Association between time of day for rapid response team activation and mortality.

PURPOSE: To evaluate the frequency of rapid response team (RRT) calls by time of day and their association with in-hospital mortality. MATERIALS AND METHODS: This was a retrospective cohort study of all RRT calls at a tertiary teaching hospital in Porto Alegre, Brazil. Patients were categorized according to the time of initial RRT activation. Activations were classified as daytime (7:00-18:59) or nighttime (19:00-6:59). The primary outcome was in-hospital mortality rate. The secondary outcome was ICU admission within 48 h of RRT assessment. RESULTS: During the study period, 4522 patients were included in the final analysis. Cardiovascular and respiratory changes were more common causes of nighttime activation, whereas neurological and laboratory changes were more common during the daytime. The in-hospital mortality rate was 23.9% (1081/4522). Nighttime RRT calls were not associated with worse outcomes than daytime calls. However, a decrease in the number of calls was observed during nursing handover periods (7:00, 13:00 and 19:00). Two time periods were associated with increased adjusted odds for mortality: 12:00-13:00 (adjusted OR 2.277; 95% CI 1.392-3.725) and 19:00-20:00 (adjusted OR 1.873; CI 1.873; 95% 1.099-3.190). CONCLUSION: We found that nighttime RRT calls were not associated with worse outcomes than daytime RRT calls. However, a decrease in the number of calls and higher mortality was observed during nursing handover periods.

Cost-effectiveness of mechanical thrombectomy for acute ischemic stroke in Brazil: Results from the RESILIENT trial.

BACKGROUND: The RESILIENT trial demonstrated the clinical benefit of mechanical thrombectomy in patients presenting acute ischemic stroke secondary to anterior circulation large vessel occlusion in Brazil. AIMS: This economic evaluation aims to assess the cost-utility of mechanical thrombectomy in the RESILIENT trial from a public healthcare perspective. METHODS: A cost-utility analysis was applied to compare mechanical thrombectomy plus standard medical care (n = 78) vs. standard medical care alone (n = 73), from a subset sample of the RESILIENT trial (151 of 221 patients). Real-world direct costs were considered, and utilities were imputed according to the Utility-Weighted modified Rankin Score. A Markov model was structured, and probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of results. RESULTS: The incremental costs and quality-adjusted life years gained with mechanical thrombectomy plus standard medical care were estimated at Int$ 7440 and 1.04, respectively, compared to standard medical care alone, yielding an incremental cost-effectiveness ratio of Int$ 7153 per quality-adjusted life year. The deterministic sensitivity analysis demonstrated that mRS-6 costs of the first year most affected the incremental cost-effectiveness ratio. After 1000 simulations, most of results were below the cost-effective threshold. CONCLUSIONS: The intervention's clear long-term benefits offset the initially higher costs of mechanical thrombectomy in the Brazilian public healthcare system. Such therapy is likely to be cost-effective and these results were crucial to incorporate mechanical thrombectomy in the Brazilian public stroke centers.

Health-related quality of life associated with diabetic retinopathy in patients at a public primary care service in southern Brazil.

OBJECTIVE: This study aimed to establish the utility values of different health states associated with diabetic retinopathy in a Brazilian sample to provide input to model-based economic evaluations. METHODS: This cross-sectional study was performed in a sample of patients with type 2 diabetes mellitus (T2D) who underwent teleophthalmology screening at a primary care service from 2014 to 2016. Five diabetic retinopathy health states were defined: absent, non-sight-threatening, sight-threatening, and bilateral blindness. Utility values were estimated using the Brazilian EuroQol five dimensions (EQ-5D) tariffs. Descriptive statistics were calculated. Analysis of covariance was performed to adjust the utility values for potential confounders. RESULTS: The study included 206 patients. The mean (± standard deviation [SD]) utility value was 0.765 ± 0.19 (95% confidence interval [CI], 0.740-0.790). The adjusted mean utility value was 0.748 (95% CI, 0.698-0.798) in patients without diabetic retinopathy, 0.752 (95% CI, 0.679-0.825) in those with non-sight-threatening state, 0.628 (95% CI, 0.521-0.736) in those with sight-threatening state, and 0.355 (95% CI, 0.105-0.606) in those with bilateral blindness. A significant utility decrement was found between patients without diabetic retinopathy and those with a sight-threatening health state (0.748 vs. 0.628, respectively, p = 0.04). CONCLUSION: The findings suggest that a later diabetic retinopathy health state is associated with a decrement in utility value compared with the absence of retinopathy in patients with T2D. The results may be useful as preliminary input to model-based economic evaluations. Further research is needed to investigate the impact of diabetic retinopathy on health-related quality of life in a sample more representative of the Brazilian population.

