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PURPOSE: Metadata for data dIscoverability aNd study rEplicability in obseRVAtional studies (MINERVA), a European Medicines Agency-funded project (EUPAS39322), defined a set of metadata to describe real-world data sources (RWDSs) and piloted metadata collection in a prototype catalogue to assist investigators from data source discoverability through study conduct. METHODS: A list of metadata was created from a review of existing metadata catalogues and recommendations, structured interviews, a stakeholder survey, and a technical workshop. The prototype was designed to comply with the FAIR principles (findable, accessible, interoperable, reusable), using MOLGENIS software. Metadata collection was piloted by 15 data access partners (DAPs) from across Europe. RESULTS: A total of 442 metadata variables were defined in six domains: institutions (organizations connected to a data source); data banks (data collections sustained by an organization); data sources (collections of linkable data banks covering a common underlying population); studies; networks (of institutions); and common data models (CDMs). A total of 26 institutions were recorded in the prototype. Each DAP populated the metadata of one data source and its selected data banks. The number of data banks varied by data source; the most common data banks were hospital administrative records and pharmacy dispensation records (10 data sources each). Quantitative metadata were successfully extracted from three data sources conforming to different CDMs and entered into the prototype. CONCLUSIONS: A metadata list was finalized, a prototype was successfully populated, and a good practice guide was developed. Setting up and maintaining a metadata catalogue on RWDSs will require substantial effort to support discoverability of data sources and reproducibility of studies in Europe.
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Metadados , Estudos Observacionais como Assunto , Europa (Continente) , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , Estudos Observacionais como Assunto/métodos , Coleta de Dados/métodos , Coleta de Dados/normas , Bases de Dados Factuais/estatística & dados numéricos , Software , Farmacoepidemiologia/métodosRESUMO
BACKGROUND: Older patients with type 2 diabetes mellitus (T2D) have an increased risk of hypoglycaemic episodes when using sulphonylureas or insulin. In the Netherlands, guidelines exist for reducing glucose-lowering medication in older patients. However, evidence is lacking that a medication reduction in older patients can be safely pursued. Here, we will examine if promoting the deprescribing of insulin/sulphonylureas with a deprescribing programme (DPP) in general practice affects T2D-complications in older overtreated patients. METHODS: We will perform a 1:1 cluster randomised controlled trial in 86 general practices in the Netherlands. The DPP will consist of education sessions with general practitioners and practice nurses about reducing glucose-lowering medication in older patients (≥ 70 years). Topics of the sessions include the necessity of deprescribing, tools to initiate deprescribing and strategies to discuss deprescribing with patients (shared decision making). The DPP further includes a support programme with practice visits. The study will employ a selection tool to identify possibly overtreated older patients from the electronic medical records of the general practitioner. Eligibility for enrolment in the study will be based on HbA1c targets indicated by the Dutch guidelines, which depend on age, diabetes duration, presence of frailty, and life expectancy. The control group will provide usual care. We aim to include 406 patients. The follow-up period will be 2 years. For the primary outcome, the effect of the DPP on T2D-complications will be assessed by counting the cumulative incidence of events related to under- and overtreatment in T2D as registered in the electronic medical records. We shall perform an intention-to-treat analysis and an analysis including only patients for whom deprescribing was initiated. The implementation of the DPP in general practice will be evaluated quantitatively and qualitatively using the Extended Normalisation Process Theory (ENPT) and the Reach, Efficacy - Adoption, Implementation and Maintenance (RE-AIM) model. Other secondary outcomes include quality of life, cognitive functioning, events related to overtreatment or undertreatment, biomarkers of health, amount of blood glucose-lowering medication prescriptions, and cost-effectiveness. DISCUSSION: This study will provide insight into the safety and feasibility of a programme aimed at deprescribing sulphonylureas/insulin in older people with T2D who are treated in general practice. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN50008265 , registered 09 March, 2023.
