Comparison of FDA accelerated vs regular pathway approvals for lung cancer treatments between 2006 and 2018.

Regulatory agencies around the world have been using flexible requirements for approval of new drugs, especially for cancer drugs. The US Food and Drug Administration (FDA) is mostly the first agency to approve new drugs worldwide, mainly due to the faster terms of the accelerated pathway and breakthrough therapy designation. Surrogate endpoints and preliminary data (e.g. single-arm and phase 2 studies) are used for these new approvals, however larger effect sizes are expected. We aim to compare FDA Accelerated vs Regular Pathway approvals and Breakthrough therapy designations (BTD) for lung cancer treatments between 2006 and 2018 regarding study design, sample size, outcome measures and effect size. We assessed the FDA database to collect data from studies that formed the basis of approvals of new drugs or indications for lung cancer spanning from 2006 to 2018. We found that accelerated pathway approvals are based on significantly more single-arm studies with small sample sizes and surrogate primary endpoints. However, effect size was not different between the pathways. A large proportion of studies used to support regular pathway approvals also showed these characteristics that are related to low quality and uncertain evidence. Compared to other approvals, BTD were more frequently based on single-arm studies. There was no significant difference in use of surrogate endpoints or sample size. 44% of BTD were based on studies demonstrating large effect sizes, proportionally more than approvals not receiving this designation. In conclusion, based on the indicators of evidence quality we extracted, criteria's for granting accelerated approval and breakthrough therapy designation seen not clear. Faster approvals are in the majority full of uncertainties which should be viewed with caution and the patient have to be communicated to allow shared decision making. Post-marketing validation is essential.

U.S. Food and Drug Administration anticancer drug approval trends from 2016 to 2018 for lung, colorectal, breast, and prostate cancer.

OBJECTIVE: This paper aims to describe the clinical and regulatory aspects of new drugs and indications that were approved for lung, breast, prostate, and colorectal cancer, from 2016 to 2018, in order to provide health technology assessment trends in oncology. METHODS: Data were collected from the US Food and Drug Administration (FDA) online database for new medications and indications approved for the above-mentioned types of cancer. Data regarding clinical study characteristics and regulatory information were collected. RESULTS: From 2016 to 2018, 53 percent of the FDA approvals of new drugs and indications for the most incident cancers were for oral protein kinase inhibitor monotherapy for advanced lung cancer. Since 2018, four drugs were approved as tumor-agnostic therapies. A biomarker was included in 72 percent of indications, and 58 percent of approvals were for targeted therapies, potentially heralding an end to research into conventional cytotoxic agents. A special designation for faster approval was granted in 78 percent of new approvals. The majority of the studies were open label randomized controlled trials (RCTs) (44 percent), followed by blind RCTs, single-arm clinical trials, and cohort studies. Only 14 percent of studies used overall survival as the primary end point; the vast majority used surrogate end points, and did not use patient-important outcomes. Three biosimilars were approved in the period. CONCLUSION: Advanced lung cancer therapy, mainly targeted drugs, accounted for 53 percent of approvals. Special designations for faster approval were used in 78 percent of FDA approvals, and four drugs were approved for tumor-agnostic treatment-a new form of approval.

Níveis de prevenção cardiovascular / Cardiovascular disease prevention levels

Epidemiologia clínica é o campo de conhecimento que estuda as melhores práticas assistenciais, com foco nos interesses do paciente de compartilhar as decisões com os médicos e demais profissionais de saúde que realizam o atendimento ou prestam cuida-dos. Vale-se da mesma metodologia usada pela epidemiologia tradicional para qualificar e desenvolver a pesquisa aplicada à prática clínica. A vacinação contra a febre amarela, mostra bem a diferença entre os interesses da epidemiologia clínica e os da epidemiologia tradicional. A estratégia populacional pode trazer muitos benefícios para a coletividade que, no geral, apresenta baixo risco e muitos malefícios para um grupo muito menor de indivíduos de alto risco. Os padrões de ações preventivas modificam-se de acordo com a evolução no tempo. Além da prevenção primordial, primária, secundária e terciária este texto discute a prevenção quaternária por meio de ações que visam evitar os danos associados ao uso excessivo de procedimentos diagnósticos e terapêuticos. O diálogo sobre saúde é um contraponto entre o saber científico e o saber popular, a informação dada a partir do conhecimento prévio do indivíduo e da comunidade deve respeitar seus valores, como exemplificado por trabalhos realizados em escolas de ensino fundamental.

