Development and validation of a machine learning model to predict the use of renal replacement therapy in 14,374 patients with COVID-19.

PURPOSE: To develop a model to predict the use of renal replacement therapy (RRT) in COVID-19 patients. MATERIALS AND METHODS: Retrospective analysis of multicenter cohort of intensive care unit (ICU) admissions of Brazil involving COVID-19 critically adult patients, requiring ventilatory support, admitted to 126 Brazilian ICUs, from February 2020 to December 2021 (development) and January to May 2022 (validation). No interventions were performed. RESULTS: Eight machine learning models' classifications were evaluated. Models were developed using an 80/20 testing/train split ratio and cross-validation. Thirteen candidate predictors were selected using the Recursive Feature Elimination (RFE) algorithm. Discrimination and calibration were assessed. Temporal validation was performed using data from 2022. Of 14,374 COVID-19 patients with initial respiratory support, 1924 (13%) required RRT. RRT patients were older (65 [53-75] vs. 55 [42-68]), had more comorbidities (Charlson's Comorbidity Index 1.0 [0.00-2.00] vs 0.0 [0.00-1.00]), had higher severity (SAPS-3 median: 61 [51-74] vs 48 [41-58]), and had higher in-hospital mortality (71% vs 22%) compared to non-RRT. Risk factors for RRT, such as Creatinine, Glasgow Coma Scale, Urea, Invasive Mechanical Ventilation, Age, Chronic Kidney Disease, Platelets count, Vasopressors, Noninvasive Ventilation, Hypertension, Diabetes, modified frailty index (mFI) and Gender, were identified. The best discrimination and calibration were found in the Random Forest (AUC [95%CI]: 0.78 [0.75-0.81] and Brier's Score: 0.09 [95%CI: 0.08-0.10]). The final model (Random Forest) showed comparable performance in the temporal validation (AUC [95%CI]: 0.79 [0.75-0.84] and Brier's Score, 0.08 [95%CI: 0.08-0.1]). CONCLUSIONS: An early ML model using easily available clinical and laboratory data accurately predicted the use of RRT in critically ill patients with COVID-19. Our study demonstrates that using ML techniques is feasible to provide early prediction of use of RRT in COVID-19 patients.

Delirium severity and outcomes of critically ill COVID-19 patients / Gravidade do delirium e desfechos de pacientes críticos com COVID-19

ABSTRACT Objective: To investigate the impact of delirium severity in critically ill COVID-19 patients and its association with outcomes. Methods: This prospective cohort study was performed in two tertiary intensive care units in Rio de Janeiro, Brazil. COVID-19 patients were evaluated daily during the first 7 days of intensive care unit stay using the Richmond Agitation Sedation Scale, Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and Confusion Method Assessment for Intensive Care Unit-7 (CAM-ICU-7). Delirium severity was correlated with outcomes and one-year mortality. Results: Among the 277 COVID-19 patients included, delirium occurred in 101 (36.5%) during the first 7 days of intensive care unit stay, and it was associated with a higher length of intensive care unit stay in days (IQR 13 [7 - 25] versus 6 [4 - 12]; p < 0.001), higher hospital mortality (25.74% versus 5.11%; p < 0.001) and additional higher one-year mortality (5.3% versus 0.6%, p < 0.001). Delirium was classified by CAM-ICU-7 in terms of severity, and higher scores were associated with higher in-hospital mortality (17.86% versus 34.38% versus 38.46%, 95%CI, p value < 0.001). Severe delirium was associated with a higher risk of progression to coma (OR 7.1; 95%CI 1.9 - 31.0; p = 0.005) and to mechanical ventilation (OR 11.09; 95%CI 2.8 - 58.5; p = 0.002) in the multivariate analysis, adjusted by severity and frailty. Conclusion: In patients admitted with COVID-19 in the intensive care unit, delirium was an independent risk factor for the worst prognosis, including mortality. The delirium severity assessed by the CAM-ICU-7 during the first week in the intensive care unit was associated with poor outcomes, including progression to coma and to mechanical ventilation.