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Glicemia , Desprescrições , Diabetes Mellitus Tipo 2 , Controle Glicêmico , Hipoglicemiantes , Ensaios Clínicos Controlados Aleatórios como Assunto , Compostos de Sulfonilureia , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Idoso , Compostos de Sulfonilureia/uso terapêutico , Compostos de Sulfonilureia/efeitos adversos , Países Baixos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Resultado do Tratamento , Insulina/uso terapêutico , Fatores Etários , Biomarcadores/sangue , Fatores de Tempo , Estudos Multicêntricos como Assunto , Hemoglobinas Glicadas/metabolismo , Educação de Pacientes como Assunto/métodos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemia/sangueRESUMO
Aims/Hypothesis: Only a few studies reported the incidence of type 2 diabetes (T2D). Understanding recent trends in diabetes is vital for planning future diabetes care. This study updated national trends in the prevalence and incidence of type 2 diabetes (T2D) in the Netherlands from 2004-2020. Methods: The DIAbetes, MANagement and Treatment (DIAMANT) cohort was used. A cross-sectional design with yearly measurements for the study period was used. The prevalence was calculated by dividing the total number of people with T2D by the total number of all residents. The incidence was calculated by dividing new cases of T2D by the resident population at risk during the calendar year of interest. Results: Among men, the prevalence of T2D in the Netherlands increased from 2.3% in 2004 to 6.3% in 2020. Women's prevalence increased from 2.3% in 2004 to 5.3% in 2020. During 2005-2009, the incidence rate for both men and women was relatively stable Between 2010 and 2020, the incidence rate fell about 1.5 per 1000 in both men and women. Conclusion: From 2004-2020, the prevalence of T2D in the Netherlands more than doubled, with a decreasing incidence from 2010 onwards.
Research in context What is already known about this subject? Many studies have reported the increasing prevalence of type 2 diabetes (T2D). However, only a few studies reported the incidence.In a recent systematic review of all these studies, the incidence fell in over a third of the most high-income populations and increased in a minority of populations. Data from the Netherlands were included, but they date back to 1996.Understanding recent trends in diabetes, the prevalence and incidence are vital for planning future diabetes care.What is the key question? To update national trends in the prevalence and incidence of T2D in the Netherlands for 2004-2020.What are the new findings? During 2004-2020, the prevalence of T2D in the Netherlands more than doubled, with a decreasing incidence from 2010 onwards.How might this impact on clinical practice in the foreseeable future? It demonstrates the effectiveness of preventive strategies, public health education and awareness campaigns contributing to this trend.
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OBJECTIVES: To describe opportunities and challenges experienced from the four pharmacoepidemiological database studies included in the rivaroxaban post authorisation safety study (PASS) programme and propose ways to maximise the value of population-based observational research when addressing regulatory requirements. DESIGN: PASS programme of rivaroxaban carried out as part of the regulatory postapproval commitment to the European Medicines Agency. SETTING: Clinical practice in Germany, the Netherlands, Sweden and the UK (electronic health records)-undertaken by pharmacoepidemiology research teams using country-specific databases with different coding structures. PARTICIPANTS: 355 152 patients prescribed rivaroxaban and 338 199 patients prescribed vitamin K antagonists. RESULTS: Two major challenges that were encountered throughout the lengthy PASS programme were related to: (1) finalising country-tailored study designs before the extent of rivaroxaban uptake was known, and (2) new research questions that arose during the programme (eg, those relating to an evolving prescribing landscape). RECOMMENDATIONS: We advocate the following strategies to help address these major challenges (should they arise in any future PASS): conducting studies based on a common data model that enable the same analytical tools to be applied when using different databases; maintaining early, clear, continuous communication with the regulator (including discussing the potential benefit of studying drug use as a precursor to planning a safety study); consideration of adaptive designs whenever uncertainty exists and following an initial period of data collection; and setting milestones for the review of study objectives.
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Projetos de Pesquisa , Rivaroxabana , Humanos , Europa (Continente) , Estudos Longitudinais , AnticoagulantesRESUMO
BACKGROUND: The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. METHODS: Cohorts were created using electronic healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients with a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome (hospitalization for intracranial, gastrointestinal, urogenital or other bleeding), death or study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed. RESULTS: Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled, mean age, 59.9-63.8 years. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher incidence rates for gastrointestinal bleeding in rivaroxaban users than in vitamin K antagonist users. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes. CONCLUSIONS: This study provides further data from routine clinical practice that broadly support safety profile of rivaroxaban for VTE indication and complement findings from previous randomized clinical trials.
