Frontline treatment for transplant-eligible multiple myeloma: A 6474 patients network meta-analysis.

Autologous transplantation continues to be the cornerstone of younger and fit multiple myeloma patients. It is known that frontline induction therapy before transplantation can influence post-transplant results. Therefore, best frontline treatment for transplant-eligible patients should be based on best available evidence to guide therapy. Furthermore, until now due to data scarcity, it was not possible to thoroughly compare lenalidomide to other regimens in this setting. We performed a systematic review and network (mixed treatment comparison) meta-analysis of 21 clinical trial publications, enrolling 6474 patients and comparing 11 different treatment frontline setting regimens regarding survival, response, and safety outcomes. OS analysis showed superiority of CRD (cyclophosphamide-lenalidomide-dexamethasone) over TD-based (thalidomide-dexamethasone, HR = 0.76,0.62-0.90), VAD-based (HR = 0.71,0.52-0.90), and Z-Dex (idarubicin-dexamethasone, HR = 0.37,0.17-0.76) regimens. Concerning PFS, VTD (bortezomib-thalidomide-dexametasone) showed superior results when compared with TD-based (HR = 0.66,0.51-0.84), VAD-based (HR = 0.61,0.46-0.82), Z-Dex (HR = 0.42,0.22-0.78), and high dose dexamethasone (Dex, HR = 0.62,0.41-0.90) regimens. Bortezomib/thalidomide regimens were not superior to lenalidomide, considering these outcomes. Also, concerning complete and overall response, VTD ranked first among other regimens, showing clear superiority over thalidomide-only containing protocols. Safety outcome evaluated infectious, cardiac, gastrointestinal, neurological, thrombotic, and hematological grade 3 to 4 adverse events. Risk of thrombotic events was higher with TAD (thalidomide-doxorubicin-dexamethasone), neurological with PAD (bortezomib-doxorubicin-dexamethasone), infectious with Dex, hematological with Z-Dex, gastrointestinal with VTD, and cardiac with PAD regimens. Our study endorses current recommendations on combined immunomodulatory drugs and proteasome inhibitors frontline regimens (in triplets) in transplant-eligible multiple myeloma patients, but also formally demonstrates the favorable performance of lenalidomide in overall and progression-free survival, when compared with bortezomib/thalidomide protocols.

Hospital quality indicators: a systematic review.

PURPOSE: The purpose of this paper is to identify and describe hospital quality indicators, classifying them according to Donabedian's structure, process and outcome model and in specific domains (quality, safety, infection and mortality) in two care divisions: inpatient and emergency services. DESIGN/METHODOLOGY/APPROACH: A systematic review identified hospital clinical indicators. Two independent investigators evaluated 70 articles/documents located in electronic databases and nine documents from the grey literature, 35 were included in the systematic review. FINDINGS: In total, 248 hospital-based indicators were classified as infection, safety, quality and mortality domains. Only 10.2 percent were identified in more than one article/document and 47 percent showed how they were calculated/obtained. Although there are scientific papers on developing, validating and hospital indicator assessment, most indicators were obtained from technical reports, government publications or health professional associations. RESEARCH LIMITATIONS/IMPLICATIONS: This review identified several hospital structure, process and outcome quality indicators, which are used by different national and international groups in both research and clinical practice. Comparing performance between healthcare organizations was difficult. Common clinical care standard indicators used by different networks, programs and institutions are essential to hospital quality benchmarking. ORIGINALITY/VALUE: To the authors' knowledge, this is the first systematic review to identify and describe hospital quality indicators after a comprehensive search in MEDLINE/PubMed, etc., and the grey literature, aiming to identify as many indicators as possible. Few studies evaluate the indicators, and most are found only in the grey literature, and have been published mostly by government agencies. Documents published in scientific journals usually refer to a specific indicator or to constructing an indicator. However, indicators most commonly found are not supported by reliability or validity studies.

Conventional and high-dose daunorubicin and idarubicin in acute myeloid leukaemia remission induction treatment: a mixed treatment comparison meta-analysis of 7258 patients.

