Custo Direto do Tratamento do Acidente Vascular Cerebral Isquêmico na Perspectiva de um Hospital Público Terciário (Direct Cost of Treating Ischemic Stroke From the Perspective of a Tertiary Public Hospital).

OBJECTIVES: To measure the direct cost of treating acute ischemic stroke (IS) from the perspective of a public hospital in Brazil (HCFMB) and compare it with the reimbursement by the Unified Health System (SUS), through the Procedure Table Management System, Medicines, Orthoses/Prostheses and Special Materials of the Unified Health System (SIGTAP). METHODS: We performed a micro-costing study; four scenarios were evaluated: standard (1); alteplase (2); alteplase and mechanical thrombectomy (3); mechanical thrombectomy (4). Based on the number of patients hospitalized for ischemic stroke in 2019, hospital cost, and SUS billing were calculated for each scenario. Hospital costs were adjusted for inflation using CCEMG-EPPI-Centre Cost Converter. RESULTS: In 2019, 258 patients were hospitalized due to IS, 89.5% in scenario 1, 8% in scenario 2, 1.5% in scenario 3, 1% in scenario 4. From the hospital's perspective, the cost per patient was estimated at R$7780.13, R$15 741.23, R$28 988.49, R$25 739.79, for scenarios 1, 2, 3 and 4, respectively. The reimbursement by SIGTAP was estimated at R$3079.87, R$5417.21, R$10 901.92, R$10 286.28, respectively. If thrombectomy had been included in the SIGTAP, the last two values would be R$25 393.34 and R$24 248.89. CONCLUSIONS: The hospital cost of treating acute IS in 2019 was estimated at R$2 295 209, the SUS reimbursement at R$889 391.54. With the inclusion of thrombectomy at SIGTAP, this reimbursement would be R$975 282.44, and the loss in the cost of HCFMB per patient in relation to reimbursement by the SUS is greater in scenarios without this procedure.

A Microcost Analysis of the Use of Personal Protective Equipment During and Before the COVID-19 Pandemic From a Hospital Perspective.

OBJECTIVES: To calculate the direct cost of personal protective equipment (PPE) used during the COVID-19 pandemic from the perspective of a Brazilian tertiary public hospital. METHODS: We evaluated the cost of PPE during the pandemic to the cost before (2021 vs 2019, respectively) using the microcosting method. Cost estimates were converted into US dollars in 2023, taking inflation into account and using purchasing power parity conversion rates. Our expenses included gloves, disposable gowns, head coverings, masks, N95 respirators, and eye protection. The number of PPE used was determined by the hospital's usual protocol, the total number of hospitalized patients, and the number of days of hospitalization. We used the following variables for uncertainty analysis: PPE adherence, an interquartile range of median length of hospitalization, and variance in the cost of each PPE. RESULTS: In 2021, 26 618 individuals were hospitalized compared with 31 948 in 2019. The median length of stay was 6 and 4 days, respectively. The total and per-patient direct cost of PPE were projected to be 2 939 935.47 US dollar (USD) and 110.45 USD, respectively, during the pandemic, and 1 570 124.08 USD and 49.15 USD, respectively, before the pandemic. The individual cost of PPE was the most influential cost variable. CONCLUSIONS: According to the hospital's perspective, the total estimated direct cost of PPE during the COVID-19 pandemic was nearly twice as high as the previous year. This difference might be explained by the 3-fold increase in PPE in the treatment of patients with COVID-19 compared with patients without isolation precautions.

Accuracy of the 10 µg desmopressin test for differential diagnosis of Cushing syndrome: a systematic review and meta-analysis.

We evaluated the accuracy of the 10 µg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome (EAS). A systematic review of studies on diagnostic test accuracy in patients with CD, NNH, or EAS subjected to the desmopressin test obtained from LILACS, PubMed, EMBASE, and CENTRAL databases was performed. Two reviewers independently selected the studies, assessed the risk of bias, and extracted the data. Hierarchical and bivariate models on Stata software were used for meta-analytical summaries. The certainty of evidence was measured using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation Working Group) approach. In total, 14 studies were included: 3 studies on differentiated CD versus NNH and 11 studies on differentiated CD versus EAS. Considering ΔACTH in 8 studies involving 429 patients, the pooled sensitivity for distinguishing CD from EAS was 0.85 (95% confidence interval [CI]: 0.80-0.89, I2 = 17.6%) and specificity was 0.64 (95% CI: 0.49-0.76, I2 = 9.46%). Regarding Δcortisol in 6 studies involving 233 participants, the sensitivity for distinguishing CD from EAS was 0.81 (95% CI: 0.74-0.87, I2 = 7.98%) and specificity was 0.80 (95% CI: 0.61-0.91, I2 = 12.89%). The sensitivity and specificity of the combination of ΔACTH > 35% and Δcortisol > 20% in 5 studies involving 511 participants were 0.88 (95% CI: 0.79-0.93, I2 = 35%) and 0.74 (95% CI: 0.55-0.87, I2 = 27%), respectively. The pooled sensitivity for distinguishing CD from NNH in 3 studies involving 170 participants was 0.88 (95% CI: 0.79-0.93) and the specificity was 0.94 (95% CI: 0.86-0.97). Based on the desmopressin test for differentiating CD from EAS, considering ΔACTH, Δcortisol, or both percent increments, 15%, 19%, or 20% of patients with CD, respectively, would be incorrectly classified as having EAS. For CD versus NNH, 11% of patients with CD would be falsely diagnosed as having NNH, whereas 7% of patients with NNH would be falsely diagnosed as having CD. However, in all hierarchical plots, the prediction intervals were considerably wider than the confidence intervals. This indicates low confidence in the estimated accuracy, and the true accuracy is likely to be different. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=85634, identifier CRD42018085634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=68317, identifier CRD42017068317.

Treatment of non-functioning pituitary adenoma with cabergoline: a systematic review and meta-analysis.

PURPOSE: To make a systematic review and meta-analysis of studies evaluating the effect of cabergoline (CBG) in the treatment of non-functioning pituitary adenomas (NFPAs). METHODS: The primary outcome was tumor shrinkage, using as cut-off a reduction of at least 20% of the NFPA size from baseline. The secondary outcomes were prevention of tumor progression, clinically required additional interventions and adverse events (AE). Search strategies were applied to MEDLINE, EMBASE, LILACS and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Random meta-analysis for the proportion of tumor shrinkage, prevention of tumor progression, clinically required additional interventions and frequency of AE were conducted. RESULTS: Five studies were included. The meta-analysis of proportion was 19% for tumor shrinkage (95% CI 8-38%, 4 studies, 108 participants), 50% for prevention of tumor progression (95% CI 35-64%, 5 studies, 187 participants), 14% for clinically required additional interventions (95% CI 6-30%, 4 studies, 128 participants) and 2% for adverse events (95% CI 1-6%, 3 studies, 157 participants). CONCLUSIONS: Effect of CBG to promote tumor shrinkage in NFPAs was low, while prevention of tumor progression after surgery was seen in half of the cases, with a low frequency of adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020206778.

Effect of bortezomib on the treatment of multiple myeloma: a systematic review protocol.

INTRODUCTION: Multiple myeloma (MM) is an incurable malignant neoplasm that accounts for approximately 1% of all cancers and 10% of haematological malignancies. Bortezomib is one of the most commonly used medications in first-line treatment and subsequent relapses, either as a single agent or in combination with other therapies. This study aims to assess the effects of bortezomib on the overall survival (OS), progression-free survival, overall response rate, time to next treatment, health-related quality of life, compliance, adverse events and treatment-related death in patients with MM. METHODS AND ANALYSIS: We have performed a systematic review and meta-analysis and will include both randomised and non-randomised controlled studies where the effect of bortezomib was compared in similar or dissimilar background therapies in each arm. General and adaptive search strategies have been created for the following electronic health databases: Embase, Medline, LILACS and CENTRAL. Two reviewers have independently selected eligible studies, will assess the risk of bias, and will extract data from the included studies. Similar outcomes will be plotted in the meta-analysis using the Stata Statistical Software V.17. The relative risk will be calculated with a 95% CI as the effect size of bortezomib. For the OS and progression-free survival, we calculate the overall OR from the HRs of each included study. Peto's one-step OR will be calculated for event rates below 1%. We will use the Grading of Recommendations Assessment, Development and Evaluation system to evaluate the certainty of evidence. ETHICS AND DISSEMINATION: As no primary data collection will be undertaken, formal ethical assessment is not required. We plan to present the results of this systematic review in a peer-reviewed scientific journal, conferences and popular press. PROSPERO REGISTRATION NUMBER: CRD42020151142.

Effectiveness of Strategies for Nutritional Therapy for Patients with Type 2 Diabetes and/or Hypertension in Primary Care: A Systematic Review and Meta-Analysis.

A central aspect to the management of type 2 Diabetes Mellitus (T2DM) and hypertension is promoting a healthy lifestyle, and nutritional therapy (NT) can support patients achieving glycemic control and blood pressure targets. This systematic review aimed to evaluate the effectiveness of NT in the management of patients with T2DM and/or hypertension in primary care. Primary outcomes were HbA1c, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Thirty-nine studies were included, thirty on T2DM and nine on hypertension. With a moderate quality of evidence, educational/counseling programs and food replacement programs in primary care likely reduce HbA1c on patients with T2DM (mean difference (MD): -0.37, 95% CI: -0.57 to -0.17, 7437 patients, 27 studies; MD: -0.54, 95% CI: -0.75 to -0.32, 440 patients, 2 studies, respectively). Mediterranean diet for T2DM was accessed by one study, and no difference between the groups was found. Educational and counseling programs likely reduce DBP in patients with hypertension (MD: -1.79, 95% CI: -3.46, -0.12, 2840 patients, 9 studies, moderate quality of the evidence), but the effect in SBP was unclear due to risk of bias and imprecision. Nutritional therapy strategies (i.e., educational/counseling programs and food replacement programs) in primary care improved HbA1c in patients with T2DM and DBP in individuals with hypertension.

Effectiveness of testosterone replacement in men with obesity: a systematic review and meta-analysis.

OBJECTIVE: This systematic review evaluated the effect of testosterone replacement therapy (TRT) in men with obesity having low testosterone levels (LTLs). DESIGN AND METHODS: Search strategies were performed in MEDLINE, Embase, LILACS, and CENTRAL databases. Two reviewers selected the studies, assessed the risk of bias, and extracted data from the included studies. A random-effects model was used to pool results across studies, and the Grading of Recommendations Assessment, Development, and Evaluation was used to evaluate the certainty of evidence. RESULTS: A total of 16 randomized controlled trials were included. With moderate certainty of the evidence, no difference was found between TRT and placebo regarding total adverse events, TRT led to a 2-kg lean body mass gain and slightly improved low-density lipoprotein (LDL), without effects on the blood pressure. Due to imprecision/heterogeneity, effects in cardiovascular events (relative risk: 0.52, 95% CI: 0.26 to 1.05, 7 trials, 583 participants), high-density lipoprotein, hematocrit, prostate-specific antigen, HbA1c, and quality of life were unclear. TRT was effective for waist circumference and BMI; however, large between-study heterogeneity was found, with 95% prediction intervals crossing the null effect line. Meta-regression revealed that the average age of participants was a significant modifier for both outcomes. CONCLUSION: TRT slightly improved the lean body mass and LDL in men with obesity having LTLs but did not affect the blood pressure. The effects of TRT on cardiovascular events, HbA1c, and quality of life are unclear. The mean age of participants significantly modified the effect of TRT on weight loss.

Association between a soy-based infant diet and the onset of puberty: A systematic review and meta-analysis.

The objective of this systematic review was to evaluate the association between a soy-based infant diet and the onset of puberty. We included studies in which children were fed a soy-based diet, and we compared them with those who were not. The primary outcomes were the onset of puberty in girls (thelarche, pubarche, and menarche age), boys (pubarche, voice change, testicular and penis enlargement age), and both (risk of delayed and precocious puberty [PP]). Search strategies were performed in PubMed, Embase, LILACS, and CENTRAL databases. Two reviewers selected eligible studies, assessed the risk of bias, and extracted data from the included studies. The odds ratio (OR) and mean difference (MD) were calculated with a 95% confidence interval (CI) as a measure of the association between soy consumption and outcomes. We used a random-effects model to pool results across studies and the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the certainty of evidence. We included eight studies in which 598 children consumed a soy-based diet but 2957 did not. The primary outcomes that could be plotted in the meta-analysis were the risk of PP and age at menarche. There was no statistical difference between groups for PP (OR: 0.51, 95% CI: 0.09 to 2.94, 3 studies, 206 participants, low certainty of evidence). No between-group difference was observed in menarche age (MD 0.14 years, 95% CI -0.16 to 0.45, 3 studies, 605 children, low certainty of evidence). One study presented this outcome in terms of median and interquartile range, and although the onset of menarche was marginally increased in girls who received a soy-based diet, the reported age was within the normal age range for menarche. We did not find any association between a soy-based infant diet and the onset of puberty in boys or girls. Trial Registration: PROSPERO registration: CRD42018088902.

Effectiveness of non-pharmacological strategies in the management of type 2 diabetes in primary care: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Despite the increasing number of drugs and various guidelines on the management of type 2 diabetes mellitus (T2DM), several patients continue with the disease uncontrolled. There are several non-pharmacological treatments available for managing T2DM, but various of them have never been compared directly to determine the best strategies. OBJECTIVE: This study will evaluate the comparative effects of non-pharmacological strategies in the management of T2DM in primary care or community settings. METHODS AND ANALYSIS: We will perform a systematic review and network meta-analysis (NMA), and will include randomised controlled trials if one of the following interventions were applied in adult patients with T2DM: nutritional therapy, physical activity, psychological interventions, social interventions, multidisciplinary lifestyle interventions, diabetes self-management education and support (DSMES), technology-enabled DSMES, interventions delivered only either by pharmacists or by nurses, self-blood glucose monitoring in non-insulin-treated T2DM, health coaching, benchmarking and usual care. The primary outcome will be glycaemic control (glycated haemoglobin (HbA1c) (%)), and the secondary outcomes will be weight loss, quality of life, patient satisfaction, frequency of cardiovascular events and deaths, number of patients in each group with HbA1c <7, adverse events and medication adherence. We have developed search strategies for Embase, Medline, Latin American and Caribbean Health Sciences Literature, Cochrane Central Register of Controlled Trials, Trip database, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature Australasian Medical Index and Chinese Biomedical Literature Database. Four reviewers will assess the studies for their eligibility and their risk of bias in pairs and independently. An NMA will be performed using a Bayesian hierarchical model, and the treatment hierarchy will be obtained using the surface under the cumulative ranking curve. To determine our confidence in an overall treatment ranking from the NMA, we will follow the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: As no primary data collection will be undertaken, no formal ethical assessment is required. We plan to present the results of this systematic review in a peer-reviewed scientific journal, conferences and the popular press. PROSPERO REGISTRATION NUMBER: CRD42019127856.

Effectiveness of strategies for nutritional therapy for patients with type 2 diabetes and/or hypertension in primary care: protocol of a systematic review of randomised controlled trials.

