Julián Librero

Accuracy of pharmaceutical advertisements in medical journals.

BACKGROUND Because of the effect of the ever-growing evidence-based medicine movement on prescribing behaviour of doctors, the pharmaceutical industry incorporates bibliographical references to clinical trials that endorse their products in their advertisements. We aimed to assess whether the references about efficacy, safety, convenience, or cost of antihypertensive and lipid-lowering drugs included in advertisements supported the promotional claims. METHODS We assessed all advertisements for antihypertensive and lipid-lowering drugs published in six Spanish medical journals in 1997 that had at least one bibliographical reference. Two pairs of investigators independently reviewed the advertisements to see whether the studies quoted to endorse the advertising messages supported the corresponding claims. FINDINGS We identified 264 different advertisements for antihypertensive drugs and 23 different advertisements for lipid-lowering drugs. We recorded at least one reference in 31 advertisements in the antihypertensive group and at least one reference in every seven advertisements in the lipid-lowering group, providing a total of 125 promotional claims with references. We could not retrieve 23 (18%) references from monographic works and non-published data on file. 79 (63%) of the 125 references were from journals with a high impact factor; 84 (82%) of the 102 references retrieved were from randomised clinical trials. In 45 claims (44.1%; 95% CI 34.3-54.3) the promotional statement was not supported by the reference, most frequently because the slogan recommended the drug in a patient group other than that assessed in the study. INTERPRETATION Doctors should be cautious in assessment of advertisements that claim a drug has greater efficacy, safety, or convenience, even though these claims are accompanied by bibliographical references to randomised clinical trials published in reputable medical journals and seem to be evidence-based.

Is there much variation in variation? Revisiting statistics of small area variation in health services research

BackgroundThe importance of Small Area Variation Analysis for policy-making contrasts with the scarcity of work on the validity of the statistics used in these studies. Our study aims at 1) determining whether variation in utilization rates between health areas is higher than would be expected by chance, 2) estimating the statistical power of the variation statistics; and 3) evaluating the ability of different statistics to compare the variability among different procedures regardless of their rates.MethodsParametric bootstrap techniques were used to derive the empirical distribution for each statistic under the hypothesis of homogeneity across areas. Non-parametric procedures were used to analyze the empirical distribution for the observed statistics and compare the results in six situations (low/medium/high utilization rates and low/high variability). A small scale simulation study was conducted to assess the capacity of each statistic to discriminate between different scenarios with different degrees of variation.ResultsBootstrap techniques proved to be good at quantifying the difference between the null hypothesis and the variation observed in each situation, and to construct reliable tests and confidence intervals for each of the variation statistics analyzed. Although the good performance of Systematic Component of Variation (SCV), Empirical Bayes (EB) statistic shows better behaviour under the null hypothesis, it is able to detect variability if present, it is not influenced by the procedure rate and it is best able to discriminate between different degrees of heterogeneity.ConclusionThe EB statistics seems to be a good alternative to more conventional statistics used in small-area variation analysis in health service research because of its robustness.

Inter-hospital variations in caesarean sections. A risk adjusted comparison in the Valencia public hospitals

BACKGROUND The aim of this study was to describe the variability in caesarean rates in the public hospitals in the Valencia Region, Spain, and to analyse the association between caesarean sections and clinical and extra-clinical factors. METHODS Analysis of data contained in the Minimum Basic Data Set (MBDS) compiled for all births in 11 public hospitals in Valencia during 1994–1995 (n=36 819). Bivariate and multivariate analyses were used to evaluate the association between caesarean section rates and specific risk factors. The multivariate model was used to construct predictions about caesarean rates for each hospital, for comparison with rates observed. RESULTS Caesarean rates were 17.6% (inter-hospital range: 14.7% to 25.0%), with ample variability between hospitals in the diagnosis of maternal-fetal risk factors (particularly dystocia and fetal distress), and the indication for caesarean in the presence of these factors. Multivariate analysis showed that maternal-fetal risk factors correlated strongly with caesarean section, although extra-clinical factors, such as the day of the week, also correlated positively. After adjusting for the risk factors, the inter-hospital variation in caesarean rates persisted. CONCLUSIONS Although certain limitations (imprecision of some diagnoses and information biases in the MBDS) make it impossible to establish unequivocal conclusions, results show a high degree of variability among hospitals when opting for caesarean section. This variability cannot be justified by differences in obstetric risks.

Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial

BackgroundPostoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery.MethodsThis is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra- and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra- and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications.DiscussionThe Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications.Trial registrationRegistered on 5 June 2014 with identification no. NCT02158923.

