Dolores Montero

Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study

Abstract Objective: To examine the association between selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding. Design: Population based case-control study. Setting: General practices included in the UK general practice research database. Subjects: 1651 incident cases of upper gastrointestinal bleeding and 248 cases of ulcer perforation among patients aged 40 to 79 years between April 1993 and September 1997 and 10 000 controls matched for age, sex, and year that the case was identified. Interventions: Review of computer profiles for all potential cases, and an internal validation study to confirm the accuracy of the diagnosis on the basis of the computerised information. Main outcome measures: Current use of selective serotonin reuptake inhibitors or other antidepressants within 30 days before the index date. Results: Current exposure to selective serotonin reuptake inhibitors was identified in 3.1% (52 of 1651) of patients with upper gastrointestinal bleeding but only 1.0% (95 of 10 000) of controls, giving an adjusted rate ratio of 3.0 (95% confidence interval 2.1 to 4.4). This effect measure was not modified by sex, age, dose, or treatment duration. A crude incidence of 1 case per 8000 prescriptions was estimated. A small association was found with non-selective serotonin reuptake inhibitors (relative risk 1.4, 1.1 to 1.9) but not with antidepressants lacking this inhibitory effect. None of the groups of antidepressants was associated with ulcer perforation. The concurrent use of selective serotonin reuptake inhibitors with non-steroidal anti-inflammatory drugs increased the risk of upper gastrointestinal bleeding beyond the sum of their independent effects (15.6, 6.6 to 36.6). A smaller interaction was also found between selective serotonin reuptake inhibitors and low dose aspirin (7.2, 3.1 to 17.1). Conclusions: Selective serotonin reuptake inhibitors increase the risk of upper gastrointestinal bleeding. The absolute effect is, however, moderate and about equivalent to low dose ibuprofen. The concurrent use of non-steroidal anti-inflammatory drugs or aspirin with selective serotonin reuptake inhibitors greatly increases the risk of upper gastrointestinal bleeding.

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.

Hypnotic Drug Use in Spain: A Cross-Sectional Study Based on a Network of Community Pharmacies

OBJECTIVE: To investigate how hypnotic drugs are used in Spain, specifically, (1) to characterize the user population in some simple demographic (e.g., sex, age) and clinical (e.g., type of insomnia, type of physician who prescribed the drug) variables; (2) to estimate the proportion of long-term users (>3 mo); (3) to determine the frequency of different administration schedules; (4) to determine whether the kind of hypnotic drug prescribed according to the duration of its effect correlates with the type of sleep disorder or patient age; and (5) to compare the dosage used by the elderly with that used by adults. DESIGN: Cross-sectional pharmacy-based study. SETTING: A network of 318 community pharmacies throughout Spain. SUBJECTS: Patients (n = 5324) requesting a hypnotic drug for insomnia who agreed to take part in the study. MAIN OUTCOME MEASURES: Distribution of the use of hypnotic drugs by age, sex, type of insomnia, type of physician, specific hypnotic drug, daily dosage, treatment schedule, and duration of treatment. RESULTS: Women (67%) and the elderly (58%) constituted the largest subgroups in the sample. Difficulties in sleep onset and in sleep maintenance as single disorders were reported by 38% and 37% of users, respectively. Prescriptions were written by general practitioners in 80% of cases. Daily use was reported by 88% and long-term use (>3 mo) by 72% of the users. Long-term treatment was two- to threefold more frequent in the elderly than in middle-aged subjects. Intermediate-action hypnotic drugs were used by 59% of subjects, short-action drugs by 24%, and long-action drugs by 17%. The type of hypnotic drug prescribed was not related to the kind of sleep disorder or the age of patients. Specialists prescribed long-action hypnotic drugs more often than did general practitioners. No relevant differences were observed between dosages used by the elderly and those used by adults. In both groups the dosage taken by most patients, regardless of the drug, corresponded to the available strength. Substitution drugs for triazolam belonged to the intermediate-action class in 53% of the cases. CONCLUSIONS: Recommendations on hypnotic drug use are largely not followed in Spain. Most patients are taking hypnotic drugs daily, over long time periods, and without an adequate dosage titration according to age. Measures should be taken to correct this situation.