Clinical Epidemiology is the field of knowledge that studies the best care practices, focusing on the patient's interest in sharing decisions with physicians and other health professionals who provide treatment or health care. It employs the same methodology used by traditional epidemiology to qualify and develop research applied to clinical practice. Vaccination against yellow fever clearly shows the difference between the interests of clinical epidemiology and those of traditional epidemiology. Population strategy can produce many benefits for society as a whole, which generally involves a lower risk, to the detriment of a much smaller group of high-risk individuals. Preventive care patterns change according to temporal evolution. In addition to primordial, primary, secondary and tertiary prevention, this text also discusses quaternary prevention through actions aimed at avoiding the damage associated with the excessive use of diagnostic and therapeutic procedures. The dialogue on health is a counterpoint between scientific knowledge and common knowledge. Information produced from the prior knowledge of the individual and the community must respect their values, as exemplified by work carried out in elementary schools

Ice pack induced perineal analgesia after spontaneous vaginal birth: Randomized controlled trial.

BACKGROUND: Ice-pack is widely used for alleviating postpartum perineal pain sustained after birth related perineal trauma. However, it lacks robust evidence on timing and frequency of applications, to ensure the effective and safe use of this therapy. AIMS: To evaluate if a 10min ice-pack application relieved postpartum perineal pain and if the analgesic effect was maintained for up to 2h. METHODS: A randomised controlled trial conducted from December 2012 to February 2013 with 69 primiparous women ≥18 years old, 6-24h postpartum, with perineal pain ≥3, who had not received anti-inflammatory medication or analgesics after childbirth, who were randomised to a single ice-pack application on the perineum for 10min or standard care. The primary and secondary outcomes were a reduction ≥30% in perineal pain intensity, immediately after the application and the maintenance of the analgesic effect for up to 2h, respectively. FINDINGS: Immediately post-intervention, the proportion of women whose perineal pain decreased ≥30% was significantly higher in the experimental group. Within 2h, there was no significant difference in the pain levels in both groups. Within 2h, for 61.9% and 89.3% of women in the experimental and control group, respectively, the perineal pain levels remained unchanged. For the remaining participants, perineal pain was increasing after an average time of 1h 45min and 1h 56min for the experimental and control groups, respectively. CONCLUSION: By applying an ice-pack for 10min to the perineum, effective pain relief is achieved, that is maintained for between 1h 45min and 2h.

Staying in the labor force among patients with rheumatoid arthritis and associated factors in Southern Brazil.

BACKGROUND: Rheumatoid arthritis primarily affects the working-age population and may cause key functional and work limitations. As the disease progresses, individuals become increasingly unable to conduct daily activities, which has a substantial personal and socioeconomic impact. Fairly recent prior studies showed that patients with RA stop working 20 years earlier than age-matched controls. Factors related to sociodemographic, clinical, care and disease profiles might affect the loss of work capacity. The purpose of this study was to assess the factors associated with the prevalence of working patients with rheumatoid arthritis in the municipality of Blumenau. METHODS: A cross-sectional, population-based study was conducted between July 2014 and January 2015, with 296 individuals aged 20 years or older, male and female, living in Blumenau, Santa Catarina state, Brazil, and diagnosed with rheumatoid arthritis according to the 1987 American College of Rheumatology criteria. The prevalence of working patients with RA was assessed by employment status self-reporting during the interview. The chi-squared test, Wald test and Poisson regression analysis were used to test the possible associations between the independent variables and outcome. RESULTS: The prevalence of working patients with rheumatoid arthritis was 44.3%. Patients aged 20 to 59 years had a 90% higher prevalence of outcome than subjects aged 60 years or older. The prevalence of working patients was 132% and 73% higher among individuals with low income and high functional disability, measured using the Health Assessment Questionnaire (HAQ), respectively. CONCLUSION: The prevalence of working RA patients was highest among adult patients with low income and high functional disability. The first variable is directly related to the individual characteristic, the second reflects the socioeconomic context of the patient, and the third reflects the degree of disability caused by the disease, which may be modifiable by health professionals.

Prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis in Southern Brazil.

OBJECTIVE: To estimate the prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis. METHODS: A cross-sectional study using the American College of Rheumatology diagnostic criteria in order to select patients seen at primary or secondary health care units in Blumenau, Santa Catarina, Southern Brazil, in 2014. The presence of ischemic heart disease was defined as an acute myocardial infarction with percutaneous coronary intervention or coronary artery bypass graft surgery that has occurred after diagnosis. Fischer's exact test, Wald's linear trend test, and multivariate logistic regression analysis were used to test the associations. RESULTS: Among 296 patients (83.1% female) with a mean age of 56.6 years and a mean rheumatoid arthritis duration of 11.3 years, 13 reported having acute myocardial infarction requiring a percutaneous or surgical reperfusion procedure, a prevalence of 4.4% (95% CI 2.0-6.7). Diabetes Mellitus (odds ratio [OR] 4.9 [95% CI 1.6-13.8]) and disease duration >10 years (OR 8.2 [95% CI 1.8-39.7]) were the only factors associated with an ischemic disease that remained in the final model, after the multivariate analysis. CONCLUSION: The prevalence of acute myocardial infarction was similar to that observed in other studies. Among the traditional risk factors, Diabetes Mellitus, and among the factors related to rheumatoid arthritis, disease duration, were the variables associated with comorbidity.

Prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis in Southern Brazil / Prevalência de doença isquêmica cardíaca e fatores associados em pacientes com artrite reumatoide no Sul do Brasil

Abstract Objective: To estimate the prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis. Methods: A cross-sectional study using the American College of Rheumatology diagnostic criteria in order to select patients seen at primary or secondary health care units in Blumenau, Santa Catarina, Southern Brazil, in 2014. The presence of ischemic heart disease was defined as an acute myocardial infarction with percutaneous coronary intervention or coronary artery bypass graft surgery that has occurred after diagnosis. Fischer's exact test, Wald's linear trend test, and multivariate logistic regression analysis were used to test the associations. Results: Among 296 patients (83.1% female) with a mean age of 56.6 years and a mean rheumatoid arthritis duration of 11.3 years, 13 reported having acute myocardial infarction requiring a percutaneous or surgical reperfusion procedure, a prevalence of 4.4% (95% CI 2.0-6.7). Diabetes Mellitus (odds ratio [OR] 4.9 [95% CI 1.6-13.8]) and disease duration >10 years (OR 8.2 [95% CI 1.8-39.7]) were the only factors associated with an ischemic disease that remained in the final model, after the multivariate analysis. Conclusion: The prevalence of acute myocardial infarction was similar to that observed in other studies. Among the traditional risk factors, Diabetes Mellitus, and among the factors related to rheumatoid arthritis, disease duration, were the variables associated with comorbidity.

Resumo Objetivo: Estimar a prevalência da doença isquêmica cardíaca e os fatores associados em pacientes com artrite reumatoide. Métodos: Estudo transversal que usou o critério diagnóstico do Colégio Americano de Reumatologia para selecionar pacientes atendidos nas unidades de saúde da atenção primária ou secundária em Blumenau, Santa Catarina, sul do Brasil, em 2014. A presença de doença cardíaca isquêmica foi definida com infarto agudo do miocárdio com intervenção coronariana percutânea ou cirurgia de revascularização do miocárdio que tenha ocorrido depois do diagnóstico. Para testar as associações usou-se o teste exato de Fischer, o teste de tendência linear de Wald e a análise de regressão logística multivariada. Resultados: Entre 296 pacientes, 83,1% de mulheres, com média de 56,6 anos, tempo médio de artrite reumatoide de 11,3 anos, 13 relatam ter tido infarto agudo do miocárdio que necessitou de procedimento de reperfusão percutânea ou cirúrgica, prevalência de 4,4% (IC 95% 2,0-6,7). O diabetes melittus (razão de chance de 4,9 [IC 95% 1,6-13,8]) e o tempo de doença maior do que 10 anos (razão de chance de 8,2 [IC 95% 1,8-39,7]) foram os únicos fatores associados com a doença isquêmica que permaneceram no modelo final após análise multivariada. Conclusão: A prevalência de infarto agudo do miocárdio foi semelhante com a observada em outros estudos. Entre os fatores de risco tradicionais e entre os fatores relacionados à artrite reumatoide, o diabetes melittus e o tempo de doença foram as variáveis associadas à comorbidade

A method for cohort selection of cardiovascular disease records from an electronic health record system.

INTRODUCTION: An electronic healthcare record (EHR) system, when used by healthcare providers, improves the quality of care for patients and helps to lower costs. Information collected from manual or electronic health records can also be used for purposes not directly related to patient care delivery, in which case it is termed secondary use. EHR systems facilitate the collection of this secondary use data, which can be used for research purposes like observational studies, taking advantage of improvement in the structuring and retrieval of patient information. However, some of the following problems are common when conducting a research using this kind of data: (i) Over time, systems and data storage methods become obsolete; (ii) Data concerns arise since the data is being used in a context removed from its original intention; (iii) There are privacy concerns when sharing data about individual subjects; (iv) The partial availability of standard medical vocabularies and natural language processing tools for non-English language limits information extraction from structured and unstructured data in the EHR systems. A systematic approach is therefore needed to overcome these, where local data processing is performed prior to data sharing. METHOD: The proposed study describes a local processing method to extract cohorts of patients for observational studies in four steps: (1) data reorganization from an existing local logical schema into a common external schema over which information can be extracted; (2) cleaning of data, generation of the database profile and retrieval of indicators; (3) computation of derived variables from original variables; (4) application of study design parameters to transform longitudinal data into anonymized data sets ready for statistical analysis and sharing. Mapping from the local logical schema into a common external schema must be performed differently for each EHR and is not subject of this work, but step 2, 3 and 4 are common to all EHRs. The external schema accepts parameters that facilitate the extraction of different cohorts for different studies without having to change the extraction algorithms, and ensures that, given an immutable data set, can be done by the idempotent process. Statistical analysis is part of the process to generate the results necessary for inclusion in reports. The generation of indicators to describe the database allows description of its characteristics, highlighting study results. The set extraction/statistical processing is available in a version controlled repository and can be used at any time to reproduce results, allowing the verification of alterations and error corrections. This methodology promotes the development of reproducible studies and allows potential research problems to be tracked upon extraction algorithms and statistical methods RESULTS: This method was applied to an admissions database, SI3, from the InCor-HCFMUSP, a tertiary referral hospital for cardiovascular disease in the city of São Paulo, as a source of secondary data with 1116848 patients records from 1999 up to 2013. The cleaning process resulted in 313894 patients records and 27698 patients in the cohort selection, with the following criteria: study period: 2003-2013, gender: Male, Female, age:≥18years old, at least 2 outpatient encounters, diagnosis of cardiovascular disease (ICD-10 codes: I20-I25, I64-I70 and G45). An R script provided descriptive statistics of the extracted cohort. CONCLUSION: This method guarantees a reproducible cohort extraction for use of secondary data in observational studies with enough parameterization to support different study designs and can be used on diverse data sources. Moreover it allows observational electronic health record cohort research to be performed in a non-English language with limited international recognized medical vocabulary.