Previous meta-analyses suggested that acute myeloid leukaemia induction regimens containing idarubicin (IDA) or high-dose daunorubicin (HDD) induce higher rates of complete remission (CR) than conventional-dose daunorubicin (CDD), with a possible benefit in overall survival. However, robust comparisons between these regimens are still lacking. We conducted a mixed treatment comparison meta-analysis regarding these three regimens. Mixed treatment comparison is a statistical method of data summarization that aggregates data from both direct and indirect effect estimates. Literature search strategy included MEDLINE, EMBASE, Cochrane, Scielo and LILACS, from inception until August 2013 and resulted in the inclusion of 17 trials enrolling 7258 adult patients. HDD [relative risk (RR) 1.13; 95% credible interval (CrI) 1.02-1.26] and IDA (RR 1.13; 95% CrI 1.05-1.23) showed higher CR rates than CDD. IDA also led to lower long-term overall mortality rates when compared with CDD (RR 0.93, 95% CrI 0.86-0.99), whereas HDD and CDD were no different (RR 0.94, 95% CrI 0.85-1.02). HDD and IDA comparison did not reach statistically significant differences in CR (RR 1.00; 95% CrI 0.89-1.11) and in long-term mortality (RR 1.01, 95% CrI 0.91-1.11). IDA and HDD are consistently superior to CDD in inducing CR, and IDA was associated with lower long-term mortality. On the basis of these findings, we recommend incorporation of IDA and HDD instead of the traditional CDD as standard treatments for acute myeloid leukaemia induction. The lack of HDD benefit on mortality, when compared with CDD in this study, should be cautiously addressed, because it may have been susceptible to underestimation because of statistical power limitations.

Physical activity and cardiovascular risk factors in children: meta-analysis of randomized clinical trials.

OBJECTIVE: To assess the effects of physical activity interventions in preventing cardiovascular risk factors in childhood through a systematic review and meta-analysis of randomized clinical trials (RCTs). METHODS: A search of online databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted from inception until June 2013. RCTs enrolling children 6-12years old conducted physical activity interventions longer than 6months, assessing their effect on body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC) and triglycerides (TG) were included. Data analysis was performed using a random-effects model. RESULTS: Of 23.091 articles retrieved, 11 RCTs (10.748 subjects) were included. Physical activity interventions were not associated with reductions of BMI [-0.03kg/m(2) (95%CI -0.16, 0.13) I(2) 0%]. However, there was an association between the interventions and reduction of SBP [-1.25mmHg (95%CI -2.47, -0.02) I(2) 0%], DBP [-1.34mmHg (95%CI -2.57, -0.11) I(2) 43%] and TG [-0.09mmol/L (95%CI -0.14, -0.04) I(2) 0%], and increase of TC [0.14mmol/L (95%CI 0.01, 0.27) I(2) 0%]. CONCLUSION: As physical activity intervention programs lasting longer than 6months are associated with reductions in blood pressure levels and triglycerides, they should be considered to be included in prevention programs for cardiovascular diseases in schoolchildren.

Surgical Management of Obesity in Brazil: Proposal for a Value-Based Healthcare Model and Preliminary Results.

OBJECTIVES: To describe the implementation and 1-year results of a value-based bariatric surgery program in Brazil. METHODS: The study was conducted at a private hospital in São Paulo, Brazil (Hospital Alemão Oswaldo Cruz). A value-based healthcare program was implemented by designing an episode of care for eligible patients and developing a bundled payment model in which a single payment was made for the bariatric surgery covering the preoperative workup and ending 30 days after discharge. Assessment of outcomes included complication rate, hospital length of stay, intensive care admissions, reoperations, readmissions, and visits to the emergency department in the 30-day postoperative period. The results were compared with real-world evidence retrieved from a Brazilian private insurance database containing information on bariatric procedures performed in similar institutions (benchmark group). RESULTS: Eighty-three patients were enrolled in the value-based healthcare program (80.7% women; 18.0% with type 2 diabetes mellitus; 31.0% with high blood pressure). The mean age was 40.9 years, and body mass index was 42.1 kg/m2. The outcomes recorded in the benchmark group versus the value-based healthcare group involved complication rate, 2.6% versus 1.4% (P = 0.69); length of stay, 2.5 versus 2.0 days (P = 0.0001); intensive care admissions, 4.0% versus 1.2% (P = 0.31); emergency care visits, 15.0% versus 6.0% (P = 0.04); and readmissions, 2.3% versus 0 (P = 0.35), with an estimated cost reduction of 7.1%. CONCLUSIONS: These initial results showed favorable surgical and 30-day outcomes, demonstrating the benefits of a value-based approach for the surgical management of obesity and its comorbidities.

