[Pharmacological treatment of the heart failure according to the ventricular ejection fraction in primary care]. / Tratamiento farmacológico de la insuficiencia cardíaca según la fracción de eyección ventricular en atención primaria.

Despite better diagnoses and treatments, heart failure (HF) is an important cause of death in Spain. The objective of this study is to describe the characteristics and treatment of a population with chronic HF classified according to the left ventricular ejection fraction (LVEF). Population-based observational cohort study in Primary Health Care. Catalonia, Spain, during 2014-2018. Adults with HF classified by the LVEF. Analysis of electronic health data registered in SIDIAP (Information System for Research in Primary Care). Demographics, LVEF, comorbidities, and use of drugs for HF. 10,130 patients were included; 18.9% with LVEF<40 (HFrEF), 15.9% with LVEF 40-49 (HFmEF) and 65.2% with LVEF≥50 (HFpEF), this last group with a higher proportion of women (57.5%) and higher mean age (80.2 years-old). People with HFmEF were similar to those with HFrEF in age, gender, comorbidities and treatment. The most frequent comorbidities were hypertension (78.3%), dyslipidaemia (54%) and atrial fibrillation (41.5%). The most frequent pharmacological treatments were ß blockers with differences according to the LVEF [HFrEF 1515 (79.2%), HFmEF 1142 (70.8%) and HFpEF 3371 (51%)], followed by loop diuretics (65.7%). HF is a prevalent disease. Having information on LVEF could guide its pharmacological management. The HF population has persistent cardiovascular risk factors and habits. Treatment and population characteristics of patients with HFmEF are similar to those with HFrEF.

Pharmacological treatment after acute coronary syndrome: Baseline clinical characteristics and gender differences in a population-based cohort study.

OBJECTIVE: To describe baseline socio-demographic and clinical characteristics and drugs prescribed for secondary prevention after a first episode of ACS and to assess differences between men and women. SETTING: PHC in Catalonia. DATA SOURCE: SIDIAP (Information System for Research in Primary Care). PARTICIPANTS: Patients who suffered an ACS during 2009-2016 and followed-up in PHC centres of the Catalan Health Institute in Catalonia. INTERVENTIONS: Not applicable. MAIN MEASURES: Socio-demographic and clinical characteristics at baseline: sex, age, socioeconomic index, toxic habits, comorbidities, study drugs (prescribed for cardiovascular secondary prevention: antiplatelets, betablockers, statins, drugs acting on the renin-angiotensin system) and comedications. RESULTS: 8071 patients included, 71.3% of them were men and 80.2% had an acute myocardial infarction. Their mean age was 65.3 and women were older than men. The most frequent comorbidities were hypertension, dyslipidaemia and diabetes and they were more common in women. Antiplatelets (91.3%) and statins (85.7%) were the study drugs most prescribed. The uses of all comedications were significantly higher in women, except for nitrates. The combination of four study groups was initially prescribed in 47.7% of patients and combination of beta-blockers, statins and antiplatelets was prescribed in 18.4%. More men than women received all recommended pharmacological groups. CONCLUSION: Women were older, had more comorbidities and received more comedications. Most patients were treated with a combination of four or three study drugs for secondary prevention. Men initiated more drug treatments for secondary prevention and dual antiplatelet therapy than women. EUPAS REGISTER: EUPAS19017.

Risk of ischaemic stroke associated with antiepileptic drugs: a population-based case-control study in Catalonia.

