Queixas técnicas e eventos adversos a medicamentos notificados em um hospital sentinela do interior de São Paulo, 2009-2010

Objective: to describe technical complaints and adverse drug events reported in a sentinel hospital in São Paulo state in 2009 and 2010. Methods: This is a descriptive study. Information was obtained from the sentinel hospital Risk Management database. Results: we found 199 reports related to drugs: 70.0% were technical complaints, 21.0% ineffective therapy and 9.0% adverse reaction to medication. The pharmacological groups with highest number of reports were: drugs that act on alimentary tract and metabolism (25.1%), the nervous system (25.1%) and anti-infective drugs for systemic use (22.1%). Conclusion: technical complaints and adverse drug events were frequent, despite recognized underreporting. The characterization of these events could inform the adoption of control measures and permanent educational actions in health services in order to prevent their occurrence.

Reações adversas a medicamentos levando crianças a atendimento na emergência hospitalar

Determinou-se incidência de reações adversas a medicamentos (RAM) que levaram crianças a atendimento de emergência em um hospital universitário de São Paulo, SP. Foram analisadas, retrospectivamente, 23.286 fichas de atendimento (FA) em emergência pediátrica, a partir de código CID que indicasse possível RAM. Observaram-se 83 (0,36%) RAMs. A maioria ocorreu na faixa etária entre 1 a 5 anos com leve predominância no sexo masculino (51,8%). Os medicamentos mais implicados foram antibacterianos para uso sistêmico (53,0%), vacinas (9,6%) e analgésicos (7,2%). A maior parte das RAMs foram manifestações dérmicas (54,2%) ou gastrointestinais (22,9%). Duas RAMs foram consideradas graves (2,4%) e levaram a internação; enquanto 61,4% foram leves e 36,1% foram moderadas. A incidência foi inferior à literatura, provavelmente por ser estudo retrospectivo, utilizando-se o CID para seleção das FA. Observou-se que, no Brasil, as RAMs levam crianças a atendimento de emergência, com características semelhantes às de outros países. Intervenções são necessárias para melhorar o diagnóstico e a utilização de antimicrobianos, uma vez que foram os medicamentos mais implicados nas RAMs observadas. A pesquisa no setor de emergência hospitalar é importante para se conhecer as RAMs que ocorrem fora do contexto hospitalar, podendo contribuir para identificar aquelas de maior gravidade. A metodologia utilizada, apesar das limitações, requer poucos recursos humanos e materiais, sendo uma boa alternativa para um diagnóstico inicial, que deve ser sucedido por estudos mais elaborados e de maior sensibilidade para detectar essas reações e propor medidas dirigidas à sua prevenção.

La responsabilità civile da prodotto farmaceutico

Il tema della ricerca ha riguardato preliminarmente la definizione di farmaco descritta nel d.lgs. n. 219 del 2006 (Codice dei farmaci per uso umano). Oltre al danno prodotto da farmaci, la ricerca ha approfondito anche la tutela ex ante ed ex post riguardante la produzione di dispositivi medici (Direttiva della Comunità Economica Europea n. 42 del 1993 e Direttiva della Comunità Economica Europea n. 374 del 1985). E’ stato necessario soffermarsi sull’analisi del concetto di precauzione per il quale nell’ambito di attività produttive, come quelle che cagionano inquinamento ambientale, o “pericolose per la salute umana” come quelle riguardanti la produzione di alimenti e farmaci, è necessario eliminare i rischi non conosciuti nella produzione di questi ultimi al fine di garantire una tutela completa della salute. L’analisi della Direttiva della Comunità Economica Europea n. 374 del 1985 nei suoi aspetti innovativi ha riguardato l’esame dei casi di danno da farmaco (Trib. Roma, 20 Giugno 2002, Trib. Roma 27 Giugno 1987, Trib. Milano 19 Novembre 1987, Cassazione Civile n. 6241 del 1987): profilo critico è quello riguardante la prova liberatoria, mentre l'art. 2050 prevede che «si debbano adottare tutte le misure necessarie per evitare il danno», l'art. 118, lett. e), c. cons.) prevede una serie di casi di esonero di responsabilità del produttore (tra cui il rischio di sviluppo). Dall'analisi emerge poi la necessità da parte del produttore di continuo utilizzo del duty to warn (Art. 117 del Codice del Consumo lett. A e B ): esso consiste nel dovere continuo di informazione del produttore tramite i suoi rappresentanti e il bugiardino presente nelle confezioni dei farmaci. Tale dovere è ancor più importante nel caso della farmacogenetica, infatti, al fine di evitare reazioni avverse nel bugiardino di alcuni farmaci verrà prescritta la necessità di effettuare un test genetico prima dell’assunzione.

