.8)). Patients in the COVID-19 hospitalised cohort with hypertension were more likely to have acute respiratory distress syndrome (ranging from 0.1% (95% CI 0.0 to 0.2) to 65.6% (95% CI 62.5 to 68.7) vs from 0.1% (95% CI 0.0 to 0.2) to 54.7% (95% CI 50.5 to 58.9)), arrhythmia (ranging from 0.5% (95% CI 0.3 to 0.7) to 45.8% (95% CI 42.6 to 49.0) vs from 0.4% (95% CI 0.3 to 0.5) to 36.8% (95% CI 32.7 to 40.9)) and increased mortality (ranging from 1.8% (95% CI 0.4 to 3.2) to 25.1% (95% CI 23.0 to 27.2) vs from 0.7% (95% CI 0.5 to 0.9) to 10.9% (95% CI 10.4 to 11.4)) than patients without hypertension. CONCLUSIONS: COVID-19 patients with hypertension were more likely to suffer severe outcomes, hospitalisations and deaths compared with those without hypertension.},
   keywords = {*covid-19
COVID-19 Testing
Cohort Studies
Comorbidity
Female
Hospitalization
Humans
*Hypertension/epidemiology
Middle Aged
Retrospective Studies
SARS-CoV-2
Covid-19
epidemiology
hypertension ,
ISSN = 2044-6055 ,
DOI = 10.1136/bmjopen-2021-057632},
   year = {2021},
   type = {Journal Article}
}

BACKGROUND: As large-scale immunization programs against COVID-19 proceed around the world, safety signals will emerge that need rapid evaluation. We report population-based, age- and sex-specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases. METHODS: This multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom, and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain-Barre syndrome, hemorrhagic and non-hemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, and transverse myelitis. We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare. FINDINGS: We analysed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction, Guillain-Barre syndrome) increased with age, while others (e.g., anaphylaxis, appendicitis) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged ≥85 years. INTERPRETATION: We report robust baseline rates of prioritised AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 vaccines. , DOI = 10.1101/2021.03.25.21254315

@article{RN354,
   author = {Li, X. and Ostropolets, A. and Makadia, R. and Shaoibi, A. and Rao, G. and Sena, A. G. and Martinez-Hernandez, E. and Delmestri, A. and Verhamme, K. and Rijnbeek, P. R. and Duarte-Salles, T. and Suchard, M. and Ryan, P. and Hripcsak, G. and Prieto-Alhambra, D.},
   title = {Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study},
   journal = {medRxiv},
   note = {Li, Xintong Ostropolets, Anna Makadia, Rupa Shaoibi, Azza Rao, Gowtham Sena, Anthony G Martinez-Hernandez, Eugenia Delmestri, Antonella Verhamme, Katia Rijnbeek, Peter R Duarte-Salles, Talita Suchard, Marc Ryan, Patrick Hripcsak, George Prieto-Alhambra, Daniel R01 LM006910/LM/NLM NIH HHS/United States Preprint United States 2021/04/02 medRxiv. 2021 Apr 17:2021.03.25.21254315. doi: 10.1101/2021.03.25.21254315. Preprint.},
   abstract = {BACKGROUND: As large-scale immunization programs against COVID-19 proceed around the world, safety signals will emerge that need rapid evaluation. We report population-based, age- and sex-specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases. METHODS: This multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom, and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain-Barre syndrome, hemorrhagic and non-hemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, and transverse myelitis. We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare. FINDINGS: We analysed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction, Guillain-Barre syndrome) increased with age, while others (e.g., anaphylaxis, appendicitis) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged ≥85 years. INTERPRETATION: We report robust baseline rates of prioritised AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 vaccines. , DOI = 10.1101/2021.03.25.21254315},
   year = {2021},
   type = {Journal Article}
}

INTRODUCTION: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records. METHODS AND ANALYSIS: This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported. ETHICS AND DISSEMINATION: Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences.

@article{RN414,
   author = {Sing, C. W. and Lin, T. C. and Bartholomew, S. and Bell, J. S. and Bennett, C. and Beyene, K. and Bosco-Lévy, P. and Chan, A. H. Y. and Chandran, M. and Cheung, C. L. and Doyon, C. Y. and Droz-Perroteau, C. and Ganesan, G. and Hartikainen, S. and Ilomaki, J. and Jeong, H. E. and Kiel, D. P. and Kubota, K. and Lai, E. C. and Lange, J. and Lewiecki, E. M. and Liu, J. and Man, K. K. C. and Mendes de Abreu, M. and Moore, N. and O'Kelly, J. and Ooba, N. and Pedersen, A. B. and Prieto-Alhambra, D. and Shin, J. Y. and Sørensen, H. T. and Tan, K. B. and Tolppanen, A. M. and Verhamme, K. M. C. and Wang, G. H. and Watcharathanakij, S. and Zhao, H. and Wong, I. C. K.},
   title = {Global epidemiology of hip fractures: a study protocol using a common analytical platform among multiple countries},
   journal = {BMJ Open},
   volume = {11},
   number = {7},
   pages = {e047258},
   note = {2044-6055 Sing, Chor-Wing Orcid: 0000-0002-2180-3676 Lin, Tzu-Chieh Bartholomew, Sharon Bell, J Simon Bennett, Corina Beyene, Kebede Bosco-Lévy, Pauline Chan, Amy Hai Yan Chandran, Manju Cheung, Ching-Lung Doyon, Caroline Y Droz-Perroteau, Cécile Ganesan, Ganga Hartikainen, Sirpa Ilomaki, Jenni Jeong, Han Eol Kiel, Douglas P Kubota, Kiyoshi Lai, Edward Chia-Cheng Lange, Jeff Lewiecki, E Michael Liu, Jiannong Man, Kenneth K C Orcid: 0000-0001-8645-1942 Mendes de Abreu, Mirhelen Orcid: 0000-0002-2264-0442 Moore, Nicolas O'Kelly, James Ooba, Nobuhiro Pedersen, Alma B Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Shin, Ju-Young Orcid: 0000-0002-2791-1037 Sørensen, Henrik T Tan, Kelvin Bryan Tolppanen, Anna-Maija Verhamme, Katia M C Orcid: 0000-0001-8162-4904 Wang, Grace Hsin-Min Watcharathanakij, Sawaeng Zhao, Hongxin Orcid: 0000-0001-7906-2797 Wong, Ian C K Journal Article Research Support, Non-U.S. Gov't England 2021/07/30 BMJ Open. 2021 Jul 28;11(7):e047258. doi: 10.1136/bmjopen-2020-047258.},
   abstract = {INTRODUCTION: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records. METHODS AND ANALYSIS: This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported. ETHICS AND DISSEMINATION: Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences.},
   keywords = {Aged
Asia
Europe
*Hip Fractures/epidemiology
Humans
Incidence
Middle Aged
Retrospective Studies
South America
calcium & bone
diabetes & endocrinology
epidemiology
public health ,
ISSN = 2044-6055 ,
DOI = 10.1136/bmjopen-2020-047258},
   year = {2021},
   type = {Journal Article}
}

BACKGROUND: SARS-CoV-2 is straining health care systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate patients who require hospitalization from those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision-making during the pandemic. However, the model is at high risk of bias according to the prediction model risk of bias assessment criteria, and it has not been externally validated. OBJECTIVE: The aim of this study was to externally validate the C-19 index across a range of health care settings to determine how well it broadly predicts hospitalization due to pneumonia in COVID-19 cases. METHODS: We followed the Observational Health Data Sciences and Informatics (OHDSI) framework for external validation to assess the reliability of the C-19 index. We evaluated the model on two different target populations, 41,381 patients who presented with SARS-CoV-2 at an outpatient or emergency department visit and 9,429,285 patients who presented with influenza or related symptoms during an outpatient or emergency department visit, to predict their risk of hospitalization with pneumonia during the following 0-30 days. In total, we validated the model across a network of 14 databases spanning the United States, Europe, Australia, and Asia. RESULTS: The internal validation performance of the C-19 index had a C statistic of 0.73, and the calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data, the model obtained C statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US, and South Korean data sets, respectively. The calibration was poor, with the model underestimating risk. When validated on 12 data sets containing influenza patients across the OHDSI network, the C statistics ranged between 0.40 and 0.68. CONCLUSIONS: Our results show that the discriminative performance of the C-19 index model is low for influenza cohorts and even worse among patients with COVID-19 in the United States, Spain, and South Korea. These results suggest that C-19 should not be used to aid decision-making during the COVID-19 pandemic. Our findings highlight the importance of performing external validation across a range of settings, especially when a prediction model is being extrapolated to a different population. In the field of prediction, extensive validation is required to create appropriate trust in a model.

@article{RN397,
   author = {Reps, J. M. and Kim, C. and Williams, R. D. and Markus, A. F. and Yang, C. and Duarte-Salles, T. and Falconer, T. and Jonnagaddala, J. and Williams, A. and Fernández-Bertolín, S. and DuVall, S. L. and Kostka, K. and Rao, G. and Shoaibi, A. and Ostropolets, A. and Spotnitz, M. E. and Zhang, L. and Casajust, P. and Steyerberg, E. W. and Nyberg, F. and Kaas-Hansen, B. S. and Choi, Y. H. and Morales, D. and Liaw, S. T. and Abrahão, M. T. F. and Areia, C. and Matheny, M. E. and Lynch, K. E. and Aragón, M. and Park, R. W. and Hripcsak, G. and Reich, C. G. and Suchard, M. A. and You, S. C. and Ryan, P. B. and Prieto-Alhambra, D. and Rijnbeek, P. R.},
   title = {Implementation of the COVID-19 Vulnerability Index Across an International Network of Health Care Data Sets: Collaborative External Validation Study},
   journal = {JMIR Med Inform},
   volume = {9},
   number = {4},
   pages = {e21547},
   note = {2291-9694 Reps, Jenna M Orcid: 0000-0002-2970-0778 Kim, Chungsoo Orcid: 0000-0003-1802-1777 Williams, Ross D Orcid: 0000-0001-7723-417x Markus, Aniek F Orcid: 0000-0001-5779-4794 Yang, Cynthia Orcid: 0000-0001-6769-3153 Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 Falconer, Thomas Orcid: 0000-0001-6904-1394 Jonnagaddala, Jitendra Orcid: 0000-0002-9912-2344 Williams, Andrew Orcid: 0000-0002-0692-412x Fernández-Bertolín, Sergio Orcid: 0000-0002-0029-6564 DuVall, Scott L Orcid: 0000-0002-4898-3865 Kostka, Kristin Orcid: 0000-0003-2595-8736 Rao, Gowtham Orcid: 0000-0002-4949-7236 Shoaibi, Azza Orcid: 0000-0002-6976-2594 Ostropolets, Anna Orcid: 0000-0002-0847-6682 Spotnitz, Matthew E Orcid: 0000-0003-2869-0237 Zhang, Lin Orcid: 0000-0002-2064-8440 Casajust, Paula Orcid: 0000-0003-2733-5436 Steyerberg, Ewout W Orcid: 0000-0002-7787-0122 Nyberg, Fredrik Orcid: 0000-0003-0892-5668 Kaas-Hansen, Benjamin Skov Orcid: 0000-0003-1023-0371 Choi, Young Hwa Orcid: 0000-0001-5254-3101 Morales, Daniel Orcid: 0000-0002-0063-8069 Liaw, Siaw-Teng Orcid: 0000-0001-5989-3614 Abrahão, Maria Tereza Fernandes Orcid: 0000-0003-2701-670x Areia, Carlos Orcid: 0000-0002-4668-7069 Matheny, Michael E Orcid: 0000-0003-3217-4147 Lynch, Kristine E Orcid: 0000-0002-2221-2421 Aragón, María Orcid: 0000-0002-5990-6953 Park, Rae Woong Orcid: 0000-0003-4989-3287 Hripcsak, George Orcid: 0000-0003-2664-7614 Reich, Christian G Orcid: 0000-0002-3641-055x Suchard, Marc A Orcid: 0000-0001-9818-479x You, Seng Chan Orcid: 0000-0002-5052-6399 Ryan, Patrick B Orcid: 0000-0002-9727-2138 Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Rijnbeek, Peter R Orcid: 0000-0003-0621-1979 R01 LM006910/LM/NLM NIH HHS/United States T15 LM007079/LM/NLM NIH HHS/United States Journal Article Canada 2021/03/05 JMIR Med Inform. 2021 Apr 5;9(4):e21547. doi: 10.2196/21547.},
   abstract = {BACKGROUND: SARS-CoV-2 is straining health care systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate patients who require hospitalization from those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision-making during the pandemic. However, the model is at high risk of bias according to the prediction model risk of bias assessment criteria, and it has not been externally validated. OBJECTIVE: The aim of this study was to externally validate the C-19 index across a range of health care settings to determine how well it broadly predicts hospitalization due to pneumonia in COVID-19 cases. METHODS: We followed the Observational Health Data Sciences and Informatics (OHDSI) framework for external validation to assess the reliability of the C-19 index. We evaluated the model on two different target populations, 41,381 patients who presented with SARS-CoV-2 at an outpatient or emergency department visit and 9,429,285 patients who presented with influenza or related symptoms during an outpatient or emergency department visit, to predict their risk of hospitalization with pneumonia during the following 0-30 days. In total, we validated the model across a network of 14 databases spanning the United States, Europe, Australia, and Asia. RESULTS: The internal validation performance of the C-19 index had a C statistic of 0.73, and the calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data, the model obtained C statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US, and South Korean data sets, respectively. The calibration was poor, with the model underestimating risk. When validated on 12 data sets containing influenza patients across the OHDSI network, the C statistics ranged between 0.40 and 0.68. CONCLUSIONS: Our results show that the discriminative performance of the C-19 index model is low for influenza cohorts and even worse among patients with COVID-19 in the United States, Spain, and South Korea. These results suggest that C-19 should not be used to aid decision-making during the COVID-19 pandemic. Our findings highlight the importance of performing external validation across a range of settings, especially when a prediction model is being extrapolated to a different population. In the field of prediction, extensive validation is required to create appropriate trust in a model.},
   keywords = {C-19
Covid-19
bias
datasets
decision-making
external validation
hospitalization
modeling
observation
prediction
prognostic model
risk
transportability ,
ISSN = 2291-9694 (Print) ,
DOI = 10.2196/21547},
   year = {2021},
   type = {Journal Article}
}

OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age

@article{RN301,
   author = {Duarte-Salles, T. and Vizcaya, D. and Pistillo, A. and Casajust, P. and Sena, A. G. and Lai, L. Y. H. and Prats-Uribe, A. and Ahmed, W. U. and Alshammari, T. M. and Alghoul, H. and Alser, O. and Burn, E. and You, S. C. and Areia, C. and Blacketer, C. and DuVall, S. and Falconer, T. and Fernandez-Bertolin, S. and Fortin, S. and Golozar, A. and Gong, M. and Tan, E. H. and Huser, V. and Iveli, P. and Morales, D. R. and Nyberg, F. and Posada, J. D. and Recalde, M. and Roel, E. and Schilling, L. M. and Shah, N. H. and Shah, K. and Suchard, M. A. and Zhang, L. and Zhang, Y. and Williams, A. E. and Reich, C. G. and Hripcsak, G. and Rijnbeek, P. and Ryan, P. and Kostka, K. and Prieto-Alhambra, D.},
   title = {Thirty-Day Outcomes of Children and Adolescents With COVID-19: An International Experience},
   journal = {Pediatrics},
   volume = {148},
   number = {3},
   note = {1098-4275 Duarte-Salles, Talita Vizcaya, David Pistillo, Andrea Casajust, Paula Sena, Anthony G Lai, Lana Yin Hui Prats-Uribe, Albert Ahmed, Waheed-Ul-Rahman Alshammari, Thamir M Alghoul, Heba Alser, Osaid Burn, Edward You, Seng Chan Areia, Carlos Blacketer, Clair DuVall, Scott Falconer, Thomas Fernandez-Bertolin, Sergio Fortin, Stephen Golozar, Asieh Gong, Mengchun Tan, Eng Hooi Huser, Vojtech Iveli, Pablo Morales, Daniel R Nyberg, Fredrik Posada, Jose D Recalde, Martina Roel, Elena Schilling, Lisa M Shah, Nigam H Shah, Karishma Suchard, Marc A Zhang, Lin Zhang, Ying Williams, Andrew E Reich, Christian G Hripcsak, George Rijnbeek, Peter Ryan, Patrick Kostka, Kristin Prieto-Alhambra, Daniel Comparative Study Journal Article Research Support, Non-U.S. Gov't United States 2021/05/30 Pediatrics. 2021 Sep;148(3):e2020042929. doi: 10.1542/peds.2020-042929. Epub 2021 May 28.},
   abstract = {OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death. RESULTS: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable (n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza. CONCLUSIONS: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19.},
   keywords = {Adolescent
Age Distribution
*COVID-19/complications/diagnosis/epidemiology
Child
Child, Preschool
Cohort Studies
Comorbidity
Databases, Factual
Diagnosis, Differential
Female
France/epidemiology
Germany/epidemiology
Hospitalization/statistics & numerical data
Humans
Infant
Infant, Newborn
Influenza, Human/complications/diagnosis/epidemiology
Male
Republic of Korea/epidemiology
Spain/epidemiology
Symptom Assessment
Time Factors
Treatment Outcome
United States/epidemiology
*COVID-19 Drug Treatment ,
ISSN = 0031-4005 ,
DOI = 10.1542/peds.2020-042929},
   year = {2021},
   type = {Journal Article}
}

PURPOSE: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease. METHODS: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. RESULTS: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer's disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-D-aspartate blocker memantine in AUH. CONCLUSION: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer's Disease patients from across Europe.

@article{RN331,
   author = {James, G. and Collin, E. and Lawrance, M. and Mueller, A. and Podhorna, J. and Zaremba-Pechmann, L. and Rijnbeek, P. and van der Lei, J. and Avillach, P. and Pedersen, L. and Ansell, D. and Pasqua, A. and Mosseveld, M. and Grosdidier, S. and Gungabissoon, U. and Egger, P. and Stewart, R. and Celis-Morales, C. and Alexander, M. and Novak, G. and Gordon, M. F.},
   title = {Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe},
   journal = {Soc Psychiatry Psychiatr Epidemiol},
   volume = {56},
   number = {3},
   pages = {409-416},
   note = {1433-9285 James, Glen Orcid: 0000-0003-0080-3156 Collin, Estelle Lawrance, Marcus Mueller, Achim Podhorna, Jana Zaremba-Pechmann, Liliana Rijnbeek, Peter van der Lei, Johan Avillach, Paul Pedersen, Lars Ansell, David Pasqua, Alessandro Mosseveld, Mees Grosdidier, Solène Gungabissoon, Usha Egger, Peter Stewart, Robert Celis-Morales, Carlos Alexander, Myriam Novak, Gerald Gordon, Mark Forrest MC_PC_17214/MRC_/Medical Research Council/United Kingdom 115372/emif/ Journal Article Germany 2020/06/05 Soc Psychiatry Psychiatr Epidemiol. 2021 Mar;56(3):409-416. doi: 10.1007/s00127-020-01872-2. Epub 2020 Jun 3.},
   abstract = {PURPOSE: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease. METHODS: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. RESULTS: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer's disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-D-aspartate blocker memantine in AUH. CONCLUSION: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer's Disease patients from across Europe.},
   keywords = {*Alzheimer Disease/diagnosis/drug therapy
*Electronic Health Records
Europe
Galantamine
Humans
Indans
Italy
Netherlands
Phenylcarbamates
Piperidines
Retrospective Studies
Alzheimer’s disease
Dementia
Epidemiology
Real-world data ,
ISSN = 0933-7954 ,
DOI = 10.1007/s00127-020-01872-2},
   year = {2021},
   type = {Journal Article}
}

Background: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response [1,2]. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) [3] Characterizing Health Associated Risks, and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Methods: We conducted a descriptive cohort study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11 (th) June 2020 and are iteratively updated via GitHub [4]. Findings: We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19 , and 113,627 hospitalized with COVID-19 requiring intensive services . All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts, and are available in an interactive website: https://data.ohdsi.org/Covid19CharacterizationCharybdis/. Interpretation: CHARYBDIS findings provide benchmarks that contribute to our understanding of COVID-19 progression, management and evolution over time. This can enable timely assessment of real-world outcomes of preventative and therapeutic options as they are introduced in clinical practice. , DOI = 10.21203/rs.3.rs-279400/v1

@article{RN395,
   author = {Prieto-Alhambra, D. and Kostka, K. and Duarte-Salles, T. and Prats-Uribe, A. and Sena, A. and Pistillo, A. and Khalid, S. and Lai, L. and Golozar, A. and Alshammari, T. M. and Dawoud, D. and Nyberg, F. and Wilcox, A. and Andryc, A. and Williams, A. and Ostropolets, A. and Areia, C. and Jung, C. Y. and Harle, C. and Reich, C. and Blacketer, C. and Morales, D. and Dorr, D. A. and Burn, E. and Roel, E. and Tan, E. H. and Minty, E. and DeFalco, F. and de Maeztu, G. and Lipori, G. and Alghoul, H. and Zhu, H. and Thomas, J. and Bian, J. and Park, J. and Roldán, J. M. and Posada, J. and Banda, J. M. and Horcajada, J. P. and Kohler, J. and Shah, K. and Natarajan, K. and Lynch, K. and Liu, L. and Schilling, L. and Recalde, M. and Spotnitz, M. and Gong, M. and Matheny, M. and Valveny, N. and Weiskopf, N. and Shah, N. and Alser, O. and Casajust, P. and Park, R. W. and Schuff, R. and Seager, S. and DuVall, S. and You, S. C. and Song, S. and Fernández-Bertolín, S. and Fortin, S. and Magoc, T. and Falconer, T. and Subbian, V. and Huser, V. and Ahmed, W. U. and Carter, W. and Guan, Y. and Galvan, Y. and He, X. and Rijnbeek, P. and Hripcsak, G. and Ryan, P. and Suchard, M.},
   title = {Unraveling COVID-19: a large-scale characterization of 4.5 million COVID-19 cases using CHARYBDIS},
   journal = {Res Sq},
   note = {Prieto-Alhambra, Daniel Orcid: 0000-0002-3950-6346 Kostka, Kristin Orcid: 0000-0003-2595-8736 Duarte-Salles, Talita Prats-Uribe, Albert Orcid: 0000-0003-1202-9153 Sena, Anthony Orcid: 0000-0001-8630-5347 Pistillo, Andrea Khalid, Sara Lai, Lana Golozar, Asieh Orcid: 0000-0002-4243-155x Alshammari, Thamir M Dawoud, Dalia Nyberg, Fredrik Orcid: 0000-0003-0892-5668 Wilcox, Adam Andryc, Alan Williams, Andrew Orcid: 0000-0002-0692-412x Ostropolets, Anna Areia, Carlos Jung, Chi Young Harle, Christopher Reich, Christian Blacketer, Clair Morales, Daniel Dorr, David A Burn, Edward Orcid: 0000-0002-9286-1128 Roel, Elena Orcid: 0000-0002-1964-3546 Tan, Eng Hooi Minty, Evan DeFalco, Frank de Maeztu, Gabriel Lipori, Gigi Alghoul, Heba Orcid: 0000-0001-8234-5843 Zhu, Hong Thomas, Jason Orcid: 0000-0003-3892-7197 Bian, Jiang Orcid: 0000-0002-2238-5429 Park, Jimyung Roldán, Jordi Martínez Posada, Jose Orcid: 0000-0003-3864-0241 Banda, Juan M Horcajada, Juan P Kohler, Julianna Shah, Karishma Natarajan, Karthik Orcid: 0000-0002-9066-9431 Lynch, Kristine Liu, Li Schilling, Lisa Recalde, Martina Spotnitz, Matthew Gong, Mengchun Matheny, Michael Valveny, Neus Weiskopf, Nicole Shah, Nigam Orcid: 0000-0001-9385-7158 Alser, Osaid Casajust, Paula Orcid: 0000-0003-2733-5436 Park, Rae Woong Schuff, Robert Seager, Sarah DuVall, Scott You, Seng Chan Song, Seokyoung Fernández-Bertolín, Sergio Fortin, Stephen Magoc, Tanja Falconer, Thomas Subbian, Vignesh Huser, Vojtech Ahmed, Waheed-Ul-Rahman Orcid: 0000-0003-0880-0355 Carter, William Guan, Yin Galvan, Yankuic He, Xing Rijnbeek, Peter Hripcsak, George Ryan, Patrick Suchard, Marc Orcid: 0000-0001-9818-479x INV-016201/GATES/Bill & Melinda Gates Foundation/United States INV-016910/GATES/Bill & Melinda Gates Foundation/United States T15 LM007079/LM/NLM NIH HHS/United States P30 AG059307/AG/NIA NIH HHS/United States T15 LM007442/LM/NLM NIH HHS/United States R01 LM006910/LM/NLM NIH HHS/United States UL1 TR002369/TR/NCATS NIH HHS/United States WT_/Wellcome Trust/United Kingdom INV-019257/GATES/Bill & Melinda Gates Foundation/United States Preprint United States 2021/03/11 Res Sq. 2021 Mar 1:rs.3.rs-279400. doi: 10.21203/rs.3.rs-279400/v1. Preprint.},
   abstract = {Background: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response [1,2]. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) [3] Characterizing Health Associated Risks, and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Methods: We conducted a descriptive cohort study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11 (th) June 2020 and are iteratively updated via GitHub [4]. Findings: We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19 , and 113,627 hospitalized with COVID-19 requiring intensive services . All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts, and are available in an interactive website: https://data.ohdsi.org/Covid19CharacterizationCharybdis/. Interpretation: CHARYBDIS findings provide benchmarks that contribute to our understanding of COVID-19 progression, management and evolution over time. This can enable timely assessment of real-world outcomes of preventative and therapeutic options as they are introduced in clinical practice. , DOI = 10.21203/rs.3.rs-279400/v1},
   year = {2021},
   type = {Journal Article}
}

PURPOSE: Current guidelines have no sex-specific dosage advice for metoprolol. To evaluate whether women and men are prescribed the same dose a cohort analysis was performed in the population-based Rotterdam Study (RS). Results were replicated in the Integrated Primary Care Information (IPCI) database of automated general practice data. METHODS: The mean daily starting doses of metoprolol in both sexes were compared with independent-samples t-tests and a linear regression analysis was used to adjust in the RS for co-variables, notably, cardiovascular comorbidity, migraine, age, SBP, DBP, BMI, socioeconomic status, use of other antihypertensive drugs, smoking, and alcohol. In the IPCI-database, adjustment was for age only. RESULTS: The mean daily starting dose was statistically significantly lower in women than in men in both the RS and IPCI database, with a mean difference of 4.8 mg (95%CI -7.8, -1.8) and 4.6 mg (95%CI -5.3,-4.0), respectively. Statistical significance remained after adjustment in both databases. CONCLUSIONS: Women received lower starting doses of metoprolol than men in two independent data collections despite non-sex specific cardiovascular guideline recommendations. This example of real-life pharmacotherapy can lead to a form of confounding by contraindication in pharmacoepidemiology.

