Risk of thrombotic events and other complications in anticoagulant users infected with SARS‑CoV‑2: an observational cohort study in primary health care in SIDIAP (Catalonia, Spain)

COVID-19; Anticoagulants orals; Esdeveniments trombòtics; Atenció primàriaCOVID-19; Oral anticoagulants; Thrombotic events; Primary health careCOVID-19; Anticoagulantes orales; Eventos trombóticos; Atención primariaBackground: The risk of thromboembolic events and COVID-19 complications in anticoagulated patients once hos‑ pitalized has been widely analyzed. We aim to assess these outcomes in primary health care (PHC) patients chronically treated with oral anticoagulants (OAC) in comparison with non-treated. Methods: Cohort study including adults with COVID-19 diagnosis in the PHC records in Catalonia, Spain; from March to June 2020. Patients were matched between exposed and non-exposed to OAC based on age and gender in a 1:2 design. Data source is the Information System for Research in Primary Care (SIDIAP). Results: We included 311,542 individuals with COVID-19. After propensity score matching, we obtained a cohort of 20,360 people, 10,180 exposed and 10,180 non-exposed to OAC. Their mean age was 79.9 and 52.1% were women. Patients exposed to OAC had a higher frequency of comorbidities than non-exposed. Anticoagulated patients had a higher risk of hospital admission (IRR 1.16, 95% CI 1.03–1.29), and of stroke and pulmonary embolism than nonanticoagulated (IRR 1,80, 95% CI 1.06–3.06). The risk of pneumonia was not diferent between groups (IRR 1.04, 95% CI 0.84–1.30). We found a lower risk of death in patients exposed to OAC (IRR 0.60, 95% CI 0.55–0.65). Conclusions: OAC users in our study had more comorbidities and were older than non-users, well known risks for hospitalization being confrmed with our results. We also found in our study that OAC exposure was not associated to an increased risk in the mortality rate, and it was associated with higher risks of hospital admission and thrombo‑ embolic events, although we cannot assess the efect of the interventions applied during hospital admission on the outcomes studied, as our database is a PHC database

Automatic Estimation of the Most Likely Drug Combination in Electronic Health Records Using the Smooth Algorithm: Development and Validation Study

Electronic health records; Data mining; Drug combinationRegistres sanitaris electrònics; Mineria de dades; Combinació de fàrmacsRegistros electrónicos de salud; Procesamiento de datos; Combinación de fármacosBackground: Since the use of electronic health records (EHRs) in an automated way, pharmacovigilance or pharmacoepidemiology studies have been used to characterize the therapy using different algorithms. Although progress has been made in this area for monotherapy, with combinations of 2 or more drugs the challenge to characterize the treatment increases significantly, and more research is needed. Objective: The goal of the research was to develop and describe a novel algorithm that automatically returns the most likely therapy of one drug or combinations of 2 or more drugs over time. Methods: We used the Information System for Research in Primary Care as our reference EHR platform for the smooth algorithm development. The algorithm was inspired by statistical methods based on moving averages and depends on a parameter Wt, a flexible window that determines the level of smoothing. The effect of Wt was evaluated in a simulation study on the same data set with different window lengths. To understand the algorithm performance in a clinical or pharmacological perspective, we conducted a validation study. We designed 4 pharmacological scenarios and asked 4 independent professionals to compare a traditional method against the smooth algorithm. Data from the simulation and validation studies were then analyzed. Results: The Wt parameter had an impact over the raw data. As we increased the window length, more patient were modified and the number of smoothed patients augmented, although we rarely observed changes of more than 5% of the total data. In the validation study, significant differences were obtained in the performance of the smooth algorithm over the traditional method. These differences were consistent across pharmacological scenarios. Conclusions: The smooth algorithm is an automated approach that standardizes, simplifies, and improves data processing in drug exposition studies using EHRs. This algorithm can be generalized to almost any pharmacological medication and model the drug exposure to facilitate the detection of treatment switches, discontinuations, and terminations throughout the study period

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. (C) 2020 The Authors. Published by Elsevier Espana, S.L.U

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

© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/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 9,105 (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.Peer ReviewedPostprint (author's final draft

Pharmacological treatment of the heart failure according to the ventricular ejection fraction in primary care

Insuficiencia cardíaca; Función ventricular; Tratamiento farmacológico; Atención primaria de saludInsuficiència cardíaca; Funció ventricular; Tractament farmacològic; Atenció primària de salutHeart failure; Ventricular function; Pharmacotherapy; Primary health careDespite 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 β 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.Objetivo: Aunque se dispone de mejores diagnósticos y tratamientos, la insuficiencia cardíaca (IC) es una causa importante de muerte en Espana. El objetivo de este estudio es describir el tratamiento y las características de la población con IC crónica, clasificada según la fracción de eyección del ventrículo izquierdo (FEVI). Diseno: Estudio observacional de cohortes de base poblacional en atención primaria (AP). Emplazamiento: Cataluna, 2014-2018. Participantes: Se incluyeron pacientes adultos con diagnóstico incidente de IC clasificada según la FEVI. Intervención: Análisis de los datos de salud registrados en la base de datos Sistema de Información para el Desarrollo de la Investigación en AP (SIDIAP). Variables principales: Demográficas, FEVI, comorbilidades y uso de fármacos para la IC. Resultados: Se incluyeron 10.130 pacientes; el 18,9% con FEVI < 40 (ICFEr), el 15,9% con FEVI 40-49 (ICFEi) y el 65,2% con FEVI ≥ 50 (ICFEp), este último grupo con mayor proporción de mujeres (57,5%) y una mayor edad media (80,2 anos). La población con ICFEi era similar a la de ICFEr en edad, género, comorbilidades o tratamiento. Las comorbilidades más frecuentes eran la hipertensión (78.3%), la dislipemia (54%) y la fibrilación auricular (41,5%). Los tratamientos más frecuentes fueron los -bloqueantes, con diferencias según la FEVI (FEVIr 1.515 [79,2%], FEVIi 1.142 [70,8%] y FEVIp 3.371 [51,0%]), seguido de los diuréticos de asa (65,7%). Conclusiones: El tratamiento farmacológico de la IC varía en función de la FEVI. El tratamiento y las características poblacionales de los pacientes con ICFEi son similares a aquellos con ICFEr

Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis : a study protocol of an open randomised clinical trial in primary care

Introduction Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis. Methods and analysis This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 μg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence. Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit. Ethics and dissemination The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals. Trial registration number NCT03738917; Pre-results

Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis: a study protocol of an open randomised clinical trial in primary care

Introduction: Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis. Methods and analysis: This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 µg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence. Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit. Ethics and dissemination: The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals. Trial registration: number NCT03738917; Pre-results

From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

In 2019, the Innovative Medicines Initiative (IMI) funded the ConcePTION project—Building an ecosystem for better monitoring and communicating safety of medicines use in pregnancy and breastfeeding: validated and regulatory endorsed workflows for fast, optimised evidence generation—with the vision that there is a societal obligation to rapidly reduce uncertainty about the safety of medication use in pregnancy and breastfeeding. The present paper introduces the set of concepts used to describe the European data sources involved in the ConcePTION project and illustrates the ConcePTION Common Data Model (CDM), which serves as the keystone of the federated ConcePTION network. Based on data availability and content analysis of 21 European data sources, the ConcePTION CDM has been structured with six tables designed to capture data from routine healthcare, three tables for data from public health surveillance activities, three curated tables for derived data on population (e.g., observation time and mother-child linkage), plus four metadata tables. By its first anniversary, the ConcePTION CDM has enabled 13 data sources to run common scripts to contribute to major European projects, demonstrating its capacity to facilitate effective and transparent deployment of distributed analytics, and its potential to address questions about utilization, effectiveness, and safety of medicines in special populations, including during pregnancy and breastfeeding, and, more broadly, in the general population

Lactic acidosis associated with metformin in patients with moderate to severe chronic kidney disease : Study protocol for a multicenter population-based case-control study using health databases

Background: The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis. However, the information available in patients with moderate-severe chronic kidney disease is scarce. Methods: The ALIMAR-C2 study is a case-control study to assess the association between metformin and lactic acidosis in patients with type 2 diabetes mellitus and moderate-severe chronic kidney disease. The study will be performed with computerized registered electronic health records from eight Spanish hospitals linked to their corresponding primary care health areas from 2010 to 2016, comprising approximately 22.1 million person-years of follow-up. Logistic regression will be used to assess the crude and adjusted risk of lactic acidosis associated with metformin use overall and stratifying by use and dose categories, and chronic kidney disease stage. The overall case fatality rate of lactic acidosis, as well as the case fatality rate stratified by chronic kidney disease stage, will be calculated. Discussion: The ALIMAR-C2 study will provide useful information about the risk of lactic acidosis in type 2 diabetes mellitus patients with renal impairment using metformin