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

The use and adherence of oral anticoagulants in Primary Healthcare in Catalunya: a real-world data cohort study

Background The use of direct oral anticoagulants (DOAC) for stroke prevention in non-valvular atrial fibrillation (NVAF) has not been previously assessed in our setting. 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. Methods Population-based cohort study including all NVAF adult patients initiating OAC for stroke prevention in August 2013-December 2015. Persistence was measured in patients initiating OAC in August 2013-December 2014. Data source is SIDIAP, which captures electronic health records from Primary Health Care in the Catalan Health Institute, covering approximately 5.8 million people. Results 51,690 NVAF patients initiated OAC; 47,197 (91.3%) were naive to OAC and 32,404 initiated acenocoumarol (62.7%). 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. 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 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.Preprin

Análisis bibliométrico de la autoría femenina en artículos originales en la revista Atencion Primaria

Atenció primària de salut; Autories; Bibliometria; Distribució per sexe; Diferència de gèneresAtención primaria de salud; Autorías; Bibliometría; Distribución por sexo; Sesgo de génerosPrimary health care; Authorship; Bibliometrics; Gender distribution; Gender biasObjetivos: Determinar el porcentaje de autorías femeninas en artículos originales publicados durante dos períodos en la revista “Atención Primaria” y evaluar si existen diferencias entre categorías de autoría (primera, última autora y coautora) entre ambos. Diseño: Estudio transversal Emplazamiento: Producción científica femenina publicada durante 2007-08 y 2017-18. Participantes: Centrado en los artículos originales. Mediciones principales: Se recogieron en un formulario “ad hoc” las variables: género en base al nombre del autor/a, número total de mujeres y hombres que figuraban como autores/as y orden de autoría. Se calcularon las frecuencias absolutas y relativas y se utilizó la prueba del ji-cuadrado para determinar la evolución de los porcentajes por tipo de autoría y género. Resultados: Se analizaron un total de 108 artículos en el período 2007-08 y 100 en el 2017-18. No se observaron diferencias estadísticamente significativas entre el promedio de autoras y autores dentro y entre los períodos. En 2007-08 se identificaron un total de 548 autorías y en 2017-18 540, el porcentaje de autoras fue del 48,7% y del 54,4% respectivamente. Únicamente se observó un aumento del porcentaje de primeras autoras interperíodo. Conclusiones: Prácticamente una de cada dos autorías de artículos originales publicados en la revista “Atención Primaria” era femenina. Asimismo, se observó un incremento significativo en el porcentaje de primeras autoras entre ambos períodos. No obstante, y a pesar del mayor número de trabajadoras sanitarias, las últimas autoras se mantienen sin cambios, lo que apunta a la persistencia de infrarrepresentatividad femenina.Objectives: To determine the percentage of female authors in original articles published during 2 periods, 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 2 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 2 authors 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 2 periods. 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

Linaclotide utilization and potential for off-label use and misuse in three European countries

INTRODUCTION Linaclotide is approved for adults with moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C). Linaclotide is not indicated for weight loss or for patients with inflammatory bowel disease (IBD); it is contraindicated in patients with mechanical bowel obstruction (MBO). Some patients with obesity or eating disorders (ED) may use linaclotide off-label for weight loss or as a laxative. OBJECTIVES To describe the use of linaclotide in clinical practice, including patients with potential for off-label use or misuse. METHODS Post-authorization safety study conducted in three databases from the linaclotide launch date to 2017: the Clinical Practice Research Datalink in the United Kingdom (UK), the Information System for Research in Primary Care database in Spain and the linked Patient, Prescription and Causes of Death Registries in Sweden. Cohorts of patients were identified as having IBS using diagnostic and treatment codes; IBS subtypes were identified using symptoms and treatment codes; patients with obesity, ED, MBO, and IBD were identified using diagnostic codes or body mass index. RESULTS There were 1319, 1981, and 5081 linaclotide users from the United Kingdom, Spain, and Sweden with a median age of 45, 57, and 51 years, respectively; most were females. In the United Kingdom, Spain, and Sweden, respectively: 59.0%, 60.3%, and 31.3% of linaclotide users had an IBS diagnosis recorded, and among those, 68.8%, 61.3%, and 92.7% were classified as IBS-C. The proportions of linaclotide users considered at risk for potential off-label use for weight loss or as a laxative were 17.1%, 29.7%, and 1.7%, and the proportions of users considered at risk of misuse due to a history of MBO or IBD were 3.5%, 4.6%, and 5.7% in the United Kingdom, Spain, and Sweden, respectively. CONCLUSIONS Potential linaclotide off-label use and misuse appears limited, as evidenced by the small sizes of the patient subgroups at risk for off-label use and misuse

Determinantes del consumo de antidepresivos en varios países europeos. Fracción atribuible poblacional del uso de antidepresivos en la fractura de cadera