@article{RN321,
   author = {Hendriksen, L. C. and Verhamme, K. M. C. and Van der Linden, P. D. and Stricker, B. H. and Visser, L. E.},
   title = {Women are started on a lower daily dose of metoprolol than men irrespective of dose recommendations: A potential source of confounding by contraindication in pharmacoepidemiology},
   journal = {Pharmacoepidemiol Drug Saf},
   volume = {30},
   number = {7},
   pages = {952-959},
   note = {1099-1557 Hendriksen, Linda C Orcid: 0000-0003-0534-4841 Verhamme, Katia M C Van der Linden, Paul D Stricker, Bruno H Visser, Loes E Journal Article Research Support, Non-U.S. Gov't England 2021/03/07 Pharmacoepidemiol Drug Saf. 2021 Jul;30(7):952-959. doi: 10.1002/pds.5220. Epub 2021 Mar 29.},
   abstract = {PURPOSE: Current guidelines have no sex-specific dosage advice for metoprolol. To evaluate whether women and men are prescribed the same dose a cohort analysis was performed in the population-based Rotterdam Study (RS). Results were replicated in the Integrated Primary Care Information (IPCI) database of automated general practice data. METHODS: The mean daily starting doses of metoprolol in both sexes were compared with independent-samples t-tests and a linear regression analysis was used to adjust in the RS for co-variables, notably, cardiovascular comorbidity, migraine, age, SBP, DBP, BMI, socioeconomic status, use of other antihypertensive drugs, smoking, and alcohol. In the IPCI-database, adjustment was for age only. RESULTS: The mean daily starting dose was statistically significantly lower in women than in men in both the RS and IPCI database, with a mean difference of 4.8 mg (95%CI -7.8, -1.8) and 4.6 mg (95%CI -5.3,-4.0), respectively. Statistical significance remained after adjustment in both databases. CONCLUSIONS: Women received lower starting doses of metoprolol than men in two independent data collections despite non-sex specific cardiovascular guideline recommendations. This example of real-life pharmacotherapy can lead to a form of confounding by contraindication in pharmacoepidemiology.},
   keywords = {Antihypertensive Agents
Cohort Studies
Contraindications
Female
Humans
Male
*Metoprolol
*Pharmacoepidemiology
Pharmacoepidemiology
drug utilization
evidence-based medicine
prescribing ,
ISSN = 1053-8569 (Print) 1053-8569 ,
DOI = 10.1002/pds.5220},
   year = {2021},
   type = {Journal Article}
}

Strontium ranelate use, compared with oral bisphosphonates, is not associated with increased risk of AMI in patients with no contraindications for SR use. However, current strontium ranelate (compared with current bisphosphonate) appears associated with 25-30% excess risk of VTE and 35% excess risk of CVDeath. INTRODUCTION: Evaluate the risk of cardiac and thromboembolic events among new users of SR and oral BPs without contraindications for SR. METHODS: We conducted three multi-national, multi-database (Aarhus-Denmark, HSD-Italy, IPCI-Netherlands, SIDIAP-Spain, THIN-UK) case-control studies nested within a cohort of new users of SR/BP. We matched cases of acute myocardial infarction (AMI), venous thromboembolism (VTE), and cardiovascular death (CVDeath), up to 10 controls on gender, year of birth, index date, and country. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) according to current SR vs current BP use and current vs past SR use, adjusting for potential confounders. Data were pooled using random effects meta-analysis. RESULTS: No excess risk of AMI (5477 cases/54,674 controls) was found with current SR vs current BP (OR 0.89 (95%CI 0.70, 1.12)) nor with current vs past SR use (0.71(0.56, 0.91)). For VTE (5614 cases/6036 controls), an excess risk was found with current SR compared with current BP use, 1.24 (0.96, 1.61), and current vs past SR use, 1.30 (1.04, 1.62). For CVDeath (3019 cases/29,871 controls), an increased risk was seen with current SR vs current BP use, 1.35 (1.02, 1.80), but not with current vs past SR use (0.68 (0.48, 0.96)). CONCLUSION: In patients without contraindications for SR, we found no evidence of an increased risk of AMI but a 25-30% excess risk of VTE and a 35% excess risk of CVDeath with current SR vs current BP users. This is despite a reduction in risk in CVDeath with current vs past SR users. The latter disparity could still be partially explained by cessation of preventative therapies in end-of-life or residual confounding by indication.

@article{RN257,
   author = {Ali, M. S. and Berencsi, K. and Marinier, K. and Deltour, N. and Perez-Guthann, S. and Pedersen, L. and Rijnbeek, P. and Lapi, F. and Simonetti, M. and Reyes, C. and Van der Lei, J. and Sturkenboom, M. and Prieto-Alhambra, D.},
   title = {Comparative cardiovascular safety of strontium ranelate and bisphosphonates: a multi-database study in 5 EU countries by the EU-ADR Alliance},
   journal = {Osteoporos Int},
   volume = {31},
   number = {12},
   pages = {2425-2438},
   note = {1433-2965 Ali, M S Orcid: 0000-0002-4192-7908 Berencsi, K Marinier, K Deltour, N Perez-Guthann, S Pedersen, L Rijnbeek, P Lapi, F Simonetti, M Reyes, C Van der Lei, J Sturkenboom, M Prieto-Alhambra, D ./Servier through a research grant to the EU-ADR Alliance/},
   abstract = {Strontium ranelate use, compared with oral bisphosphonates, is not associated with increased risk of AMI in patients with no contraindications for SR use. However, current strontium ranelate (compared with current bisphosphonate) appears associated with 25-30% excess risk of VTE and 35% excess risk of CVDeath. INTRODUCTION: Evaluate the risk of cardiac and thromboembolic events among new users of SR and oral BPs without contraindications for SR. METHODS: We conducted three multi-national, multi-database (Aarhus-Denmark, HSD-Italy, IPCI-Netherlands, SIDIAP-Spain, THIN-UK) case-control studies nested within a cohort of new users of SR/BP. We matched cases of acute myocardial infarction (AMI), venous thromboembolism (VTE), and cardiovascular death (CVDeath), up to 10 controls on gender, year of birth, index date, and country. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) according to current SR vs current BP use and current vs past SR use, adjusting for potential confounders. Data were pooled using random effects meta-analysis. RESULTS: No excess risk of AMI (5477 cases/54,674 controls) was found with current SR vs current BP (OR 0.89 (95%CI 0.70, 1.12)) nor with current vs past SR use (0.71(0.56, 0.91)). For VTE (5614 cases/6036 controls), an excess risk was found with current SR compared with current BP use, 1.24 (0.96, 1.61), and current vs past SR use, 1.30 (1.04, 1.62). For CVDeath (3019 cases/29,871 controls), an increased risk was seen with current SR vs current BP use, 1.35 (1.02, 1.80), but not with current vs past SR use (0.68 (0.48, 0.96)). CONCLUSION: In patients without contraindications for SR, we found no evidence of an increased risk of AMI but a 25-30% excess risk of VTE and a 35% excess risk of CVDeath with current SR vs current BP users. This is despite a reduction in risk in CVDeath with current vs past SR users. The latter disparity could still be partially explained by cessation of preventative therapies in end-of-life or residual confounding by indication.},
   keywords = {*Bone Density Conservation Agents/adverse effects
Case-Control Studies
*Diphosphonates/adverse effects
Humans
Italy
Netherlands
Spain
Thiophenes
Acute myocardial infarction
Cardiovascular death
Embolism
Oral bisphosphonates
Osteoporosis
Safety
Strontium ranelate
Venous thrombosis ,
ISSN = 0937-941x ,
DOI = 10.1007/s00198-020-05580-0},
   year = {2020},
   type = {Journal Article}
}

@article{RN258,
   author = {Ali, M. S. and Berencsi, K. and Marinier, K. and Deltour, N. and Perez-Guthann, S. and Pedersen, L. and Rijnbeek, P. and Lapi, F. and Simonetti, M. and Reyes, C. and Van der Lei, J. and Sturkenboom, M. and Prieto-Alhambra, D.},
   title = {Comparative cardiovascular safety of strontium ranelate and bisphosphonates: a multi-database study in 5 EU countries by the EU-ADR Alliance},
   journal = {Osteoporosis International , DOI = 10.1007/s00198-020-05580-0},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089093737&doi=10.1007%2fs00198-020-05580-0&partnerID=40&md5=09bb063a048b8d64df6b03ef87a33bf0https://link.springer.com/content/pdf/10.1007/s00198-020-05580-0.pdf},
   year = {2020},
   type = {Journal Article}
}

The original version of this article, published on 26 November 2019 contained a mistake. , ISSN = 0937-941x , DOI = 10.1007/s00198-020-05314-2

@article{RN269,
   author = {Berencsi, K. and Sami, A. and Ali, M. S. and Marinier, K. and Deltour, N. and Perez-Gutthann, S. and Pedersen, L. and Rijnbeek, P. and Van der Lei, J. and Lapi, F. and Simonetti, M. and Reyes, C. and Sturkenboom, Mcjm and Prieto-Alhambra, D.},
   title = {Correction to: Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance},
   journal = {Osteoporos Int},
   volume = {31},
   number = {4},
   pages = {799},
   note = {1433-2965 Berencsi, K Sami, A Ali, M S Marinier, K Deltour, N Perez-Gutthann, S Pedersen, L Rijnbeek, P Van der Lei, J Lapi, F Simonetti, M Reyes, C Sturkenboom, M C J M Prieto-Alhambra, D Published Erratum England 2020/02/07 Osteoporos Int. 2020 Apr;31(4):799. doi: 10.1007/s00198-020-05314-2.},
   abstract = {The original version of this article, published on 26 November 2019 contained a mistake. , ISSN = 0937-941x , DOI = 10.1007/s00198-020-05314-2},
   year = {2020},
   type = {Journal Article}
}

BACKGROUND: To demonstrate how the Observational Healthcare Data Science and Informatics (OHDSI) collaborative network and standardization can be utilized to scale-up external validation of patient-level prediction models by enabling validation across a large number of heterogeneous observational healthcare datasets. METHODS: Five previously published prognostic models (ATRIA, CHADS(2), CHADS(2)VASC, Q-Stroke and Framingham) that predict future risk of stroke in patients with atrial fibrillation were replicated using the OHDSI frameworks. A network study was run that enabled the five models to be externally validated across nine observational healthcare datasets spanning three countries and five independent sites. RESULTS: The five existing models were able to be integrated into the OHDSI framework for patient-level prediction and they obtained mean c-statistics ranging between 0.57-0.63 across the 6 databases with sufficient data to predict stroke within 1 year of initial atrial fibrillation diagnosis for females with atrial fibrillation. This was comparable with existing validation studies. The validation network study was run across nine datasets within 60 days once the models were replicated. An R package for the study was published at https://github.com/OHDSI/StudyProtocolSandbox/tree/master/ExistingStrokeRiskExternalValidation. CONCLUSION: This study demonstrates the ability to scale up external validation of patient-level prediction models using a collaboration of researchers and a data standardization that enable models to be readily shared across data sites. External validation is necessary to understand the transportability or reproducibility of a prediction model, but without collaborative approaches it can take three or more years for a model to be validated by one independent researcher. In this paper we show it is possible to both scale-up and speed-up external validation by showing how validation can be done across multiple databases in less than 2 months. We recommend that researchers developing new prediction models use the OHDSI network to externally validate their models.

@article{RN398,
   author = {Reps, J. M. and Williams, R. D. and You, S. C. and Falconer, T. and Minty, E. and Callahan, A. and Ryan, P. B. and Park, R. W. and Lim, H. S. and Rijnbeek, P.},
   title = {Feasibility and evaluation of a large-scale external validation approach for patient-level prediction in an international data network: validation of models predicting stroke in female patients newly diagnosed with atrial fibrillation},
   journal = {BMC Med Res Methodol},
   volume = {20},
   number = {1},
   pages = {102},
   note = {1471-2288 Reps, Jenna M Orcid: 0000-0002-2970-0778 Williams, Ross D You, Seng Chan Falconer, Thomas Minty, Evan Callahan, Alison Ryan, Patrick B Park, Rae Woong Lim, Hong-Seok Rijnbeek, Peter R01 LM011369/LM/NLM NIH HHS/United States HI16C0992/Health Promotion Administration, Ministry of Health and Welfare (TW)/International 806968/Innovative Medicines Initiative Joint Undertaking/International Journal Article Research Support, Non-U.S. Gov't England 2020/05/08 BMC Med Res Methodol. 2020 May 6;20(1):102. doi: 10.1186/s12874-020-00991-3.},
   abstract = {BACKGROUND: To demonstrate how the Observational Healthcare Data Science and Informatics (OHDSI) collaborative network and standardization can be utilized to scale-up external validation of patient-level prediction models by enabling validation across a large number of heterogeneous observational healthcare datasets. METHODS: Five previously published prognostic models (ATRIA, CHADS(2), CHADS(2)VASC, Q-Stroke and Framingham) that predict future risk of stroke in patients with atrial fibrillation were replicated using the OHDSI frameworks. A network study was run that enabled the five models to be externally validated across nine observational healthcare datasets spanning three countries and five independent sites. RESULTS: The five existing models were able to be integrated into the OHDSI framework for patient-level prediction and they obtained mean c-statistics ranging between 0.57-0.63 across the 6 databases with sufficient data to predict stroke within 1 year of initial atrial fibrillation diagnosis for females with atrial fibrillation. This was comparable with existing validation studies. The validation network study was run across nine datasets within 60 days once the models were replicated. An R package for the study was published at https://github.com/OHDSI/StudyProtocolSandbox/tree/master/ExistingStrokeRiskExternalValidation. CONCLUSION: This study demonstrates the ability to scale up external validation of patient-level prediction models using a collaboration of researchers and a data standardization that enable models to be readily shared across data sites. External validation is necessary to understand the transportability or reproducibility of a prediction model, but without collaborative approaches it can take three or more years for a model to be validated by one independent researcher. In this paper we show it is possible to both scale-up and speed-up external validation by showing how validation can be done across multiple databases in less than 2 months. We recommend that researchers developing new prediction models use the OHDSI network to externally validate their models.},
   keywords = {*Atrial Fibrillation/diagnosis/epidemiology
Feasibility Studies
Female
Humans
Prognosis
Reproducibility of Results
*Stroke/diagnosis/epidemiology
Collaborative network
External validation
Patient-level prediction
Prognostic model
Transportability ,
ISSN = 1471-2288 ,
DOI = 10.1186/s12874-020-00991-3},
   year = {2020},
   type = {Journal Article}
}

BACKGROUND: Adrenal suppression is a side effect of long-term use of inhaled corticosteroids (ICS). Hair cortisol concentration (HCC) measurement is a noninvasive tool for measuring adrenal function that may be useful for asthmatic patients who are on long-term ICS treatment. The aim of this study was to compare HCC between children with and without asthma and to explore the association between HCC and ICS dose in asthmatic children. METHODS: A cross-sectional observational study in subjects with or without asthma (n = 72 and 226, respectively, age 6-21 years). Hair samples were obtained from the posterior vertex for each subject and data on medication use were collected using questionnaires. HCC was analyzed by liquid chromatography-mass spectrometry in the most proximal 3 cm of hair. RESULTS: Median HCC was significantly lower in subjects with asthma than in subjects without asthma: 1.83 pg/mg and 2.39 pg/mg, respectively (P value after adjustment for age, sex, and body mass index: .036). Median HCC was 1.98 pg/mg in asthmatics using no ICS, 1.84 pg/mg in those using a low dose, 1.75 pg/mg in those on a medium dose, and 1.46 in those using a high ICS dose (P = .54). CONCLUSION: We observed a significantly lower HCC in asthmatics than in healthy controls and a nonsignificant trend of lower HCC with increasing ICS dose. Whether HCC measurement may be used to detect individuals at risk for hypocortisolism and may be useful to monitor adrenal function in asthmatic children using ICS needs to be further investigated.

@article{RN266,
   author = {Baan, E. J. and van den Akker, E. L. T. and Engelkes, M. and de Rijke, Y. B. and de Jongste, J. C. and Sturkenboom, Mcjm and Verhamme, K. M. and Janssens, H. M.},
   title = {Hair cortisol and inhaled corticosteroid use in asthmatic children},
   journal = {Pediatr Pulmonol},
   volume = {55},
   number = {2},
   pages = {316-321},
   note = {1099-0496 Baan, Esmé J Orcid: 0000-0002-0735-4296 van den Akker, Erica L T Engelkes, Marjolein de Rijke, Yolanda B de Jongste, Johan C Sturkenboom, Miriam C J M Verhamme, Katia M Janssens, Hettie M Journal Article Research Support, Non-U.S. Gov't United States 2019/10/28 Pediatr Pulmonol. 2020 Feb;55(2):316-321. doi: 10.1002/ppul.24551. Epub 2019 Oct 25.},
   abstract = {BACKGROUND: Adrenal suppression is a side effect of long-term use of inhaled corticosteroids (ICS). Hair cortisol concentration (HCC) measurement is a noninvasive tool for measuring adrenal function that may be useful for asthmatic patients who are on long-term ICS treatment. The aim of this study was to compare HCC between children with and without asthma and to explore the association between HCC and ICS dose in asthmatic children. METHODS: A cross-sectional observational study in subjects with or without asthma (n = 72 and 226, respectively, age 6-21 years). Hair samples were obtained from the posterior vertex for each subject and data on medication use were collected using questionnaires. HCC was analyzed by liquid chromatography-mass spectrometry in the most proximal 3 cm of hair. RESULTS: Median HCC was significantly lower in subjects with asthma than in subjects without asthma: 1.83 pg/mg and 2.39 pg/mg, respectively (P value after adjustment for age, sex, and body mass index: .036). Median HCC was 1.98 pg/mg in asthmatics using no ICS, 1.84 pg/mg in those using a low dose, 1.75 pg/mg in those on a medium dose, and 1.46 in those using a high ICS dose (P = .54). CONCLUSION: We observed a significantly lower HCC in asthmatics than in healthy controls and a nonsignificant trend of lower HCC with increasing ICS dose. Whether HCC measurement may be used to detect individuals at risk for hypocortisolism and may be useful to monitor adrenal function in asthmatic children using ICS needs to be further investigated.},
   keywords = {Administration, Inhalation
Adrenal Cortex Hormones/administration & dosage/*therapeutic use
Anti-Asthmatic Agents/*therapeutic use
Asthma/*drug therapy
Child
Child, Preschool
Cross-Sectional Studies
Drug-Related Side Effects and Adverse Reactions/drug therapy
Female
Hair/chemistry
Humans
Hydrocortisone/*analysis
Male
adrenal insufficiency
asthma
diagnostic techniques and procedures
drug-related side effects and adverse reactions
glucocorticoids ,
ISSN = 8755-6863 (Print) 1099-0496 ,
DOI = 10.1002/ppul.24551},
   year = {2020},
   type = {Journal Article}
}

@article{RN267,
   author = {Baan, E. J. and van den Akker, E. L. T. and Engelkes, M. and de Rijke, Y. B. and de Jongste, J. C. and Sturkenboom, M. C. J. M. and Verhamme, K. M. and Janssens, H. M.},
   title = {Hair cortisol and inhaled corticosteroid use in asthmatic children},
   journal = {Pediatric Pulmonology},
   volume = {55},
   number = {2},
   pages = {316-321 , DOI = 10.1002/ppul.24551},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074632627&doi=10.1002%2fppul.24551&partnerID=40&md5=8263ccb286e649e83804225e5040f7b7https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003950/pdf/PPUL-55-316.pdf},
   year = {2020},
   type = {Journal Article}
}

INTRODUCTION: In May 2013 and March 2014, the European Medicines Agency (EMA) issued two decisions restricting the use of strontium ranelate (SR). These risk minimisation measures (RMM) introduced new contraindications and limited the indications of SR therapy. The EMA required an assessment of the impact of RMMs on the use of SR in Europe. Methods design: multi-national, multi-database cohort Setting: electronic medical record databases based on hospital (Denmark) and primary care provenance (Italy, Spain, the Netherlands, UK). PARTICIPANTS: the database source populations were included for population-based analyses, and SR users for patient-level analyses. INTERVENTION: New RMMs included contraindications (ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension) and restricted SR indication to severe osteoporosis with initiation by experienced physician and not as first line anti-osteoporosis therapy. METHODS: Prevalence and incidence rates of SR use in the population; prevalence of contraindications and restricted indications in SR users, plus 1-year therapy persistence. Drug use measures were calculated in three periods for comparison: reference (2004 to May 2013), transition (June 2013 to March 2014) and assessment (from April 2014 to end 2016). RESULTS: The study population included 143 million person-years(PY) of follow-up and 76,141 incident episodes of SR treatment. Average monthly prevalence rates of SR use dropped by 86.4% from 62.6/10,000 PY (95 CI 62.4-62.9) in the reference to 8.5 (8.5-8.6) in the assessment period. Similarly, the incidence rate of SR use fell by 97.3% from 7.4/10,000 PY (7.4-7.4) to 0.2 (0.2-0.2) between the reference and assessment period. The prevalence of any contraindication decreased, whilst the prevalence of restricted indications increased in these periods. One-year persistence decreased in the assessment compared with reference period. CONCLUSIONS: Our study demonstrates a substantial impact of the regulatory action to restrict use of SR in Europe: SR utilisation overall decreased strongly. The proportion of patients fulfilling the restricted indications, without contraindications, increased after the proposed RMMs.

@article{RN270,
   author = {Berencsi, K. and Sami, A. and Ali, M. S. and Marinier, K. and Deltour, N. and Perez-Gutthann, S. and Pedersen, L. and Rijnbeek, P. and Van der Lei, J. and Lapi, F. and Simonetti, M. and Reyes, C. and Sturkenboom, Mcjm and Prieto-Alhambra, D.},
   title = {Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance},
   journal = {Osteoporos Int},
   volume = {31},
   number = {4},
   pages = {721-755},
   note = {1433-2965 Berencsi, K Sami, A Ali, M S Marinier, K Deltour, N Perez-Gutthann, S Pedersen, L Rijnbeek, P Van der Lei, J Lapi, F Simonetti, M Reyes, C Sturkenboom, M C J M Prieto-Alhambra, D Orcid: 0000-0002-3950-6346 NA/Servier/ Journal Article England 2019/11/07 Osteoporos Int. 2020 Apr;31(4):721-755. doi: 10.1007/s00198-019-05181-6. Epub 2019 Nov 6.},
   abstract = {INTRODUCTION: In May 2013 and March 2014, the European Medicines Agency (EMA) issued two decisions restricting the use of strontium ranelate (SR). These risk minimisation measures (RMM) introduced new contraindications and limited the indications of SR therapy. The EMA required an assessment of the impact of RMMs on the use of SR in Europe. Methods design: multi-national, multi-database cohort Setting: electronic medical record databases based on hospital (Denmark) and primary care provenance (Italy, Spain, the Netherlands, UK). PARTICIPANTS: the database source populations were included for population-based analyses, and SR users for patient-level analyses. INTERVENTION: New RMMs included contraindications (ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension) and restricted SR indication to severe osteoporosis with initiation by experienced physician and not as first line anti-osteoporosis therapy. METHODS: Prevalence and incidence rates of SR use in the population; prevalence of contraindications and restricted indications in SR users, plus 1-year therapy persistence. Drug use measures were calculated in three periods for comparison: reference (2004 to May 2013), transition (June 2013 to March 2014) and assessment (from April 2014 to end 2016). RESULTS: The study population included 143 million person-years(PY) of follow-up and 76,141 incident episodes of SR treatment. Average monthly prevalence rates of SR use dropped by 86.4% from 62.6/10,000 PY (95 CI 62.4-62.9) in the reference to 8.5 (8.5-8.6) in the assessment period. Similarly, the incidence rate of SR use fell by 97.3% from 7.4/10,000 PY (7.4-7.4) to 0.2 (0.2-0.2) between the reference and assessment period. The prevalence of any contraindication decreased, whilst the prevalence of restricted indications increased in these periods. One-year persistence decreased in the assessment compared with reference period. CONCLUSIONS: Our study demonstrates a substantial impact of the regulatory action to restrict use of SR in Europe: SR utilisation overall decreased strongly. The proportion of patients fulfilling the restricted indications, without contraindications, increased after the proposed RMMs.},
   keywords = {*Bone Density Conservation Agents/therapeutic use
Cohort Studies
Europe/epidemiology
Health Policy
Humans
Italy
Netherlands
*Organometallic Compounds
Spain
Thiophenes/*therapeutic use
Pharmacoepidemiology
Risk minimisation measures
Strontium ranelate ,
ISSN = 0937-941x ,
DOI = 10.1007/s00198-019-05181-6},
   year = {2020},
   type = {Journal Article}
}

@article{RN271,
   author = {Berencsi, K. and Sami, A. and Ali, M. S. and Marinier, K. and Deltour, N. and Perez-Gutthann, S. and Pedersen, L. and Rijnbeek, P. and Van der Lei, J. and Lapi, F. and Simonetti, M. and Reyes, C. and Sturkenboom, M. C. J. M. and Prieto-Alhambra, D.},
   title = {Impact of risk minimisation measures on the use of strontium ranelate in Europe: a multi-national cohort study in 5 EU countries by the EU-ADR Alliance},
   journal = {Osteoporosis International},
   volume = {31},
   number = {4},
   pages = {721-755 , DOI = 10.1007/s00198-019-05181-6},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074813652&doi=10.1007%2fs00198-019-05181-6&partnerID=40&md5=8213e0e6255322f0322bee0b1bfa241chttps://link.springer.com/content/pdf/10.1007/s00198-019-05181-6.pdf},
   year = {2020},
   type = {Journal Article}
}

BACKGROUND: There are sparse real-world data on severe asthma exacerbations (SAE) in children. This multinational cohort study assessed the incidence of and risk factors for SAE and the incidence of asthma-related rehospitalization in children with asthma. METHODS: Asthma patients 5-17 years old with ≥1 year of follow-up were identified in six European electronic databases from the Netherlands, Italy, the UK, Denmark and Spain in 2008-2013. Asthma was defined as ≥1 asthma-specific disease code within 3 months of prescriptions/dispensing of asthma medication. Severe asthma was defined as high-dosed inhaled corticosteroids plus a second controller. SAE was defined by systemic corticosteroids, emergency department visit and/or hospitalization all for reason of asthma. Risk factors for SAE were estimated by Poisson regression analyses. RESULTS: The cohort consisted of 212 060 paediatric asthma patients contributing to 678 625 patient-years (PY). SAE rates ranged between 17 and 198/1000 PY and were higher in severe asthma and highest in severe asthma patients with a history of exacerbations. Prior SAE (incidence rate ratio 3-45) and younger age increased the SAE risk in all countries, whereas obesity, atopy and GERD were a risk factor in some but not all countries. Rehospitalization rates were up to 79% within 1 year. CONCLUSIONS: In a real-world setting, SAE rates were highest in children with severe asthma with a history of exacerbations. Many severe asthma patients were rehospitalized within 1 year. Asthma management focusing on prevention of SAE is important to reduce the burden of asthma.

@article{RN303,
   author = {Engelkes, M. and Baan, E. J. and de Ridder, M. A. J. and Svensson, E. and Prieto-Alhambra, D. and Lapi, F. and Giaquinto, C. and Picelli, G. and Boudiaf, N. and Albers, F. and Evitt, L. A. and Cockle, S. and Bradford, E. and Van Dyke, M. K. and Suruki, R. and Rijnbeek, P. and Sturkenboom, Mcjm and Janssens, H. M. and Verhamme, K. M. C.},
   title = {Incidence, risk factors and re-exacerbation rate of severe asthma exacerbations in a multinational, multidatabase pediatric cohort study},
   journal = {Pediatr Allergy Immunol},
   volume = {31},
   number = {5},
   pages = {496-505},
   note = {1399-3038 Engelkes, Marjolein Baan, Esme J Orcid: 0000-0002-0735-4296 de Ridder, Maria A J Svensson, Elisabeth Prieto-Alhambra, Daniel Lapi, Francesco Giaquinto, Carlo Picelli, Gino Boudiaf, Nada Albers, Frank Orcid: 0000-0001-7039-4621 Evitt, Lee A Cockle, Sarah Bradford, Eric Van Dyke, Melissa K Orcid: 0000-0001-7246-2093 Suruki, Robert Rijnbeek, Peter Sturkenboom, Miriam C J M Janssens, Hettie M Verhamme, Katia M C Journal Article Research Support, Non-U.S. Gov't England 2020/03/03 Pediatr Allergy Immunol. 2020 Jul;31(5):496-505. doi: 10.1111/pai.13237. Epub 2020 Mar 20.},
   abstract = {BACKGROUND: There are sparse real-world data on severe asthma exacerbations (SAE) in children. This multinational cohort study assessed the incidence of and risk factors for SAE and the incidence of asthma-related rehospitalization in children with asthma. METHODS: Asthma patients 5-17 years old with ≥1 year of follow-up were identified in six European electronic databases from the Netherlands, Italy, the UK, Denmark and Spain in 2008-2013. Asthma was defined as ≥1 asthma-specific disease code within 3 months of prescriptions/dispensing of asthma medication. Severe asthma was defined as high-dosed inhaled corticosteroids plus a second controller. SAE was defined by systemic corticosteroids, emergency department visit and/or hospitalization all for reason of asthma. Risk factors for SAE were estimated by Poisson regression analyses. RESULTS: The cohort consisted of 212 060 paediatric asthma patients contributing to 678 625 patient-years (PY). SAE rates ranged between 17 and 198/1000 PY and were higher in severe asthma and highest in severe asthma patients with a history of exacerbations. Prior SAE (incidence rate ratio 3-45) and younger age increased the SAE risk in all countries, whereas obesity, atopy and GERD were a risk factor in some but not all countries. Rehospitalization rates were up to 79% within 1 year. CONCLUSIONS: In a real-world setting, SAE rates were highest in children with severe asthma with a history of exacerbations. Many severe asthma patients were rehospitalized within 1 year. Asthma management focusing on prevention of SAE is important to reduce the burden of asthma.},
   keywords = {Adolescent
Adrenal Cortex Hormones/therapeutic use
*Anti-Asthmatic Agents/therapeutic use
*Asthma/drug therapy
Child
Child, Preschool
Cohort Studies
Disease Progression
Europe/epidemiology
Female
Humans
Incidence
Male
Risk Factors
asthma: epidemiology
asthma: risk factors
epidemiology: prevalence ,
ISSN = 0905-6157 (Print) 0905-6157 ,
DOI = 10.1111/pai.13237},
   year = {2020},
   type = {Journal Article}
}

@article{RN304,
   author = {Engelkes, M. and Baan, E. J. and de Ridder, M. A. J. and Svensson, E. and Prieto-Alhambra, D. and Lapi, F. and Giaquinto, C. and Picelli, G. and Boudiaf, N. and Albers, F. and Evitt, L. A. and Cockle, S. and Bradford, E. and Van Dyke, M. K. and Suruki, R. and Rijnbeek, P. and Sturkenboom, M. C. J. M. and Janssens, H. M. and Verhamme, K. M. C.},
   title = {Incidence, risk factors and re-exacerbation rate of severe asthma exacerbations in a multinational, multidatabase pediatric cohort study},
   journal = {Pediatric Allergy and Immunology},
   volume = {31},
   number = {5},
   pages = {496-505 , DOI = 10.1111/pai.13237},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85082070094&doi=10.1111%2fpai.13237&partnerID=40&md5=9f37851e9d613e5cd0d1aa8bd1590591https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/pai.13237?download=true},
   year = {2020},
   type = {Journal Article}
}

BACKGROUND: Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. METHODS: A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia. RESULTS: Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52-0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17-0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57-1.37). CONCLUSIONS: Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk.

