Renal Outcomes of Vasopressin and Its Analogs in Distributive Shock: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVES: To systematically review the literature and synthesize evidence concerning the effects of vasopressin and its analogs compared with other vasopressors in distributive shock, focusing on renal outcomes. DATA SOURCES: We performed a systematic review in MEDLINE, Embase, Cochrane Central, and Clinicaltrials.gov databases. STUDY SELECTION: Randomized clinical trials that compared vasopressin and its analogs with other vasopressors and reported renal outcomes in adult patients with distributive shock. DATA EXTRACTION: Paired reviewers independently screened citations, conducted data extraction and assessed risk of bias. Three prespecified subgroup analyses were conducted. Three main outcomes related to acute renal failure were analyzed: the need for renal replacement therapy, acute kidney injury incidence, and acute kidney injury-free days. I test was used to evaluate heterogeneity between studies. Substantial heterogeneity was defined as I greater than 50%. A random-effects model with Mantel-Haenszel weighting was used for all analyses. Heterogeneity was explored using subgroup analysis. The quality of evidence for intervention effects was summarized using Grading of Recommendations Assessment, Development, and Evaluation methodology. This study was registered in the PROSPERO database (CRD42017054324). DATA SYNTHESIS: Three-thousand twenty-six potentially relevant studies were identified, and 30 articles were reviewed in full. Seventeen studies met the inclusion criteria, including a total of 2,833 individuals. Of these, 11 studies (2,691 individuals) were suitable for quantitative meta-analysis. Overall, the evidence was of low to moderate quality. Patients who received vasopressin and its analogs had a reduced need for renal replacement therapy (odds ratio, 0.59 [0.37-0.92]; p = 0.02; I = 49%) and a lower acute kidney injury incidence (odds ratio, 0.58 [0.37-0.92]; p = 0.02; I = 63%). These results should be interpreted with caution, due to excessive heterogeneity. Acute kidney injury-free data was not pooled, since the small number of studies and extreme heterogeneity. CONCLUSIONS: In patients with distributive shock, vasopressin and its analogs use is associated with a reduced need for renal replacement therapy and lower acute kidney injury incidence. These results are supported by high risk of bias evidence.

Educational interventions in childhood obesity: a systematic review with meta-analysis of randomized clinical trials.

OBJECTIVE: To assess the effectiveness of educational interventions including behavioral modification, nutrition and physical activity to prevent or treat childhood obesity through a systematic review and meta-analysis of randomized trials. METHOD: A search of databases (PubMed, EMBASE and Cochrane CENTRAL) and references of published studies (from inception until May 2012) was conducted. Eligible studies were randomized trials enrolling children 6 to 12 years old and assessing the impact of educational interventions during 6 months or longer on waist circumference, body mass index (BMI), blood pressure and lipid profile to prevent or treat childhood obesity. Calculations were performed using a random effects method and pooled-effect estimates were obtained using the final values. RESULTS: Of 22.852 articles retrieved, 26 trials (23.617 participants) were included. There were no differences in outcomes assessed in prevention studies. However, in treatment studies, educational interventions were associated with a significant reduction in waist circumference [-3.21 cm (95%CI -6.34, -0.07)], BMI [-0.86 kg/m(2) (95%CI -1.59, -0.14)] and diastolic blood pressure [-3.68 mmHg (95%CI -5.48, -1.88)]. CONCLUSIONS: Educational interventions are effective in treatment, but not prevention, of childhood obesity and its consequences.

Cost-effectiveness of supervised exercise therapy in heart failure patients.

