ABSTRACT
PURPOSE: This study aims to validate major bleeding (MB) cases within a cohort of new users of direct oral anticoagulants (DOACs) in Electronic health records (EHRs) from primary care in Spain (BIFAP), introducing more efficient techniques and automating the process of validation in the pharmacoepidemiologic research with EHR data as much as possible. METHODS: Registered bleedings were identified in a cohort of new users of DOACs in BIFAP using ICPC 2 and ICD 9 codes; we ascertained these bleedings as MB through a validation strategy based on the MB definition from the International Society on Thrombosis and Hemostasis, which used hospitalization and critical localization as proxies. We assessed hospitalization with hospital discharge information (only available for some years and regions) and a free text-based algorithm created to identify hospitalization in EHR's clinical notes. Incidence rates (IR) of MB were evaluated by bleeding type. RESULTS: The study cohort included 104 614 patients, with 274521.5 p-y of follow up. There were 6143 registered bleedings during the study period (519 intracranial bleeding - ICB, 4606 gastrointestinal bleeding - GIB, 1018 extracranial bleeding - ECB), from which 1679 were confirmed as MB (416 ICB, 1086 GIB, and 177 ECB). The free text-based semi-automatic algorithm had moderate recall (0.59), but high specificity (0.99), and precision (0.94). CONCLUSION: The combination of hospitalization and critical localization is a valid approach to validate MB in EHRs with incomplete information. The use of more automatic methods for case validation instead of manual review of clinical notes is favored.
Subject(s)
Anticoagulants , Gastrointestinal Hemorrhage , Databases, Factual , Humans , Primary Health Care , Spain/epidemiologyABSTRACT
PURPOSE: Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) is a population based database administered by the AEMPS (Spanish Agency for Medicines) of longitudinal electronic medical records (EMR) of patients attended in primary care. Its main purpose is to serve as source of information for independent studies on drug safety and support of medicines regulation activities. This article aim is to describe the characteristics of BIFAP, how to access the database and a summary of its potential for research. METHODS: Health problems are registered by primary care physicians as episodes of care and include socio-demographic data, results of diagnostic procedures, lifestyle data, general data, and interventions. A proportion of data on hospitalizations and specialist care are currently available through linkage with other data sources. EMRs of the Spanish healthcare system are provided by the regional administrations. Specific data extraction and standardization processes are performed. RESULTS: BIFAP includes data from 12 million patients starting in 2001 and updated annually. Validation of drug and diagnosis definitions has been ascertained. Participation in international collaborative projects and a number of articles in peer reviewed journals reflect its contribution to the knowledge of the risks associated with medicines and drug utilization patterns. CONCLUSIONS: BIFAP is a useful tool for generating scientific evidence on medicines related issues, helping regulatory decision making in Europe. The main strengths of BIFAP are related to large sample size, population-based, longitudinal nature and annual update of data. BIFAP shares common challenges with similar data sources including accurate and efficient identification of health outcomes and of treatment exposure.
Subject(s)
Databases, Factual/statistics & numerical data , Pharmacoepidemiology/methods , Electronic Health Records/statistics & numerical data , Humans , Primary Health Care/statistics & numerical data , Sample Size , SpainABSTRACT
OBJETIVO: Comprobar el diagnóstico asociado al tratamiento específico para demencia en la historia clínica electrónica de atención primaria (HCE-AP) y analizar los factores asociados a la calidad del registro. MÉTODO: Estudio descriptivo de los pacientes con anticolinesterásicos o memantina registrados en la Base para Investigación Farmacoepidemiológica en atención primaria (BIFAP) 2011: 24.575 pacientes entre 2002 y 2011. Los diagnósticos asociados a la primera prescripción de estos fármacos se agruparon en 5 categorías: «demencia», «alteraciones de memoria», «enfermedades relacionadas con demencia», «procesos intercurrentes» y «códigos de conveniencia». Se calculó la prevalencia de cada categoría por edad y sexo en cada año de estudio (IC 95%) y se analizaron asociaciones y tendencia 2002-2011, utilizando diferencias de proporciones para muestras independientes y regresión logística binaria. RESULTADOS: El 56,5% (IC 95%: 55,8-57,1) de los pacientes tenían asociado código «demencia» a la primera prescripción. Se registró mejor en mujeres (OR: 1,09 [IC 95%: 1,03-1,15]) y al aumentar el tiempo transcurrido (OR: 1,07 [IC 95%: 1,06-1,08] por cada año de seguimiento). Los «códigos de conveniencia» (16,3% [IC 95%: 15,8-16,7]) se utilizaron más en mujeres y ≥ 80 años; las «alteraciones de memoria» (12,4% [IC 95%: 12,0-12,8]), «enfermedades relacionadas» (4,6% [IC 95%: 4,4-4,8]) y «procesos intercurrentes» (10,3% [IC 95%: 9,9-10,6]) más en hombres y < 80 años. De 2002 a 2011 mejoró el uso de «códigos de conveniencia». CONCLUSIONES: Casi la mitad de los pacientes con anticolinesterásicos o memantina no tienen registrado diagnóstico de demencia en su HCE-AP. El registro mejora al aumentar el tiempo de seguimiento. Se requieren mejoras de la HCE-AP, coordinación asistencial adecuada y actitud activa para aumentar la calidad del registro de demencia