Estudio de la utilización de ticlopidina en oficinas de farmacia de España

Fundamento En 1997 se puso en marcha un programa dirigido a los prescriptores a fin de mejorar la utilizacion de ticlopidina. Se analiza si se alcanzo dicho objetivo. Pacientes y metodos Se realizo un estudio de corte transversal en oficinas de farmacia. Resultados De los 346 pacientes entrevistados, el 56% presentaban una indicacion de ticlopidina que no se encontraba entre las especificaciones de la ficha tecnica, el 23% utilizaban dosis diferentes de las recomendadas y solo el 28% se realizaron todos los analisis quincenales correspondientes. Conclusiones El uso de ticlopidina en Espana no es coherente con la ficha tecnica, y el programa disenado para mejorarlo no ha dado resultados satisfactorios.

Organization of Spanish Pharmacovigilance in the Multinational Situation: An Overview

The Spanish Pharmacovigilance System is a decentralized system that was developed in 1982. Today, there are 15 operational regional centers and a coordinating center that safeguards harmonization in working procedures. Health professionals and pharmaceutical companies are obliged to report suspected adverse drug reactions. All domestic reports, irrespective of reporter and sender, are individually evaluated and registered into the Farmacovigilancia Española-Datos de Reacciones Adversas (FEDRA) database. Over the last few years the number of reports received annually has reached a plateau between 5,000 and 6,000; the contribution of the pharmaceutical companies to spontaneous reporting, although increasing, represented only 7% of the reports in 1995. Approval of the European legislation has had a clear impact on the amount of information received and exchanged, which is obviously influencing the procedures of the Spanish Pharmacovigilance System. The enormous effort toward risk identification that Europe is performing should be followed, from the perspective of the Pharmacovigilance Unit, by the creation of networks for improving accuracy in risk estimation.

Trends in attention-deficit hyperactivity disorder medication use: a retrospective observational study using population-based databases

BACKGROUND The use of medications to treat attention deficit hyperactivity disorder (ADHD) has increased, but the prevalence of ADHD medication use across different world regions is not known. Our objective was to determine regional and national prevalences of ADHD medication use in children and adults, with a specific focus on time trends in ADHD medication prevalence. METHODS We did a retrospective, observational study using population-based databases from 13 countries and one Special Administrative Region (SAR): four in Asia and Australia, two in North America, five in northern Europe, and three in western Europe. We used a common protocol approach to define study populations and parameters similarly across countries and the SAR. Study populations consisted of all individuals aged 3 years or older between Jan 1, 2001, and Dec 31, 2015 (dependent on data availability). We estimated annual prevalence of ADHD medication use with 95% CI during the study period, by country and region and stratified by age and sex. We reported annual absolute and relative percentage changes to describe time trends. FINDINGS 154·5 million individuals were included in the study. ADHD medication use prevalence in 2010 (in children aged 3-18 years) varied between 0·27% and 6·69% in the countries and SAR assessed (0·95% in Asia and Australia, 4·48% in North America, 1·95% in northern Europe, and 0·70% in western Europe). The prevalence of ADHD medication use among children increased over time in all countries and regions, and the absolute increase per year ranged from 0·02% to 0·26%. Among adults aged 19 years or older, the prevalence of any ADHD medication use in 2010 varied between 0·003% and 1·48% (0·05% in Asia and Australia, 1·42% in North America, 0·47% in northern Europe, and 0·03% in western Europe). The absolute increase in ADHD medication use prevalence per year ranged from 0·0006% to 0·12%. Methylphenidate was the most commonly used ADHD medication in most countries. INTERPRETATION Using a common protocol and data from 13 countries and one SAR, these results show increases over time but large variations in ADHD medication use in multiple regions. The recommendations of evidence-based guidelines need to be followed consistently in clinical practice. Further research is warranted to describe the safety and effectiveness of ADHD medication in the short and long term, and to inform evidence-based guidelines, particularly in adults. FUNDING None.

