The low health literacy in Latin America and the Caribbean: a systematic review and meta-analysis.

BACKGROUND: Health literacy (HL) impacts people's health and well-being. In Latin America and the Caribbean (LAC), there are no general estimates of the prevalence of low HL. This study aimed to estimate the prevalence of low HL among citizens of LAC and identify the tools used to measure it. METHODS: We included observational studies quantifying the prevalence of low HL in people living in LAC. We searched PubMed, CINAHL, EMBASE, ERIC, LILACS, PsycINFO, Redalyc, SciELO, Web of Science, PQDT, and the reference lists of the included studies in June 2023. Two reviewers independently conducted the selection, extraction, and risk of bias assessment using the JBI Critical Appraisal Tools. Meta-analysis of proportions using random effects models was used to summarize the prevalence of low HL estimated. This prevalence was measured in each study using different classification methods: word recognition items, reading and numeracy comprehension items, and self-reported comprehension items. RESULTS: Eighty four studies involving 23,914 participants from 15 countries were included. We identified 23 tools to assess HL, and most of the studies were carried out in health services. The pooled prevalence of low HL were 44.02% (95%CI: 36.12-52.24) for reading and numeracy comprehension items, 50.62% (95%CI: 41.82-59.39) for word recognition items, and 41.73% (95%CI: 31.76-52.43) for self-reported comprehension items. CONCLUSION: Despite the variability in the prevalence of low HL and a diversity of tools, the average of low HL is of concern. Almost half of the participants in the included studies have low HL. Most of the studies targeted users of healthcare services. Further research investigating the prevalence of low HL in the general population and actions focused on health education, communication, and information are necessary. TRIAL REGISTRATION: PROSPERO (CRD42021250286).

Imaging associations enhance the understanding of ECG abnormalities in male Brazilian football players: findings from the B-Pro Foot ECG study.

OBJECTIVES: To evaluate the prevalence of abnormal ECG findings and their association with imaging results in male Brazilian football players. METHODS: The 'B-Pro Foot ECG' is a multicentre observational study conducted in 82 Brazilian professional clubs. It analysed 6125 players aged 15-35 years (2496 white, 2004 mixed-race and 1625 black individuals) who underwent cardiovascular screening from 2002 to 2023. All ECGs were reviewed by two experienced cardiologists in the athlete's care. Those with abnormal findings underwent further investigations, including a transthoracic echocardiogram (TTE). Cardiac magnetic resonance (CMR) was subsequently performed based on TTE findings or clinical suspicion. RESULTS: In total, 180 (3%) players had abnormal ECGs and 176 (98%) showed normal TTE results. Athletes aged 26-35 years had a higher prevalence of abnormal ECGs than younger athletes (15-25 years). Black players had a higher prevalence of T-wave inversion (TWI) in the inferior leads than white players (2.6% vs 1.4%; p=0.005), as well as in V5 (2.9%) and V6 (2.1%) compared with white (1.2% and 1.0%; p<0.001) and mixed-race (1.5% and 1.2%; p<0.05) players, respectively. TTE parameters were similar across ethnicities. However, four out of 75 players with inferolateral TWI showed abnormal TTEs and CMR findings consistent with cardiomyopathies. CMR also showed cardiomyopathies or myocarditis in four players with inferolateral TWI and normal TTEs. In total, nine (0.1%) athletes were diagnosed with cardiac diseases and were followed for 40±30 months, with no cardiac events documented. CONCLUSION: This study found a 3% prevalence of abnormal ECGs in male Brazilian football players. Inferolateral TWI was associated with cardiac pathologies confirmed by CMR, even in athletes with a normal TTE.

What Powers Trastuzumab's Cardiotoxicity? Decoding Mitochondrial-Related Gene Expression Through Integrative Review and Meta-Analysis in Cardiomyocytes.