CD8+ T cells and NK cells from blister fluid of an EEM/SJS overlap highly express Fas ligand and Granulysin

INTRODUCTION Erythema exsudativum multiforme majus (EEMM) and Stevens-Johnson Syndrome (SJS) are severe cutaneous reaction patterns caused by infections or drug hypersensitivity. The mechanism by which widespread keratinocyte death is mediated by the immune system in EEMM/SJS are still to be elucidated. Here, we characterized the blister cells isolated from a patient with EEMM/SJS overlap and investigated its cause. METHODS Clinical classification of the cutaneous eruption was done according to the consensus definition of severe blistering skin reactions and histological analysis. Common infectious causes of EEMM were investigated using standard clinical techniques. T cell reactivity for potentially causative drugs was assessed by lymphocyte transformation tests (LTT). Lymphocytes isolated from blister fluid were analyzed for their expression of activation markers and cytotoxic molecules using flow cytometry. RESULTS The healthy 58 year-old woman suffered from mild respiratory tract infection and therefore started treatment with the secretolytic drug Ambroxol. One week later, she presented with large palmar and plantar blisters, painful mucosal erosions, and flat atypical target lesions and maculae on the trunc, thus showing the clinical picture of an EEMM/SJS overlap (Fig. 1). This diagnosis was supported by histology, where also eosinophils were found to infiltrate the upper dermis, thus pointing towards a cutaneous adverse drug reaction (cADR). Analysis of blister cells showed that they mainly consisted of CD8+ and CD4+ T cells and a smaller population of NK cells. Both the CD8+ T cells and the NK cells were highly activated and expressed Fas ligand and the cytotoxic molecule granulysin (Fig. 2). In addition, in comparison to NK cells from PBMC, NK cells in blister fluids strongly upregulated the expression of the skin-homing chemokine receptor CCR4 (Fig 4). Surprisingly, the LTT performed on PBMCs in the acute phase was positive for Ambroxol (SI=2.9) whereas a LTT from a healthy but exposed individual did not show unspecific proliferation. Laboratory tests for common infectious causes of EEMM were negative (HSV-1/-2, M. pneumoniae, Parvovirus B19). However, 6 weeks later, specific proliferation to Ambroxol could no longer be observed in the LTT (Fig 4.).

A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer

Anthracyclines are used in over 50% of childhood cancer treatment protocols, but their clinical usefulness is limited by anthracycline-induced cardiotoxicity (ACT) manifesting as asymptomatic cardiac dysfunction and congestive heart failure in up to 57% and 16% of patients, respectively. Candidate gene studies have reported genetic associations with ACT, but these studies have in general lacked robust patient numbers, independent replication or functional validation. Thus, the individual variability in ACT susceptibility remains largely unexplained. We performed a genome-wide association study in 280 patients of European ancestry treated for childhood cancer, with independent replication in similarly treated cohorts of 96 European and 80 non-European patients. We identified a nonsynonymous variant (rs2229774, p.Ser427Leu) in RARG highly associated with ACT (P = 5.9 × 10(-8), odds ratio (95% confidence interval) = 4.7 (2.7-8.3)). This variant alters RARG function, leading to derepression of the key ACT genetic determinant Top2b, and provides new insight into the pathophysiology of this severe adverse drug reaction.

Polypharmacy and inappropriate medication use in patients with dementia: an underresearched problem