Statins Use and Risk of Cataracts: Firm Conclusions Are Still Far Off

The authors analyzed 14 studies including both rando-mized and observational data and observed a significantdecreased risk of cataracts with statins use. Briefly, the authorsconcluded that ‘‘this meta-analysis indicates a clinically rele-vant protective effect in preventing cataracts (...), it includesall published reports on the topic and that the effect is consis-tent when analyzed from various aspects.’’ However, we wouldlike to reflect on some limitations that may impact on theresults presented by the authors.We acknowledge that systematic reviews and meta-analyses have become more widely accepted as a useful toolto critically assess the totality of evidence in a research ques-tion. When performed well and reported transparently, incor-porating explicit and detailed methods and results, theyproduce information that can have undoubtedly major impacton medical practice.

Uso de olmesartán en la prevención o retraso de la nefropatía diabética, algunas consideraciones

We read with great interest the scientific letter recently published in your journal by Consuegra-Sánchez et al. entitled ‘‘Increased mortality in patients with diabetes associated with olmesartan for the prevention/delay of microalbuminuria onset: a matter of concern?’’ The authors presented a meta-analysis of randomized clinical trials with placebo controls analyzing the combined effects of angiotensin-II receptor blockers (ARBs) on mortality in patients with type 2 diabetes mellitus. Without a doubt, this is an interesting study that showed the absence of allcause risk of mortality in the diabetic population being treated with ARBs, but we would like to make a few clarifications regarding the results presented. First, the title used poses a direct question regarding olmesartan, which invites reflection on the part of the reader, above all following the publication of the results from the Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study. However, the combination of the results from the 5 trials analyzed, which covered 4 different drugs (irbesartan, candesartan, losartan, and olmesartan) is insufficient to respond to such a question.