RESUMO Objetivo: Investigar como a gravidade do delirium afeta pacientes graves com COVID-19 e sua associação com os desfechos. Métodos: Estudo de coorte prospectivo realizado em duas unidades de terapia intensiva terciárias no Rio de Janeiro (RJ). Os pacientes com COVID-19 foram avaliados diariamente durante os primeiros 7 dias de internação na unidade de terapia intensiva usando a escala de agitação e sedação de Richmond, a Confusion Assessment Method for Intensive Care Unit (CAM-ICU) e a Confusion Assessment Method for Intensive Care Unit-7 (CAM-ICU-7). A gravidade do delirium foi correlacionada com os desfechos e a mortalidade em 1 ano. Resultados: Entre os 277 pacientes com COVID-19 incluídos, o delirium ocorreu em 101 (36,5%) durante os primeiros 7 dias de internação na unidade de terapia intensiva e foi associado a maior tempo de internação na unidade de terapia intensiva em dias (IQ: 13 [7 - 25] versus 6 [4 - 12]; p < 0,001), maior mortalidade hospitalar (25,74% versus 5,11%; p < 0,001) e maior mortalidade em 1 ano (5,3% versus 0,6%, p < 0,001). O delirium foi classificado pela CAM-ICU-7 em termos de gravidade, e escores maiores foram associados à maior mortalidade hospitalar (17,86% versus 34,38% versus 38,46%, IC95%, valor de p < 0,001). O delirium grave foi associado a um risco maior de progressão ao coma (RC de 7,1; IC95% 1,9 - 31,0; p = 0,005) e à ventilação mecânica (RC de 11,09; IC95% 2,8 - 58,5; p = 0,002) na análise multivariada, ajustada por gravidade e fragilidade Conclusão: Em pacientes internados com COVID-19 na unidade de terapia intensiva, o delirium foi fator de risco independente para o pior prognóstico, incluindo mortalidade. A gravidade do delirium avaliada pela CAM-ICU-7 durante a primeira semana na unidade de terapia intensiva foi associada a desfechos desfavoráveis, incluindo a progressão ao coma e à ventilação mecânica.

Serum from patients with asthma potentiates macrophage phagocytosis and human mesenchymal stromal cell therapy in experimental allergic asthma.

BACKGROUND/AIMS: Although several studies have demonstrated that mesenchymal stromal cells (MSCs) exhibit beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been controversial. Recent evidence has shown that MSCs modify their in vivo immunomodulatory actions depending on the specific inflammatory environment encountered. Accordingly, we assessed whether the therapeutic properties of human mesenchymal stromal cells (hMSCs) could be potentiated by conditioning these cells with serum (hMSC-serum) obtained from patients with asthma and then transplanted in an experimental model of house dust mite (HDM)-induced allergic asthma. METHODS: hMSC and hMSC-serum were administered intratracheally 24 h after the final HDM challenge. hMSC viability and inflammatory mediator production, lung mechanics and histology, bronchoalveolar lavage fluid (BALF) cellularity and biomarker levels, mitochondrial structure and function as well as macrophage polarization and phagocytic capacity were assessed. RESULTS: Serum preconditioning led to: (i) increased hMSC apoptosis and expression of transforming growth factor-ß, interleukin (IL)-10, tumor necrosis factor-α-stimulated gene 6 protein and indoleamine 2,3-dioxygenase-1; (ii) fission and reduction of the intrinsic respiratory capacity of mitochondria; and (iii) polarization of macrophages to M2 phenotype, which may be associated with a greater percentage of hMSCs phagocytosed by macrophages. Compared with mice receiving hMSCs, administration of hMSC-serum led to further reduction of collagen fiber content, eotaxin levels, total and differential cellularity and increased IL-10 levels in BALF, improving lung mechanics. hMSC-serum promoted greater M2 macrophage polarization as well as macrophage phagocytosis, mainly of apoptotic hMSCs. CONCLUSIONS: Serum from patients with asthma led to a greater percentage of hMSCs phagocytosed by macrophages and triggered immunomodulatory responses, resulting in further reductions in both inflammation and remodeling compared with non-preconditioned hMSCs.

Telemedicine Support for Primary Care Providers versus Usual Care in Patients with Heart Failure: Protocol of a Pragmatic Cluster Randomised Trial within the Brazilian Heart Insufficiency with Telemedicine (BRAHIT) Study.