Echoendoscopy in Preoperative Evaluation of Esophageal Adenocarcinoma and Gastroesophageal Junction: Systematic Review and Meta-analysis.

Esophageal adenocarcinomas of the esophagus and esophagogastric junction constitute a global health problem, the incidence of which has increased in recent decades. It has a poor prognosis and a low 5-year survival rate. Its treatment is based on preoperative clinical staging, in which echoendoscopy plays an essential role. The aim of this study was to evaluate the current accuracy of echoendoscopy in the staging of esophageal and esophogogastric junction adenocarcinomas. A systematic review was performed in PubMed, Embase and Portal BVS using the search terms Esophageal Neoplasm, Esophagus Neoplasms, Esophagus Cancers, Esophageal Cancers, EUS, EUS-FNA, Endoscopic Ultrasonography, Echo Endoscopy, Endosonographies and Endoscopic Ultrasound, with subsequent meta-analysis of the data found. The accuracy of tumor (T) staging was 65.55%. For T1, sensitivity was 64.7%, and specificity 89.1%, with an accuracy of 89.6%. For T2, sensitivity and specificity were 35.7% and 89.2%, respectively, with an accuracy of 87.1%. For T3, sensitivity and specificity were 82.5% and 83%, respectively, with an accuracy of 87%. For T4, sensitivity and specificity were 38.6% and 94%, respectively, with an accuracy of 66.4%. For node (N) staging, sensitivity was 77.3% and specificity 67.4%, with an accuracy of 77.9%. Echoendoscopy exhibits suboptimal accuracy in preoperative staging of esophageal adenocarcinoma and esophagogastric junction.

The impact of 5-alpha-reductase inhibitors on mortality in a prostate cancer chemoprevention setting: a meta-analysis.

PURPOSE: This study aims to evaluate the impact of 5-alpha-reductase inhibitors (5ARI) for prostate cancer (PCa) primary prevention on specific and overall mortality (primary outcomes), the incidence of PCa diagnosis and disease aggressiveness (secondary outcomes). METHODS: We searched MEDLINE, EMBASE, Cochrane, ClinicalTrials and BVS through April 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement to identify randomized clinical trials (RCT) and cohort studies (CS). We included articles with data on mortality or PCa incidence for men using 5ARI previously to PCa diagnosis. RESULTS: Regarding the included studies, nine had data on mortality, 16 on PCa incidence and 12 on Gleason scores (GS). We found that the use of 5ARI had no impact on overall mortality (RR 0.93 95% CI 0.78-1.11) and PCa-related mortality (RR 1.35 95% CI 0.50-3.94), nor on high-grade PCa diagnosis (RR 1.06 95% CI 0.72-1.56). We identified a relative risk reduction of 24% in moderate-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.98) and low-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.97) Also, a reduction of 26% in overall PCa diagnosis was observed in the RCT subgroup analysis (RR 0.74 95% CI 0.65-0.84). CONCLUSION: 5ARI significantly reduced the risk of being diagnosed with PCa, not increasing high-grade disease, overall or cancer-specific mortality. Due to the relatively short mean follow-up of most studies, the mortality analysis is limited.