Sistema español de farmacovigilancia de las vacunas

En relación con el trabajo publicado por Sánchez-Ramón et al., titulado Alopecia universal en un adulto tras la vacunación de rutina con toxoide tetánico, relativo a un efecto adverso asociado a la vacunación antitetánica, nos gustarı́a realizar algunos comentarios. En España, al igual que en todos los paı́ses de nuestro entorno, las vacunas están sometidas a los mismos requerimientos que el resto de los medicamentos para su autorización de comercialización. Como cualquier medicamento, las vacunas se asocian a efectos adversos; algunos se conocen en el momento de su autorización y otros, por su menor frecuencia de aparición, una vez son comercializadas. Por tanto, la notificación de sospechas de reacciones adversas (RA) por los profesionales sanitarios, junto con su registro y análisis, es esencial para la identificación de posibles nuevos riesgos asociados a su uso. Esta materia supone la tarea principal del Sistema Español de Farmacovigilancia de Medicamentos de Uso Humano (SEFV-H), integrado por la Agencia Española de Medicamentos y Productos Sanitarios, los centros de farmacovigilancia de las Comunidades Autónomas y los profesionales sanitarios, sistema que cuenta ya con más de 25 años de trayectoria. La actividad principal del SEFV-H se basa, pues, en la notificación espontánea de sospechas de RA a los medicamentos, incluidas las vacunas. Los profesionales sanitarios que intervienen en la atención de la población vacunada deben remitir las sospechas de RA al centro de farmacovigilancia de su Comunidad Autónoma, utilizando un formato estándar que se conoce como «tarjeta amarilla». Una vez recibidas las notificaciones, los centros analizan la información y la integran en una base de datos común denominada FEDRA (Farmacovigilancia Española, Datos de Reacciones Adversas), que constituye una herramienta para la detección de posibles nuevos problemas de seguridad asociados a los medicamentos, incluidas las vacunas. En esta base de datos también se integran las sospechas de RA de las que han tenido conocimiento los laboratorios farmacéuticos, y las recogidas en estudios observacionales, otros programas y la literatura cientı́fica. Esto último es bien conocido por los editores de las revistas españolas, a quienes el SEFV-H ha solicitado que sigan las recomendaciones internacionales para publicar sospechas de RA y ası́ facilitar la detección de posibles duplicidades en la notificación de los casos. En España se recomienda que cuando una vacuna lleva poco tiempo comercializada se notifiquen, además de todas las sospechas de RA, cualquier acontecimiento ligado a la vacunación. Ası́ se recomendó, por ejemplo, durante la reciente campaña de vacunación de la gripe pandémica. En algunos paı́ses existen sistemas diferenciados para notificar las sospechas de RA asociadas a vacunas, como sucede en Canadá y en los EE.UU., con el sistema VAERS (Vaccine Adverse Event Reporting System), citado por los autores. La información recogida por el SEFV-H se integra con la del resto de paı́ses de la Unión Europea, en una base de datos gestionada por la Agencia Europea de Medicamentos. Con ello se pretende aumentar la eficiencia y rapidez en la identificación de posibles nuevos riesgos asociados a los medicamentos. Cuando se detecta un riesgo importante a través del análisis de las sospechas de RA y/o de otras fuentes de datos, se da a conocer a los profesionales sanitarios a través de las notas informativas e informes mensuales públicos de la Agencia Española de Medicamentos y Productos Sanitarios y a través de los boletines de los centros de farmacovigilancia de las Comunidades Autónomas, además de reflejarlos en la ficha técnica del medicamento (disponibles en la página web de la Agencia, www.aemps.gob.es). La farmacovigilancia es actualmente una de las prioridades de las agencias de regulación de medicamentos en Europa, y prueba de ello es la reciente publicación de una nueva legislación en este sentido, el Reglamento 1235/2010/UE y la Directiva 2010/84/UE, que incluyen aspectos novedosos, entre ellos facilitar la notificación de sospechas de RA por los ciudadanos y de hacer pública información sobre las sospechas de RA que se recogen. En el SEFV-H trabajamos para fomentar la notificación de sospechas de RA, mejorar los sistemas para detectar lo más precozmente posible nuevos aspectos que afecten a la seguridad de los medicamentos, e informar a los profesionales sanitarios y al público sobre todas estas cuestiones. En nuestra opinión, la eficiencia de este sistema no depende de que exista un programa diferente para la recogida de RA a vacunas, sino de la colaboración de todos en la vigilancia de su seguridad y efectividad. Un reto para todos los profesionales de la salud.

Perfil clínico-epidemiológico de pacientes que inician terapia intensiva con estatinas para la prevención secundaria de enfermedad vascular en España

Background: The new recommendations regarding the utilization of high potency statins (intensive therapy) for the treatment of cardiovascular disease have been based on the extrapolation of data coming from clinical trials. The objective is to describe the clinical-epidemiological profile of statin therapy users for the secondary prevention of cardiovascular disease in Spain and to examine the predictors for intensive therapy initiation. Methods: Cross-sectional study from a sample of 88,751 patients aged ≥45 years-old with previous cardiovascular disease which initiated statin therapy between 1st January 2007 to 31st December 2011. Dose treatments >40 mg simvastatin daily (or equivalent dose if different statin) were considered intensive therapy treatment. Multivariable logistic regression models were built for dependent summary variables to examine the association between and the intensive therapy utilization (vs low-moderate intensity therapy). Results: 16,857 adult patients receiving a first prescription of statin for the secondary prevention of cardiovascular diseases were identified. Predictors for intensive therapy initiation were year of statin prescription, male gender (adjusted OR: 1.70; 95% CI: 1.44-2.00), age >75 years-old (1.39; 1.15-1.69), previous history of coronary artery disease (1.71; 1.44-2.04), previous history of transient ischemic attack (1.24; 0,97-1.59), smoking (1.62; 1.34-1.95), hypertension (1.41; 1.20-1.65) and recent use of fibrates (2.32; 1.27-4.26). Conclusions: The onset of intensive therapy with statins in secondary was determined by the type of vascular event and age (>75 years-old in which the risk benefit balance could be controversial). No statistically significant differences were found according to the LDL-c levels.