Heart failure is a prevalent condition and a frequent cause of hospital readmissions and poor quality of life. Teleconsultation support from cardiologists to primary care physicians managing patients with heart failure may improve care, but the effect on patient-relevant outcomes is unclear. We aim to evaluate whether collaboration through a novel teleconsultation platform in the Brazilian Heart Insufficiency with Telemedicine (BRAHIT) project, tested on a previous feasibility study, can improve patient-relevant outcomes. We will conduct a parallel-group, two-arm, cluster-randomised superiority trial with a 1:1 allocation ratio, with primary care practices from Rio de Janeiro as clusters. Physicians from the intervention group practices will receive teleconsultation support from a cardiologist to assist patients discharged from hospitals after admission for heart failure. In contrast, physicians from the control group practices will perform usual care. We will include 10 patients per each of the 80 enrolled practices (n = 800). The primary outcome will be a composite of mortality and hospital admissions after six months. Secondary outcomes will be adverse events, symptoms frequency, quality of life, and primary care physicians' compliance with treatment guidelines. We hypothesise that teleconsulting support will improve patient outcomes.

Gait speed, muscle strength, and functional status predict 30-day unplanned hospital readmission of critical care survivors.

BACKGROUND AND PURPOSE: Despite intense efforts, predicting hospital readmission risks remains an imprecise task. Growing evidence suggests that unmeasured patient-related factors, such as functional impairment, seem to be strongly associated with acute readmission and have yet to be extensively explored. We hypothesized that gait speed, hand grip strength, and the Functional independence measure (FIM) might be associated with acute rehospitalization rates after an ICU stay. METHODS: In our study, we assessed gait speed using a 10-m walk test. Muscle strength was determined by a hydraulic handgrip dynamometer and functional status through the FIM. Our primary outcome was the cumulative incidence of the first unplanned early rehospitalization (occurring within 30 days of hospital discharge) for the entire cohort, and a Receiver Operator Characteristic (ROC) analysis was used to determine the accuracy of gait speed, handgrip strength, and FIM domains in predicting hospital readmission. RESULTS: ROC analysis indicated that the gait speed (AUC 0.96 95% CI 0.93 to 0.99), FIM score (AUC 0.96 95% CI 0.94 to 0.99) and handgrip strength (0.85 95% CI 0.76 to 0.94) were considered accurate predictors of unplanned readmission in the population studied. Additionally, we found that each 0.1 m/s lower gait speed was associated with a 10% higher odd of unplanned readmissions. CONCLUSION: Hence, our results suggest gait speed, handgrip strength and functional status demonstrated high potential to contribute to the determination of 30-day unplanned hospital readmission prediction of critical care survivors.

Factors associated with non-completion of TB preventive treatment in Brazil.

BACKGROUND: Among Brazilian initiatives to scale up TB preventive therapy (TPT) are the adoption of the 3HP regimen (12 weekly doses of rifapentine and isoniazid [INH]) in 2021 and the implementation in 2018 of the TPT surveillance information system. Since then, 63% of the 76,000 eligible individuals notified completed TPT. Recommended regimens in this period were 6H, 9H (6 or 9 months of INH) and 4R (4 months of rifampicin).OBJECTIVE: To analyse the factors associated with TPT non-completion.METHODS: We analysed the cohort of TPT notifications from 2018 to 2020. Robust variance Poisson regression model was used to verify the association of TPT non-completion with sociodemographic, clinical and epidemiological variables.RESULTS: Of the 39,973 TPT notified in the study period, 8,534 (21.5%) were non-completed, of which 7,858 (92.1%) were lost to follow-up. Age 15-60 years (relative risk [RR] 1.27, 95% confidence interval [95% CI] 1.20-1.35), TPT with isoniazid (RR 1.40, 95% CI 1.19-1.64) and Black/mixed race (RR 1.17, 95% CI 1.09-1.25) were associated with a higher risk of non-completion.CONCLUSION: Individuals in situations of social and financial vulnerability such as being Black/pardo race, younger and on longer TPT regimens were more likely to be associated with TPT incompletion.

Perceptions of plagiarism among PhDs across the sciences, engineering, humanities, and arts: Results from a national survey in Brazil.

Plagiarism allegations are not rare in the history of science, and credit for prior work was and continues to be a source of disputes, involving notions of priority of discovery and of plagiarism. However, consensus over what constitutes plagiarism among scientists from different fields cannot be taken for granted. We conducted a national survey exploring perceptions of plagiarism among PhD holders registered in the database of the Brazilian National Council for Scientific and Technological Development. This survey was sent to 143,405 PhD holders across the fields, in the sciences, engineering, humanities, and arts, with a response rate of about 20%. The results suggest that core principles about plagiarism are shared among this multidisciplinary community, corroborating Robert K. Merton's observations that concerns over plagiarism and priority disputes are not field specific. This study offers insight into the way plagiarism is perceived in this community and sheds light on the problem for international collaborative research networks. The data focus on a particular research system in Latin America, but, given the cultural similarities that bind most Latin American nations, these results may be relevant to other PhD populations in the region and should provide an opportunity for comparison with studies from other emerging, non-Anglophone regions.

