"Real-world" effectiveness of methylphenidate in improving the academic achievement of Attention-Deficit Hyperactivity Disorder diagnosed students-A systematic review.

WHAT IS KNOWN AND OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) symptoms usually impairs academic achievement and can trigger the onset of medication. Methylphenidate is a drug widely prescribed to treat ADHD. However, systematic reviews of randomized clinical trials suggest that it does not lead to great improvements in academic performance. Thus, we aimed to evaluate the evidence on the "real-world" effectiveness of methylphenidate in improving the academic achievement of ADHD students. METHODS: We conducted a systematic review of observational studies retrieved from five electronic databases, besides a manual search and search in grey literature. Studies evaluating treatment with methylphenidate compared to no treatment or other pharmacological/non-pharmacological alternatives used in ADHD were included. The risk of bias of the selected studies was assessed using adapted versions of the Newcastle-Ottawa Scale. RESULTS AND DISCUSSION: Nine studies (from ten reports) were included in the review: four cohorts, two before-and-after designs and three cross-sectional studies. They involved 12,269 children and adolescents aged 6-18 years. The doses of methylphenidate ranged from 10 to 72 mg/day, and the duration of the treatment from 2.6 months to 4.25 years. Five of these studies concluded that methylphenidate improves academic performance. However, three of the four lowest-bias risk studies concluded that the drug is ineffective. Five studies assessed the long-term use of methylphenidate, and four of them concluded that it does not result in better outcomes in the school setting. Most included studies had considerable limitations and significant heterogeneity regarding methodological design and academic performance measurement criteria. WHAT IS NEW AND CONCLUSION: Although some studies indicate that the short-term use of methylphenidate may improve outcomes in the school environment, the available evidence does not support the establishment of adequate conclusions about the real benefits of methylphenidate in the academic improvement of ADHD students.

Prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among university students / Prevalência e fatores associados ao uso de metilfenidato para neuroaprimoramento farmacológico entre estudantes universitários

ABSTRACT Objective To estimate the prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among undergraduate students. Methods Simple random sample of students of the Universidade Federal de Minas Gerais (n=438), invited to answer an online questionnaire about the use of methylphenidate. Data collection occurred from September 2014 to January 2015. The sample was described by means of proportions, means and standard deviations. A multivariate analysis was performed using the Classification and Regression Tree algorithm to classify the cases of use of methylphenidate for cognitive enhancement in groups, based on the exposure variables. Results Out of 378 students included, 5.8% (n=22) reported using methylphenidate for cognitive enhancement; in that, 41% (9/22) in the 4 weeks prior to the survey. The housing situation was the variable most often associated with the use of methylphenidate for cognitive enhancement. Eleven students reported using methylphenidate for cognitive enhancement and other purposes 4 weeks prior to the survey, 27% of whom had no medical prescription to purchase it. Conclusion The use of methylphenidate for cognitive enhancement is frequent among Brazilian undergraduate students and should be considered a serious public health problem, especially due to risks of harm and adverse effects associated with its use.

RESUMO Objetivo Estimar a prevalência e os fatores associados ao uso de metilfenidato para neuroaprimoramento entre estudantes universitários. Métodos Amostra aleatória simples de discentes da Universidade Federal de Minas Gerais (n=438), convidados a responder um questionário online sobre o consumo de metilfenidato. A coleta ocorreu de setembro de 2014 a janeiro de 2015. A amostra foi descrita em termos de proporções, médias e desvio padrão. A análise multivariada foi realizada utilizando o algoritmo Classification and Regression Tree para classificação dos casos de uso do metilfenidato para neuroaprimoramento em grupos, com base nas variáveis de exposição. Resultados Dos 378 alunos incluídos, 5,8% (n=22) declararam ter feito uso de metilfenidato para neuroaprimoramento, sendo 41% (9/22) nas 4 semanas anteriores à pesquisa. A situação da moradia foi a variável mais associada ao uso de metilfenidato para neuroaprimoramento. Relataram o uso do metilfenidato para neuroaprimoramento e outros fins nas 4 semanas anteriores à pesquisa 11 estudantes, sendo que 27% não apresentaram prescrição médica para adquiri-lo. Conclusão O uso de metilfenidato para neuroaprimoramento ocorre no meio acadêmico brasileiro e deve ser considerado sério problema de saúde pública, principalmente diante dos riscos de danos e efeitos adversos associados ao seu uso.