INTRODUCTION: Despite the increasing number of drugs available and various guidelines on the management of type 2 diabetes mellitus (T2DM) and hypertension, an expressive number of patients continue with these diseases uncontrolled. Nutrition therapy (NT) plays a fundamental role in the prevention and management of these comorbidities, as well as in the prevention of complications related to them. The objective of this review is to evaluate the effectiveness of NT strategies in the management of patients with T2DM and/or hypertension in primary care. The selected strategies did not substitute pharmaceutical treatment but instead focused on preventing a sedentary lifestyle and stimulating healthy nutrition. METHODS AND ANALYSIS: We will perform a systematic review according to Cochrane methodology of randomised controlled trials, wherein patients with T2DM and/or hypertension were allocated into one of the two groups: NT strategy, which may be of dietary quality or energy restriction, and conventional treatment. The primary outcomes will be glycaemic and blood pressure (BP) control, measured by final glycosylated hemoglobin (HbA1c) (%) and BP (mm Hg), respectively. Four general and adaptive search strategies have been created for the Embase, Medline, Latin American and Caribbean Health Sciences Literature (LILACS) and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. Two reviewers will independently select eligible studies, assess the risk of bias and extract data from the included studies. Similar outcomes measured in at least two trials will be plotted in the meta-analysis using Review Manager V.5.3. The quality of evidence of the effect estimate of the intervention will be generated according to the Grading of Recommendations Assessment, Development, and Evaluation Working Group. ETHICS AND DISSEMINATION: As no primary data collection will be undertaken, formal ethical assessment is not required. We plan to present the results of this systematic review in a peer-reviewed scientific journal, conferences and the popular press. PROSPERO REGISTRATION NUMBER: Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 20 December 2018 (Registration number CRD42018118117).

Effectiveness and safety of carbohydrate counting in the management of adult patients with type 1 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the effectiveness and safety of carbohydrate counting (CHOC) in the treatment of adult patients with type 1 diabetes mellitus (DM1). MATERIALS AND METHODS: We performed a systematic review of randomized studies that compared CHOC with general dietary advice in adult patients with DM1. The primary outcomes were changes in glycated hemoglobin (HbA1c), quality of life, and episodes of severe hypoglycemia. We searched the following electronic databases: Embase, PubMed, Lilacs, and the Cochrane Central Register of Controlled Trials. The quality of evidence was analyzed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: A total of 3,190 articles were identified, and two reviewers independently screened the titles and abstracts. From the 15 potentially eligible studies, five were included, and 10 were excluded because of the lack of randomization or different control/intervention groups. Meta-analysis showed that the final HbA1c was significantly lower in the CHOC group than in the control group (mean difference, random, 95% CI: -0.49 (-0.85, -0.13), p = 0.006). The meta-analysis of severe hypoglycemia and quality of life did not show any significant differences between the groups. According to the GRADE, the quality of evidence for severe hypoglycemia, quality of life, and change in HbA1c was low, very low, and moderate, respectively. CONCLUSION: The meta-analysis showed evidence favoring the use of CHOC in the management of DM1. However, this benefit was limited to final HbA1c, which was significantly lower in the CHOC than in the control group.

Effectiveness and safety of carbohydrate counting in the management of adult patients with type 1 diabetes mellitus: a systematic review and meta-analysis

Abstract Objective: This study aimed to evaluate the effectiveness and safety of carbohydrate counting (CHOC) in the treatment of adult patients with type 1 diabetes mellitus (DM1). Materials and methods: We performed a systematic review of randomized studies that compared CHOC with general dietary advice in adult patients with DM1. The primary outcomes were changes in glycated hemoglobin (HbA1c), quality of life, and episodes of severe hypoglycemia. We searched the following electronic databases: Embase, PubMed, Lilacs, and the Cochrane Central Register of Controlled Trials. The quality of evidence was analyzed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: A total of 3,190 articles were identified, and two reviewers independently screened the titles and abstracts. From the 15 potentially eligible studies, five were included, and 10 were excluded because of the lack of randomization or different control/intervention groups. Meta-analysis showed that the final HbA1c was significantly lower in the CHOC group than in the control group (mean difference, random, 95% CI: −0.49 (-0.85, −0.13), p = 0.006). The meta-analysis of severe hypoglycemia and quality of life did not show any significant differences between the groups. According to the GRADE, the quality of evidence for severe hypoglycemia, quality of life, and change in HbA1c was low, very low, and moderate, respectively. Conclusion: The meta-analysis showed evidence favoring the use of CHOC in the management of DM1. However, this benefit was limited to final HbA1c, which was significantly lower in the CHOC than in the control group.