Health-related quality of life associated with diabetic retinopathy in patients at a public primary care service in southern Brazil

ABSTRACT Objective This study aimed to establish the utility values of different health states associated with diabetic retinopathy in a Brazilian sample to provide input to model-based economic evaluations. Subjects and methods This cross-sectional study was performed in a sample of patients with type 2 diabetes mellitus (T2D) who underwent teleophthalmology screening at a primary care service from 2014 to 2016. Five diabetic retinopathy health states were defined: absent, non-sight-threatening, sight-threatening, and bilateral blindness. Utility values were estimated using the Brazilian EuroQol five dimensions (EQ-5D) tariffs. Descriptive statistics were calculated. Analysis of covariance was performed to adjust the utility values for potential confounders. Results The study included 206 patients. The mean (± standard deviation [SD]) utility value was 0.765 ± 0.19 (95% confidence interval [CI], 0.740-0.790). The adjusted mean utility value was 0.748 (95% CI, 0.698-0.798) in patients without diabetic retinopathy, 0.752 (95% CI, 0.679-0.825) in those with non-sight-threatening state, 0.628 (95% CI, 0.521-0.736) in those with sight-threatening state, and 0.355 (95% CI, 0.105-0.606) in those with bilateral blindness. A significant utility decrement was found between patients without diabetic retinopathy and those with a sight-threatening health state (0.748 vs. 0.628, respectively, p = 0.04). Conclusions The findings suggest that a later diabetic retinopathy health state is associated with a decrement in utility value compared with the absence of retinopathy in patients with T2D. The results may be useful as preliminary input to model-based economic evaluations. Further research is needed to investigate the impact of diabetic retinopathy on health-related quality of life in a sample more representative of the Brazilian population.

Man vs. machine: Predicting hospital bed demand from an emergency department.

BACKGROUND: The recent literature reports promising results from using intelligent systems to support decision making in healthcare operations. Using these systems may lead to improved diagnostic and treatment protocols and to predict hospital bed demand. Predicting hospital bed demand in emergency department (ED) attendances could help resource allocation and reduce pressure on busy hospitals. However, there is still limited knowledge on whether intelligent systems can operate as fully autonomous, user-independent systems. OBJECTIVE: Compare the performance of a computer-based algorithm and humans in predicting hospital bed demand (admissions and discharges) based on the initial SOAP (Subjective, Objective, Assessment, Plan) records of the ED. METHODS: This was a retrospective cohort study that compared the performance of humans and machines in predicting hospital bed demand from an ED. It considered electronic medical records (EMR) of 9030 patients (230 used as a testing set, and hence evaluated both by humans and by an algorithm, and 8800 used as a training set exclusively by the algorithm) who visited the ED of a tertiary care and teaching public hospital located in Porto Alegre, Brazil between January and December 2014. The machine role was played by Support Vector Machine Classifier and the human prediction was performed by four ED physicians. Predictions were compared in terms of sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC). RESULTS: All graders achieved similar accuracies. The accuracy by AUROC for the testing set was 0.82 [95% confidence interval (CI) of 0.77-0.87], 0.80 (95% CI: 0.75-0.85), 0.76 (95% CI: 0.71-0.81) for novice physicians, machine, experienced physicians, respectively. Processing time per test EMR was 0.00812±0.0009 seconds. In contrast, novice physicians took on average 156.80 seconds per test EMR, while experienced physicians took on average 56.40 seconds per test EMR. CONCLUSIONS: Our data indicated that the system could predict patient admission or discharge states with 80% accuracy, which was similar the performance of novice and experienced physicians. These results suggested that the algorithm could operate as an autonomous and independent system to complete this task.

A population-based study of tuberculosis incidence among rheumatic disease patients under anti-TNF treatment.