Electronic prescription: frequency and severity of medication errors.

OBJECTIVE: To assess the frequency and severity of prescriptions errors with potentially dangerous drugs (heparin and potassium chloride for injection concentrate) before and after the introduction of a computerized provider order entry (CPOE) system. METHODS: This is a retrospective study that compared errors in manual/pre-typed prescriptions in 2007 (Stage 1) with CPOE prescriptions in 2014 (Stage 2) (Total = 1,028 prescriptions), in two high-complexity hospitals of Belo Horizonte, Brasil. RESULTS: An increase of 25% in the frequency of errors in Hospital 1 was observed after the intervention (p<0.001). In contrast, a decreased error frequency of 85% was observed in Hospital 2 (p<0.001). Regarding potassium chloride, the error rate remained unchanged in Hospital 1 (p>0.05). In Hospital 2, a significant decrease was recorded in Stage 2 (p<0.001). A reduced error severity with heparin (p<0.001) was noted, while potassium chloride-related prescription severity remain unchanged (p> 0.05). CONCLUSIONS: The frequency and severity of medication errors after the introduction of CPOE was affected differently in the two hospitals, which shows a need for thorough observation when the prescription system is modified. Control of new potential errors introduced and their causes for the adoption of measures to prevent these events must be in place during and after the implementation of this technology.

Electronic prescription: frequency and severity of medication errors

SUMMARY OBJECTIVE: To assess the frequency and severity of prescriptions errors with potentially dangerous drugs (heparin and potassium chloride for injection concentrate) before and after the introduction of a computerized provider order entry (CPOE) system. METHODS: This is a retrospective study that compared errors in manual/pre-typed prescriptions in 2007 (Stage 1) with CPOE prescriptions in 2014 (Stage 2) (Total = 1,028 prescriptions), in two high-complexity hospitals of Belo Horizonte, Brasil. RESULTS: An increase of 25% in the frequency of errors in Hospital 1 was observed after the intervention (p<0.001). In contrast, a decreased error frequency of 85% was observed in Hospital 2 (p<0.001). Regarding potassium chloride, the error rate remained unchanged in Hospital 1 (p>0.05). In Hospital 2, a significant decrease was recorded in Stage 2 (p<0.001). A reduced error severity with heparin (p<0.001) was noted, while potassium chloride-related prescription severity remain unchanged (p> 0.05). CONCLUSIONS: The frequency and severity of medication errors after the introduction of CPOE was affected differently in the two hospitals, which shows a need for thorough observation when the prescription system is modified. Control of new potential errors introduced and their causes for the adoption of measures to prevent these events must be in place during and after the implementation of this technology.

RESUMO OBJETIVO: Avaliar a frequência e a gravidade de erros em prescrições envolvendo medicamentos potencialmente perigosos (heparina e cloreto de potássio concentrado injetável) antes e após a introdução de um sistema de prescrição eletrônica. MÉTODOS: Trata-se de estudo retrospectivo que comparou erros em prescrições manuais e pré-digitadas de 2007 (Fase 1) com prescrições eletrônicas de 2014 (Fase 2) (total = 1.028 prescrições), em dois hospitais de alta complexidade de Belo Horizonte. RESULTADOS: Foi observado no hospital 1 aumento de 25% dos erros depois da intervenção (p<0,001), e no hospital 2 foi verificada redução de 85% (p<0,001). Para o cloreto de potássio, a frequência de erros permaneceu a mesma no hospital 1 (p>0,05), independentemente da fase e, no hospital 2, ocorreu redução significativa na fase 2 (p<0,001). Foi identificada redução da gravidade dos erros com a heparina (p<0,001), mas não houve alteração na gravidade dos erros com cloreto de potássio (p>0,05). CONCLUSÕES: A frequência e a gravidade dos erros de medicação após a introdução de prescrição eletrônica foram impactadas de forma diferente nos dois hospitais, demonstrando necessidade de observação criteriosa quando o sistema de prescrição é modificado. Durante e após a implantação dessa tecnologia, deve existir controle dos novos erros potenciais introduzidos e suas causas para a adoção de medidas de prevenção desses eventos.

Prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among university students.