Trastuzumab is a monoclonal antibody used in oncotherapy for HER2-positive tumors. However, as an adverse effect, trastuzumab elevates the risk of heart failure, implying the involvement of energy production and mitochondrial processes. Past studies with transcriptome analysis have offered insights on pathways related to trastuzumab safety and toxicity but limited study sizes hinder conclusive findings. Therefore, we meta-analyzed mitochondria-related gene expression data in trastuzumab-treated cardiomyocytes. We searched the transcriptome databases for trastuzumab-treated cardiomyocytes in the ArrayExpress, DDBJ Omics Archive, Gene Expression Omnibus, Google Scholar, PubMed, and Web of Science repositories. A subset of 1270 genes related to mitochondrial functions (biogenesis, organization, mitophagy, and autophagy) was selected from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology Resource databases to conduct the present meta-analysis using the Metagen package (Study register at PROSPERO: CRD42021270645). Three datasets met the inclusion criteria and 1243 genes were meta-analyzed. We observed 69 upregulated genes after trastuzumab treatment which were related mainly to autophagy (28 genes) and mitochondrial organization (28 genes). We also found 37 downregulated genes which were related mainly to mitochondrial biogenesis (11 genes) and mitochondrial organization (24 genes). The present meta-analysis indicates that trastuzumab therapy causes an unbalance in mitochondrial functions, which could, in part, help explain the development of heart failure and yields a list of potential molecular targets. These findings contribute to our understanding of the molecular mechanisms underlying the cardiotoxic effects of trastuzumab and may have implications for the development of targeted therapies to mitigate such effects.

Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis.

INTRODUCTION: This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). METHODS: In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. RESULTS: Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. CONCLUSION: Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

The use of blue dye alone for sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initially node-positive breast cancer.

INTRODUCTION: False-negative sentinel lymph node biopsy (SLNB) rates following neoadjuvant chemotherapy (NACT) in initially node-positive (cN1/2) breast cancer patients are high, but decrease when lymph nodes are clipped, ≥3 sentinel lymph nodes (SLN) are removed or dual-tracer localization (radioisotope and blue dye) is used. Radiotracer, however, is often unavailable and outcomes with blue dye alone are unknown. MATERIALS AND METHODS: Initially cT1-4, cN1/2 patients treated with NACT in 2013-2023 who underwent SLNB using blue dye alone were evaluated regarding SLN identification, axillary recurrence, disease-free and overall survival rates. RESULTS: Of 119 patients included, 19 remained cN1/2 after NACT. SLNB was performed using blue dye alone in 100 ycN0 cases (84%), with an identification rate of 96%. The SLN was negative in 70/119 cases (i.e. 59% avoided axillary dissection). The number of SLN detected was ≥3 in 55/70 cases (78%) (median 3.1; 1-6). Median age was 49 years (25-84). Most were T2 (n = 40, 57.1%), N1 (n = 64, 91.4%). Predominant subtypes were ERBB2 (52.9%) and triple-negative (20%). No axillary recurrence occurred over a median 36-month period. Five-year disease-free and overall survival were, respectively, 85.9% (95%CI: 74-99.8) and 96.3% (95%CI: 89.4-100). The ERBB2 subtype (1.99, 95%CI: 1.02-3.85, p = 0.04) and N1 lymph node status (2.58, 95%CI: 1.54-9.10, p = 0.03) were associated with a greater likelihood of undergoing SLNB alone without axillary dissection. CONCLUSIONS: SLNB with blue dye alone following NACT in initially cN1/2 patients avoided axillary dissection in almost 60% of cases, with no recurrences during the period evaluated. Longer follow-up studies are necessary.

The effect of different levothyroxine administration regimens on thyroid hormone levels: a systematic review, pairwise, and network meta-analysis.

INTRODUCTION: This systematic review aimed to compare the effect of alternative levothyroxine administration regimens on thyroid hormone levels and patient-reported outcomes (PROs) among adults with hypothyroidism. METHODS: We searched PubMed, Embase, CENTRAL, CINAHL, LILACS, SciELO, Scopus, Web of Science, OpenGrey, ProQuest, ClinicalTrials.gov, and ICTRP from inception to May/2023 for randomized controlled trials (RCTs). We assessed the risk of bias with Cochrane Risk of Bias 2.0 tool. We analyzed TSH levels by pairwise and network meta-analyses (NMA). The FT4 levels and PROs were qualitatively assessed. RESULTS: We included 14 RCTs (906 participants) comparing different regimens, as bedtime vs. before breakfast. A total of 12 RCTs were at high risk of bias. Seven RCTs were included in the TSH meta-analysis, where the mean difference (MD) and 95% confidence interval (CI) were as follows: bedtime vs before breakfast (4 RCTs) 0.69 (-1.67-3.04), I2 = 92%, very low certainty evidence; weekly dose vs before breakfast (2 RCTs) 1.68 (0.94-2.41), I2 = 0%, low certainty evidence; and at breakfast vs before breakfast (1 RCT) 0.65 (-1.11-2.41), very low certainty evidence. The NMA showed no evidence of differences in TSH level with different regimens. CONCLUSION: The evidence is insufficient to determine the most effective levothyroxine administration regimen for hypothyroidism. SYSTEMATIC REVIEW REGISTRATION: PROSPERO - CRD42021279375.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Cancer Risk Factors in Southern Brazil: Report of a Comprehensive, Matched Case-Control Study.