@article{RN378,
   author = {Newby, D. and Prieto-Alhambra, D. and Duarte-Salles, T. and Ansell, D. and Pedersen, L. and van der Lei, J. and Mosseveld, M. and Rijnbeek, P. and James, G. and Alexander, M. and Egger, P. and Podhorna, J. and Stewart, R. and Perera, G. and Avillach, P. and Grosdidier, S. and Lovestone, S. and Nevado-Holgado, A. J.},
   title = {Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: a multi-national multi-database case-control study},
   journal = {Alzheimers Res Ther},
   volume = {12},
   number = {1},
   pages = {38},
   note = {1758-9193 Newby, Danielle Prieto-Alhambra, Daniel Duarte-Salles, Talita Ansell, David Pedersen, Lars van der Lei, Johan Mosseveld, Mees Rijnbeek, Peter James, Glen Alexander, Myriam Egger, Peter Podhorna, Jana Stewart, Robert Perera, Gayan Avillach, Paul Grosdidier, Solène Lovestone, Simon Nevado-Holgado, Alejo J},
   abstract = {BACKGROUND: Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. METHODS: A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia. RESULTS: Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52-0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17-0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57-1.37). CONCLUSIONS: Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk.},
   keywords = {Aged
*Antirheumatic Agents/therapeutic use
*Arthritis, Rheumatoid/drug therapy/epidemiology
Case-Control Studies
*Dementia/drug therapy/epidemiology
Female
Humans
Male
Methotrexate/therapeutic use
Middle Aged
Netherlands
Retrospective Studies
Risk Factors
Anti-inflammatory drugs
Case-control study
DMARDs
Dementia
Emif
European Medical Information Framework
Inflammation
Methotrexate
Rheumatoid arthritis
Sulfasalazine ,
DOI = 10.1186/s13195-020-00606-5},
   year = {2020},
   type = {Journal Article}
}

@article{RN379,
   author = {Newby, D. and Prieto-Alhambra, D. and Duarte-Salles, T. and Ansell, D. and Pedersen, L. and Van Der Lei, J. and Mosseveld, M. and Rijnbeek, P. and James, G. and Alexander, M. and Egger, P. and Podhorna, J. and Stewart, R. and Perera, G. and Avillach, P. and Grosdidier, S. and Lovestone, S. and Nevado-Holgado, A. J.},
   title = {Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: A multi-national multi-database case-control study},
   journal = {Alzheimer's Research and Therapy},
   volume = {12},
   number = {1 , DOI = 10.1186/s13195-020-00606-5},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083071675&doi=10.1186%2fs13195-020-00606-5&partnerID=40&md5=1636c9188dc6ed5e77e151c9f2ca3258https://alzres.biomedcentral.com/track/pdf/10.1186/s13195-020-00606-5},
   year = {2020},
   type = {Journal Article}
}

@article{RN380,
   author = {Newby, D. and Prieto-Alhambra, D. and Duarte-Salles, T. and Ansell, D. and Pedersen, L. and Van Der Lei, J. and Mosseveld, M. and Rijnbeek, P. and James, G. and Alexander, M. and Egger, P. and Podhorna, J. and Stewart, R. and Perera, G. and Avillach, P. and Grosdidier, S. and Lovestone, S. and Nevado-Holgado, A. J.},
   title = {Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: A multi-national multi-database case-control study},
   journal = {Alzheimer's Research and Therapy},
   volume = {12},
   number = {1 , DOI = 10.1186/s13195-020-00606-5},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083071675&doi=10.1186%2fs13195-020-00606-5&partnerID=40&md5=1636c9188dc6ed5e77e151c9f2ca3258https://alzres.biomedcentral.com/track/pdf/10.1186/s13195-020-00606-5},
   year = {2020},
   type = {Journal Article}
}

BACKGROUND: Data on the risk of death following an asthma exacerbation are scarce. With this multinational cohort study, we assessed all-cause mortality rates, mortality rates following an exacerbation, and patient characteristics associated with all-cause mortality in asthma. METHODS: Asthma patients aged ≥18 years and with ≥1 year of follow-up were identified in 5 European electronic databases from the Netherlands, Italy, UK, Denmark and Spain during the study period January 1, 2008-December 31, 2013. Patients with asthma-COPD overlap were excluded. Severe asthma was defined as use of high dose ICS + use of a second controller. Severe asthma exacerbations were defined as emergency department visits, hospitalizations or systemic corticosteroid use, all for reason of asthma. RESULTS: The cohort consisted of 586,436 asthma patients of which 42,611 patients (7.3%) had severe asthma. The age and sex standardized all-cause mortality rates ranged between databases from 5.2 to 9.5/1000 person-years (PY) in asthma, and between 11.3 and 14.8/1000 PY in severe asthma. The all-cause mortality rate in the first week following a severe asthma exacerbation ranged between 14.1 and 59.9/1000 PY. Mortality rates remained high in the first month following a severe asthma exacerbation and decreased thereafter. Higher age, male gender, comorbidity, smoking, and previous severe asthma exacerbations were associated with mortality. CONCLUSION: All-cause mortality following a severe exacerbation is high, especially in the first month following the event. Smoking cessation, comorbidity-management and asthma-treatment focusing on the prevention of exacerbations might reduce associated mortality.

@article{RN305,
   author = {Engelkes, M. and de Ridder, M. A. and Svensson, E. and Berencsi, K. and Prieto-Alhambra, D. and Lapi, F. and Giaquinto, C. and Picelli, G. and Boudiaf, N. and Albers, F. C. and Cockle, S. M. and Bradford, E. S. and Suruki, R. Y. and Brusselle, G. G. and Rijnbeek, P. R. and Sturkenboom, M. C. and Verhamme, K. M.},
   title = {Multinational cohort study of mortality in patients with asthma and severe asthma},
   journal = {Respir Med},
   volume = {165},
   pages = {105919},
   note = {1532-3064 Engelkes, Marjolein de Ridder, Maria Aj Svensson, Elisabeth Berencsi, Klara Prieto-Alhambra, Daniel Lapi, Francesco Giaquinto, Carlo Picelli, Gino Boudiaf, Nada Albers, Frank C Cockle, Sarah M Bradford, Eric S Suruki, Robert Y Brusselle, Guy Go Rijnbeek, Peter R Sturkenboom, Miriam Cjm Verhamme, Katia Mc Journal Article Research Support, Non-U.S. Gov't England 2020/03/17 Respir Med. 2020 Apr-May;165:105919. doi: 10.1016/j.rmed.2020.105919. Epub 2020 Mar 2.},
   abstract = {BACKGROUND: Data on the risk of death following an asthma exacerbation are scarce. With this multinational cohort study, we assessed all-cause mortality rates, mortality rates following an exacerbation, and patient characteristics associated with all-cause mortality in asthma. METHODS: Asthma patients aged ≥18 years and with ≥1 year of follow-up were identified in 5 European electronic databases from the Netherlands, Italy, UK, Denmark and Spain during the study period January 1, 2008-December 31, 2013. Patients with asthma-COPD overlap were excluded. Severe asthma was defined as use of high dose ICS + use of a second controller. Severe asthma exacerbations were defined as emergency department visits, hospitalizations or systemic corticosteroid use, all for reason of asthma. RESULTS: The cohort consisted of 586,436 asthma patients of which 42,611 patients (7.3%) had severe asthma. The age and sex standardized all-cause mortality rates ranged between databases from 5.2 to 9.5/1000 person-years (PY) in asthma, and between 11.3 and 14.8/1000 PY in severe asthma. The all-cause mortality rate in the first week following a severe asthma exacerbation ranged between 14.1 and 59.9/1000 PY. Mortality rates remained high in the first month following a severe asthma exacerbation and decreased thereafter. Higher age, male gender, comorbidity, smoking, and previous severe asthma exacerbations were associated with mortality. CONCLUSION: All-cause mortality following a severe exacerbation is high, especially in the first month following the event. Smoking cessation, comorbidity-management and asthma-treatment focusing on the prevention of exacerbations might reduce associated mortality.},
   keywords = {Adrenal Cortex Hormones
Age Factors
Asthma/*mortality
Cause of Death
Cohort Studies
Comorbidity
Disease Progression
Drug Utilization
Emergency Service, Hospital/statistics & numerical data
Europe/epidemiology
Female
Hospitalization/statistics & numerical data
Humans
Male
Severity of Illness Index
Sex Factors
Smoking/adverse effects
Asthma epidemiology
Mortality
Severe asthma ,
ISSN = 0954-6111 ,
DOI = 10.1016/j.rmed.2020.105919},
   year = {2020},
   type = {Journal Article}
}

@article{RN306,
   author = {Engelkes, M. and de Ridder, M. A. and Svensson, E. and Berencsi, K. and Prieto-Alhambra, D. and Lapi, F. and Giaquinto, C. and Picelli, G. and Boudiaf, N. and Albers, F. C. and Cockle, S. M. and Bradford, E. S. and Suruki, R. Y. and Brusselle, G. G. and Rijnbeek, P. R. and Sturkenboom, M. C. and Verhamme, K. M.},
   title = {Multinational cohort study of mortality in patients with asthma and severe asthma},
   journal = {Respiratory Medicine},
   volume = {165 , DOI = 10.1016/j.rmed.2020.105919},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85080978918&doi=10.1016%2fj.rmed.2020.105919&partnerID=40&md5=d0bc9ae222ac23f653c5c6a3fd10b161https://pdf.sciencedirectassets.com/272432/1-s2.0-S0954611120X00059/1-s2.0-S0954611120300597/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEAEaCXVzLWVhc3QtMSJHMEUCIDf8wvVMDfMrRW2eWBUPOcCQpcVXG%2BMxd3F3D%2BhGj1aLAiEArvYSn5jaxAnFGyUaMmJqw8%2BX6%2FxILFz%2Fy6hbldpa2yEqtAMIKhADGgwwNTkwMDM1NDY4NjUiDI0MAWjG5QcQkXhA1SqRA7TTvpQK9F%2FPvjK%2BL6PypRP21E8qc1%2FIhy4k%2B1NI3MRQmGbQo8mQRrP9qossLG3CsejsBC7tpdmYCKYWdy%2FPeGOu7AmtdVautQ%2FCsw%2BiWta4Xj2zOa9a%2B6zA7xeVcT17qnhIkV2VWbYYo1rRX%2FJt1%2FLEkt4JkzBvpSiXGn5GFqgoxQXIbRUYz0HyFGmVbEGFNUB2C1QZx%2B8%2FTRt7abd2suDLEtykzSNoHGTbG2jnpAU2%2BBOluIJ6%2FIJ1e16O4Z6q7tm288aua1nLpPwkrvjOUHSr9DyRGCG0pjWqrytH7boIZQXrH7MmFIj1589dehH1fvnd81akxJSdccAU%2BIEUaE0P6BzOe7Gff8xYnkh%2FmHCSPaKOSWMGPPjXLoyZR64rJcUDrTd%2BDuh8bHCtrRDRiXzSXAfZqYzR7fhovkmpjRV9G8wNut%2FYwhqb4VvBUYcuhTjhWwnMG05nWONo6icWJohrjg1kUognV5%2F8OjJFTOkc29ljjo0Z9Rd4K8BdDaq1ZiSmno9zGGb2s%2F%2B05VVytPVLMJbd%2BvQFOusBdyLmxkk8uhsFxeFs2VQ9y9AlQXQ7AZqafX%2B8%2B25sJZsErPKwJwCj0ej0tVkohVlNznMa3fFQZaL%2FBd7RBStGAVrRoP1wOkFMUURrMOEfWsOdG3NjdzkGm%2F85TgpAUv0%2BoKePvpruLKiPz%2Fivig0xvt1NqhSo8E4pTtCpgiAMKSbYOzyvxa5MBjSgkBalFhjk0ShNojowzvLBTwAAlRGFPU7SnhzmWdRhIB9CzCcTV9Mf71Gp1v0IdzNZMZsTaUjwfJlJcClW%2BKoMWybo7PAtxjvGlx%2BHJSm0B3N%2BQPDoSzul2bHhLCtCMhNSGQ%3D%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20200421T090833Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYUZFNOPVY%2F20200421%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=e3a6a4a048a5d0dc6c69d02ac331b0d54cd9d277f120679a55c3c62dd50855db&hash=4be0ab03c65f47ef8bf78ea160fa20833329737284aabeec3e4b3bc59d7b03c4&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S0954611120300597&tid=spdf-c1e52348-00eb-4a9a-a362-247cbaebc4ae&sid=223c17b953b8574f2d98d0f-db35cdd3752agxrqb&type=client},
   year = {2020},
   type = {Journal Article}
}

OBJECTIVES: To examine the incidence, prevalence and trends for opioid prescriptions in patients with OA. Furthermore, types of opioids prescribed and long-term prescription rates were examined. Finally, the patient characteristics associated with the prescription of opioids were assessed. METHODS: A population-based cohort study was conducted using the Integrated Primary Care Information database. Incidence and prevalence of opioid prescriptions were calculated for the period 2008-2017. Logistic regression was used to assess which patient characteristics were associated with opioid prescriptions. RESULTS: In total, 157 904 OA patients were included. The overall prescription rate remained fairly stable, at around 100 incident and 170 prevalent prescriptions per 1000 person years. However, the incident prescription rate for oxycodone increased from 7.1 to 40.7 per 1000 person years and for fentanyl from 4.2 to 7.4 per 1000 person years. The incident prescription rate for paracetamol/codeine decreased from 63.0 to 13.3 per 1000 person years. Per follow-up year, long-term use was found in 3% of the patients with incident OA. Finally, factors associated with more prescriptions were increasing age, OA in ≥2 joint groups [odds ratio (OR) 1.56; 95% CI: 1.51, 1.65] and the presence of other musculoskeletal disorders (OR 4.91; 95% CI: 4.76, 5.05). Men were less likely to be prescribed opioids (OR 0.78; 95% CI: 0.76, 0.80). CONCLUSION: Prescription rates for opioids remained stable, but types of opioids prescribed changed. Oxycodone and fentanyl were increasingly prescribed, while prescriptions of paracetamol/codeine decreased. Since the benefit of opioids for OA pain is questionable and side effects are common, opioids should be prescribed with caution.

@article{RN445,
   author = {van den Driest, J. J. and Schiphof, D. and de Wilde, M. and Bindels, P. J. E. and van der Lei, J. and Bierma-Zeinstra, S. M. A.},
   title = {Opioid prescriptions in patients with osteoarthritis: a population-based cohort study},
   journal = {Rheumatology (Oxford)},
   volume = {59},
   number = {9},
   pages = {2462-2470},
   note = {1462-0332 van den Driest, Jacoline J Schiphof, Dieuwke de Wilde, Marcel Bindels, Patrick J E van der Lei, Johan Bierma-Zeinstra, Sita M A Evaluation Study Journal Article England 2020/01/22 Rheumatology (Oxford). 2020 Sep 1;59(9):2462-2470. doi: 10.1093/rheumatology/kez646.},
   abstract = {OBJECTIVES: To examine the incidence, prevalence and trends for opioid prescriptions in patients with OA. Furthermore, types of opioids prescribed and long-term prescription rates were examined. Finally, the patient characteristics associated with the prescription of opioids were assessed. METHODS: A population-based cohort study was conducted using the Integrated Primary Care Information database. Incidence and prevalence of opioid prescriptions were calculated for the period 2008-2017. Logistic regression was used to assess which patient characteristics were associated with opioid prescriptions. RESULTS: In total, 157 904 OA patients were included. The overall prescription rate remained fairly stable, at around 100 incident and 170 prevalent prescriptions per 1000 person years. However, the incident prescription rate for oxycodone increased from 7.1 to 40.7 per 1000 person years and for fentanyl from 4.2 to 7.4 per 1000 person years. The incident prescription rate for paracetamol/codeine decreased from 63.0 to 13.3 per 1000 person years. Per follow-up year, long-term use was found in 3% of the patients with incident OA. Finally, factors associated with more prescriptions were increasing age, OA in ≥2 joint groups [odds ratio (OR) 1.56; 95% CI: 1.51, 1.65] and the presence of other musculoskeletal disorders (OR 4.91; 95% CI: 4.76, 5.05). Men were less likely to be prescribed opioids (OR 0.78; 95% CI: 0.76, 0.80). CONCLUSION: Prescription rates for opioids remained stable, but types of opioids prescribed changed. Oxycodone and fentanyl were increasingly prescribed, while prescriptions of paracetamol/codeine decreased. Since the benefit of opioids for OA pain is questionable and side effects are common, opioids should be prescribed with caution.},
   keywords = {Adult
Aged
Aged, 80 and over
Analgesics, Opioid/*therapeutic use
Databases, Factual
Drug Prescriptions/*statistics & numerical data
Female
Humans
Logistic Models
Male
Middle Aged
Netherlands
Osteoarthritis/*drug therapy
Practice Patterns, Physicians'/*statistics & numerical data
Primary Health Care/*statistics & numerical data
analgesics
opioids
osteoarthritis
pain ,
ISSN = 1462-0324 (Print) 1462-0324 ,
DOI = 10.1093/rheumatology/kez646},
   year = {2020},
   type = {Journal Article}
}

INTRODUCTION: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS: Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION: This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols.

@article{RN332,
   author = {Janssen, O. and Vos, S. J. B. and García-Negredo, G. and Tochel, C. and Gustavsson, A. and Smith, M. and Ly, A. and Nelson, M. and Baldwin, H. and Sudlow, C. and Bexelius, C. and Jindra, C. and Vaci, N. and Bauermeister, S. and Gallacher, J. and Ponjoan, A. and Dufouil, C. and Garre Olmo, J. and Pedersen, L. and Skoog, I. and Hottgenroth, A. and Visser, P. J. and van der Lei, J. and Diaz, C.},
   title = {Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube},
   journal = {Alzheimers Dement},
   volume = {16},
   number = {3},
   pages = {461-471},
   note = {1552-5279 Janssen, Olin Vos, Stephanie J B García-Negredo, Glòria Tochel, Claire Gustavsson, Anders Smith, Michael Ly, Amanda Nelson, Mia Baldwin, Helen Sudlow, Catherine Bexelius, Christin Jindra, Christoph Vaci, Nemanja Bauermeister, Sarah Gallacher, John Ponjoan, Anna Dufouil, Carole Garre Olmo, Josep Pedersen, Lars Skoog, Ingmar Hottgenroth, Antje Visser, Pieter Jelle van der Lei, Johan Diaz, Carlos MR/L023784/1/MRC_/Medical Research Council/United Kingdom MR/009076/1/MRC_/Medical Research Council/United Kingdom 116020/Innovative Medicines Initiative/International European Federation of Pharmaceutical Industries and Associations/International Journal Article Research Support, Non-U.S. Gov't United States 2020/03/12 Alzheimers Dement. 2020 Mar;16(3):461-471. doi: 10.1016/j.jalz.2019.09.087. Epub 2020 Jan 6.},
   abstract = {INTRODUCTION: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS: Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION: This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols.},
   keywords = {*Activities of Daily Living
*Alzheimer Disease/psychology/therapy
Comorbidity
Data Interpretation, Statistical
*Disease Progression
Europe
Humans
Stakeholder Participation
Alzheimer's disease
Disease spectrum
Gap analysis
Outcomes
ROADMAP project
Real-world data
Stakeholders ,
ISSN = 1552-5260 ,
DOI = 10.1016/j.jalz.2019.09.087},
   year = {2020},
   type = {Journal Article}
}

@article{RN333,
   author = {Janssen, O. and Vos, S. J. B. and García-Negredo, G. and Tochel, C. and Gustavsson, A. and Smith, M. and Ly, A. and Nelson, M. and Baldwin, H. and Sudlow, C. and Bexelius, C. and Jindra, C. and Vaci, N. and Bauermeister, S. and Gallacher, J. and Ponjoan, A. and Dufouil, C. and Garre Olmo, J. and Pedersen, L. and Skoog, I. and Hottgenroth, A. and Visser, P. J. and van der Lei, J. and Diaz, C.},
   title = {Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube},
   journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
   volume = {16},
   number = {3},
   pages = {461-471 , DOI = 10.1016/j.jalz.2019.09.087},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85081912473&doi=10.1016%2fj.jalz.2019.09.087&partnerID=40&md5=da69adee11c030d4a2076dcc60983969https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1016/j.jalz.2019.09.087},
   year = {2020},
   type = {Journal Article}
}

BACKGROUND: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. METHODS: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I (2) value was less than 0·4. FINDINGS: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]). INTERPRETATION: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment. FUNDING: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations. , ISSN = 2665-9913 , DOI = 10.1016/s2665-9913(20)30276-9

@article{RN351,
   author = {Lane, J. C. E. and Weaver, J. and Kostka, K. and Duarte-Salles, T. and Abrahao, M. T. F. and Alghoul, H. and Alser, O. and Alshammari, T. M. and Biedermann, P. and Banda, J. M. and Burn, E. and Casajust, P. and Conover, M. M. and Culhane, A. C. and Davydov, A. and DuVall, S. L. and Dymshyts, D. and Fernandez-Bertolin, S. and Fišter, K. and Hardin, J. and Hester, L. and Hripcsak, G. and Kaas-Hansen, B. S. and Kent, S. and Khosla, S. and Kolovos, S. and Lambert, C. G. and van der Lei, J. and Lynch, K. E. and Makadia, R. and Margulis, A. V. and Matheny, M. E. and Mehta, P. and Morales, D. R. and Morgan-Stewart, H. and Mosseveld, M. and Newby, D. and Nyberg, F. and Ostropolets, A. and Park, R. W. and Prats-Uribe, A. and Rao, G. A. and Reich, C. and Reps, J. and Rijnbeek, P. and Sathappan, S. M. K. and Schuemie, M. and Seager, S. and Sena, A. G. and Shoaibi, A. and Spotnitz, M. and Suchard, M. A. and Torre, C. O. and Vizcaya, D. and Wen, H. and de Wilde, M. and Xie, J. and You, S. C. and Zhang, L. and Zhuk, O. and Ryan, P. and Prieto-Alhambra, D.},
   title = {Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study},
   journal = {Lancet Rheumatol},
   volume = {2},
   number = {11},
   pages = {e698-e711},
   note = {2665-9913 Lane, Jennifer C E Weaver, James Kostka, Kristin Duarte-Salles, Talita Abrahao, Maria Tereza F Alghoul, Heba Alser, Osaid Alshammari, Thamir M Biedermann, Patricia Banda, Juan M Burn, Edward Casajust, Paula Conover, Mitchell M Culhane, Aedin C Davydov, Alexander DuVall, Scott L Dymshyts, Dmitry Fernandez-Bertolin, Sergio Fišter, Kristina Hardin, Jill Hester, Laura Hripcsak, George Kaas-Hansen, Benjamin Skov Kent, Seamus Khosla, Sajan Kolovos, Spyros Lambert, Christophe G van der Lei, Johan Lynch, Kristine E Makadia, Rupa Margulis, Andrea V Matheny, Michael E Mehta, Paras Morales, Daniel R Morgan-Stewart, Henry Mosseveld, Mees Newby, Danielle Nyberg, Fredrik Ostropolets, Anna Park, Rae Woong Prats-Uribe, Albert Rao, Gowtham A Reich, Christian Reps, Jenna Rijnbeek, Peter Sathappan, Selva Muthu Kumaran Schuemie, Martijn Seager, Sarah Sena, Anthony G Shoaibi, Azza Spotnitz, Matthew Suchard, Marc A Torre, Carmen O Vizcaya, David Wen, Haini de Wilde, Marcel Xie, Junqing You, Seng Chan Zhang, Lin Zhuk, Oleg Ryan, Patrick Prieto-Alhambra, Daniel OHDSI-COVID-19 consortium WT_/Wellcome Trust/United Kingdom P30 AG059307/AG/NIA NIH HHS/United States R01 LM006910/LM/NLM NIH HHS/United States RES 13-457/RD/ORD VA/United States Journal Article England 2020/08/31 Lancet Rheumatol. 2020 Nov;2(11):e698-e711. doi: 10.1016/S2665-9913(20)30276-9. Epub 2020 Aug 21.},
   abstract = {BACKGROUND: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. METHODS: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I (2) value was less than 0·4. FINDINGS: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]). INTERPRETATION: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment. FUNDING: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations. , ISSN = 2665-9913 , DOI = 10.1016/s2665-9913(20)30276-9},
   year = {2020},
   type = {Journal Article}
}

@article{RN330,
   author = {James, G. and Collin, E. and Lawrance, M. and Mueller, A. and Podhorna, J. and Zaremba-Pechmann, L. and Rijnbeek, P. and van der Lei, J. and Avillach, P. and Pedersen, L. and Ansell, D. and Pasqua, A. and Mosseveld, M. and Grosdidier, S. and Gungabissoon, U. and Egger, P. and Stewart, R. and Celis-Morales, C. and Alexander, M. and Novak, G. and Gordon, M. F.},
   title = {Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe},
   journal = {Social Psychiatry and Psychiatric Epidemiology , DOI = 10.1007/s00127-020-01872-2},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85085988074&doi=10.1007%2fs00127-020-01872-2&partnerID=40&md5=a7868077f8e2700cfd5aec2531b6e0c9https://link.springer.com/content/pdf/10.1007/s00127-020-01872-2.pdf},
   year = {2020},
   type = {Journal Article}
}

OBJECTIVE: The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations. DESIGN: Case-control study. SETTING: Six European electronic health records databases. PARTICIPANTS: 291 780 cases at the date of first-recorded dementia diagnosis, compared with 29 170 549 controls randomly selected from the same databases, age matched and sex matched at this index date. EXPOSURE: The following measures were extracted whenever recorded within each dataset: BMI (kg/m(2)), SBP and DBP (mm Hg) and serum total cholesterol (mmol/L). Levels for each of these variables were defined within six 2-year time intervals over the 12 years prior to the index date. MAIN OUTCOMES: Case-control differences in exposures of interest were modelled for each time period and adjusted for demographic and clinical factors (ischaemic/unspecified stroke, type 2 diabetes mellitus, acute myocardial infarction, hypertension diagnosis, antihypertensive medication, cholesterol-lowering medication). Coefficients and interactions with time period were meta-analysed across the six databases. RESULTS: Mean BMI (coefficient -1.16 kg/m(2); 95% CI -1.38 to 0.93) and SBP (-2.83 mm Hg; 95% CI -4.49 to -1.16) were lower in cases at diagnosis, and case-control differences were greater in more recent time periods, as indicated by significant case-x-time interaction and case-x-time-squared interaction terms. Time variations in coefficients for cholesterol levels were less consistent between databases and those for DBP were largely not significant. CONCLUSION: Routine clinical data show emerging divergence in levels of BMI and SBP prior to the diagnosis of dementia but less evidence for DBP or total cholesterol levels. These divergences should receive at least some consideration in routine dementia risk screening, although underlying mechanisms still require further investigation.

@article{RN392,
   author = {Perera, G. and Rijnbeek, P. R. and Alexander, M. and Ansell, D. and Avillach, P. and Duarte-Salles, T. and Gordon, M. F. and Lapi, F. and Mayer, M. A. and Pasqua, A. and Pedersen, L. and van Der Lei, J. and Visser, P. J. and Stewart, R.},
   title = {Vascular and metabolic risk factor differences prior to dementia diagnosis: a multidatabase case-control study using European electronic health records},
   journal = {BMJ Open},
   volume = {10},
   number = {11},
   pages = {e038753},
   note = {2044-6055 Perera, Gayan Orcid: 0000-0002-3414-303x Rijnbeek, P R Alexander, Myriam Ansell, David Avillach, Paul Duarte-Salles, Talita Orcid: 0000-0002-8274-0357 Gordon, Mark Forrest Lapi, Francesco Mayer, Miguel Angel Pasqua, Alessandro Pedersen, Lars van Der Lei, Johan Visser, Pieter Jelle Stewart, Robert MC_PC_17214/MRC_/Medical Research Council/United Kingdom MR/T045302/1/MRC_/Medical Research Council/United Kingdom Journal Article Research Support, Non-U.S. Gov't England 2020/11/17 BMJ Open. 2020 Nov 14;10(11):e038753. doi: 10.1136/bmjopen-2020-038753.},
   abstract = {OBJECTIVE: The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations. DESIGN: Case-control study. SETTING: Six European electronic health records databases. PARTICIPANTS: 291 780 cases at the date of first-recorded dementia diagnosis, compared with 29 170 549 controls randomly selected from the same databases, age matched and sex matched at this index date. EXPOSURE: The following measures were extracted whenever recorded within each dataset: BMI (kg/m(2)), SBP and DBP (mm Hg) and serum total cholesterol (mmol/L). Levels for each of these variables were defined within six 2-year time intervals over the 12 years prior to the index date. MAIN OUTCOMES: Case-control differences in exposures of interest were modelled for each time period and adjusted for demographic and clinical factors (ischaemic/unspecified stroke, type 2 diabetes mellitus, acute myocardial infarction, hypertension diagnosis, antihypertensive medication, cholesterol-lowering medication). Coefficients and interactions with time period were meta-analysed across the six databases. RESULTS: Mean BMI (coefficient -1.16 kg/m(2); 95% CI -1.38 to 0.93) and SBP (-2.83 mm Hg; 95% CI -4.49 to -1.16) were lower in cases at diagnosis, and case-control differences were greater in more recent time periods, as indicated by significant case-x-time interaction and case-x-time-squared interaction terms. Time variations in coefficients for cholesterol levels were less consistent between databases and those for DBP were largely not significant. CONCLUSION: Routine clinical data show emerging divergence in levels of BMI and SBP prior to the diagnosis of dementia but less evidence for DBP or total cholesterol levels. These divergences should receive at least some consideration in routine dementia risk screening, although underlying mechanisms still require further investigation.},
   keywords = {Aged
Aged, 80 and over
Blood Pressure
Case-Control Studies
*Dementia/diagnosis/epidemiology
Diabetes Mellitus, Type 2
Electronic Health Records
Female
Humans
Hypertension
Male
Risk Factors
dementia
epidemiology
health informatics
mental health
physiology ,
ISSN = 2044-6055 ,
DOI = 10.1136/bmjopen-2020-038753},
   year = {2020},
   type = {Journal Article}
}

@article{RN340,
   author = {Karimi, L. and Vijverberg, S. J. H. and Farzan, N. and Ghanbari, M. and Verhamme, K. M. C. and Maitland-van der Zee, A. H.},
   title = {FCER2 T2206C variant associated with FENO levels in asthmatic children using inhaled corticosteroids: The PACMAN study},
   journal = {Clinical and Experimental Allergy},
   volume = {49},
   number = {11},
   pages = {1429-1436 , DOI = 10.1111/cea.13460},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85071638448&doi=10.1111%2fcea.13460&partnerID=40&md5=e479de37bc31790fc1e25335d43f05db},
   year = {2019},
   type = {Journal Article}
}

@article{RN251,
   author = {Afzal, Z. and Masclee, G. M. C. and Sturkenboom, M. C. J. M. and Kors, J. A. and Schuemie, M. J.},
   title = {Generating and evaluating a propensity model using textual features from electronic medical records},
   journal = {PLoS ONE},
   volume = {14},
   number = {3 , DOI = 10.1371/journal.pone.0212999},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062402296&doi=10.1371%2fjournal.pone.0212999&partnerID=40&md5=b8d2e3931273fc637c4bfe29b655151chttps://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0212999&type=printable},
   year = {2019},
   type = {Journal Article}
}

@article{RN322,
   author = {Hernandez-Pacheco, N. and Farzan, N. and Francis, B. and Karimi, L. and Repnik, K. and Vijverberg, S. J. and Soares, P. and Schieck, M. and Gorenjak, M. and Forno, E. and Eng, C. and Oh, S. S. and Pérez-Méndez, L. and Berce, V. and Tavendale, R. and Samedy, L. A. and Hunstman, S. and Hu, D. and Meade, K. and Farber, H. J. and Avila, P. C. and Serebrisky, D. and Thyne, S. M. and Brigino-Buenaventura, E. and Rodriguez-Cintron, W. and Sen, S. and Kumar, R. and Lenoir, M. and Rodriguez-Santana, J. R. and Celedón, J. C. and Mukhopadhyay, S. and Potočnik, U. and Pirmohamed, M. and Verhamme, K. M. and Kabesch, M. and Palmer, C. N. A. and Hawcutt, D. B. and Flores, C. and Maitland-van der Zee, A. H. and Burchard, E. G. and Pino-Yanes, M.},
   title = {Genome-wide association study of inhaled corticosteroid response in admixed children with asthma},
   journal = {Clinical and Experimental Allergy},
   volume = {49},
   number = {6},
   pages = {789-798 , DOI = 10.1111/cea.13354},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061585893&doi=10.1111%2fcea.13354&partnerID=40&md5=9270a65ad82278f7ee7ea1b6ab984e1ahttps://onlinelibrary.wiley.com/doi/full/10.1111/cea.13354},
   year = {2019},
   type = {Journal Article}
}

@article{RN381,
   author = {Noels, E. C. and Hollestein, L. M. and van Egmond, S. and Lugtenberg, M. and van Nistelrooij, L. P. J. and Bindels, P. J. E. and van der Lei, J. and Stern, R. S. and Nijsten, T. and Wakkee, M.},
   title = {Healthcare utilization and management of actinic keratosis in primary and secondary care: a complementary database analysis},
   journal = {British Journal of Dermatology},
   volume = {181},
   number = {3},
   pages = {544-553 , DOI = 10.1111/bjd.17632},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062265150&doi=10.1111%2fbjd.17632&partnerID=40&md5=ce84f07b899cd6d454449d0b8fa0b2b3https://onlinelibrary.wiley.com/doi/full/10.1111/bjd.17632https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850060/pdf/BJD-181-544.pdf},
   year = {2019},
   type = {Journal Article}
}

@article{RN426,
   author = {Sultana, J. and Leal, I. and de Wilde, M. and de Ridder, M. and van der Lei, J. and Sturkenboom, M. and Trifiro’, G.},
   title = {Identifying Data Elements to Measure Frailty in a Dutch Nationwide Electronic Medical Record Database for Use in Postmarketing Safety Evaluation: An Exploratory Study},
   journal = {Drug Safety},
   volume = {42},
   number = {6},
   pages = {713-719 , DOI = 10.1007/s40264-018-00785-z},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059817613&doi=10.1007%2fs40264-018-00785-z&partnerID=40&md5=3b50306ad21eb82759c960953f8add4bhttps://link.springer.com/content/pdf/10.1007%2Fs40264-018-00785-z.pdf},
   year = {2019},
   type = {Journal Article}
}

@article{RN396,
   author = {Rasenberg, N. and Bierma-Zeinstra, S. M. A. and Bindels, P. J. and van Middelkoop, M. and van der Lei, J.},
   title = {Incidence, prevalence, and management of plantar heel pain: A retrospective cohort study in Dutch primary care},
   journal = {British Journal of General Practice},
   volume = {69},
   number = {688},
   pages = {E801-E808 , DOI = 10.3399/bjgp19X706061},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074378522&doi=10.3399%2fbjgp19X706061&partnerID=40&md5=7cfe875fc50ee336ba01ae9c80c52d69https://bjgp.org/content/69/688/e801.long},
   year = {2019},
   type = {Journal Article}
}

@article{RN282,
   author = {Cheung, K. and Verhamme, K. M. C. and Herings, R. and Visser, L. E. and Stricker, B. H.},
   title = {Methylphenidate Treatment Initiated during Childhood Is Continued in Adulthood in Half of the Study Population},
   journal = {Journal of Child and Adolescent Psychopharmacology},
   volume = {29},
   number = {6},
   pages = {426-432 , DOI = 10.1089/ca 2018.0170},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85069957320&doi=10.1089%2fcap.2018.0170&partnerID=40&md5=80058fd9b67307e96271f548697652eb},
   year = {2019},
   type = {Journal Article}
}

@article{RN255,
   author = {Alexander, M. and Loomis, A. K. and Van Der Lei, J. and Duarte-Salles, T. and Prieto-Alhambra, D. and Ansell, D. and Pasqua, A. and Lapi, F. and Rijnbeek, P. and Mosseveld, M. and Avillach, P. and Egger, P. and Dhalwani, N. N. and Kendrick, S. and Celis-Morales, C. and Waterworth, D. M. and Alazawi, W. and Sattar, N.},
   title = {Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: Findings from matched cohort study of 18 million European adults},
   journal = {The BMJ},
   volume = {367 , DOI = 10.1136/bmj.l5367},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073065818&doi=10.1136%2fbmj.l5367&partnerID=40&md5=f911169924d6ff70d019d33582d914cehttps://www.bmj.com/content/bmj/367/bmj.l5367.full.pdf},
   year = {2019},
   type = {Journal Article}
}

@article{RN487,
   author = {Wakkee, M. and van Egmond, S. and Louwman, M. and Bindels, P. and van der Lei, J. and Nijsten, T. and Hollestein, L.},
   title = {Opportunities for improving the efficiency of keratinocyte carcinoma care in primary and specialist care: Results from population-based Dutch cohort studies},
   journal = {European Journal of Cancer},
   volume = {117},
   pages = {32-40 , DOI = 10.1016/j.ejca.2019.05.010},
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   year = {2019},
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@article{RN256,
   author = {Alexander, M. and Loomis, A. K. and Van Der Lei, J. and Duarte-Salles, T. and Prieto-Alhambra, D. and Ansell, D. and Pasqua, A. and Lapi, F. and Rijnbeek, P. and Mosseveld, M. and Waterworth, D. M. and Kendrick, S. and Sattar, N. and Alazawi, W.},
   title = {Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: Real-world study of 18 million patients in four European cohorts},
   journal = {BMC Medicine},
   volume = {17},
   number = {1 , DOI = 10.1186/s12916-019-1321-x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065878944&doi=10.1186%2fs12916-019-1321-x&partnerID=40&md5=a05608b81e8f78fcd5d8c38aba2b5f47https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-019-1321-x},
   year = {2019},
   type = {Journal Article}
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@article{RN352,
   author = {Legdeur, N. and Van Der Lee, S. J. and De Wilde, M. and Van Der Lei, J. and Muller, M. and Maier, A. B. and Visser, P. J.},
   title = {The association of vascular disorders with incident dementia in different age groups},
   journal = {Alzheimer's Research and Therapy},
   volume = {11},
   number = {1 , DOI = 10.1186/s13195-019-0496-x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065887913&doi=10.1186%2fs13195-019-0496-x&partnerID=40&md5=3558786eaf71446947241df10ab4e943https://alzres.biomedcentral.com/track/pdf/10.1186/s13195-019-0496-x},
   year = {2019},
   type = {Journal Article}
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@article{RN375,
   author = {Mulder, M. and Baan, E. and Verbon, A. and Stricker, B. and Verhamme, K.},
   title = {Trends of prescribing antimicrobial drugs for urinary tract infections in primary care in the netherlands: A population-based cohort study},
   journal = {BMJ Open},
   volume = {9},
   number = {5 , DOI = 10.1136/bmjopen-2018-027221},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065960593&doi=10.1136%2fbmjopen-2018-027221&partnerID=40&md5=883ed6509c0b8d23cf23260d2d132824https://bmjopen.bmj.com/content/bmjopen/9/5/e027221.full.pdf},
   year = {2019},
   type = {Journal Article}
}

@article{RN265,
   author = {Baan, E. J. and Janssens, H. M. and Kerckaert, T. and Bindels, P. J. E. and De Jongste, J. C. and Sturkenboom, M. C. J. M. and Verhamme, K. M. C.},
   title = {Antibiotic use in children with asthma: Cohort study in UK and Dutch primary care databases},
   journal = {BMJ Open},
   volume = {8},
   number = {11 , DOI = 10.1136/bmjopen-2018-022979},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057522195&doi=10.1136%2fbmjopen-2018-022979&partnerID=40&md5=24f653171cef398bd2110fc40cbaf372},
   year = {2018},
   type = {Journal Article}
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@article{RN389,
   author = {Patadia, V. K. and Schuemie, M. J. and Coloma, P. M. and Herings, R. and van der Lei, J. and Sturkenboom, M. and Trifirò, G.},
   title = {Can electronic health records databases complement spontaneous reporting system databases? A historical-reconstruction of the association of rofecoxib and acute myocardial infarction},
   journal = {Frontiers in Pharmacology},
   volume = {9},
   number = {JUN , DOI = 10.3389/fphar.2018.00594},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048044960&doi=10.3389%2ffphar.2018.00594&partnerID=40&md5=24f2341c7c0126d0f3a2f9b4cb2b581ehttps://fjfsdata01prod.blob.core.windows.net/articles/files/339489/pubmed-zip/.versions/1/.package-entries/fphar-09-00594/fphar-09-00594.pdf?sv=2015-12-11&sr=b&sig=WpdYdFKbOK0PgjHxwQ3P9zHuCfzeC%2F958Xt%2FzdXM2UQ%3D&se=2019-10-10T12%3A03%3A20Z&sp=r&rscd=attachment%3B%20filename%2A%3DUTF-8%27%27fphar-09-00594.pdf},
   year = {2018},
   type = {Journal Article}
}

@article{RN383,
   author = {Osokogu, O. U. and Khan, J. and Nakato, S. and Weibel, D. and de Ridder, M. and Sturkenboom, M. C. J. M. and Verhamme, K.},
   title = {Choice of time period to identify confounders for propensity score matching, affected the estimate: a retrospective cohort study of drug effectiveness in asthmatic children},
   journal = {Journal of Clinical Epidemiology},
   volume = {101},
   pages = {107-115.e3 , DOI = 10.1016/j.jclinepi.2018.01.008},
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@article{RN391,
   author = {Perera, G. and Pedersen, L. and Ansel, D. and Alexander, M. and Arrighi, H. M. and Avillach, P. and Foskett, N. and Gini, R. and Gordon, M. F. and Gungabissoon, U. and Mayer, M. A. and Novak, G. and Rijnbeek, P. and Trifirò, G. and van der Lei, J. and Visser, P. J. and Stewart, R.},
   title = {Dementia prevalence and incidence in a federation of European Electronic Health Record databases: The European Medical Informatics Framework resource},
   journal = {Alzheimer's and Dementia},
   volume = {14},
   number = {2},
   pages = {130-139 , DOI = 10.1016/j.jalz.2017.06.2270},
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   year = {2018},
   type = {Journal Article}
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@article{RN323,
   author = {Hofman, R. and Veldhuijzen, I. K. and Van Der Lei, J. and Richardus, J. H.},
   title = {Follow-up diagnosis, follow-up and referral of patients with hepatitis B and C},
   journal = {Nederlands Tijdschrift voor Geneeskunde},
   volume = {162},
   number = {17},
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   year = {2018},
   type = {Journal Article}
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@article{RN384,
   author = {Osokogu, O. U. and Pacurariu, A. and Mosseveld, M. and Rijnbeek, P. and Weibel, D. and Verhamme, K. and Sturkenboom, M. C. J. M.},
   title = {Impact of different assumptions on estimates of childhood diseases obtained from health care data: A retrospective cohort study},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {27},
   number = {6},
   pages = {612-620 , DOI = 10.1002/pds.4413},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045922770&doi=10.1002%2fpds.4413&partnerID=40&md5=5baf7717ec8034182d1a63724485ef1ehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001570/pdf/PDS-27-612.pdf},
   year = {2018},
   type = {Journal Article}
}

@article{RN489,
   author = {Weibel, D. and Sturkenboom, M. and Black, S. and de Ridder, M. and Dodd, C. and Bonhoeffer, J. and Vanrolleghem, A. and van der Maas, N. and Lammers, G. J. and Overeem, S. and Gentile, A. and Giglio, N. and Castellano, V. and Kwong, J. C. and Murray, B. J. and Cauch-Dudek, K. and Juhasz, D. and Campitelli, M. and Datta, A. N. and Kallweit, U. and Huang, W. T. and Huang, Y. S. and Hsu, C. Y. and Chen, H. C. and Giner-Soriano, M. and Morros, R. and Gaig, C. and Tió, E. and Perez-Vilar, S. and Diez-Domingo, J. and Puertas, F. J. and Svenson, L. W. and Mahmud, S. M. and Carleton, B. and Naus, M. and Arnheim-Dahlström, L. and Pedersen, L. and DeStefano, F. and Shimabukuro, T. T.},
   title = {Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines – Multi-country assessment},
   journal = {Vaccine},
   volume = {36},
   number = {41},
   pages = {6202-6211 , DOI = 10.1016/j.vaccine.2018.08.008},
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   year = {2018},
   type = {Journal Article}
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@article{RN407,
   author = {Schurink-van't Klooster, T. M. and Kemmeren, J. M. and van der Maas, N. A. T. and van de Putte, E. M. and ter Wolbeek, M. and Nijhof, S. L. and Vanrolleghem, A. M. and van Vliet, J. A. and Sturkenboom, M. and de Melker, H. E.},
   title = {No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls},
   journal = {Vaccine},
   volume = {36},
   number = {45},
   pages = {6796-6802 , DOI = 10.1016/j.vaccine.2018.09.019},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055190651&doi=10.1016%2fj.vaccine.2018.09.019&partnerID=40&md5=0575f51db25774efd906eb8d45da67c0},
   year = {2018},
   type = {Journal Article}
}

@article{RN452,
   author = {Van Leeuwen, K. D. B. and Bohnen, A. M. and Jacobs, M. L. and Van Der Lei, J. and Janssens, H. J. E. M. and Koffeman, A. R. and Bindels, P. J. E. and Bierma-Zeinstra, S. M. A.},
   title = {Patient-reported gout attack frequency and allopurinol use in general practice in the Netherlands: A prospective observational cohort study protocol},
   journal = {BMJ Open},
   volume = {8},
   number = {11 , DOI = 10.1136/bmjopen-2018-024335},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057265753&doi=10.1136%2fbmjopen-2018-024335&partnerID=40&md5=d624a300b9e6cf41d7421f8b29dbe9cdhttps://bmjopen.bmj.com/content/bmjopen/8/11/e024335.full.pdf},
   year = {2018},
   type = {Journal Article}
}

@article{RN254,
   author = {Alexander, M. and Loomis, A. K. and Fairburn-Beech, J. and van der Lei, J. and Duarte-Salles, T. and Prieto-Alhambra, D. and Ansell, D. and Pasqua, A. and Lapi, F. and Rijnbeek, P. and Mosseveld, M. and Avillach, P. and Egger, P. and Kendrick, S. and Waterworth, D. M. and Sattar, N. and Alazawi, W.},
   title = {Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease},
   journal = {BMC Medicine},
   volume = {16},
   number = {1 , DOI = 10.1186/s12916-018-1103-x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052323930&doi=10.1186%2fs12916-018-1103-x&partnerID=40&md5=5858258e62d9ecd2c007154a2effff47https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-018-1103-x},
   year = {2018},
   type = {Journal Article}
}

@article{RN364,
   author = {Masclee, G. M. C. and Straatman, H. and Arfè, A. and Castellsague, J. and Garbe, E. and Herings, R. and Kollhorst, B. and Lucchi, S. and Perez-Gutthann, S. and Romio, S. and Schade, R. and Schink, T. and Schuemie, M. J. and Scotti, L. and Varas-Lorenzo, C. and Valkhoff, V. E. and Villa, M. and Sturkenboom, M. C. J. M.},
   title = {Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project},
   journal = {PloS one},
   volume = {13},
   number = {11},
   pages = {e0204746 , DOI = 10.1371/journal.pone.0204746},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055913698&doi=10.1371%2fjournal.pone.0204746&partnerID=40&md5=cc962778deb1b93b445b79edff481905},
   year = {2018},
   type = {Journal Article}
}

@article{RN403,
   author = {Schink, T. and Kollhorst, B. and Lorenzo, C. V. and Arfè, A. and Herings, R. and Lucchi, S. and Romio, S. and Schade, R. and Schuemie, M. J. and Straatman, H. and Valkhoff, V. and Villa, M. and Sturkenboom, M. and Garbe, E.},
   title = {Risk of ischemic stroke and the use of individual non-steroidal anti-inflammatory drugs: A multi-country european database study within the SOS Project},
   journal = {PLoS ONE},
   volume = {13},
   number = {9 , DOI = 10.1371/journal.pone.0203362},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85053632920&doi=10.1371%2fjournal.pone.0203362&partnerID=40&md5=0e9db65e0ece17da80df1dbb772a5343},
   year = {2018},
   type = {Journal Article}
}

@article{RN312,
   author = {Ferrajolo, C. and Verhamme, K. M. C. and Trifirò, G. and ‘t Jong, G. W. and Picelli, G. and Giaquinto, C. and Mazzaglia, G. and Stricker, B. H. and Rossi, F. and Capuano, A. and Sturkenboom, M. C. J. M.},
   title = {Antibiotic-Induced Liver Injury in Paediatric Outpatients: A Case-Control Study in Primary Care Databases},
   journal = {Drug Safety},
   volume = {40},
   number = {4},
   pages = {305-315 , DOI = 10.1007/s40264-016-0493-y},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85007155225&doi=10.1007%2fs40264-016-0493-y&partnerID=40&md5=2bbe2eb5785d69b69cb8bc4967f006e9https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362651/pdf/40264_2016_Article_493.pdf},
   year = {2017},
   type = {Journal Article}
}

@article{RN314,
   author = {Gadroen, K. and Kemmeren, J. M. and Bruijning-Verhagen, P. C. and Straus, S. M. and Weibel, D. and de Melker, H. E. and Sturkenboom, M. C.},
   title = {Baseline incidence of intussusception in early childhood before rotavirus vaccine introduction, the netherlands, january 2008 to december 2012},
   journal = {Eurosurveillance},
   volume = {22},
   number = {25 , DOI = 10.2807/1560-7917.es.2017.22.25.30556},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021719321&doi=10.2807%2f1560-7917.ES.2017.22.25.30556&partnerID=40&md5=8fe7cb1dedf44c40cc71114eea2e9785},
   year = {2017},
   type = {Journal Article}
}

@article{RN349,
   author = {La Gamba, F. and Corrao, G. and Romio, S. and Sturkenboom, M. and Trifirò, G. and Schink, T. and de Ridder, M.},
   title = {Combining evidence from multiple electronic health care databases: performances of one-stage and two-stage meta-analysis in matched case-control studies},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {26},
   number = {10},
   pages = {1213-1219 , DOI = 10.1002/pds.4280},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85030149271&doi=10.1002%2fpds.4280&partnerID=40&md5=a43a61db206c69f9efeb2597dd307fb4https://onlinelibrary.wiley.com/doi/full/10.1002/pds.4280},
   year = {2017},
   type = {Journal Article}
}

@article{RN310,
   author = {Farzan, N. and Vijverberg, S. J. and Andiappan, A. K. and Arianto, L. and Berce, V. and Blanca-López, N. and Bisgaard, H. and Bønnelykke, K. and Burchard, E. G. and Campo, P. and Canino, G. and Carleton, B. and Celedón, J. C. and Chew, F. T. and Chiang, W. C. and Cloutier, M. M. and Daley, D. and Den Dekker, H. T. and Dijk, F. N. and Duijts, L. and Flores, C. and Forno, E. and Hawcutt, D. B. and Hernandez-Pacheco, N. and De Jongste, J. C. and Kabesch, M. and Koppelman, G. H. and Manolopoulos, V. G. and Melén, E. and Mukhopadhyay, S. and Nilsson, S. and Palmer, C. N. and Pino-Yanes, M. and Pirmohamed, M. and Potočnki, U. and Raaijmakers, J. A. and Repnik, K. and Schieck, M. and Sio, Y. Y. and Smyth, R. L. and Szalai, C. and Tantisira, K. G. and Turner, S. and Van Der Schee, M. P. and Verhamme, K. M. and Maitland-Van Der Zee, A. H.},
   title = {Rationale and design of the multiethnic Pharmacogenomics in Childhood Asthma consortium},
   journal = {Pharmacogenomics},
   volume = {18},
   number = {10},
   pages = {931-943 , DOI = 10.2217/pgs-2017-0035},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85024501836&doi=10.2217%2fpgs-2017-0035&partnerID=40&md5=a0de7f491ff6f3f50d85241ea2476d1chttps://www.futuremedicine.com/doi/pdfplus/10.2217/pgs-2017-0035},
   year = {2017},
   type = {Journal Article}
}

@article{RN393,
   author = {Poluzzi, E. and Diemberger, I. and De Ridder, M. and Koci, A. and Clo, M. and Oteri, A. and Pecchioli, S. and Bezemer, I. and Schink, T. and Pilgaard Ulrichsen, S. and Boriani, G. and Sturkenboom, M. C. J. and De Ponti, F. and Trifirò, G.},
   title = {Use of antihistamines and risk of ventricular tachyarrhythmia: a nested case-control study in five European countries from the ARITMO project},
   journal = {European Journal of Clinical Pharmacology},
   volume = {73},
   number = {11},
   pages = {1499-1510 , DOI = 10.1007/s00228-017-2317-0},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85027865287&doi=10.1007%2fs00228-017-2317-0&partnerID=40&md5=fd9a89b4d1ee66dcda06664c33bfb354https://link.springer.com/content/pdf/10.1007%2Fs00228-017-2317-0.pdf},
   year = {2017},
   type = {Journal Article}
}

@article{RN433,
   author = {Trifirò, G. and De Ridder, M. and Sultana, J. and Oteri, A. and Rijnbeek, P. and Pecchioli, S. and Mazzaglia, G. and Bezemer, I. and Garbe, E. and Schink, T. and Poluzzi, E. and Frøslev, T. and Molokhia, M. and Diemberger, I. and Sturkenboom, M. C. J. M.},
   title = {Use of azithromycin and risk of ventricular arrhythmia},
   journal = {Cmaj},
   volume = {189},
   number = {15},
   pages = {E560-E568 , DOI = 10.1503/cmaj.160355},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018467666&doi=10.1503%2fcmaj.160355&partnerID=40&md5=6fa9c1f74d0012e79029d969e5f203b9https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392117/pdf/189e560.pdf},
   year = {2017},
   type = {Journal Article}
}

@article{RN425,
   author = {Sultana, J. and Leal, I. and De Ridder, M. and Sturkenboom, M. and Trifiró, G.},
   title = {Antipsychotic use in dementia patients in a general practice setting: A Dutch population-based study},
   journal = {Epidemiology and Psychiatric Sciences},
   volume = {25},
   number = {4},
   pages = {403-406 , DOI = 10.1017/s2045796016000111},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961207600&doi=10.1017%2fS2045796016000111&partnerID=40&md5=7393abb87a8147de1d30f3a3db75a99ahttps://www.cambridge.org/core/services/aop-cambridge-core/content/view/66C62221A7628E74A687342187752972/S2045796016000111a.pdf/div-class-title-antipsychotic-use-in-dementia-patients-in-a-general-practice-setting-a-dutch-population-based-study-div.pdf},
   year = {2016},
   type = {Journal Article}
}