Patient adherence to ischemic heart disease treatment.

INTRODUCTION:: The effectiveness of the treatment of chronic diseases depends on the participation of the patient, influenced by different sociocultural factors, which are not fully recognized by the treatment routine. OBJECTIVE:: To search for some of these factors that hinder or facilitate adherence to treatment and use of healthcare resources, approaching patients with ischemic heart disease. METHOD:: A cross-sectional study was conducted using face-to-face interviews. We applied semi-structured questionnaires to 347 individuals and recorded 141 interviews for qualitative analysis. Descriptors were selected to identify eight categories of analyses. The quantitative data were submitted to descriptive analysis of frequency. RESULTS:: Only 2% had good medication adherence according to score on Morisky questionnaire. About 23% bought statins; the others obtained statin in the public health institution. Thirty-six speeches were selected and classified according to the following categories: knowledge about disease and medication, difficulty of acquisition, self management of treatment, difficulties of access to health services, side effect of statins, caregiver support, transportation to health services and concerns about the disease progression. However, it was noticed that about 1/3 of the care outside the research institution can be characterized as an attempt to bring rationalization to the health system. CONCLUSION:: The improved adherence to chronic treatment of ischemic heart disease depends on the establishment of effective flows for referral and counter-referral from one care unit to another, relevant information and clarification of the questions for the patients and the attention of health professionals to the many social and cultural factors involved in treatment adherence. New research should be focused on educational groups by integrated multidisciplinary teams in order to share treatment decisions, thereby increasing the patient's commitment to his own health.

Impact of rheumatoid arthritis in the public health system in Santa Catarina, Brazil: a descriptive and temporal trend analysis from 1996 to 2009.

INTRODUCTION: There are few studies that carried out a descriptive and trend analysis based on available data from the Unified Health System (SUS) between pre- and post-free dispensing of pharmacological treatment of rheumatoid arthritis (RA) from the perspective of the public health system, in terms of the direct cost of the disease among adults and elderly residents of the State of Santa Catarina, Brazil. This study aims to characterize the direct cost of medical and surgical procedures before and after the dispensing of drugs in this state. METHODS: This is a time series-type study with a cross-sectional survey of data from the Hospital (SIH) and Outpatient (SIA) Information System of SUS during the period from 1996 to 2009. RESULTS: Between 1996 and 2009, the total expenditure for hospital- and outpatient pharmacological treatment of rheumatoid arthritis was R$ 26,659,127.20. After the dispensing of drug treatment by SUS a decrease of 36% in the number of hospital admissions was observed; however, an increase of 19% in clinical procedures was noted. CONCLUSION: During the observed period, a reduction in the number of hospital admissions for both clinical and orthopedic surgical procedures related to this disease was observed. Nevertheless, there was an increase in the cost of medical admissions.

Impact of rheumatoid arthritis in the public health system in Santa Catarina, Brazil: a descriptive and temporal trend analysis from 1996 to 2009 / Impacto da artrite reumatoide no sistema público de saúde em Santa Catarina, Brasil: análise descritiva e de tendência temporal de 1996 a 2009

ABSTRACT Introduction: There are few studies that carried out a descriptive and trend analysis based on available data from the Unified Health System (SUS) between pre- and post-free dispensing of pharmacological treatment of rheumatoid arthritis (RA) from the perspective of the public health system, in terms of the direct cost of the disease among adults and elderly residents of the State of Santa Catarina, Brazil. This study aims to characterize the direct cost of medical and surgical procedures before and after the dispensing of drugs in this state. Methods: This is a time series-type study with a cross-sectional survey of data from the Hospital (SIH) and Outpatient (SIA) Information System of SUS during the period from 1996 to 2009. Results: Between 1996 and 2009, the total expenditure for hospital- and outpatient pharmacological treatment of rheumatoid arthritis was R$ 26,659,127.20. After the dispensing of drug treatment by SUS a decrease of 36% in the number of hospital admissions was observed; however, an increase of 19% in clinical procedures was noted. Conclusion: During the observed period, a reduction in the number of hospital admissions for both clinical and orthopedic surgical procedures related to this disease was observed. Nevertheless, there was an increase in the cost of medical admissions.