SNPs, adipokynes and adiposity in children with asthma.

OBJECTIVES: Asthma and obesity are complex disorders influenced by environmental and genetic factors. We performed an integrative review of genetic polymorphisms and adipokines effects in children and adolescents with asthma and obesity. DATA SOURCES: Articles focused on these issues were collected from SciELO, PubMed, LILACS, Embase and ScienceDirect electronic databases, in 2009-2020 period. STUDY SELECTIONS: 22 articles were selected, including clinical trials, analyses approaches, case-control studies, meta-analysis and Mendelian randomization studies. RESULTS: Leptin concentrations were higher in obesity and asthma. The high value of BMI and Leptin indicated severe asthma. Adiponectin may be reduced in obese children. The high value of BMI and low level of Adiponectin may indicate severe asthma. Some linkage of PRKCA gene, asthma and BMI was observed. FTO T allele rs62048379 was positively associated with overweight/obesity, related to protein and PUFA:SFA ratio intake and influences the choice of more energy-dense foods. FTO rs9939609 effects are more pronounced among children with insufficient vitamin D levels. CONCLUSION: Leptin may be a potential predictor for asthma control in children. BMI and Adiponectin could have certain predictive value for asthma. FTO gene was related to a higher mean BMI Z-score and accelerated developmental age per allele. Strong genetic heterogeneity influencing on asthma and obesity susceptibilities is evident and related to distinct genetic features. GWAS with childhood obesity in asthma contributed to greater insights, mainly on later childhood. Standardized definitions for asthma and overweight/obesity in studies approaching adipokines and SNPs would provide stronger evidence in deciding the best management.

Delirium severity and outcomes of critically ill COVID-19 patients.

OBJECTIVE: To investigate the impact of delirium severity in critically ill COVID-19 patients and its association with outcomes. METHODS: This prospective cohort study was performed in two tertiary intensive care units in Rio de Janeiro, Brazil. COVID-19 patients were evaluated daily during the first 7 days of intensive care unit stay using the Richmond Agitation Sedation Scale, Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and Confusion Method Assessment for Intensive Care Unit-7 (CAM-ICU-7). Delirium severity was correlated with outcomes and one-year mortality. RESULTS: Among the 277 COVID-19 patients included, delirium occurred in 101 (36.5%) during the first 7 days of intensive care unit stay, and it was associated with a higher length of intensive care unit stay in days (IQR 13 [7 - 25] versus 6 [4 - 12]; p < 0.001), higher hospital mortality (25.74% versus 5.11%; p < 0.001) and additional higher one-year mortality (5.3% versus 0.6%, p < 0.001). Delirium was classified by CAM-ICU-7 in terms of severity, and higher scores were associated with higher in-hospital mortality (17.86% versus 34.38% versus 38.46%, 95%CI, p value < 0.001). Severe delirium was associated with a higher risk of progression to coma (OR 7.1; 95%CI 1.9 - 31.0; p = 0.005) and to mechanical ventilation (OR 11.09; 95%CI 2.8 - 58.5; p = 0.002) in the multivariate analysis, adjusted by severity and frailty. CONCLUSION: In patients admitted with COVID-19 in the intensive care unit, delirium was an independent risk factor for the worst prognosis, including mortality. The delirium severity assessed by the CAM-ICU-7 during the first week in the intensive care unit was associated with poor outcomes, including progression to coma and to mechanical ventilation.

Impact of Subsyndromal Delirium Occurrence and Its Trajectory during ICU Stay.

Despite recent advances in the field, the association between subsyndromal delirium (SSD) in the ICU and poor outcomes is not entirely clear. We performed a retrospective multicentric observational study analyzing mental status during the first 72 h of ICU stay. Of the 681 patients included, SSD occurred in 22.7%. Considering the worst cognitive assessment during the first 72 h, 233 (34%) patients had normal mental status, 124 (18%) patients had SSD and 324 (48%) patients had delirium or coma. SSD was not independently associated with an increased risk of death when compared with normal mental status (OR 95%IC 1.0 vs. 1.35 [0.73−1.49], p = 0.340), but was associated with a longer ICU LOS (7.0 (4−12) vs. 4 (3−8) days, p < 0.001). SSD patients who deteriorated to delirium or coma (21%) had a longer ICU LOS in comparison with those who improved or maintained mental status (8 (5−11) vs. 6 (4−8) days, p = 0.025), but did not have an increase in mortality. The main factors associated with the progression from SSD to delirium or coma were the use of mechanical ventilation, the use of intravenous benzodiazepines and a baseline APACHE II score > 23 points. Our findings support the association of SSD with increased ICU LOS, but not with ICU mortality. Monitoring the trajectory of SSD early at ICU admission can help to identify patients with increased risk of conversion from SSD to delirium or coma.

Determinants of losses in the tuberculosis infection cascade of care among children and adolescent contacts of pulmonary tuberculosis cases: A Brazilian multi-centre longitudinal study.

Background: Approximately 10% of the global tuberculosis (TB) burden is in children. Identification, diagnosis, and early treatment of Mycobacterium tuberculosis infection (TBI) is critical to prevent progression to TB in children. The risk of TB, including severe disease, is highest in children <5 years old. We evaluated the cascade of TBI care among child and adolescent TB contacts to identify factors associated with losses in the cascade. Methods: Close contacts ≤ 18 years old of pulmonary TB patients enrolled between 2015 and 2019 in a multi-centre Brazilian cohort were followed for up to 24 months and classified according to age groups: <5 years, 5-9 years, 10-14 years and 15-18 years. Data on clinical investigation, radiographic examination, IGRA testing at baseline and 6 months, initiation and completion of TB preventive treatment (TPT) were collected. Multivariable regression analyses identified factors associated with TBI and losses in the cascade of care in children and adolescents. Findings: Among 1795 TB contacts initially identified, 530 (29·5%) were ≤18 years old. Losses for all steps in the cascade were especially high in children <5 years old (88%) because at this age all contacts are recommended to initiate TPT. As a proportion of all children, completion of TPT was low (between 10% and 13%) in all age-groups. Furthermore, multivariable regression revealed that younger age of contacts and TB index cases who were female, had pulmonary cavities, and persistent cough were independently associated with losses in the cascade of care among persons ≤18 years old. Interpretation: Losses in the TBI cascade were the highest among children <5 years, which was the group at highest risk for TB among the four age groups. The findings highlight the need to improve screening, initiation, and completion of TPT of young children who are close contacts of people with TB in Brazil. Funding: National Institutes of Allergy and Infectious Diseases.

Thesis and dissertations examining tuberculosis in Brazil between 2013 and 2019: an overview.

BACKGROUND: Tuberculosis (TB) remains a serious public health problem, with approximately 10 million new cases reported annually. Knowledge about the quantitative evolution of theses and dissertations (T&Ds) examining human TB in Brazil can contribute to generating strategic planning for training professionals in this field and disease control. Therefore, this study highlights the role of T&Ds on TB in national scientific disclosures. METHODS: An integrative review related to TB was performed, including T&Ds produced in Brazil and completed between 2013 and 2019. RESULTS: A total of 559,457 T&Ds were produced, of which 1,342 were associated with TB, accounting for 0.24% of the total number of T&Ds in Brazil. This was evidenced by a predominance of themes such as attention/health care, epidemiology, and TB treatment, and 80.2% of the T&Ds on TB were related to the large areas of health and biological sciences. Only 19.7% of T&Ds were associated with groups of patients considered at risk for TB, and 50.9% were produced in southeastern Brazil. The 1,342 T&Ds on TB were developed in 416 postgraduate programs linked to 121 higher education institutions (HEIs). We highlight that 72.7% of T&Ds on TB were produced in federal HEIs, 27.4% in state HEIs, and 8.5% in private HEIs. CONCLUSIONS: Strategic themes, such as TB control, require public policies that aim to increase the number of doctors and masters with expertise in TB, with geographic uniformity, and in line with the priorities for disease control.

Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.

Recurrent WWTR1 S89W mutations and Hippo pathway deregulation in clear cell carcinomas of the cervix.

Clear cell carcinoma (CCC) of the cervix (cCCC) is a rare and aggressive type of human papillomavirus (HPV)-negative cervical cancer with limited effective treatment options for recurrent or metastatic disease. Historically, CCCs of the lower genital tract were associated with in utero diethylstilbestrol exposure; however, the genetic landscape of sporadic cCCCs remains unknown. Here we sought to define the molecular underpinning of cCCCs. Using a combination of whole-exome, targeted capture, and RNA-sequencing, we identified pathogenic genetic alterations in the Hippo signaling pathway in 50% (10/20) of cCCCs, including recurrent WWTR1 S89W somatic mutations in 40% (4/10) of the cases harboring mutations in the Hippo pathway. Irrespective of the presence or absence of Hippo pathway genetic alterations, however, all primary cCCCs analyzed in this study (n = 20) harbored features of Hippo pathway deregulation at the transcriptomic and protein levels. In vitro functional analysis revealed that expression of the WWTR1 S89W mutation leads to reduced binding of TAZ to 14-3-3, promoting constitutive nuclear translocation of TAZ and Hippo pathway repression. WWTR1 S89W expression was found to lead to acquisition of oncogenic behavior, including increased proliferation, migration, and colony formation in vitro as well as increased tumorigenesis in vivo, which could be reversed by targeted inhibition of the TAZ/YAP1 complex with verteporfin. Finally, xenografts expressing WWTR1 S89W displayed a shift in tumor phenotype, becoming more infiltrative as well as less differentiated, and were found to be composed of cells with conspicuous cytoplasmic clearing as compared to controls. Our results demonstrate that Hippo pathway alterations are likely drivers of cCCCs and likely contribute to the clear cell phenotype. Therapies targeting this pathway may constitute a new class of treatment for these rare, aggressive tumors. © 2022 The Pathological Society of Great Britain and Ireland.

The Effect of Diabetes and Prediabetes on Antituberculosis Treatment Outcomes: A Multicenter Prospective Cohort Study.

BACKGROUND: It is unclear whether diabetes or prediabetes affects unfavorable treatment outcomes and death in people with tuberculosis (PWTB). METHODS: Culture-confirmed, drug-susceptible PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between 2015 and 2019 (N = 643) were stratified based on glycemic status according to baseline glycated hemoglobin. Unfavorable tuberculosis (TB) outcome was defined as treatment failure or modification, recurrence, or death; favorable outcome was cure or treatment completion. We corroborated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015-2019 (N = 20 989). Logistic regression models evaluated associations between glycemic status and outcomes. RESULTS: In both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with smoking, illicit drug use, and human immunodeficiency virus infection. Diabetes, but not prediabetes, was associated with unfavorable outcomes in the RePORT-Brazil (adjusted relative risk [aRR], 2.45; P < .001) and SINAN (aRR, 1.76; P < .001) cohorts. Furthermore, diabetes was associated with high risk of death (during TB treatment) in both RePORT-Brazil (aRR, 2.16; P = .040) and SINAN (aRR, 1.93; P = .001). CONCLUSIONS: Diabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve TB treatment outcomes in persons with diabetes are needed.

The five times sit-to-stand test: safety, validity and reliability with critical care survivors's at ICU discharge.

BACKGROUND: The Five Times Sit-to-Stand Test (FTSST) has been found reliable, safe and valid for measuring healthy adults' lower limb muscle strength and for determining balance control, fall risk, and exercise capacity among older examinees. We believe that the FTSST has the potential to be a straightforward, low cost and valuable tool for identifying muscle disability and functional status following critical illness. The aim of our study was to establish the applicability, safety, and psychometric qualities of FTSST in patients at Intensive Care Unit (ICU) discharge. METHODS: In our study applicability was determined by assessing the percentage of patients who could perform the test at ICU discharge. Safety was assessed by examining data regarding any exacerbated haemodynamic and respiratory responses or adverse events associated with the test. For assessing FTSST reliability, intraclass correlation coefficients (ICCs), standard error of measurement (SEM) and Bland-Altman plot were used. For assessing concurrent validity handgrip strength, ICU length of stay, duration of invasive ventilation, Simplified Acute Physiology Score 3 (SAPS3) and age variables were used. For investigating predictive validity, correlations between the FTSST and measures of hospital length of stay and functional independence were evaluated. RESULTS: Only 30% of ICU survivors (n = 261 out of 817) were eligible to perform the FTSST and 7% of patients who performed the test (n = 10 out of 142) presented adverse events. Both inter (ICC 0.92 CI95% 0.89-0.94) and intra-rater (ICC 0.95 CI95% 0.93-0.96) reliability were excellent and higher scores were associated with lower muscle strength, longer hospital stay and greater functional impairment at hospital discharge in adult survivors of critical diseases. CONCLUSION: Our results suggest that the FTSST may be applicable only to high-functioning critical care survivors. In this specifical population, FTSST is a safe, easy to perform, valid and reliable measure that can be applied to fall risk and functional recovery management.