OBJECTIVE: To estimate the prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among undergraduate students. METHODS: Simple random sample of students of the Universidade Federal de Minas Gerais (n=438), invited to answer an online questionnaire about the use of methylphenidate. Data collection occurred from September 2014 to January 2015. The sample was described by means of proportions, means and standard deviations. A multivariate analysis was performed using the Classification and Regression Tree algorithm to classify the cases of use of methylphenidate for cognitive enhancement in groups, based on the exposure variables. RESULTS: Out of 378 students included, 5.8% (n=22) reported using methylphenidate for cognitive enhancement; in that, 41% (9/22) in the 4 weeks prior to the survey. The housing situation was the variable most often associated with the use of methylphenidate for cognitive enhancement. Eleven students reported using methylphenidate for cognitive enhancement and other purposes 4 weeks prior to the survey, 27% of whom had no medical prescription to purchase it. CONCLUSION: The use of methylphenidate for cognitive enhancement is frequent among Brazilian undergraduate students and should be considered a serious public health problem, especially due to risks of harm and adverse effects associated with its use.

Erros de prescrição e administração envolvendo um medicamento potencialmente perigoso / Prescription and administration errors involving a potentially dangerous medicine

Objetivo: identificar os principais erros de prescrição e administração de enoxaparina. Método: estudo transversal, de abordagem quantitativa. Observação de todos os técnicos de enfermagem do serviço diurno da unidade de terapia intensiva, clínica médica e cirúrgica em administrações de enoxaparina e suas respectivas prescrições, conforme o cálculo amostral. Na administração foi utilizada técnica de observação direta e na prescrição checklist do protocolo de prescrição uso e administração de medicamentos. Os softwares EpiData3.1 e SPSS 21.0 auxiliaram na tabulação e análise dos dados, apresentados em tabelas. Resultados: foram analisadas 175 prescrições e administrações. Os principais erros de prescrição foram idade incorreta do paciente e ausência da duração do tratamento. Para os erros de administração, identificou-se dose administrada incorreta, ausência da identificação do paciente no leito, técnica incorreta de administração e horário incorreto. Conclusão: foram demonstrados pontos de fragilidades que levam a erros de medicação, sendo necessário o aperfeiçoamento do sistema de prescrição e administração.

Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012. OBJECTIVES: The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH). SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use the accepted definition of HIT. This was defined as a relative reduction in the platelet count of 50% or greater from the postoperative peak (even if the platelet count at its lowest remained greater than 150 x 109/L) occurring within five to 14 days after the surgery, with or without a thrombotic event occurring in this timeframe. Additionally, we required circulating antibodies associated with the syndrome to have been investigated through laboratory assays. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. Disagreements were resolved by consensus with participation of a third author. MAIN RESULTS: In this update, we included three trials involving 1398 postoperative participants. Participants were submitted to general surgical procedures, minor and major, and the minimum mean age was 49 years. Pooled analysis showed a significant reduction in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.07 to 0.73); low-quality evidence. The number needed to treat for an additional beneficial outcome (NNTB) was 59. The risk of HIT was consistently reduced comparing participants undergoing major surgical procedures exposed to LMWH or UFH (RR 0.22, 95% CI 0.06 to 0.75); low-quality evidence. The occurrence of HIT complicated by venous thromboembolism was significantly lower in participants receiving LMWH compared with UFH (RR 0.22, 95% CI 0.06 to 0.84); low-quality evidence. The NNTB was 75. Arterial thrombosis occurred in only one participant who received UFH. There were no amputations or deaths documented. Although limited evidence is available, it appears that HIT induced by both types of heparins is common in people undergoing major surgical procedures (incidence greater than 1% and less than 10%). AUTHORS' CONCLUSIONS: This updated review demonstrated low-quality evidence of a lower incidence of HIT, and HIT complicated by venous thromboembolism, in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. Similarily, the risk of HIT in people undergoing major surgical procedures was lower when treated with LMWH compared to UFH (low-quality evidence). The quality of the evidence was downgraded due to concerns about the risk of bias in the included studies and imprecision of the study results. These findings may support current clinical use of LMWH over UFH as front-line heparin therapy. However, our conclusions are limited and there was an unexpected paucity of RCTs including HIT as an outcome. To address the scarcity of clinically-relevant information on HIT, HIT must be included as a core harmful outcome in future RCTs of heparin.