OBJECTIVE: To ascertain the diagnosis associated with specific treatment for dementia in the Primary Care Electronic Clinical Record (PC-ECR) and to analyse the factors associated with the quality of registration. METHODS: Descriptive study of patients taking cholinesterase inhibitors or memantine registered in Database for pharmacoepidemiological research in PC (BIFAP) 2011: 24,575 patients between 2002 and 2011. Diagnoses associated with first prescription of these drugs were grouped into 5 categories: 'dementia', 'memory impairment', 'dementia-related diseases', 'intercurrent processes' and 'convenience codes'. We calculated the prevalence of each category by age and sex for each study year (95% CI) and analysed the associations and trend for 2002-2011 using difference in proportions in independent samples and binary logistic regression. RESULTS: A code of 'dementia' was associated with first prescription in 56.5% (95% CI: 55.8-57.1) of PATIENTS: It was higher in women [OR 1.09 (95% CI: 1.03-1.15)] and with increasing follow-up time [OR 1.07 (95% CI: 1.06-1.08) for each year of follow-up]. 'Convenience codes' [16.3% (95% CI: 15.8-16.7)] were coded more frequently in women and in those ≥ 80 years; 'Memory impairment' [12.4% (95% CI: 12.0-12.8)], 'related diseases' [4.6% (95% CI: 4.4-4.8)] and 'intercurrent processes' [10.3% (95% CI: 9.9-10.6)] were used more in men and in persons < 80 years. Between 2002 and 2011 improved the use of 'convenience codes'. CONCLUSIONS: Almost half of the patients taking cholinesterase inhibitors or memantine do not have a diagnosis of dementia registered in their PC-ECR. Registration improves with increasing time of follow-up. Improvements are needed in the PC-ECR, adequate care coordination, and proactive approach to increase the quality of dementia registration
Subject(s)
Humans , Male , Female , Clinical Record , Dementia/diagnosis , Dementia/epidemiology , Electronic Health Records/organization & administration , Electronic Health Records/standards , Electronic Health Records , Pharmacoepidemiology/organization & administration , Pharmacoepidemiology/statistics & numerical data , Memantine/therapeutic use , Medical Records/legislation & jurisprudence , Medical Records/standards , Forms and Records Control/organization & administration , Forms and Records Control/standards , Primary Health Care/methods , Primary Health Care/trends , Primary Health Care , Logistic ModelsABSTRACT
OBJECTIVE: To ascertain the diagnosis associated with specific treatment for dementia in the Primary Care Electronic Clinical Record (PC-ECR) and to analyse the factors associated with the quality of registration. METHODS: Descriptive study of patients taking cholinesterase inhibitors or memantine registered in Database for pharmacoepidemiological research in PC (BIFAP) 2011: 24,575 patients between 2002 and 2011. Diagnoses associated with first prescription of these drugs were grouped into 5 categories: "dementia", "memory impairment", "dementia-related diseases", "intercurrent processes" and "convenience codes". We calculated the prevalence of each category by age and sex for each study year (95%CI) and analysed the associations and trend for 2002-2011 using difference in proportions in independent samples and binary logistic regression. RESULTS: A code of "dementia" was associated with first prescription in 56.5% (95%CI: 55.8-57.1) of patients. It was higher in women [OR1.09 (95%CI: 1.03-1.15)] and with increasing follow-up time [OR1.07 (95%CI: 1.06-1.08) for each year of follow-up]. "Convenience codes" [16.3% (95%CI: 15.8-16.7)] were coded more frequently in women and in those ≥80 years; "Memory impairment" [12.4% (95%CI: 12.0-12.8)], "related diseases" [4.6% (95%CI: 4.4-4.8)] and "intercurrent processes" [10.3% (95%CI: 9.9-10.6)] were used more in men and in persons <80 years. Between 2002 and 2011 improved the use of "convenience codes". CONCLUSIONS: Almost half of the patients taking cholinesterase inhibitors or memantine do not have a diagnosis of dementia registered in their PC-ECR. Registration improves with increasing time of follow-up. Improvements are needed in the PC-ECR, adequate care coordination, and proactive approach to increase the quality of dementia registration.