BACKGROUND: Cerebrovascular disorders have occurred more frequently in some Central Nervous System (CNS) disorders, such as epilepsy. Some CNS drugs have been associated with increased stroke risk. Our aim was to estimate the risk of ischaemic stroke in patients exposed to antiepileptic drugs (AED). METHODS: Population-based matched case-control study using SIDIAP database, based in electronic health records from primary healthcare from Catalonia, Spain. Cases were those patients with a registered diagnosis of first stroke during 2009-2014. Up to 10 controls were selected for each case and matched by sex, age, and geographic area and without a prior diagnosis of stroke. We considered global drug exposure to AED, past and current exposure and exposure in monotherapy to each AED. RESULTS: 2,865 cases and 19,406 controls were exposed to AED during the study period. Global exposure to levetiracetam [(ORadj3.3, CI95 % 2.8-4.0)], phenytoin [ORadj1.5, CI95 % 1.2-41.9)], and valproic acid [(ORadj 1.3, CI95 % 1.1-1.6)], showed significantly association to ischaemic stroke that was also maintained with current exposure of levetiracetam [ORadj4.1, CI95 % 3.3-5.2)] and valproic acid [ORadj1.4, CI95 % 1.1-1.9)]. Current levetiracetam monotherapy showed a very high risk of ischaemic stroke [(ORadj 5.1, CI95 % 3.7-6.9)]. CONCLUSIONS: Drugs used for other conditions than epilepsy (pregabalin, gabapentin) were the most used AED and both did not show a risk. Levetiracetam shows a risk for stroke even when assessed in current monotherapy. The lack of data regarding the link with diagnosis and severity in our study makes it necessary to conduct further studies to confirm or dismiss our results, focussing on levetiracetam.

Impact of adherence to drugs for secondary prevention on mortality and cardiovascular morbidity: A population-based cohort study. IMPACT study.

PURPOSE: Adherence to pharmacological therapy for secondary prevention after an acute coronary syndrome (ACS) reduces the risk of new cardiovascular events. However, several studies showed poor adherence. Our study aim was to assess the risk of a composite endpoint of major cardiovascular events (MACE) and all-cause mortality according to the adherence to these drugs in patients after an ACS in a primary health care cohort. METHODS: Population-based observational cohort study of patients with a first episode of ACS during 2009-2016. DATA SOURCE: Information System for Research in Primary Care (SIDIAP) database. Drug adherence was evaluated through proportion of days covered (PDC). RESULTS: We included 7152 patients and 5692 (79.6%) were adherent (PDC ≥ 75%) to the study drugs during the first year after the event. Adherents to any combination showed a significant reduction of the composite endpoint risk (HR 0.80 [0.73-0.88]), and a significant lower probability of the composite endpoint than nonadherents for all drugs, except beta-blockers. Adherents to 2 (HR 1.2; 95% CI 1.0-1.3) and 1 drug (HR 1.5; 95% CI 1.2-1.8) had higher composite endpoint risk compared to adherents to 4-3 drugs. CONCLUSION: Adherence to any combination of recommended drugs reduced the composite endpoint risk, regardless the number of drugs prescribed. Adherence to a combination of 4-3 drugs was significantly associated with a reduced mortality risk compared with adherents to 2 or 1, but it was not significant for MACE.

[Bibliometric analysis of female authorship in original articles in the journal ATENCIÓN PRIMARIA]. / Análisis bibliométrico de la autoría femenina en artículos originales en la revista ATENCIÓN PRIMARIA.

OBJECTIVES: To determine the percentage of female authors in original articles published during 2periods, in the journal of Atención Primaria (Primary Care), and to examine the differences between the categories of authorship (first, last author, and co-author) between both periods. DESIGN: Cross-sectional study. SETTING: Feminine scientific production published during the periods 2007-2008 and 2017-2018. PARTICIPANTS: The study was focused on original articles. MAIN MEASUREMENTS: The following variables were collected in an ad hoc form: gender based on the name of the author, total number of women and men appearing as authors, and order of authorship. Absolute and relative authorship frequencies were calculated, and the χ2 test was used to examine the evolution of the percentages by type of authorship and gender. RESULTS: A total of 108 articles were analysed in 2007-2008, and 100 in 2017-2018. No statistically significant differences were observed between the mean numbers of women authors within and between periods. In 2007-2008 a total of 548 female authors were identified and 540 in 2017-2018, the percentage of female authors was 48.7% and 54.4%, respectively. Only an increase in the percentage of first authors was observed between periods. CONCLUSIONS: Practically one out of every 2authors of original articles published in the journal Atención Primaria was female. There was also a significant increase in the percentage of female first authors between the 2periods. Nevertheless, and despite the greater number of health workers, the number of latest female authors remain unchanged, which points to the persistence of female under-representation.