OBJECTIVE: Exercise therapy in heart failure (HF) patients is considered safe and has demonstrated modest reduction in hospitalization rates and death in recent trials. Previous cost-effectiveness analysis described favorable results considering long-term supervised exercise intervention and significant effectiveness of exercise therapy; however, these evidences are now no longer supported. To evaluate the cost-effectiveness of supervised exercise therapy in HF patients under the perspective of the Brazilian Public Healthcare System. METHODS: We developed a Markov model to evaluate the incremental cost-effectiveness ratio of supervised exercise therapy compared to standard treatment in patients with New York Heart Association HF class II and III. Effectiveness was evaluated in quality-adjusted life years in a 10-year time horizon. We searched PUBMED for published clinical trials to estimate effectiveness, mortality, hospitalization, and utilities data. Treatment costs were obtained from published cohort updated to 2008 values. Exercise therapy intervention costs were obtained from a rehabilitation center. Model robustness was assessed through Monte Carlo simulation and sensitivity analysis. Cost were expressed as international dollars, applying the purchasing-power-parity conversion rate. RESULTS: Exercise therapy showed small reduction in hospitalization and mortality at a low cost, an incremental cost-effectiveness ratio of Int$26,462/quality-adjusted life year. Results were more sensitive to exercise therapy costs, standard treatment total costs, exercise therapy effectiveness, and medications costs. Considering a willingness-to-pay of Int$27,500, 55% of the trials fell below this value in the Monte Carlo simulation. CONCLUSIONS: In a Brazilian scenario, exercise therapy shows reasonable cost-effectiveness ratio, despite current evidence of limited benefit of this intervention.

Functional electrical stimulation in the treatment of patients with chronic heart failure: a meta-analysis of randomized controlled trials.

Functional electrical stimulation (FES) produces beneficial effects in the treatment of patients with chronic heart failure (CHF), but studies carried out in these patients show small sample sizes and conflicting results. The aim of this meta-analysis was to systematically review the effect of treatment with FES compared with conventional aerobic exercise training (CA) or control group in patients with CHF. The search strategy included MEDLINE, LILACS, Physiotherapy Evidence Database and Cochrane Library. Randomized trials comparing FES versus CA or control group in the treatment of patients with CHF were included. Two reviewers independently extracted the data. Main analysis used a fixed-effects model. The search retrieved 794 articles, from which seven studies were included. Treatment with FES provided a smaller gain in peak VO2 compared with CA {-0.74 ml/kg per min [95% confidence interval (CI): -1.38 to -0.10]}. There was no difference in the muscle strength [-0.33 Nm (95% CI: -4.56 to 3.90)] and in the distance of the 6-min walk test [2.73 m (95% CI: -15.39 to 20.85)] on comparing FES with CA. An increase in peak VO2 of 2.78 ml/kg per min (95% CI: 1.44-4.13) was observed in FES versus the control group. Treatment with FES provides a similar gain in the distance of the 6-min walk test and in the muscle strength when compared with CA, but a small gain in the peak VO2. An increase in the peak VO2 can be obtained with FES as compared with the control group. Thus, FES may be an alternative in relation with CA for patients with CHF and with those who are unable to perform this kind of exercise.

Breast cancer survival in Brazil: How much health care access impact on cancer outcomes?

BACKGROUND: Breast cancer has a high incidence and increasing mortality in Southern Brazil. The present study evaluated clinical and sociodemographic characteristics, and their association with overall survival in a private cancer center. METHODS: 1113 breast cancer patients were included in this study. The association between survival and clinicopathological and sociodemographic characteristics was analyzed using Cox regression and Kaplan-Meyer curves. RESULTS: Median age at diagnosis was 52 years (SD 13.5). Most patients were diagnosed in stages 0 and I (62.7%), while only 1.3% had stage IV disease. Five- and 10-year overall survival were 93.5% and 83.8%, respectively. According to multivariate analysis, age at diagnosis (HR 1.05; CI95 1.03-1.06), staging (stage III: HR 4.04; CI95 1.34-12.19; stage IV: HR 9.61; CI95 2.17-42.50), high KI67 (HR 5.46; CI95 1.27-23.32) and distant recurrence (HR 7.28; CI95 4.79-11.06) were significantly associated with survival. Smoking status, years of education, BMI, and tumor biological status were not significantly associated with mortality. CONCLUSIONS: This cohort of Brazilian patients, who received timely and appropriate treatment, achieved outcomes that are comparable to those from high income countries. Breast cancer mortality seems dependent on the quality of health care available to patients.

A model to optimize public health care and downstage breast cancer in limited-resource populations in southern Brazil. (Porto Alegre Breast Health Intervention Cohort).

