Prediction of Liver Steatosis Applying a New Score in Subjects from the Brazilian Longitudinal Study of Adult Health.

GOALS: To develop a noninvasive algorithm for diagnosis of liver steatosis and to compare its diagnostic value with available predictive models. BACKGROUND: Liver steatosis represents the most frequent liver disease worldwide. STUDY: This cross-sectional study analyzed data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Patients were randomly divided into training (n=6571) and validation (n=3286) cohort. Abdominal ultrasound (US), used to grade steatosis, and overnight fasting blood tests were performed at the same day. Fatty Liver Index (FLI), Hepatic Steatosis Index, and Nonalcoholic Fatty Liver Disease-Liver Fat Score were calculated. A backward stepwise multivariate logistic regression analysis was used to develop the new predictive model, Steato-ELSA. RESULTS: In total, 9857 subjects [58% female, age=51 (interquartile range, 45 to 58) years, body mass index=26.4 (23.9 to 29.6) Kg/m] were included. Body mass index, waist circumference, homeostasis model of assessment of insulin resistance, transaminases, and triglycerides were independently associated with steatosis in the multivariate model (Hosmer-Lemeshow P=0.279). In the validation cohort, the area under the receiver-operator characteristics (95% confidence interval) for prediction of mild and moderate steatosis were: (i) 0.768 (0.751-0.784) and 0.829 (0.810-0.848) for Steato-ELSA; (ii) 0.762 (0.745-0.779) and 0.819 (0.799-0.838) for Fatty Liver Index; (iii) 0.743 (0.727-0.761) and 0.800 (0.779-0.822) for Hepatic Steatosis Index; and (iv) 0.719 (0.701-0.737) and 0.769 (0.747-0.791) for Nonalcoholic Fatty Liver Disease-Liver Fat Score. Steato-ELSA performed significantly better than other models and yielded sensitivity (Se)/specificity (Sp) (95% confidence interval): (i) for mild steatosis (score ≥0.386): Se=65.6% (63.0-68.3) and Sp=73.7% (71.8-75.6); (ii) for moderate steatosis (score ≥0.403): Se=83.5% (80.0-86.9) and Sp=68.7% (67.0-70.4). CONCLUSIONS: Steato-ELSA is an accurate and inexpensive tool that uses simple parameters to identify individuals at high risk of liver steatosis.

Effect Estimates in Randomized Trials and Observational Studies: Comparing Apples With Apples.

Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration.

Single nucleotide polymorphisms of cytokine-related genes and association with clinical outcome in a Chagas disease case-control study from Brazil.

BACKGROUND: The severity of chronic chagasic cardiomyopathy (CCC), the most frequent clinical outcome of Chagas disease (CD), has been associated with cytokine-enriched heart tissue inflammation, and high serum levels of transforming growth factor (TGFß), interferon-gamma (IFNγ), and tumour necrosis factor (TNF). Conversely, increased interleukin (IL)-10 serum concentrations have been associated with asymptomatic CD. Cytokines and cytokine-related gene polymorphisms may control cytokine expression and have been proposed to contribute to CCC outcomes. OBJECTIVES: We evaluated the association of 13 cytokine-related genes (TGFB: rs8179181, rs8105161, rs1800469; IL10: rs1800890, rs1800871, rs1800896; IFNG: rs2430561; TNF: rs1800629; BAT1: rs3853601; LTA: rs909253, rs2239704; TNFR1: rs767455; TNFR2: rs1061624) with risk and progression of CCC. FINDINGS: Four hundred and six seropositive patients from CD endemic areas in the state of Pernambuco, north-eastern Brazil, were classified as non-cardiopathic (A, 110) or cardiopathic (mild, B1, 163; severe, C, 133). We found no evidence of TGFB, IL10, TNF, or TNFR1/2 gene polymorphisms associated with CCC risk or progression. Only BAT1 rs3853601 -22G carriers (B1 vs. C: OR = 0.5; p-value = 0.03) and IFNG rs2430561 +874AT (A vs. C: OR = 0.7; p-value = 0.03; A vs. B1+C: OR = 0.8; p-value = 0.02) showed a significant association with protection from cardiopathy in a logistic regression analysis with adjustment for gender and ethnicity; however, the association disappeared after performing adjustment for multiple testing. A systematic review of TNF rs1800629 -308G>A publications included five studies for meta-analysis (534 CCC and 472 asymptomatic patients) and showed no consensus in pooled odds ratio (OR) estimates for A allele or A carriers (OR = 1.4 and 1.5; p-values = 0.14 and 0.15, respectively). In CD patients, TNF serum levels were increased, but not affected by the TNF rs1800629 -308A allele. MAIN CONCLUSIONS: Our data suggest no significant contribution of the analysed gene variants of cytokine-related molecules to development/severity of Chagas' heart disease, reinforcing the idea that parasite/host interplay is critical to CD outcomes.