[Effectiveness, safety and costs of stroke prevention in non-valvular auricular fibrillation. Study of cohorts matched by Propensity score]. / Efectividad, seguridad y costes de la prevención tromboembólica en fibrilación auricular. Estudio de cohortes apareado por Propensity score.

OBJECTIVE: To analyze the use, effectiveness, safety and costs of stroke prevention in non-valvular atrial fibrillation (AF) in patients initiating treatment with dabigatran or vitamin K antagonists (VKA). SETTING: Primary Care (PC) at the Catalan Health Institute (ICS) in Catalonia, during 2011-2013. PARTICIPANTS: Patients attended in ICS PC centres with a registered diagnosis of AF who initiate dabigatran or VKA. INTERVENTIONS: Not applicable MAIN MEASUREMENTS: Number of prescriptions and reimbursements of dabigatran and VKA, incidence of stroke and haemorrhages, incidence of mortatlity, number of sickness leave, and costs associated to all the previous variables. RESULTS: 14,930 patients were included; 94.6% initiated VKA and 5.4%, dabigatran. Dabigatran patients were younger and with less comorbidity. There were no statistically significant differences between VKA and dabigatran in the risk of stroke, haemorrhages or death. The costs associated to AF management were higher for PC visits in the VKA group, and higher for laboratory and pharmacy in the dabigatran group, although overall costs were not statistically different. CONCLUSIONS: Most patients initiated VKA. We found no differences between VKA and dabigatran in the risk of stroke, haemorrhages or mortality.

The use and adherence of oral anticoagulants in Primary Health Care in Catalunya, Spain: A real-world data cohort study.

OBJECTIVE: We aimed to describe sociodemographic, comorbidities, co-medication and risk of thromboembolic events and bleeding in patients with NVAF initiating oral anticoagulants (OAC) for stroke prevention, and to estimate adherence and persistence to OAC. SETTING: Primary Health Care (PHC) in the Catalan Health Institute (ICS), Catalunya, Spain. PARTICIPANTS: All NVAF adult patients initiating OAC for stroke prevention in August 2013-December 2015. METHODS: Population-based cohort study. Persistence was measured in patients initiating OAC in August 2013-December 2014. DATA SOURCE: SIDIAP, which captures electronic health records from PHC in the (ICS), covering approximately 5.8 million people. RESULTS: 51,690 NVAF patients initiated OAC; 47,197 (91.3%) were naive to OAC and 32,404 (62.7%) initiated acenocoumarol. Mean age was 72.8 years (SD 12.3) and 49.4% were women. Platelet-aggregation inhibitors were taken by 9105 (17.6%) of the patients. Persistence and adherence were estimated up to the end of follow-up. For 22,075 patients, persistence was higher among the non-naive patients [n=258 (61.7%)] than among the naive [n=11,502 (53.1%)]. Adherence was estimated for patients initiating DOAC and it was similar in naive and non-naive patients. Among the naive to DOAC treatment, those starting rivaroxaban showed a highest proportion [(n=360 (80.1%)] of good adherence at implementation (MPR>80%) while patients starting dabigatran were less adherent [n=203 (47.8%)]. CONCLUSIONS: Acenocoumarol was the most frequently prescribed OAC as first therapy in NVAF patients. Non-naive to DOAC showed better persistence than naive. Rivaroxaban showed higher proportion of adherent patients during the implementation phase than apixaban and dabigatran the lowest.

Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: A study in three European data sources.