RESUMO Introdução: Poucos estudos fizeram uma análise descritiva e de tendência dos dados disponíveis do Sistema Único de Saúde (SUS) entre os períodos pré e pós-dispensação gratuita do tratamento medicamentoso da artrite reumatoide (AR) sob a perspectiva do sistema público de saúde em termos de custo direto da doença entre adultos e idosos moradores do Estado de Santa Catarina, Brasil. O presente trabalho tem o objetivo de caracterizar o custo direto de procedimentos clínicos e cirúrgicos antes e após o fornecimento de medicamentos no estado. Métodos: Estudo do tipo série temporal com levantamentos transversais entre 1996 e 2009 dos dados do Sistema de Informação Hospitalar (SIH) e Ambulatorial (SIA) do SUS. Resultados: Entre 1996 a 2009, o gasto total para o tratamento hospitalar e medicamentoso ambulatorial da artrite reumatoide foi de R$ 26.659.127,20. Após a dispensação do tratamento medicamentoso pelo SUS observou-se queda de 36% do número de internações hospitalares. Entretanto notou-se um aumento de 19% nos procedimentos clínicos. Conclusão: No período observado notou-se uma redução do número de internações hospitalares tanto para procedimentos clínicos quanto cirúrgicos ortopédicos relacionadas a essa doença. Apesar disso, ocorreu um aumento do custo das internações clínicas.

Patient adherence to ischemic heart disease treatment / Adesão do paciente ao tratamento da doença isquêmica do coração

Summary Introduction: The effectiveness of the treatment of chronic diseases depends on the participation of the patient, influenced by different sociocultural factors, which are not fully recognized by the treatment routine. Objective: To search for some of these factors that hinder or facilitate adherence to treatment and use of healthcare resources, approaching patients with ischemic heart disease. Method: A cross-sectional study was conducted using face-to-face interviews. We applied semi-structured questionnaires to 347 individuals and recorded 141 interviews for qualitative analysis. Descriptors were selected to identify eight categories of analyses. The quantitative data were submitted to descriptive analysis of frequency. Results: Only 2% had good medication adherence according to score on Morisky questionnaire. About 23% bought statins; the others obtained statin in the public health institution. Thirty-six speeches were selected and classified according to the following categories: knowledge about disease and medication, difficulty of acquisition, self management of treatment, difficulties of access to health services, side effect of statins, caregiver support, transportation to health services and concerns about the disease progression. However, it was noticed that about 1/3 of the care outside the research institution can be characterized as an attempt to bring rationalization to the health system. Conclusion: The improved adherence to chronic treatment of ischemic heart disease depends on the establishment of effective flows for referral and counter-referral from one care unit to another, relevant information and clarification of the questions for the patients and the attention of health professionals to the many social and cultural factors involved in treatment adherence. New research should be focused on educational groups by integrated multidisciplinary teams in order to share treatment decisions, thereby increasing the patient's commitment to his own health.

Resumo Introdução: A efetividade do tratamento das doenças crônicas depende da participação do paciente, influenciada por diferentes motivos socioculturais, pouco reconhecidos pela rotina assistencial. Objetivo: Identificar os fatores de adesão ao tratamento e o uso dos recursos assistenciais de pacientes com doença isquêmica do coração. Método: Estudo transversal com entrevistas presenciais de 347 indivíduos submetidos a questionários semiestruturados, com 141 delas gravadas para análise qualitativa com identificação dos descritores distribuídos por oito categorias. Os dados quantitativos tiveram análise descritiva de frequência. Resultados: Somente 2% tiveram boa adesão medicamentosa; 23% compraram estatina, os demais obtiveram o medicamento em serviços públicos. Foram classificadas 36 falas com as categorias: conhecimento sobre a doença e o tratamento, dificuldade de aquisição do medicamento, gerenciamento pessoal do tratamento, acesso aos serviços de saúde, efeito colateral das estatinas, apoio do cuidador, transporte até o ambulatório, receios quanto à evolução da doença, efeito colateral das estatinas. Foi observado que 1/3 dos atendimentos fora da instituição podem ser caracterizados como tentativa de racionalização da rede. Conclusão: A melhora da adesão ao tratamento da doença isquêmica do coração depende do estabelecimento de fluxos efetivos para referência e contrarreferência entre unidades assistenciais; adequada informação e esclarecimento das dúvidas do paciente; atenção dos profissionais de saúde aos múltiplos fatores sociais e culturais envolvidos com a adesão. São necessários novos estudos sobre o papel da assistência farmacêutica, grupos educativos e integração da equipe multiprofissional no engajamento do paciente para compartilhar as decisões sobre o tratamento, e assim ampliar seu grau de comprometimento com a própria saúde.