Effects of Diet after Early Breast Cancer Treatment: A Systematic Review and Meta-Analysis of Clinical Trials.

PURPOSE: Randomized clinical trials (RCT) are inconclusive regarding the role of dietary interventions in anthropometric measurements and survival in breast cancer patients. Our aim was to conduct a systematic review and meta-analysis to assess the effects of diet on these outcomes in women treated for early-stage breast cancer. METHODS: Embase, MEDLINE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched for RCT comparing dietary interventions (individualized dietary counseling, prescription of a specific diet, or others) with usual care in women that were treated for early breast cancer. Primary outcomes were overall survival (OS) and disease-free survival (DFS); secondary outcome was a change in body mass index (BMI). RESULTS: We found 12 RCT eligible for analysis, 7 of which were included in the quantitative analysis. Two studies reported OS and DFS and 6 reported BMI data. The hazard ratio (HR) for OS and DFS was 0.91 (95% confidence interval [CI] 0.77-1.07, p = 0.25) and 0.92 (95% CI 0.79-1.08, p = 0.31) for the intervention and control groups, respectively. Intervention was associated with BMI reduction in subjects who received a specific diet instead of counseling or other types of intervention (-0.67; 95% CI -1.14 to -0.21). CONCLUSIONS: Despite increasing survival among breast cancer patients due to better oncological treatments, there is still a lack of prospective data regarding the effects of dietary interventions in this population. We found positive association between prescription of specific diets in terms of anthropometric measures; there were no differences in OS or DFS.

Cost-effectiveness of implantable cardioverter-defibrillators in Brazil: primary prevention analysis in the public sector.

BACKGROUND: Several studies have demonstrated the effectiveness and cost-effectiveness of implantable cardioverter-defibrillators (ICDs) in chronic heart failure (CHF) patients. Despite its widespread use in developing countries, limited data exist on its cost-effectiveness in these settings. OBJECTIVE: To evaluate the cost-effectiveness of ICD in CHF patients under the perspective of the Brazilian Public Healthcare System (PHS). METHODS: We developed a Markov model to evaluate the incremental cost-effectiveness ratio (ICER) of ICD compared with conventional therapy in patients with CHF and New York Heart Association class II and III. Effectiveness was evaluated in quality-adjusted life years (QALYs) and time horizon was 20 years. We searched MEDLINE for clinical trials and cohort studies to estimate data from effectiveness, complications, mortality, and utilities. Costs from the PHS were retrieved from national administrative databases. The model's robustness was assessed through Monte Carlo simulation and one-way sensitivity analysis. Costs were expressed as international dollars, applying the purchasing power parity conversion rate (PPP US$). RESULTS: ICD therapy was more costly and more effective, with incremental cost-effectiveness estimates of PPP US$ 50,345/QALY. Results were more sensitive to costs related to the device, generator replacement frequency and ICD effectiveness. In a simulation resembling the MADIT-I population survival and ICD benefit, the ICER was PPP US$ 17,494/QALY and PPP US$ 15,394/life years. CONCLUSIONS: In a Brazilian scenario, where ICD cost is proportionally more elevated than in developed countries, ICD therapy was associated with a high cost-effectiveness ratio. The results were more favorable for a patient subgroup at increased risk of sudden death.

Laparoscopic vs open colorectal surgery: Economic and clinical outcomes in the Brazilian healthcare.