Prescription, dispensation and marketing patterns of methylphenidate / Padrões de prescrição, dispensação e comercialização de metilfenidato

OBJECTIVE To analyze the patterns and legal requirements of methylphenidate consumption. METHODS We conducted a cross-sectional study of the data from prescription notification forms and balance lists of drugs sales – psychoactive and others – subject to special control in the fifth largest city of Brazil, in 2006. We determined the defined and prescribed daily doses, the average prescription and dispensation periods, and the regional sales distribution in the municipality. In addition, we estimated the costs of drug acquisition and analyzed the individual drug consumption profile using the Lorenz curve. RESULTS The balance lists data covered all notified sales of the drug while data from prescription notification forms covered 50.6% of the pharmacies that sold it, including those with the highest sales volumes. Total methylphenidate consumption was 0.37 DDD/1,000 inhabitants/day. Sales were concentrated in more developed areas, and regular-release tablets were the most commonly prescribed pharmaceutical formulation. In some regions of the city, approximately 20.0% of the prescriptions and dispensation exceeded 30 mg/day and 30 days of treatment. CONCLUSIONS Methylphenidate was widely consumed in the municipality and mainly in the most developed areas. Of note, the consumption of formulations with the higher abuse risk was the most predominant. Both its prescription and dispensation contrasted with current pharmacotherapeutic recommendations and legal requirements. Therefore, the commercialization of methylphenidate should be monitored more closely, and its use in the treatment of behavioral changes of psychological disorders needs to be discussed in detail, in line with the concepts of the quality use of medicines. .

OBJETIVO Analisar padrões e requisitos legais do consumo de metilfenidato. MÉTODOS Estudo transversal realizado em Belo Horizonte, MG, em 2006. Foram analisados dados de notificações de receitas de metilfenidato e de balanços de vendas de medicamentos – psicoativos e outros – sujeitos a controle especial. Determinou-se a dose diária definida, a dose diária prescrita, o período médio de prescrição e de dispensação, bem como a distribuição regional das vendas desse medicamento no município. Foram estimados, ainda, os gastos com a aquisição do medicamento e analisado o perfil de consumo individual do fármaco por meio da Curva de Lorenz. RESULTADOS Os dados dos balanços mensais de comercialização de psicotrópicos cobriram toda a comercialização notificada do fármaco, enquanto aqueles coletados nas notificações de receita cobriram 50,6% das farmácias que o comercializaram, incluindo aquelas de maior volume de venda. O consumo de metilfenidato foi 0,37 DDD/1.000 habitantes/dia. As vendas concentraram-se em áreas mais desenvolvidas e as formulações farmacêuticas de liberação não controlada foram as mais prescritas. A prescrição e a dispensação com dosagens > 30 mg/dia e período de tratamento > 30 dias apresentaram valores em torno de 20,0% em algumas regiões da cidade. CONCLUSÕES O consumo de metilfenidato apresentou-se elevado no município, maior em áreas mais favorecidas economicamente e predominando o consumo de formulações com maior risco de abuso. Tanto a prescrição quanto a dispensação apresentaram características não compatíveis com as recomendações farmacoterapêuticas e determinações legais. O controle de venda do fármaco ...

Lipodystrophy among patients with HIV infection on antiretroviral therapy: a systematic review protocol.

INTRODUCTION: Lipodystrophy is a frequent and disfiguring adverse effect of antiretroviral therapy (ART) in patients with HIV. It affects the quality of life of the patient and adherence to treatment, and generates new needs for comprehensive healthcare services. The aim of this study will be to conduct a systematic review of the literature from observational studies and describe lipodystrophy among patients with HIV infection during current or previous use of ART. METHODS AND ANALYSIS: A systematic review of observational studies published in MEDLINE, CINAHL, LILACS, EMBASE and International Pharmaceutical Abstracts will be carried out. Citations of included studies will be checked to identify additional studies not identified in the electronic searches. It will include any observational study that considered lipodystrophy as the primary or secondary outcome and that had enrolled adolescent and adult patients with HIV infection who were on current or previous ART for at least 6 months. Data extraction and analysis will be performed independently by two reviewers. The extracted data will be discussed, decisions documented and, where necessary, the authors of the studies will be contacted for clarification. Measures of frequency, prevalence and incidence of lipodystrophy will be stratified according to definition, method of diagnosis and risk factors of the outcome. ETHICS AND DISSEMINATION: Ethics is not required given this is a protocol for a systematic review. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. Updates of the review will be conducted to inform and guide healthcare practice. PROTOCOL REGISTRATION: PROSPERO-42013005450.

Prescription, dispensation and marketing patterns of methylphenidate.

