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Purpose: We aimed to estimate the absolute (incidence) and relative (hazard ratio; HR) risk of agranulocytosis associated with metamizole in comparison with non-steroidal antiinflammatory drugs (NSAIDs). Methods: A cohort study of new users of metamizole versus NSAIDs was performed with BIFAP (Pharmacoepidemiologic Research Database in Public Health Systems; Spain). Patients aged ≥ 2 years in 2005–2022 were followed up from the day after their first metamizole or NSAID dispensation till the end of the treatment period to identify patients hospitalized due to idiosyncratic agranulocytosis. Incidence rate (IR) and adjusted HR of agranulocytosis with metamizole versus NSAID were estimated assuming the onset date of agranulocytosis was the date of hospitalization sensitivity analysis or 7 days before (main analysis). In secondary analyses, we used (1) opioids-paracetamol as negative control and (2) any hospitalized neutropenia as outcome (assuming the onset was 7 days before). Results: The cohorts included 444,972 new users of metamizole, 3,814,367 NSAID, and 3,129,221 opioids-paracetamol on continuous treatment during a median of 37–40 days. Overall, 26 hospitalized agranulocytosis occurred, 5 in the first week (and so removed in main analysis) and 21 thereafter. IR of agranulocytosis was 14.20 (N = 5 cases) and 8.52 (N = 3), 1.95 (N = 6) and 1.62 (N = 5), and 4.29 (N = 15) and 3.72 (N = 13)/107 person-weeks of continuous treatment using the date of hospitalization or 7 days before, respectively. Two, 0 and 2 of cases identified in both analyses had neoplasia in every cohort, respectively. HR of agranulocytosis associated with metamizole was 7.20 [95% CI: 1.92–26.99] and 4.40 [0.90–21.57] versus NSAID, and 3.31 [1.17–9.34] and 2.45 [0.68–8.83] versus opioid-paracetamol, respectively. HR of neutropenia with metamizole was 2.98 [1.57–5.65] versus NSAID. Conclusions: Agranulocytosis was very rare but more common (above 4 times more) with metamizole than other analgesics. The impact of the drug-induced agranulocytosis was less precise with metamizole than the comparators due to its lower use, which precluded to find statistical differences in main analysis. The increased risk of hospitalized neutropenias with metamizole supports the link with its severity although triggers unavailable during the follow-up (ex. cytotoxic medication) can not be discarded. [ABSTRACT FROM AUTHOR]

Background: Uterine fibroids (UFs) are the most common benign tumour in women, and many undergo hysterectomy or uterus-preserving procedures (UPPs) to manage their symptoms. We aimed to validate the recording of UFs in a primary care database, The Health Improvement Network (THIN), and to determine the incidence of UFs in the UK.Methods: In this observational study, women in THIN aged 15-54 years between January 2000 and December 2009 with no previous record of UFs, hysterectomy or UPPs were identified. Individuals were followed up until there was a Read code indicating UFs, they reached 55 years of age or died, or the study ended. Among those without a UF code, women were identified with a code for hysterectomy, UPPs or heavy menstrual bleeding (HMB). Anonymized patient profiles from each category were randomly selected and reviewed. Subsequently, primary care physicians were asked to complete questionnaires to verify the diagnosis for a randomly selected subgroup.Results: In total, 737,638 women were identified who met the initial inclusion criteria. The numbers of women with a code for UFs, hysterectomy, UPPs and HMB were 9380, 11,002, 3220 and 60,915, respectively; the proportions of confirmed cases of UFs were 88.8, 29.7, 57.7 and 15.9 %. The estimated number of women with UFs was 23,140 (64.0 % without a recorded UF diagnosis). The overall incidence of UFs was 5.8 per 1000 woman-years.Conclusions: UFs were confirmed in a high proportion of women with UF Read codes. However, almost two-thirds of cases were identified among women with a code for hysterectomy, UPPs or HMB. These results show that UFs are under-recorded in UK primary care, and suggest that primary care physicians tend to code the symptoms of UFs more often than the diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence of hysterectomy and uterus-preserving procedures (UPPs) among women with uterine fibroids (UFs) and the incidence of further procedures after a UPP.Study Design: This was an observational study using a primary care database, The Health Improvement Network (THIN). Women in THIN with UFs aged 15-54 years between January 2000 and December 2009 were eligible for study. The UPPs examined were myomectomy, endometrial ablation (EA) and uterine artery embolization (UAE). Using Read codes, women were followed up until one of the following was met: there was a record of hysterectomy or UPPs, they died or the study ended (end of 2010).Results: The cumulative incidence of hysterectomy or UPPs was 23.6% at 1 year, and 40.9% after the follow-up period (median 3.6 years). At the end of the follow-up period, the cumulative incidences of hysterectomy, myomectomy, EA and UAE were 33.0%, 3.9%, 6.4% and 1.9%, respectively. For women initially treated with a UPP, the cumulative incidence of second procedures was 11.5% at 1 year. At the end of the follow-up period (median 2.7 years), the cumulative incidence of further procedures was 26.1%, and the cumulative incidences of women undergoing hysterectomy, myomectomy, EA and UAE were 19.0%, 4.3%, 3.4% and 1.4%, respectively.Conclusions: Women considering UPPs for the management of UFs should be made aware that the incidence of further treatments is high, with hysterectomy being the most frequent procedure undergone. [ABSTRACT FROM AUTHOR]