@article{RN328,
   author = {Huijgen, N. A. and de Ridder, M. A. J. and Verhamme, K. M. and Dohle, G. R. and Vanrolleghem, A. M. and Sturkenboom, M. C. J. M. and Laven, J. S. E. and Steegers-Theunissen, R. P. M.},
   title = {Are proton-pump inhibitors harmful for the semen quality of men in couples who are planning pregnancy?},
   journal = {Fertility and Sterility},
   volume = {106},
   number = {7},
   pages = {1666-1672.e2 , DOI = 10.1016/j.fertnstert.2016.09.010},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84998727488&doi=10.1016%2fj.fertnstert.2016.09.010&partnerID=40&md5=b7bfaa9ef179e81e0cc42088ef1d40dbhttp://ac.els-cdn.com/S0015028216628005/1-s2.0-S0015028216628005-main.pdf?_tid=040d3172-cd0e-11e6-840f-00000aab0f02&acdnat=1482937256_ef6a083839235b59d73416eeb4820ef7},
   year = {2016},
   type = {Journal Article}
}

@article{RN273,
   author = {Blok, C. G. H. and De Ridder, M. A. J. and Verhamme, K. M. C. and Moorman, P. W.},
   title = {Hypertension in older patients, a retrospective cohort study},
   journal = {BMC Geriatrics},
   volume = {16},
   number = {1 , DOI = 10.1186/s12877-016-0316-0},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84978477247&doi=10.1186%2fs12877-016-0316-0&partnerID=40&md5=42e3b117402881c016a90b5a53552fffhttp://download.springer.com/static/pdf/117/art%253A10.1186%252Fs12877-016-0316-0.pdf?originUrl=http%3A%2F%2Fbmcgeriatr.biomedcentral.com%2Farticle%2F10.1186%2Fs12877-016-0316-0&token2=exp=1482937293~acl=%2Fstatic%2Fpdf%2F117%2Fart%25253A10.1186%25252Fs12877-016-0316-0.pdf*~hmac=1a0307896aecf01368f0747ba8ba4aa984e1d0dd2c64d4f03358903358d1f08e},
   year = {2016},
   type = {Journal Article}
}

@article{RN402,
   author = {Roberto, G. and Leal, I. and Sattar, N. and Loomis, A. K. and Avillach, P. and Egger, P. and Van Wijngaarden, R. and Ansell, D. and Reisberg, S. and Tammesoo, M. L. and Alavere, H. and Pasqua, A. and Pedersen, L. and Cunningham, J. and Tramontan, L. and Mayer, M. A. and Herings, R. and Coloma, P. and Lapi, F. and Sturkenboom, M. and Van Der Lei, J. and Schuemie, M. J. and Rijnbeek, P. and Gini, R.},
   title = {Identifying cases of type 2 diabetes in heterogeneous data sources: Strategy from the EMIF project},
   journal = {PLoS ONE},
   volume = {11},
   number = {8 , DOI = 10.1371/journal.pone.0160648},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84990232922&doi=10.1371%2fjournal.pone.0160648&partnerID=40&md5=83b81104ac8f8982992e219517017a42http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0160648&type=printable},
   year = {2016},
   type = {Journal Article}
}

@article{RN259,
   author = {Arfè, A. and Scotti, L. and Varas-Lorenzo, C. and Nicotra, F. and Zambon, A. and Kollhorst, B. and Schink, T. and Garbe, E. and Herings, R. and Straatman, H. and Schade, R. and Villa, M. and Lucchi, S. and Valkhoff, V. and Romio, S. and Thiessard, F. and Schuemie, M. and Pariente, A. and Sturkenboom, M. and Corrao, G. and Safety of Non-steroidal Anti-inflammatory Drugs Project, Consortium},
   title = {Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study},
   journal = {BMJ (Clinical research ed )},
   volume = {354},
   pages = {i4857 , DOI = 10.1136/bmj.i4857},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85006347139&doi=10.1136%2fbmj.i4857&partnerID=40&md5=2491b37fff09339de67e8c2038958fe3},
   year = {2016},
   type = {Journal Article}
}

@article{RN385,
   author = {Oteri, A. and Mazzaglia, G. and Pecchioli, S. and Molokhia, M. and Ulrichsen, S. P. and Pedersen, L. and Poluzzi, E. and De Ponti, F. and Garbe, E. and Schink, T. and Herings, R. and Bezemer, I. D. and Sturkenboom, M. C. J. M. and Trifirò, G.},
   title = {Prescribing pattern of antipsychotic drugs during the years 1996–2010: a population-based database study in Europe with a focus on torsadogenic drugs},
   journal = {British Journal of Clinical Pharmacology},
   pages = {487-497 , DOI = 10.1111/bc 12955},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84978674801&doi=10.1111%2fbcp.12955&partnerID=40&md5=9df3f0b5918595926ac30d0ce47c36fdhttp://onlinelibrary.wiley.com/store/10.1111/bcp.12955/asset/bcp12955.pdf?v=1&t=ix92m3r5&s=d948bd02d9b37da9e489510ce110f4dc941afc02},
   year = {2016},
   type = {Journal Article}
}

@article{RN307,
   author = {Engelkes, M. and Janssens, H. M. and de Jongste, J. C. and Sturkenboom, M. C. J. M. and Verhamme, K. M. C.},
   title = {Prescription patterns, adherence and characteristics of non-adherence in children with asthma in primary care},
   journal = {Pediatric Allergy and Immunology},
   volume = {27},
   number = {2},
   pages = {201-208 , DOI = 10.1111/pai.12507},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84959334407&doi=10.1111%2fpai.12507&partnerID=40&md5=ddf50aa6cbd6450b65103c9ebfb1b777http://onlinelibrary.wiley.com/store/10.1111/pai.12507/asset/pai12507.pdf?v=1&t=ix92fi82&s=e0bea1354a54b8d8e7b01764233becf04fb4940e},
   year = {2016},
   type = {Journal Article}
}

@article{RN309,
   author = {Engelkes, M. and Janssens, H. M. and de Ridder, M. A. J. and Sturkenboom, M. C. J. M. and de Jongste, J. C. and Verhamme, K. M. C.},
   title = {Real life data on incidence and risk factors of severe asthma exacerbations in children in primary care},
   journal = {Respiratory Medicine},
   volume = {119},
   pages = {48-54 , DOI = 10.1016/j.rmed.2016.08.016},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84983687013&doi=10.1016%2fj.rmed.2016.08.016&partnerID=40&md5=875ef01426ea761ab8405e8e2490e3cbhttp://ac.els-cdn.com/S0954611116302049/1-s2.0-S0954611116302049-main.pdf?_tid=f0de3d8a-cd0d-11e6-b715-00000aacb35e&acdnat=1482937224_0d3b39339ccd092d8822eb2a31e504db},
   year = {2016},
   type = {Journal Article}
}

@article{RN284,
   author = {Coloma, P. M. and de Ridder, M. and Bezemer, I. and Herings, R. M. C. and Gini, R. and Pecchioli, S. and Scotti, L. and Rijnbeek, P. and Mosseveld, M. and van der Lei, J. and Trifirò, G. and Sturkenboom, M.},
   title = {Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study},
   journal = {Osteoporosis International},
   volume = {27},
   number = {5},
   pages = {1857-1867 , DOI = 10.1007/s00198-015-3441-2},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84951837058&doi=10.1007%2fs00198-015-3441-2&partnerID=40&md5=4676abcca990e245d4e2a1b62bb74615https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839043/pdf/198_2015_Article_3441.pdf},
   year = {2016},
   type = {Journal Article}
}

@article{RN337,
   author = {Joore, I. K. and Twisk, D. E. and Vanrolleghem, A. M. and De Ridder, M. and Geerlings, S. E. and Van Bergen, J. E. A. M. and Van Den Broek, I. V.},
   title = {The need to scale up HIV indicator condition-guided testing for early case-finding: a case-control study in primary care},
   journal = {BMC Family Practice},
   volume = {17},
   number = {1},
   pages = {1-10 , DOI = 10.1186/s12875-016-0556-2},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84995487928&doi=10.1186%2fs12875-016-0556-2&partnerID=40&md5=e62e7d4df7415390940a383baf9a23dahttp://download.springer.com/static/pdf/573/art%253A10.1186%252Fs12875-016-0556-2.pdf?originUrl=http%3A%2F%2Fbmcfampract.biomedcentral.com%2Farticle%2F10.1186%2Fs12875-016-0556-2&token2=exp=1482937389~acl=%2Fstatic%2Fpdf%2F573%2Fart%25253A10.1186%25252Fs12875-016-0556-2.pdf*~hmac=b0ca90b7bb26a7ffb827681e8f58fadcc3a177c9ef5551785a7993c9a87dbdfe},
   year = {2016},
   type = {Journal Article}
}

@article{RN272,
   author = {Bezemer, I. D. and Verhamme, K. M. C. and Gini, R. and Mosseveld, M. and Rijnbeek, P. R. and Trifirò, G. and Sturkenboom, M. C. J. M. and Penning-Van Beest, F. J. A. and Herings, R. M. C.},
   title = {Use of oral contraceptives in three European countries: A population-based multi-database study},
   journal = {European Journal of Contraception and Reproductive Health Care},
   volume = {21},
   number = {1},
   pages = {81-87 , DOI = 10.3109/13625187.2015.1102220},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84953838875&doi=10.3109%2f13625187.2015.1102220&partnerID=40&md5=2ae44ea058de0b32552e18da34f72900},
   year = {2016},
   type = {Journal Article}
}

@article{RN290,
   author = {De Bie, S. and Kaguelidou, F. and Verhamme, K. M. C. and De Ridder, M. and Picelli, G. and Straus, S. M. J. M. and Giaquinto, C. and Stricker, B. H. and Bielicki, J. and Sharland, M. and Sturkenboom, M. C. J. M.},
   title = {Using prescription patterns in primary care to derive new quality indicators for childhood community antibiotic prescribing},
   journal = {Pediatric Infectious Disease Journal},
   volume = {35},
   number = {12},
   pages = {1317-1323 , DOI = 10.1097/inf.0000000000001324},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84987597535&doi=10.1097%2fINF.0000000000001324&partnerID=40&md5=732ab4434558cf5223bffb836d1d6021http://ovidsp.tx.ovid.com/ovftpdfs/FPDDNCLBDCODKJ00/fs046/ovft/live/gv023/00006454/00006454-201612000-00009.pdf},
   year = {2016},
   type = {Journal Article}
}

@article{RN344,
   author = {Koffeman, A. R. and Van Buul, A. R. and Valkhoff, V. E. and Jong, G. W. and Bindels, P. J. and Sturkenboom, M. C. and Van der Lei, J. and Luijsterburg, P. A. and Bierma-Zeinstra, S. M.},
   title = {Adverse drug reactions in a primary care population prescribed non-steroidal anti-inflammatory drugs},
   journal = {Scand J Prim Health Care},
   volume = {33},
   number = {3},
   pages = {163-9 , ISSN = 1502-7724 (Electronic) 0281-3432 (Linking)},
   url = {http://www.tandfonline.com/doi/pdf/10.3109/02813432.2015.1067513},
   year = {2015},
   type = {Journal Article}
}

@article{RN368,
   author = {Mor, A. and Frøslev, T. and Thomsen, R. W. and Oteri, A. and Rijnbeek, P. and Schink, T. and Garbe, E. and Pecchioli, S. and Innocenti, F. and Bezemer, I. and Poluzzi, E. and Sturkenboom, M. C. and Trifirò, G. and Søgaard, M.},
   title = {Antibiotic use varies substantially among adults: a cross-national study from five European Countries in the ARITMO project},
   journal = {Infection},
   volume = {43},
   number = {4},
   pages = {453-472 , DOI = 10.1007/s15010-015-0768-8},
   url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84938422629&partnerID=40&md5=0aed9fcd221f16892dc8525287599f38http://download.springer.com/static/pdf/178/art%253A10.1007%252Fs15010-015-0768-8.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs15010-015-0768-8&token2=exp=1454578102~acl=%2Fstatic%2Fpdf%2F178%2Fart%25253A10.1007%25252Fs15010-015-0768-8.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs15010-015-0768-8*~hmac=86cafa54cd341fd41df5249e58f05a9e463dcf0f0e163233f7e6e2dff33384d0},
   year = {2015},
   type = {Journal Article}
}

@article{RN281,
   author = {Cheung, K. and Aarts, N. and Noordam, R. and Van Blijderveen, J. C. and Sturkenboom, M. C. and Ruiter, R. and Visser, L. E. and Stricker, B. H.},
   title = {Antidepressant use and the risk of suicide: A population-based cohort study},
   journal = {Journal of Affective Disorders},
   volume = {174},
   pages = {479-484 , DOI = 10.1016/j.jad.2014.12.032},
   url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84920169204&partnerID=40&md5=8cae45ff310ad80588bf31ea14c2b675http://ac.els-cdn.com/S0165032714008180/1-s2.0-S0165032714008180-main.pdf?_tid=b08e62f0-cb1f-11e5-b4c7-00000aab0f27&acdnat=1454577447_1253212d490e972f230b38cef319fda7},
   year = {2015},
   type = {Journal Article}
}

@article{RN478,
   author = {Vermeer-de Bondt, P. E. and Schoffelen, T. and Vanrolleghem, A. M. and Isken, L. D. and Van Deuren, M. and Sturkenboom, M. C. J. M. and Timen, A.},
   title = {Coverage of the 2011 Q fever vaccination campaign in the Netherlands, using retrospective population-based prevalence estimation of cardiovascular risk-conditions for chronic Q fever},
   journal = {PLoS ONE},
   volume = {10},
   number = {4 , DOI = 10.1371/journal.pone.0123570},
   url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84929347178&partnerID=40&md5=ef452cd4223611dab299de59a51de686http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0123570&representation=PDF},
   year = {2015},
   type = {Journal Article}
}

@article{RN342,
   author = {Klooster, T. M. S. V. and de Ridder, M. A. J. and Kemmeren, J. M. and van der Lei, J. and Dekker, F. and Sturkenboom, M. and de Melker, H. E.},
   title = {Examining a possible association between human papilloma virus (HPV) vaccination and migraine: results of a cohort study in the Netherlands},
   journal = {European Journal of Pediatrics},
   volume = {174},
   number = {5},
   pages = {641-649 , DOI = 10.1007/s00431-014-2444-x},
   url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84928545937&partnerID=40&md5=65c6747c9beea074bcb242c1eddf6c6ehttp://download.springer.com/static/pdf/798/art%253A10.1007%252Fs00431-014-2444-x.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00431-014-2444-x&token2=exp=1454578060~acl=%2Fstatic%2Fpdf%2F798%2Fart%25253A10.1007%25252Fs00431-014-2444-x.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs00431-014-2444-x*~hmac=08dde9284e457f410fc2d9d0dfa6a550eecd38036ba5aeef3ca6398dcf0ef078},
   year = {2015},
   type = {Journal Article}
}

@article{RN362,
   author = {Masclee, G. M. C. and Coloma, P. M. and Kuipers, E. J. and Sturkenboom, M. C. J. M.},
   title = {Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs},
   journal = {American Journal of Gastroenterology},
   volume = {110},
   number = {5},
   pages = {749-759 , DOI = 10.1038/ajg.2015.119},
   url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84928928129&partnerID=40&md5=a516d1b05026442281a2de8e4a6552c1http://www.nature.com/ajg/journal/v110/n5/pdf/ajg2015119a.pdf},
   year = {2015},
   type = {Journal Article}
}

@article{RN363,
   author = {Masclee, G. M. C. and Coloma, P. M. and Spaander, M. C. W. and Kuipers, E. J. and Sturkenboom, M. C. J. M.},
   title = {NSAIDs, statins, low-dose aspirin and PPIs, and the risk of oesophageal adenocarcinoma among patients with Barrett's oesophagus: A populationbased case-control study},
   journal = {BMJ Open},
   volume = {5},
   number = {1 , DOI = 10.1136/bmjopen-2014-006640},
   url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84922373073&partnerID=40&md5=b4277ac91e48080a6bd311dec11ac692http://bmjopen.bmj.com/content/5/1/e006640.full.pdf},
   year = {2015},
   type = {Journal Article}
}

@article{RN382,
   author = {Noordam, R. and Aarts, N. and Verhamme, K. M. and Sturkenboom, M. C. and Stricker, B. H. and Visser, L. E.},
   title = {Prescription and indication trends of antidepressant drugs in the Netherlands between 1996 and 2012: a dynamic population-based study},
   journal = {Eur J Clin Pharmacol},
   volume = {71},
   number = {3},
   pages = {369-75 , ISSN = 1432-1041 (Electronic) 0031-6970 (Linking)},
   url = {http://download.springer.com/static/pdf/672/art%253A10.1007%252Fs00228-014-1803-x.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00228-014-1803-x&token2=exp=1454578191~acl=%2Fstatic%2Fpdf%2F672%2Fart%25253A10.1007%25252Fs00228-014-1803-x.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs00228-014-1803-x*~hmac=8deb969ce4f76c57584d414a2c48e605154bdd0e893371da8170c8969f02a069},
   year = {2015},
   type = {Journal Article}
}

@article{RN268,
   author = {Bardai, A. and Blom, M. T. and Van Noord, C. and Verhamme, K. M. and Sturkenboom, M. C. J. M. and Tan, H. L.},
   title = {Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications},
   journal = {Heart},
   volume = {101},
   number = {1},
   pages = {14-22 , DOI = 10.1136/heartjnl-2014-305664},
   url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84919731231&partnerID=40&md5=d2d439994762f9f02413a3bbebbfb317http://heart.bmj.com/content/101/1/17.full.pdf},
   year = {2015},
   type = {Journal Article}
}

@article{RN289,
   author = {de Bie, S. and Coloma, P. M. and Ferrajolo, C. and Verhamme, K. M. and Trifiro, G. and Schuemie, M. J. and Straus, S. M. and Gini, R. and Herings, R. and Mazzaglia, G. and Picelli, G. and Ghirardi, A. and Pedersen, L. and Stricker, B. H. and van der Lei, J. and Sturkenboom, M. C. and consortium, Eu-Adr},
   title = {The role of electronic healthcare record databases in paediatric drug safety surveillance: a retrospective cohort study},
   journal = {Br J Clin Pharmacol},
   volume = {80},
   number = {2},
   pages = {304-14 , ISSN = 1365-2125 (Electronic) 0306-5251 (Linking)},
   url = {http://onlinelibrary.wiley.com/store/10.1111/bcp.12610/asset/bcp12610.pdf?v=1&t=ik81ldds&s=e82c3ffa79879e2d20df5a2323193e705db55334},
   year = {2015},
   type = {Journal Article}
}

@article{RN488,
   author = {Warle-van Herwaarden, M. F. and Koffeman, A. R. and Valkhoff, V. E. and t Jong, G. W. and Kramers, C. and Sturkenboom, M. C. and De Smet, P. A.},
   title = {Time-trends in the prescribing of gastroprotective agents to primary care patients initiating low-dose aspirin or non-steroidal anti-inflammatory drugs: a population-based cohort study},
   journal = {Br J Clin Pharmacol},
   volume = {80},
   number = {3},
   pages = {589-98 , ISSN = 1365-2125 (Electronic) 0306-5251 (Linking)},
   url = {http://onlinelibrary.wiley.com/store/10.1111/bcp.12626/asset/bcp12626.pdf?v=1&t=ik81lo4k&s=4d46ff98e9f9ad1fca939ee57090f34f1f57b144},
   year = {2015},
   type = {Journal Article}
}

@article{RN308,
   author = {Engelkes, M. and Janssens, H. M. and de Ridder, M. A. and de Jongste, J. C. and Sturkenboom, M. C. and Verhamme, K. M.},
   title = {Time trends in the incidence, prevalence and age at diagnosis of asthma in children},
   journal = {Pediatr Allergy Immunol},
   volume = {26},
   number = {4},
   pages = {367-74 , ISSN = 1399-3038 (Electronic) 0905-6157 (Linking)},
   url = {http://onlinelibrary.wiley.com/store/10.1111/pai.12376/asset/pai12376.pdf?v=1&t=ik81m4su&s=8600577307304e127ad948c180dab1c4d3602804},
   year = {2015},
   type = {Journal Article}
}

@article{RN324,
   author = {Holstiege, J. and Enders, D. and Schink, T. and Innocenti, F. and Oteri, A. and Bezemer, I. and Kaguelidou, F. and Molokhia, M. and Poluzzi, E. and Puccini, A. and Ulrichsen, S. P. and Sturkenboom, M. C. and Trifirò, G. and Garbe, E.},
   title = {Trends in paediatric macrolide use in five European countries - A population-based study},
   journal = {European Journal of Clinical Pharmacology},
   volume = {71},
   number = {8},
   pages = {991-999 , DOI = 10.1007/s00228-015-1870-7},
   url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84937730287&partnerID=40&md5=f46a2f588031311cb0e54dfb769a5643http://download.springer.com/static/pdf/372/art%253A10.1007%252Fs00228-015-1870-7.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00228-015-1870-7&token2=exp=1454578116~acl=%2Fstatic%2Fpdf%2F372%2Fart%25253A10.1007%25252Fs00228-015-1870-7.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1007%252Fs00228-015-1870-7*~hmac=3c3d17194fc912177ee970b8ae5ba166d192638574ed665944e13943c67b703d},
   year = {2015},
   type = {Journal Article}
}

@article{RN386,
   author = {Pacurariu, A. C. and Straus, S. M. and Trifiro, G. and Schuemie, M. J. and Gini, R. and Herings, R. and Mazzaglia, G. and Picelli, G. and Scotti, L. and Pedersen, L. and Arlett, P. and van der Lei, J. and Sturkenboom, M. C. and Coloma, P. M.},
   title = {Useful Interplay Between Spontaneous ADR Reports and Electronic Healthcare Records in Signal Detection},
   journal = {Drug Saf},
   volume = {38},
   number = {12},
   pages = {1201-10 , ISSN = 0114-5916 (Print) 0114-5916 (Linking)},
   url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659852/pdf/40264_2015_Article_341.pdf},
   year = {2015},
   type = {Journal Article}
}

@article{RN442,
   author = {Van Blijderveen, J. C. and Straus, S. M. and De Ridder, M. A. and Stricker, B. H. and Sturkenboom, M. C. and Verhamme, K. M.},
   title = {Adherence to renal function monitoring guidelines in patients starting antihypertensive therapy with diuretics and RAAS inhibitors: A retrospective cohort study},
   journal = {Drug Safety},
   volume = {37},
   number = {5},
   pages = {369-377 , DOI = 10.1007/s40264-014-0160-0},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84901911216&doi=10.1007%2fs40264-014-0160-0&partnerID=40&md5=28ba041381ad9b44974445948ced5e75},
   year = {2014},
   type = {Journal Article}
}

@article{RN444,
   author = {Van Blijderveen, J. C. and Straus, S. M. and Zietse, R. and Stricker, B. H. and Sturkenboom, M. C. and Verhamme, K. M.},
   title = {A population-based study on the prevalence and incidence of chronic kidney disease in the Netherlands},
   journal = {International Urology and Nephrology},
   volume = {46},
   number = {3},
   pages = {583-592 , DOI = 10.1007/s11255-013-0563-3},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84896927018&doi=10.1007%2fs11255-013-0563-3&partnerID=40&md5=b5552f0267fad1fc4dc339089478fb32},
   year = {2014},
   type = {Journal Article}
}

@article{RN252,
   author = {Afzal, Z. and Pons, E. and Kang, N. and Sturkenboom, M. C. J. M. and Schuemie, M. J. and Kors, J. A.},
   title = {ContextD: An algorithm to identify contextual properties of medical terms in a dutch clinical corpus},
   journal = {BMC Bioinformatics},
   volume = {15},
   number = {1 , DOI = 10.1186/s12859-014-0373-3},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84923933223&doi=10.1186%2fs12859-014-0373-3&partnerID=40&md5=a2b014343bedde1a4c392aba69895b9a},
   year = {2014},
   type = {Journal Article}
}

@article{RN388,
   author = {Patadia, V. K. and Schuemie, M. J. and Coloma, P. and Herings, R. and van der Lei, J. and Straus, S. and Sturkenboom, M. and Trifirò, G.},
   title = {Evaluating performance of electronic healthcare records and spontaneous reporting data in drug safety signal detection},
   journal = {International Journal of Clinical Pharmacy},
   volume = {37},
   number = {1},
   pages = {94-104 , DOI = 10.1007/s11096-014-0044-5},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84925534127&doi=10.1007%2fs11096-014-0044-5&partnerID=40&md5=8f963fc1281b80116576c024a1290e20},
   year = {2014},
   type = {Journal Article}
}

@article{RN343,
   author = {Koffeman, A. R. and Valkhoff, V. E. and Jong, G. W. and Warlé-Van Herwaarden, M. F. and Bindels, P. J. and Sturkenboom, M. C. and Luijsterburg, P. A. and Bierma-Zeinstra, S. M.},
   title = {Ischaemic cardiovascular risk and prescription of non-steroidal anti-inflammatory drugs for musculoskeletal complaints},
   journal = {Scandinavian Journal of Primary Health Care},
   volume = {32},
   number = {2},
   pages = {90-98 , DOI = 10.3109/02813432.2014.929810},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84902687608&doi=10.3109%2f02813432.2014.929810&partnerID=40&md5=399456b49ddb66aa881205bdb6645f1f},
   year = {2014},
   type = {Journal Article}
}

@article{RN453,
   author = {Van Lier, A. and Van Erp, J. and Donker, G. A. and Van der Maas, N. A. T. and Sturkenboom, M. C. J. M. and De Melker, H. E.},
   title = {Low varicella-related consultation rate in the Netherlands in primary care data},
   journal = {Vaccine},
   volume = {32},
   number = {28},
   pages = {3517-3524 , DOI = 10.1016/j.vaccine.2014.04.034},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84901468739&doi=10.1016%2fj.vaccine.2014.04.034&partnerID=40&md5=3c7a81624a1555197cea4b281ebd6061},
   year = {2014},
   type = {Journal Article}
}

@article{RN443,
   author = {Van Blijderveen, J. C. and Straus, S. M. and Rodenburg, E. M. and Zietse, R. and Stricker, B. H. and Sturkenboom, M. C. and Verhamme, K. M.},
   title = {Risk of hyponatremia with diuretics: Chlorthalidone versus hydrochlorothiazide},
   journal = {American Journal of Medicine},
   volume = {127},
   number = {8},
   pages = {763-771 , DOI = 10.1016/j.amjmed.2014.04.014},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905658328&doi=10.1016%2fj.amjmed.2014.04.014&partnerID=40&md5=e3b0ea998faa59003477580df7f7d5f8},
   year = {2014},
   type = {Journal Article}
}

@article{RN365,
   author = {Masclee, G. M. C. and Valkhoff, V. E. and Coloma, P. M. and De Ridder, M. and Romio, S. and Schuemie, M. J. and Herings, R. and Gini, R. and Mazzaglia, G. and Picelli, G. and Scotti, L. and Pedersen, L. and Kuipers, E. J. and Van Der Lei, J. and Sturkenboom, M. C. J. M.},
   title = {Risk of upper gastrointestinal bleeding from different drug combinations},
   journal = {Gastroenterology},
   volume = {147},
   number = {4},
   pages = {784-792.e9 , DOI = 10.1053/j.gastro.2014.06.007},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84921651673&doi=10.1053%2fj.gastro.2014.06.007&partnerID=40&md5=b99d76ee9db083e7e11cd66d1adc9752},
   year = {2014},
   type = {Journal Article}
}

@article{RN311,
   author = {Ferrajolo, C. and Coloma, P. M. and Verhamme, K. M. C. and Schuemie, M. J. and De Bie, S. and Gini, R. and Herings, R. and Mazzaglia, G. and Picelli, G. and Giaquinto, C. and Scotti, L. and Avillach, P. and Pedersen, L. and Rossi, F. and Capuano, A. and Van Der Lei, J. and Trifiro, G. and Sturkenboom, M. C. J. M.},
   title = {Signal detection of potentially drug-induced acute liver injury in children using a multi-country healthcare database network},
   journal = {Drug Safety},
   volume = {37},
   number = {2},
   pages = {99-108 , DOI = 10.1007/s40264-013-0132-9},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897944112&doi=10.1007%2fs40264-013-0132-9&partnerID=40&md5=5dd2fc4e117b9d66d49282abc917fb43},
   year = {2014},
   type = {Journal Article}
}