Multimorbidity and polypharmacy are increasingly prevalent across healthcare systems and settings as global demographic trends shift towards increased proportions of older people in populations. Numerous studies have demonstrated an association between polypharmacy and potentially inappropriate prescribing (PIP), and have reported high prevalence of PIP across settings of care in Europe and North America and, as a consequence, increased risk of adverse drug reactions, healthcare utilisation, morbidity and mortality. These studies have not focused specifically on people with dementia, despite the high risk of adverse drug reactions and PIP in this patient cohort. This narrative review considers the evidence currently available in the area, including studies examining prevalence of PIP in older people with dementia, how appropriateness of prescribing is assessed, the medications most commonly implicated, the clinical consequences, and research priorities to optimise prescribing for this vulnerable patient group. Although there has been considerable research effort to develop criteria to assess medication appropriateness in older people in recent years, the majority of tools do not focus on people with dementia. Of the limited number of tools available, most focus on the advanced stages of dementia in which life-expectancy is limited. The development of tools to assess medication appropriateness in people with mild-to-moderate dementia or across the full spectrum of disease severity represents an important gap in the research literature and is beginning to attract research interest, with recent studies considering the medication regimen as a whole, or misprescribing, overprescribing or underprescribing of certain medications/medication classes including anticholinergics, psychotropics, antibiotics and analgesics. Further work is required in development and validation of criteria to assess prescribing appropriateness in this vulnerable patient population, to determine prevalence of PIP in large cohorts of people with the full spectrum of dementia variants and severities and to examine the impact of PIP on health outcomes.

Intravascular Lymphoma as an Uncommon Cause of Anasarca

Objectives: To report a case of intravascular lymphoma (IVL) in a Caucasian patient who presented with anasarca as his sole clinical sign. Material and Methods: A man presented with anasarca-type oedema and fatigue. After excluding heart failure, hepatic cirrhosis, nephrotic syndrome, hypothyroidism, AL-amyloidosis and adverse drug reaction which can all cause oedema, we turned our attention to capillary permeability disorders. Results: Closer review of the bone marrow aspirate demonstrated haemophagocytic histiocytosis, while core, renal and duodenal biopsies showed a B-cell IVL. Conclusion: The differential diagnosis of anasarca, a relatively common clinical sign, should include IVL although the diagnosis may still be challenging.

Community pharmacists’ understanding, attitudes, practice and perceived barriers related to providing pharmaceutical care: a questionnaire-based survey in Macao

Purpose: To explore the knowledge, attitudes, practice and perceived barriers of community pharmacists regarding provision of pharmaceutical care as well as provide recommendations on how to advance the service during the early stage of development in Macao. Methods: A questionnaire comprising 10 items was used to collect respondents’ demographic information and to evaluate their understanding of pharmaceutical care, attitude towards service provision, current practice and perceived barriers. Descriptive and comparative analysis of the results was conducted. Results: While 95 % of the participating pharmacists agreed that patients’ health was their primary responsibility, only 57 % believed that they can provide better pharmaceutical care in the future. The majority spent most of their work time counselling patients (90 %) and checking prescription (70 %). Only a small portion monitored adverse drug reaction and drug compliance (44 %), engaged in health screening or drug safety promotion (20 %) or maintained patient medication records (4 %). Insufficient communication with physicians (90 %), lack of time (79 %) and lack of physical space at the pharmacy (76 %) were considered the most significant barriers. Conclusion: A suboptimal level of pharmaceutical care is provided by pharmacists in Macao. Considering the barriers identified and integrating other country experiences, establishing an enabling atmosphere using policy and regulatory measures is the fundamental element for advancing pharmaceutical care by community pharmacists.

Implementación de criterios de Beers en pacientes con atención domiciliaria mayores de 75 años polimedicados y la identificación de las reacciones cruzadas

Introducción: El incremento de la población geriátrica es una realidad a nivel mundial y con esto los modelos de atención domiciliaria toman gran relevancia para dar respuesta a las diferentes patologías que requieran su seguimiento. Se ha evidenciado que en dicho seguimiento, el fenómeno de la polimedicación se presenta con frecuencia, con el riesgo de generar efectos cruzados y reacciones adversas que incrementan el deterioro clínico de los pacientes. Objetivo: Determinar los posibles efectos cruzados de la Polimedicación no pertinente en pacientes mayores de 75 años con hipertensión arterial más enfermedad neurodegenerativa en atención domiciliaria de una EPS del régimen contributivo en Bogotá, con base en los criterios de Beers.