Subject(s)
Dementia/diagnosis , Electronic Health Records , Registries , Aged , Aged, 80 and over , Cholinesterase Inhibitors/therapeutic use , Dementia/drug therapy , Female , Humans , Male , Memantine/therapeutic use , Middle Aged , Primary Health Care , Quality Control , SpainABSTRACT
OBJECTIVES: To quantify the risk of non-fatal acute myocardial infarction (AMI) among users of allopurinol. METHODS: We carried out a population-based case-control study over the period 2001-2007 in patients aged 40-90â years. Patients who had prescriptions of allopurinol or an episode of AMI before the start date of follow-up were excluded from the main analysis. Allopurinol initiators were classified as current users if their last prescription ended in the 30-day window before the recorded date of AMI for cases and a random date for controls. The association between use of allopurinol and non-fatal AMI was measured through an OR and adjusted for confounding factors by an unconditional logistic regression. RESULTS: We identified 3171 cases of non-fatal AMI and 18â 525 controls. Cases had a lower prevalence of current use of allopurinol (0.82%) than controls (1.03%), yielding to an OR of 0.52 (95% CI 0.33 to 0.83). The decreased risk was driven by men (OR in men=0.44; 95% CI 0.25 to 0.76; OR in women=0.90; 0.36 to 2.23). No difference by age was observed. The effect was only observed at higher doses (300â mg or greater OR=0.30; 0.13 to 0.72; <300â mg OR=0.67; 0.37 to 1.23) and with prolonged treatments (<31â days, OR=1.12 (0.55 to 2.29); 31-180â days, OR=0.61; 0.29 to 1.29; >180â days OR=0.21; 0.08 to 0.53; p for trend=0.001). Among those with a previous AMI, allopurinol use also showed a significant reduced risk of recurrence (OR=0.16; 0.04 to 0.76). CONCLUSIONS: The present study supports the hypothesis that allopurinol is associated with a reduced risk of non-fatal AMI, which seems to be dose-dependent and duration-dependent.
Subject(s)
Allopurinol/therapeutic use , Free Radical Scavengers/therapeutic use , Myocardial Infarction/prevention & control , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Gout/complications , Humans , Hyperuricemia/complications , Male , Middle Aged , Myocardial Infarction/complications , Risk Factors , Uric Acid/metabolismABSTRACT
PURPOSE: The purpose of this study is to estimate the risk of nonfatal acute myocardial infarction (AMI) associated with traditional NSAIDs (tNSAIDs), non-narcotic analgesics (paracetamol and metamizole), and symptomatic slow-acting drugs in osteoarthritis (SYSADOAs) overall and in different subgroups of patients. METHODS: We performed a nested case-control study using a Primary Care Database (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria), over the study period, 2001-2007. We included patients aged 40-90 years, with nonfatal AMI and randomly selected controls matched for age, sex and calendar year. Exposure to drugs was assessed within a 30-day window before the index date. RESULTS: We did not find an association with nonfatal AMI in patients at low-intermediate background cardiovascular risk (odds ratio = 0.92; 95% confidence interval: 0.76-1.12), whereas there was a moderate significant association among those at high risk (1.28; 1.06-1.54) or when tNSAIDs were used for longer than 365 days (1.43; 1.12-1.82). The greatest risk occurred when these two conditions were combined (1.80; 1.26-2.58). The risk varied across individual tNSAIDs, with ibuprofen (0.95; 0.78-1.16) in the lower and aceclofenac (1.59; 1.15-2.19) in the upper part of the range. Low-dose aspirin did not modify the risk profile showed by any of the individual tNSAIDs examined. Paracetamol (0.84; 0.74-0.95), metamizole (1.06; 0.87-1.29) and SYSADOAs (0.68; 0.47-0.99) were not associated with an increased risk overall or in any subgroup of patients. CONCLUSIONS: The risk of nonfatal AMI varied with individual tNSAIDs, duration of treatment and background cardiovascular risk. Paracetamol, metamizole and SYSADOAs did not increase the risk in any of the conditions examined.