Laparoscopic surgery has become the preferred surgical approach of several colorectal conditions. However, the economic results of this are quite controversial. The degree of adoption of laparoscopic technology, as well as the aptitude of the surgeons, can have an influence not only in the clinical outcomes but also in the total procedure cost. The aim of this study was to evaluate the clinical and economic outcomes of laparoscopic colorectal surgeries, compared to open procedures in Brazil.All patients who underwent elective colorectal surgeries between January 2012 and December 2013 were eligible to the retrospective cohort. The considered follow-up period was within 30 days from the index procedure. The outcomes evaluated were the length of stay, blood transfusion, intensive care unit admission, in-hospital mortality, use of antibiotics, the development of anastomotic leakage, readmission, and the total hospital costs including re-admissions.Two hundred eighty patients, who met the eligibility criteria, were included in the analysis. Patients in the laparoscopic group had a shorter length of stay in comparison with the open group (6.02 ±â€Š3.86 vs 9.86 ±â€Š16.27, P < .001). There were no significant differences in other clinical outcomes between the 2 groups. The total costs were similar between the 2 groups, in the multivariate analysis (generalized linear model ratio of means 1.20, P = .074). The cost predictors were the cancer diagnosis and age.Laparoscopic colorectal surgery presents a 17% decrease in the duration of the hospital stay without increasing the total hospitalization costs. The factors associated with increased hospital costs were age and the diagnosis of cancer.

Protocol implementation for venous thromboembolism prophylaxis: a before-and-after study in medical and surgical patients. / Implementação de protocolo para profilaxia de tromboembolismo venoso: um estudo antes e depois em pacientes clínicos e cirúrgicos.

OBJECTIVE: This study aimed to assess the adequacy of venous thromboembolism (VTE) prophylaxis prescription after a protocol implementation. METHODS: This was a before-and-after study conducted in a tertiary care hospital in Rio Grande do Sul, Southern Brazil. Medical and surgical inpatients aged 18 years or older were assessed for VTE risk and subsequently for thromboprophylaxis adequacy, according to their risk. The evaluations occurred before and after the protocol strategy implementation; it consisted of an online platform to access the protocol, a public posting of the protocol diagram, clinical alerts on the medical staff TV, e-mail alerts, and pop-up alerts on the computerized physician order entry system. The main outcome measure was the adequacy of VTE prophylaxis prescription according to the protocol. RESULTS: A total of 429 patients were evaluated for thromboprophylaxis adequacy (213 before and 216 after). The prevalence of adequacy increased from 54% to 63% (pre and post-intervention, respectively), and after adjustment for patient type and phase of the study, the prevalence ratio reached (PR)=1.20, 95% confidence interval (CI) 1.02-1.42. CONCLUSION: The results showed that the overall appropriateness of thromboprophylaxis prescription was weakly improved. Despite these results, this study provides evidence to date a bunch of strategies for protocol implementations in private institutions in middle-income countries with an open medical staff, as there are few studies investigating these simple and pragmatic interventions.

OBJETIVO: Este estudo visou avaliar a adequação da prescrição de profilaxia de tromboembolismo venoso (TEV) após a implementação do protocolo. MÉTODOS: Trata-se de um estudo antes e depois realizado em um hospital de cuidados terciários no Rio Grande do Sul, Brasil. Pacientes clínicos e cirúrgicos internados, com 18 anos ou mais, foram avaliados para o risco de TEV e, posteriormente, para adequação da tromboprofilaxia, de acordo com o risco. As avaliações ocorreram antes e depois de uma estratégia de implementação de protocolo, que consistiu em uma plataforma on-line para acessar o protocolo, uma postagem pública do diagrama do protocolo, alertas clínicos na sala de convívio médico, alertas de e-mail e alertas pop-up no sistema informatizado de prescrição médica. O Desfecho principal foi a adequação da prescrição de profilaxia do TEV de acordo com o protocolo. RESULTADOS: Foram avaliados 429 pacientes para adequação da tromboprofilaxia (213 antes e 216 depois). A prevalência de adequação aumentou de 54% para 63% (pré e pós-intervenção, respectivamente) e após o ajuste por tipo de paciente e fase do estudo, a razão de prevalência atingiu (RP) = 1,20, intervalo de confiança de 95% (IC) 1,02-1,42. CONCLUSÕES: os resultados mostraram que a adequação geral da prescrição de tromboprofilaxia foi discretamente melhorada. Apesar desses resultados, este estudo fornece evidências, até o momento, de uma série de estratégias para implementar o protocolo em instituições privadas em países de renda média com uma equipe médica aberta, pois há poucas pesquisas investigando esse tipo de intervenção simples e pragmática.