OBJECTIVE To analyze the patterns and legal requirements of methylphenidate consumption. METHODS We conducted a cross-sectional study of the data from prescription notification forms and balance lists of drugs sales - psychoactive and others - subject to special control in the fifth largest city of Brazil, in 2006. We determined the defined and prescribed daily doses, the average prescription and dispensation periods, and the regional sales distribution in the municipality. In addition, we estimated the costs of drug acquisition and analyzed the individual drug consumption profile using the Lorenz curve. RESULTS The balance lists data covered all notified sales of the drug while data from prescription notification forms covered 50.6% of the pharmacies that sold it, including those with the highest sales volumes. Total methylphenidate consumption was 0.37 DDD/1,000 inhabitants/day. Sales were concentrated in more developed areas, and regular-release tablets were the most commonly prescribed pharmaceutical formulation. In some regions of the city, approximately 20.0% of the prescriptions and dispensation exceeded 30 mg/day and 30 days of treatment. CONCLUSIONS Methylphenidate was widely consumed in the municipality and mainly in the most developed areas. Of note, the consumption of formulations with the higher abuse risk was the most predominant. Both its prescription and dispensation contrasted with current pharmacotherapeutic recommendations and legal requirements. Therefore, the commercialization of methylphenidate should be monitored more closely, and its use in the treatment of behavioral changes of psychological disorders needs to be discussed in detail, in line with the concepts of the quality use of medicines.

Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction.

Heparin is a natural agent with antithrombotic action, commercially available for therapeutic use as unfractionated heparin and low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin that promotes antibody-mediated platelet activation. HIT is defined as a relative reduction in platelet count of 50% (even when the platelet count at its lowest level is above>150 x 10(9)/L) occurring within five to 14 days after initiation of the therapy. Thrombocytopenia is the main feature that directs the clinical suspicion of the reaction and the increased risk of thromboembolic complications is the most important and paradoxical consequence. The diagnosis is a delicate issue, and requires a combination of clinical probability and laboratory tests for the detection of platelet activation induced by HIT antibodies. The absolute risk of HIT has been estimated between 1% and 5% under treatment with unfractionated heparin, and less than 1% with low molecular weight heparin. However, high-quality evidence about the risk of HIT from randomized clinical trials is scarce. In addition, information on the frequency of HIT in developing countries is not widely available. This review aims to provide a better understanding of the key features of this reaction and updated information on its frequency to health professionals and other interested parties. Knowledge, familiarity, and access to therapeutic options for the treatment of this adverse reaction are mandatory to minimize the associated risks, improving patient safety.

Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction / Trombocitopenia induzida por heparina: revisão de conceitos de uma importante reação adversa a medicamentos

Heparin is a natural agent with antithrombotic action, commercially available for therapeutic use as unfractionated heparin and low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin that promotes antibodymediated platelet activation. HIT is defined as a relative reduction in platelet count of 50% (even when the platelet count at its lowest level is above > 150 x 10(9)/L) occurring within five to 14 days after initiation of the therapy. Thrombocytopenia is the main feature that directs the clinical suspicion of the reaction and the increased risk of thromboembolic complications is the most important and paradoxical consequence. The diagnosis is a delicate issue, and requires a combination of clinical probability and laboratory tests for the detection of platelet activation induced by HIT antibodies. The absolute risk of HIT has been estimated between 1% and 5% under treatment with unfractionated heparin, and less than 1% with low molecular weight heparin. However, high-quality evidence about the risk of HIT from randomized clinical trials is scarce. In addition, information on the frequency of HIT in developing countries is not widely available. This review aims to provide a better understanding of the key features of this reaction and updated information on its frequency to health professionals and other interested parties. Knowledge, familiarity, and access to therapeutic options for the treatment of this adverse reaction are mandatory to minimize the associated risks, improving patient safety.

