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.

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.

Immunotherapy-based first-line treatment of intermediate- and poor-risk advanced renal cell carcinoma: number needed to treat and cost of preventing an event from the perspective of the Brazilian private healthcare system / Tratamento baseado em imunoterapia para primeira linha do carcinoma renal avançado com risco intermediário ou alto: número necessário a tratar e custo para prevenir um evento na perspectiva do sistema privado de saúde brasileiro

Objective: To perform an analysis over time of the number needed to treat (NNT) and the cost of preventing an event (COPE) for nivolumab + ipilimumab (NIVO+IPI) and pembrolizumab + axitinib (PEMBRO+AXI) as first-line treatments for advanced renal cell carcinoma patients with intermediate or poor-risk, under the Brazilian private healthcare system perspective. Methods: The NNT for overall survival (OS) and progression-free survival (PFS) from 12-month to maximum available follow-up from CheckMate 214 and KEYNOTE-426 studies were used to estimate the COPE. Treatment costs were estimated considering the labeled dosing and median PFS as a proxy for treatment duration. Results: The OS NNT for NIVO+IPI decreased from 12 to 8 and for PEMBRO+AXI increased slightly from 7 to 8 at 12 and 42 months, respectively. For PFS, NNT for NIVO+IPI decreased from 15 to 6, and for PEMBRO+AXI increased from 7 to 10 at 12 and 30 months. The estimated treatment cost is R$ 638,620 for an estimated median of 11.2 months of NIVO+IPI treatment and R$ 966,818 for 13.8 months of PEMBRO+AXI treatment. COPE for OS at 12 and 42 months was R$ 7,663,440 and R$ 5,108,960 with NIVO+IPI and R$ 6,047,417 and R$ 7,734,547 with PEMBRO+AXI. For PFS, COPE at 12 and 30 months was R$ 9,579,300 and R$ 3,831,720 with NIVO+IPI and R$ 6,047,417 and R$ 9,668,184 with PEMBRO+AXI. Conclusions: Treatment with NIVO+IPI results in lower COPE than PEMBRO+AXI from month 18 onwards, driven by lower treatment costs and improved NNT over time with NIVO+IPI

Objetivo: Analisar ao longo do tempo o número necessário a tratar (NNT) e o custo para prevenir um evento (COPE) para nivolumabe + ipilimumabe (NIVO+IPI) e pembrolizumabe + axitinibe (PEMBRO+AXI) na primeira linha de tratamento do carcinoma de células renais avançado com risco intermediário ou alto na perspectiva do sistema suplementar de saúde brasileiro. Métodos: O NNT para sobrevida global (SG) e sobrevida livre de progressão (SLP) para 12 meses até o máximo de tempo de seguimento disponível dos estudos CheckMate 214 e KEYNOTE-426 foi usado para estimar o COPE. Custos de tratamento foram estimados considerando a dosagem em bula e a mediana de SLP como aproximação para duração de tratamento. Resultados: O NNT de SG para NIVO+IPI reduziu de 12 para 8 e para PEMBRO+AXI subiu de 7 para 8 em 12 e 42 meses, respectivamente. Para SLP, NIVO+IPI teve redução de 15 para 6 e para PEMBRO+AXI aumentou de 7 para 10 em 12 e 30 meses. O custo estimado é de R$ 638.620 para mediana de 11,2 meses de tratamento com NIVO+IPI e de R$ 966.818 para 13,8 meses com PEMBRO+AXI. O COPE para SG foi de R$ 7.663.440 e R$ 5.108.960 com NIVO+IPI e de R$ 6.047.417 e R$ 7.734.547 com PEMBRO+AXI para 12 e 42 meses. Para SLP, foi de R$ 9.579.300 e R$ 3.831.720 com NIVO+IPI e de R$ 6.047.417 e R$ 9.668.184 com PEMBRO+AXI em 12 e 30 meses. Conclusões: O tratamento com NIVO+IPI resulta em menor COPE, em comparação com PEMBRO+AXI, a partir de 18 meses de seguimento, justificado por menor custo de tratamento e melhora do NNT ao longo do tempo com NIVO+IPI

Cost of chronic red blood cell transfusion in the Brazilian private healthcare sector from a payer perspective / Custo de transfusão crônica de concentrado de hemácias na perspectiva do sistema de saúde suplementar brasileiro