PURPOSE: Validating cases of acute liver injury (ALI) in health care data sources is challenging. Previous validation studies reported low positive predictive values (PPVs). METHODS: Case validation was undertaken in a study conducted from 2009 to 2014 assessing the risk of ALI in antidepressants users in databases in Spain (EpiChron and SIDIAP) and the Danish National Health Registers. Three ALI definitions were evaluated: primary (specific hospital discharge codes), secondary (specific and nonspecific hospital discharge codes), and tertiary (specific and nonspecific hospital and outpatient codes). The validation included review of patient profiles (EpiChron and SIDIAP) and of clinical data from medical records (EpiChron and Denmark). ALI cases were confirmed when liver enzyme values met a definition by an international working group. RESULTS: Overall PPVs (95% CIs) for the study ALI definitions were, for the primary ALI definition, 84% (60%-97%) (EpiChron), 60% (26%-88%) (SIDIAP), and 74% (60%-85%) (Denmark); for the secondary ALI definition, 65% (45%-81%) (EpiChron), 40% (19%-64%) (SIDIAP), and 70% (64%-77%) (Denmark); and for the tertiary ALI definition, 25% (18%-34%) (EpiChron), 8% (7%-9%) (SIDIAP), and 47% (42%-52%) (Denmark). The overall PPVs were higher for specific than for nonspecific codes and for hospital discharge than for outpatient codes. The nonspecific code "unspecified jaundice" had high PPVs in Denmark. CONCLUSIONS: PPVs obtained apply to patients using antidepressants without preexisting liver disease or ALI risk factors. To maximize validity, studies on ALI should prioritize hospital specific discharge codes and should include hospital codes for unspecified jaundice. Case validation is required when ALI outpatient cases are considered.

[Community-acquired pneumonia in patients with chronic obstructive pulmonary disease treated with inhaled corticosteroids or other bronchodilators. Study PNEUMOCORT]. / Neumonías adquiridas en la comunidad en pacientes con enfermedad pulmonar obstructiva crónica tratados con corticoides inhalados u otros broncodilatadores. Estudio PNEUMOCORT.

OBJECTIVES: To analyse the risk of pneumonia and/or exacerbations in patients with chronic obstructive pulmonary disease (COPD) who receive treatment with inhaled corticosteroids (CI), in comparison with those who are not treated with inhaled corticosteroids (NCI). To estimate the risk of pneumonia according to CI dose. DESIGN: Population-based cohort study. SETTING: Primary Healthcare. Institut Català de la Salut. PARTICIPANTS: Patients ≥45 years-old diagnosed with COPD between 2007 and 2009 in the Information System for Research in Primary Care (SIDIAP). INTERVENTION: Two cohorts; patients initiating CI and patients initiating bronchodilators after COPD diagnosis. MAIN MEASUREMENTS: Demographics, smoking, medical history, pneumonias, exacerbations, vaccinations, and drug therapy. RESULTS: A total of 3,837 patients were included, 58% in the CI and 42% in the NCI group. Higher incidence rates of pneumonia and exacerbations were detected in the CI group compared with the NCI (2.18 vs. 1.37). The risk of pneumonia and severe exacerbations was not significantly different between groups, HR; 1.17 (95% CI; 0.87-1.56) and 1.06 (95% CI; 0.87-1.31), respectively. Patients in the CI group had a higher risk of mild exacerbations, HR; 1.28 (95% CI; 1.10-1.50). Variables associated with a higher risk of pneumonia were age, diabetes, previous pneumonias and bronchitis, very severe COPD, treatment with low doses of ß2-adrenergic or anticholinergic agents, and previous treatment with oral corticosteroids. CONCLUSIONS: There were no differences between cohorts in the risk of pneumonia and severe exacerbations. The risk of mild exacerbations was higher in the CI group. Pneumonias and severe exacerbations were more frequent in patients with severe COPD and in patients receiving high doses of CI.

The prevalence of narcolepsy in Catalunya (Spain).