A heparina é um agente natural com ação antitrombótica, sendo disponibilizadas para uso terapêutico a heparina não fracionadaeaheparina de baixo peso molecular. A trombocitopenia induzida por heparina (TIH) é uma reação adversa grave às heparinas mediada por anticorpos que promovem ativação de plaquetas. A TIH é definida como uma redução rela- tiva na contagem de plaquetas de 50% (mesmo se a contagem de plaquetas no seu nível mais baixo estiver acima 150 x 10(9)/L) que pode ocorrer no período de cinco a 14 dias após o início da terapia com o medicamento. A trombocitopenia é a principal característica que direciona a suspeita clínica da reação, sendo o aumento do risco de complicações tromboembólicas a consequência mais importante e paradoxal. O diagnóstico é uma questão delicada e requer a combinação da probabilidade clínica com testes laboratoriais para detectar a ativação plaquetária induzida pelos anticorpos da TIH. O risco absoluto de TIH tem sido estimado entre 1 e 5% no tratamento com heparina não fracionada e inferior a 1% no uso de heparina de baixo peso molecular. No entanto, evidências de alta qualidade provenientes de ensaios clínicos randomizados sobre a frequência dessa reação são escassas. Além disso, informações sobre a frequência de TIH em países em desenvolvimento não são amplamente disponíveis. Esta revisão teve como objetivo fornecer aos profissionais de saúde e demais interessados um melhor conhecimento sobre a TIH e as principais características dessa reação, bem como apresentar dados atualizados sobre a frequência da mesma. Conhecimento, familiaridade e acesso a opções terapêuticas para o tratamento dessa reação adversa são necessários para minimizar os riscos associados, melhorando a segurança do paciente.

Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a poorly understood paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population presenting a higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by adverse reactions such as HIT. We therefore sought to determine the relative impact of UFH and LMWH specifically on HIT in postoperative patients receiving thromboembolism prophylaxis. OBJECTIVES: The objective of this review was to compare the incidence of HIT and HIT complicated by thrombosis in patients exposed to UFH versus LMWH in randomised controlled trials (RCTs) of postoperative heparin therapy. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (March 2012) and CENTRAL (2012, Issue 2). In addition, the authors searched LILACS (March 2012) and additional trials were sought from reference lists of relevant publications. SELECTION CRITERIA: We were interested in comparing the incidence of HIT occurring during exposure to UFH or LMWH after any surgical intervention. Therefore, we studied RCTs in which participants were postoperative patients allocated to receive UFH or LMWH, in a blinded or unblinded fashion. Eligible studies were required to have as an outcome clinically diagnosed HIT, defined as a relative reduction in the platelet count of 50% or greater from the postoperative peak (even if the platelet count at its lowest remained > 150 x 10(9)/L) occurring within five to 14 days after the surgery, with or without a thrombotic event occurring in this timeframe. Additionally, circulating antibodies associated with the syndrome were required to have been investigated through laboratory assays. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. Disagreements were resolved by consensus with participation of a third author. MAIN RESULTS: In total two studies involving 923 participants met all the inclusion criteria and were included in the review. Pooled analysis showed a statistically significant reduction in the risk of HIT with LMWH compared with UFH (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.07 to 0.82; P = 0.02). This result suggests that patients treated with LMWH would have a relative risk reduction (RRR) of 76% in the probability of developing HIT compared with patients treated with UFH.Venous thromboembolism (VTE) complicating HIT occurred in 12 of 17 patients who developed HIT. Pooled analysis showed a statistically significant reduction in HIT complicated by VTE with LMWH compared with UFH (RR 0.20, 95% CI 0.04 to 0.90; P = 0.04). This result indicates that patients using LMWH would have a RRR of 80% for developing HIT complicated by VTE compared with patients using UFH. Arterial thrombosis occurred in only one patient who received UFH and there were no amputations or deaths documented. AUTHORS' CONCLUSIONS: There was a lower incidence of HIT and HIT complicated by VTE in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. This is consistent with the current clinical use of LMWH over UFH as front-line heparin therapy. However, conclusions are limited by a scarcity of high quality evidence. We did not expect the paucity of RCTs including HIT as an outcome as heparin is one of the most commonly used drugs worldwide and HIT is a life-threatening adverse drug reaction. To address the scarcity of clinically-relevant information on the topic of HIT as a whole, HIT should be included as an outcome in future RCTs of heparin, and HIT as an adverse drug reaction should be considered in clinical recommendations regarding monitoring of the platelet count for HIT.

[Use of benzodiazepines in local public health services in Coronel Fabriciano in the State of Minas Gerais]. / Utilização de benzodiazepínicos no Serviço Municipal de Saúde de Coronel Fabriciano, Minas Gerais.