Real-world evidence of health outcomes and medication use 24 months after bariatric surgery in the public healthcare system in Brazil: a retrospective, single-center study.

OBJECTIVES: The number of bariatric procedures has significantly increased in Brazil, especially in the public Unified Health System. The present study describes health outcomes and medication use in obese patients treated in a major hospital that performs publicly funded surgery in Brazil. METHODS: A retrospective, single center study was conducted to collect real-world evidence of health outcomes and medication use in 247 obese patients (female, 82.2%) who underwent open Roux-en-Y gastric bypass. Changes in weight and body mass index (BMI), presence of apnea, hypertension, and type 2 diabetes (T2D), and medication use (hypertension, diabetes, and dyslipidemia) were assessed preoperatively and up to 24 months postoperatively. The mean cost of medications was calculated for the 12-month preoperative and 24-month postoperative periods. RESULTS: During the surgery, the mean age of patients was 43.42 years (standard deviation [SD], 10.9 years), and mean BMI was 46.7 kg/m2 (SD, 6.7 kg/m2). At 24 months, significant declines were noted in weight (mean, -37.6 kg), BMI (mean, -14.3 kg/m2); presence of T2D, hypertension, and apnea (-29.6%, -50.6%, and -20.9%, respectively); and number of patients using medications (-66.67% for diabetes, -41.86% for hypertension, and -55.26% for dyslipidemia). The mean cost of medications (total costs for all medications) decreased by >50% in 12-24 postoperative months compared to that in 12 preoperative months. CONCLUSION: Roux-en-Y gastric bypass successfully reduced weight, BMI, and comorbidities and medication use and cost at 24 months in Brazilian patients treated in the public Unified Health System.

Healthcare Utilization and Costs Reduction after Radiofrequency Ablation For Atrial Fibrillation in the Brazilian Private Healthcare System.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia worldwide, with significantly associated hospitalizations. Considering its growing incidence, the AF related economic burden to healthcare systems is increasing. Healthcare expenditures might be substantially reduced after AF radiofrequency ablation (AFRA). OBJECTIVE: To compare resource utilization and costs before and after AFRA in a cohort of patients from the Brazilian private healthcare system. METHODS: We conducted a retrospective cohort study, based on patients' billing information from an administrative database. Eighty-three adult patients who had an AFRA procedure between 2014 and 2015 were included. Healthcare resource utilization related to cardiovascular causes, including ambulatory and hospital care, as well as its costs, were analyzed. A p-value of less than 0.05 was considered statistically significant. RESULTS: Mean follow-up was 14.7 ± 7.1 and 10.7 ± 5.4 months before and after AFRA, respectively. The 1-year AF recurrence-free rate was 83.6%. Before AFRA, median monthly total costs were Brazilian Reais (BRL) 286 (interquartile range [IQR]: 137-766), which decreased by 63.5% (p = 0.001) after the procedure, to BRL 104 (IQR: 57-232). Costs were reduced both in the emergency (by 58.6%, p < 0.001) and outpatient settings (by 56%, p < 0.001); there were no significant differences in the outpatient visits, inpatient elective admissions and elective admission costs before and after AFRA. The monthly median emergency department visits were reduced (p < 0.001). CONCLUSION: In this cohort, overall healthcare costs were reduced by 63.5%. A longer follow-up could be useful to evaluate if long-term cost reduction is maintained.

Upfront treatment for newly diagnosed transplant-ineligible multiple myeloma patients: A systematic review and network meta-analysis of 14,533 patients over 29 randomized clinical trials.