Previous studies have estimated an overall prevalence for narcolepsy between 15 and 70 cases per 100 000 inhabitants. We aimed to estimate the prevalence of narcolepsy in Catalunya (Catalonia), a north-east region of Spain (7 424 754 inhabitants), on 31 December 2014 by identifying all living subjects diagnosed with narcolepsy. First, we identified patients diagnosed by one of the 13 sleep, paediatric or neurological departments that perform tests regularly to diagnose narcolepsy. In a second phase, we searched for additional patients with narcolepsy in a clinical database of the primary health-care system. Clinical files were reviewed and narcolepsy diagnosis validated according to the Brighton Collaboration case definitions. Three hundred and twenty-five patients had a validated diagnosis of narcolepsy in the specialized centres (mean age: 44.6 years, range: 6-89; male: 60.3%; 85% with narcolepsy type 1), including 17.8% cases in Brighton, definition level 1, 62.5% in level 2, 15.4% in level 3 and 4.3% in level 4a. The overall prevalence for narcolepsy was 4.4; 3.7 for narcolepsy type 1 and 0.7 cases per 100 000 inhabitants for narcolepsy type 2. Fifty-six additional narcoleptic patients were identified in the primary health-care system, increasing the overall prevalence to 5.2 cases per 100 000 inhabitants. Prevalence rates for narcolepsy type 1 increased from childhood to adulthood, but in subjects aged more than 50 years there was a substantial drop in prevalence rates, suggesting the presence of a significant pool of undiagnosed cases in this population. Narcolepsy can be considered a rare neurological disorder in Catalunya.

Safety of cilostazol in peripheral artery disease: a cohort from a primary healthcare electronic database.

BACKGROUND: Cilostazol has been associated with spontaneous reports of cardiovascular adverse events and serious bleeding. The objective of this study is to determine the relative risk of cardiovascular adverse events or haemorrhages in patients with peripheral artery disease treated with cilostazol in comparison to pentoxifylline users. METHODS: Population-based cohort study including all individuals older than 40 who initiated cilostazol or pentoxifylline during 2009-2011 in SIDIAP database. The two treatment groups were matched through propensity score (PS). RESULTS: Nine thousand one hundred twenty-nine patients met inclusion criteria and after PS matching, there were 2905 patients in each group. 76% of patients were men, with similar mean ages in both groups (68.8 for cilostazol and 69.4 for pentoxifylline). There were no differences in bleeding, cerebrovascular and cardiovascular events between both groups. CONCLUSIONS: Patients treated with cilostazol were different from those treated with pentoxifylline at baseline, so they were matched through PS. We did not find differences between treatment groups in the incidence of bleeding or cardiovascular and cerebrovascular events. Cilostazol should be used with precaution in elderly polymedicated patients.

Effectiveness of risk minimization measures for the use of cilostazol in United Kingdom, Spain, Sweden, and Germany.

PURPOSE: The purpose of the study is to evaluate the effectiveness of risk minimization measures-labeling changes and communication to health care professionals-recommended by the European Medicines Agency for use of cilostazol for the treatment of intermittent claudication in Europe. METHODS: Observational study of cilostazol in The Health Improvement Network (United Kingdom), EpiChron Cohort (Spain), SIDIAP (Spain), Swedish National Databases, and GePaRD (Germany). Among new users of cilostazol, we compared the prevalence of conditions targeted by the risk minimization measures in the periods before (2002-2012) and after (2014) implementation. Conditions evaluated were prevalence of smoking, cardiovascular conditions, concurrent use of ≥2 antiplatelet agents, concurrent use of potent CYP3A4/CYP2C19 inhibitors and high-dose cilostazol, early monitoring of all users, and continuous monitoring of users at high cardiovascular risk. RESULTS: We included 22 593 and 1821 new users of cilostazol before and after implementation of risk minimization measures, respectively. After implementation, the frequency of several conditions related to the labeling changes improved in all the study populations: prevalence of use decreased between 13% (EpiChron) and 57% (SIDIAP), frequency of cardiovascular contraindications decreased between 8% (GePaRD) and 84% (EpiChron), and concurrent use of high-dose cilostazol and potent CYP3A4/CYP2C19 inhibitors decreased between 6% (Sweden) and 100% (EpiChron). The frequency of other conditions improved in most study populations, except smoking, which decreased only in EpiChron (48% reduction). CONCLUSIONS: This study indicates that the risk minimization measures implemented by the EMA for the use of cilostazol have been effective in all European countries studied, except for smoking cessation before initiating cilostazol, which remains an area of improvement.