Age-standardized mortality rates related to viral hepatitis in Brazil.

BACKGROUND: Liver-related mortality has been increasing worldwide. We aimed to estimate the age-standardized mortality rates from viral hepatitis in Brazil. METHODS: The Brazilian National Death Registry was analyzed from 2008 to 2014. Viral hepatitis deaths were defined by the following ICD-10 codes in the death certificate: hepatitis A [B15.0; B15.9]; hepatitis B [B16.2; B16.9; B18.1]; hepatitis C [B17.1; B18.2]; hepatitis Delta [B16.0; B16.1; B18.0; B17.0] and other viral hepatitis [B17.2; B17.8; B18.8; B18.9; B19.0; B19.9]. Crude mortality rates were calculated by the ratio between total number of deaths and estimated population. Mortality rates were age-standardized by the direct method using the WHO standard population. RESULTS: Thirty four thousand ,nine hundred seventy eight deaths had viral hepatitis mentioned in their death certificate [65% male, aged 58 years, 73% associated with hepatitis C]. Age-standardized mortality rate (95% CI) due to viral hepatitis was 2.695 (2.667-2.724) deaths per 100,000 inhabitants: South region had the higher rates [3.997 (3.911-4.085)]. Mortality rates associated with hepatitis A and Delta were 0.032 (0.029-0.035) and 0.028 (0.025-0.031), respectively. Hepatitis C mortality rates were 4-fold higher than those associated with hepatitis B [1.964 (1.940-1.989) vs 0.500 (0.488-0.512)]. South region had the higher rates for hepatitis C [3.163 (3.087-3.241)] and North had the higher rates for hepatitis A [0.066 (0.049-0.087)], B [0.986 (0.918-1.058)] and Delta [0.220 (0.190-0.253)]. CONCLUSION: Viral hepatitis remains a major public health issue in Brazil. Mortality rates were not homogeneous across the country, suggesting that health policies should be customized according to geographical location.

Long-term protection from isoniazid preventive therapy for tuberculosis in HIV-infected patients in a medium-burden tuberculosis setting: the TB/HIV in Rio (THRio) study.

BACKGROUND: The duration of protection against tuberculosis provided by isoniazid preventive therapy is not known for human immunodeficiency virus (HIV)-infected individuals living in settings of medium tuberculosis incidence. METHODS: We conducted an individual-level analysis of participants in a cluster-randomized, phased-implementation trial of isoniazid preventive therapy. HIV-infected patients who had positive tuberculin skin tests (TSTs) were followed until tuberculosis diagnosis, death, or administrative censoring. Nelson-Aalen cumulative hazard plots were generated and hazards were compared using the log-rank test. Cox proportional hazards models were fitted to investigate factors associated with tuberculosis diagnosis. RESULTS: Between 2003 and 2009, 1954 patients with a positive TST were studied. Among these, 1601 (82%) initiated isoniazid. Overall tuberculosis incidence was 1.39 per 100 person-years (PY); 0.53 per 100 PY in those who initiated isoniazid and 6.52 per 100 PY for those who did not (adjusted hazard ratio [aHR], 0.17; 95% confidence interval [CI], .11-.25). Receiving antiretroviral therapy at time of a positive TST was associated with a reduced risk of tuberculosis (aHR, 0.69; 95% CI, .48-1.00). Nelson-Aalen plots of tuberculosis incidence showed a constant risk, with no acceleration in 7 years of follow-up for those initiating isoniazid preventive therapy. CONCLUSIONS: Isoniazid preventive therapy significantly reduced tuberculosis risk among HIV-infected patients with a positive TST. In a medium-prevalence setting, 6 months of isoniazid in HIV-infected patients with positive TST reduces tuberculosis risk over 7 years of follow-up, in contrast to results of studies in higher-burden settings in Africa.