La depresión se calcula se convertirá en la segunda causa de incapacidad calculada en años de vida ajustados por discapacidad en el año 2020. Los antidepresivos son fármacos que han demostrado ser eficaces en el tratamiento de la depresión. Su consumo ha experimentado un importante crecimiento en las últimas décadas. Se ha debatido a cerca de su posible uso excesivo y de los riesgos asociados a su utilización, lo que hace necesaria una adecuada valoración beneficio riesgo. El objetivo de esta tesis era determinar si existían diferencias en el consumo de fármacos antidepresivos en diversos países europeos, situados en el Norte y el Sur de Europa. Tras realizar una visión global del consumo de antidepresivos en Dinamarca, Noruega, Suecia, Cataluña y Véneto estudiamos cómo se distribuía el consumo de los mismos por edad y sexo y también según los principales grupos de antidepresivos y los distintos principios activos de cada subgrupo. Quisimos profundizar en qué posibles determinantes podrían estar relacionados con el consumo de antidepresivos desde un punto de vista económico, sociodemográfico, sanitario y cultural, en cada uno de los cinco países de estudio y en global con el consumo de antidepresivos en los países. Por último hemos querido determinar el impacto en la población que podría tener el consumo de los antidepresivos respecto a la fractura de cadera en 5 países europeos, en este caso en vez de datos de la región italiana del Véneto, los datos fueron de la provincia italiana de Caserta. Para conseguir estos tres objetivos, durante los 4 años de desarrollo de la tesis obtuvimos datos de consumo de antidepresivos y de los usuarios de estos fármacos directamente de web de bases de datos de cada uno de los países nórdicos. En el caso de Cataluña, Véneto y Caserta nos fueron proporcionados los datos por los proveedores de las correspondientes bases de datos. Estudiamos la posible relación que podrían tener variables económicas, sociodemográficas, sanitarias y culturales con el consumo de los fármacos antidepresivos en cada uno de estos países y si, de manera global, podíamos establecer una relación del consumo con las variables estudiadas. Para la estimación del porcentaje de las fracturas de cadera que podrían ser debidas al uso de antidepresivos obtuvimos el número de usuarios de antidepresivos en cada país y utilizamos el riesgo relativo calculado en un meta-análisis previamente publicado para realizar el cálculo de esta estimación, denominada Fracción Atribuible Poblacional. Los resultados obtenidos mostraron que no había claras diferencias en el consumo de antidepresivos entre el Norte y Sur de Europa, al obtener resultados más similares entre Dinamarca, Suecia y Cataluña (mayor consumo) y un consumo menor para Noruega y Véneto. La prevalencia de exposición a antidepresivos aumentaba con la edad y fue mayor en mujeres que en hombres. El análisis intra-países mostró que el desempleo y la tasa de psiquiatras estaba relacionado con el consumo de antidepresivos de manera estadísticamente significativa. En el análisis ajustado por los determinantes (gasto farmacéutico y médicos generales) que demostraron una fuerte correlación con el uso de antidepresivos a nivel entre-países fueron dos de las seis dimensiones culturales descritas por Hofstede las que mostraron su relación con el consumo de antidepresivos: la Orientación a largo plazo en sentido positivo y la Masculinidad en sentido inverso. Resultó de la estimación de la fracción atribuible poblacional que un porcentaje no despreciable de las fracturas de cadera podrían ser debidas al consumo de fármacos antidepresivos en Dinamarca, Noruega, Suecia, Cataluña y Caserta, aunque ésta fue mucho menor para el grupo de los antidepresivos tricíclicos que para los inhibidores selectivos de la recaptación de serotonina.Depression is calculated to become the second cause of disability expressed in disability adjusted life years in 2020. Antidepressants are drugs that have proven to be effective for the treatment of depression. Antidepressants use has increased in the last decades. A debate about their excessive use and the risks associated with their consumption has made the benefit risk assessment a major. The aim of this thesis was to determine if there were differences in the use of antidepressants among countries from the North and the South of Europe. After a whole vision of the consumption of antidepressants in Denmark, Norway, Sweden, Catalonia and Veneto we studied how they were distributed by sex and age and also by principal groups of antidepressants and different principle substances. We investigated further which determinants could be related with the antidepressant use from an economic, sociodemographic, health and cultural point of view in each of the five European countries and with antidepressants consumption globally. For the last we estimated the impact on the population that the use of antidepressants in 5 European countries could have in hip fracture, for this las objective we used data from Caserta province (Italy) instead of Veneto region. To achieve these objectives, during the four years carrying out this thesis, data of the consumption of antidepressants and of their users were obtained from the web pages of each Nordic country. For Catalonia, Veneto and Caserta the data were provided after request. We studied the possible correlation that economic, sociodemographic, health and cultural variables could have with the antidepressant use with in these countries and between them. To estimate the percentage of hip fractures that could be due to the use of antidepressants we obtained the number of antidepressants users in each country and with the relative risk of a meta-analysis already published we calculated the population attributable risk. The results showed no differences in the consumption of antidepressants between the North and South of Europe, as Denmark, Sweden and Catalonia showed a higher consumption than Norway and Veneto, The prevalence of antidepressant use was higher with age and in women. The with-in countries showed that unemployment and psychiatrist rate were statistically significant related with the antidepressant use. The adjusted relation by the determinants (pharmaceutical expenditure and general practitioners) that have showed a strong correlation in the between-countries showed a correlation with two of the six cultural dimensions described by Hofstede: Long time orientation in a positive sense and Masculinity in a negative one. After calculating the population attributable fraction a not depreciable number of hip fractures could be due to antidepressants consumption in Denmark, Norway, Sweden, Catalonia and Caserta, but this estimation was much lower for the tricyclic group than for the serotonin selective reuptake inhibitors one. The prevalence of exposure to antidepressants increased with age and it was higher in women, so also the population attributable fraction