Efficacy and safety of topical application of 15% and 10% potassium hydroxide for the treatment of Molluscum contagiosum.

BACKGROUND/OBJECTIVES: Molluscum contagiosum is the most common skin infection in children. One topical treatment used for Molluscum contagiosum is potassium hydroxide. The objective of this study was to compare the efficacy of potassium hydroxide topical treatment at different concentrations with that of placebo in terms of complete clearing of Molluscum contagiosum lesions and to assess the safety and tolerance of potassium hydroxide topical treatment. METHODS: This was a double-blind randomized clinical trial of three treatments (potassium hydroxide 10%, potassium hydroxide 15%, placebo) applied once daily up to complete clearing of lesions (maximum duration 60 days) in 53 children aged 2-6 years in primary health care pediatric offices in Catalonia, Spain. RESULTS: In the intention-to-treat analysis, potassium hydroxide 10% (58.8%, P = .03) and potassium hydroxide 15% (64.3%, P = .02) had efficacy superior to that of placebo (18.8%). The number of Molluscum contagiosum lesions was significantly reduced with potassium hydroxide 10% and 15%. The main efficacy outcome was achieved in 58.8% of children in the potassium hydroxide 10% group (P = .03 vs placebo) and in 64.3% of children in the potassium hydroxide 15% group (P = .02 vs placebo). Potassium hydroxide 10% and 15% were not significantly different in efficacy from each other. Potassium hydroxide 10% and placebo were better tolerated than potassium hydroxide 15%. No adverse events were reported during the study period. CONCLUSIONS: Potassium hydroxide 10% and 15% demonstrated high rates of efficacy in clearing Molluscum contagiosum lesions, with potassium hydroxide 10% being better tolerated.

Dabigatran and vitamin K antagonists' use in naïve patients with non-valvular atrial fibrillation: a cross-sectional study of primary care-based electronic health records.

PURPOSE: The purpose of this study was to characterize the profile of patients with non-valvular atrial fibrillation who start an anticoagulant treatment after diagnosis with dabigatran and compare it with those who start with vitamin K antagonists (VKAs). METHODS: We analysed primary health care-based electronic health records data from 15,075 people with new diagnosis of atrial fibrillation who initiated treatment with dabigatran or VKA spanning 2011-2013. Logistic regression analysis for determination of factors associated with initiation of dabigatran was performed. RESULTS: We identified 14,266 (94.6%) people who initiated VKA and 809 (5.4%) who initiated dabigatran. Mean age of people treated with dabigatran was lower than in VKA patients (73.7 vs 75.5 years, p < 0.001). People (90.5%) in VKA group and 83.6% in the dabigatran group had a high risk of stroke, according to CHA2DS2VASc score. There was higher proportion of people with hypertension, diabetes mellitus, dyslipidaemia, and chronic kidney disease among people treated with VKA. The proportion of people with a history of cerebral haemorrhage and stroke was higher among dabigatran patients compared with VKA patients (1.4 vs 0.6%, p = 0.015 and 14.0% vs 10.8%, p = 0.006, respectively). Multivariable logistic model showed that treatment with dabigatran was associated with male sex, history of stroke and Mortalidad en áreas pequeñas Españolas y Desigualdades Socioeconómicas index. CONCLUSIONS: Most patients recently diagnosed with non-valvular atrial fibrillation initiated treatment with VKA. Primary healthcare patients with non-valvular atrial fibrillation initiating dabigatran are younger, had a lower risk of stroke or bleeding, fewer comorbidity and more history of stroke and intracranial haemorrhage compared to those who were initiated on VKA.

Effectiveness and safety of drugs used for stroke prevention in a cohort of non-valvular atrial fibrillation patients from a primary care electronic database.