BACKGROUND: Breast cancer (BC) is a major public health problem, with rising incidence in many regions of the globe. Although mortality has recently dropped in developed countries, death rates are still increasing in some developing countries, as seen in Brazil. Among the reasons for this phenomenon are the lack of structured screening programs, a long waiting period between diagnosis and treatment, and lack of access to health services for a large proportion of the Brazilian population. METHODS AND DESIGN: Since 2004, an intervention study in a cohort of women in Southern Brazil, denominated Porto Alegre Breast Health Intervention Cohort, is being conducted in order to test the effectiveness and cost-effectiveness of a model for BC early detection and treatment. In this study, over 4,000 women from underserved communities aged 40 to 69 years are being screened annually with mammography and clinical breast examination performed by a multidisciplinary team, which also involves nutritional counseling and genetic cancer risk assessment. Risk factors for BC development are also being evaluated. Active search of participants by lay community health workers is one of the major features of our program. The accrual of new participants was concluded in 2006 and the study will last for 10 years. The main goal of the study is to demonstrate significant downstaging of BC in an underserved population through proper screening, attaining a higher rate of early-stage BC diagnoses than usually seen in women diagnosed in the Brazilian Public Health System. Preliminary results show a very high BC incidence in this population (117 cases per 100,000 women per year), despite a low prevalence of classical risk factors. DISCUSSION: This study will allow us to test a model of BC early diagnosis and treatment and evaluate its cost-effectiveness in a developing country where the mortality associated with this disease is very high. Also, it might contribute to the evaluation of risk factors in a population with a different ethnic background from that studied in developed countries. If our model is proven effective, it may be replicated in other parts of the globe where BC is also a major public health problem.

The Clinical and Economic Burden of Colorectal Anastomotic Leaks: Middle-Income Country Perspective.

PURPOSE: Anastomotic leaks (AL) present a significant source of clinical and economic burden on patients undergoing colorectal surgeries. This study was aimed at evaluating the clinical and economic consequences of AL and its risk factors. METHODS: A retrospective cohort study was conducted between 2012 and 2013 based on the billing information of 337 patients who underwent low anterior resection (LAR). The outcomes evaluated were the development of AL, use of antibiotics, 30-day readmission and mortality, and total hospital costs, including readmissions and length of stay (LOS). The risk factors for AL, as well as the relationship between AL and clinical outcomes, were analyzed using multivariable Poisson regression. Generalized linear models (GLM) were employed to evaluate the association between AL and continuous outcomes (LOS and costs). RESULTS: AL was detected in 6.8% of the patients. Emergency surgery (aRR 2.56; 95% CI: 1.15-5.71, p = 0.021), blood transfusion (aRR 4.44; 95% CI: 1.86-10.64, p = 0.001), and cancer diagnosis (aRR 2.51; 95% CI: 1.27-4.98, p = 0.008) were found to be independent predictors of AL. Patients with AL showed higher antibiotic usage (aRR 1.69; 95% CI: 1.37-2.09, p < 0.001), 30-day readmission (aRR 3.34; 95% CI: 1.53-7.32, p = 0.003) and mortality (aRR 13.49; 95% CI: 4.10-44.35, p < 0.001), and longer LOS (39.6 days, as opposed to 7.5 days for patients without AL, p < 0.001). Total hospital costs amounted to R$210,105 for patients with AL in comparison with R$34,270 for patients without AL (p < 0.001). In multivariable GLM, the total hospital costs for AL patients were 4.66 (95% CI: 3.38-6.23, p < 0.001) times higher than those for patients without AL. CONCLUSIONS: AL leads to worse clinical outcomes and increases hospital costs by 4.66 times. The risk factors for AL were found to be emergency surgery, blood transfusion, and cancer diagnosis.

Association of anemia with clinical outcomes in stable coronary artery disease.