Custo-efetividade do uso associado de estabilizadores de humor e antipsicóticos atípicos na terapia de manutenção do transtorno bipolar no Sistema Único de Saúde / Cost-effectiveness of mood stabilizers and atypical antipsychotics in maintenance therapy of bipolar disorder in the Brazilian Unified Health System

RESUMOObjetivo: Avaliar a custo-efetividade da associação de antipsicóticos atípicos e estabilizadores de humor na terapia de manutenção do transtorno bipolar no Sistema Único de Saúde (SUS). Métodos: Assumindo os custos diretos na perspectiva do SUS, construiu-se um modelo de Markov com as transições entre eutimia, mania, depressão, descontinuação e morte. Dados foram obtidos de ensaios clínicos, coortes prospectivas e bases assistenciais do SUS (valores correntes de 2015). Com uma coorte hipotética (n = 2000, idade = 40 anos), foram simulados ciclos trimestrais no horizonte de até 30 anos (ou efetividade < 1 dia em remissão). Adotaram-se taxas de desconto, correção de meio de ciclo e análises de sensibilidade. Resultados: Os dados de eficácia permitiram apenas a análise da associação com a quetiapina. No horizonte temporal de 12 anos (48 ciclos), ocorreram 512 episódios agudos (depressão: 285, mania: 227) com a monoterapia de lítio ou valproato e 306com associação de quetiapina (depressão: 166, mania: 139). A razão de custo-efetividade incremental (RCEI) da associação com a quetiapina foi de R$ 807,95 por mês adicional em remissão. A análise de sensibilidade demonstrou robustez do modelo, sendo a variação da dose e do preço da quetiapina seus maiores modificadores (amplitude da RCEI de R$ 541,60 a R$ 1.770,05). Conclusões: A terapia de manutenção com a associação da quetiapina ao lítio ou valproato demonstrou ser potencialmentecusto-efetiva. Considerando que o uso de antipsicóticos atípicos não é desprovido de riscos, a estratégia estudada pode ser uma alternativa terapêutica em populações específicas do SUS

ABSTRACTObjective: To evaluate the cost-effectiveness of the combination of atypical antipsychotic and mood stabilizers in maintenance treatment of bipolar disorder in the Brazilian Unified Health System (SUS). Methods: Taking direct costs, from the perspective of SUS, we built a Markov model withtransitions between the states: euthymia, mania, depression, discontinuation and death. Data were extracted from clinical trials, prospective cohorts and SUS databases (current values of 2015). In a hypothetical cohort (n = 2,000, age = 40 years), maintenance therapy was simulated over quarterly cycles through a timeframe up to 30 years (until effectiveness < 1 day in remission). Discount rates and half-cycle correction were applied and sensitivity analyses were run. Results: The efficacy data enabled to include only a combination with quetiapine in the analysis. After twelve years (48 cycles), there were 512 acute episodes (depression: 285, mania: 227) for monotherapy with lithium or valproate against 306 (depression: 166, mania 139) for the quetiapine combination. The incremental cost-effectiveness ratio (ICER) for the quetiapine combination was R$ 807.95 per additional month in remission. The sensitivity analysis demonstrated the model?s robustness, while dosage and quetiapine-price variations had most impact in ICER (ranging from R$ 541.60 to R$ 1,770.05 per additional month in remission). Conclusion: Maintenance therapy with the combination of quetiapine andlithium or valproate seems to be cost-effective. As the use of atypical antipsychotics is also associated with risks, the studied strategy can be a therapeutic alternative for specific populations in SUS.

School-based physical activity and nutritional education interventions on body mass index: a meta-analysis of randomised community trials - project PANE.

OBJECTIVE: To evaluate the effect of school-based physical activity (PA) and nutritional education (NE) interventions on children's and adolescents' body mass index. METHODS: We conducted a systematic search in fourteen databases until September 2012 for randomised controlled trials on PA and NE, conducted in the school setting, and delivered to children and adolescents. Additionally, we performed a cross-reference check in related papers. The title and abstract review and the quality assessment were performed by two independent researchers. The software EPPI-Reviewer3 was used to store, manage and analyse all data. The meta-analysis was conducted using the random-effects model, and the outcomes were reported as standardised mean difference (SMD). As a secondary analysis, we pooled together the interventions that considered PA or NE alone. RESULTS: Thirty-eight studies met the eligibility criteria. The main analysis showed a SMD between intervention and control groups of -0.03 (95% CI: -0.09, 0.04; n=28,870; I(2)=83%). When we considered all 57 trials, there was no difference between the results of the primary analysis. CONCLUSION: The synthesis of school-based PA and NE interventions showed no statistically significant mean reduction on children's and adolescents' body mass index. The high heterogeneity among studies requires caution in the generalisation of the results.

The effect of school-based physical activity interventions on body mass index: a meta-analysis of randomized trials.