PURPOSE: The aim of this study was to assess effectiveness and safety of antithrombotics for stroke prevention in non-valvular atrial fibrillation in real-use conditions. METHODS: We used a population-based retrospective cohort study. Information emerges from SIDIAP, a database containing anonymized information from electronic health records from 274 primary healthcare centres of the Catalan Health Institute, Catalonia (Spain), with a reference population of 5 835 000 people. Population includes all adults with a new diagnosis of non-valvular atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of antithrombotics' effectiveness was stroke. The main outcomes of safety were cerebral and gastrointestinal haemorrhages. We also estimated all-cause mortality. We used multivariable Cox proportional hazard models to examine association between antithrombotic treatment and main outcomes. RESULTS: We included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence interval (CI), 0.58-0.91), also seen in patients with CHADS2 ≥ 2, HR 0.65 (95%CI, 0.49-0.86), and CHA2 DS2 -VASc ≥ 2, HR 0.66 (95%CI, 0.52-0.84). We observed a higher risk of digestive bleeding with antiplatelets, HR 1.32 (95%CI, 1.01-1.73). Both VKA and antiplatelets were associated with reduction of all-cause mortality risk; HR 0.55 (95%CI, 0.49-0.62) and HR 0.89 (95%CI, 0.80-0.97), respectively. CONCLUSIONS: This study found a stroke-risk reduction associated with VKA and an increased risk of gastrointestinal bleeding associated with platelet-aggregation inhibitors in comparison with untreated patients. Both antithrombotic groups showed a reduction in all-cause mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Characterization of new users of cilostazol in the UK, Spain, Sweden, and Germany.

PURPOSE: To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. METHODS: New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing. RESULTS: We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. CONCLUSIONS: In this collaborative European study, most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events. © 2017 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

Treatment of hypertension during pregnancy: a cohort of pregnancy episodes from the SIDIAP database, Catalonia, Spain.

Introduction: Hypertension during pregnancy is one of the most frequent causes of maternal and fetal morbimortality. Perinatal and maternal death and disability rates have decreased by 30%, but hypertension during pregnancy has increased by approximately 10% in the last 30 years. This research aimed to describe the pharmacological treatment and pregnancy outcomes of pregnancies with hypertension. Methods: We carried out an observational cohort study from the Information System for the Development of Research in Primary Care (SIDIAP) database. Pregnancy episodes with hypertension (ICD-10 codes for hypertension, I10-I15 and O10-O16) were identified. Antihypertensives were classified according to the ATC WHO classification: ß-blocking agents (BBs), calcium channel blockers (CCBs), agents acting on the renin-angiotensin system (RAS agents), diuretics, and antiadrenergic agents. Exposure was defined for hypertension in pregnancies with ≥2 prescriptions during the pregnancy episode. Descriptive statistics for diagnoses and treatments were calculated. Results: In total, 4,839 pregnancies with hypertension diagnosis formed the study cohort. There were 1,944 (40.2%) pregnancies exposed to an antihypertensive medication. There were differences in mother's age, BMI, and alcohol intake between pregnancies exposed to antihypertensive medications and those not exposed. BBs were the most used (n = 1,160 pregnancy episodes; 59.7%), followed by RAS agents (n = 825, 42.4%), and CCBs were the least used (n = 347, 17.8%). Discussion: Pregnancies involving hypertension were exposed to antihypertensive medications, mostly BBs. We conduct a study focused on RAS agent use during pregnancy and its outcomes in the offspring.

Drug Exposure During Pregnancy: A Case-Control Study from a Primary Care Database.