In this study, indications for benzodiazepines in the healthcare services of the city of Coronel Fabriciano (State of Minas Gerais, Brazil) were analyzed in terms of compliance with the indications established in the literature. The study was carried out using all prescriptions for benzodiazepines in municipal healthcare units between September and October 2006, as well as the prescription form filled out by the prescriber and computer files. A total of 1866 prescriptions were analyzed; 59.7% were for diazepam and the rest were for clonazepam. The mean daily dose per 1000 inhabitants/day was 24.69 for diazepam and 3.58 for clonazepam. Approximately 50% of the indications were as a hypnotic or anti-anxiety medication; 21.9% were for "chronic use/dependence" and the rest were for other indications. Among the prescriptions that fulfilled the inclusion criteria for the analysis of indication adequacy (1618), approximately 70% were found to be inadequate considering the indication and duration of treatment. It revealed a high percentage of the inadequate use of benzodiazepines, especially due to prolonged use and the treatment of cases considered by the prescribers as chronic use/dependence. Thus, healthcare services bear responsibility for the maintenance of dependence.

Utilização de benzodiazepínicos no Serviço Municipal de Saúde de Coronel Fabriciano, Minas Gerais / Use of benzodiazepines in local public health services in Coronel Fabriciano in the State of Minas Gerais

Neste estudo foram avaliadas as indicações de benzodiazepínicos no Serviço Municipal de Saúde de Coronel FabricianoMG, verificando sua conformidade com o preconizado pela literatura. O estudo avaliou todas as receitas desses medicamentos provenientes das Unidades Municipais de Saúde no período de Setembro a Outubro de 2006, os formulários de indicação clínica preenchidos pelo prescritor e cadastros informatizados do serviço. Analisaram-se 1.866 receitas, sendo 59,7 por cento do Diazepam e o restante do Clonazepam. A Dose Diária Definida por mil habitantes por dia foi de 24,69 para o Diazepam e de 3,58 para o Clonazepam. Cerca de 50 por cento das indicações relatadas pelos médicos foram como hipnótico ou ansiolítico, 21,9 por cento para "uso crônico/dependência" e o restante para outras indicações. Das receitas que atenderam aos critérios de inclusão para análise da adequação da indicação (1618), cerca de 70 por cento foram consideradas não adequadas, tendo em vista a indicação e o tempo de tratamento. Houve um alto percentual de inadequação na utilização de benzodiazepínicos, principalmente pelo uso prolongado e para atender a casos considerados pelos prescritores como uso crônico/dependência. Assim, há responsabilidade do serviço de saúde na manutenção da dependência.

In this study, indications for benzodiazepines in the healthcare services of the city of Coronel Fabriciano (State of Minas Gerais, Brazil) were analyzed in terms of compliance with the indications established in the literature. The study was carried out using all prescriptions for benzodiazepines in municipal healthcare units between September and October 2006, as well as the prescription form filled out by the prescriber and computer files. A total of 1866 prescriptions were analyzed; 59.7 percent were for diazepam and the rest were for clonazepam. The mean daily dose per 1000 inhabitants/day was 24.69 for diazepam and 3.58 for clonazepam. Approximately 50 percent of the indications were as a hypnotic or anti-anxiety medication; 21.9 percent were for "chronic use/dependence" and the rest were for other indications. Among the prescriptions that fulfilled the inclusion criteria for the analysis of indication adequacy (1618), approximately 70 percent were found to be inadequate considering the indication and duration of treatment. It revealed a high percentage of the inadequate use of benzodiazepines, especially due to prolonged use and the treatment of cases considered by the prescribers as chronic use/dependence. Thus, healthcare services bear responsibility for the maintenance of dependence.

Heparin pharmacovigilance in Brazil.

OBJECTIVE: To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. METHODS: The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009) were searched. A survey with industries having an active permission for marketing the drug in Brazil was conducted. RESULTS: Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10% less anticoagulant activity than that previously produced and this change may have clinical implications. CONCLUSIONS: Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.

[Factors associated with benzodiazepine prescription by local health services in Coronel Fabriciano, Minas Gerais State, Brazil]. / Fatores associados ao uso de benzodiazepínicos no serviço municipal de saúde da cidade de Coronel Fabriciano, Minas Gerais, Brasil.