BACKGROUND: Although anemia is pathophysiologically associated with myocardial ischemia, there are scarce data on its clinical impact in patients with stable coronary artery disease on contemporary treatment. This study aims to describe the prevalence of anemia, and its association with symptoms and outcomes in this population. METHODS: We conducted a prospective cohort study in stable documented coronary artery disease patients. Anemia criteria was hemoglobin (Hb) <12 g/dl in women and <13 g/dl in men. Hemoglobin levels were divided in quartiles (Q) adjusted for sex. Major events included acute coronary syndromes, stroke and cardiovascular deaths. Secondary outcomes were presence of angina and chronic use of nitrates. Cox regression models were used to evaluate the independent effect of anemia on clinical outcomes. RESULTS: Among 310 patients, 71 (23%) met criteria for anemia. After a mean follow-up of 44+/-23 months, hemoglobin levels had a marked association with occurrence of major events (27% in Q1, 7% in Q2, 8% in Q3 and 12% in Q4; P<0.01). In multivariate analysis, anemia was independently associated with an increased risk of death [hazard ratio (HR) 6.5, 95% confidence interval (1.7-24.2)], major events [HR 3.3 (1.7-6.5)] and revascularization procedures [HR 2.3 (1.3-4.1)]. Persistent of angina symptoms (32 vs. 18%, P=0.01) and chronic use of nitrates (35 vs. 21%, P=0.02) were also more frequent among patients with anemia at baseline. CONCLUSIONS: In patients with stable ischemic heart disease, presence of anemia, even mild, is associated with a worse prognosis. Strategies aiming at identifying reversible causes of anemia or new treatments should be evaluated in prospective clinical trials.

Terlipressin versus noradrenaline in the treatment of hepatorenal syndrome: systematic review with meta-analysis and full economic evaluation.

OBJECTIVE: The aim of this study was to compare the efficacy and costs of terlipressin and noradrenaline for the treatment of hepatorenal syndrome from the perspective of the Brazilian public health system and that of a major private health insurance. METHODS: Comparison of efficacy was performed through a systematic review with a meta-analysis of randomized-controlled trials using a random-effects model. Economic evaluation was carried out through cost minimization. RESULTS: Four studies (154 patients) were included in the meta-analysis. There was no evidence of a difference between treatments with terlipressin or noradrenaline in terms of 30-day survival (risk ratio=1.04, 95% confidence interval=0.84-1.30, P=0.70). From the perspective of the public health system, costs of the treatments with terlipressin or noradrenaline were Int$7437.04 and Int$8406.41, respectively. From the perspective of the private health insurance, costs of treatments with terlipressin and noradrenaline were Int$13,484.57 and Int$15,061.01, respectively. CONCLUSION: There was no evidence of superiority between treatment strategies using terlipressin or noradrenaline in terms of the survival of patients with hepatorenal syndrome, but the strategy using terlipressin was more economical under two different perspectives.

Spontaneous Breathing Trials With T-Piece or Pressure Support Ventilation.

Spontaneous breathing trials (SBTs) are among the most commonly employed techniques to facilitate weaning from mechanical ventilation. The preferred SBT technique, however, is still unclear. To clarify the preferable SBT (T-piece or pressure support ventilation [PSV]), we conducted this systematic review. We then searched the MEDLINE, EMBASE, SciELO, Google Scholar, CINAHL, ClinicalTrials.gov, and Cochrane CENTRAL databases through June 2015, without language restrictions. We included randomized controlled trials involving adult subjects being weaned from mechanical ventilation comparing T-piece with PSV and reporting (1) weaning failure, (2) re-intubation rate, (3) ICU mortality, or (4) weaning duration. Anticipating clinical heterogeneity among the included studies, we compared prespecified subgroups: (1) simple, difficult, or prolonged weaning and (2) subjects with COPD. We summarized the quality of evidence for intervention effects using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. We identified 3,674 potentially relevant studies and reviewed 23 papers in full. Twelve studies (2,161 subjects) met our inclusion criteria. Overall, the evidence was of very low to low quality. SBT technique did not influence weaning success (risk ratio 1.23 [0.94-1.61]), ICU mortality (risk ratio 1.11 [0.80-1.54]), or re-intubation rate (risk ratio 1.21 [0.90-1.63]). Prespecified subgroup analysis suggested that PSV might be superior to T-piece with regard to weaning success for simple-to-wean subjects (risk ratio 1.44 [1.11-1.86]). For the prolonged-weaning subgroup, however, T-piece was associated with a shorter weaning duration (weighted mean difference -3.08 [-5.24 to -0.92] d). In conclusion, low-quality evidence is available concerning this topic. PSV may be associated with lower weaning failure rates in the simple-to-wean subgroup. In contrast, in prolonged-weaning subjects, T-piece may be related to a shorter weaning duration, although this is at high risk of bias. Further study of the difficult-to-wean and COPD subgroups is required.

