Risk of nonfatal acute myocardial infarction associated with non-steroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study.

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.

Oral bisphosphonates are associated with increased risk of subtrochanteric and diaphyseal fractures in elderly women: a nested case-control study.

OBJECTIVES: To evaluate the association between bisphosphonate use and the risk of atypical femoral fractures among women aged 65 or older. DESIGN: Nested case-control study. SETTING: General practice research database in Spain. EXPOSURES: Use of oral bisphosphonates before the occurrence of atypical fractures among cases or the corresponding index date among controls. Bisphosphonate use was categorised as ever versus never users. Ever users were divided according to the total time since first prescription. MAIN OUTCOME MEASURES: Cases were defined as women aged 65 years or older with a first diagnosis of subtrochanteric or diaphyseal fracture, recorded in the BIFAP database between 1 January 2005 and 31 December 2008, and with at least 1 year of follow-up before the index date. For each case, five age-matched and calendar-year-matched controls without a history of hip or atypical fracture were randomly selected from the database. STATISTICAL ANALYSIS: OR of atypical femoral fracture by bisphosphonate use was determined using conditional logistic regression. Models were adjusted for comorbidities and use of other medications. RESULTS: The analysis included 44 cases and 220 matched controls (mean age, 82 years). Ever use of bisphosphonates was more frequent in cases than controls (29.6% vs 10.5%). In multivariate analyses, OR (95% CI) of atypical femoral fracture was 4.30 (1.55 to 11.9) in ever versus never users of bisphosphonates. The risk increased with long-term use, with an OR of 9.46 (2.17 to 41.3) comparing those using bisphosphonates over 3 years versus no users (p for trend=0.01). CONCLUSIONS: Bisphosphonate use was associated with an increased risk of subtrochanteric or diaphyseal fractures in elderly women in a low fracture risk population, with a higher risk among long-term bisphosphonate users.

Upper gastrointestinal bleeding associated with NSAIDs, other drugs and interactions: a nested case-control study in a new general practice database.

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.

Risk of meningioma among users of high doses of cyproterone acetate as compared with the general population: evidence from a population-based cohort study.

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.

Influenza vaccination in old adults in Spain.

BACKGROUND: to describe population patterns of influenza vaccination, and to analyse the effect of a set of demographic, socio-economic status, lifestyles, health status, and health services variables, on the likelihood of being vaccinated in the those > or = 65 years. METHODS: Cross-sectional study. From the 1997 National Health Survey those > or = 65 years old were selected. Adjusted odds ratios were calculated through multiple logistic regression models, reporting having an influenza vaccination last season as a dependent variable. RESULTS: A total sample of 1148 was analysed: 51.3% of subjects reported having received a vaccination last year. Adjusted odds ratios showed that the risk of not having been vaccinated was higher for people from 65-69 years (OR: 1.70; 95% CI [1.32-2.19]), women (OR: 1.48; 95% CI [1.14-1.92]), residents in cities of more than 1 million inhabitants (OR: 1.74; 95% CI [1.12-2.70]), smokers (OR: 1.92; 95% CI [1.24-2.96]), having high-risk chronic conditions (OR: 1.41; 95% CI [1.08-1.85]), and for those whose last physician visit was between 2 weeks and 6 months ago (OR: 1.40; 95% CI [1.07-1.85]), and more than 6 months ago (OR: 2.13; 95% CI [1.52-2.98]). CONCLUSION: Influenza vaccination levels are sub-optimal. Factors that have been identified as barriers to receiving this effective intervention are: younger age, female sex, less contact with the health care system, smokers, and not having high-risk chronic conditions. No effect was found for socio-economic status or variables related with health, functional status or other health-related behaviours. This study may contribute to identifying population groups who could be targeted for health promotion interventions aimed to improve their influenza vaccination uptake.

[Determination of influenza vaccination in persons 65 years of age and older]. / Determinantes de la vacunación de la gripe en personas mayores de 65 años.

BACKGROUND: Influenza vaccination is an effective preventive intervention to reduce the negative consequences of this disease. The objective of this work is to describe population patterns of use of influenza vaccination, to analyze the effect of a set of variables on the likelihood of being vaccinated and of having a proactive attitude towards the vaccine in the age group of 65 year and over. METHODS: Cross sectional study. From the Spanish National Health Survey of 1997 those 65 and more year old were selected. The association of reporting having had an influenza vaccination last as year or having asked for the vaccine was estimated. RESULTS: A total sample of 1,148 was analyzed. Overall, 51.3% of subjects reported having received a vaccination last year. 18.0% of them reported having asked for the vaccine. Odds Ratios statistically associated with the vaccination were: 70 to 74 year 1.6 (1.2-2.2), 75 and older 2.0 (1.5-2.8), male 1.4 (1.1-1.9), residents in towns with less than 10,001 inhabitants 1.6 (1.0-2.6), non smokers 2.1 (1.3-3.5), with a last visit to a physician in the last two weeks 1.8 (1.3-2.6). Odds Ratios statistically associated with having a proactive attitude towards the vaccine were: finished studies with more than 15 year 1.8 (1.1-2.9), no consumption of medicine in the last two weeks 1.9 (1.1-3.6), and self-reported health as good or very good 1.7 (1.1-2.9). CONCLUSIONS: Overall influenza vaccination levels are not appropriate. Several factors have been identified as barriers for receiving this effective intervention. No association was found with socio-economic status. Some differences were also found regarding having a positive attitude towards the vaccine. This study may contribute to identifying population groups who are not receiving influenza vaccination and for designing strategies aimed to enhance influenza vaccination among them.

Determinantes de la vacunación de la gripe en personas mayores de 65 años / Determinants of Influenza Vaccination in People 65 and Older

Fundamentos: La vacuna de la gripe es una intervención preventiva efectiva para reducir las consecuencias de dicha enfermedad. El objetivo de este trabajo es describir los patrones poblacionales de vacunación de la gripe, y analizar el efecto de un conjunto de variables en la probabilidad de vacunarse y en tener una actitud proactiva en relación con la vacuna en el grupo de edad de 65 años y más. Método: Estudio transversal. De la Encuesta Nacional de Salud de 1997 se seleccionaron los casos con 65 y más años. Se estimó la asociación de haber recibido la vacuna de la gripe el año pasado o haberla solicitado con un conjunto de variables con regresión logística multivariable. Resultados: Se analizó una muestra total de 1.148 de casos. Globalmente, el 51,3 per cent de los sujetos declararon haber recibido la vacuna el último año, y el 18,0 per cent de ellos declararon haberla solicitado. Las Odds Ratios estadísticamente asociados con la vacunación fueron: 70 a 74 años 1,6 (1,2-2,2), mayores de 74 años 2,0 (1,5-2,8), hombres 1,4 (1,1-1,9), residentes en poblaciones de menos de 10.001 habitantes 1,6 (1,0-2,6), no fumadores 2,1 (1,3-3,5), con una última visita al médico hace menos de 2 semanas 1,8 (1,3-2,6). Los Odds Ratios estadísticamente asociados con la actitud positiva hacia la vacuna fueron: estudios terminados con más de 15 años 1,8 (1,1-2.9), no consumir medicamentos 1,9 (1,1-3,6), y tener una percepción de salud buena o muy buena 1,7 (1,1-2,9).Conclusiones: El nivel general de vacunación es bajo. Diversos factores se han identificado como barreras para recibir esta intervención efectiva. No se encontró una asociación con nivel socio-económico. También existen diferencias en relación con la actitud positiva hacia la vacuna. Este estudio puede contribuir a identificar grupos de población que no están recibiendo la vacuna de la gripe y para diseñar estrategias destinadas a incrementar la vacunación en dichos grupos (AU)