Numerous countries have witnessed increasing misuse of benzodiazepines. This cross-sectional study assessed the factors associated with prescription of benzodiazepines for users of the Municipal Health Service in Colonel Fabriciano, Minas Gerais State, Brazil. Data were collected from official records on drug prescription (n = 1,866) from September to October 2006. Bivariate and multivariate analyses using Poisson regression were performed. Prolonged benzodiazepine use was independently associated with benzodiazepine type and patient participation in health programs. Concomitant use of other psychoactive drugs was independently associated with age and participation in health programs. Type of benzodiazepine (clonazepam or diazepam) was independently associated with age and gender, as well as with participation in health programs. Factors associated with benzodiazepine prescription show the problem's extent and should be considered in planning interventions to rationalize the use of these drugs in Brazil, particularly through health program planning.

Fatores associados ao uso de benzodiazepínicos no serviço municipal de saúde da cidade de Coronel Fabriciano, Minas Gerais, Brasil / Factors associated with benzodiazepine prescription by local health services in Coronel Fabriciano, Minas Gerais State, Brazil

O uso inadequado de benzodiazepínicos é observado em diversos países. Este estudo transversal avaliou os fatores associados à prescrição de benzodiazepínicos para os usuários do Serviço Municipal de Saúde de Coronel Fabriciano, Minas Gerais, Brasil. A coleta de dados foi feita a partir da notificação das receitas (n = 1.866), entre setembro e outubro de 2006. Análises bivariada e multivariada, utilizando regressão de Poisson, foram executadas. O uso prolongado de benzodiazepínicos foi associado independentemente com o tipo de benzodiazepínico prescrito e cadastro em programas de saúde. O uso concomitante de outros psicofármacos foi associado independentemente com a idade e cadastro nos programas de saúde. O tipo de benzodiazepínico utilizado (Diazepam ou Clonazepam) esteve independentemente associado com a idade e sexo dos pacientes, bem como, com a participação em programas de saúde. Os fatores associados à prescrição de benzodiazepínicos evidenciam a amplitude do problema e devem ser considerados no planejamento de intervenções para a racionalização da utilização desses medicamentos no município, particularmente na organização dos programas de saúde.

Numerous countries have witnessed increasing misuse of benzodiazepines. This cross-sectional study assessed the factors associated with prescription of benzodiazepines for users of the Municipal Health Service in Colonel Fabriciano, Minas Gerais State, Brazil. Data were collected from official records on drug prescription (n = 1,866) from September to October 2006. Bivariate and multivariate analyses using Poisson regression were performed. Prolonged benzodiazepine use was independently associated with benzodiazepine type and patient participation in health programs. Concomitant use of other psychoactive drugs was independently associated with age and participation in health programs. Type of benzodiazepine (clonazepam or diazepam) was independently associated with age and gender, as well as with participation in health programs. Factors associated with benzodiazepine prescription show the problem's extent and should be considered in planning interventions to rationalize the use of these drugs in Brazil, particularly through health program planning.

Farmacovigilância da heparina no Brasil / Heparin pharmacovigilance in Brazil

OBJETIVO: Investigar a origem das preparações de heparina, na forma farmacêutica injetável, disponíveis no mercado brasileiro, discutindo o impacto do perfil dos produtos comercializados e das alterações na monografia da heparina na segurança do fármaco. MÉTODOS: Pesquisou-se o banco de dados de Produtos Registrados das Empresas de Medicamentos da Anvisa e o Dicionário de Especialidades Farmacêuticas (DEF 2008/2009). Foi realizado inquérito com as indústrias com autorização ativa para o comércio do fármaco no Brasil. RESULTADOS: Cinco indústrias possuem autorização para o comércio de heparina não fracionada no Brasil. Três são de origem suína e duas de origem bovina, sendo que apenas uma possui essa informação explicitada na bula. A efetividade e a segurança da heparina, estudadas em populações estrangeiras, podem não representar a nossa realidade, já que a maioria dos países não produz a heparina bovina. A heparina atualmente comercializada tem, ainda, aproximadamente 10 por cento menos atividade anticoagulante que a anteriormente produzida, e essa alteração pode ter implicações clínicas. CONCLUSÃO: Evidências acerca da ausência de intercambialidade de doses entre as heparinas de origem bovina e suína e o diferenciado perfil de segurança entre esses fármacos indicam necessidade de acompanhamento do tratamento e da resposta dos pacientes. Eventos que ameacem a segurança do paciente devem ser comunicados ao sistema da farmacovigilância do país.

OBJECTIVE: To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. METHODS: The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009) were searched. A survey with industries having an active permission for marketing the drug in Brazil was conducted. RESULTS: Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10 percent less anticoagulant activity than that previously produced and this change may have clinical implications. CONCLUSIONS: Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.