[Annual cost of ischemic heart disease in Brazil. Public and private perspective]. / Custo anual do manejo da cardiopatia isquêmica crônica no Brasil. Perspectiva pública e privada.

OBJECTIVE: To estimate the annual cost of coronary artery disease (CAD) management in Public Health Care System (SUS) and HMOs values in Brazil. METHODS: Cohort study, including ambulatory patients with proven CAD. Clinic visits, exams, procedures, hospitalizations and medications were considered to estimate direct costs. Values of appointments and exams were obtained from the SUS and the Medical Procedure List (LPM 1999) reimbursement tables. Costs of cardiovascular events were obtained from admissions in public and private hospitals with similar diagnoses-related group classifications in 2002. The price of medications used was the lowest found in the market. RESULTS: The 147 patients (65 +/- 12 years old, 63% men, 69% hypertensive, 35% diabetic and 59% with previous AMI) had an average follow-up of 24 +/- 8 months. The average estimated annual cost per patient was R$ 2,733.00, for the public sector, and R$ 6,788.00, for private and fee-for-service plans. Expenses with medications (R$ 1,154.00) represented 80% and 55% of outpatient costs, and 41% and 17% of total expenses, in public and non-public sectors, respectively. The occurrence of cardiovascular event had a great impact (R$ 4,626.00 vs. R$ 1,312.00, in SUS, and R$ 13,453.00 vs. R$ 1,789.00, for HMOs, p<0.01) on the results. CONCLUSION: The average annual cost of CAD management was high, being the pharmacological treatment the main determinant of public costs. Such estimates may subsidize economical analyses in this area, and foster related healthcare policies.

Adherence to a breast cancer screening program and its predictors in underserved women in southern Brazil.

BACKGROUND: Adherence to breast cancer screening is a key element to ensure effectiveness of programs aiming at downstaging of breast cancer. In this study, we evaluated adherence to a screening program and its predictors in underserved women in southern Brazil. METHODS: Attendance to the program, which is based on yearly mammogram and clinical examination, was evaluated prospectively. Mean time frames between visits were calculated. Possible predictors of adherence (defined as mean intervals ≤18 mo), such as socioeconomic indicators and health/lifestyle behaviors, were investigated. RESULTS: A total of 3,749 women (age 51 ± 8 y, illiteracy rate of 6.8%, 57.4% with parity ≥3) were analyzed. Median time between screening rounds was 16.5 months (interquartile range, 13.1-25.7), and median number of rounds attended was 3 (interquartile range, 2-4); 57.6% had mean intervals ≤18, and 71% ≤24 months. The most important independent predictors of adherence were high genetic risk [relative risk (RR), 1.25; 95% confidence interval (95% CI), 1.11-1.40], illiteracy (RR, 0.77; 95% CI, 0.67-0.90), parity ≥5 (RR, 0.89; 95% CI, 0.83-0.96), and smoking (RR, 0.82; 95% CI, 0.77-0.88). CONCLUSIONS: Although the proposed screening interval was 1 year, compliance to biannual screening (accepted in several international programs) was high, especially when considering the low socioeconomic level of the sample. IMPACT: This project aims to test a breast cancer screening model for underserved populations in limited-resource countries where adherence is an issue. The identification of worst adherence predictors can point to interventions to improve outcomes of similar public health screening strategies.

The quality of reporting of trial abstracts is suboptimal: survey of major general medical journals.

OBJECTIVE: To evaluate the quality of reporting of abstracts describing randomized controlled trials (RCTs) published in four major general medical journals. STUDY DESIGN AND SETTING: Systematic survey of published RCT abstracts, with two reviewers independently extracting data. We searched MEDLINE and identified 227 RCT abstracts published in the New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), British Medical Journal (BMJ), and The Lancet in the year 2006. RESULTS: Most abstracts identified the study as a randomized trial (98.7%), reported the objectives (92.5%), described the population (90.3%), detailed the intervention (81.5%), and defined the primary outcome (71.3%). Methodological quality was poorly reported: one (0.4%) described allocation concealment; 21 (9.3%) clearly specified blinding; 51 (22.5%) described intention-to-treat analysis; and 32 (14.1%) outlined losses to follow-up. Most of the abstracts reported the effect size and the confidence intervals (62.3%), but just half of them reported side effects or harms. CONCLUSION: The quality of reporting of RCT abstracts published in main general medical journals is suboptimal. Space limitations notwithstanding, with the recent recommendations from the CONSORT for Abstracts, it is expected that the transparency of abstract reporting can and should improve.