INTRODUCTION: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The advent of immunobiologic therapy with TNF inhibitors agents, has been associated with a significant increase in incident cases of tuberculosis in this population. OBJECTIVE: To estimate the incidence of tuberculosis in patients receiving TNF inhibitors therapy for rheumatic diseases. As secondary objectives, we sought to evaluate mortality and the clinical impact of screening for latent tuberculosis infection. METHODS: This retrospective study included patients with rheumatic diseases of Public Health System from the Brazilian state, a high TB incidence area, who received prescriptions of TNF inhibitors agents between 2006 and 2016. RESULTS: A total of 5853 rheumatic disease patients were included. Patients were predominantly women (68.7%) aged 49.5 (± 14.7) years old. Forty-three cases of TB were found (2.86 cases per 1000 person-years; 18 times higher than in the general population). Adalimumab and certolizumab users presented a higher risk for TB development compared to etanercept users (RR: 3.11, 95%CI 1.16-8.35; 7.47, 95%CI 1.39-40.0, respectively). In a subgroup of patients, screening for latent tuberculosis infection was performed in 86% of patients, and 30.2% had a positive tuberculin skin test. Despite latent TB treatment, TB was diagnosed in 2 out of 74 (2.7%) patients. Overall, TB diagnosis did not increase mortality. CONCLUSION: In this population-based study of rheumatic disease patients from a high incident area, TNF inhibitor exposure was associated with an 18-time increased TB incidence. Adalimumab and certolizumab were associated with greater and earlier TB diagnosis compared to etanercept.

An 8-step framework for implementing time-driven activity-based costing in healthcare studies.

Micro-costing studies still deserving for methods orientation that contribute to achieve a patient-specific resource use level of analysis. Time-driven activity-based costing (TDABC) is often employed by health organizations in micro-costing studies with that objective. However, the literature shows many deviations in the implementation of TDABC, which might compromise the accuracy of the results obtained. One reason for that can be attributed to the non-existence of a step-by-step orientation to conduct cost analytics with the TDABC specific for micro-costing studies in healthcare. This article aimed at exploring the literature and practical cases to propose an eight-step framework to apply TDABC in micro-costing studies for health care organizations. The 8-step TDABC framework is presented and detailed exploring online spreadsheets already coded to demonstrate data structure and math formula building. A list of analyses that can be performed is suggested, including an explanation about the information that each analysis can provide to increase the organization capability to orient decision making. The case study developed show that actual micro-costing of health care processes can be achieved with the 8-step TDABC framework and its use in future researches can contribute to increase the number of studies that achieve high-quality level in cost information, and consequently, in health resource evaluation.

Continuous Intravenous Inotropes in Ward Units: Expanding Therapy Outside Intensive Care using a Safety-Oriented Protocol.

Selected clinically stable patients with heart failure (HF) who require prolonged intravenous inotropic therapy may benefit from its continuity out of the intensive care unit (ICU). We aimed to report on the initial experience and safety of a structured protocol for inotropic therapy in non-intensive care units in 28 consecutive patients hospitalized with HF that were discharged from ICU. The utilization of low to moderate inotropic doses oriented by a safety-focused process of care may reconfigure their role as a transition therapy while awaiting definitive advanced therapies and enable early ICU discharge.

Quality indicators in type 2 diabetes patient care: analysis per care-complexity level.

BACKGROUND: This study was developed to evaluate quality indicators in type 2 diabetes patient care at the Unified Public Health System's primary and tertiary health care centers within a local population. METHODS: This was a retrospective cohort of 488 patients with type 2 diabetes (148 in each primary health care unit, ESF and UBS, and 192 at the tertiary health care unit) with a 1-year follow-up to evaluate the following care quality indicators: nephropathy, neuropathy and retinopathy tests, yearly lipid profile and nutritional assessments, and an inquiry about tobacco use. The presence of > 50% of the quality of care assessment measures was considered acceptable. Indicators were also evaluated in relation to patients without proper diabetes control (HbA1c > 8.5%). RESULTS: In the results, a high percentage of patients were excluded specifically for not presenting the two HbA1c tests within a year (n = 208, 58.1% at ESF; n = 225, 58.4% at UBS; and n = 39, 16.9% at the tertiary health care unit). From the included patients, only 7 (4.7%) at ESF, 7 (4.7%) at UBS, and 52 (27.0%) at the tertiary health care unit showed > 50% of the quality criteria covered. When only patients without proper diabetes control were evaluated, none of them at any of the health care units showed all the quality criteria covered. CONCLUSIONS: Our results show a low percentage of care assessment measures at each evaluated health care unit, pointing out the need to improve the protocols and care lines of diabetic patients.