Gene polymorphisms in patients with pulmonary tuberculosis from Mozambique.

Several host and environmental factors contribute to tuberculosis outcome, interestingly single nucleotide polymorphisms (SNPs) in candidate genes have been evaluated in populations with different ethnicities and TB infection. In the present study we focused on SNPs in cytokine and inflammatory mediator genes: tumor necrosis factor (TNF) -308G>A (rs1800629), interleukin-10 (IL10) -819C>T (rs1800871), interferon-gamma (IFNG) +874T>A (rs2430561), and leukotriene A4 hydrolase (LTA4H) rs1978331, rs17525495 and rs2660898 in a case-control study involving 102 pulmonary tuberculosis patients and 456 controls from Mozambique. LTA4H, IL10 and IFNG SNPs showed no associations with pulmonary tuberculosis. However, distribution of the TNF -308A allele, genotype and carrier frequencies showed a significant risk association with tuberculosis that was maintained after adjustment for non-genetic variables and Bonferroni correction (AA genotype, OR = 1.9, p Bonf < 0.001; A allele OR = 2.9, p Bonf = 0.005 and GA/AA carrier OR = 2.6, p Bonf = 0.035). Interestingly, this association has not been reported in a sub-Saharan African population before. Our results suggest a role of -308 TNF polymorphism and tuberculosis susceptibility.

A systematic review of the angular values obtained by computerized photogrammetry in sagittal plane: a proposal for reference values.

OBJECTIVE: Reference values for postural alignment in the coronal plane, as measured by computerized photogrammetry, have been established but not for the sagittal plane. The objective of this study is to propose reference values for angular measurements used for postural analysis in the sagittal plane for healthy adults. METHODS: Electronic databases (PubMed, BVS, Cochrane, Scielo, and Science Direct) were searched using the following key words: evaluation, posture, photogrammetry, and software. Articles published between 2006 and 2012 that used the PAS/SAPO (postural assessment software) were selected. Another inclusion criterion was the presentation of, at least, one of the following measurements: head horizontal alignment, pelvic horizontal alignment, hip angle, vertical alignment of the body, thoracic kyphosis, and lumbar lordosis. Angle samples of the selected articles were grouped 2 by 2 in relation to an overall average, which made possible total average, variance, and SD calculations. RESULTS: Six articles were included, and the following average angular values were found: 51.42° ± 4.87° (head horizontal alignment), -12.26° ± 5.81° (pelvic horizontal alignment), -6.40° ± 3.86° (hip angle), and 1.73° ± 0.94° (vertical alignment of the body). None of the articles contained the measurements for thoracic kyphosis and lumbar lordosis. CONCLUSION: The reference values can be adopted as reference for postural assessment in future researches if the same anatomical points are considered.

Toll-like receptor 1 N248S single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection.

Conflicting findings about the association between leprosy and TLR1 variants N248S and I602S have been reported. Here, we performed case-control and family based studies, followed by replication in 2 case-control populations from Brazil, involving 3162 individuals. Results indicated an association between TLR1 248S and leprosy in the case-control study (SS genotype odds ratio [OR], 1.81; P = .004) and the family based study (z = 2.02; P = .05). This association was consistently replicated in other populations (combined OR, 1.51; P < .001), corroborating the finding that 248S is a susceptibility factor for leprosy. Additionally, we demonstrated that peripheral blood mononuclear cells (PBMCs) carrying 248S produce a lower tumor necrosis factor/interleukin-10 ratio when stimulated with Mycobacterium leprae but not with lipopolysaccharide or PAM3cysK4. The same effect was observed after infection of PBMCs with the Moreau strain of bacillus Calmette-Guerin but not after infection with other strains. Finally, molecular dynamics simulations indicated that the Toll-like receptor 1 structure containing 248S amino acid is different from the structure containing 248N. Our results suggest that TLR1 248S is associated with an increased risk for leprosy, consistent with its hypoimmune regulatory function.

Persistent high mortality rates for Diabetes Mellitus and Hypertension after excluding deaths associated with COVID-19 in Brazil, 2020-2022.

INTRODUCTION: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a significant public health challenge globally, with Brazil being no exception. Excess mortality during this period reached alarming levels. Cardiovascular diseases (CVD), Systemic Hypertension (HTN), and Diabetes Mellitus (DM) were associated with increased mortality. However, the specific impact of DM and HTN on mortality during the pandemic remains poorly understood. METHODS: This study analyzed mortality data from Brazil's mortality system, covering the period from 2015 to 2022. Data included all causes of death as listed on death certificates, categorized by International Classification of Diseases 10th edition (ICD-10) codes. Population data were obtained from the Brazilian Census. Mortality ratios (MRs) were calculated by comparing death rates in 2020, 2021, and 2022 to the average rates from 2015 to 2019. Adjusted MRs were calculated using Poisson models. RESULTS: Between 2015 and 2022, Brazil recorded a total of 11,423,288 deaths. Death rates remained relatively stable until 2019 but experienced a sharp increase in 2020 and 2021. In 2022, although a decrease was observed, it did not return to pre-pandemic levels. This trend persisted even when analyzing records mentioning DM, HTN, or CVD. Excluding death certificates mentioning COVID-19 codes, the trends still showed increases from 2020 through 2022, though less pronounced. CONCLUSION: This study highlights the persistent high mortality rates for DM and HTN in Brazil during the years 2020-2022, even after excluding deaths associated with COVID-19. These findings emphasize the need for continued attention to managing and preventing DM and HTN as part of public health strategies, both during and beyond the COVID-19 pandemic. There are complex interactions between these conditions and the pandemic's impact on mortality rates.

Smoking Cessation Is Associated With Short-Term Improvement of Vascular Health in a Cohort of People Living With HIV in Rio de Janeiro, Brazil.

Smoking is highly prevalent in people living with HIV/AIDS (PLHA), leading to detrimental effects in different tissues. We examined the effects of nicotine replacement therapy (NRT) on smoking cessation and vascular health. From December 2019 to October 2021, we prospectively enrolled PLHA who were actively smoking. The primary outcome was endothelial function measured by brachial artery flow-mediated dilatation (FMD). We evaluated the percent change in FMD compared to the baseline measure (Δ%FMD) to detect improvements among participants who quit smoking. To confirm the results, we used linear regression models to account for classical cardiovascular (CV) confounders. We included 117 participants with median age of 45.5 years (IQR= 36.4-54.8); 22 (20.4%) had hypertension, 9 (8.3%) had diabetes, almost half were smoking 20+ cigarettes/day (41.7%). After 12 weeks 30.76% participants quit smoking. Comparison of Δ%FMD change from baseline to week 12 showed that among participants adherent to therapy, there has been an increase in Δ%FMD when compared to those who relapsed (1.17% [0.29-2.98] vs -0.19% [-1.95-0.91], p<0.001). After adjustment for CV factors, multiple linear regression showed that Δ%FMD in participants who quit smoking presented a 2.54 mean increase in comparison to those who continued smoking (p=0.007). In conclusion, this study provides evidence that a strategy of NRT and counseling is modestly effective for smoking cessation in PLHA and improves vascular health in a short period of time. This reinforces the importance of the widespread anti-tobacco programs in HIV clinics and the expected impact lowering the incidence of future cardiovascular events.

Metabolic syndrome in HIV-infected individuals: underlying mechanisms and epidemiological aspects.

The success of highly active antiretroviral therapy (HAART) has determined a dramatic decline in AIDS- and immunodeficiency-related causes of death in the HIV-infected population. As life-expectancy increases, such individuals have become gradually exposed not only to the effects of aging itself, but also to the influence of environmental risk factors, which are known to act in the general population. These features can lead to obesity, diabetes mellitus and ultimately cardiovascular diseases (CVD). Metabolic complications and abnormal fat distribution were frequently observed after a few years of antiretroviral therapy and, as the array of antiretroviral drugs became broader, long term metabolic alterations are becoming far more common worldwide. Nevertheless, the risk of not being on HAART is overwhelmingly greater than the metabolic adverse events in terms of morbidity and mortality events. HIV/HAART-induced metabolic unbalances overlap in some extent the components of Metabolic Syndrome (MetS) and its high rates in the HIV population place infected individuals in an elevated CVD risk category. MetS can explain at least in part the emergence of CVD as the major morbidity and mortality conditions in the HIV population. In this review we convey information on the underlying aspects of MetS during HIV infection, highlighting some physiopathological and epidemiological features of this comorbidity along with the role played by HIV itself and the synergy action of some antiretroviral drugs. Considerations on MetS management in the HIV population are also depicted.

Mortality rates by gender and sexual orientation reveal a disproportionally high mortality among cisgender men of unknown sexual orientation and men who have sex with women in a cohort of people living with HIV in Rio de Janeiro, Brazil.

BACKGROUND: Antiretroviral therapy use has led to a decline in HIV-related mortality yet disparities by gender and/or sexual orientation may exist. In this study, we estimated hazards of death in people living with HIV (PLWH) according to gender and sexual orientation. METHODS: We included PLWH ≥ 18 years enrolled between 2000 and 2018 at INI/Fiocruz, Rio de Janeiro, Brazil. Participants were grouped as cisgender or transgender women, cisgender men who have sex with men (MSM) or men who have sex with women, or cisgender men with unknown sexual orientation. We assessed disparities in the hazard of death using Cox proportional hazards models. RESULTS: Among 5,576 PLWH, median age at enrollment was 35 years, 39% were MSM, 28% cisgender women, 23% men who have sex with women, 5% transgender women, and 5% men with unknown sexual orientation. A total of 795 deaths occurred in 39,141 person-years of follow-up. Mortality rates per 1,000 person-years were: 82.4 for men with unknown sexual orientation, 24.5 for men who have sex with women, 18.3 for cisgender, 16.6 for transgender women, and 15.1 for MSM. Compared to MSM, men with unknown sexual orientation had the highest death hazard ratio (adjusted hazard ratio [aHR] 2.93, 95% confidence interval [CI] 2.35-3.81), followed by men who have sex with women (aHR 1.17, 95%CI 0.96, 1.43); death hazard ratios for cisgender and transgender women were not statistically different. CONCLUSION: We observed disparities in the hazard of death for men with unknown sexual orientation and men who have sex with women despite universal access to antiretroviral therapy in Brazil. Future work should characterize and assist men with unknown sexual orientation with tailored policies and interventions. Increased hazard of death was not observed for transgender women, which probably results from interventions implemented in our service to reach, engage, retain, and support this population.

The functional assessment of patients with pulmonary multidrug-resistant tuberculosis.

BACKGROUND: Tuberculosis (TB) remains an important public health problem worldwide, as its residual lesions result in functional and quality of life impairments. Few studies have investigated multiple-drug-resistant pulmonary TB (MDR-TB), and the literature regarding the functional parameters of this group of patients is scarce. Functional characterization may point to the need for post-treatment intervention measures that optimize the quality of life in patients with MDR-TB. Thus, this study sought to analyze the respiratory function, functional capacity, and quality of life of patients who were treated for MDR pulmonary TB. METHODS: This study investigated a cross-sectional cohort of MDR-TB patients who underwent drug treatment for at least 18 months. Patients who had associated diseases (human immunodeficiency virus [HIV], severe heart disease, and hypertension) or disabilities that prevented them from walking were excluded. The subjects underwent the following assessments: forced spirometry, a chest radiograph, the 6-min walk test, a bioelectrical impedance analysis, maximal inspiratory and expiratory pressures, and a health-related quality of life questionnaire. RESULTS: Eighteen patients who met the eligibility criteria were enrolled. Spirometric evaluation showed that 78% of the subjects had abnormal patterns. The maximal respiratory pressures were significantly decreased in all subjects, despite the fact that their nutritional status was within the normal range. The distance completed in the 6-min walk test was less than expected in 72% of the subjects. All of the subjects who were evaluated had residual lesions, and 78% reported a worsening in their quality of life. CONCLUSIONS: In conclusion MDR-TB cured subjects exhibit impaired respiratory function and a mildly reduced functional capacity and quality of life, suggesting that a portion of these patients may require a pulmonary rehabilitation approach.

TNF -308G>A single nucleotide polymorphism is associated with leprosy among Brazilians: a genetic epidemiology assessment, meta-analysis, and functional study.

Leprosy is an infectious disease caused by Mycobacterium leprae. Tumor necrosis factor (TNF) plays a key role in the host response. Some association studies have implicated the single nucleotide polymorphism TNF -308G>A in leprosy susceptibility, but these results are still controversial. We first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308A allele (odds ratio [OR] = 0.77; P = .005). Next, results of a meta-analysis reinforced this association after inclusion of our new data (OR = 0.74; P = .04). Furthermore, a subgroup analysis including only Brazilian studies suggested that the association is specific to this population (OR = 0.63; P = .005). Finally, functional analyses using whole blood cultures showed that patients carrying the -308A allele produced higher TNF levels after lipopolysaccharide (LPS) (6 hours) and M. leprae (3 hours) stimulation. These results reinforce the association between TNF and leprosy and suggest the -308A allele as a marker of disease resistance, especially among Brazilians.

Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Aim: Previous studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy. Methods: Patients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6-12 months after treatment, and intention-to-treat analysis was used. Results: We screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60-0.97) vs. 66% (95% CI 0.40-0.86), p = 0.47, at 6 months and 68% (95% CI 0.43-0.87) vs. 72% (95% CI 0.46-0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO2 max) showed an improving trend in the G-CSF group. Conclusion: G-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02154269].

Long-term pulmonary rehabilitation progressively reduces hospitalizations and mortality in patients with severe COPD: a 5-year follow-up.

BACKGROUND: Pulmonary rehabilitation (PR) is recognized as a multidisciplinary intervention designed to reduce symptoms, improve functional status, and prevent acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). AIM: This study was aimed at evaluating the effects of a long-term PR program on the hospitalization rate and mortality of patients with severe and very severe COPD. DESIGN: Longitudinal, prospective study. SETTING: Pulmonary rehabilitation program at our institution. POPULATION: A cohort of 195 patients undergoing a PR program was followed up for 5 years. They were divided into three groups: control (PR<3 months), partial adherence (PR>6 and ≤18 months) and adherence (PR=24 months). METHODS: This was a prospective study where All patients were evaluated every 6 months (D0, D6, D12, D18 and D24, and mapped annually concerning hospitalizations and mortality). Data were analyzed by medians and interquartile ranges, and Kruskal-Wallis non-parametric comparative tests were applied. Comparisons of time to first admission and time to death were made using the Kaplan-Meier estimators, and the factors associated with these outcomes were modeled using semi-parametric Cox models. RESULTS: The results demonstrated a significant reduction in the rate of hospitalization and mortality. The protective effect seems to be dependent on the lengths of stay of patients in the PR program. CONCLUSIONS: A multi-disciplinary, long-term PR program with individually tailored 96-week supervised interventions, reduces hospitalization rates and mortality in patients with severe and very severe COPD in a 5-year follow-up period. This protective effect on hospitalization and mortality is obtained from at least 18 months of intervention. Patients who stay longer in the PR program appear to experience a longer protective effect at the end of treatment. CLINICAL REHABILITATION IMPACT: This long-term PR program for patients with severe and very severe COPD produced progressively favorable clinical effects, thus reducing the frequency of hospitalizations and mortality in this population.

Four-year adiposity change and remission of hypertension: an observational evaluation from the Longitudinal Study of Adult Health (ELSA-Brasil).

The degree to which weight reduction leads to the remission of hypertension in population studies is not clear. We investigated whether the changes in adiposity measures predicted the remission of hypertension in a racially admixed population over a mean 4-year follow-up. All 4847 hypertensive individuals at baseline (2008-2010) from the multicenter Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were included. Changes in weight, waist circumference (WC), or body mass index (BMI) (reduction or increase ≥5% from baseline values, vs stability) and remission of hypertension (SBP < 140 and DBP < 90 mmHg and no use of antihypertensive medication at follow-up visit, in 2012-2014) were investigated using mixed effects logistic regression models. Proportional attributable benefit was additionally calculated. Analyses were stratified by sex and antihypertensive medication use at baseline. Remission of hypertension was 11.3% (n = 546). Among men, after adjustments, the reduction of weight (OR = 1.52 95% CI 1.10-2.10), WC (OR = 1.56 95% CI 1.04-2.35) or BMI (OR = 1.60 95% CI 1.13-2.27) was associated with the remission of hypertension. Among those not taking antihypertensive medication at baseline, after adjustments, the reduction of weight (OR = 1.64 95% CI 1.18-2.27), WC (OR = 1.76 95% CI 1.18-2.61) or BMI (OR = 1.57 95% CI 1.10-2.25) was associated with the remission of hypertension. Proportional attributable benefit among those with adiposity reduction was about 30%, indicating its potential for prevention. In conclusion, our study reinforces the role of adiposity-reducing strategies (e.g., healthy diet and regular physical activity) for the treatment and prevention of hypertension, which might have potential applications for clinical practice.

Quantitative PCR for leprosy diagnosis and monitoring in household contacts: A follow-up study, 2011-2018.

Household contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6-290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.

Quantitative polymerase chain reaction in paucibacillary leprosy diagnosis: A follow-up study.

OBJECTIVE: The diagnosis of paucibacillary (PB) leprosy cases remains a challenge because of the absence of a confirmatory laboratory method. While quantitative polymerase chain reaction (qPCR) has been shown to provide reliable sensitivity and specificity in PB diagnoses, a thorough investigation of its efficacy in clinical practice has not yet been published. The present study evaluated patients with suspected leprosy skin lesions by using qPCR to identify PB individuals in the Leprosy Outpatient clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. METHODS: One hundred seventy-two suspected PB cases were included in the study. The patients were evaluated by a dermatologist at three different times. The clinical dermato-neurological examination and collected samples were performed on the first visit. On the second visit, the results of the histopathological analysis and PCR assay (DNA-based Mycobacterium leprae qPCR-targeting 16S gene) results were analyzed, and a decision regarding multi-drug therapy was made. A year later, the patients were re-examined, and the consensus diagnosis was established. RESULTS: In 58% (100/172) of cases, a conclusive diagnosis via histopathological analysis was not possible; however, 30% (30/100) of these cases had a positive PCR. One hundred ten patients (110/172) attended the third visit. The analysis showed that while the sensitivity of the histopathological test was very low (35%), a qPCR alone was more effective for identifying leprosy, with 57% sensitivity. CONCLUSION: The use of qPCR in suspected PB cases with an inconclusive histology improved the sensitivity of leprosy diagnoses.