PURPOSE: To evaluate cancer risk factors among cancer cases and controls from Southern Brazil, to analyze a multigene hereditary panel testing (MGPT, 26 genes) for breast cancer (BC) and colorectal cancer (CCR) cases diagnosed age younger than 50 years and to characterize them for hereditary cancer syndrome (HCS) phenotypes. METHODS: A case-control (matched by age group and sex) study was conducted on regional cancer. Data on exposure factors and first-/second-degree family history of cancer (1/2FHC) were collected. The MGPT was performed using Illumina next-generation sequencing technology. RESULTS: A total of 1,007 cases and 1,007 controls were included. The most frequent cancers were BC (n = 311), CCR (n = 147), prostate (n = 132), and lung cancers (n = 89). It was independently associated with cancer, 1/2FHC, tobacco consumption (TC), pesticide exposure (PE), solvent/glue exposure, and BMI <24. BC was associated with 1/2FHC, TC, and hormone replacement therapy use; CCR with 1/2FHC, TC, and BMI <24; prostate cancer with 1/2FHC, TC, and alcohol consumption; and lung cancer with 1/2FHC, TC, PE, and BMI <24. MGPT identified pathogenic/likely pathogenic mutations in 24 (32%) women with BC and in three (18%) women and four (24%) men diagnosed with CCR at under 50 years. Among the tested patients under 50 years with diagnosed BC and CCR, 98.6% and 97% present criteria for HCS, respectively. CONCLUSION: This study confirmed the association of several factors associated with BC, CCR, prostate, and lung cancers and reinforced the importance of evaluating FHC and genetic testing, especially for patients under 50 years with diagnosed BC or CCR. A better understanding of population-specific cancer risk factors builds on sustainable data for developing prevention strategies. These efforts increase the commitment to early detection and surveillance.

Pressure injury prevention measures: overview of systematic reviews.

OBJECTIVE: Summarizing the evidence from systematic reviews regarding the comparison the effectiveness of interventions to prevent pressure injuries. METHOD: Overview of systematic reviews conducted in accordance with Cochrane guidelines. A search was performed in databases, repositories and systematic review registration sites. RESULTS: 15 reviews were included in this overview. The sensitivity analysis showed a reduction in the incidence of pressure injuries with nutritional supplementation compared to the standard hospital diet (Relative Risk (RR) = 0.83; 95% Confidence Interval (CI): 0.72-0.95). There was evidence of the superiority of constant low-pressure surfaces (RR = 0.38; 95% CI;0.24-0.61), alternating pressure devices (RR = 0.31; 95% CI:0.17-0.58) and alternative foams (RR = 0.40; 95% CI:0.21-0.74) when compared to the standard hospital mattress or standard foam. The use of a silicone cover reduced the incidence of pressure injuries by 75% (RR = 0.25; 95%CI:0.16-0.41) when compared to no cover. CONCLUSION: Although some interventions have been shown to be effective in reducing the incidence of pressure injury, the evidence is limited or very limited and subject to change. Registration CRD42017064586.

Real-Life Data on Hydroxychloroquine or Chloroquine with or Without Azithromycin in COVID-19 Patients: A Retrospective Analysis in Brazil. / Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil.

BACKGROUND: Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. OBJECTIVES: To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. METHODS: A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. RESULTS: From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). CONCLUSION: COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar.

FUNDAMENTO: Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. OBJETIVOS: Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. MÉTODOS: Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. RESULTADOS: Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). CONCLUSÃO: Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar.

The role of colonoscopy in young patients with rectal bleeding: a systematic review and meta-analysis.

