Development and Validation of a Predictive Model of Success in Bariatric Surgery.

PURPOSE: There are no criteria to establish priority for bariatric surgery candidates in the public health system in several countries. The aim of this study is to identify preoperative characteristics that allow predicting the success after bariatric surgery. MATERIALS AND METHODS: Four hundred and sixty-one patients submitted to Roux-en-Y gastric bypass were included. Success of the surgery was defined as the sum of five outcome variables, assessed at baseline and 12 months after the surgery: excess weight loss, use of continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) as a treatment for obstructive sleep apnea (OSA), daily number of antidiabetics, daily number of antihypertensive drugs, and all-cause mortality. Partial least squares (PLS) regression and multiple linear regression were performed to identify preoperative predictors. We performed a 90/10 split of the dataset in train and test sets and ran a leave-one-out cross-validation on the train set and the best PLS model was chosen based on goodness-of-fit criteria. RESULTS: The preoperative predictors of success after bariatric surgery included lower age, presence of non-alcoholic fatty liver disease and OSA, more years of CPAP/BiPAP use, negative history of cardiovascular disease, and lower number of antihypertensive drugs. The PLS model displayed a mean absolute percent error of 0.1121 in the test portion of the dataset, leading to accurate predictions of postoperative outcomes. CONCLUSION: This success index allows prioritizing patients with the best indication for the procedure and could be incorporated in the public health system as a support tool in the decision-making process.

Short-acting insulin analogues versus regular human insulin on postprandial glucose and hypoglycemia in type 1 diabetes mellitus: a systematic review and meta-analysis.

INTRODUCTION: Strict glucose control using multiple doses of insulin is the standard treatment for type 1 diabetes mellitus (T1DM), but increased risk of hypoglycemia is a frequent drawback. Regular insulin in multiple doses is important for achieving strict glycemic control for T1DM, but short-acting insulin analogues may be better in reducing hypoglycemia and postprandial glucose levels. OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of short-acting insulin analogues vs regular human insulin on hypoglycemia and postprandial glucose in patients with T1DM. METHODS: Searches were run on the electronic databases MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and DARE for RCTs published until August 2017. To be included in the study, the RCTs had to cover a minimum period of 4 weeks and had to assess the effects of short-acting insulin analogues vs regular human insulin on hypoglycemia and postprandial glucose levels in patients with T1DM. Two independent reviewers extracted the data and assessed the quality of the selected studies. The primary outcomes analyzed were hypoglycemia (total episodes, nocturnal hypoglycemia, and severe hypoglycemia) and postprandial glucose (at all times, after breakfast, after lunch, and after dinner). Glycated hemoglobin (HbA1c) levels and quality of life were considered secondary outcomes. The risk of bias of each RCT was assessed using the Cochrane Collaboration Risk of Bias table, while the quality of evidence for each outcome was assessed using the GRADEpro software. The pooled mean difference in the number of hypoglycemic episodes and postprandial glucose between short-acting insulin analogues vs. regular human insulin was calculated using the random-effects model. RESULTS: Of the 2897 articles retrieved, 22 (6235 patients) were included. Short-acting insulin analogues were associated with a decrease in total hypoglycemic episodes (risk rate 0.93, 95% CI 0.87-0.99; 6235 patients; I2 = 81%), nocturnal hypoglycemia (risk rate 0.55, 95% CI 0.40-0.76, 1995 patients, I2 = 84%), and severe hypoglycemia (risk rate 0.68, 95% CI 0.60-0.77; 5945 patients, I2 = 0%); and with lower postprandial glucose levels (mean difference/MD - 19.44 mg/dL; 95% CI - 21.49 to - 17.39; 5031 patients, I2 = 69%) and lower HbA1c (MD - 0,13%; IC 95% - 0.16 to - 0.10; 5204 patients; I2 = 73%) levels. CONCLUSIONS: Short-acting insulin analogues are superior to regular human insulin in T1DM patients for the following outcomes: total hypoglycemic episodes, nocturnal hypoglycemia, severe hypoglycemia, postprandial glucose, and HbA1c.

Estimated costs of hospitalization due to coronary artery disease attributable to familial hypercholesterolemia in the Brazilian public health system.

OBJECTIVE: Cardiovascular diseases are the leading cause of death in Brazil, imposing substantial economic burden on the health care system. Familial hypercholesterolemia (FH) is known to greatly increase the risk of premature coronary artery disease (CAD). This study aimed to estimate the economic impact of hospitalizations due to CAD attributable to FH in the Brazilian Unified Health Care System (SUS). SUBJECTS AND METHODS: Retrospective, cross-sectional study of data obtained from the Hospital Information System of the SUS (SIHSUS). We selected all adults (≥ 20 years of age) hospitalized from 2012--2014 with primary diagnoses related to CAD (ICD-10 I20 to I25). Attributable risk methodology estimated the contribution of FH in the outcomes of interest, using international data for prevalence (0.4% and 0.73%) and relative risk for events (RR = 8.56). RESULTS: Assuming an international prevalence of FH of 0.4% and 0.73%, of the 245,981 CAD admissions/year in Brazil, approximately 7,249 and 12,915, respectively, would be attributable to an underlying diagnosis --of FH. The total cost due to CAD per year, considering both sexes and all adults, was R$ 985,919,064, of which R$ 29,053,500 and R$ 51,764,175, respectively, were estimated to be attributable to FH. The average cost per FH-related CAD event was R$ 4,008. CONCLUSION: Based on estimated costs of hospitalization for CAD, we estimated that 2.9-5.3% are directed to FH patients. FH can require early specific therapies to lower risk in families. It is mandatory to determine the prevalence of FH and institute appropriate treatment to minimize the clinical and economic impact of this disease in Brazil.