@article{RN325,
   author = {Holstiege, J. and Schink, T. and Molokhia, M. and Mazzaglia, G. and Innocenti, F. and Oteri, A. and Bezemer, I. and Poluzzi, E. and Puccini, A. and Ulrichsen, S. P. and Sturkenboom, M. C. and Trifirò, G. and Garbe, E.},
   title = {Systemic antibiotic prescribing to paediatric outpatients in 5 European countries: A population-based cohort study},
   journal = {BMC Pediatrics},
   volume = {14},
   number = {1 , DOI = 10.1186/1471-2431-14-174},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84937729728&doi=10.1186%2f1471-2431-14-174&partnerID=40&md5=58e608a6f46fe88216a07b83b8c80ca2},
   year = {2014},
   type = {Journal Article}
}

@article{RN361,
   author = {Masclee, G. M. C. and Coloma, P. M. and De Wilde, M. and Kuipers, E. J. and Sturkenboom, M. C. J. M.},
   title = {The incidence of Barrett's oesophagus and oesophageal adenocarcinoma in the United Kingdom and the Netherlands is levelling off},
   journal = {Alimentary Pharmacology and Therapeutics},
   volume = {39},
   number = {11},
   pages = {1321-1330 , DOI = 10.1111/apt.12759},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84899996484&doi=10.1111%2fapt.12759&partnerID=40&md5=90f9cc5d3bb8e38fba38b21dcce88ae3},
   year = {2014},
   type = {Journal Article}
}

@article{RN387,
   author = {Patadia, V. K. and Coloma, P. and Schuemie, M. J. and Herings, R. and Gini, R. and Mazzaglia, G. and Picelli, G. and Fornari, C. and Pedersen, L. and Van Der Lei, J. and Sturkenboom, M. and Trifirò, G.},
   title = {Using real-world healthcare data for pharmacovigilance signal detection-the experience of the EU-ADR project},
   journal = {Expert Review of Clinical Pharmacology},
   volume = {8},
   number = {1},
   pages = {95-102 , DOI = 10.1586/17512433.2015.992878},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84916925627&doi=10.1586%2f17512433.2015.992878&partnerID=40&md5=f039f64bf24aa1102daef222e7067a45},
   year = {2014},
   type = {Journal Article}
}

@article{RN437,
   author = {Valkhoff, V. E. and Coloma, P. M. and Masclee, G. M. C. and Gini, R. and Innocenti, F. and Lapi, F. and Molokhia, M. and Mosseveld, M. and Nielsson, M. S. and Schuemie, M. and Thiessard, F. and Van Der Lei, J. and Sturkenboom, M. C. J. M. and Trifirò, G.},
   title = {Validation study in four health-care databases: Upper gastrointestinal bleeding misclassification affects precision but not magnitude of drug-related upper gastrointestinal bleeding risk},
   journal = {Journal of Clinical Epidemiology},
   volume = {67},
   number = {8},
   pages = {921-931 , DOI = 10.1016/j.jclinepi.2014.02.020},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84902887264&doi=10.1016%2fj.jclinepi.2014.02.020&partnerID=40&md5=f7a1ed3aaa33d1f7b99c2c338cb60985},
   year = {2014},
   type = {Journal Article}
}

@article{RN427,
   author = {Sutterland, A. L. and Dieleman, J. and Storosum, J. G. and Voordouw, B. A. C. and Kroon, J. and Veldhuis, J. and Denys, D. A. J. P. and De Haan, L. and Sturkenboom, M. C. J. M.},
   title = {Annual incidence rate of schizophrenia and schizophrenia spectrum disorders in a longitudinal population-based cohort study},
   journal = {Social Psychiatry and Psychiatric Epidemiology},
   volume = {48},
   number = {9},
   pages = {1357-1365 , DOI = 10.1007/s00127-013-0651-9},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84884586496&doi=10.1007%2fs00127-013-0651-9&partnerID=40&md5=355a7010da8b1c525ad78e5b3ca58709},
   year = {2013},
   type = {Journal Article}
}

@article{RN283,
   author = {Coloma, P. M. and Avillach, P. and Salvo, F. and Schuemie, M. J. and Ferrajolo, C. and Pariente, A. and Fourrier-Réglat, A. and Molokhia, M. and Patadia, V. and Van Der Lei, J. and Sturkenboom, M. and Trifirò, G.},
   title = {A reference standard for evaluation of methods for drug safety signal detection using electronic healthcare record databases},
   journal = {Drug Safety},
   volume = {36},
   number = {1},
   pages = {13-23 , DOI = 10.1007/s40264-012-0002-x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876548863&doi=10.1007%2fs40264-012-0002-x&partnerID=40&md5=397f19e6817c70a53b2b15be8f13df23},
   year = {2013},
   type = {Journal Article}
}

@article{RN250,
   author = {Afzal, Z. and Engelkes, M. and Verhamme, K. M. C. and Janssens, H. M. and Sturkenboom, M. C. J. M. and Kors, J. A. and Schuemie, M. J.},
   title = {Automatic generation of case-detection algorithms to identify children with asthma from large electronic health record databases},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {22},
   number = {8},
   pages = {826-833 , DOI = 10.1002/pds.3438},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84880712055&doi=10.1002%2fpds.3438&partnerID=40&md5=e61ea02633bf4485bfafa33a155c5284},
   year = {2013},
   type = {Journal Article}
}

@article{RN366,
   author = {Masclee, G. M. C. and Valkhoff, V. E. and Van Soest, E. M. and Schade, R. and Mazzaglia, G. and Molokhia, M. and Trifirò, G. and Goldstein, J. L. and Hernández-Díaz, S. and Kuipers, E. J. and Sturkenboom, M. C. J. M.},
   title = {Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: What to prescribe in daily clinical practice?},
   journal = {Alimentary Pharmacology and Therapeutics},
   volume = {38},
   number = {2},
   pages = {178-189 , DOI = 10.1111/apt.12348},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84879195648&doi=10.1111%2fapt.12348&partnerID=40&md5=302736c6364eb44632bb326757134d3f},
   year = {2013},
   type = {Journal Article}
}

@article{RN285,
   author = {Coloma, P. M. and Schuemie, M. J. and Trifirò, G. and Furlong, L. and van Mulligen, E. and Bauer-Mehren, A. and Avillach, P. and Kors, J. and Sanz, F. and Mestres, J. and Oliveira, J. L. and Boyer, S. and Helgee, E. A. and Molokhia, M. and Matthews, J. and Prieto-Merino, D. and Gini, R. and Herings, R. and Mazzaglia, G. and Picelli, G. and Scotti, L. and Pedersen, L. and van der Lei, J. and Sturkenboom, M.},
   title = {Drug-Induced Acute Myocardial Infarction: Identifying 'Prime Suspects' from Electronic Healthcare Records-Based Surveillance System},
   journal = {PLoS ONE},
   volume = {8},
   number = {8 , DOI = 10.1371/journal.pone.0072148},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84883144641&doi=10.1371%2fjournal.pone.0072148&partnerID=40&md5=b7235435f2faa502995e9e1d2454c063},
   year = {2013},
   type = {Journal Article}
}

@article{RN490,
   author = {Wijnans, L. and Dieleman, J. and Voordouw, B. and Sturkenboom, M.},
   title = {Effectiveness of MF59™ Adjuvanted Influenza A(H1N1)pdm09 Vaccine in Risk Groups in the Netherlands},
   journal = {PLoS ONE},
   volume = {8},
   number = {4 , DOI = 10.1371/journal.pone.0063156},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84876982504&doi=10.1371%2fjournal.pone.0063156&partnerID=40&md5=1bfc7af3907c918bfcafddc0fb9bfebc},
   year = {2013},
   type = {Journal Article}
}

@article{RN263,
   author = {Avillach, P. and Coloma, P. M. and Gini, R. and Schuemie, M. and Mougin, F. and Dufour, J. C. and Mazzaglia, G. and Giaquinto, C. and Fornari, C. and Herings, R. and Molokhia, M. and Pedersen, L. and Fourrier-Réglat, A. and Fieschi, M. and Sturkenboom, M. and van der Lei, J. and Pariente, A. and Trifirò, G.},
   title = {Harmonization process for the identification of medical events in eight European healthcare databases: The experience from the EU-ADR project},
   journal = {Journal of the American Medical Informatics Association},
   volume = {20},
   number = {1},
   pages = {184-192 , DOI = 10.1136/amiajnl-2012-000933},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84871888534&doi=10.1136%2famiajnl-2012-000933&partnerID=40&md5=5efb3a982e166d340ae7ba514f990511},
   year = {2013},
   type = {Journal Article}
}

@article{RN288,
   author = {Coloma, P. M. and Valkhoff, V. E. and Mazzaglia, G. and Nielsson, M. S. and Pedersen, L. and Molokhia, M. and Mosseveld, M. and Morabito, P. and Schuemie, M. J. and Van Der Lei, J. and Sturkenboom, M. and Trifirò, G.},
   title = {Identification of acute myocardial infarction from electronic healthcare records using different disease coding systems: A validation study in three European countries},
   journal = {BMJ Open},
   volume = {3},
   number = {6 , DOI = 10.1136/bmjopen-2013-002862},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84878752226&doi=10.1136%2fbmjopen-2013-002862&partnerID=40&md5=aa4ac519426a96a74d35d496e33c9f25},
   year = {2013},
   type = {Journal Article}
}

@article{RN313,
   author = {Ferrajolo, C. and Verhamme, K. M. C. and Trifirò, G. and T Jong, G. W. and Giaquinto, C. and Picelli, G. and Oteri, A. and De Bie, S. and Valkhoff, V. E. and Schuemie, M. J. and Mazzaglia, G. and Cricelli, C. and Rossi, F. and Capuano, A. and Sturkenboom, M. C. J. M.},
   title = {Idiopathic acute liver injury in paediatric outpatients: Incidence and signal detection in two european countries},
   journal = {Drug Safety},
   volume = {36},
   number = {10},
   pages = {1007-1016 , DOI = 10.1007/s40264-013-0045-7},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885452246&doi=10.1007%2fs40264-013-0045-7&partnerID=40&md5=dca8d73b8e6d7c9129db678eb705a103},
   year = {2013},
   type = {Journal Article}
}

@article{RN253,
   author = {Afzal, Z. and Schuemie, M. J. and Van Blijderveen, J. C. and Sen, E. F. and Sturkenboom, M. C. and Kors, J. A.},
   title = {Improving sensitivity of machine learning methods for automated case identification from free-text electronic medical records},
   journal = {BMC Medical Informatics and Decision Making},
   volume = {13},
   number = {1 , DOI = 10.1186/1472-6947-13-30},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84874398938&doi=10.1186%2f1472-6947-13-30&partnerID=40&md5=fe350a51119e61b46aa1b72b2ba14dd1},
   year = {2013},
   type = {Journal Article}
}

@article{RN348,
   author = {Kroon, J. S. and Wohlfarth, T. D. and Dieleman, J. and Sutterland, A. L. and Storosum, J. G. and Denys, D. and de Haan, L. and Sturkenboom, M. C.},
   title = {Incidence rates and risk factors of bipolar disorder in the general population: A population-based cohort study},
   journal = {Bipolar Disorders},
   volume = {15},
   number = {3},
   pages = {306-313 , DOI = 10.1111/bdi.12058},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84877331601&doi=10.1111%2fbdi.12058&partnerID=40&md5=f71a5026a6ce3cd6e20a8ec610379302},
   year = {2013},
   type = {Journal Article}
}

@article{RN300,
   author = {Dodd, C. N. and Romio, S. A. and Black, S. and Vellozzi, C. and Andrews, N. and Sturkenboom, M. and Zuber, P. and Hua, W. and Bonhoeffer, J. and Buttery, J. and Crawford, N. and Deceuninck, G. and de Vries, C. and De Wals, P. and Gimeno, M. V. G. and Heijbel, H. and Hughes, H. and Hur, K. and Hviid, A. and Kelman, J. and Kilpi, T. and Chuang, S. K. and Macartney, K. and Rett, M. and Lopez-Callada, V. R. and Salmon, D. and Sanchez, F. G. and Sanz, N. and Silverman, B. and Storsaeter, J. and Thirugnanam, U. and van der Maas, N. and Yih, K. and Zhang, T. and Izurieta, H. and Addis, A. and Akhtar, A. and Cope, J. and Davis, R. and Gargiullo, P. and Kurz, X. and Law, B. and Sahinovic, I. and Tokars, J. and Serrano, P. and Cheng, A. and Andrews, N. and Charles, P. and Clothier, H. and Day, B. and Day, T. and Gates, P. and MacDonnell, R. and Roberts, L. and Rodriguez-Casero, V. and Wijeratne, T. and Kiers, L. and Blyth, C. and Booy, R. and Elliott, E. and Gold, M. and Marshall, H. and McIntyre, P. and Richmond, P. and Royle, J. and Wood, N. and Zurynski, Y. and Calvo, G. and Campins, M. and Corominas, N. and Torres, F. and Valls, J. and Vilella, A. and Dutra, D. and Eick-Cost, A. and Jackson, H. M. and Garman, P. and Hu, Z. and Rigo, M. and Badoo, J. and Cho, D. and Polakowski, L. L. and Sandhu, S. K. and Sun, G. and Chan, H. S. S. and Chan, K. Y. and Cheung, R. and Cheung, Y. F. and Cherk, S. and Chuang, S. K. and Fok, J. W. M. and Fung, B. H. and Ko, K. F. and Lau, K. W. and Lau, K. K. and Li, P. and Liu, H. T. and Liu, S. H. and Mok, T. and So, J. and others },
   title = {International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines},
   journal = {Vaccine},
   volume = {31},
   number = {40},
   pages = {4448-4458 , DOI = 10.1016/j.vaccine.2013.06.032},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84882864368&doi=10.1016%2fj.vaccine.2013.06.032&partnerID=40&md5=07f7e473947ccdd58a16d5d5acd50daa},
   year = {2013},
   type = {Journal Article}
}

@article{RN438,
   author = {Valkhoff, V. E. and Schade, R. and t Jong, G. W. and Romio, S. and Schuemie, M. J. and Arfe, A. and Garbe, E. and Herings, R. and Lucchi, S. and Picelli, G. and Schink, T. and Straatman, H. and Villa, M. and Kuipers, E. J. and Sturkenboom, M. C. J. M.},
   title = {Population-based analysis of non-steroidal anti-inflammatory drug use among children in four European countries in the SOS project: What size of data platforms and which study designs do we need to assess safety issues?},
   journal = {BMC Pediatrics},
   volume = {13},
   number = {1 , DOI = 10.1186/1471-2431-13-192},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84887647359&doi=10.1186%2f1471-2431-13-192&partnerID=40&md5=22e712e25ae3dfec8cd5fdd1a8e4a1a3},
   year = {2013},
   type = {Journal Article}
}

@article{RN405,
   author = {Schuemie, M. J. and Gini, R. and Coloma, P. M. and Straatman, H. and Herings, R. M. C. and Pedersen, L. and Innocenti, F. and Mazzaglia, G. and Picelli, G. and Van Der Lei, J. and Sturkenboom, M. C. J. M.},
   title = {Replication of the OMOP experiment in europe: Evaluating methods for risk identification in electronic health record databases},
   journal = {Drug Safety},
   volume = {36},
   number = {SUPPL.1},
   pages = {S159-S169 , DOI = 10.1007/s40264-013-0109-8},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84892947900&doi=10.1007%2fs40264-013-0109-8&partnerID=40&md5=5f4d63cad97db0f7d3f1d19539ed6f2b},
   year = {2013},
   type = {Journal Article}
}

@article{RN491,
   author = {Wijnans, L. and Lecomte, C. and de Vries, C. and Weibel, D. and Sammon, C. and Hviid, A. and Svanström, H. and Mølgaard-Nielsen, D. and Heijbel, H. and Dahlström, L. A. and Hallgren, J. and Sparen, P. and Jennum, P. and Mosseveld, M. and Schuemie, M. and van der Maas, N. and Partinen, M. and Romio, S. and Trotta, F. and Santuccio, C. and Menna, A. and Plazzi, G. and Moghadam, K. K. and Ferro, S. and Lammers, G. J. and Overeem, S. and Johansen, K. and Kramarz, P. and Bonhoeffer, J. and Sturkenboom, M. C. J. M.},
   title = {The incidence of narcolepsy in Europe: Before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns},
   journal = {Vaccine},
   volume = {31},
   number = {8},
   pages = {1246-1254 , DOI = 10.1016/j.vaccine.2012.12.015},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84873082021&doi=10.1016%2fj.vaccine.2012.12.015&partnerID=40&md5=f8c1c1f4c72415a69d0d0d7fdfbc7276},
   year = {2013},
   type = {Journal Article}
}

@article{RN469,
   author = {Verhamme, K. M. C. and Afonso, A. and Romio, S. and Stricker, B. C. and Brusselle, G. G. O. and Sturkenboom, M. C. J. M.},
   title = {Use of tiotropium Respimat Soft Mist Inhaler versus HandiHaler and mortality in patients with COPD},
   journal = {European Respiratory Journal},
   volume = {42},
   number = {3},
   pages = {606-615 , DOI = 10.1183/09031936.00005813},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84883495199&doi=10.1183%2f09031936.00005813&partnerID=40&md5=e697fbab355308cf2eb77bdf83dbebdf},
   year = {2013},
   type = {Journal Article}
}

@article{RN440,
   author = {Valkhoff, V. E. and Van Soest, E. M. and Mazzaglia, G. and Molokhia, M. and Schade, R. and Trifiro, G. and Goldstein, J. L. and Hernandez-Diaz, S. and Kuipers, E. J. and Sturkenboom, M. C. J. M.},
   title = {Adherence to gastroprotection during cyclooxygenase 2 inhibitor treatment and the risk of upper gastrointestinal tract events: A population-based study},
   journal = {Arthritis and Rheumatism},
   volume = {64},
   number = {8},
   pages = {2792-2802 , DOI = 10.1002/art.34433},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864115219&doi=10.1002%2fart.34433&partnerID=40&md5=6e0f9dcd7968e09131708f6438f9c6d8},
   year = {2012},
   type = {Journal Article}
}

@article{RN406,
   author = {Schuemie, M. J. and Sen, E. and t Jong, G. W. and Van Soest, E. M. and Sturkenboom, M. C. and Kors, J. A.},
   title = {Automating classification of free-text electronic health records for epidemiological studies},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {21},
   number = {6},
   pages = {651-658 , DOI = 10.1002/pds.3205},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84862170821&doi=10.1002%2fpds.3205&partnerID=40&md5=e255c1eb26450c8efecc2f8b777b66d7},
   year = {2012},
   type = {Journal Article}
}

@article{RN287,
   author = {Coloma, P. M. and Trifirò, G. and Schuemie, M. J. and Gini, R. and Herings, R. and Hippisley-Cox, J. and Mazzaglia, G. and Picelli, G. and Corrao, G. and Pedersen, L. and van der Lei, J. and Sturkenboom, M.},
   title = {Electronic healthcare databases for active drug safety surveillance: Is there enough leverage?},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {21},
   number = {6},
   pages = {611-621 , DOI = 10.1002/pds.3197},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84859874348&doi=10.1002%2fpds.3197&partnerID=40&md5=0d1e083d92fab35295457d3f1d7d2619},
   year = {2012},
   type = {Journal Article}
}

@article{RN439,
   author = {Valkhoff, V. E. and Van Soest, E. M. and Masclee, G. M. C. and De Bie, S. and Mazzaglia, G. and Molokhia, M. and Kuipers, E. J. and Sturkenboom, M. C. J. M.},
   title = {Prescription of nonselective NSAIDs, coxibs and gastroprotective agents in the era of rofecoxib withdrawal - A 617 400-patient study},
   journal = {Alimentary Pharmacology and Therapeutics},
   volume = {36},
   number = {8},
   pages = {790-799 , DOI = 10.1111/apt.12028},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84866365307&doi=10.1111%2fapt.12028&partnerID=40&md5=02530e8a8271bc1de7b47180567909ff},
   year = {2012},
   type = {Journal Article}
}

@article{RN367,
   author = {Mokhles, M. M. and Trifirò, G. and Dieleman, J. P. and Haag, M. D. and Van Soest, E. M. and Verhamme, K. M. C. and Mazzaglia, G. and Herings, R. and De Luise, C. and Ross, D. and Brusselle, G. and Colao, A. and Haverkamp, W. and Schade, R. and Van Camp, G. and Zanettini, R. and Sturkenboom, M. C. J. M.},
   title = {The risk of new onset heart failure associated with dopamine agonist use in Parkinson's disease},
   journal = {Pharmacological Research},
   volume = {65},
   number = {3},
   pages = {358-364 , DOI = 10.1016/j.phrs.2011.11.009},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84857055235&doi=10.1016%2fj.phrs.2011.11.009&partnerID=40&md5=e404d73bea8a1885e08220b7907786c1},
   year = {2012},
   type = {Journal Article}
}

@article{RN470,
   author = {Verhamme, K. M. C. and Afonso, A. S. M. and van Noord, C. and Haag, M. D. and Koudstaal, P. J. and Brusselle, G. G. O. and Sturkenboom, M. C. J. M.},
   title = {Tiotropium Handihaler and the risk of cardio- or cerebrovascular events and mortality in patients with COPD},
   journal = {Pulmonary Pharmacology and Therapeutics},
   volume = {25},
   number = {1},
   pages = {19-26 , DOI = 10.1016/j.pupt.2011.10.004},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84856791095&doi=10.1016%2fj.pupt.2011.10.004&partnerID=40&md5=15610a941df11da1ddb7bbc98934da63},
   year = {2012},
   type = {Journal Article}
}

@article{RN404,
   author = {Schuemie, M. J. and Coloma, P. M. and Straatman, H. and Herings, R. M. C. and Trifirò, G. and Matthews, J. N. and Prieto-Merino, D. and Molokhia, M. and Pedersen, L. and Gini, R. and Innocenti, F. and Mazzaglia, G. and Picelli, G. and Scotti, L. and Van Der Lei, J. and Sturkenboom, M. C. J. M.},
   title = {Using electronic health care records for drug safety signal detection: A comparative evaluation of statistical methods},
   journal = {Medical Care},
   volume = {50},
   number = {10},
   pages = {890-897 , DOI = 10.1097/MLR.0b013e31825f63bf},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84866563491&doi=10.1097%2fMLR.0b013e31825f63bf&partnerID=40&md5=cd5ea038317f092791d4d9fa0e185899},
   year = {2012},
   type = {Journal Article}
}

@article{RN412,
   author = {Sen, E. F. and Verhamme, K. M. C. and Neubert, A. and Hsia, Y. and Murray, M. and Felisi, M. and Giaquinto, C. and T Jong, G. W. and Picelli, G. and Baraldi, E. and Nicolosi, A. and Ceci, A. and Wong, I. C. and Sturkenboom, M. C. J. M.},
   title = {Assessment of Pediatric asthma drug use in three European countries; A TEDDY study},
   journal = {European Journal of Pediatrics},
   volume = {170},
   number = {1},
   pages = {81-92 , DOI = 10.1007/s00431-010-1275-7},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79151484020&doi=10.1007%2fs00431-010-1275-7&partnerID=40&md5=d596de72993d5b38fe380b5bb871cd7c},
   year = {2011},
   type = {Journal Article}
}

@article{RN286,
   author = {Coloma, P. M. and Schuemie, M. J. and Trifirò, G. and Gini, R. and Herings, R. and Hippisley-Cox, J. and Mazzaglia, G. and Giaquinto, C. and Corrao, G. and Pedersen, L. and Van Der Lei, J. and Sturkenboom, M.},
   title = {Combining electronic healthcare databases in Europe to allow for large-scale drug safety monitoring: The EU-ADR Project},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {20},
   number = {1},
   pages = {1-11 , DOI = 10.1002/pds.2053},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-78650362198&doi=10.1002%2fpds.2053&partnerID=40&md5=22edc4ba0152c84c10123dcd7802c83f},
   year = {2011},
   type = {Journal Article}
}

@article{RN249,
   author = {Afonso, A. S. M. and Verhamme, K. M. C. and Sturkenboom, M. C. J. M. and Brusselle, G. G. O.},
   title = {COPD in the general population: Prevalence, incidence and survival},
   journal = {Respiratory Medicine},
   volume = {105},
   number = {12},
   pages = {1872-1884 , DOI = 10.1016/j.rmed.2011.06.012},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80054997007&doi=10.1016%2fj.rmed.2011.06.012&partnerID=40&md5=d81acb079f7d606ed803de9ac8b80b05},
   year = {2011},
   type = {Journal Article}
}

@article{RN415,
   author = {Steens, A. and Wijnans, E. G. and Dieleman, J. P. and Sturkenboom, M. C. J. M. and van der Sande, M. A. B. and van der Hoek, W.},
   title = {Effectiveness of a MF-59™-adjuvanted pandemic influenza vaccine to prevent 2009 A/H1N1 influenza-related hospitalisation; a matched case-control study},
   journal = {BMC Infectious Diseases},
   volume = {11 , DOI = 10.1186/1471-2334-11-196},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79960556293&doi=10.1186%2f1471-2334-11-196&partnerID=40&md5=e6990779df0265df928b82988297f4cb},
   year = {2011},
   type = {Journal Article}
}

@article{RN411,
   author = {Sen, E. F. and Verhamme, K. M. C. and Felisi, M. and t Jong, G. W. and Giaquinto, C. and Picelli, G. and Ceci, A. and Sturkenboom, M. C. J. M.},
   title = {Effects of safety warnings on prescription rates of cough and cold medicines in children below 2 years of age},
   journal = {British Journal of Clinical Pharmacology},
   volume = {71},
   number = {6},
   pages = {943-950 , DOI = 10.1111/j.1365-2125.2010.03860.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79955789406&doi=10.1111%2fj.1365-2125.2010.03860.x&partnerID=40&md5=bb330d560b36e5f7f40aa47c0a26bce9},
   year = {2011},
   type = {Journal Article}
}

@article{RN435,
   author = {Trifirò, G. and Patadia, V. and Schuemie, M. J. and Coloma, P. M. and Gini, R. and Herings, R. and Hippisley-Cox, J. and Mazzaglia, G. and Giaquinto, C. and Scotti, L. and Pedersen, L. and Avillach, P. and Sturkenboom, M. C. and van der Lei, J. and Eu-Adr, Group},
   title = {EU-ADR healthcare database network vs. spontaneous reporting system database: preliminary comparison of signal detection},
   journal = {Studies in health technology and informatics},
   volume = {166},
   pages = {25-30},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79960993889&partnerID=40&md5=aad7976293e7849d6c44f9553b65b6e0},
   year = {2011},
   type = {Journal Article}
}

@article{RN451,
   author = {Van Der Maas, N. A. T. and Kramer, M. A. and Jacobs, B. C. and Van Soest, E. M. and Dieleman, J. P. and Kemmeren, J. M. and De Melker, H. E. and Sturkenboom, M. C. J. M.},
   title = {Guillain-Barré syndrome: Background incidence rates in the Netherlands},
   journal = {Journal of the Peripheral Nervous System},
   volume = {16},
   number = {3},
   pages = {243-249 , DOI = 10.1111/j.1529-8027.2011.00356.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80054995317&doi=10.1111%2fj.1529-8027.2011.00356.x&partnerID=40&md5=4e2a49c059c2740db24be213ca4fb299},
   year = {2011},
   type = {Journal Article}
}

@article{RN401,
   author = {Risselada, R. and De Vries, L. M. and Dippel, D. W. J. and Van Kooten, F. and Van Der Lugt, A. and Niessen, W. J. and Firouzian, A. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {Incidence, treatment, and case-fatality of non-traumatic subarachnoid haemorrhage in the Netherlands},
   journal = {Clinical Neurology and Neurosurgery},
   volume = {113},
   number = {6},
   pages = {483-487 , DOI = 10.1016/j.clineuro.2011.02.015},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79958121164&doi=10.1016%2fj.clineuro.2011.02.015&partnerID=40&md5=2969c93aee84a37a3b742f8bcc2352e5},
   year = {2011},
   type = {Journal Article}
}

@article{RN248,
   author = {Afonso, A. S. M. and Verhamme, K. M. C. and Stricker, B. H. C. and Sturkenboom, M. C. J. M. and Brusselle, G. G. O.},
   title = {Inhaled anticholinergic drugs and risk of acute urinary retention},
   journal = {BJU International},
   volume = {107},
   number = {8},
   pages = {1266-1272 , DOI = 10.1111/j.1464-410X.2010.09600.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79954486779&doi=10.1111%2fj.1464-410X.2010.09600.x&partnerID=40&md5=6971287a3b8cf4711b68e0a41b94817c},
   year = {2011},
   type = {Journal Article}
}

@article{RN455,
   author = {Van Noord, C. and Sturkenboom, M. C. J. M. and Straus, S. M. J. M. and Witteman, J. C. M. and Stricker, B. H. Ch},
   title = {Non-cardiovascular drugs that inhibit hERG-encoded potassium channels and risk of sudden cardiac death},
   journal = {Heart},
   volume = {97},
   number = {3},
   pages = {215-220 , DOI = 10.1136/hrt.2009.188367},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-78651228024&doi=10.1136%2fhrt.2009.188367&partnerID=40&md5=f697d49a9a38e53d5a00ad191c371951},
   year = {2011},
   type = {Journal Article}
}

@article{RN462,
   author = {Van Soest, E. M. and Valkhoff, V. E. and Mazzaglia, G. and Schade, R. and Molokhia, M. and Goldstein, J. L. and Hernández-Díaz, S. and Trifirò, G. and Dieleman, J. P. and Kuipers, E. J. and Sturkenboom, M. C. J. M.},
   title = {Suboptimal gastroprotective coverage of NSAID use and the risk of upper gastrointestinal bleeding and ulcers: An observational study using three European databases},
   journal = {Gut},
   volume = {60},
   number = {12},
   pages = {1650-1659 , DOI = 10.1136/gut.2011.239848},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80655144428&doi=10.1136%2fgut.2011.239848&partnerID=40&md5=798de701c5a09d31a330806bc8924135},
   year = {2011},
   type = {Journal Article}
}

@article{RN341,
   author = {Kaur, G. and Verhamme, K. M. C. and Dieleman, J. P. and Vanrolleghem, A. and Van Soest, E. M. and Stricker, B. H. C. and Sturkenboom, M. C. J. M.},
   title = {Association between calcium channel blockers and gingival hyperplasia},
   journal = {Journal of Clinical Periodontology},
   volume = {37},
   number = {7},
   pages = {625-630 , DOI = 10.1111/j.1600-051X.2010.01574.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77953563372&doi=10.1111%2fj.1600-051X.2010.01574.x&partnerID=40&md5=7b712ede1751ba29014578f571b8285a},
   year = {2010},
   type = {Journal Article}
}

@article{RN326,
   author = {Hsia, Y. and Neubert, A. and Sturkenboom, M. C. J. M. and Murray, M. L. and Verhamme, K. M. C. and Sen, F. and Giaquinto, C. and Ceci, A. and Wong, I. C. K.},
   title = {Comparison of antiepileptic drug prescribing in children in three European countries},
   journal = {Epilepsia},
   volume = {51},
   number = {5},
   pages = {789-796 , DOI = 10.1111/j.1528-1167.2009.02331.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77951532694&doi=10.1111%2fj.1528-1167.2009.02331.x&partnerID=40&md5=ccec9044edc9a863c086f478f127604b},
   year = {2010},
   type = {Journal Article}
}

@article{RN447,
   author = {Van Den Haak, P. and Heintjes, E. and Plat, A. W. and Jan Meerding, W. and Webb, K. and Sturkenboom, M. C. and Herings, R. M. C.},
   title = {Determination of non-treatment with statins of high risk patients in the Netherlands},
   journal = {Current Medical Research and Opinion},
   volume = {26},
   number = {2},
   pages = {271-278 , DOI = 10.1185/03007990903435184},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-74549130119&doi=10.1185%2f03007990903435184&partnerID=40&md5=cc5602639949205ea5363aab7dde377e},
   year = {2010},
   type = {Journal Article}
}

@article{RN454,
   author = {Van Noord, C. and Dieleman, J. P. and Van Herpen, G. and Verhamme, K. and Sturkenboom, M. C. J. M.},
   title = {Domperidone and ventricular arrhythmia or sudden cardiac death: A population-based case-control study in the Netherlands},
   journal = {Drug Safety},
   volume = {33},
   number = {11},
   pages = {1003-1014 , DOI = 10.2165/11536840-000000000-00000},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77957763739&doi=10.2165%2f11536840-000000000-00000&partnerID=40&md5=4da0d566cb50eadb9f114ab1d16857ca},
   year = {2010},
   type = {Journal Article}
}

@article{RN346,
   author = {Koopman, J. S. H. A. and Huygen, Frank J. and Dieleman, J. P. and de Mos, M. and Sturkenboom, M. C. J. M.},
   title = {Pharmacological Treatment of Neuropathic Facial Pain in the Dutch General Population},
   journal = {Journal of Pain},
   volume = {11},
   number = {3},
   pages = {264-272 , DOI = 10.1016/j.jpain.2009.07.001},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77649238767&doi=10.1016%2fj.jpain.2009.07.001&partnerID=40&md5=ef5776b075145272adeca77ea5cf8641},
   year = {2010},
   type = {Journal Article}
}

@article{RN434,
   author = {Trifirò, G. and Dieleman, J. and Sen, E. F. and Gambassi, G. and Sturkenboom, M. C. J. M.},
   title = {Risk of Ischemic Stroke Associated with Antidepressant Drug Use in Elderly Persons},
   journal = {Journal of Clinical Psychopharmacology},
   volume = {30},
   number = {3},
   pages = {252-258 , DOI = 10.1097/JCP.0b013e3181dca10a},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77952373634&doi=10.1097%2fJCP.0b013e3181dca10a&partnerID=40&md5=d4ebfd822ab5e01437b7ddc1afd9dc0c},
   year = {2010},
   type = {Journal Article}
}

@article{RN377,
   author = {Neubert, A. and Verhamme, K. and Murray, M. L. and Picelli, G. and Hsia, Y. and Sen, F. E. and Giaquinto, C. and Ceci, A. and Sturkenboom, M. and Wong, I. C. K.},
   title = {The prescribing of analgesics and non-steroidal anti-inflammatory drugs in paediatric primary care in the UK, Italy and the Netherlands},
   journal = {Pharmacological Research},
   volume = {62},
   number = {3},
   pages = {243-248 , DOI = 10.1016/j.phrs.2010.04.006},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77954145330&doi=10.1016%2fj.phrs.2010.04.006&partnerID=40&md5=517e423474200d0086070589a2bdd40b},
   year = {2010},
   type = {Journal Article}
}

@article{RN441,
   author = {Valkhoff, V. E. and Van Soest, E. M. and Sturkenboom, M. C. J. M. and Kuipers, E. J.},
   title = {Time-trends in gastroprotection with nonsteroidal anti-inflammatory drugs (NSAIDs)},
   journal = {Alimentary Pharmacology and Therapeutics},
   volume = {31},
   number = {11},
   pages = {1218-1228 , DOI = 10.1111/j.1365-2036.2010.04281.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77951802445&doi=10.1111%2fj.1365-2036.2010.04281.x&partnerID=40&md5=4f9e32701b9a119791c9b4dfd3b81525},
   year = {2010},
   type = {Journal Article}
}

@article{RN315,
   author = {Gardarsdottir, H. and Egberts, A. C. G. and van Dijk, L. and Sturkenboom, M. C. J. M. and Heerdink, E. R.},
   title = {An algorithm to identify antidepressant users with a diagnosis of depression from prescription data},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {18},
   number = {1},
   pages = {7-15 , DOI = 10.1002/pds.1677},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-59049083703&doi=10.1002%2fpds.1677&partnerID=40&md5=c18df824a7422266491711e5f351f2bb},
   year = {2009},
   type = {Journal Article}
}

@article{RN492,
   author = {Willemen, M. J. C. and Mantel-Teeuwisse, A. K. and Straus, S. M. J. M. and Leufkens, H. G. M. and Egberts, A. C. G. and Sturkenboom, M. C. J. M.},
   title = {Cardiovascular and psychiatric risk profile and patterns of use in patients starting anti-obesity drugs},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {18},
   number = {7},
   pages = {631-638 , DOI = 10.1002/pds.1759},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-69049111139&doi=10.1002%2fpds.1759&partnerID=40&md5=01ff9b6b6d395e113f50983683d46a17},
   year = {2009},
   type = {Journal Article}
}

@article{RN293,
   author = {de Mos, M. and Huygen, F. J. P. M. and Stricker, B. H. Ch and Dieleman, J. P. and Sturkenboom, M. C. J. M.},
   title = {Estrogens and the risk of complex regional pain syndrome (CRPS)},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {18},
   number = {1},
   pages = {44-52 , DOI = 10.1002/pds.1683},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-59049085727&doi=10.1002%2fpds.1683&partnerID=40&md5=36fd371029addff71f2fe55d614e3dc0},
   year = {2009},
   type = {Journal Article}
}

@article{RN345,
   author = {Koopman, J. S. H. A. and Dieleman, J. P. and Huygen, F. J. and de Mos, M. and Martin, C. G. M. and Sturkenboom, M. C. J. M.},
   title = {Incidence of facial pain in the general population},
   journal = {Pain},
   volume = {147},
   number = {1-3},
   pages = {122-127 , DOI = 10.1016/j.pain.2009.08.023},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-70449712610&doi=10.1016%2fj.pain.2009.08.023&partnerID=40&md5=d038774d337054225c92c01fee6fe502},
   year = {2009},
   type = {Journal Article}
}

@article{RN294,
   author = {De Mos, M. and Huygen, F. J. P. M. and Van Der Hoeven-Borgman, M. and Dieleman, J. P. and Stricker, B. H. C. and Sturkenboom, M. C. J. M.},
   title = {Outcome of the complex regional pain syndrome},
   journal = {Clinical Journal of Pain},
   volume = {25},
   number = {7},
   pages = {590-597 , DOI = 10.1097/AJP.0b013e3181a11623},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-70350703424&doi=10.1097%2fAJP.0b013e3181a11623&partnerID=40&md5=17f8cd14a8a1035fdf405cb344ba6c74},
   year = {2009},
   type = {Journal Article}
}

@article{RN420,
   author = {Sturkenboom, M. and Felisi, M. and Manfredi, C. and Neubert, A. and Cantarutti, L. and Padula, R. and Sen, F. and Verhamme, K.},
   title = {Paediatric status and off-label use of drugs in children in Italy, United Kingdom and the Netherlands},
   journal = {Pharmaceuticals Policy and Law},
   volume = {11},
   number = {1-2},
   pages = {51-59 , DOI = 10.3233/ppl-2009-0210},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85013576957&doi=10.3233%2fPPL-2009-0210&partnerID=40&md5=2bdae722b899154dc34846fdc0b1c9ab},
   year = {2009},
   type = {Journal Article}
}

@article{RN295,
   author = {De Mos, M. and Huygen, F. J. P. M. and Van Der Hoeven-Borgman, M. and Dieleman, J. P. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {Referral and treatment patterns for complex regional pain syndrome in the Netherlands},
   journal = {Acta Anaesthesiologica Scandinavica},
   volume = {53},
   number = {6},
   pages = {816-825 , DOI = 10.1111/j.1399-6576.2009.01927.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-67149111707&doi=10.1111%2fj.1399-6576.2009.01927.x&partnerID=40&md5=60373c8ad970e1702727affbbbcdd2b0},
   year = {2009},
   type = {Journal Article}
}

@article{RN448,
   author = {van der Hooft, C. S. and Dieleman, J. P. and Siemes, C. and Aarnoudse, A. L. H. J. and Verhamme, K. M. C. and Strieker, B. H. C. H. and Sturkenboom, M. C. J. M.},
   title = {Adverse drug reaction-related hospitalisations: A population-based cohort study},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {17},
   number = {4},
   pages = {365-371 , DOI = 10.1002/pds.1565},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-42149085112&doi=10.1002%2fpds.1565&partnerID=40&md5=d28443d293c27c45937ad6c0219941d5},
   year = {2008},
   type = {Journal Article}
}

@article{RN376,
   author = {Neubert, A. and Sturkenboom, M. C. J. M. and Murray, M. L. and Verhamme, K. M. C. and Nicolosi, A. and Giaquinto, C. and Ceci, A. and Wong, I. C. K.},
   title = {Databases for pediatric medicine research in Europe - Assessment and critical appraisal},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {17},
   number = {12},
   pages = {1155-1167 , DOI = 10.1002/pds.1661},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-58149361632&doi=10.1002%2fpds.1661&partnerID=40&md5=ebe83d4d39e9a435826374279a973d12},
   year = {2008},
   type = {Journal Article}
}

@article{RN477,
   author = {Verhamme, K. M. C. and Sturkenboom, M. C. J. M. and Stricker, B. H. Ch and Bosch, R.},
   title = {Drug-induced urinary retention: Incidence, management and prevention},
   journal = {Drug Safety},
   volume = {31},
   number = {5},
   pages = {373-388 , DOI = 10.2165/00002018-200831050-00002},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-42449098439&doi=10.2165%2f00002018-200831050-00002&partnerID=40&md5=59279df9a81f53a76d982121729e5d40},
   year = {2008},
   type = {Journal Article}
}

@article{RN424,
   author = {Sturkenboom, M. C. J. M. and Verhamme, K. M. C. and Nicolosi, A. and Murray, M. L. and Neubert, A. and Caudri, D. and Picelli, G. and Sen, E. F. and Giaquinto, C. and Cantarutti, L. and Baiardi, P. and Felisi, M. G. and Ceci, A. and Wong, I. C. K.},
   title = {Drug use in children: Cohort study in three European countries},
   journal = {Bmj},
   volume = {337},
   number = {7682},
   pages = {1338-1341},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-57449103531&partnerID=40&md5=30a1a35c8bd77bdd7d5ce003eec288e0},
   year = {2008},
   type = {Journal Article}
}

@article{RN459,
   author = {Van Soest, E. M. and Dieleman, J. P. and Sturkenboom, M. C. J. M. and Siersema, P. D. and Kuipers, E. J.},
   title = {Gastro-oesophageal reflux, medical resource utilization and upper gastrointestinal endoscopy in patients at risk of oesophageal adenocarcinoma},
   journal = {Alimentary Pharmacology and Therapeutics},
   volume = {28},
   number = {1},
   pages = {137-143 , DOI = 10.1111/j.1365-2036.2008.03693.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-44649100138&doi=10.1111%2fj.1365-2036.2008.03693.x&partnerID=40&md5=53c2a8905877e52f82a7339c249d6483},
   year = {2008},
   type = {Journal Article}
}

@article{RN298,
   author = {Dieleman, J. P. and Kerklaan, J. and Huygen, F. J. P. M. and Bouma, P. A. D. and Sturkenboom, M. C. J. M.},
   title = {Incidence rates and treatment of neuropathic pain conditions in the general population},
   journal = {Pain},
   volume = {137},
   number = {3},
   pages = {681-688 , DOI = 10.1016/j.pain.2008.03.002},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-47049115005&doi=10.1016%2fj.pain.2008.03.002&partnerID=40&md5=d45c64ef79f35f7ff2810426098e03b3},
   year = {2008},
   type = {Journal Article}
}

@article{RN292,
   author = {de Mos, M. and Huygen, F. J. P. M. and Dieleman, J. P. and Koopman, J. S. H. A. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {Medical history and the onset of complex regional pain syndrome (CRPS)},
   journal = {Pain},
   volume = {139},
   number = {2},
   pages = {458-466 , DOI = 10.1016/j.pain.2008.07.002},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-53049095930&doi=10.1016%2fj.pain.2008.07.002&partnerID=40&md5=a096f5aa3757e15e5a941325ddb5677b},
   year = {2008},
   type = {Journal Article}
}

@article{RN456,
   author = {van Oijen, M. G. H. and Dieleman, J. P. and Laheij, R. J. F. and Sturkenboom, M. C. J. M. and Jansen, J. B. M. J. and Verheugt, F. W. A.},
   title = {Peptic Ulcerations Are Related to Systemic Rather Than Local Effects of Low-Dose Aspirin},
   journal = {Clinical Gastroenterology and Hepatology},
   volume = {6},
   number = {3},
   pages = {309-313 , DOI = 10.1016/j.cgh.2007.12.018},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-39949085414&doi=10.1016%2fj.cgh.2007.12.018&partnerID=40&md5=ab80e62e988771c1fe4087c98021709f},
   year = {2008},
   type = {Journal Article}
}

@article{RN423,
   author = {Sturkenboom, M. C. J. M. and Dieleman, J. P. and Picelli, G. and Mazzaglia, G. and Mozaffari, E. and Filippi, A. and Cricelli, C. and van der Lei, J.},
   title = {Prevalence and treatment of hypertensive patients with multiple concomitant cardiovascular risk factors in The Netherlands and Italy},
   journal = {Journal of Human Hypertension},
   volume = {22},
   number = {10},
   pages = {704-713 , DOI = 10.1038/jhh.2008.82},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-52949149675&doi=10.1038%2fjhh.2008.82&partnerID=40&md5=9f591771141cf73b3febc6037a599fce},
   year = {2008},
   type = {Journal Article}
}

@article{RN463,
   author = {Van Soest, E. M. and Van Rossum, L. G. M. and Dieleman, J. P. and Van Oijen, M. G. H. and Siersema, P. D. and Sturkenboom, M. C. J. M. and Kuipers, E. J.},
   title = {Proton pump inhibitors and the risk of colorectal cancer},
   journal = {American Journal of Gastroenterology},
   volume = {103},
   number = {4},
   pages = {966-973 , DOI = 10.1111/j.1572-0241.2007.01665.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-41849129233&doi=10.1111%2fj.1572-0241.2007.01665.x&partnerID=40&md5=20db44793ac759d689066252498ff340},
   year = {2008},
   type = {Journal Article}
}

@article{RN461,
   author = {Van Soest, E. M. and Sturkenboom, M. C. J. M. and Dieleman, J. P. and Verhamme, K. M. C. and Siersema, P. D. and Kuipers, E. J.},
   title = {Adherence to gastroprotection and the risk of NSAID-related upper gastrointestinal ulcers and haemorrhage},
   journal = {Alimentary Pharmacology and Therapeutics},
   volume = {26},
   number = {2},
   pages = {265-275 , DOI = 10.1111/j.1365-2036.2007.03358.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-34250814228&doi=10.1111%2fj.1365-2036.2007.03358.x&partnerID=40&md5=ce045222b706020a24f849b6ce9637c3},
   year = {2007},
   type = {Journal Article}
}

@article{RN436,
   author = {Trifirò, G. and Verhamme, K. M. C. and Ziere, G. and Caputi, A. P. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {All-cause mortality associated with atypical and typical antipsychotics in demented outpatients},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {16},
   number = {5},
   pages = {538-544 , DOI = 10.1002/pds.1334},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-34249660551&doi=10.1002%2fpds.1334&partnerID=40&md5=df42e73223a98e0c02b5bd22885cd204},
   year = {2007},
   type = {Journal Article}
}

@article{RN466,
   author = {Van Wyk, J. T. and Van Wijk, M. A. M. and Sturkenboom, M. C. J. M. and Moorman, P. W. and Van Der Lei, J.},
   title = {Identification and registration of the four 'conventional' cardiovascular disease risk factors in general practice},
   journal = {Huisarts en Wetenschap},
   volume = {50},
   number = {9},
   pages = {421-425},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-34548834984&partnerID=40&md5=93283eccaf4f3a48505daec1db1fe6d6},
   year = {2007},
   type = {Journal Article}
}

@article{RN476,
   author = {Verhamme, K. M. C. and Mosis, G. and Dieleman, J. P. and Stricker, B. H. C. and Sturkenboom, M. C. J. M.},
   title = {Increased risk of gastrointestinal bleeding or ulcers when using spironolactone: A case-control study},
   journal = {Nederlands Tijdschrift voor Geneeskunde},
   volume = {151},
   number = {27},
   pages = {1515-1521},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-34547231191&partnerID=40&md5=6fcedf71fb851e859a58f8cd87c7f956},
   year = {2007},
   type = {Journal Article}
}

@article{RN329,
   author = {Hutchison, A. and Farmer, R. and Verhamme, K. and Berges, R. and Navarrete, R. V.},
   title = {The Efficacy of Drugs for the Treatment of LUTS/BPH, A Study in 6 European Countries},
   journal = {European Urology},
   volume = {51},
   number = {1},
   pages = {207-216 , DOI = 10.1016/j.eururo.2006.06.012},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33751393127&doi=10.1016%2fj.eururo.2006.06.012&partnerID=40&md5=78bdb6a169fe5bb7488ff0f8bc3349d8},
   year = {2007},
   type = {Journal Article}
}

@article{RN291,
   author = {de Mos, M. and de Bruijn, A. G. J. and Huygen, F. J. P. M. and Dieleman, J. P. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {The incidence of complex regional pain syndrome: A population-based study},
   journal = {Pain},
   volume = {129},
   number = {1-2},
   pages = {12-20 , DOI = 10.1016/j.pain.2006.09.008},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-34047262684&doi=10.1016%2fj.pain.2006.09.008&partnerID=40&md5=573b3006e8d5f30512b86a60a42b4e2a},
   year = {2007},
   type = {Journal Article}
}

@article{RN457,
   author = {Van Soest, E. M. and Dieleman, J. P. and Siersema, P. D. and Schoof, L. and Sturkenboom, M. C. J. M. and Kuipers, E. J.},
   title = {Tricyclic antidepressants and the risk of reflux esophagitis},
   journal = {American Journal of Gastroenterology},
   volume = {102},
   number = {9},
   pages = {1870-1877 , DOI = 10.1111/j.1572-0241.2007.01320.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-34548139333&doi=10.1111%2fj.1572-0241.2007.01320.x&partnerID=40&md5=3e17470a9c72de3b97894a2bd45354ee},
   year = {2007},
   type = {Journal Article}
}

@article{RN483,
   author = {Voordouw, B. C. G. and Sturkenboom, M. C. J. M. and Dieleman, J. P. and Stijnen, T. and Van Der Lei, J. and Stricker, B. H. C.},
   title = {Annual influenza vaccination in community-dwelling elderly individuals and the risk of lower respiratory tract infections or pneumonia},
   journal = {Archives of Internal Medicine},
   volume = {166},
   number = {18},
   pages = {1980-1985 , DOI = 10.1001/archinte.166.18.1980},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33749541973&doi=10.1001%2farchinte.166.18.1980&partnerID=40&md5=107a73cb82efca6a086b177028a68348},
   year = {2006},
   type = {Journal Article}
}

@article{RN371,
   author = {Mosis, G. and Dieleman, J. P. and Stricker, B. Ch and van der Lei, J. and Sturkenboom, M. C. J. M.},
   title = {A randomized database study in general practice yielded quality data but patient recruitment in routine consultation was not practical},
   journal = {Journal of Clinical Epidemiology},
   volume = {59},
   number = {5},
   pages = {497-502 , DOI = 10.1016/j.jclinepi.2005.11.007},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33646037361&doi=10.1016%2fj.jclinepi.2005.11.007&partnerID=40&md5=f10e86581adbdd4548eabbf49093820f},
   year = {2006},
   type = {Journal Article}
}

@article{RN373,
   author = {Mosis, G. and Stijnen, T. and Castellsague, J. and Dieleman, J. P. and Van Der Lei, J. and Stricker, B. H. C. and Sturkenboom, M. C. J. M.},
   title = {Channeling and prevalence of cardiovascular contraindications in users of cyclooxygenase 2 selective nonsteroidal antiinflammatory drugs},
   journal = {Arthritis Care and Research},
   volume = {55},
   number = {4},
   pages = {537-542 , DOI = 10.1002/art.22096},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33747874024&doi=10.1002%2fart.22096&partnerID=40&md5=db961f1821cbe09a0b3f3ae9dc0a300d},
   year = {2006},
   type = {Journal Article}
}

@article{RN320,
   author = {Greving, J. P. and Denig, P. and van der Veen, W. J. and Beltman, F. W. and Sturkenboom, M. C. J. M. and Haaijer-Ruskamp, F. M.},
   title = {Determinants for the adoption of angiotensin II receptor blockers by general practitioners},
   journal = {Social Science and Medicine},
   volume = {63},
   number = {11},
   pages = {2890-2898 , DOI = 10.1016/j.socscimed.2006.07.019},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33750065438&doi=10.1016%2fj.socscimed.2006.07.019&partnerID=40&md5=9a2b41144fc52613d83200f923cc5c77},
   year = {2006},
   type = {Journal Article}
}

@article{RN460,
   author = {Van Soest, E. M. and Siersema, P. D. and Dieleman, J. P. and Sturkenboom, M. C. J. M. and Kuipers, E. J.},
   title = {Persistence and adherence to proton pump inhibitors in daily clinical practice},
   journal = {Alimentary Pharmacology and Therapeutics},
   volume = {24},
   number = {2},
   pages = {377-385 , DOI = 10.1111/j.1365-2036.2006.02982.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33745673105&doi=10.1111%2fj.1365-2036.2006.02982.x&partnerID=40&md5=48ae28d21de715d4096542de33154e22},
   year = {2006},
   type = {Journal Article}
}

@article{RN475,
   author = {Verhamme, K. M. C. and Mosis, G. and Dieleman, J. P. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {Spironolactone and risk of upper gastrointestinal events: Population based case-control study},
   journal = {British Medical Journal},
   volume = {333},
   number = {7563},
   pages = {330-333 , DOI = 10.1136/bmj.38883.479549.2F},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33747617316&doi=10.1136%2fbmj.38883.479549.2F&partnerID=40&md5=5d19dac8f6542ad9e94960b695d4feea},
   year = {2006},
   type = {Journal Article}
}

@article{RN374,
   author = {Mosis, G. and Vlug, A. E. and Mosseveld, M. and Dieleman, J. P. and Stricker, B. C. and Van Der Lei, J. and Sturkenboom, M. C. J. M.},
   title = {A technical infrastructure to conduct randomized database studies facilitated by a general practice research database},
   journal = {Journal of the American Medical Informatics Association},
   volume = {12},
   number = {6},
   pages = {602-607 , DOI = 10.1197/jamia.M1803},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-27744515619&doi=10.1197%2fjamia.M1803&partnerID=40&md5=1a7e70e5549e869609063ea1b67141d2},
   year = {2005},
   type = {Journal Article}
}

@article{RN299,
   author = {Dieleman, J. P. and Van Wyk, J. T. and Van Wijk, M. A. M. and Van Herpen, G. and Straus, S. M. J. M. and Dunselman, H. and Sturkenboom, M. C. J. M.},
   title = {Differences between statins on clinical endpoints: A population-based cohort study},
   journal = {Current Medical Research and Opinion},
   volume = {21},
   number = {9},
   pages = {1461-1468 , DOI = 10.1185/030079905x61866},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-25444485767&doi=10.1185%2f030079905X61866&partnerID=40&md5=2a8acadfa1293f65a762f96e25006f17},
   year = {2005},
   type = {Journal Article}
}

@article{RN465,
   author = {Van Wyk, J. T. and Van Wijk, M. A. M. and Sturkenboom, M. C. J. M. and Moorman, P. W. and Van Der Lei, J.},
   title = {Identification of the four conventional cardiovascular disease risk factors by Dutch general practitioners},
   journal = {Chest},
   volume = {128},
   number = {4},
   pages = {2521-2527 , DOI = 10.1378/chest.128.4.2521},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-27144489012&doi=10.1378%2fchest.128.4.2521&partnerID=40&md5=a97ffab27a46ed20bbace4ecd914b137},
   year = {2005},
   type = {Journal Article}
}

@article{RN449,
   author = {Van Der Hooft, C. S. and T Jong, G. W. and Dieleman, J. P. and Verdamme, K. M. C. and Van Der Cammen, T. J. M. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {Inappropriate drug prescribing in older adults: The updated 2002 Beers criteria - A population-based cohort study},
   journal = {British Journal of Clinical Pharmacology},
   volume = {60},
   number = {2},
   pages = {137-144 , DOI = 10.1111/j.1365-2125.2005.02391.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-23044459969&doi=10.1111%2fj.1365-2125.2005.02391.x&partnerID=40&md5=8eaa8dee7c88749dabaca0b141be3cbe},
   year = {2005},
   type = {Journal Article}
}