This study reviewed the effectiveness of school-based physical activity interventions aimed at reducing overweight, obesity and hypertension in children. We searched 14 databases and analyzed studies published between April 2009 and September 2012. Only randomized controlled trials performed at the school level that included elements of physical activity but did not include nutritional co-interventions were analyzed. Studies were assessed by two recommended tools (EPHPP and GRADE), and the standardized mean differences with 95% confidence intervals were collected for a random-effect meta-analysis. A total of 12 papers were included in the meta-analysis, and these were divided according to three outcomes: body mass index (11 trials, n = 4,273, -0.02, 95% CI: -0.13 to 0.17, p = 0.8); body weight (5 trials, n = 1,330, -0.07, 95% CI: -0.18 to 0.04, p = 0.2); and blood pressure (6 trials, n = 1,549), including systolic (0.11, 95% CI: -0.10 to 0.31, p = 0.3) and diastolic pressure (-0.00, 95% CI: -0.10 to 0.10, p = 0.9). This meta-analysis of data from 11 randomized, school-based physical activity interventions suggests that, regardless of the potential benefits of physical activity in the school environment, the interventions did not have a statistically significant effect. However, it is difficult to generalize from these results because the duration, intensity and type of physical activity used in the interventions varied greatly.

The effect of school-based physical activity interventions on body mass index: a meta-analysis of randomized trials

This study reviewed the effectiveness of school-based physical activity interventions aimed at reducing overweight, obesity and hypertension in children. We searched 14 databases and analyzed studies published between April 2009 and September 2012. Only randomized controlled trials performed at the school level that included elements of physical activity but did not include nutritional co-interventions were analyzed. Studies were assessed by two recommended tools (EPHPP and GRADE), and the standardized mean differences with 95% confidence intervals were collected for a random-effect meta-analysis. A total of 12 papers were included in the meta-analysis, and these were divided according to three outcomes: body mass index (11 trials, n  =  4,273, −0.02, 95% CI: −0.13 to 0.17, p  =  0.8); body weight (5 trials, n  =  1,330, −0.07, 95% CI: −0.18 to 0.04, p  =  0.2); and blood pressure (6 trials, n  =  1,549), including systolic (0.11, 95% CI: −0.10 to 0.31, p  =  0.3) and diastolic pressure (−0.00, 95% CI: −0.10 to 0.10, p  =  0.9). This meta-analysis of data from 11 randomized, school-based physical activity interventions suggests that, regardless of the potential benefits of physical activity in the school environment, the interventions did not have a statistically significant effect. However, it is difficult to generalize from these results because the duration, intensity and type of physical activity used in the interventions varied greatly.

The effect of participation in school-based nutrition education interventions on body mass index: a meta-analysis of randomized controlled community trials.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of school-based nutrition education interventions in reducing or preventing overweight and obesity among children and adolescents. METHODS: We conducted a systematic search of 14 databases until May 2010 and cross-reference check in 8 systematic reviews (SRs) for studies published that described randomized controlled trials conducted in schools to reduce or prevent overweight in children and adolescents. An additional search was carried out using PubMed for papers published through May 2012, and no further papers were identified. Body mass index (BMI) was the primary outcome. The title and abstract review and the quality assessment were performed independently by two researchers. The software EPPI-Reviewer3 was used to store, manage and analyze all data. This SR is registered at ClinicalTrials.gov (NCT00985972). RESULTS: From the 4888 references initially retrieved, only 8 met the eligibility criteria for a random-effects meta-analysis. The total population consisted of 8722 children and adolescents. Across the studies, there was an average treatment effect of -0.33 kg/m(2) (-0.55, -0.11 95% CI) on BMI, with 84% of this effect explained by the highest quality studies. CONCLUSION: This systematic review provides evidence that school-based nutrition education interventions are effective in reducing the BMI of children and adolescents.

Factors associated with maternal intrapartum transfers from a freestanding birth centre in São Paulo, Brazil: a case control study.

OBJECTIVES: to identify factors associated with maternal intrapartum transfer from a freestanding birth centre to hospital. DESIGN: case-control study with retrospective data collection. PARTICIPANTS AND SETTINGS: cases included all 111 women transferred from a freestanding birth centre in Sao Paulo to the referral hospital, from March 2002 to December 2009. The controls were 456 women who gave birth in the birth centre during the same period who were not transferred, randomly selected with four controls for each case. METHODS: data were obtained from maternal records. Factors associated with maternal intrapartum transfers were initially analysed using a χ(2) test of association. Variables with p<0.20 were then included in multivariate analyses. A multiple logistic regression model was built using stepwise forward selection; variables which reached statistical significance at p<0.05 were considered to be independently associated with maternal transfer. FINDINGS: during the study data collection period, 111 (4%) of 2,736 women admitted to the centre were transferred intrapartum. Variables identified as independently associated factors for intrapartum transfer included nulliparity (OR 5.1, 95% CI 2.7-9.8), maternal age ≥35 years (OR 5.4, 95% CI 2.1-13.4), not having a partner (OR 2.8, 95% CI 1.5-5.3), cervical dilation ≤3 cm on admission to the birth centre (OR 1.9, 95% CI 1.1-3.2) and between 5 and 12 antenatal appointments at the birth centre (OR 3.8, 95% CI 1.9-7.5). In contrast, a low correlation between fundal height and pregnancy gestation (OR 0.3, 95% CI 0.2-0.6) appeared to be protective against transfer. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: identifying factors associated with maternal intrapartum transfer could support decision making by women considering options for place of birth, and support the content of appropriate information about criteria for admission to a birth centre. Findings add to the evidence base to support identification of women in early labour who may experience later complications and could support timely implementation of appropriate interventions associated with reducing transfer rates.

Predictors of the risk of falls among elderly with chronic atrial fibrillation.

OBJECTIVES: Though elderly persons with chronic atrial fibrillation have more comorbidities that could limit indications for the chronic use of anticoagulants, few studies have focused on the risk of falls within this particular group. To evaluate the predictors of the risk of falls among elderly with chronic atrial fibrillation, a cross-sectional, observational study was performed. METHODS: From 295 consecutive patients aged 60 years or older with a history of atrial fibrillation who were enrolled within the last 2 years in the cardiogeriatrics outpatient clinic of the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 107 took part in this study. Their age was 77.9±6.4 years, and 62 were female. They were divided into two groups: a) no history of falls in the previous year and b) a history of one or more falls in the previous year. Data regarding the history of falls and social, demographic, anthropometric, and clinical information were collected. Multidimensional assessment instruments and questionnaires were applied. RESULTS: At least one fall was reported in 55 patients (51.4%). Among them, 27 (49.1%) presented recurrent falls, with body lesions in 90.4% and fractures in 9.1% of the cases. Multivariate logistic regression showed that self-reported difficulty maintaining balance, use of amiodarone, and diabetes were independent variables associated with the risk of falls, with a sensitivity of 92.9% and a specificity of 44.9%. CONCLUSION: In a group of elderly patients with chronic atrial fibrillation who were relatively independent and able to attend an outpatient clinic, the occurrence of falls with recurrence and clinical consequences was high. Difficulty maintaining balance, the use of amiodarone and a diagnosis of diabetes mellitus were independent predictors of the risk for falls. Thus, simple clinical data predicted falls better than objective functional tests.

A randomised clinical trial of the effect of low-level laser therapy for perineal pain and healing after episiotomy: a pilot study.

OBJECTIVE: to evaluate the effects of low-level laser therapy for perineal pain and healing after episiotomy. DESIGN: a double-blind, randomised, controlled clinical trial comparing perineal pain scores and episiotomy healing in women treated with low-level laser therapy (LLLT) and with the simulation of the treatment. SETTING: the study was conducted in the Birth Centre and rooming-in units of Amparo Maternal, a maternity service located in the city of São Paulo, Brazil. PARTICIPANTS: fifty-two postpartum women who had had mediolateral episiotomies during their first normal delivery were randomly divided into two groups of 26: an experimental group and a control group. INTERVENTION: in the experimental group, the women were treated with LLLT. Irradiation was applied at three points directly on the episiotomy after the suture and in three postpartum sessions: up to 2 hrs postpartum, between 20 and 24 hrs postpartum and between 40 and 48 hrs postpartum. The LLLT was performed with diode laser, with a wavelength of 660 nm (red light), spot size of 0.04 cm(2), energy density of 3.8 J/cm(2), radiant power of 15 mW and 10s per point, which resulted in an energy of 0.15 J per point and a total energy of 0.45 J per session. The control group participants also underwent three treatment sessions, but without the emission of radiation (simulation group), to assess the possible effects of placebo treatment. MAIN OUTCOMES: perineal pain scores, rated on a scale from 0 to 10, were evaluated before and immediately after the irradiation in the three sessions. The healing process was assessed using the REEDA scale (Redness, Edema, Echymosis, Discharge Aproximation) before each laser therapy session and 15 and 20 days after the women's discharge. FINDINGS: comparing the pain scores before and after the LLLT sessions, the experimental group presented a significant within-group reduction in mean pain scores after the second and third sessions (p=0.003 and p<0.001, respectively), and the control group showed a significant reduction after the first treatment simulation (p=0.043). However, the comparison of the perineal pain scores between the experimental and control groups indicated no statistical difference at any of the evaluated time points. There was no significant difference in perineal healing scores between the groups. All postpartum women approved of the low-level laser therapy. CONCLUSIONS: this pilot study showed that LLLT did not accelerate episiotomy healing. Although there was a reduction in perineal pain mean scores in the experimental group, we cannot conclude that the laser relieved perineal pain. This study led to the suggestion of a new research proposal involving another irradiation protocol to evaluate LLLT's effect on perineal pain relief.