Objective: In the private healthcare sector in Brazil, the dearth of information regarding transfusion cost may compromise the management of conditions requiring long-term transfusion. Therefore, the present study aimed to estimate the cost of chronic red blood cell (RBC) transfusion in this context. Methods: A payer perspective was chosen for the analysis. A survey performed by an expert advisory board gathered information on the amounts reimbursed by health plans to blood centers per outpatient transfusion of a single RBC bag in multitransfused patients. Survey results were contrasted to RBC transfusion cost calculated using Brazilian Hierarchical Classification of Medical Procedures (CBHPM) parameters from 2018 and 2010, the latter suggested by the advisory board as more accurately reflecting market prices. Results: Six blood centers in the South and Southeast of Brazil were surveyed. The median amount reimbursed per RBC unit was R$ 1,066.44 (interquartile range: R$ 665.00-1,252.00). The mean amount reimbursed was R$ 959.54 ± R$ 337.14 (minimum: R$ 295.00 ­ maximum: R$ 1,980.00). Using 2018 CBHPM parameters, the cost of transfusing one RBC unit was calculated as R$ 1,905.18. Using 2010 CBHPM parameters, the cost was R$ 1,119.69 per RBC unit. Conclusions: Analyses using 2018 CBHPM parameters may lead to overestimation of transfusion cost. The best estimate for outpatient transfusion of one RBC bag in the private health care sector in Brazil lies between the observed reimbursed values and 2010 CBHPM cost. The present results provide valuable information for future cost-effectiveness analyses focusing on disorders whose treatment involves routine RBC transfusion.

A carência de informações sobre custo de transfusão sanguínea na saúde suplementar brasileira pode comprometer análises econômicas e eventuais decisões relacionadas a esse procedimento no longo prazo. O objetivo deste estudo foi estimar o custo de transfusão crônica de concentrado de hemácias (CH) nesse contexto. Métodos: Foi escolhida a perspectiva do pagador. Uma pesquisa foi realizada com especialistas para levantamento de valores reembolsados para transfusão de uma bolsa de CH em pacientes politransfundidos. Os resultados da pesquisa foram comparados ao custo de transfusão de CH calculado utilizando a Classificação Brasileira Hierarquizada de Procedimentos Médicos (CBHPM), edições de 2018 e 2010, sendo a edição mais antiga sugerida pelos especialistas como estando mais de acordo com a realidade de mercado. Resultados: Seis hemocentros localizados no Sul e Sudeste do Brasil foram incluídos. Os valores mediano e médio reembolsados aos hemocentros foram R$ 1.066,44 (amplitude interquartil: R$ 665,00-1.252,00) e R$ 959,54 ± R$ 337,14 (mínimo: R$ 295,00 ­ máximo: R$ 1.980,00), respectivamente. Com base nos parâmetros da CBHPM 2018 e 2010, os custos de transfusão calculados para uma bolsa de CH foram R$ 1.905,18 e R$ 1.119,69, respectivamente. Conclusões: Análises utilizando parâmetros da CBHPM 2018 podem superestimar os custos de transfusão de CH. Na perspectiva do sistema de saúde suplementar brasileiro, a melhor estimativa de custo de transfusão por bolsa de CH está entre o valor reembolsado e o valor calculado utilizando a CBHPM 2010. O presente estudo apresenta informações importantes para futuras análises de custo-efetividade de patologias que envolvem tratamentos à base de politransfusão de CH.

Custo-efetividade de alteplase no tratamento de acidente vascular cerebral isquêmico até quatro horas e meia após início dos sintomas: perspectiva do Sistema Único de Saúde do Brasil (SUS) / Cost-effectiveness of alteplase for treatment of ischemic stroke up to four and a half hours after the onset of symptoms: a Brazilian Public Health System (SUS) perspective

Objetivo: Analisar o custo-efetividade da trombólise com alteplase no tratamento de acidente vascular isquêmico (AVCi) agudo em até 4,5 horas após início dos sintomas em comparação com tratamento clínico conservador, sob a perspectiva do Sistema Único de Saúde (SUS) no Brasil. Métodos: Construiu-se um modelo de Markov para simular o tratamento de AVCi agudo e suas consequências em curto e longo prazo. Foram conduzidas análises de custo-efetividade (anos de vida ganhos, AVG) e custo-utilidade (anos de vida ajustados pela qualidade de vida, QALY), considerando um horizonte temporal de tempo de vida. Parâmetros de eficácia e segurança foram obtidos em uma metanálise de dados individuais, considerando tratamento em até 3 horas e 3-4,5 horas. Os custos agudos e crônicos foram obtidos por análise secundária de dados de um hospital público brasileiro e expressos em reais (R$). Foram conduzidas análises de sensibilidade determinística e probabilística. Utilizou-se como limiar de disposição a pagar (LDP) 1 PIB (produto interno bruto) per capita para 2019 no Brasil (R$ 31.833,50). Resultados: O tratamento com alteplase vs. conservador resultou em incremento de 0,22 AVG, 0,32 QALY e R$ 4.320,12 em custo, com razão de custo-efetividade incremental (RCEI) estimada em R$ 19.996,43/AVG e R$ 13.383,64/QALY. Ambas as estimativas foram mais sensíveis a variações na efetividade e nos custos de tratamento agudo com alteplase. Para RCEI/AVG e RCEI/QALY, 70,7% e 93,1% das simulações na análise de sensibilidade probabilística estavam abaixo do LDP, respectivamente. Conclusões: O tratamento com alteplase até 4,5 horas após o início dos sintomas tem elevada probabilidade de ser custo-efetivo na perspectiva do SUS.

Objective: To assess the cost-effectiveness of thrombolysis with alteplase for the treatment of acute ischemic stroke up to 4.5 hours after the onset of symptoms as compared to conservative medical treatment from the perspective of the Brazilian Public Health System. Methods: A Markov model was used to simulate the treatment of acute stroke and the associated short- and long-term consequences. Cost-effectiveness (life-years gained, LYG) and cost-utility (quality-adjusted life years, QALY) analyses were performed considering a lifetime horizon. Efficacy and safety parameters were obtained from a meta-analysis of individual data, considering treatment within 3 hours and 3-4.5 hours after the onset of symptoms. Acute and chronic costs were derived from a secondary analysis of data obtained from a Brazilian public hospital and expressed in Brazilian reais (R$). Probabilistic and deterministic sensitivity analyses were performed. The willingness to pay threshold (WPT) was established as 1 GDP per capita for 2019 in Brazil (R$ 31,833.50). Results: Treatment with alteplase vs. conservative medical treatment was associated with an increase of 0.22 in LYG, 0.32 in QALY, and R$ 4,320.12 in cost. The incremental cost-effectiveness ratio (ICER) was estimated as R$ 19,996.43/LYG and R$ 13,383.64/QALY. Variations in effectiveness and costs of acute alteplase treatment had the greatest impact on sensitivity analyses. Considering ICER/LYG and ICER /QALY, 70.7% and 93.1% of the simulations in probabilistic sensitivity analysis were below the WPT, respectively. Conclusions: Treatment with alteplase up to 4.5 hours after the onset of symptoms has a high probability of being cost-effective from the perspective of the Brazilian Public Health System.

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.

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.

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.

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

RESUMO 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.

ABSTRACT 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.

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.

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.

Healthcare Utilization and Costs Reduction after Radiofrequency Ablation For Atrial Fibrillation in the Brazilian Private Healthcare System / Redução na Utilização de Recursos em Saúde e dos Custos após Ablação por Radiofrequência da Fibrilação Arial na Saúde Suplementar Brasileira

Abstract 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.

Resumo Fundamento: A fibrilação atrial (FA) é a arritmia mais comum em todo o mundo, com hospitalizações significativamente associadas. Considerando sua crescente incidência, a carga econômica relacionada à FA para os sistemas de saúde está aumentando. Os gastos com saúde podem ser substancialmente reduzidos após a ablação por radiofrequência (ARF). Objetivo: Comparar a utilização de recursos e os custos anteriores e posteriores à ARF em uma coorte de pacientes do sistema de saúde privado brasileiro. Métodos: Foi realizado um estudo de coorte retrospectivo, com base nas informações de cobrança dos pacientes de um banco de dados administrativo. Foram incluídos oitenta e três pacientes adultos que passaram pelo procedimento de ARF entre 2014 e 2015. A utilização de recursos de saúde relacionados às causas cardiovasculares, incluindo atendimento ambulatorial e hospitalar, assim como seus custos, foram analisados. Um valor de p inferior a 0,05 foi considerado estatisticamente significativo. Resultados: O seguimento médio foi de 14,7 ± 7,1 e 10,7 ± 5,4 meses antes e após a ARF, respectivamente. A taxa de FA livre de recidiva em 1 ano foi de 83,6%. Antes da ARF, a mediana dos custos totais mensais foi de R$286,00 (intervalo interquartil [IIQ]: 137-766), com redução de 63,5% (p = 0,001) após o procedimento, para um valor de R$104 (IIQ: 57-232). Os custos foram reduzidos tanto na emergência (em 58,6%, p < 0,001) como no ambiente ambulatorial (em 56%, p < 0,001); não houve diferenças significativas nas consultas ambulatoriais, internações eletivas e custos de internação eletiva antes e depois da ARF. As medianas das consultas mensais no setor de emergência foram reduzidas (p < 0,001). Conclusão: Nesta coorte, os custos gerais com saúde foram reduzidos em 63,5%. Um seguimento mais longo pode ser útil para avaliar se a redução de custos em longo prazo é mantida.

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.

Custo-efetividade da empagliflozina em pacientes com diabetes mellitus do tipo 2 com alto risco cardiovascular na perspectiva da saúde suplementar / Cost-effectiveness of empagliflozin in patients with type 2 diabetes mellitus with high cardiovascular risk in the Brazilian private healthcare system perspective

Objetivo: Avaliar a custo-efetividade da empagliflozina adicionada ao cuidado usual para tratamento de diabetes mellitus tipo 2 (DM2) no cenário da saúde suplementar brasileira. Métodos: Foi utilizada simulação de eventos discretos, com dados de efetividade baseados no estudo EMPA-REG OUTCOME. Foram incluídos pacientes com DM2 e alto risco cardiovascular (histórico de cardiopatia isquêmica, acidente vascular cerebral ou doença vascular periférica). O horizonte temporal foi o tempo de vida; a taxa de desconto foi de 5% ao ano. Os dados de utilidade foram predominantemente de estudos brasileiros. Para estimar os custos de eventos/condições com diferença estatisticamente significativa no EMPA-REG OUTCOME (insuficiência cardíaca, diálise, morte cardiovascular), foi feita uma revisão sistemática, que identificou estudos com dados da saúde suplementar. O limiar de disposição a pagar utilizado foi 1 produto interno bruto (PIB) per capita (2017: R$ 31.587). Foram conduzidas análises de sensibilidade determinísticas e probabilísticas. Resultados: No caso-base, a empagliflozina gerou ganho de 0,66 ano de vida ajustado para qualidade (QALY) na comparação com o cuidado usual, com acréscimo de R$ 12.630 e relação de custo-efetividade incremental (RCEI) de R$ 18.895/QALY. Na análise determinística, nenhuma variação de parâmetro resultou em RCEI acima do limiar. A análise probabilística teve RCEI média de R$ 19.878/QALY (intervalo de credibilidade de 2,5% a 97,5%: R$ 5.237-R$ 36.451). Considerando 1 PIB per capita, 50% das simulações seriam custo-efetivas; para 2 PIB per capita, o percentual ultrapassaria 90%. Conclusão: Considerando o limiar de custo-efetividade adotado, de 1 PIB per capita, a empagliflozina se mostrou custo-efetiva em relação ao cuidado usual na perspectiva da saúde suplementar brasileira.

Objective: To evaluate the cost-effectiveness of empagliflozin added to usual care in type 2 diabetes mellitus (T2DM) in the private healthcare sector. Methods: We used a discrete events simulation model with effectiveness data based on the EMPA-REG OUTCOME trial. The population included patients with T2DM at high cardiovascular risk (history of ischemic heart disease, stroke, or peripheral vascular disease). A lifetime horizon and a 5% annual discount rate were used. The utility data used were predominantly from Brazilian studies. To estimate the cost of events/conditions with statistically significant difference in the EMPA-REG OUTCOME trial (heart failure, dialysis, cardiovascular death), a systematic review was performed to identify studies with data from the private healthcare system. A willingness-to-pay threshold of 1 GDP per capita (2017: R$ 31,587) was considered. Deterministic sensitivity analysis and a probabilistic sensitivity analysis were performed. Results: In the base case, empagliflozin generated incremental 0.66 QALY as compared to usual care, with an added cost of R$ 12,630 and incremental cost-effectiveness ratio (ICER) of R$ 18,895/QALY. None of the parameter variations evaluated by deterministic analysis generated ICERs above the cost-effectiveness threshold. Probabilistic sensitivity analysis revealed mean ICER of R$ 19,878/QALY (credibility interval 2.5% to 97.5%: R$ 5,237 to R$ 36,451). Considering 1 GDP per capita, 50% of the simulations would be cost-effective; considering 2 GDP per capita, over 90% would be cost-effective. Conclusion: Considering a threshold of 1 GDP per capita, the study shows that empagliflozin was cost-effective from the perspective of the Brazilian private healthcare sector.

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.

Análise de custo-efetividade da abiraterona para câncer de próstata metastático resistente à castração em pacientes com uso prévio de quimioterapia / Cost-effectiveness analysis of abiraterone for metastatic, castrateresistant prostate cancer following previous chemotherapy

Objetivo: Avaliar a custo-utilidade e o impacto orçamentário (IO) da abiraterona para o tratamento de câncer de próstata resistente à castração, em pacientes previamente tratados com docetaxel. Métodos: Foi construído um modelo de Markov com ciclos mensais sob a perspectiva do Sistema Único de Saúde (SUS), em um horizonte temporal de cinco anos e taxa de desconto de 5%. A estimativa de efetividade foi oriunda do principal ensaio clínico dessa condição de saúde. Para dados de utilidade, aplicaram-se estimativas internacionais, enquanto para custos se utilizaram tabelas de remuneração do SUS. Para o IO, a população-alvo foi estimada com base em dados do Departamento de Informática do SUS (DATASUS). Resultados: A abiraterona ocasionou ganho de 1,045 ano de vida ajustado para qualidade (QALY) e 1,609 ano de vida ganho (AVG), enquanto para o placebo esses valores foram de 0,763 e 1,299, respectivamente. O custo total na estratégia abiraterona foi de R$ 83.295 e para o placebo, de R$ 2.895. A relação de custo-efetividade incremental (RCEI) foi de R$ 284.416 por QALY ganho. Em nenhuma das análises de sensibilidade os valores ficaram abaixo de R$ 100.000 por QALY. Mesmo quando variados simultaneamente seis parâmetros, todos no seu limite mais favorável à abiraterona, os resultados seguiram elevados, com RCEI de R$ 98.330 por QALY. O IO foi de R$ 270 milhões em cinco anos no cenário mais conservador (tempo médio de tratamento de 7,4 meses e 10% de novos casos/ano). Conclusão: A abiraterona se mostrou pouco custo-efetiva nesta situação clínica, com RCEI superior a nove vezes o PIB per capita por QALY, sendo os resultados robustos em análise de sensibilidade.

Objective: To evaluate the cost-utility and the budget impact (BI) of abiraterone in patients with castration-resistant prostate cancer previously treated with docetaxel. Methods: A Markov model was constructed, with monthly cycles, under the perspective of the Brazilian Public Healthcare System (SUS), in a 5-year time horizon, and with a 5% discount rate. The effectiveness estimate was obtained from the pivotal clinical trial for abiraterone in this health condition. For utility data, international estimates were applied; while for costs, SUS reimbursement information were used. In the BI analysis, the target population was estimated with claims data from DATASUS. Results: Abiraterone resulted in a gain of 1.045 quality-adjusted life years (QALY) and 1.609 life years gained (LYG), while for placebo these values were 0.763 and 1.299, respectively. The total cost for the abiraterone strategy was BRL 83,295, and for placebo, BRL 2,895. The incremental cost-effectiveness ratio (ICER) was BRL 284,416 per QALY gained. None of the estimates from the sensitivity analysis was below BRL 100,000 per QALY. Even when six parameters were variated simultaneously in the range more favorable to abiraterone, the results were still elevated, with an ICER of BRL 98,330 per QALY. The BI was BRL 270 million in 5 years in the most conservative scenario (average time of the treatment of 7.4 months and 10% of the new cases/year). Conclusion: Abiraterone shows unfavorable cost-effective results for this clinical condition in Brazil, with an ICER above 9 times the per capita per QALY. Results were robust in sensitivity analysis.

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.