Continuous Intravenous Inotropes in Ward Units: Expanding Therapy Outside Intensive Care using a Safety-Oriented Protocol / Inotrópicos Intravenosos Contínuos em Unidades de Enfermaria: Expandindo o Tratamento Além da Unidade de Terapia Intensiva Utilizando um Protocolo Orientado em Segurança

Abstract Selected clinically stable patients with heart failure (HF) who require prolonged intravenous inotropic therapy may benefit from its continuity out of the intensive care unit (ICU). We aimed to report on the initial experience and safety of a structured protocol for inotropic therapy in non-intensive care units in 28 consecutive patients hospitalized with HF that were discharged from ICU. The utilization of low to moderate inotropic doses oriented by a safety-focused process of care may reconfigure their role as a transition therapy while awaiting definitive advanced therapies and enable early ICU discharge.

Resumo Pacientes selecionados com insuficiência cardíaca (IC), clinicamente estáveis que necessitam de terapia inotrópica intravenosa prolongada podem se beneficiar de sua continuidade fora da unidade de terapia intensiva (UTI). Nosso objetivo foi relatar a experiência inicial e a segurança de um protocolo estruturado para terapia inotrópica em unidades de terapia não-intensiva em 28 pacientes consecutivos hospitalizados com IC que receberam alta da UTI. A utilização de doses inotrópicas baixas a moderadas, orientadas por um processo de cuidado focado na segurança, pode reconfigurar seu papel como terapia de transição enquanto aguarda terapias avançadas definitivas e permite a alta precoce da UTI.

Estudos de Microcusteio aplicados a avaliações econômicas em saúde: uma proposta metodológica para o Brasil / Microcosting methods applied to health economic assessment: a Brazilian methods guideline

Objetivo: No cenário da avaliação de tecnologias em saúde (ATS), as estimativas de custos são um fator crítico no desenvolvimento das avaliações econômicas completas, especialmente pelo uso de diferentes metodologias de custeio. A fim de contribuir com a acurácia dos dados de custos usados nessas análises, este artigo sugere recomendações para apuração de custos em saúde no Brasil. Métodos: Reuniram-se pesquisadores de ATS de diferentes expertises e centros de pesquisa do Brasil, e ao longo de dois anos foram conduzidas revisões da literatura nacional e internacional e discussões sobre as formas de abordar a temática. Três simpósios foram realizados reunindo os pesquisadores com o propósito de alcançar o consenso entre os autores sobre as melhores recomendações para a realização de estudos de Microcusteio. Resultados: Consolidou-se em forma de uma recomendação este artigo que representa uma versão compacta da diretriz completa a ser publicada pela Rede Brasileira de Avaliação de Tecnologias em Saúde. A metodologia de Microcusteio é considerada como padrão-ouro para a identificação dos custos em saúde. Os métodos de definição do estudo, coleta e análise de dados apresentados são descritos de modo a permitir uma valoração dos custos validada e homogênea, principalmente para o uso dessa informação em avaliações econômicas de saúde. Conclusão: Essa recomendação tem o propósito de aumentar a acurácia das estimativas dos custos de saúde no nosso meio e homogeneizar a comunicação entre estudos conduzidos por diferentes grupos de pesquisa. Por fim, é esperado que a utilização dessas recomendações contribua para que as decisões baseadas em dados econômicos sejam mais acuradas e equânimes quando da incorporação de tecnologias no país.