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Fibrilação Atrial , Tromboembolia Venosa , Humanos , Pessoa de Meia-Idade , Rivaroxabana/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Fibrinolíticos/uso terapêutico , Vitamina K , Inibidores do Fator Xa/efeitos adversosRESUMO
BACKGROUND: In patients with ischaemic heart disease (IHD) aged >â¯70 years, Dutch and European guidelines recommend different treatment targets: low-density lipoprotein cholesterol (LDL-c) <â¯2.6 versus <â¯1.4â¯mmol/l and systolic blood pressure (SBP) <â¯140 versus <â¯130â¯mmâ¯Hg, respectively. How this impacts cardiovascular event-free life expectancy has not been investigated. The study objective was to compare estimated lifelong treatment benefits of implementing Dutch and European LDLc and SBP targets. METHODS: Data from patients aged 71-80 years hospitalised for IHD in 2017-2019 were extracted from the PHARMO Database Network, which links primary and secondary healthcare settings, with follow-up until 31 December 2020. Potential benefit according to treatment strategy (in gain in event-free years) was estimated using the SMART-REACH model. RESULTS: Of the 3003 eligible patients, 1186 (39%) had missing LDLc and/or SBP measurements. Of the 1817 included patients (36% women, median age at event: 74 years (interquartile range (IQR): 72-77), 84% achieved the Dutch targets for both LDLc and SBP; for European targets, this was 23% and 61%, respectively. If Dutch targets were met for LDLc and SBP (nâ¯= 1281), the additional effect of reaching European targets was a median gain of 0.6 event-free life years (IQR: 0.3-1.0). The greatest effect could be reached in patients not reaching Dutch targets (nâ¯= 501), with a median gain of 0.6 (IQR: 0.2-1.2) and 1.7 (IQR: 1.2-2.5) event-free years with Dutch versus European targets. CONCLUSION: In patients aged >â¯70 years with IHD, implementation of European targets resulted in a greater gain of event-free years compared with Dutch targets, especially in patients with poorer risk factor control. The considerable number of patients with missing risk factor documentation suggested additional opportunities for risk reduction.
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BACKGROUND: People living with chronic obstructive pulmonary disease (COPD) have an increased risk of experiencing cardiovascular (CV) events, particularly after an exacerbation. Such CV burden is not yet known for incident COPD patients. We examined the risk of severe CV events in incident COPD patients in periods following either moderate and/or severe exacerbations. METHODS: Persons aged ≥ 40 years with an incident COPD diagnosis from the PHARMO Data Network were included. Exposed time periods included 1-7, 8-14, 15-30, 31-180 and 181-365 days following an exacerbation. Moderate exacerbations were defined as those managed in outpatient settings; severe exacerbations as those requiring hospitalisation. The outcome was a composite of time to first severe CV event (acute coronary syndrome, heart failure decompensation, cerebral ischaemia, or arrhythmia) or death. Hazard ratios (HR) were estimated for association between each exposed period and outcome. RESULTS: 8020 patients with newly diagnosed COPD were identified. 2234 patients (28%) had ≥ 1 exacerbation, 631 patients (8%) had a non-fatal CV event, and 461 patients (5%) died during a median follow-up of 36 months. The risk of experiencing the composite outcome was increased following a moderate/severe exacerbation as compared to time periods of stable disease [range of HR: from 15.3 (95% confidence interval 11.8-20.0) in days 1-7 to 1.3 (1.0-1.8) in days 181-365]. After a moderate exacerbation, the risk was increased over the first 180 days [HR 2.5 (1.3-4.8) in days 1-7 to 1.6 (1.3-2.1) in days 31-180]. After a severe exacerbation, the risk increased substantially and remained higher over the year following the exacerbation [HR 48.6 (36.9-64.0) in days 1-7 down to 1.6 (1.0-2.6) in days 181-365]. Increase in risk concerned all categories of severe CV events. CONCLUSIONS: Among incident COPD patients, we observed a substantial risk increase of severe CV events or all-cause death following either a moderate or severe exacerbation of COPD. Increase in risk was highest in the initial period following an exacerbation. These findings highlight the significant cardiopulmonary burden among people living with COPD even with a new diagnosis.