Subject(s)
Analgesics, Non-Narcotic/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Myocardial Infarction/chemically induced , Osteoarthritis/drug therapy , Adult , Aged , Aged, 80 and over , Analgesics, Non-Narcotic/therapeutic use , Cardiovascular Diseases/epidemiology , Case-Control Studies , Delayed-Action Preparations , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Myocardial Infarction/epidemiology , Risk FactorsABSTRACT
AIM: To test the ability a new Spanish primary care research database (BIFAP) to capture the association between upper gastrointestinal bleeding (UGIB) and NSAIDs and other drugs and compare the results with previous studies. METHODS: We performed a nested case-control study in persons aged 40-90 years old included in the period 2001-2005. Potential cases were selected through a computer search followed by an individual blinded review. Controls matched for age, sex and calendar year were randomly selected. The exposure window was defined as 0-30 days before the index date. Adjusted odds ratios were obtained through unconditional logistic regression models. RESULTS: In a study cohort of 669,115 subjects (1,576,442 person-years) we retrieved 1,193 valid incident cases. Increased risks were found with current use of NSAIDs (RR = 1.72; 95 %CI: 1.41-2.09), metamizole (1.52; 1.09-2.13), low-dose aspirin (1.74; 1.37-2.21), other antiplatelet drugs (1.73; 1.27-2.36), and oral anticoagulants (2.00; 1.44-2.77). We did not find an increased risk with current use of oral corticosteroids (1.11; 0.66-1.86), SSRIs (1.05; 0.77-1.42), or paracetamol (1.00; 0.82-1.23). Acid-suppressing drugs reduced the risk among users of NSAIDs (0.58; 0.39-0.85), particularly in users with antecedents of peptic ulcer (0.16; 0.05-0.58). We detected a decreasing time-trend in the relative risk and the population attributable proportion associated with NSAIDs over the study period. CONCLUSIONS: The increased risk of UGIB associated with NSAIDs was lower than previously reported, which could partly be explained by methodological differences, but a decreasing burden over time of this drug safety problem is suggested. BIFAP has shown to be a valuable tool for pharmacoepidemiological research.
Subject(s)
Adverse Drug Reaction Reporting Systems , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Databases, Factual , Gastrointestinal Hemorrhage/chemically induced , General Practice , Adult , Aged , Aged, 80 and over , Case-Control Studies , Drug Interactions , Female , Gastrointestinal Hemorrhage/epidemiology , Gastrointestinal Hemorrhage/prevention & control , Histamine H2 Antagonists/therapeutic use , Humans , Incidence , Logistic Models , Male , Middle Aged , Odds Ratio , Proton Pump Inhibitors/therapeutic use , Registries , Risk Assessment , Risk Factors , Spain/epidemiology , Time FactorsABSTRACT
AIM: Information from the spontaneous reporting system raised the hypothesis of an increased risk of meningioma in patients treated with high doses of cyproterone acetate (CPA). The objective of this study was to test the hypothesis of an increased risk of meningioma among users of high dose CPA as compared with non-users in a medical records computerized database. METHODS: A retrospective cohort study was performed in a Spanish primary care database (BIFAP). Meningioma incidence rates were compared in patients exposed to high dose CPA (users) with those non-exposed and with those exposed to low dose CPA. Poisson regression analysis was used to estimate the incidence rate ratios after adjusting for age and gender. RESULTS: Among 2474 users of high dose cyproterone (6663 person-years) four meningioma cases were identified, resulting in an incidence rate (IR) of 60.0 (95% CI 16.4, 153.7) per 100,000 person-years, which was significantly higher than that observed among the non-users (IR 6.6; 95% CI 6.0, 7.3) and among women users of low dose cyproterone (IR 0.0, 95% CI upper limit 5.5). After adjusting for age and gender, patients exposed to high dose CPA showed an increased risk of meningioma of 11.4 (95% CI 4.3, 30.8) as compared with non-users. CONCLUSIONS: The results of this study support the hypothesis that the exposure to high dose CPA increases the risk of meningioma.