Objective: In the context of health technology assessment (HTA), cost estimates are a critical factor in the development of economic evaluations, especially through the use of different costing methodologies. In order to contribute to the accuracy of the cost data used in these analyzes, this article suggests recommendations to develop health cost analysis in Brazil. Methods: HTA researchers with heterogeneous background and from different Brazilian research centers were engaged on the development of this health cost analysis recommendation over two years. Reviews of national and international literature and discussions on how to approach the theme were conducted. Three symposia were held bringing together the researchers with the purpose of reaching consensus among the authors on the best recommendations for micro-accounting studies. Results: This article was consolidated as a recommendation, which represents a compact version of the complete guideline that will be published by the Brazilian Health Technology Assessment Network (REBRATS). The Microcosting methodology is considered as a gold standard for the analysis of health costs. Methods to define the study, to perform data collection and analysis are described in order to allow a validated and homogeneous cost evaluation, mainly for the use of this information in economic health assessments. Conclusion: This recommendation is intended to increase the health cost estimated accuracy in our country and to homogenize the communication between studies conducted by different research groups. Finally, it is expected that the use of these recommendations will contribute to make decisions based on economic data more accurate and equitable when incorporating health technologies in the country.

Statin Treatments And Dosages In Children With Familial Hypercholesterolemia: Meta-Analysis / Tratamentos e Dosagens de Estatinas em Crianças com Hipercolesterolemia Familiar: Uma Meta-Análise

Abstract Background: Children with familial hypercholesterolemia may develop early endothelial damage leading to a high risk for the development of cardiovascular disease (CVD). Statins have been shown to be effective in lowering LDL cholesterol levels and cardiovascular events in adults. The effect of statin treatment in the pediatric population is not clearly demonstrated. Objective: To systematically review the literature to evaluate the effects of different statins and dosages in total cholesterol levels in children and adolescents with familial hypercholesterolemia. We also aimed to evaluate statin safety in this group. Methods: PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO and LILACS databases, were searched for articles published from inception until February 2016. Two independent reviewers performed the quality assessment of the included studies. We performed a meta-analysis with random effects and inverse variance, and subgroup analyses were performed. Results: Ten trials involving a total of 1543 patients met the inclusion criteria. Our study showed reductions in cholesterol levels according to the intensity of statin doses (high, intermediate and low): (-104.61 mg/dl, -67.60 mg/dl, -56.96 mg/dl) and in the low-density lipoprotein cholesterol level: [-105.03 mg/dl (95% CI -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (95% CI -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (95% CI -67.83, -50.11), I2 93.8%. The duration of statin therapy in the studies ranged from 8 to 104 weeks, precluding conclusions about long-term effects. Conclusion: Statin treatment is efficient in lowering lipids in children with FH. There is need of large, long-term and randomized controlled trials to establish the long-term safety of statins.

Resumo Fundamentos: Crianças com hipercolesterolemia familiar podem desenvolver dano endotelial precoce, aumentando o risco de desenvolver doenças cardiovasculares. As estatinas tiveram sua eficácia em diminuir níveis de colesterol LDL e eventos cardiovasculares em adultos comprovada. O efeito das estatinas na população pediátrica não está claramente demonstrado. Objetivo: Revisar sistematicamente a literatura para avaliar os efeitos e a segurança de diferentes estatinas e suas dosagens nos níveis de colesterol total em crianças e adolescentes com hipercolesterolêmica familiar. Métodos: Artigos publicados desde o início até fevereiro de 2016 foram pesquisados nas bases PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO e LILACS. Dois revisores independentes avaliaram a qualidade dos estudos incluídos. Realizamos meta-análise com efeitos aleatórios e variância inversa. Análises de subgrupos foram realizadas. Resultados: Dez ensaios envolvendo 1.543 pacientes preencheram os critérios de inclusão. Em nosso estudo, as análises demostraram reduções nos níveis de colesterol, de acordo com a intensidade das doses de estatina (alta, intermediária e baixa): (-104,61 mg/dl, -67,60 mg/dl, -56,96 mg/dl) e no nível de lipoproteínas de baixa densidade: [-105,03 mg/dl (IC95% -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (IC95% -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (IC95% -67.83, -50.11), I2 93,8%. A duração da terapia com estatina variou de 8 a 104 semanas, impedindo conclusões sobre os efeitos a longo prazo. Conclusão: O tratamento com estatinas é eficiente na redução de lipídios em crianças com hipercolesterolemia familiar. É necessário realizar ensaios controlados randomizados de longo prazo para estabelecer a segurança do uso de estatinas a longo prazo.

Statin Treatments And Dosages In Children With Familial Hypercholesterolemia: Meta-Analysis.

BACKGROUND: Children with familial hypercholesterolemia may develop early endothelial damage leading to a high risk for the development of cardiovascular disease (CVD). Statins have been shown to be effective in lowering LDL cholesterol levels and cardiovascular events in adults. The effect of statin treatment in the pediatric population is not clearly demonstrated. OBJECTIVE: To systematically review the literature to evaluate the effects of different statins and dosages in total cholesterol levels in children and adolescents with familial hypercholesterolemia. We also aimed to evaluate statin safety in this group. METHODS: PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO and LILACS databases, were searched for articles published from inception until February 2016. Two independent reviewers performed the quality assessment of the included studies. We performed a meta-analysis with random effects and inverse variance, and subgroup analyses were performed. RESULTS: Ten trials involving a total of 1543 patients met the inclusion criteria. Our study showed reductions in cholesterol levels according to the intensity of statin doses (high, intermediate and low): (-104.61 mg/dl, -67.60 mg/dl, -56.96 mg/dl) and in the low-density lipoprotein cholesterol level: [-105.03 mg/dl (95% CI -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (95% CI -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (95% CI -67.83, -50.11), I2 93.8%. The duration of statin therapy in the studies ranged from 8 to 104 weeks, precluding conclusions about long-term effects. CONCLUSION: Statin treatment is efficient in lowering lipids in children with FH. There is need of large, long-term and randomized controlled trials to establish the long-term safety of statins.

Drug-Related Morbidity in Brazil: A Cost-of-Illness Model.

OBJECTIVES: To estimate the proportion of patients with drug-related morbidities (DRMs), DRM preventability, and the cost of illness of the DRMs in Brazil. METHODS: We used the decision-analytic model initially developed by Johnson and Bootman (Drug-related morbidity and mortality. A cost-of-illness model. J Manag Care Pharm 1996;2:39-47), which was adapted to the reality of the present study. A hypothetical cohort of patients in ambulatory care setting was simulated considering the perspective of the Brazilian public health system. Direct costs related to health care were obtained from the national databases, and the probability of occurrence of DRMs was established by a panel of clinical experts. Sensitivity analyses were conducted. RESULTS: An estimated 59% ± 14% of all patients assisted by the health system suffer some DRMs. Given these cases, 53% ± 18% were considered preventable. The average cost of managing a patient with any DRM was US $155. The cost of illness of the DRMs in Brazil would account for nearly US $18 billion (US $9-$27 billion) (best and worst case scenarium) annually. This amount is 5 times higher than what the Ministry of Health spends to guarantee free medicines in Brazil. Hospitalizations and long-term stays in hospital correspond to 75% of this cost. The sensitivity analysis showed that the model is sensitive to variations in these two outcomes. CONCLUSIONS: According to the model, a large proportion of patients experience DRM and the economic impact to solve these problems is substantial for the health system. Considering that more than half of these cases are preventable, it could be possible to achieve an enormous saving of resources through actions that improve the process of medication use.

Elevated red blood cell distribution width at ICU discharge is associated with readmission to the intensive care unit.