Choice of treatment for newly diagnosed transplant-ineligible multiple myeloma poses a difficult task due to an ever-increasing plethora of different regimens. Attempting to clarify this subject, we performed a systematic review and Bayesian network meta-analysis of 29 randomized clinical trials, enrolling 14,533 patients, and comparing 25 different treatment regimens regarding overall survival(OS), progression-free survival(PFS), complete response(CR), overall response rate(ORR) and toxicity. Head-to-head comparisons for all regimens and ranking of best treatments are reported. OS analysis showed superiority of lenalidomide(R) and bortezomib(V) containing regimens over thalidomide(T) protocols (e.g. Rd/CTD-HR:0.7;95%CrI:0.53-0.93, VMP/TD-HR:95%0.45;CrI:0.29-0.69). Concerning PFS, daratumumab(D) plus V (Dara-VMP) showed superior results over R (e.g. Dara-VMP/MPR-HR:0.52;95%CrI:0.34-0.77), V plus T (Dara-VMP/VTd-HR:0.56;95%CrI:0.37-0.65) and T (Dara-VMP/CTD-HR:0.34;95%CrI:0.23-0.49) containing regimens. Also, VRd and VMPT-VT performed well over other regimens. Dara-VMP showed superior response rates over R (ORR Dara-VMP/MPR-RR:6.27;95%CrI:2.18-18.95, CR Dara-VMP/MPR-RR:1.53;95%CrI:1.21-1.96) and T (ORR Dara-VMP/MPT-T-RR:4.05;95%CrI:1.19-13.26, CR Dara-VMP/MPT-T-RR:1.42;95%CrI:1.09-1.85; ORR Dara-VMP/CTD-RR:2.72;95%CrI:1.2-6.31, CR Dara-VMP/CTD-RR:1.2;95%CrI:1.05-1.36) including a higher rate of complete remission even when compared to VRd (RR:1.29;95%CrI:1.01-1.66). A higher rate of grade 3-4 adverse events was found for RD and CPR (thrombotic); VTd, VTP and VMPT-VT (neurological); RD and VAD (infectious); MPR-R and VAD (hematological); Vd and VTd (gastrointestinal); VAD, VMPCc and RD (cardiovascular). These results confirm obsolescence of classical regimens (such as VAD and MP) while pointing out benefits in efficacy resulting from incorporation of quadruplets and triplets combining new agents (Dara-VMP, VRd and VMPT-VT) and supports current rational of treatment until progression or prohibitive toxicity, especially when including lenalidomide. Based on this data, we would recommended incorporation of strategies combining novel agents (monoclonal antibodies, immunomodulatory imide drugs and proteasome inhibitors) in triplets or quadruplets and/or those comprising long term use of lenalidomide as standard frontline treatments. Moreover, this study settles daratumumab's place as an attractive alternative for upfront treatment.

Body Weight and Breast Cancer: Nested Case-Control Study in Southern Brazil.

BACKGROUND: Current studies have shown that fast weight gain may be more important than body mass index on the incidence of breast cancer. The aim of this study was to evaluate the association between body weight and breast cancer. PATIENTS AND METHODS: This was a case-control study nested in a cohort of a breast cancer mammography screening program in Southern Brazil. A trained investigator administered a standardized interview to collect sociodemographic and clinical data, and body weight history (weight at menarche, at marriage, at first and last pregnancy, and at menopause). Current anthropometric measurements were also made. RESULTS: Fifty-seven women with cancer (66.7% postmenopausal) and 159 controls were included. Current age (60.3 ± 10.4 vs. 55.8 ± 8.4 years, P < .01), marital status (49.1% vs. 64.8% with a partner, P = .03), and physical activity (48.2% vs. 32.3% sedentary, P = .01) were significantly different between cases and controls, respectively. Odds ratio showed that age and current waist circumference were associated with postmenopausal cancer. No difference was found in relation to body weight at different stages of life. CONCLUSION: Women with social vulnerability recruited at a mammography screening program in Southern Brazil showed a large weight gain during life, but no significant differences were found in body weight between women with or without breast cancer.

Roux-En-Y Gastric Bypass in Type 2 Diabetes Patients with Mild Obesity: a Systematic Review and Meta-analysis.