Purpose: We aim to estimate the incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) among tetrazepam users and compare it with benzodiazepine users in a Spanish primary care database (BIFAP). The incidence in the general population (GenPop) and among phenytoin new users (as a positive control) was also estimated. Methods: We identified a cohort of GenPop free of SJS/TEN ( N = 3,155,364). Cohort entry was the date after 1 year of register with the physician during 2001-2011. No age restrictions were applied. Patients were followed from entry up to the first of the following: a record of SJS/TEN (potential cases), death, end of information, or December 2011. History of potential cases were manually reviewed blinded to exposure and considered 'probable' when diagnosed in referral reports. Three cohorts of patients newly prescribed with benzodiazepines ( N = 531,813), tetrazepam ( N = 343,568), or phenytoin ( N = 4993) were extracted from the GenPop cohort. Incidence rate (cases per million person-years (py)) for the GenPop and cumulative incidence (per million new users) during the first 9 weeks after each drug prescription were computed. Results: In the GenPop, 48 probable cases (38 SJS and 10 TEN) were identified (3.21/million py; 3.37 in men and 2.94 in women). In the benzodiazepines cohort, 2 probable TEN cases was identified (3.76/mill.). In the tetrazepam cohort, 1 probable SJS/TEN case was identified (2.91/mill.). In the phenytoin cohort, 4 probable cases (2 SJS and 2 TEN) were identified (801.12/mill.). Conclusions: The incidence of SJS/TEN in tetrazepam users was very rare and similar to benzodiazepines users. The incidence in the GenPop and among users of phenytoin agreed with the literature. [ABSTRACT FROM AUTHOR]

The exact mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may increase coronary risk is not completely understood. The aim of this study was to quantify the risk for each type of acute coronary syndrome (ACS) associated using NSAIDs and the role played by dose, duration, and patient characteristics. A prospective case-control study was performed, interviewing 2,954 patients hospitalized for ACS at 32 Spanish hospitals and a similar number of age-matched controls using a structured questionnaire collecting information on the use of NSAIDs, risk factors, and cardiovascular history. Odds ratios (ORs) for any type and each ACS type were calculated adjusted for gender, body mass index, other risk factors, and concomitant medications by conditional logistic regression. The adjusted OR of ACS associated with the current use of NSAIDs was 1.16 (95% confidence interval [CI] 0.95 to 1.42). The risk was increased in patients consuming high doses (OR 1.64, 95% CI 1.06 to 2.53) and those with previous ischemic heart disease (OR 1.84, 95% CI 1.13 to 3.00). The hazard was driven mostly by the increase in the risk for non-ST-segment elevation ACS (OR 1.20, 95% CI 0.99 to 1.47), whereas NSAIDs did not increase the risk for ST-segment elevation myocardial infarction (OR 1.00, 95% CI 0.80 to 1.26). In conclusion, the use of NSAIDs was associated with a small, nonsignificant overall coronary risk that was more apparent for non-ST-segment elevation ACS. This risk was stronger when NSAIDs were used at high doses or in patients with previous ischemic heart disease. [Copyright &y& Elsevier]