Estimated costs of hospitalization due to coronary artery disease attributable to familial hypercholesterolemia in the Brazilian public health system

ABSTRACT Objective: Cardiovascular diseases are the leading cause of death in Brazil, imposing substantial economic burden on the health care system. Familial hypercholesterolemia (FH) is known to greatly increase the risk of premature coronary artery disease (CAD). This study aimed to estimate the economic impact of hospitalizations due to CAD attributable to FH in the Brazilian Unified Health Care System (SUS). Subjects and methods: Retrospective, cross-sectional study of data obtained from the Hospital Information System of the SUS (SIHSUS). We selected all adults (≥ 20 years of age) hospitalized from 2012­-2014 with primary diagnoses related to CAD (ICD-10 I20 to I25). Attributable risk methodology estimated the contribution of FH in the outcomes of interest, using international data for prevalence (0.4% and 0.73%) and relative risk for events (RR = 8.56). Results: Assuming an international prevalence of FH of 0.4% and 0.73%, of the 245,981 CAD admissions/year in Brazil, approximately 7,249 and 12,915, respectively, would be attributable to an underlying diagnosis ­­of FH. The total cost due to CAD per year, considering both sexes and all adults, was R$ 985,919,064, of which R$ 29,053,500 and R$ 51,764,175, respectively, were estimated to be attributable to FH. The average cost per FH-related CAD event was R$ 4,008. Conclusion: Based on estimated costs of hospitalization for CAD, we estimated that 2.9-5.3% are directed to FH patients. FH can require early specific therapies to lower risk in families. It is mandatory to determine the prevalence of FH and institute appropriate treatment to minimize the clinical and economic impact of this disease in Brazil.

Disease and Economic Burden of Hospitalizations Attributable to Diabetes Mellitus and Its Complications: A Nationwide Study in Brazil.

Diabetes is associated with a significant burden globally. The costs of diabetes-related hospitalizations are unknown in most developing countries. The aim of this study was to estimate the total number and economic burden of hospitalizations attributable to diabetes mellitus (DM) and its complications in adults from the perspective of the Brazilian Public Health System in 2014. Data sources included the National Health Survey (NHS) and National database of Hospitalizations (SIH). We considered diabetes, its microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary heart disease, cerebrovascular disease, and peripheral arterial disease), respiratory and urinary tract infections, as well as selected cancers. Assuming that DM patients are hospitalized for these conditions more frequently that non-DM individuals, we estimated the etiological fraction of each condition related to DM, using the attributable risk methodology. We present number, average cost per case, and overall costs of hospitalizations attributable to DM in Brazil in 2014, stratified by condition, state of the country, gender and age group. In 2014, a total of 313,273 hospitalizations due to diabetes in adults were reported in Brazil (4.6% of total adult hospitalization), totaling (international dollar) Int$264.9 million. The average cost of an adult hospitalization due to diabetes was Int$845, 19% higher than hospitalization without DM. Hospitalizations due to cardiovascular diseases related to diabetes accounted for the higher proportion of costs (47.9%), followed by microvascular complications (25.4%) and DM per se (18.1%). Understanding the costs of diabetes and its major complications is crucial to raise awareness and to support the decision-making process on policy implementation, also allowing the assessment of prevention and control strategies.

Annual Direct Medical Costs of Diabetic Foot Disease in Brazil: A Cost of Illness Study.

The aim of this study was to estimate the annual costs for the treatment of diabetic foot disease (DFD) in Brazil. We conducted a cost-of-illness study of DFD in 2014, while considering the Brazilian Public Healthcare System (SUS) perspective. Direct medical costs of outpatient management and inpatient care were considered. For outpatient costs, a panel of experts was convened from which utilization of healthcare services for the management of DFD was obtained. When considering the range of syndromes included in the DFD spectrum, we developed four well-defined hypothetical DFD cases: (1) peripheral neuropathy without ulcer, (2) non-infected foot ulcer, (3) infected foot ulcer, and (4) clinical management of amputated patients. Quantities of each healthcare service was then multiplied by their respective unit costs obtained from national price listings. We then developed a decision analytic tree to estimate nationwide costs of DFD in Brazil, while taking into the account the estimated cost per case and considering epidemiologic parameters obtained from a national survey, secondary data, and the literature. For inpatient care, ICD10 codes related to DFD were identified and costs of hospitalizations due to osteomyelitis, amputations, and other selected DFD related conditions were obtained from a nationwide hospitalization database. Direct medical costs of DFD in Brazil was estimated considering the 2014 purchasing power parity (PPP) (1 Int$ = 1.748 BRL). We estimated that the annual direct medical costs of DFD in 2014 was Int$ 361 million, which denotes 0.31% of public health expenses for this period. Of the total, Int$ 27.7 million (13%) was for inpatient, and Int$ 333.5 million (87%) for outpatient care. Despite using different methodologies to estimate outpatient and inpatient costs related to DFD, this is the first study to assess the overall economic burden of DFD in Brazil, while considering all of its syndromes and both outpatients and inpatients. Although we have various reasons to believe that the hospital costs are underestimated, the estimated DFD burden is significant. As such, public health preventive strategies to reduce DFD related morbidity and mortality and costs are of utmost importance.