This study aimed to evaluate the effectiveness of only Roux-en-Y gastric bypass (RYGB) in patients with type 2 diabetes (T2D) and body mass index (BMI) of 30-40 kg/m2. A literature search was performed on MEDLINE, Embase, and Cochrane CENTRAL. The searches were performed in February 2017. English was the target language of the publications. The PICO question was used to determine eligibility for studies to be included: population, patient with BMI 30-40 kg/m2; intervention, RYGB; comparison, control group with medical care alone; and outcome, metabolic outcomes. Only randomized clinical trials (RCT) were selected. The main outcome was T2D remission. Secondary outcomes were metabolic effect of RYGB, such as hypertension and dyslipidemia. A total of five RCTs were included. The studies included a larger proportion of women, and the average time of T2D duration ranged between 6 and 10 years with 43.3% of the patients having a BMI below 35 kg/m2. Despite randomization, the baseline demographics such as age, HbA1c, and duration of diabetes were often less favorable in the surgical group. At the longest follow-up, RYGB significantly improves total and partial type 2 remission, OR 17.48 (95% CI 4.28-71.35) and OR 20.71 (95% CI 5.16-83.12), respectively. HbA1c also reduces at longest follow-up in the surgery group (- 1.83 (95% CI - 2.14; - 1.51)). All these three outcomes revealed high level of evidence according to GRADE evaluation. There is already strong evidence that RYGB improves metabolic outcomes for at least 5 years in patients with class I obesity.

What is the impact on the healthcare system if access to bariatric surgery is delayed?

BACKGROUND: Bariatric surgery has been available as part of the Brazilian Public Health System for patients with body mass index>40 kg/m2 (or>35 kg/m2 with co-morbidities) since 1999. However, access to surgery is challenging, with eligible patients waiting up to 7 years before surgery. OBJECTIVE: Our objective was to compare costs and effectiveness of different waiting times before surgery versus prompt surgery. SETTINGS: Public practice. METHODS: A Markov microsimulation model compared 5 different strategies: no surgery, prompt surgery, and delaying surgery for 1, 2, 4, and 7 years. Markov tracker variables and states reflected changes in body mass index, type 2 diabetes status (including remission and relapse), and cardiovascular events. Time horizon was 20 years; discount rate, 5%; and the perspective of the Brazilian Public Health System. Effectiveness was calculated as quality adjusted life years. RESULTS: Prompt surgery was the least costly and most effective strategy compared with any delay. Costs increased and effectiveness diminished progressively with the length of delays. Waiting 7 years for surgery was the most expensive and least effective strategy. Prompt surgery maintained dominance in 99.9%, 90.7%, 96.1%, and 94.2% of simulations in probabilistic sensitivity analyses versus 1-, 2-, 4-, and 7-year delays, respectively. Immediate surgery was very cost effective compared with no surgery in the case base. In the scenario with all patients having type 2 diabetes, immediate surgery was dominant to any strategy, including the no surgery group. CONCLUSIONS: Delaying bariatric operations is more expensive and less effective compared with prompt surgery and very cost effective compared with no surgery. Public health systems should pursue strategies to accelerate access to surgery to decrease obesity related complications and mortality of patients, but also to improve cost effectiveness.

Effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery: protocol for a systematic review, meta-analysis, and trial sequential analysis.

BACKGROUND: Preliminary evidence suggests statins may reduce major perioperative vascular events. However, evidence is limited to observational studies, underpowered trials, and non-comprehensive systematic reviews. This review aims to assess the effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery. METHODS: We will search MEDLINE/PubMed, EMBASE, LILACS, CENTRAL, Web of Science, and CINAHL for randomized controlled trials assessing the effects of perioperative statin use in adults undergoing non-cardiac surgery and reporting cardiovascular complications. For patients already using statins for hyperlipidemia, a preoperative loading dose of statin is required in the experimental group. We will place no language or publication restriction on our search. Teams of two reviewers will independently assess eligibility and risk of bias, and will extract data from the included trials. Our primary outcome is a combination of cardiovascular mortality or non-fatal myocardial infarction. We will also assess the following outcomes: individual components of the primary outcome, all-cause mortality, total myocardial infarction, elevated troponin in the first seven postoperative days, total stroke, total venous thromboembolism, postoperative atrial fibrillation, elevation of creatine phosphokinase or liver enzymes, and rates of myalgia or rhabdomyolysis. We will conduct meta-analyses using random-effects model and will use trial sequential analysis to establish monitoring boundaries to limit global type I error due to repetitive testing for our primary outcome. We will rate the quality of evidence using the GRADE system. DISCUSSION: The results of this systematic review may help to inform clinical practice and also the design of future large-scale randomized trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035987.