Variabilidad en la utilización de recursos hospitalarios en pacientes con enfermedad pulmonar obstructivav crónica (EPOC)

Objetivo Analizar los factores asociados a la duracion de la estancia y el gasto farmaceutico en pacientes ingresados por enfermedad pulmonar obstructiva cronica (EPOC) y evaluar si la atencion por diferentes facultativos implica un uso diferencial de estos recursos. Metodos Cohorte retrospectiva de 1.033 ingresos por EPOC en el Hospital de Mataro (1996–1998) en la que se analizaron los factores asociados a la duracion de la estancia y el gasto en farmacos a partir del Conjunto Minimo de Datos Basicos, las bases de datos de analisis clinicos y la base de datos de la unidosis de farmacia. Se analizaron tam-bien las diferencias entre los pacientes atendidos por cada facultativo y se desarrollaron modelos de regresion lineal multiple con objeto de valorar la presencia de diferencias en funcion de la atencion por uno u otro medico. Resultados La duracion de la estancia aumento con la mayor edad, el numero de ingresos, la presencia de fibrila-cion auricular o insuficiencia respiratoria, las alteraciones ventilatorias, la cronicidad, un valor de ventilacion espiratoria maxima en el primer segundo inferior al 50% y la atencion por determinados facultativos. El gasto farmaceutico mostro un comportamiento similar. Aunque los pacientes atendidos por los diferentes medicos fueron muy homogeneos, la estancia mediana segun facultativos vario desde 9 a 11 dias, y la mediana de gasto farmaceutico, desde 7.258 hasta 9.049 ptas. Tras eliminar el efecto de las diversas covariables mediante analisis de regresion multiple, se mantuvo el comportamiento diferencial entre facultativos. Conclusiones Las diferencias entre medicos en cuanto a duracion de la estancia hospitalaria y consumo farmaceutico son importantes y persisten tras controlar el efecto de las diferencias relativas a la gravedad de los pacientes atendidos.

Análisis poblacional por áreas de salud de las variaciones en consumo, precio y gasto de medicamentos cardiovasculares en 8 Comunidades Autónomas, España, 2005

Fundamentos: La variabilidad en la utilizacion de medicamentos cardiovasculares tiene especial interes por su elevado consumo poblacional, su alto gasto, y disponer de solidas evidencias que apoyan su uso. El objetivo de este estudio es describir la variabilidad en dispensacion, precio medio e importe de 11 subgrupos de medicamentos cardiovasculares por areas de salud. Metodos: Estudio poblacional descriptivo de la dispensacion, precio medio y gasto de 11 subgrupos de medicamentos cardiovasculares por areas de salud en el ano 2005, seguido de analisis de la variabilidad observada. El individuo de analisis son las 93 areas de salud de las 8 Comunidades Autonomas participantes. Medidas de resultados: Dosis diarias definidas consumidas por cada 1000 pensionistas y dia (DDD/1000p/Dia), gasto por 100 habitantes y ano (euros por 100 pensionistas), precio medio de la DDD (euros por DDD), razones de utilizacion estandarizadas. Analisis descriptivo de la dispensacion, precio, gasto y razones estandarizadas de utilizacion. Analisis de la variabilidad utilizando los estadisticos del «analisis de areas pequenas». Resultados: El consumo de medicamentos cardiovasculares oscilo entre 324 DDD/1000p/Dia para los medicamentos con accion sobre el sistema renina-angiotensina y 6,5 DDD/1000p/Dia para diureticos antialdosteronicos. La variacion en consumo para las areas situadas en el percentil 5 y 95 oscilo entre 1,8 veces (digitalicos) y 17,2 veces (flavonoides). La variacion en los precios medios fue menor que en el consumo (1,1 veces para doxazosina y 3,7 para flavonoides) y la variacion en gasto fue similar a la del consumo (entre 2,0 veces para digitalicos y 13,0 veces para flavonoides). Conclusiones: Una notable variabilidad entre areas de salud en el consumo de medicamentos cardiovasculares junto a las mas discretas variaciones en precio se traduce en grandes diferencias en el gasto poblacional.

Medida del resultado de las intervenciones sanitarias en España: una aproximación mediante el análisis temporal y espacial de la mortalidad evitable entre 1986-2001

Background: Many studies have proposed Avoidable Mortality (ME) to monitor the performance of health services although its usefulness is limited by the multiplicity of the avoidable mortality lists being used. Time trends from 1986-2001 and the geographical distribution of avoidable mortality by provinces, are presented for Spain. Methods: An Avoidable Mortality consensus list is being used. It includes avoidable mortality through the intervention of health services (ISAS in Spanish) and through health policy interventions (IPSI in Spanish). Time trends are analyzed adjusting Poisson or Joinpoint regression models and the annual percentages of change (APC) are estimated. Changes in geographical distribution between the first half of the analysed period and the second are tested by means of standard mortality ratios (SMR) and comparative mortality rates (CMR) for each province. Results: Between 1986 and 2001 avoidable mortality decreased (APC: -1.68; CI: -1.99 and -1.38) slightly more than non-avoidable mortality (APC: -1.28; CI: -1.40 and -1.17). Higher reduction was observed for ISAS mortality (APC: -2.77; CI: -2.89 and -2.65) and an irregular trend for IPSI (between 1986-1990 increase APC: 4.86; CI: 3.32 and 6.41, between 1990-95 stabilization APC: -0.03; CI: -2.32 and 2.31 and finally 1995-2001 decrease APC: -3.57; CI: -4.72 and -2.40). Conclusions: Avoidable mortality decreased more than non avoidable mortality and important geographical variability can be observed among provinces which should be monitored in order to identify the health services weaknesses. The higher ISAS mortality was observed in southern provinces and the higher IPSI mortality in some areas on the coast. The pattern is somewhat similar for both analyzed periods.

Effect of cost sharing on adherence to evidence-based medications in patients with acute coronary syndrome

Objectives Cost-sharing scheme for pharmaceuticals in Spain changed in July 2012. Our aim was to assess the impact of this change on adherence to essential medication in patients with acute coronary syndrome (ACS) in the region of Valencia. Methods Population-based retrospective cohort of 10 563 patients discharged alive after an ACS in 2009–2011. We examined a control group (low-income working population) that did not change their coinsurance status, and two intervention groups: pensioners who moved from full coverage to 10% coinsurance and middle-income to high-income working population, for whom coinsurance rose from 40% to 50% or 60%. Weekly adherence rates measured from the date of the first prescription. Days with available medication were estimated by linking prescribed and filled medications during the follow-up period. Results Cost-sharing change made no significant differences in adherence between intervention and control groups for essential medications with low price and low patient maximum coinsurance, such as antiplatelet and beta-blockers. For costlier ACE inhibitor or an angiotensin II receptor blocker (ACEI/ARB) and statins, it had an immediate effect in the proportion of adherence in the pensioner group as compared with the control group (6.8% and 8.3% decrease of adherence, respectively, p<0.01 for both). Adherence to statins decreased for the middle-income to high-income group as compared with the control group (7.8% increase of non-adherence, p<0.01). These effects seemed temporary. Conclusions Coinsurance changes may lead to decreased adherence to proven, effective therapies, especially for higher priced agents with higher patient cost share. Consideration should be given to fully exempt high-risk patients from drug cost sharing.

Adherence to oral anticoagulants in patients with atrial fibrillation—a population-based retrospective cohort study linking health information systems in the Valencia region, Spain: a study protocol

Introduction Adherence to oral anticoagulation (OAC) treatment, vitamin K antagonists or new oral anticoagulants, is an essential element for effectiveness. Information on adherence to OAC in atrial fibrillation (AF) and the impact of adherence on clinical outcomes using real-world data barely exists. We aim to describe the patterns of adherence to OAC over time in patients with AF, estimate the associated factors and their impact on clinical events, and assess the same issues with conventional measures of primary and secondary adherence—proportion of days covered (PDC) and persistence—in routine clinical practice. Methods and analysis This is a population-based retrospective cohort study including all patients with AF treated with OAC from 2010 to date in Valencia, Spain; data will be obtained from diverse electronic records of the Valencia Health Agency. Primary outcome measure: adherence trajectories. Secondary outcomes: (1) primary non-adherence; (2) secondary adherence: (a) PDC, (b) persistence. Clinical outcomes: hospitalisation for haemorrhagic or thromboembolic events and death during follow-up. Analysis: (1) description of baseline characteristics, adherence patterns (trajectory models or latent class growth analysis models) and conventional adherence measures; (2) logistic or Cox multivariate regression models, to assess the associations between adherence measures and the covariates, and logistic multinomial regression models, to identify characteristics associated with each trajectory; (3) Cox proportional hazard models, to assess the relationship between adherence and clinical outcomes, with propensity score adjustment applied to further control for potential confounders; (4) to estimate the importance of different healthcare levels in the variations of adherence, logistic or Cox multilevel regression models. Ethics and dissemination This study has been approved by the corresponding Clinical Research Ethics Committee. We plan to disseminate the projects findings through peer-reviewed publications and presentations at relevant health conferences. Policy reports will also be prepared in order to promote the translation of our findings into policy and clinical practice.

Edad relativa de los ninos en clase y tratamiento farmacologico del trastorno por deficit de atencion/hiperactividad. Estudio poblacional en un departamento de salud §

BACKGROUND AND OBJECTIVE Previous studies in various countries have shown that the youngest school children in the same class-grade are more likely to be treated for attention-deficit/hyperactivity disorder (ADHD) than their older classmates. The aim of this study is to determine in the Spanish setting whether younger relative age children in each grade have a higher prevalence of treatment for ADHD. SUBJECTS AND METHODS Population, observational, cross-sectional study in a health department, using prevalence data (November 2013) of treatment for ADHD in children aged 6-12 years. Data was obtained from the information systems of the Valencia Ministry of Health and multivariate models were used to estimate the prevalence ratio of treatment according to the month of birth of children in each grade. RESULTS Twenty thousand two hundred and thirty-seven children were included of whom 1.73% were treated for ADHD (boys: 2.70%; girls: 0.71%) in October 2013. The prevalence of treatment increased with age, in males, and in youngest children (born in the last months of each year). In the multivariate analysis, the prevalence of treatment in the youngest children (born in the months of August to December) was 2.5 to 3 times higher than in their older classmates (born in January). CONCLUSIONS The younger children relative to their classmates are more likely to be treated pharmacologically with methylphenidate and/or atomoxetine.