Hemodynamic monitoring in obese patients: the impact of body mass index on cardiac output and stroke volume.

OBJECTIVE: Interpreting hemodynamic parameters in critically ill obese patients can be difficult as the effects of body mass index (BMI) on cardiac output (CO) and stroke volume (SV) at the extremes of body size remains unknown. We examined the relationship between BMI and both CO and SV for patients with varying body sizes. DESIGN: Retrospective cohort analysis. SETTING: A large tertiary care academic medical center. PATIENTS: A total of 700 consecutive adults who were found to have disease-free coronary arteries and a cardiac output measurement (thermodilution or Fick method) during coronary angiography between July 1, 2000, and July 31, 2004. MEASUREMENTS AND RESULTS: We examined the relationship between BMI (mean, 28 kg/m(2); range, 10.6-91.6 kg/m(2)) and cardiac hemodynamics after adjusting for demographic (age, sex) and clinical (diabetes, smoking status, valvular heart disease, medications, indications for catheterization) characteristics using multivariable regression. Body mass index was positively correlated with CO and SV. Each 1 kg/m increase in BMI was associated with a 0.08 L/min (95% confidence interval [CI], 0.06-0.10; p < .001) increase in CO and 1.35 mL (95% CI, 0.96-1.74; p < .001) increase in SV. There was no significant association between BMI and both cardiac index (0.003 L/min/m(2); 95% CI, -0.008-0.014; p = .571) and stroke volume index (0.17 mL/m(2); 95% CI, -0.03-0.37; p = .094). CONCLUSION: Variations in BMI translate into predictable but only modest differences in CO and SV, even at the extremes of body size. Indexing hemodynamic measurements to body surface area attenuates the effects of BMI. Body habitus should not appreciably complicate the interpretation of hemodynamic measurements.

Custo anual do manejo da cardiopatia isquêmica crônica no Brasil: perspectiva pública e privada / Annual cost of ischemic heart disease in Brazil: public and private perspective

OBJETIVO: Estimar o custo anual do manejo da doenca arterial coronária (DAC) em valores do SUS e convênios. MÉTODOS: Estudo de coorte, incluindo pacientes ambulatoriais com DAC comprovada. Considerou-se para estimar custos diretos: consultas, exames, procedimentos, internacões e medicamentos. Valores de consultas e exames foram obtidos da tabela SUS e da Lista de Procedimentos Médicos (LPM). Valores de eventos cardiovasculares foram obtidos de internacões em hospital público e privado com estas classificacões diagnósticas em 2002. O preco dos fármacos utilizado foi o de menor custo no mercado. RESULTADOS: Os 147 pacientes (65n12 anos, 63 por cento homens, 69 por cento hipertensos, 35 por cento diabéticos e 59 por cento com IAM prévio) tiveram acompanhamento médio de 24n8 meses. O custo anual médio estimado por paciente foi de R$ 2.733,00, pelo SUS, e R$ 6.788,00, para convênios. O gasto com medicamentos ($ 1.154,00) representou 80 por cento e 55 por cento dos custos ambulatoriais, e 41 por cento e 17 por cento dos gastos totais, pelo SUS e para convênios, respectivamente. A ocorrência de evento cardiovascular teve grande impacto (R$ 4.626,00 vs. R$ 1.312,00, pelo SUS, e R$ 13.453,00 vs. R$ 1.789,00, para convênios, p<0,01). CONCLUSAO: O custo médio anual do manejo da DAC foi elevado, sendo o tratamento farmacológico o principal determinante dos custos públicos. Essas estimativas podem subsidiar análises econômicas nesta área, sendo úteis para nortear políticas de saúde pública.