The costs of type 2 diabetes mellitus outpatient care in the Brazilian public health system.

OBJECTIVE: The prevalence of type 2 diabetes has shown a significant increase in parallel with health care costs. The objective of the Brazilian Study on Diabetes Costs (ESCUDI study) was to estimate direct and indirect costs of type 2 diabetes outpatient care in the Brazilian Public Health Care System. METHODS: Data were collected from different levels of health care in eight Brazilian cities in 2007. A total of 1000 outpatients were interviewed and had their medical records data analyzed. Direct medical costs included expenses with medications, diagnostic tests, procedures, blood glucose test strips, and office visits. Nonmedical direct costs included expenses with diet products, transportation, and caregivers. Absenteeism, sick leave, and early retirement were classified as indirect costs. RESULTS: Total annual cost for outpatient care was US$2108 per patient, out of which US$1335 per patient of direct costs (63.3%) and US$773 per patient of indirect costs (36.7%). Costs escalated as duration of diabetes and level of health care increased. Patients with both microvascular and macrovascular complications had higher costs (US$3199 per patient) compared to those with either microvascular (US$2062 per patient) or macrovascular (US$2517 per patient) complications only. The greatest portion of direct costs was attributed to medication (48.2%). CONCLUSIONS: Diabetes treatment leads to elevated costs both to Brazilian Public Health Care System and society. Costs increased along with duration of disease, level of care and presence of chronic complications, which suggested a need to reallocate health resources focusing on primary prevention of diabetes and its complications.

[Vascular dysfunction in metabolic disorders: evaluation of some therapeutic interventions]. / Dysfonctionnement vasculaire dans les désordres métaboliques: evaluation de quelques essais thérapeutiques.

Cardiovascular diseases continue to be the main cause of death in most industrialized countries. Endothelial dysfunction, a systemic process, is the earliest known marker of atherosclerosis and has become a major focus in acute ischemic disorders. We are investigating the hypothesis that, in these diseases, microvascular and endothelial dysfunctions occur simultaneously and precede the onset of macrovascular disease. We studied, to our knowledge for the first time in the same subjects, microvascular and endothelial functions in 11 patients with type 2 diabetes. 36 metabolic syndrome patients (NCEP-ATPIII criteria) and 25 young obese women matched with healthy controls. Micro vascular morphology and hemodynamics were evaluated non-invasively by means of nailfold videocapillaroscopy. Red blood cell velocity (RBCV, mm/s) was measured at rest and after release from 60 s of arterial occlusion (RBCVmax, mm/s) at the finger base, along with the time to reach RBCVmax (TRBCVmax, s), by video analysis with Cap Image software. Venous occlusion plethysmography was performed after intra-arterial infusions of acetylcholine and sodium nitroprusside to assess endo thelial-dependent and -independent vasodilation, respectively. We found similar results in the three groups of subjects, namely a significant decrease in RBCVmax, an increase in TRBCVmax, and a decrease in endothelial-dependent vasodilation. These findings clearly demonstrate that the two dysfunctions occur simultaneously in these groups of patients. Several mechanisms which could impair micro vascular and endothelial functions are associated with insulin resistance, and drugs that act on insulin resistance might thus be beneficial. Metformin, given to 16 first-degree relatives of patients with type 2 diabetes mellitus, who had the metabolic syndrome and normal glucose tolerance (ADA criteria), improved endothelial-dependent vasodilation and microcirculatory function. Rosiglitazone, given to 18 patients with the metabolic syndrome, enhanced vascular responses by improving endothelial function and increasing adiponectin levels. Increased triglyceride storage is often associated with insulin resistance, contributing to free fatty acid (FFA) overexposure. The two drugs tested here stimulate AMP-activated protein kinase, which promotes FFA oxidation and thus reduces oxidative stress, and might therefore attenuate endothelial lipotoxicity. The results strongly suggest that targeting micro vascular and endothelial dysfunctions in patients with metabolic disorders might help to prevent cardiovascular events, and warrant long-term clinical trials.

Metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance.

OBJECTIVE: Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The study included 31 subjects (age 38.3 +/- 7.6 years and BMI 36.3 +/- 5.2 kg/m2), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n = 15) or metformin (n = 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 microg/min) and independent (sodium nitroprusside 2, 4, and 8 microg/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment. RESULTS: The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters. CONCLUSIONS: We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects.