Miguel Gil

Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project

Studies on drug utilization usually do not allow direct cross‐national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases.

Risk of ischemic stroke associated with non-steroidal anti- inflammatory drugs and paracetamol: a population-based case-control study

To assess the risk of non‐fatal ischemic stroke associated with non‐steroidal anti‐inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied.

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†

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.

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.

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.

Antiepileptic drug use in seven electronic health record databases in Europe : a methodologic comparison

The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries due to use of different type of data sources, time periods, population distribution, and methodologic differences. This study aimed to measure prevalence of AED prescribing across seven European routine health care databases in Spain, Denmark, The Netherlands, the United Kingdom, and Germany using a standardized methodology and to investigate sources of variation.

Patients with Breast Cancer and Negative Sentinel Lymph Node Biopsy without Additional Axillary Lymph Node Dissection: A Follow-Up Study of up to 5 Years

Objective: To analyze the rate of axillary recurrences and survival in patients operated on for breast cancer who had not undergone an axillary lymph node dissection (ALND) because of a negative sentinel node biopsy. Methods: The study includes 97 patients operated on for breast cancer and selective node biopsy from June 2000 to December 2001 who had a negative sentinel node biopsy and did not undergo ALND. Mean age was 58.2 years (55.9–60.5). Follow-up was done up to 5 years. After surgery all patients underwent clinical examination. Complementary treatment depended on the hospital protocol. Rate of axillary recurrences, presence of distant metastases and survival (Kaplan-Meier method) were studied. Results: After a median follow-up of 4.1 years (2.18–5.25), only 2/95 patients (2.1%) developed distant metastases. Four patients died but only the death of the patient who presented multiple metastases was related to the primary breast cancer (1%). The 5-year overall survival rate was 96%. Conclusions: (1) Only 1/95 patients studied developed nodal extra-axillary recurrence together with distant metastases. (2) The results obtained support the selective sentinel node biopsy as an accurate technique in the axillary stratification of patients with breast cancer, offering in the cases of negative sentinel node biopsy a safe axillary control after a 5-year follow-up.

Prevalence of antibiotic use : a comparison across various European health care data sources

There is widespread concern about increases in antibiotic use, but comparative data from different European countries on rates of use are lacking. This study was designed to measure and understand the variation in antibiotic utilization across five European countries.

Trends in the surgical procedures of women with incident breast cancer in Catalonia, Spain, over a 7-year period (2005–2011)

BackgroundBreast cancer (BC) is the most frequent cancer in women, accounting for 28% of all tumors among women in Catalonia (Spain). Mastectomy has been replaced over time by breast-conserving surgery (BCS) although not as rapidly as might be expected. The aim of this study was to assess the evolution of surgical procedures in incident BC cases in Catalonia between 2005 and 2011, and to analyze variations based on patient and hospital characteristics.MethodsWe processed data from the Catalonian Health Service’s Acute Hospital Discharge database (HDD) using ASEDAT software (Analysis, Selection and Extraction of Tumor Data) to identify all invasive BC incident cases according to the codes 174.0-174.9 of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) that were attended for the one-year periods in 2005, 2008 and 2011. Patients were classified according to surgical procedures (BCS vs mastectomy, and immediate vs delayed reconstruction), and results were compared among periods according to age, stage, comorbidity and hospital level.ResultsBC surgical procedures were performed in more than 80% of patients. Surgical cases showed a significant increasing trend in the proportion of women aged 50–69 years, more advanced disease stages, higher comorbidity and they were attended in hospitals of less complexity level throughout the study period. Similar pattern was found for patients treated with BCS, which increased significantly from 67.9% in 2005 to 74.0% in 2011.Simple lymph node removal increased significantly (from 48.8% to 71.4% and from 63.6% to 67.8% for 2005 and 2011 in conservative and radical surgery, respectively). A slightly increase in the proportion of mastectomized young women (from 28% in 2005 to 34% in 2011) was detected, due to multiple factors. About 22% of women underwent post-mastectomy breast reconstruction, this being mostly immediate.ConclusionsThe use of HDD linked to the ASEDAT allowed us to evaluate BC surgical treatment in Catalonia. A consolidating increasing trend of BCS was observed in women aged 50–69 years, which corresponds with the pattern in most European countries. Among the mastectomized patients, immediate breast reconstructions have risen significantly over the period 2005–2011.

Understanding inconsistency in the results from observational pharmacoepidemiological studies : the case of antidepressant use and risk of hip/femur fractures

Results from observational studies on the same exposure–outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs.