Josep Maria Arnau

Perfil da automedicação no Brasil

INTRODUCTION The data presented are part of a World Health Organization (WHO) multicenter study of self-medication in Latin America. Brazilian sites included: Belo Horizonte, Fortaleza, the city of S. Paulo and outlying locations. The objective was to characterize self-medication practices by analyzing drugs sought by consumers in pharmacies without a physicians prescription. MATERIAL AND METHOD Drugs were classified according to the Anatomic Therapeutic Classification codes, and analyzed with respect to 1) intrinsic value; 2) recognition as an essential drug (by either WHO or Brazil); 3) number of active ingredients; and 4) requirement for prescription. RESULTS Five thousand, three hundred and thirty-two (5,332) different drugs, with 785 distinct active ingredients were sought. Of these, 49.5% were fixed dose combinations, 53.0% were of little intrinsic value, 44.1% required a physicians prescription, 71.0% were not essential drugs, and 40.0% of requests were based on prior prescriptions from the physician. The drugs most requested were analgesics (17.3%), nasal descongestants (7.0%), antirheumatic anti-inflammatory drugs (5.6%), and systemic anti-infective drugs (5.6%). CONCLUSIONS Self-medication in Brazil reflects the needs and habits of the population. It is strongly influenced by physicians-prescribing habits and by the inadequate selectivity of the Brazilian pharmaceutical market.

A critical review of guidelines for low back pain treatment

Main problem: Little is known about the methodological quality of guidelines for low back pain treatment. We evaluated the methods used by the developers according to established standards. Methods: PubMed, guideline databases, and the World Wide Web were used to identify guidelines. Seventeen guidelines met the inclusion criteria: interventions for low back pain stated, recommendations based on or explicitly linked to evidence, and English version available. Guidelines were evaluated independently by two appraisers using a practical tool for this purpose, Users’ Guides to the Medical Literature, and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Results: Thirteen guidelines (76%) specified the most important therapies applied, but only nine (53%) included a complete description of the target population. Explicit processes to identify, select, and combine evidence were described in only six guidelines (35%). Few guidelines (3; 18%) explicitly considered all main outcomes when formulating therapeutic recommendations, and none contained a process to determine the relative value of different outcomes. Methodological criteria for grading the strength of the recommendations varied, and were often insufficiently specified. None of the guidelines assessed the impact of uncertainty associated with the evidence and values used. According to AGREE the quality score was highest for the scope and purpose, and clarity and presentation domains, and lowest for editorial independence and applicability. With regard to the recommendations, there was consensus for some of the interventions for acute pain (analgesics and NSAIDs, maintaining physical activity, and avoiding excessive bed rest), but explicit recommendations were lacking or ambiguous for 41% of the interventions. Most of the guidelines did not contemplate specific recommendations for chronic pain. Conclusions: A small number of the available guidelines for low back pain treatment achieved acceptable results for specific quality criteria. In general, the methods to develop the guidelines’ therapeutic recommendations need to be more rigorous, more explicit and better explained. In addition, greater importance should be placed on the recommendations for chronic pain.

An Intervention to Improve Spontaneous Adverse Drug Reaction Reporting by Hospital Physicians : A Time Series Analysis in Spain

AbstractBackground: Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is scarce and several obstacles to such reporting have been identified previously. Objective: To assess the effectiveness of a multifaceted intervention based on healthcare management agreements for improving spontaneous reporting of ADRs by physicians in a hospital setting. Methods: In 2003, the spontaneous reporting of ADRs was included as one of the objectives of hospital physicians at the Vall d’Hebron Hospital, Barcelona, Spain, within the context of management agreements between clinical services and hospital managers. A continuous intervention related to these management agreements, including periodic educational meetings and economic incentives, was then initiated. We carried out an ecological time series analysis and assessed the change in the total number of spontaneous reports of ADRs, and the number of serious ADRs, unexpected ADRs, and ADRs associated with new drugs between a period previous to the intervention (from 1998 to 2002) and the period during the intervention (from 2003 to 2005). A time series analysis with ARIMA (Auto-Regressive Integrated Moving Average) models was performed. Results: The median number of reported ADRs per year increased from 40 (range 23–55) in the first period to 224 (range 98–248) in the second period. In the first period, the monthly number of reported ADRs was stable (3.47 per month; 95% CI 1.90, 5.03), but in the second period the number increased progressively (increase of 0.74 per month; 95% CI 0.62, 0.86). In the second period, the proportion of reported serious ADRs increased nearly 2-fold (63.1% vs 32.5% in the first period). The absolute number of previously unknown or poorly known ADRs increased 4-fold in the second period (54 vs 13 in the first period). There was also an increase in the absolute number of suspected pharmacological exposures to new drugs (97 vs 28) and in the number of different new drugs suspected of causing ADRs (50 vs 19). Conclusion: A continuous intervention based on healthcare management agreements with economic incentives and educational activities is associated with a quantitative and qualitative improvement of spontaneous reporting of ADRs by hospital physicians.