Descriptive Text Mining in ambito medico: applicazione della metodologia POIROT

Poiché la nostra conoscenza collettiva continua ad essere digitalizzata e memorizzata, diventa più difficile trovare e scoprire ciò che stiamo cercando. Abbiamo bisogno di nuovi strumenti computazionali per aiutare a organizzare, rintracciare e comprendere queste vaste quantità di informazioni. I modelli di linguaggio sono potenti strumenti che possono essere impiegati per estrarre conoscenza statisticamente significativa ed interpretabile tramite apprendimento non supervisionato, testuali o nel codice sorgente. L’obiettivo di questa tesi è impiegare una metodologia di descriptive text mining, denominata POIROT, per analizzare i rapporti medici del dataset Adverse Drug Reaction (ADE). Si vogliono stabilire delle correlazioni significative che permettano di comprendere le ragioni per cui un determinato rapporto medico fornisca o meno informazioni relative a effetti collaterali dovuti all’assunzione di determinati farmaci.

Action following the discovery of a global association between the whole genome and adverse event risk in a clinical drug-development programme

Observation of adverse drug reactions during drug development can cause closure of the whole programme. However, if association between the genotype and the risk of an adverse event is discovered, then it might suffice to exclude patients of certain genotypes from future recruitment. Various sequential and non-sequential procedures are available to identify an association between the whole genome, or at least a portion of it, and the incidence of adverse events. In this paper we start with a suspected association between the genotype and the risk of an adverse event and suppose that the genetic subgroups with elevated risk can be identified. Our focus is determination of whether the patients identified as being at risk should be excluded from further studies of the drug. We propose using a utility function to? determine the appropriate action, taking into account the relative costs of suffering an adverse reaction and of failing to alleviate the patient's disease. Two illustrative examples are presented, one comparing patients who suffer from an adverse event with contemporary patients who do not, and the other making use of a reference control group. We also illustrate two classification methods, LASSO and CART, for identifying patients at risk, but we stress that any appropriate classification method could be used in conjunction with the proposed utility function. Our emphasis is on determining the action to take rather than on providing definitive evidence of an association. Copyright (C) 2008 John Wiley & Sons, Ltd.

Impact Of Drug Formulation And Free Platinum/cisplatin Ratio On Hypersensitivity Reactions To Cisplatin: Formulation Matters.

Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.

Adverse reactions following mass drug administration with diethylcarbamazine in lymphatic filariasis endemic areas in the Northeast of Brazil

INTRODUCTION: The Global Programme to Eliminate Lymphatic Filariasis was launched with the goal of eliminating this disease via the annual mass drug administration (MDA) of a single dose of antifilarial drugs. Adverse drug reactions following MDA are a major factor of poor treatment adherence in several countries. This study assessed the occurrence of adverse drug reactions (ADRs) following the first round of mass treatment in two communities treated with different dosages of diethylcarbamazine (DEC) in the City of Recife, Brazil. METHODS: Population-based cross-sectional surveys were conducted in a random sample of the population living in both communities (Areas I and II). The dose of DEC recommended by the WHO (6mg/kg) was calculated based on the individual's weight-for-age. In Area II, weight differences between the genders were also considered when determining dosage. Data were obtained through interviews conducted in the first 12 to 48h and on the 5th day after MDA during household visits. RESULTS: A total of 487 and 365 individuals were interviewed in Areas I and II, respectively. The prevalence of ADRs in Area I (23.6; 95%CI: 19.1-29.5) was higher than in Area II (16.2; 95%CI:11.9-21.5)(p=0.0078). The prevalence of ADRs among females was higher than in males in Area I (p=0.0021). In Area II, no significant difference between the genders was observed (p=0.1840). Age was not associated with ADRs in either area. CONCLUSIONS: Adjusting MDA dosage schedules according to weight-for-age and sex may be may contribute to reduce the occurrence of adverse drug reactions in the population.

Approach to the patient with drug allergy

Clinicians commonly encounter patients who report to have drug allergy. In a large part, such allergy corresponds to adverse drug reactions, which are not immune mediated. The incriminated drug need not always be avoided for further therapy. On the other hand, drug allergy may manifest in many unexpected clinical pictures and thus not be recognized. There is no single standardized diagnostic test to confirm the immune-mediated mechanism and to identify the causative drug. Therefore, immune-mediated drug hypersensitivity reactions and their causative drugs have to be considered by the constellation of exposure, timing, and clinical features, including the pattern of organ manifestation. Prior experience with the drug is also an important feature. An allergologic workup with additional investigation may provide some help. Patients should be informed carefully about their drug allergy, whereby symptoms, drug that elicits reaction, modes of diagnosis of drug allergy, and possibly alternatives should be indicated in their allergy passport.