BACKGROUND: Red blood cell distribution width (RDW) is a predictor of mortality in critically ill patients. Our objective was to investigate the association between the RDW at ICU discharge and the risk of ICU readmission or unexpected death in the ward. METHODS: A secondary analysis of prospectively collected data study was conducted including patients discharged alive from the ICU to the ward. The target variable was the RDW collected at ICU discharge. Elevated RDW was defined as an RDW > 16%. Outcomes of interest included readmission to the ICU, unexpected death in the ward and in-hospital death. Variables with a p-value <0.1 in the univariate analysis or with biological plausibility for the occurrence of the outcome were included in the Cox proportional hazards model for adjustment. RESULTS: We included 813 patients. A total of 138 readmissions to the ICU and 44 unexpected deaths in the ward occurred. Elevated RDW at ICU discharge was independently associated with readmission to the ICU or unexpected death in the ward after multivariable adjustment (HR: 1.901; 95% CI 1.357-2.662). Other variables associated with this outcome included age, tracheostomy and mean corpuscular volume (MCV) at ICU discharge. Similar results were obtained after the exclusion of unexpected deaths in the ward (HR 1.940; CI 1.312-2.871) and for in-hospital deaths (HR 1.716; 95% CI 1.141-2.580). CONCLUSIONS: Elevated RDW at ICU discharge is independently associated with ICU readmission and in-hospital death.

Diretriz metodológica para estudos de avaliação econômica de tecnologias em saúde no Brasil / Methodological guidelines for economic evaluation studies of health technologies in Brazil

Objetivos: Resumir os principais pontos da Diretriz de Avaliação Econômica em Saúde (AES) do Ministério da Saúde. Métodos: As diretrizes para AES no Brasil foram desenvolvidas por intermédio de múltiplas rodadas de trabalho iterativas por grupo multidisciplinar de especialistas em economia da saúde e foram submetidas à consulta pública. Resultados: O problema deve ser definido por meio de uma questão de pesquisa estruturada. O estudo pode ser baseado em dados primários ou em modelagem, em que o primeiro aumenta a validade interna dos resultados e o segundo, a capacidade de generalização do estudo. Quando o trabalho for baseado em modelagem e focado em doença crônica, o modelo de Markov pode ser usualmente empregado, quando não houver necessidades que apontem para simulação de eventos discretos (como competição dos indivíduos por recursos escassos) ou modelos de transmissão dinâmica (em vacinação e/ou doenças infecciosas com alta transmissão entre indivíduos). O horizonte temporal preferencial é o de tempo de vida, e a taxa de desconto padrão é de 5% para custo e efetividade. Os custos devem representar a perspectiva do Sistema Único de Saúde (SUS), podendo ser estimados por macrocusteio ou microcusteio. Sempre que possível, os resultados devem ser apresentados no formato de custo por ano de vida salvo ajustado para qualidade, para facilitar comparações com outros estudos. Análises de sensibilidade devem ser extensamente empregadas, de forma a avaliar o impacto da incerteza nos resultados produzidos. Conclusões: Espera-se que, com a padronização da metodologia proposta na Diretriz, a produção de AES no país tenha incremento na sua qualidade e reprodutibilidade.

Objectives: To summarize the main points from the Brazilian's Ministry of Health Economic Evaluations (HEE) guideline. Methods: The guideline was developed through multiple rounds of iterative work, conducted by a multidisciplinary team of specialists in health economics, and where submitted to public consultation. Results: The decision problem should be defined through a structured research question. The study can be either primary data or model-based; in the first case, there is greater internal validity, while the second generates a superior generalizability. When the study is model-based and focused on a chronic disease, a Markov model can be usually employed, except for situations that points towards the need of a discrete event simulation (such as competition of individuals for scarce resources) or a dynamic transition model (for example, vaccination models and infectious diseases with high transmission rates between individuals). The preferred time horizon is the lifetime one, and the default discount rate is 5% for both costs and effectiveness. Costs should represent the Unified Health System (SUS) perspective and can be estimated through either gross-costing or micro-costing. Results should be presented as costs per quality adjusted life years (QALYs) whenever possible, to facilitate comparison with other studies. Sensitivity analyses should be widely employed, in order to evaluate the impact of uncertainty in the results produced by the model. Conclusions: It is expected that, with the standardization proposed in this guideline, the HEE production in Brazil has gains in quality and reproducibility.