PURPOSE: Anal bleeding is a frequent complaint in the coloproctological practice. Although usually associated with common anorectal disorders, it may represent a sign of an occult colorectal carcinoma. Our purpose was to evaluate the accuracy of the colonoscopy for detection of neoplastic lesions in patients under 50 years of age with rectal bleeding. METHODS: This systematic review and meta-analysis searched publications in PubMed, Web of Science, and Cochrane Library databases up to August, 2023. Cross-sectional and case-control studies including patients under 50 years with rectal bleeding evaluated by colonoscopy were included. Primary outcome was prevalence of neoplastic lesions (adenomas and adenocarcinomas). Secondary outcomes were prevalence of those lesions according to age and anatomic location. The study was registered on PROSPERO (CRD42021257859) on July 5, 2021. RESULTS: Nine studies comprising 4162 patients were analyzed. A total of 398 patients with adenomas and 40 patients with adenocarcinoma were identified. Prevalence of neoplastic lesions (adenomas and carcinomas) was 10%. In patients under 40 years, the prevalence of neoplastic lesions was 7% (6% of adenomas, 1% of carcinomas). Among patients aged 40-50 years the prevalence was 15%, 14%, and 1%, respectively. Most lesions (71%) were located distally to splenic flexure. CONCLUSION: About 10% of patients under 50 years with anal bleeding will have a neoplastic lesion detected through colonoscopy. The greatest benefit of the procedure is observed between 40 and 50 years. Almost 30% of the neoplastic lesions were found in the proximal colon and could not be detected without the performance of a complete colonoscopy.

COVID-19 outcomes in people living with HIV: Peering through the waves.

OBJECTIVE: To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. METHODS: This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. RESULTS: Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). CONCLUSIONS: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group.

Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. METHODS: A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. RESULTS: Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. CONCLUSION: Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.

The power of the placebo effect in diabetes: A systematic review and meta-analysis.

This review aims to identify the magnitude of the placebo effect in people with type 2 diabetes mellitus. Literature research was conducted Medline, Embase and Virtual Health Library for studies published between the date of inception and June 2021. The eligibility criteria included randomized controlled trials, showing comparison to placebo, having participants with type 2 diabetes mellitus, and having glycated hemoglobin (HbA1c) as the primary outcome. Meta-analysis was conducted with the effect of changing HbA1c in relation to the baseline. Exploration of heterogeneity was performed.The meta-analysis showed an increase in the average of HbA1c compared to the baseline of 0.14% (95% CI: 0.07-0.21). There was a significant difference between follow-up times (p = 0.03) and between administration routes (p = 0.01), with an increase in HbA1c in the oral route [0.15% (95% CI: 0.07-0.23)]. The meta-regression of the year of publication showed a significant downward trend (p = 0.01) of the increase in HbA1c compared to the baseline.In this study, the expected placebo effect of Hba1c reduction was not found; instead, higher Hba1c levels were observed in the control groups, although this effect was reduced over the years. Registration: PROSPERO ID CRD42020172797.

Efficacy of six exercise-based interventions for individuals undergoing hemodialysis: a network meta-analysis of randomized clinical trials.

BACKGROUND: Evidence comparing different exercise modalities in individuals undergoing hemodialysis remains incipient. Our aim was to conduct a systematic review and network meta-analysis of randomized clinical trials to compare and synthesize the efficacy of five different intradialytic exercise modalities and home-based training in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Studies were searched in PubMed/MEDLINE, Cochrane Library, Embase, Cinahl, and Scopus from their inception to 19 September 2022. We used traditional random-effects models and Bayesian network meta-analysis models. The risk of bias was assessed using the RoB v.2.0 tool, and the assessment of confidence in the results through the Confidence in Network Meta-Analysis (CINeMA) tool. RESULTS: Seventy-eight studies involving 3326 participants were included. Our network meta-analysis showed that combined training was the intervention with the best performance to increase VO2 peak [mean difference (MD) = 3.94 ml/kg/min; 95% credible interval (CrI), 2.38 to 5.76] and to reduce diastolic blood pressure (MD = -5.19 mmHg; 95%CrI, -9.35 to -0.96) compared to the usual care group. Inspiratory muscle training was the intervention that most improved the 6-minute walk test distance (MD = 70.97 m; 95%CrI, 18.09 to 129.87). C-reactive protein decreased in resistance training (MD = -2.6 mg/l; 95%CrI, -4.97 to -0.33) and aerobic training (MD = -1.4 mg/l; 95%CrI, -3.15 to -0.06). Kt/V improved in aerobic training (MD = 0.11; 95%CrI, 0.02 to 0.18), and SF-36 physical functioning outcomes improved in resistance training (MD = 10.66 points; 95%Crl, 1.91 to 20.22). No intradialytic exercise modality was superior to others or comparable with home-based training in improving the evaluated outcomes. Subgroup analysis revealed that exercise interventions >12 weeks improved functional capacity more than interventions ≤12 weeks, and that combined training reduces diastolic blood pressure only after 12 weeks of follow-up. Furthermore, our results suggest that moderate or moderate-to-vigorous intensity training leads to more pronounced improvements in functional capacity, whereas mild or mild-to-moderate intensity training does not have the same effect. In this review, most of the included studies were assessed as having some concern, which resulted in a low to very low level of confidence in the overall findings. CONCLUSIONS: Both intradialytic training and home-based training can promote benefits for individuals undergoing hemodialysis, with no evidence of the superiority of either training modality over the other.

Potential and limitations of machine meta-learning (ensemble) methods for predicting COVID-19 mortality in a large inhospital Brazilian dataset.

The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48-71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors.

Association between impairment and self-rated heath: a brazilian population study considering type, origin, and degree of limitation.

BACKGROUND: Perceived health is a well-known, low-cost measure in public health, and has been used in several studies on individuals with impairment. Although many studies have related impairment to self-rated health (SRH), few have considered the origin and degree of limitation of the impairment. This study examined whether physical, hearing, or visual impairments-when analyzed according to origin (congenital or acquired) and degree of limitation (with or without)-are associated with the SRH status. METHODS: This cross-sectional study used data of 43,681 adult individuals from the Brazilian National Health Survey (NHS, 2013). The outcome SRH was dichotomized into poor (including the regular, poor, and very poor responses) or good (including the good and very good responses). Crude and adjusted (for socio-demographic characteristics and chronic diseases history) prevalence ratios (PR) estimates were evaluated using Poisson regression models with the robust variance estimator. RESULTS: Poor SRH prevalence was estimated at 31.8% (95%CI:31.0-33.0) among the non-impaired population, 65.6% (95%CI:60.6-70.0) among individuals with physical impairment, 50.3% (95%CI:45.0-56.0) for people with hearing impairment, and 55.3% (95%CI:51.8-59.0) for the visually impaired. Individuals with congenital physical impairment-with or without limitations-presented the strongest association with the poorest SRH status. Participants with non-limiting, congenital hearing impairment showed a protective factor to poor SRH (PR = 0.40 95%CI: 0.38-0.52). Individuals with acquired visual impairment with limitations demonstrated the strongest association with poor SRH (PR = 1.48 95%CI:1.47-1.49). Among the impaired population, middle-aged participants showed a stronger association with poor SRH than older adult participants. CONCLUSIONS: Impairment is associated with poor SRH status, especially among people with physical impairment. The origin and degree of limitation of each type of impairment differently impacts SRH among the impaired population.

Clinical characteristics and outcomes of hospital-manifested COVID-19 among Brazilians.

OBJECTIVES: To analyze the clinical characteristics and outcomes of admitted patients with the hospital- versus community-manifested COVID-19 and to evaluate the risk factors related to mortality in the first population. METHODS: This retrospective cohort included consecutive adult patients with COVID-19, hospitalized between March and September 2020. The demographic data, clinical characteristics, and outcomes were extracted from medical records. Patients with hospital-manifested COVID-19 (study group) and those with community-manifested COVID-19 (control group) were matched by the propensity score model. Logistic regression models were used to verify the risk factors for mortality in the study group. RESULTS: Among 7,710 hospitalized patients who had COVID-19, 7.2% developed symptoms while admitted for other reasons. Patients with hospital-manifested COVID-19 had a higher prevalence of cancer (19.2% vs 10.8%) and alcoholism (8.8% vs 2.8%) than patients with community-manifested COVID-19 and also had a higher rate of intensive care unit requirement (45.1% vs 35.2%), sepsis (23.8% vs 14.5%), and death (35.8% vs 22.5%) (P <0.05 for all). The factors independently associated with increased mortality in the study group were increasing age, male sex, number of comorbidities, and cancer. CONCLUSION: Hospital-manifested COVID-19 was associated with increased mortality. Increasing age, male sex, number of comorbidities, and cancer were independent predictors of mortality among those with hospital-manifested COVID-19 disease.

Is there a better interceptive treatment for unerupted palatally displaced canines? A network meta-analysis.

This systematic review aimed to investigate if there is a better interceptive treatment for palatally displaced canines (PDC) in the mixed dentition stage. The PubMed/MEDLINE, CENTRAL, Scopus, and EMBASE databases were searched for randomized clinical trials related to the research topic. The gray literature and reference lists were also assessed. Network meta-analysis was conducted to analyze the effects of different approaches on PDC eruption. The surface under the cumulative ranking area was calculated to rank the treatments. The certainty of the evidence was evaluated using the GRADE approach. Of the 892 eligible studies, 18 were selected for full-text analysis and 9 for meta-analysis, involving 506 participants and 730 PDC, to compare 9 approaches. The proportion of erupted PDC was significantly higher for all interceptive treatments compared with control (no intervention). Furthermore, the proportion of erupted PDC was higher in patients subjected to rapid maxillary expansion (RME) than those who underwent double extraction of primary canine and primary molar (relative risk (RR) = 2.68 ICr95%: 1.12-9.35). A higher proportion of erupted PDC was found for RME (RR = 3.07 ICr95%: 1.31-10.67), RME plus use of transpalatal arch (TA) plus extraction of primary canine(s) (EC) (RR = 1.43 ICr95%: 1.09-1.95), EC plus use of cervical pull headgear (RR = 1.38 ICr95%: 1.11-1.79), and EC plus use of TA (RR = 1.36 ICr95%: 1.00-1.9) than for EC. RME was most likely to be considered as the best interceptive treatment. Overall, the certainty of the evidence was considered low due to imprecision and indirectness. In conclusion, no intervention in the mixed dentition stage is the worst choice for PDC.

Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil / Real-Life Data on Hydroxychloroquine or Chloroquine with or Without Azithromycin in COVID-19 Patients: A Retrospective Analysis in Brazil

Resumo Fundamento Apesar da ausência de evidência mostrando benefícios da hidroxicloroquina e da cloroquina combinadas ou não à azitromicina no tratamento da covid-19, esses medicamentos têm sido amplamente prescritos no Brasil. Objetivos Avaliar desfechos, incluindo moralidade hospitalar, alterações eletrocardiográficas, tempo de internação, admissão na unidade de terapia intensiva, e necessidade de diálise e de ventilação mecânica em pacientes hospitalizados com covid-19 que receberam cloroquina ou hidroxicloroquina, e comparar os desfechos entre aqueles pacientes e seus controles pareados. Métodos Estudo multicêntrico retrospectivo do tipo coorte que incluiu pacientes com diagnóstico laboratorial de covid-19 de 37 hospitais no Brasil de março a setembro de 2020. Escore de propensão foi usado para selecionar controles pareados quanto a idade, sexo, comorbidades cardiovasculares, e uso de corticosteroides durante a internação. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Dos 7850 pacientes com covid-19, 673 (8,6%) receberam hidroxicloroquina e 67 (0,9%) cloroquina. A idade mediana no grupo de estudo foi 60 (46-71) anos e 59,1% eram mulheres. Durante a internação, 3,2% dos pacientes apresentaram efeitos adversos e 2,2% necessitaram de interromper o tratamento. Alterações eletrocardiográficas foram mais prevalentes no grupo hidroxicloroquina/cloroquina (13,2% vs. 8,2%, p=0,01), e o prolongamento do intervalo QT corrigido foi a principal diferença (3,6% vs. 0,4%, p<0,001). O tempo mediano de internação hospitalar foi maior no grupo usando CQ/HCQ em relação aos controles (9,0 [5,0-18,0] vs. 8,0 [4,0-14,0] dias). Não houve diferenças estatisticamente significativas entre os grupos quanto a admissão na unidade de terapia intensiva (35,1% vs. 32,0%; p=0,282), ventilação mecânica invasiva (27,0% vs. 22,3%; p=0,074) ou mortalidade (18,9% vs. 18,0%; p=0,682). Conclusão Pacientes com covid-19 tratados com cloroquina ou hidroxicloroquina apresentaram maior tempo de internação hospitalar, em comparação aos controles. Não houve diferença em relação a admissão em unidade de terapia intensiva, necessidade de ventilação mecânica e mortalidade hospitalar.

Abstract Background Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. Objectives To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. Methods A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. Results From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 - 71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). Conclusion COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and in-hospital mortality were similar.