G protein-coupled receptor oligomerization for what?

Although the G protein-coupled receptor (GPCR) oligomerization has been questioned during the last decade, under some premises the existence of a supramolecular organization of these receptors begins now to be widely accepted by the scientific community. Indeed, GPCR oligomers may enhance the diversity and performance by which extracellular signals are transferred to the G proteins in the process of receptor transduction, although the mechanism that underlie this phenomenon remains still unexplained. Recently, a trans-conformational switching model has been proposed as a mechanism allowing direct inhibition of receptor activation. Thus, heterotropic receptor–receptor allosteric regulations are behind the GPCR oligomeric function. Accordingly, we revise here how GPCR oligomerization impinge in several important receptor functions like biosynthesis, plasma membrane diffusion or velocity, pharmacology and signaling. Overall, the rationale of receptor oligomerization might lie in the cellular need of sensing complex extracellular signals and to translate into a simple computational mode.

An Update on Adenosine A2A Receptors as Drug Target in Parkinson's Disease

Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A(2A) receptors (A(2A)Rs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such us the dopamine D(2) receptor (D(2)R). Furthermore, it is assumed that the formation of balanced A(2A)R/D(2)R receptor oligomers are essential for correct striatal function as the allosteric receptor-receptor interactions established within the oligomer are needed for properly sensing adenosine and dopamine. Interestingly, A(2A)R activation reduces the affinity of striatal D(2)R for dopamine and the blockade of A(2A)R with specific antagonists facilitates function of the D(2)R. Thus, it may be postulated that A(2A)R antagonists are pro-dopaminergic agents. Therefore, A(2A)R antagonists will potentially reduce the effects associated with dopamine depletion in Parkinsons disease (PD). Accordingly, this class of compounds have recently attracted considerable attention as potential therapeutic agents for PD pharmacotherapy as they have shown potential effectiveness in counteracting motor dysfunctions and also displayed neuroprotective and anti-inflammatory effects in animal models of PD. Overall, we provide here an update of the current state of the art of these A(2A)R-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Effect of an intervention on the features of adverse drug reactions spontaneously reported in a hospital

ObjectivesA continuous intervention based on healthcare management agreements was associated in our hospital with an increase in the absolute number of spontaneous reporting of adverse drug reactions (ADRs), and also with an increase in the number of reports of serious or unexpected ADRs and ADRs associated with new drugs. The objective was to analyse the effect of this intervention on the features of ADRs spontaneously reported in a hospital, the drugs involved and the number of signals identified.MethodsA longitudinal study with two periods, the 1st period without intervention from 1998 to 2002 and the 2nd period with intervention from 2003 to 2005, was carried out in a tertiary teaching hospital. Changes between the two periods with regard to the following variables were analysed: the patients’ characteristics, such as gender and age; the reported ADRs, and the medical assistance required; the suspected drugs involved in the ADRs; the main signals identified.ResultsGender and age distribution of patients described in the spontaneous reports were no different in the two periods. During the second period, spontaneously reported cases requiring hospital admission and those occurring in hospital increased (236 from 2 in the first period and 277 from 99 in the first period respectively) and cases from outpatient hospital consultations began to be reported (13.9% of reports). The spontaneous reporting on all kinds of ADRs and drugs increased during the second period. Cutaneous reactions were the most frequently spontaneously reported ADRs in both periods followed by cardiovascular and neurological reactions in the first period, and haematological and gastrointestinal reactions in the second one. However, during the second period the higher increase was for endocrinological, urinary and hepatic reactions. Systemic antibiotics, anti-thrombotics and cardiac therapy drugs were the most common therapeutic subgroups reported to be suspected drugs in both periods, but in the second period the proportion of immunostimulants, beta blocking agents, immunosuppressants and psychoanaleptics increased. No signals were recognised during the first period; however, two signals and one additional safety concern were identified during the second.ConclusionAn intervention based on healthcare management agreements, was associated with an important increase in spontaneous reporting of ADRs by hospital physicians and also with a change in terms of the type of ADRs identified affecting different organs or systems, and the therapeutic groups of drugs involved. Future studies should analyse the effect of different types of intervention on the spontaneous reporting of ADRs in hospitals.

Editorial Comment: European guidelines for low back pain - a necessary step forward and an opportunity not to be missed.

view of the three documents confirms that they will lead to a change in the current situation, but also shows that additional work is needed to achieve the declared goal of improving the quality and outcome of healthcare for this condition (www.backpaineurope.org). Assessment of the three COST documents with the instruments [7,9,11] used in previous systematic reviews [2,10], allows an evaluation according to standard criteria such as rigor in the development of the guidelines, as well as guarantees of the validity, clarity, strength, and applicability of the recommendations. With regard to rigor in development and guarantees of validity, the authors performed an excellent review of the available evidence from the viewpoint of identification, selection and updating, and highly accurate synthesis and grading of the evidence. The main weak point in these domains is the fact that the method used by the panel of experts to arrive at decisions is not clearly described. In addition, the guidelines for acute and chronic pain were not submitted to external peer review before their publication. These points are more relevant in the guidelines for chronic pain, since the main contributors of some chapters assessing the interventions used for this condition are precisely the “experts” in the field under review, a fact that could imply a higher degree of subjectivity in the judgements. With regard to the clarity of the recommendations, a very positive aspect is that the guidelines clearly indicate which interventions are not, or cannot be, recommended. Nevertheless, the terminology used in the recommendations for which there is stronger evidence sometimes includes rather ambiguous statements in addition to “recommended”, such as “consider using” as well as others (“can be recommended,” “may be recommended,” “can be considered,” and “should be considered”). This limitation is more relevant in the guidelines for chronic low back pain. Although some criteria (“known concerns”) were taken into account to separate the interventions into the categories “recommended” and “consider using”, it remains unclear which of them led to the final decision for cateJosep M. Arnau Ferran Pellisé Antoni Vallano Núria Prat

Drugs in the Spanish Health System

This paper presents data on drug consumption in Spain, analyzed from a cultural as well as from a medical point of view. The overuse of medicines is an economic rather than a pharmaceutical problem, and the main characteristic of drug use in Spain seems to be the misuse of pharmacologic therapeutic strategies. Four factors which influence the quantity and quality of drug consumption are identified and analyzed: 1) the structure of the primary health care system, 2) general requirements for marketing drugs and the characteristics of pharmaceutical supply, 3) information about drugs used by health professionals, and 4) development and activities—pre-graduate teaching and continuing education—in the field of clinical pharmacology. Some recent activities in this area are also presented. These are intended as a contribution to the development of clinical pharmacology with the aim of turning benefit-risk ratios to the side of the benefit, through the promotion of a more rational drug therapy.

The DEC-net European register of paediatric drug therapy trials: contents and context

Objective To describe the results and conclusions of DEC-net, an international, publicly available register of paediatric drug therapy clinical trials, and to assess which paediatric health areas are covered by research and by which trial types.Methods The contents of the register, which was set up by four groups (Italy, UK, France, Spain) who searched for paediatric trials and collected data between 2004–2006, were analysed. The disease areas reflected were compared with those covered by published trials and Burden of Disease (BD) data.Results In all, 257 trial records were analysed, 86 of which were entered by the Italian partner, 84 by the UK partner, 56 by the French partner and 31 by the Spanish partner. Spain entered the majority of multinational trials, while the UK had the majority of single-centre national trials. Most trials were experimental (79%), and the most commonly represented diseases were neoplasms (14% trials). In all, 28% were double-blind randomised controlled trials (RCTs). The most common disease areas addressed in the 257 trials were similar to the published trials’ areas. In contrast, the primary research area was low on the BD list.Conclusions DEC-net has demonstrated that international research efforts exist, even for paediatrics, although there may be an imbalance between national and multinational studies and a limited approach to double-blind RCTs. Recent initiatives will increase the number of children participating in research, and European legislation will require prospective registration. Paediatric research priorities must be better defined, however, and this can be done by registering research and making the information available to all relevant actors.

Estrategias de intervención para el uso racional de antimicrobianos en el medio extrahospitalario

zan un seguimiento para conseguir al máximo su cumplimiento, a pesar de que no siempre consiguen este objetivo. Actualmente, las actividades de la política de antibióticos no tan sólo tienen en cuenta el problema de las resistencias sino que también incluyen como objetivo minimizar los otros problemas (el fracaso terapéutico, la toxicidad y el gasto de los antibióticos); por esta razón se utilizan criterios de relación beneficio/riesgo y coste/efectividad en la selección de antibióticos. En atención primaria se dispone de información muy detallada sobre el consumo de los antibióticos a cargo del Sistema Nacional de Salud y del gasto que generan, pero casi no hay tradición en el desarrollo de actividades en el campo de la política de antibióticos. Esto no debe extrañar si tenemos en cuenta la situación problemática en dos cuestiones que son clave: las dificultades para conseguir una información fiable, representativa y útil sobre el estado de las resistencias bacterianas y su seguimiento, y la ausencia de medidas reguladoras de la oferta de los antibióticos disponibles y del cumplimiento de los criterios de selección de antibióticos (papel que en los hospitales tiene la Comisión Farmacoterapéutica, la Comisión de Infecciones o la Comisión de Antibióticos). En el medio extrahospitalario es frecuente el uso de antibióticos en indicaciones para las que no está justificado su uso, sobre todo en las infecciones de las vías respiratorias superiores, y la automedicación con un escaso control de la dispensación de antibióticos sin receta. Si a esto se añade el papel de la autoridad reguladora y de la industria farmacéutica, hemos de reconocer que la situación es aún más compleja y difícil, ya que se comercializan muchos compuestos nuevos, que en su mayoría son incluidos en el sistema de financiación pública, y aunque su aportación es muchas veces marginal, los precios son cada vez más altos y las actividades de promoción comercial más intensas. La situación actual no creemos que tenga una solución “mágica” a corto plazo, debido a la complejidad de los factores que influyen de forma negativa sobre el uso de los antibióticos y del tiempo que llevan actuando, aunque se entiende que su abordaje es prioritario para el sistema sanitario y que estamos obligados a plantear iniciativas y acciones que faciliten posibles soluciones. Hay diversas estrategias de intervención orientadas hacia un uso racional de los medicamentos, y de los antibióticos en particular, que se suelen agrupar en dos grandes tipos, las educativas y la reguladoras. Sobre el posible efecto de las medidas reguladoras hay poca información, mientras que hay más sobre las medidas educativas y, durante los últimos años, se han publicado varias revisiones sistemáticas de los estudios que han evaluado su efectividad4-8. Aunque los estudios realizados, mayoritariamente en el ámbito hospitalario o de atención especializada, tienen limitaciones, a Hoy en día los antimicrobianos se consideran uno de los avances más importantes que la investigación farmacológica ha aportado para mejorar la salud de la población. A pesar de este hecho, también es cierto que el uso de estos fármacos a menudo es inapropiado, porque se selecciona mal a la población a tratar, no se elige el antibiótico adecuado y la pauta de tratamiento es inadecuada (dosis, intervalo de dosificación, duración del tratamiento y seguimiento). Además, la utilización inadecuada de los antibióticos tiene importantes consecuencias, porque provoca el aumento de las resistencias de los microorganismos, del fracaso del tratamiento, de los efectos adversos y del gasto. Por lo tanto, es lógico que esta cuestión del uso inadecuado de los antimicrobianos haya preocupado y siga preocupando a los médicos y a otros profesionales sanitarios, así como también a la Administración. En España la preocupación es cada vez mayor ya que, en comparación con otros países, nos encontramos en una situación doblemente desfavorable. Por un lado, hay un aumento de las resistencias de algunos microorganismos “clave”, de mayor magnitud que en otros países; y, por otro lado, hay un consumo de antimicrobianos muy elevado, sobre todo en el ámbito de atención primaria y a cargo del Sistema Nacional de Salud1-3. En un estudio internacional que comparó el consumo de antibióticos en quince países de la Unión Europea, se observó que España, junto con Francia, fue el país con un mayor consumo de antibióticos2. El uso irracional de antibióticos y sus consecuencias pueden aparecer tanto en atención primaria como en los hospitales, pero durante mucho tiempo ha sido, casi exclusivamente, en el entorno hospitalario donde se han identificado estos problemas como prioritarios, y se ha impulsado la denominada política de antibióticos. En los hospitales la política de antibióticos se ha desarrollado fundamentalmente como una respuesta al problema de las resistencias bacterianas, y uno de sus objetivos ha sido evitar la utilización de antibióticos de amplio espectro y, más en general, evitar la sobreutilización de los antibióticos para situaciones en las cuales no estaban indicados. La política de antibióticos hospitalaria ha tenido un apoyo institucional y se ha realizado en el seno de diferentes comisiones (Comisión de Infecciones, Comisión de Antibióticos, Comisión Farmacoterapéutica), que son las que establecen unos criterios de selección y utilización de antibióticos, los difunden y reali-