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Doenças Cardiovasculares , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos de Coortes , Países Baixos/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Progressão da DoençaRESUMO
Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.
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BACKGROUND: Routinely collected clinical data based on electronic medical records could be used to define frailty. AIM: To estimate the ability of four potential frailty measures that use electronic medical record data to identify older patients who were frail according to their GP. DESIGN AND SETTING: This retrospective cohort study used data from 36 GP practices in the Dutch PHARMO Data Network. METHOD: The measures were the Dutch Polypharmacy Index, Charlson Comorbidity Index (CCI), Chronic Disease Score (CDS), and Frailty Index. GPs' clinical judgement of patients' frailty status was considered the reference standard. Performance of the measures was assessed with the area under the receiver operating characteristic curve (AUC). Analyses were done in the total population and stratified by age and sex. RESULTS: Of 31 511 patients aged ≥65 years, 3735 (11.9%) patients were classified as frail by their GP. The CCI showed the highest AUC (0.79, 95% confidence interval [CI] = 0.78 to 0.80), followed by the CDS (0.69, 95% CI = 0.68 to 0.70). Overall, the measures showed poorer performance in males and females aged ≥85 years than younger age groups (AUC 0.55-0.58 in females and 0.57-0.60 in males). CONCLUSION: This study showed that of four frailty measures based on electronic medical records in primary care only the CCI had an acceptable performance to assess frailty compared with frailty assessments done by professionals. In the youngest age groups diagnostic performance was acceptable for all measures. However, performance declined with older age and was least accurate in the oldest age group, thereby limiting the use in patients of most interest.
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Fragilidade , Idoso , Masculino , Feminino , Humanos , Fragilidade/diagnóstico , Idoso Fragilizado , Estudos Retrospectivos , Avaliação Geriátrica , Doença Crônica , Atenção Primária à SaúdeRESUMO
BACKGROUND: GPs have been shown to be important providers of medical care during pregnancy, however, little evidence exists on their awareness of pregnancy when prescribing medication to women. AIM: To assess GPs' awareness of pregnancy and its association with prescribing medication with potential safety risks. DESIGN AND SETTING: Population-based study using confirmed pregnancy records linked to GP records from the PHARMO Perinatal Research Network. METHOD: GPs' awareness of pregnancy, defined as the presence of a pregnancy confirmation in the GP information system during pregnancy, was assessed from 2004 to 2020. GP prescriptions of medication with potential safety risks were selected during pregnancy and its association with GPs' awareness of pregnancy was assessed using multivariable logistic regression. RESULTS: A pregnancy confirmation was present in the GP records for 48% (n = 67 496/140 976) of selected pregnancies, increasing from 28% (n = 34/121) in 2004 to 63% in 2020 (n = 5763/9124). During 3% (n = 4489/140 976) of all pregnancies, the GP prescribed highly hazardous medication with teratogenic effects that should have been (temporarily) avoided. Pregnancy was GP confirmed for only 13% (n = 585/4489) at the first occurrence of such a prescription. Comparative analyses showed that women without a pregnancy confirmation were 59% more likely to be prescribed this highly hazardous medication (odds ratio [OR] 1.59, 95% confidence interval [CI] = 1.49 to 1.70) compared with those with a confirmed pregnancy. CONCLUSION: Results of this study indicate a potential issue with GP awareness about pregnancy status at the time medication with potential safety risks is prescribed. Although pregnancy registration by GPs improved over the years, inadequate use still seems to be made of the available information systems for appropriate drug surveillance.