Objective: Drug exposure during pregnancy is frequent, even more during first trimester as pregnant women might not be aware of their condition. We used available electronic health records (EHRs) to describe the use of medications during the first trimester in pregnant women and to compare drug exposure between those women who had an abortion (either elective or spontaneous) compared to those who had live births. Materials and Methods: Case-control study of abortions, either elective or spontaneous (cases), and live birth pregnancies (controls) in Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (Catalan Primary Health electronic health records) from 2012 to 2020. Exposure to drugs during first trimester of pregnancy was considered to estimate the association with abortion by conditional logistic regression and adjusted by health conditions and other drugs exposure. Results: Sixty thousand three hundred fifty episodes of abortions were matched to 118,085 live birth pregnancy episodes. Cases had higher rates of alcohol intake (9.9% vs. 7.2%, p < 0.001), smoking (4.5% vs. 3.6%, p < 0.001), and previous abortions (9.9% vs. 7.8%, p < 0.001). Anxiety (30.3% and 25.1%, p < 0.001), respiratory diseases (10.6% and 9.2%, p < 0.001), and migraine (8.2% and 7.3%, p < 0.001), for cases and controls, respectively, were the most frequent baseline conditions. Cases had lower rate of drug exposure, 40,148 (66.5%) versus 80,449 (68.1%), p < 0.001. Association with abortion was found for systemic antihistamines (adjusted odds ratio [ORadj] 1.23, 95% confidence interval [CI] 1.19-1.27), antidepressants (ORadj 1.11, 95% CI 1.06-1.17), anxiolytics (ORadj 1.31, 95% CI 1.26-1.73), and nonsteroidal anti-inflammatory drugs (ORadj 1. 63, 95% CI 1.59-1.67). Conclusions: These high rates of drug exposures during the first trimester of pregnancy highlights the relevance of informed prescription to women with childbearing potential.

Risk of psychiatric events in women treated with isotretinoin: a self-controlled study with SIDIAP database.

BACKGROUND: Since isotretinoin marketing, reports of psychiatric events have been noted. Howeverto date, a relation between these events and acne or isotretinoin treatment has not been clearly established. Our objective was to analyze the incidence of psychiatric events in women receiving isotretinoin. METHODS: Self-controlled study including women treated with isotretinoin from July 2014 to December 2018. Data source was SIDIAP, a primary health care-based database from Catalonia, Spain. Risk of psychiatric events was analyzed during the isotretinoin exposure and during the previous and posterior periods of non-exposure. RESULTS: We included 4,738 women in the study, 25.3% of them had history psychiatric disorders prior to receiving isotretinoin. During the follow-up, 782 (16.5%) patients were diagnosed with new mental disorders and 925 (19.5%) received new psychotropic drug prescriptions. We found a trend to an increase of new events when the previous non-exposure and the isotretinoin exposure periods were compared, with no significant differences. Incident psychiatric events during isotretinoin exposure was significantly higher in those patients with previous psychiatric history. CONCLUSIONS: We cannot conclude any causality between acne and isotretinoin and the appearance of new psychiatric events. However, we contribute to the evidence with a more robust methodological approach, which minimizes the effect of confounding variables.

Sex and gender differences in the use of oral anticoagulants for non-valvular atrial fibrillation: A population-based cohort study in primary health care in catalonia.

Objectives: To describe the sex and gender differences in the treatment initiation and in the socio-demographic and clinical characteristics of all patients initiating an oral anticoagulant (OAC), and the sex and gender differences in prescribed doses and adherence and persistence to the treatment of those receiving direct oral anticoagulants (DOAC). Material and methods: Cohort study including patients with non-valvular atrial fibrillation (NVAF) who initiated OAC in 2011-2020. Data proceed from SIDIAP, Information System for Research in Primary Care, in Catalonia, Spain. Results: 123,250 people initiated OAC, 46.9% women and 53.1% men. Women were older and the clinical characteristics differed between genders. Women had higher risk of stroke than men at baseline, were more frequently underdosed with DOAC and discontinued the DOAC less frequently than men. Conclusion: We described the dose adequacy of patients receiving DOAC, finding a high frequency of underdosing, and significantly higher in women in comparison with men. Adherence was generally high, only with higher levels in women for rivaroxaban. Persistence during the first year of treatment was also high in general, being significantly more persistent women than men in the case of dabigatran and edoxaban. Dose inadequacy, lack of adherence and of persistence can result in less effective and safe treatments. It is necessary to conduct studies analysing sex and gender differences in health and disease.