@article{RN458,
   author = {Van Soest, E. M. and Dieleman, J. P. and Siersema, P. D. and Sturkenboom, M. C. J. M. and Kuipers, E. J.},
   title = {Increasing incidence of Barrett's oesophagus in the general population},
   journal = {Gut},
   volume = {54},
   number = {8},
   pages = {1062-1066 , DOI = 10.1136/gut.2004.063685},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-22644435561&doi=10.1136%2fgut.2004.063685&partnerID=40&md5=c239be3484cb36afb07da01e2b5f83c6},
   year = {2005},
   type = {Journal Article}
}

@article{RN473,
   author = {Verhamme, K. M. C. and Dieleman, J. P. and Van Wijk, M. A. M. and Bosch, J. L. H. R. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {Low incidence of acute urinary retention in the general male population: The triumph project},
   journal = {European Urology},
   volume = {47},
   number = {4},
   pages = {494-498 , DOI = 10.1016/j.eururo.2004.11.011},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-14844360844&doi=10.1016%2fj.eururo.2004.11.011&partnerID=40&md5=10c6c2282a7c9e7c12bd35ea007e9fb5},
   year = {2005},
   type = {Journal Article}
}

@article{RN418,
   author = {Straus, S. M. J. M. and Sturkenboom, M. C. J. M. and Bleumink, G. S. and Dieleman, J. P. and Van Der Lei, J. and De Graeff, P. A. and Kingma, J. H. and Stricker, B. H. Ch},
   title = {Non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death},
   journal = {European Heart Journal},
   volume = {26},
   number = {19},
   pages = {2007-2012 , DOI = 10.1093/eurheartj/ehi312},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-26444560585&doi=10.1093%2feurheartj%2fehi312&partnerID=40&md5=b46db60d1358aa4a9dda384a5a4ebf0f},
   year = {2005},
   type = {Journal Article}
}

@article{RN474,
   author = {Verhamme, K. M. C. and Dieleman, J. P. and Van Wijk, M. A. M. and Van Der Lei, J. and Bosch, J. L. H. R. and Stricker, B. H. C. and Sturkenboom, M. C. J. M.},
   title = {Nonsteroidal anti-inflammatory drugs and increased risk of acute urinary retention},
   journal = {Archives of Internal Medicine},
   volume = {165},
   number = {13},
   pages = {1547-1551 , DOI = 10.1001/archinte.165.13.1547},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-23044451172&doi=10.1001%2farchinte.165.13.1547&partnerID=40&md5=76638a2e0b50e3a84b4cb08af99b7761},
   year = {2005},
   type = {Journal Article}
}

@article{RN372,
   author = {Mosis, G. and Koes, B. and Dieleman, J. and Stricker, B. Ch and van der Lei, J. and Sturkenboom, M. C. J. M.},
   title = {Randomised studies in general practice: How to integrate the electronic patient record},
   journal = {Informatics in Primary Care},
   volume = {13},
   number = {3},
   pages = {209-213},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-28044450890&partnerID=40&md5=a1309860aa6e7bfbe01bf2bb4e9524ae},
   year = {2005},
   type = {Journal Article}
}

@article{RN390,
   author = {Penning-Van Beest, F. J. A. and Sturkenboom, M. C. J. M. and Bemelmans, B. L. H. and Herings, R. M. C.},
   title = {Undertreatment of urinary incontinence in general practice},
   journal = {Annals of Pharmacotherapy},
   volume = {39},
   number = {1},
   pages = {17-21 , DOI = 10.1345/aph.1D491},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-11144230567&doi=10.1345%2faph.1D491&partnerID=40&md5=47698a2c264035eea896f2993abb0bb1},
   year = {2005},
   type = {Journal Article}
}

@article{RN319,
   author = {Greving, J. P. and Denig, P. and Van Der Veen, W. J. and Beltman, F. W. and Sturkenboom, M. C. J. M. and De Zeeuw, D. and Haaijer-Ruskamp, F. M.},
   title = {Uptake of angiotensin II receptor blockers in the treatment of hypertension},
   journal = {European Journal of Clinical Pharmacology},
   volume = {61},
   number = {5-6},
   pages = {461-466 , DOI = 10.1007/s00228-005-0924-7},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-27644536702&doi=10.1007%2fs00228-005-0924-7&partnerID=40&md5=bae7922659a1c5cb0020b22b0e3ff4f7},
   year = {2005},
   type = {Journal Article}
}

@article{RN482,
   author = {Voordouw, A. C. G. and Sturkenboom, M. C. J. M. and Dieleman, J. P. and Stijnen, Th and Smith, D. J. and Van Der Lei, J. and Stricker, B. H. Ch},
   title = {Annual revaccination against influenza and mortality risk in community-dwelling elderly persons},
   journal = {Journal of the American Medical Association},
   volume = {292},
   number = {17},
   pages = {2089-2095 , DOI = 10.1001/jama.292.17.2089},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-7244229602&doi=10.1001%2fjama.292.17.2089&partnerID=40&md5=a8f89e364e611058de1129a0091978bd},
   year = {2004},
   type = {Journal Article}
}

@article{RN417,
   author = {Straus, S. M. J. M. and Bleumink, G. S. and Dieleman, J. P. and Van Der Lei, J. and T Jong, G. W. and Kingma, J. H. and Sturkenboom, M. C. J. M. and Stricker, B. H. C.},
   title = {Antipsychotics and the risk of sudden cardiac death},
   journal = {Archives of Internal Medicine},
   volume = {164},
   number = {12},
   pages = {1293-1297 , DOI = 10.1001/archinte.164.12.1293},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-3042542936&doi=10.1001%2farchinte.164.12.1293&partnerID=40&md5=f4cba3607735005b7ee39462cb49536a},
   year = {2004},
   type = {Journal Article}
}

@article{RN318,
   author = {Greving, J. P. and Denig, P. and Van Der Veen, W. J. and Beltman, F. W. and Sturkenboom, M. C. J. M. and De Zeeuw, D. and Haaijer-Ruskamp, F. M.},
   title = {Does comorbidity explain trends in prescribing of newer antihypertensive agents?},
   journal = {Journal of Hypertension},
   volume = {22},
   number = {11},
   pages = {2209-2215 , DOI = 10.1097/00004872-200411000-00025},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-7744241958&doi=10.1097%2f00004872-200411000-00025&partnerID=40&md5=e891a5dfca8eb48ab55175cb6bfca56e},
   year = {2004},
   type = {Journal Article}
}

@article{RN431,
   author = {T Jong, G. W. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {Marketing in the lay media and prescriptions of terbinafine in primary care: Dutch cohort study},
   journal = {British Medical Journal},
   volume = {328},
   number = {7445},
   pages = {931},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-1942446300&partnerID=40&md5=b42444b09bad269c3d5f1186976a747e},
   year = {2004},
   type = {Journal Article}
}

@article{RN350,
   author = {Laheij, R. J. F. and Sturkenboom, M. C. J. M. and Hassing, R. J. and Dieleman, J. and Stricker, B. H. C. and Jansen, J. B. M. J.},
   title = {Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs},
   journal = {Journal of the American Medical Association},
   volume = {292},
   number = {16},
   pages = {1955-1960 , DOI = 10.1001/jama.292.16.1955},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-6944247563&doi=10.1001%2fjama.292.16.1955&partnerID=40&md5=8f9a1e2530fcf1a770998b29413a0932},
   year = {2004},
   type = {Journal Article}
}

@article{RN416,
   author = {Straus, S. M. J. M. and Bleumink, G. S. and Dieleman, J. P. and Lei Van Der, J. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {The incidence of sudden cardiac death in the general population},
   journal = {Journal of Clinical Epidemiology},
   volume = {57},
   number = {1},
   pages = {98-102 , DOI = 10.1016/s0895-4356(03)00210-5},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-1342302886&doi=10.1016%2fS0895-4356%2803%2900210-5&partnerID=40&md5=e1539ef9f19eaa3c8949704e7fda1d41},
   year = {2004},
   type = {Journal Article}
}

@article{RN336,
   author = {Jong, G. W. and Eland, I. A. and Sturkenboom, M. C. J. M. and van den Anker, J. N. and Stricker, B. H. C.},
   title = {Unlicensed and off-label prescription of respiratory drugs to children},
   journal = {European Respiratory Journal},
   volume = {23},
   number = {2},
   pages = {310-313 , DOI = 10.1183/09031936.04.00015404},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-1042292624&doi=10.1183%2f09031936.04.00015404&partnerID=40&md5=e27dd828a35ca096c0221fd9a62d4e06},
   year = {2004},
   type = {Journal Article}
}

@article{RN422,
   author = {Sturkenboom, M. C. J. M. and Burke, T. A. and Tangelder, M. J. D. and Dieleman, J. P. and Walton, S. and Goldstein, J. L.},
   title = {Adherence to proton pump inhibitors or H2-receptor antagonists during the use of non-steroidal anti-inflammatory drugs},
   journal = {Alimentary Pharmacology and Therapeutics},
   volume = {18},
   number = {11-12},
   pages = {1137-1147 , DOI = 10.1046/j.1365-2036.2003.01795.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0346433965&doi=10.1046%2fj.1365-2036.2003.01795.x&partnerID=40&md5=9a0a7dbc624dec38f48c689bb892bdc7},
   year = {2003},
   type = {Journal Article}
}

@article{RN464,
   author = {Van Wyk, J. T. and Van Wijk, M. A. and Moorman, P. W. and Mosseveld, M. and Van Der Lei, J.},
   title = {Cholgate - a randomized controlled trial comparing the effect of automated and on-demand decision support on the management of cardiovascular disease factors in primary care},
   journal = {AMIA Annual Symposium proceedings / AMIA Symposium AMIA Symposium},
   pages = {1040},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-16544374159&partnerID=40&md5=1026aa4b7b10a88b183f984d19a28ce0},
   year = {2003},
   type = {Journal Article}
}

@article{RN430,
   author = {T Jong, G. W. and Eland, I. A. and Sturkenboom, M. C. J. M. and Van Den Anker, J. N. and Stricker, B. H. C.},
   title = {Determinants for drug prescribing to children below the minimum licensed age},
   journal = {European Journal of Clinical Pharmacology},
   volume = {58},
   number = {10},
   pages = {701-705 , DOI = 10.1007/s00228-002-0554-2},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0037300489&doi=10.1007%2fs00228-002-0554-2&partnerID=40&md5=44e76fb685b927366c5f5687f16cabd4},
   year = {2003},
   type = {Journal Article}
}

@article{RN484,
   author = {Voordouw, B. C. G. and Van der Linden, P. D. and Simonian, S. and Van der Lei, J. and Sturkenboom, M. C. J. M. and Stricker, B. H. C.},
   title = {Influenza vaccination in community-dwelling elderly: Impact on mortality and influenza-associated morbidity},
   journal = {Archives of Internal Medicine},
   volume = {163},
   number = {9},
   pages = {1089-1094 , DOI = 10.1001/archinte.163.9.1089},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0038669269&doi=10.1001%2farchinte.163.9.1089&partnerID=40&md5=bbca08706391dc5c1af1eb68beff5c10},
   year = {2003},
   type = {Journal Article}
}

@article{RN471,
   author = {Verhamme, K. M. C. and Dieleman, J. P. and Bleumink, G. S. and Bosch, J. L. H. R. and Stricker, B. H. Ch and Sturkenboom, M. C. J. M.},
   title = {Treatment Strategies, Patterns of Drug Use and Treatment Discontinuation in Men with LUTS Suggestive of Benign Prostatic Hyperplasia: The Triumph Project},
   journal = {European Urology},
   volume = {44},
   number = {5},
   pages = {539-545 , DOI = 10.1016/s0302-2838(03)00376-2},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0142197657&doi=10.1016%2fS0302-2838%2803%2900376-2&partnerID=40&md5=381f0029398cb709a66385cb388f476e},
   year = {2003},
   type = {Journal Article}
}

@article{RN394,
   author = {Pont, L. G. and Sturkenboom, M. C. J. M. and van Gilst, W. H. and Denig, P. and Haaijer-Ruskamp, F. M.},
   title = {Trends in prescribing for heart failure in Dutch primary care from 1996 to 2000},
   journal = {Pharmacoepidemiology and Drug Safety},
   volume = {12},
   number = {4},
   pages = {327-334 , DOI = 10.1002/pds.809},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0038795465&doi=10.1002%2fpds.809&partnerID=40&md5=ae2238e9b03c07a83cacc8c1bca3c6f0},
   year = {2003},
   type = {Journal Article}
}

@article{RN421,
   author = {Sturkenboom, M. C. J. M. and Burke, T. A. and Dieleman, J. P. and Tangelder, M. J. D. and Lee, F. and Goldstein, J. L.},
   title = {Underutilization of preventive strategies in patients receiving NSAIDs},
   journal = {Rheumatology},
   volume = {42},
   number = {SUPPL. 3},
   pages = {iii23-iii31},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0242609399&partnerID=40&md5=f9251f790448b9e7ba198fb1b27dd142},
   year = {2003},
   type = {Journal Article}
}

@article{RN472,
   author = {Verhamme, K. M. C. and Dieleman, J. P. and Bleumink, G. S. and Van der Lei, J. and Sturkenboom, M. C. J. M.},
   title = {Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care - The triumph project},
   journal = {European Urology},
   volume = {42},
   number = {4},
   pages = {323-328 , DOI = 10.1016/s0302-2838(02)00354-8},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0036793976&doi=10.1016%2fS0302-2838%2802%2900354-8&partnerID=40&md5=f33af177e14e26b943f8589caafb4a8a},
   year = {2002},
   type = {Journal Article}
}

@article{RN468,
   author = {Verboom, P. and Hakkaart-Van Roijen, L. and Sturkenboom, M. and De Zeeuw, R. and Menke, H. and Rutten, F.},
   title = {The cost of atopic dermatitis in the Netherlands: An international comparison},
   journal = {British Journal of Dermatology},
   volume = {147},
   number = {4},
   pages = {716-724 , DOI = 10.1046/j.1365-2133.2002.04964.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0036408380&doi=10.1046%2fj.1365-2133.2002.04964.x&partnerID=40&md5=1895d80c6dff15c770e59f5924c5d09c},
   year = {2002},
   type = {Journal Article}
}

@article{RN428,
   author = {T Jong, G. W. and Eland, I. A. and De Hoog, M. and Sturkenboom, M. C. J. M. and Van den Anker, J. N. and Stricker, B. H. Ch},
   title = {Unlicensed and off-label prescription of systemic anti-infective agents to children},
   journal = {Paediatric and Perinatal Drug Therapy},
   volume = {5},
   number = {2},
   pages = {68-74 , DOI = 10.1185/146300902322125929},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0036447040&doi=10.1185%2f146300902322125929&partnerID=40&md5=d86cb40f858faab081d5b224e9e78fea},
   year = {2002},
   type = {Journal Article}
}

@article{RN429,
   author = {T Jong, G. W. and Eland, I. A. and Sturkenboom, M. C. J. M. and Van den Anker, J. N. and Stricker, B. H. C.},
   title = {Unlicensed and off label prescription of drugs to children: Population based cohort study},
   journal = {British Medical Journal},
   volume = {324},
   number = {7349},
   pages = {1313-1314},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0036607366&partnerID=40&md5=0d971fd45bb8b29c26472df9932d0d51},
   year = {2002},
   type = {Journal Article}
}

@article{RN302,
   author = {Eland, I. A. and Van der Lei, J. and Stricker, B. H. C. and Sturkenboom, M. J. C. M.},
   title = {Incidence of priapism in the general population},
   journal = {Urology},
   volume = {57},
   number = {5},
   pages = {970-972 , DOI = 10.1016/s0090-4295(01)00941-4},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0035030609&doi=10.1016%2fS0090-4295%2801%2900941-4&partnerID=40&md5=dc242e62df5c2e91e1f0bb05d45b23e4},
   year = {2001},
   type = {Journal Article}
}

@article{RN450,
   author = {Van der Linden, P. D. and Van de Lei, J. and Nab, H. W. and Knol, A. and Stricker, B. H. Ch},
   title = {Achilles tendinitis associated with fluoroquinolones},
   journal = {British Journal of Clinical Pharmacology},
   volume = {48},
   number = {3},
   pages = {433-437 , DOI = 10.1046/j.1365-2125.1999.00016.x},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032821080&doi=10.1046%2fj.1365-2125.1999.00016.x&partnerID=40&md5=a25d4c39f2d7cbd445b93c4f80ad5590},
   year = {1999},
   type = {Journal Article}
}

@article{RN480,
   author = {Vlug, A. E. and Van Der Lei, J. and Mosseveld, B. M. Th and Van Wijk, M. A. M. and Van Der Linden, P. D. and Sturkenboom, M. C. J. M. and Van Bemmel, J. H.},
   title = {Postmarketing surveillance based on electronic patient records: The IPCI project},
   journal = {Methods of Information in Medicine},
   volume = {38},
   number = {4-5},
   pages = {339-344},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-0033451352&partnerID=40&md5=59f832abbd868ec11c6e16403de2f9f4},
   year = {1999},
   type = {Journal Article}
}

OBJECTIVES: To quantify the risk of skin reactions to antibacterial drugs under everyday circumstances in a large population with automated data from general practitioners (GP). DESIGN: A retrospective cohort study in a dynamic population. SETTING: Data came from the Integrated Primary Care Information (IPCI) database. The IPCI database consists of all data on consultations, morbidity, and prescriptions and other interventions, as registered by the GP in a source population of approximately 150,000 persons. METHODS: The study period started on April 1, 1994, and ended on September 30, 1995. All patients who were treated with an antibacterial drug were enrolled on the first day of starting treatment until the end of the study period or until the occurrence of one or more of the following diagnoses within the risk period: allergic reaction, rash, erythema, pruritus and urticaria, or a notification of a skin reaction in the free text. Subsequently, patient profiles were assessed by two authors who were blinded to exposure. The risk period was defined as the legend duration of the antibacterial drug plus 14 days to control for carry-over of drug effects and delay in patient presentation. Age, gender, and comedication were examined as potential confounders. RESULTS: In the study period 13,679 patients received 19,961 prescriptions of an antibacterial drug. It concerned 5330 men (39.0%) and 8349 (61.0%) women with a mean age of 41 and 42 years, respectively. One hundred thirty-five patients developed a skin reaction in the risk period. Rash, pruritus, urticaria, and miscellaneous skin reactions were encountered in 76 (56.3%), 18 (13.3%), 19 (14.1%), and 22 (16.3%) patients, respectively. The three most frequently reported causes of skin reactions were combinations of trimethoprim with sulfonamides (2.1% of users; incidence density [ID]: 2.1/1000 exposed days), fluoroquinolones (1.6% of users; ID: 1.5/1000 person days), and penicillins (1.1% of users; ID: 1.3/1000 person days). Compared to tetracyclines, the broad-spectrum penicillins showed an incidence density ratio (IDR) of 3.7, the combination of amoxicillin with clavulanic acid of 3.3, the fluoroquinolones of 2.8, and the combination of trimethoprim with sulphonamides of 4.4. The presence of infectious mononucleosis increased the risk of rash in amoxicillin users with a factor of 58. CONCLUSIONS: We found that the frequency of skin reactions to antibacterial drugs in general practice is around 1% and highest for the combination of trimethoprim with sulphonamides, penicillins, and fluoroquinolones. The outpatient incidence for skin reactions is probably lower than the incidence in hospitalized patients. Although this may be partly explained by negative misclassification, it is also likely that the actual incidence is lower as some hospitalized patient groups may be more prone to develop a skin reaction.

@article{RN497,
   author = {van der Linden, P. D. and van der Lei, J. and Vlug, A. E. and Stricker, B. H.},
   title = {Skin reactions to antibacterial agents in general practice},
   journal = {J Clin Epidemiol},
   volume = {51},
   number = {8},
   pages = {703-8},
   note = {van der Linden, P D
van der Lei, J
Vlug, A E
Stricker, B H
Journal Article
United States
1998/09/22
J Clin Epidemiol. 1998 Aug;51(8):703-8. doi: 10.1016/s0895-4356(98)00041-9.},
   abstract = {OBJECTIVES: To quantify the risk of skin reactions to antibacterial drugs under everyday circumstances in a large population with automated data from general practitioners (GP). DESIGN: A retrospective cohort study in a dynamic population. SETTING: Data came from the Integrated Primary Care Information (IPCI) database. The IPCI database consists of all data on consultations, morbidity, and prescriptions and other interventions, as registered by the GP in a source population of approximately 150,000 persons. METHODS: The study period started on April 1, 1994, and ended on September 30, 1995. All patients who were treated with an antibacterial drug were enrolled on the first day of starting treatment until the end of the study period or until the occurrence of one or more of the following diagnoses within the risk period: allergic reaction, rash, erythema, pruritus and urticaria, or a notification of a skin reaction in the free text. Subsequently, patient profiles were assessed by two authors who were blinded to exposure. The risk period was defined as the legend duration of the antibacterial drug plus 14 days to control for carry-over of drug effects and delay in patient presentation. Age, gender, and comedication were examined as potential confounders. RESULTS: In the study period 13,679 patients received 19,961 prescriptions of an antibacterial drug. It concerned 5330 men (39.0%) and 8349 (61.0%) women with a mean age of 41 and 42 years, respectively. One hundred thirty-five patients developed a skin reaction in the risk period. Rash, pruritus, urticaria, and miscellaneous skin reactions were encountered in 76 (56.3%), 18 (13.3%), 19 (14.1%), and 22 (16.3%) patients, respectively. The three most frequently reported causes of skin reactions were combinations of trimethoprim with sulfonamides (2.1% of users; incidence density [ID]: 2.1/1000 exposed days), fluoroquinolones (1.6% of users; ID: 1.5/1000 person days), and penicillins (1.1% of users; ID: 1.3/1000 person days). Compared to tetracyclines, the broad-spectrum penicillins showed an incidence density ratio (IDR) of 3.7, the combination of amoxicillin with clavulanic acid of 3.3, the fluoroquinolones of 2.8, and the combination of trimethoprim with sulphonamides of 4.4. The presence of infectious mononucleosis increased the risk of rash in amoxicillin users with a factor of 58. CONCLUSIONS: We found that the frequency of skin reactions to antibacterial drugs in general practice is around 1% and highest for the combination of trimethoprim with sulphonamides, penicillins, and fluoroquinolones. The outpatient incidence for skin reactions is probably lower than the incidence in hospitalized patients. Although this may be partly explained by negative misclassification, it is also likely that the actual incidence is lower as some hospitalized patient groups may be more prone to develop a skin reaction.},
   keywords = {Adolescent
Adult
Aged
Anti-Infective Agents/*adverse effects
Child
Cohort Studies
Databases, Factual
Drug Eruptions/epidemiology/*etiology
Family Practice
Female
Humans
Incidence
Male
Middle Aged
Netherlands/epidemiology
Pharmacoepidemiology
Retrospective Studies},
   ISSN = {0895-4356 (Print)
0895-4356},
   DOI = {10.1016/s0895-4356(98)00041-9},
   year = {1998},
   type = {Journal Article}
}

@article{RN479,
   author = {Visser, L. E. and Vlug, A. E. and van der Lei, J. and Stricker, B. H.},
   title = {Cough due to ACE inhibitors: a case-control study using automated general practice data},
   journal = {Eur J Clin Pharmacol},
   volume = {49},
   number = {6},
   pages = {439-44 , ISSN = 0031-6970 (Print) 0031-6970 , DOI = 10.1007/bf00195928},
   year = {1996},
   type = {Journal Article}
}

Postmarketing Surveillance (PMS) concerns the investigation of side-effects of drugs after they are introduced into the market. Traditionally, data collection for PMS-studies has been paper-based. The increasing number of general practitioners (GP) that use Computer-Based Patient Records (CBPR) and the central role these general practitioners in the Netherlands play in the delivery of care makes the use of CBPRs as a resource of data for PMS studies possible. Analysis of the current available CBPRs, however, proved them insufficient for PMS studies, because too much data is available only in free text, and other necessary data for PMS is lacking. To make the CBPR suitable for PMS, we had to build a software-module that could be plugged into the computer system of the GP. The module checks the data immediately after they it has been entered into the system, and missing data is requested. Initial filed studies have shown that, with this module, the collection of PMS data is feasible.

@article{RN496,
   author = {Vlug, A. E. and van der Lei, J.},
   title = {Postmarketing surveillance with computer-based patient records},
   journal = {Medinfo},
   volume = {8 Pt 1},
   pages = {327-30},
   note = {Vlug, A E
van der Lei, J
Journal Article
Netherlands
1995/01/01
Medinfo. 1995;8 Pt 1:327-30.},
   abstract = {Postmarketing Surveillance (PMS) concerns the investigation of side-effects of drugs after they are introduced into the market. Traditionally, data collection for PMS-studies has been paper-based. The increasing number of general practitioners (GP) that use Computer-Based Patient Records (CBPR) and the central role these general practitioners in the Netherlands play in the delivery of care makes the use of CBPRs as a resource of data for PMS studies possible. Analysis of the current available CBPRs, however, proved them insufficient for PMS studies, because too much data is available only in free text, and other necessary data for PMS is lacking. To make the CBPR suitable for PMS, we had to build a software-module that could be plugged into the computer system of the GP. The module checks the data immediately after they it has been entered into the system, and missing data is requested. Initial filed studies have shown that, with this module, the collection of PMS data is feasible.},
   keywords = {*Medical Records Systems, Computerized
Netherlands
*Product Surveillance, Postmarketing/methods},
   ISSN = {1569-6332 (Print)
1569-6332},
   year = {1995},
   type = {Journal Article}
}

Computer-based patient records, although an area of active research, are not in widespread use. In June 1992, 38% of Dutch general practitioners had introduced computer-based patient records. Of these, 70% had replaced the paper patient record with a computer-based record to retrieve and record clinical data during consultations. Possible reasons for the use of computer-based patient records include the nature of Dutch general practice and the early and active role of professional organizations in recognizing the potential of computer-stored patient records. Professional organizations issued guidelines for information systems in general practice, evaluated available systems, and provided postgraduate training that prepares physicians to use the systems. In addition, professional organizations successfully urged the government to reimburse general practitioners part of the expenses related to the introduction of computer-based patient records. Our experience indicates that physicians are willing and able to integrate information technology in their practices and that professional organizations can play an active role in the introduction of information technology.

@article{RN495,
   author = {van der Lei, J. and Duisterhout, J. S. and Westerhof, H. P. and van der Does, E. and Cromme, P. V. and Boon, W. M. and van Bemmel, J. H.},
   title = {The introduction of computer-based patient records in The Netherlands},
   journal = {Ann Intern Med},
   volume = {119},
   number = {10},
   pages = {1036-41},
   note = {van der Lei, J
Duisterhout, J S
Westerhof, H P
van der Does, E
Cromme, P V
Boon, W M
van Bemmel, J H
Journal Article
United States
1993/11/15
Ann Intern Med. 1993 Nov 15;119(10):1036-41. doi: 10.7326/0003-4819-119-10-199311150-00011.},
   abstract = {Computer-based patient records, although an area of active research, are not in widespread use. In June 1992, 38% of Dutch general practitioners had introduced computer-based patient records. Of these, 70% had replaced the paper patient record with a computer-based record to retrieve and record clinical data during consultations. Possible reasons for the use of computer-based patient records include the nature of Dutch general practice and the early and active role of professional organizations in recognizing the potential of computer-stored patient records. Professional organizations issued guidelines for information systems in general practice, evaluated available systems, and provided postgraduate training that prepares physicians to use the systems. In addition, professional organizations successfully urged the government to reimburse general practitioners part of the expenses related to the introduction of computer-based patient records. Our experience indicates that physicians are willing and able to integrate information technology in their practices and that professional organizations can play an active role in the introduction of information technology.},
   keywords = {Database Management Systems
Family Practice/*organization & administration
Financing, Government
Forecasting
Humans
*Medical Records Systems, Computerized/economics/statistics & numerical
data/trends
National Health Programs
Netherlands
Practice Management, Medical/economics/*organization & administration/trends
Societies, Medical},
   ISSN = {0003-4819 (Print)
0003-4819},
   DOI = {10.7326/0003-4819-119-10-199311150-00011},
   year = {1993},
   type = {Journal Article}
}