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Prescrições , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Gravidez , Razão de ChancesRESUMO
Background: There is a need for updated incidence rates (IRs) of Lyme borreliosis (LB) in Europe, including the Netherlands. We estimated LB IRs stratified by geographic area, year, age, sex, immunocompromised status, and socioeconomic status (SES). Methods: All subjects registered in the PHARMO General Practitioner (GP) Database without prior diagnosis of LB or disseminated LB and having ≥1 year of continuous database enrolment were included. IRs and corresponding confidence intervals (CIs) of GP-recorded LB, erythema migrans (EM), and disseminated LB were estimated during the period 2015â2019. Results: We identified 14,794 events (suspected, probable, or confirmed) with a diagnostic code for LB that included 8219 with a recorded clinical manifestation: 7985 (97%) with EM and 234 (3%) with disseminated LB. National annual LB IRs were relatively consistent, ranging from 111 (95% CI 106â115) in 2019 to 131 (95% CI 126â136) in 2018 per 100,000 person-years. Incidence of LB showed a bimodal age distribution, with peak IRs observed among subjects aged 5â14 and 60â69 years in men and women. Higher LB incidence was found in subjects who were residents of the provinces of Drenthe and Overijssel, immunocompromised, or of lower SES. Similar patterns were observed for EM and disseminated LB. Conclusions: Our findings confirm that LB incidence remains substantial throughout the Netherlands with no indication of decline in the past 5 years. Foci in two provinces and among vulnerable populations suggest potential initial target groups for preventive strategies such as vaccination.
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Eritema Migrans Crônico , Medicina Geral , Doença de Lyme , Feminino , Animais , Incidência , Países Baixos/epidemiologia , Estudos de Coortes , Doença de Lyme/epidemiologia , Doença de Lyme/diagnóstico , Doença de Lyme/veterinária , Eritema Migrans Crônico/epidemiologia , Eritema Migrans Crônico/veterináriaRESUMO
INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.
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Anticorpos Monoclonais Humanizados , Psoríase , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Use of the direct oral anticoagulant rivaroxaban has strongly increased in Europe since its market approval for non-valvular atrial fibrillation in 2011. Patients characteristics of rivaroxaban initiators may have changed over time but this has not been investigated so far. OBJECTIVE: We aimed to describe time trends of patient baseline characteristics among new rivaroxaban users with non-valvular atrial fibrillation from 2011 to 2016/17 in two European countries. METHODS: We used data from Germany (German Pharmacoepidemiological Research Database) and the Netherlands (PHARMO Database Network). We included new rivaroxaban users with (i) a first dispensing between 2011 and 2016/17, (ii) ≥ 2 years of age, and (iii) a diagnosis of non-valvular atrial fibrillation and described their baseline medication and comorbidity prior to starting rivaroxaban stratified by year of inclusion. RESULTS: Overall, 130,652 new rivaroxaban users were included during the study period (Germany: N = 127,743, the Netherlands: N = 2909). The sex ratio and median age remained relatively stable over time. The proportion of patients without prior use of oral anticoagulants before initiation of rivaroxaban increased in both countries between 2011 and 2016/17 (Germany: from 51 to 76%, the Netherlands: from 57 to 85%). In Germany, we observed a relative decrease by 27% in the proportion of new rivaroxaban users with a history of ischemic stroke and by 18% in the proportion with a transient ischemic attack at baseline. No such a pattern was observed in the Netherlands. The proportion of patients with heart failure at baseline showed a three-fold increase in the Netherlands, while there was a relative decrease by 12% in Germany. CONCLUSIONS: Patient characteristics of new rivaroxaban users with non-valvular atrial fibrillation changed between 2011 and 2016/17, but changes differed between countries. These patterns have methodological implications. They have to be considered in the interpretation of observational studies comparing effectiveness and safety of oral anticoagulants, especially regarding potential bias due to unmeasured confounding.