Blinatumomabe em pacientes pediátricos com leucemia linfoblástica aguda B em primeira recidiva de alto risco: um estudo de custo-efetividade / Blinatumomab in high-risk first relapse pediatric patients with acute lymphoblastic leukemia: a cost-effectiveness analysis

Objetivo: Estimar a custo-efetividade do blinatumomabe como novo padrão no tratamento de consolidação de pacientes pediátricos com leucemia linfoblástica aguda de células precursoras B (LLA-B) em primeira recidiva de alto risco. Métodos: Um modelo de sobrevida particionado com horizonte lifetime e ciclo de quatro semanas foi construído na perspectiva do Sistema Único de Saúde (SUS). Sobrevida livre de eventos e sobrevida global foram extrapoladas com base no ensaio clínico 20120215, usando funções paramétricas. A taxa de desconto foi de 5%. O impacto de variações em pressupostos foi explorado em análises de cenário. Resultados: O custo lifetime com desconto para o caso base foi de R$ 351.615 para blinatumomabe contra R$ 97.770 para HC3 (grupo controle de quimioterapia-padrão), com ganho de 9,96 e 6,74 anos de vida ajustados para qualidade (QALYs), respectivamente. A razão de custo-efetividade incremental (RCEI) foi de R$ 78.873/QALY. Considerando um cenário sem descontos, a RCEI foi de R$ 33.731/QALY ganho. Os outros cenários com maior impacto na RCEI foram a exclusão do desperdício de blinatumomabe (isto é, considerando que a sobra em frasco-ampola de um paciente seria reaproveitada para outro paciente: R$ 35.751) e a alteração do tempo de infusão (troca de bolsa em 48 ou 96 horas em vez de 24 horas: R$ 35.515). A probabilidade de o blinatumomabe ser custo-efetivo foi de 65,7% na análise probabilística, considerando um limiar de R$ 95.501. Conclusões: Blinatumomabe é custo-efetivo para pacientes pediátricos com LLA-B derivada em primeira recidiva de alto risco na perspectiva do SUS.

Objective: To estimate the cost-effectiveness of blinatumomab as the new standard treatment of consolidation in high-risk first relapse pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL). Methods: A partitioned survival model with a lifetime horizon and a 4-week cycle was developed from the Brazilian public healthcare payer's perspective (SUS). Event-free survival and overall survival were extrapolated based on data from the 20120215 clinical trial using parametric functions. A 5% discount rate was used, and the impact of variations in model parameters and assumptions were explored in scenario analyses. Results: The discounted base case lifetime cost was R$ 351,615 for blinatumomab vs. R$ 97,770 for standard chemotherapy control group (HC3), with 9.96 QALYs gained with blinatumomab vs. 6.74 QALYs gained with HC3. The incremental costeffectiveness ratio (ICER) was R$ 78,873/QALY. Considering an undiscounted scenario, the ICER was.

TERLIPRESSIN VERSUS NORADRENALINE FOR HEPATORENAL SYNDROME. Economic evaluation under the perspective of the Brazilian Public Health System.

BACKGROUND: - Terlipressin and noradrenaline are the best studied treatments for hepatorenal syndrome, and there is no evidence of superiority of one over the other regarding to efficacy. While the former drug is more costly, the latter requires admission into an intensive care unit. OBJECTIVE: - The aim of this study was to perform an economic evaluation, comparing treatments for hepatorenal syndrome with terlipressin and noradrenaline. METHODS: - For the economic evaluation, a cost-minimization analysis was performed. Direct medical costs of the two treatment strategies were compared under the perspective of the Brazilian Public Health System as the third-party payer. A probabilistic sensitivity analysis was performed. RESULTS: - The costs of treatments with terlipressin or noradrenaline were 287.77 and 2,960.45 International Dollars (Int$) respectively. Treatment using terlipressin would save Int$2,672.68 for the Public Health System for each hospital admission related to hepatorenal syndrome. In the probabilistic sensitivity analysis, it was verified that the cost of the treatment with noradrenaline could vary between Int$2,326.53 and Int$3,644.16, while costs related to the treatment using terlipressin are not variable. CONCLUSION: - The treatment strategy using terlipressin was more economical than that using noradrenaline under the perspective of the Brazilian Public Health System as the third-party payer.