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BACKGROUND: The safety and effectiveness of rivaroxaban versus vitamin K antagonists (standard of care [SOC]) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) was evaluated in Europe. RESEARCH DESIGN AND METHODS: Observational studies were conducted in the UK, the Netherlands, Germany, and Sweden. Primary safety outcomes were hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or urogenital bleeding among new users of rivaroxaban and SOC with NVAF; outcomes were analyzed using cohort (rivaroxaban or SOC use) and nested case-control designs (current vs nonuse). Statistical analyses comparing rivaroxaban and SOC cohorts were not performed. RESULTS: Overall, 162,919 rivaroxaban users and 177,758 SOC users were identified. In the cohort analysis, incidence ranges for rivaroxaban users were 0.25-0.63 events per 100 person-years for intracranial bleeding, 0.49-1.72 for gastrointestinal bleeding, and 0.27-0.54 for urogenital bleeding. Corresponding ranges for SOC users were 0.30-0.80, 0.30-1.42, and 0.24-0.42, respectively. In the nested case-control analysis, current SOC use generally presented a greater risk of bleeding outcomes than nonuse. Rivaroxaban use (vs nonuse) was associated with a higher risk of gastrointestinal bleeding, but a similar risk of intracranial or urogenital bleeding, in most countries. Ischemic stroke incidence ranged from 0.31 to 1.52 events per 100 person-years for rivaroxaban users. CONCLUSIONS: Incidences of intracranial bleeding were generally lower with rivaroxaban than with SOC, whereas incidences of gastrointestinal and urogenital bleeding were generally higher. The safety profile of rivaroxaban for NVAF in routine practice is consistent with findings from randomized controlled trials and other studies.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do TratamentoRESUMO
Purpose: When using incomplete or non-representative real-world data (RWD), bias is more likely to occur. The aim of the current study was to assess the completeness and representativeness of the PHARMO GP data for the Dutch population. Patients and Methods: A cross-sectional study was performed. The PHARMO GP data comprise data from electronic health records registered by GPs. Data on the Dutch population were obtained from Statistics Netherlands (CBS), which offers publicly available data on several themes. The standardized difference (std.diff) was used to compare proportions between the PHARMO GP population and the Dutch population. An absolute std.diff >0.2 was considered a difference. Results: On January 1st, 2018, 3,466,321 persons were included in the PHARMO GP data (mean age: 41.6 years, 49.7% males). The sex and age distribution was similar to the Dutch population. The PHARMO GP data captured less not urbanized areas compared to the Dutch population (not urbanized areas: 9.4% vs 17.1% [std.diff: -0.23]). Regarding medication use, only the pharmacological subgroups "viral vaccines" and "hormonal contraceptives for systemic use" differed (std.diff >0.2); use in the GP data was more complete than in the Statistics Netherlands (CBS) data. No differences were observed regarding diagnoses. Conclusion: The PHARMO GP data are representative of the Dutch population with regard to the demographic characteristics and diagnoses in primary care. Medication data in the PHARMO GP data are more complete than national statistics, and differences are related to reimbursement. Use of the data and interpretation of results based on these sources should be done with experts on the data sources, the Dutch healthcare system and (pharmaco)epidemiology.
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PURPOSE: Recent studies suggest that women are more susceptible to diuretic-induced hyponatremia resulting in hospital admission than men. The aim of this study was to confirm whether these sex differences in hyponatremia-related hospital admissions in diuretic users remain after adjusting for several confounding variables such as age, dose, and concurrent medication. METHODS: In a case-control design nested in diuretic users, cases of hyponatremia associated hospital admissions between 2005 and 2017 were identified from the PHARMO Data Network. Cases were 1:10 matched to diuretic users as controls. Odds ratios (OR) with 95%CIs were calculated for women versus men and adjusted for potential confounders (age, number of diuretics, other hyponatremia-inducing drugs, chronic disease score) using unconditional logistic regression analysis. A subgroup analysis was performed for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists). RESULTS: Women had a statistically significantly higher risk of a hospital admission associated with hyponatremia than men while using diuretics (OR 1.86, 95%CI 1.64-2.11). Adjusting for the potential confounders resulted in an increased risk for women compared to men (ORadj 2.65, 95% CI 2.31-3.04). This higher risk in women was also seen in the three subgroup analyses after adjustment. CONCLUSION: Our findings show a higher risk of hyponatremia-related hospital admission in women than men while using diuretics. Further research is needed to understand the underlying mechanism of this sex difference to be able to provide sex-specific recommendations.
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Diuréticos , Hiponatremia , Humanos , Feminino , Masculino , Diuréticos/efeitos adversos , Hiponatremia/induzido quimicamente , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , HospitaisRESUMO
OBJECTIVE: To describe treatment patterns, low-density lipoprotein cholesterol (LDL-C) levels and healthcare resource utilization (HCRU) in the Netherlands in 2018 of patients with hypercholesterolaemia or mixed dyslipidaemia at high or very high cardiovascular (CV) risk. METHODS: From the PHARMO Database Network adult patients with a diagnosis or receiving lipid lowering therapy (LLT) between 2009 and 2018 were selected. Patients at high or very high CV risk according to 2016 ESC/EAS guidelines with recorded LDL-C levels who were treated with LLT or were characterized as statin intolerant in 2018 were included. LLT treatment patterns, LDL-C levels and HCRU (General Practitioner [GP] consultations and hospitalizations) were assessed. RESULTS: The study population included 54,346 patients, of which 70% were at very high CV risk and 30% at high CV risk. The majority (93%) received statin monotherapy, mostly of moderate (73%) or high (15%) intensity. Only 3% received a combination of statin and ezetimibe. Statin intolerance, based on a treatment algorithm, was estimated at 3%. Average LDL-C decreased with LLT intensity. Overall, 74% reached LDL-C < 2.5 mmol/l and 34% <1.8 mmol/l with their current treatment, and 46% reached their LDL-C goal according to 2016 ESC/EAS guidelines. The highest rates of hospitalizations and GP consultations, including home visits, were recorded in patients with peripheral artery disease or polyvascular disease. CONCLUSION: The treatment of hypercholesterolaemia and mixed dyslipidaemia in patients at high or very high CV risk in the Netherlands was suboptimal in 2018. To further lower CV risk alternative treatment strategies using add-on therapies are needed.
Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Adulto , Humanos , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/epidemiologia , LDL-Colesterol , Estudos Transversais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Países Baixos/epidemiologia , Fatores de Risco , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Fatores de Risco de Doenças Cardíacas , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/efeitos adversos , Resultado do TratamentoRESUMO
Introduction: The increasing number of people with diabetes and the unclear long-term safety and effectiveness of newer and older blood-glucose-lowering treatments emphasize the need for more pharmaco-epidemiological studies in this field. A prospective, regularly updated cohort of people with diabetes would provide quick and up-to-date information regarding prevalence, treatment, safety and effectiveness. The current aim was to describe the design of the DIAbetes MANagement and Treatment (DIAMANT) cohort. Methods: The DIAMANT cohort is a population-based, dynamic, prospective cohort of persons with diabetes. It contains real-world data (RWD) from general practitioners (GP), including diagnoses, symptoms, examinations, communication to/from specialists and medication. Diabetes is defined as a recorded diabetes diagnosis or a prescription of drugs used in diabetes. The cohort is part of the national infrastructure of "Stichting Informatievoorziening voor Zorg en Onderzoek" (STIZON) and is linked to other data sources. Results: Currently, the cohort enables access to information of 89,883 patients in 2004 to 344,914 in 2020 (6% T1D, 84% T2D and 10% unclassified type of diabetes), with 193,931 participants still registered as being present in the GP practice (active) in 2020. The frequency of follow-up of persons with diabetes is practice dependent. The Dutch guidelines advise 2-4 contacts per year with a more extensive yearly check-up. The DIAMANT cohort is updated several times a year. Anonymised data from the DIAMANT cohort are available to researchers. Discussion: The DIAMANT cohort provides the opportunity to gain RWD insights into the treatment and outcomes among people with diabetes in daily general practice. The data can be enriched by established linkages to other data sources (eg, hospital data, the Perinatal Registry, the Cancer Registry). The DIAMANT cohort serves as a start of a national infrastructure to study, manage and provide personalised care in order to ultimately improve care and outcomes for people with diabetes.
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Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39-49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed.