Underweight increases the risk of early death in tuberculosis patients.

Evidence regarding the association between BMI and mortality in tuberculosis (TB) patients is limited and inconsistent. We investigated the impact of BMI on TB-specific and non-TB-specific mortality with respect to different timing of death. All Taiwanese adults with TB in Taipei were included in a retrospective cohort study in 2012-2014. Multinomial Cox proportional hazards regression was used to evaluate the associations between BMI, cause-specific mortality and timing of death. Of 2410 eligible patients, 86·0 % (2061) were successfully treated, and TB-specific and non-TB-specific mortality occurred for 2·2 % (54) and 13·9 % (335), respectively. After controlling for potential confounders, underweight was significantly associated with a higher risk of all-cause mortality (adjusted hazard ratio (AHR) 1·57; 95 % CI 1·26, 1·95), whereas overweight was not. When cause-specific death was considered, underweight was associated with an increased risk of either TB-specific (AHR 1·85; 95 % CI 1·03, 3·33) or non-TB-specific death (AHR 1·52; 95 % CI 1·19, 1·95) during treatment. With joint consideration of cause-specific and timing of death, underweight only significantly increased the risk of TB-specific (AHR 2·23; 95 % CI 1·09, 4·59) and non-TB-specific mortality (AHR 1·81; 95 % CI 1·29, 2·55) within the first 8 weeks of treatment. This study suggests that underweight increases the risk of early death in TB patients during treatment.

Sex difference in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection.

Dietary cholesterol induces hepatic inflammation and fibrosis in animals. We aimed to determine whether dietary cholesterol affects liver-related mortality in hepatitis C virus (HCV)-infected patients. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial. The study included HCV patients with advanced fibrosis and compensated cirrhosis. The analysis included 657 patients who completed two FFQ. We assessed whether cholesterol intake, measured in mg/4184 kJ (mg/1000 kcal) of energy intake, was associated with liver-related death or transplantation. In 4·7 (sd 1·6) years, the incidence of liver-related death (n 46) or transplantation (n 52) was 31·8/1000 person-years. The relationship between cholesterol intake and liver-related death or transplantation was significantly different between men and women (test for interaction, P value=0·01). Each higher quartile of cholesterol intake was associated with an increased risk for liver-related death or transplantation in women (adjusted hazard ratio (AHR) 1·83; 95 % CI 1·12, 2·99; P trend=0·02), but not in men (AHR 0·96; 95 % CI 0·76, 1·22; P trend=0·73). Compared with women whose cholesterol intake was within the recommended guidelines (300 mg/d with a 8368 kJ (2000 kcal) diet), women who consumed more cholesterol had significantly increased risk for liver-related death or transplantation (AHR 4·04; 95 % CI 1·42, 11·5). High dietary cholesterol was associated with an increased risk for liver-related death and transplantation in HCV-infected women with advanced fibrosis or compensated cirrhosis. Future studies should assess whether reducing cholesterol intake, among women who consume an excessive amount, can decrease HCV-related mortality.

Survival analysis and predictors of mortality among adult HIV/AIDS patients initiated antiretroviral therapy from 2010 to 2015 in Dubti General Hospital, Afar, Ethiopia: A retrospective cohort study.

Background: Although antiretroviral therapy (ART) is well accepted to increase survival of patients with HIV/AIDS, AIDS related deaths continue to be a major problem in sub-Saharan Africa like Ethiopia. Studies have showed variable findings in the survival status of patients with HIV/AIDS initiating ART, and there was no such study in the study area. Therefore, purpose of this study was to determine the survival and predictors of mortality among HIV/AIDS patients starting taking ART in Dubti General Hospital, Afar, Ethiopia. Methods: A 5 year retrospective cohort study was performed among 702 HIV/AIDS patients aged ≥15 years that started ART between December 31, 2010, and December 31, 2015 in Dubti General Hospital, Afar, Ethiopia. A simple random sampling technique was used to select the study subjects from each WHO stage based stratum. Socio-demographic, clinical and survival status data were extracted by reviewing patients' records. Data were analyzed by using SPSS Version 21. Kaplan-Meier and Cox-regression models were used to estimate survival, and explore predictors of mortality. Variables with a p value of <0.05 in multivariate Cox regression analysis were considered statistically significant. Results: Among 702 study participants, 82 (11.7%) died during follow up, and the overall incidence rate of mortality was 5.81 per 100 person-years. Identified predictors of mortality were being not married (AHR = 3.71, 95% CI: 1.97-6.99), had no formal education (AHR = 2.33, 95% CI: 1.33-4.38), bedridden functional status (AHR = 5.91, 95% CI: 2.71-12.88), advanced WHO stage III and IV (AHR = 4.36, 95% CI: 2.20-8.64), BMI 16-18.4 kg/m2 (AHR = 3.03, 95% CI: 1.50-6.13), and BMI<16.0 kg/m2 (AHR = 5.47; 95% CI: 2.85-10.50), CD4 count ≤50 cells/mm3 (AHR = 6.62, 95% CI: 4.73-8.52), hemoglobin <8 g/dl (AHR = 5.21; 95% CI: 2.64-10.26), not used cotrimoxazole prophylaxis therapy (AHR = 2.78, 95% CI: 1.61-4.73), stavudine based regimen (AHR = 2.34, 95% CI: 1.32-4.13), and zidovudine based regimen (AHR = 2.49, 95% CI: 1.41-4.39). Conclusion: High mortality was observed in this cohort, and participants with stage III and IV, low CD4 count, low hemoglobin level, bed ridden functional status, low BMI should be closely monitored even with the scarce resources. In addition, the use of cotrimoxazole prophylaxis therapy should be more encouraged to increase survival.

Rate, risk factors and estimations of time to develop severe acute malnutrition after children receiving antiretroviral therapy at selected health facilities in northwest Ethiopia.

Severe acute malnutrition (SAM) affects up to 50 % of children with HIV, especially those who reside in resource-constrained healthcare setting like Ethiopia. During subsequent follow-up of children factors related to incidence of SAM after antiretroviral therapy (ART) is set on, however, there is no prior evidence. An institution-based retrospective cohort study was employed among 721 HIV-positive children from 1 January to 30 December 2021. Data were entered using Epi-Data version 3.1 and exported to STATA version 14 for analysis. Bi-variable and multivariable Cox-proportional hazard models were employed at 95 % confidence intervals to identify significant predictors for SAM. According to this result, the overall mean (±sd) age of the participants was found to be 9⋅83 (±3⋅3) years. At the end of the follow-up period, 103 (14⋅29 %) children developed SAM with a median time of 30⋅3 (13⋅4) months after ART initiation. The overall incidence density of SAM was found to be 5⋅64 per 100 child (95 % CI 4⋅68, 6⋅94). Children with CD4 counts below the threshold [AHR 2⋅6 (95 % CI 1⋅2, 2⋅9, P = 0⋅01)], disclosed HIV status [AHR 1⋅9 (95 % CI 1⋅4, 3⋅39, P = 0⋅03)] and Hgb level ≤10 mg/dl [AHR 1⋅8 (95 % CI 1⋅2, 2⋅9, P = 0⋅03)] were significant predictors for SAM. Significant predictors of acute malnutrition were having a CD4 count below the threshold, children who had previously reported their HIV status, and having haemoglobin <10 mg/dl. To ensure better health outcomes, healthcare practitioners should improve earlier nutritional screening and consistent counselling at each session of care.

Rate, risk factors and estimated time to develop attrition after under-five children started moderate acute malnutrition treatment in Gubalafto, North East Ethiopia.

Lost from follow-up, after starting moderate acute malnutrition (MAM) is an ongoing challenge of public health until the admitted children reached the standard weight of a reference child. Thus, the present study aimed to assess the rate and estimated time to attrition after under-five children started treatment for MAM in the Gubalafto district. A facility-based retrospective cohort study was employed among 487 participant children who had been managed targeted therapeutic feeding from 1 June 2018 to 1 May 2021. The overall mean (±sd) age of the participants' children was 22⋅1 (±12⋅6) months. At the end of the study period, 55 (11⋅46 %) under-five children developed attrition from the treatment after starting ready use of therapeutic feeding. After checking all assumptions, a multivariable Cox regression model was used to claim independent predictors for time to attritions. The median time of attrition after starting treatment of MAM was 13 (IQR ±9) weeks, with the overall incidence of attrition rate reported at 6⋅75 children Per Week (95 % CI 5⋅56, 9⋅6). In the final model of multivariable Cox regression, the hazard of attrition was significantly higher for children from rural residence (AHR 1⋅61; 95 % CI 1⋅18, 2⋅18; P = 0⋅001), and caregivers with their dyads did not get nutritional counselling at baseline (AHR 2⋅78; 95 % CI 1⋅34, 5⋅78; P = 0⋅001). The findings of the present study showed that nearly one in every eleven under-five children was attrition (lost to follow-up) in a median time of 13 (IQR ±9) weeks. We strongly recommended for caregivers provisions of diversification of daily nutrition supplementation of their dyads.

Dementia risk after major elective surgery based on the route of anaesthesia: A propensity score-matched population-based cohort study.

Background: Whether the route of anaesthesia is an independent risk factor for dementia remains unclear. Therefore, we conducted a propensity score-matched (PSM) population-based cohort study to compare dementia incidence among surgical patients undergoing different routes of anaesthesia. Methods: The inclusion criteria were being an inpatient >20 years of age who underwent major elective surgery, defined as those requiring GA without or with inhalation anaesthetics or regional anaesthesia, and being hospitalised for >1 day between Jan 1, 2008 and Dec 31, 2019 in Taiwan. Patients undergoing major elective surgery were categorised into three groups according to the type of anaesthesia administered: noninhalation anaesthesia, inhalation anaesthesia, and regional anaesthesia, matched at a 1:1 ratio. The incidence rate (IR) of dementia was determined. Findings: PSM yielded 63,750 patients (21,250 in the noninhalation anaesthesia group, 21,250 in the inhalation anaesthesia group, and 21,250 in the regional anaesthesia group). In the multivariate Cox regression analysis, the adjusted hazard ratios (aHRs; 95% confidence intervals) of dementia for the inhalation and noninhalation anaesthesia groups compared with the regional anaesthesia group were 20.16 (15.40-26.35; p < 0.001) and 18.33 (14.03-24.04; p < 0.001), respectively. The aHR of dementia for inhalation anaesthesia compared with noninhalation anaesthesia was 1.13 (1.03-1.22; p = 0.028). The IRs of dementia for the inhalation, noninhalation, and regional anaesthesia groups were 3647.90, 3492.00, and 272.99 per 100,000 person-years, respectively. Interpretation: In this population based cohort study, the incidence of dementia among surgical patients undergoing general anaesthesia was higher than among those undergoing regional anaesthesia. Among patients undergoing general anaesthesia, inhalation anaesthesia was associated with a higher risk of dementia than noninhalation anaesthesia. Our results should be confirmed in a randomised controlled trial. Funding: The study was partially supported by Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital (Funding Number: 10908, 10909, 11001, 11002, 11003, 11006, and 11013).

Hepatitis B virus infection combined with nonalcoholic fatty liver disease: Interaction and prognosis.

Hepatitis B virus (HBV) infection is still one kind of the infectious diseases that seriously threaten human health. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. HBV infection complicated with NAFLD is increasingly common. This review mainly describes the interaction between HBV infection and NAFLD, the interaction between steatosis and antiviral drugs, and the prognosis of HBV infection complicated with NAFLD. Most studies suggest that HBV infection may reduce the incidence of NAFLD. NAFLD can promote the spontaneous clearance of hepatitis B surface antigen (HBsAg), but whether it affects antiviral efficacy has been reported inconsistently. HBV infection combined with NAFLD can promote the progression of liver fibrosis, especially in patients with severe steatosis. The outcome of HBV infection combined with NAFLD predisposing to the progression of HCC remains controversial.

Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease.

Background & Aims: Ammonia levels predicted hospitalisation in a recent landmark study not accounting for portal hypertension and systemic inflammation severity. We investigated (i) the prognostic value of venous ammonia levels (outcome cohort) for liver-related outcomes while accounting for these factors and (ii) its correlation with key disease-driving mechanisms (biomarker cohort). Methods: (i) The outcome cohort included 549 clinically stable outpatients with evidence of advanced chronic liver disease. (ii) The partly overlapping biomarker cohort comprised 193 individuals, recruited from the prospective Vienna Cirrhosis Study (VICIS: NCT03267615). Results: (i) In the outcome cohort, ammonia increased across clinical stages as well as hepatic venous pressure gradient and United Network for Organ Sharing model for end-stage liver disease (2016) strata and were independently linked with diabetes. Ammonia was associated with liver-related death, even after multivariable adjustment (adjusted hazard ratio [aHR]: 1.05 [95% CI: 1.00-1.10]; p = 0.044). The recently proposed cut-off (≥1.4 × upper limit of normal) was independently predictive of hepatic decompensation (aHR: 2.08 [95% CI: 1.35-3.22]; p <0.001), non-elective liver-related hospitalisation (aHR: 1.86 [95% CI: 1.17-2.95]; p = 0.008), and - in those with decompensated advanced chronic liver disease - acute-on-chronic liver failure (aHR: 1.71 [95% CI: 1.05-2.80]; p = 0.031). (ii) Besides hepatic venous pressure gradient, venous ammonia was correlated with markers of endothelial dysfunction and liver fibrogenesis/matrix remodelling in the biomarker cohort. Conclusions: Venous ammonia predicts hepatic decompensation, non-elective liver-related hospitalisation, acute-on-chronic liver failure, and liver-related death, independently of established prognostic indicators including C-reactive protein and hepatic venous pressure gradient. Although venous ammonia is linked with several key disease-driving mechanisms, its prognostic value is not explained by associated hepatic dysfunction, systemic inflammation, or portal hypertension severity, suggesting direct toxicity. Impact and implications: A recent landmark study linked ammonia levels (a simple blood test) with hospitalisation/death in individuals with clinically stable cirrhosis. Our study extends the prognostic value of venous ammonia to other important liver-related complications. Although venous ammonia is linked with several key disease-driving mechanisms, they do not fully explain its prognostic value. This supports the concept of direct ammonia toxicity and ammonia-lowering drugs as disease-modifying treatment.

Multimorbidity Burden and Incident Heart Failure Among People With and Without HIV: The HIV-HEART Study.

Objective: To examine the association between multimorbidity burden and incident heart failure (HF) among people with HIV (PWH) and people without HIV (PWoH). Patients and Methods: The HIV-HEART study is a retrospective cohort study that included adult PWH and PWoH aged 21 years or older at Kaiser Permanente between 2000 and 2016. Multimorbidity burden was defined by the baseline prevalence of 22 chronic conditions and was categorized as 0-1, 2-3, and 4 or more comorbidities on the basis of distribution of the overall population. People with HIV and PWoH were followed for a first HF event, all-cause death, or up to the end of follow-up on December 31, 2016. Using Cox proportional hazard regression, hazard ratios and 95% CIs were calculated to examine the association between multimorbidity burden and incident HF among PWH and PWoH, separately. Results: The prevalences of 0-1, 2-3, and 4 or more comorbidities were 83.3%, 13.0%, and 3.7% in PWH (n=38,868), and 82.2%, 14.3%, and 3.5% in PWoH (n=386,586), respectively. After multivariable adjustment, compared with people with 0-1 comorbidities, the hazard ratios of incident HF associated with 2-3 and 4 or more comorbidities were 1.33 (95% CI, 1.04-1.71) and 2.41 (95% CI, 1.78-3.25) in PWH and 2.10 (95% CI, 1.92-2.29) and 4.09 (95% CI, 3.64-4.61) in PWoH, respectively. Conclusion: Multimorbidity was associated with a higher risk of incident HF among PWH and PWoH, with more prominent associations in PWoH and certain patient subgroups. The identification of specific multimorbidity patterns that contribute to higher HF risk in PWH may lead to future preventative strategies.

Characteristics and Factors Associated With Mortality in Patients With Coronavirus Disease 2019 and Pneumothorax.

Objective: To describe the incidence, clinical characteristics, and factors associated with mortality in patients hospitalized for coronavirus disease 2019 (COVID-19) in whom pneumothorax developed. Patients and Methods: This study was a retrospective analysis conducted using a large administrative database of adult patients hospitalized for COVID-19 in the United States from February 1, 2020, to June 10, 2021. We characterized the clinical features of patients in whom pneumothorax developed and the factors associated with mortality and stratified pneumothorax by the timing of the initiation of invasive mechanical ventilation (IMV) and by the time of hospital admission (early versus late). Results: A total of 811,065 adult patients had a positive test result for severe acute respiratory syndrome coronavirus 2, of whom 103,858 (12.8%) were hospitalized. Pneumothorax occurred in 1915 patients (0.24% overall and 1.84% among hospitalized patients). Over time, the use of steroids and remdesivir increased, whereas the use of IMV, pneumothorax rates, and mortality decreased. The clinical characteristics associated with pneumothorax were male sex; the receipt of IMV; and treatment with steroids, remdesivir, or convalescent plasma. Most patients with pneumothorax received IMV, but pneumothorax developed before the initiation of IMV and/or early during hospitalization in majority. Multivariable analysis revealed that pneumothorax increased the risk of death (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.06-1.24). In patients who did not receive IMV, pneumothorax led to nearly twice the mortality (aHR, 1.99; 95% CI, 1.56-2.54). Increased mortality was also noted when pneumothorax occurred before IMV (aHR, 1.37; 95% CI, 1.11-1.69) and within 7 days of hospital admission (aHR, 1.60; 95% CI, 1.29-1.98). Conclusion: The overall incidence of pneumothorax in patients hospitalized for COVID-19 was low. Pneumothorax is an independent risk factor for death.

Characteristics and Outcomes of Patients with Scleritis in the IRIS® Registry (Intelligent Research in Sight) Database.

Purpose: To report patient characteristics and factors associated with poor visual acuity and abnormal intraocular pressure (IOP) in patients with scleritis in the American Academy of Ophthalmology's IRIS® Registry (Intelligent Research in Sight). Design: Retrospective cohort study. Participants: Patients in the IRIS Registry with at least 3 office visits associated with an International Classification of Diseases scleritis code from 2013 through 2019. Methods: We evaluated demographic and clinical characteristics in scleritis and scleritis subtype cohorts. We conducted Cox proportional hazards and multiple logistic regression analyses to assess associations with poor best-corrected visual acuity (BCVA), vision loss, and IOP abnormalities. Main Outcome Measures: Patient characteristics, BCVA of 0.6 logarithm of the minimum angle of resolution (logMAR) or more, BCVA worsened by more than 3 logMAR units 6 months after presentation, IOP of 30 mmHg or more, and IOP of 5 mmHg or less. Results: In this cohort of 111 314 patients with scleritis, the mean ± standard deviation age was 58.5 ± 16.6 years, 66% were women, and 30% had bilateral scleritis. Patients with scleromalacia perforans were older and more likely to have bilateral disease. Multiple logistic regression analysis identified factors with increased odds for poor presenting BCVA (older age, male sex, Black race, Hispanic ethnicity, smoking, and scleritis subtypes) and at least 3 lines of vision loss 6 months after initial scleritis diagnosis (older age, smoking, and anterior scleritis). Cox proportional hazards regression modeling of BCVA of 0.6 logMAR or more showed older age (adjusted hazard ratio [aHR] per 10-year unit, 1.11), Black race (aHR, 1.19), Hispanic ethnicity (aHR, 1.22), active smoking (aHR, 1.39), former smoking (aHR, 1.26), and certain scleritis subtypes increase the risk of poor visual acuity development (P < 0.001 for all). Older age, male sex, Black race, Hispanic ethnicity, smoking, and scleritis subtypes increased the odds of IOP abnormality. Conclusions: Older age, Black or Hispanic ancestry, smoking, and specific scleritis subtypes are risk factors for worse visual and IOP outcomes in patients with scleritis in the IRIS Registry. Closer follow-up may be appropriate for older, Black, or Hispanic patients with scleritis; smokers should receive smoking cessation assistance.

Time to recovery from Covid-19 and its associated factors among patients hospitalized to the treatment center in South Central Ethiopia.

Coronavirus outbreak was a public health emergency. The surge of new confirmed cases and deaths was observed in developing countries due to the occurrence of new variants. However, factors associated with the duration of recovery among admitted patients remained uncertain. Therefore, we assessed factors associated with time to recovery from Covid-19 among hospitalized patients at the treatment center in South Central, Ethiopia. We employed a retrospective cross-sectional study among 422 patients hospitalized at Bokoji Hospital treatment center with Covid-19 from July 1, 2020, through October 30, 2021. Data were entered, coded, and analyzed using SPSS 26 version. We computed the survival probability using the Kaplan Meier method and determined factors associated with time to recovery using Cox regression analysis. Finally, the interpretation of adjusted hazard ratio (AHR) with 95% Confidence Interval (CI) and P-values less than 0.05 were declared as statistically significant. Our study found that the median time to recovery from Covid-19 infection of 13 days, with an IQR of 9-17 days. In multivariate Cox regression, ≥ 60 years old (AHR = 0.66; 95% CI: 0.49, 0.895), chronic pulmonary disease (AHR = 0.67; 95% CI: 0.455, 0.978), Male (AHR = 0.77; 95% CI: 0.611, 0.979), and being on Intranasal oxygen care (AHR = 0.56; 95% CI: 0.427-0.717) were significantly associated with time to recovery. Thus, health providers in treatment centers should give strict follow-up and priority for elders, patients with underlying diseases, and under supportive treatment during case management.

Trends and three-year outcomes of hepatitis C virus-viremic donor heart transplant for hepatitis C virus-seronegative recipients.

Objective: Heart transplants (HTs) from hepatitis C virus (HCV)-viremic donors to HCV-seronegative recipients (HCV D+/R-) have good 6-month outcomes, but practice uptake and long-term outcomes overall and among candidates on mechanical circulatory support (MCS) have yet to be established. Methods: Using the Scientific Registry of Transplant Recipients, we identified US adult HCV-seronegative HT recipients (R-) from 2015 to 2021. We classified donors as HCV-seronegative (D-) or HCV-viremic (D+). We used multivariable regression to compare post-HT extracorporeal membranous oxygenation, dialysis, pacemaker, acute rejection, and risk of post-HT mortality between HCV D+/R- and HCV D-/R-. Models were adjusted for donor, recipient, and transplant characteristics and center HT volume. We performed subgroup analyses of recipients bridged with MCS. Results: From 2015 to 2021, the number of HCV D+/R- HT increased from 1 to 181 and the number of centers performing HCV D+/R- HT increased from 1 to 60. Compared with HCV D-/R- recipients, HCV D+/R- versus D-/R- recipients overall and among patients bridged with MCS had similar odds of post-HT extracorporeal membranous oxygenation, dialysis, pacemaker, and acute rejection; and mortality risk at 30 days, 1 year, and 3 years (all P > .05). High center HT volume but not HCV D+/R- volume (<5 vs >5 in any year) was associated with lower mortality for HCV D+/R- HT. Conclusions: HCV D+/R- and D-/R- HT have similar outcomes at 3 years' posttransplant. These results underscore the opportunity provided by HCV D+/R- HT, including among the growing population bridged with MCS, and the potential benefit of further expanding use of HCV+ allografts.

In-hospital mortality and severe outcomes after hospital discharge due to COVID-19: A prospective multicenter study from Brazil.

Background: We evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort. Methods: This prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed. Findings: 1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs<40 years; age=60-69 years-aHR=1.89 (95%CI,1.08-3.32); age=70-79 years-aHR=2.52 (95%CI,1.42-4.45); age≥80-aHR=2.90 (95%CI 1.54-5.47)]; noninvasive or mechanical ventilation at admission [vs facial-mask or none; aHR=1.69 (95%CI 1.30-2.19)]; SAPS-III score≥57 [vs<57; aHR=1.47 (95%CI 1.13-1.92)] and SOFA score≥10 [vs <10; aHR=1.51 (95%CI 1.08-2.10)] were independently associated with in-hospital mortality. A total of 65 individuals [6.7% (95%CI 5.3-8.4)] had a rehospitalization or death [rate=323 (95%CI 250-417) per 1000 person-years] in a median time of 52 (range 1-280) days post-hospital discharge. Age ≥ 60 years [vs <60, aHR=2.13 (95%CI 1.15-3.94)] and SAPS-III ≥57 at admission [vs <57, aHR=2.37 (95%CI 1.22-4.59)] were independently associated with rehospitalization or death after hospital discharge. Interpretation: High in-hospital mortality rates due to COVID-19 were observed and elderly people remained at high risk of rehospitalization and death after hospital discharge. Funding: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa INOVA-FIOCRUZ.

Risk associations of long-term HbA1c variability and obesity on cancer events and cancer-specific death in 15,286 patients with diabetes - A prospective cohort study.

BACKGROUND: Obesity, cancer and diabetes frequently coexist. The association of glycaemic variability (GV) and obesity with cancer events had not been explored in diabetes. METHODS: In the prospective Hong Kong Diabetes Register cohort (1995-2019), we used cox proportional hazards models to examine the risk associations of GV with all-site cancer (primary outcome) and cause-specific death (secondary outcome). We also explored the joint association of obesity and GV with these outcomes and site-specific cancer. We expressed GV using HbA1c variability score (HVS) defined as percentage of HbA1c values varying by 0.5% compared with values in preceding visit. FINDINGS: We included 15,286 patients (type 2 diabetes: n=15,054, type 1 diabetes: n=232) with ≥10 years of diabetes and ≥3 years of observation (51.7% men, age (mean±SD): 61.04±10.73 years, HbA1c: 7.54±1.63%, body mass index [BMI]: 25.65±3.92 kg/m2, all-site cancer events: n=928, cancer death events: n=404). There were non-linear relationships between HVS and outcomes but there was linearity within the high and low HVS groups stratified by the median (IQR) value of HVS (42.31 [27.27, 56.28]). In the high HVS group, the adjusted hazard ratios (aHR) of each SD of HVS was 1.15 (95% CI: 1.04, 1.26) for all-site cancer (n=874). The respective aHRs for breast (n=77), liver (n=117) and colorectal (n=184) cancer were 1.44 (1.07, 1.94), 1.37 (1.08, 1.74), and 1.09 (0.90, 1.32). In the high GV group, the respective aHRs were 1.21 (1.06, 1.39), 1.27 (1.15, 1.40), and 1.15 (1.09, 1.22) for cancer, vascular, and noncancer nonvascular death. When stratified by obesity (BMI ≥25 kg/m2), the high HVS & obese group had the highest aHRs of 1.42 (1.16, 1.73), 2.44 (1.24, 4.82), and 2.63 (1.45, 4.74) respectively for all-site, breast, and liver cancer versus the low GV & non-obese group. The respective aHRs were 1.45 (1.07, 1.96), 1.47 (1.12, 1.93), and 1.35 (1.16, 1.57) for cancer, vascular, and noncancer nonvascular death. INTERPRETATION: Obesity and high GV were associated with increased risk of all-site, breast, liver cancer, and cancer-specific death in T2D. FUNDING: The Chinese University of Hong Kong Diabetes Research Fund.

Novel machine learning models outperform risk scores in predicting hepatocellular carcinoma in patients with chronic viral hepatitis.

BACKGROUND & AIMS: Accurate hepatocellular carcinoma (HCC) risk prediction facilitates appropriate surveillance strategy and reduces cancer mortality. We aimed to derive and validate novel machine learning models to predict HCC in a territory-wide cohort of patients with chronic viral hepatitis (CVH) using data from the Hospital Authority Data Collaboration Lab (HADCL). METHODS: This was a territory-wide, retrospective, observational, cohort study of patients with CVH in Hong Kong in 2000-2018 identified from HADCL based on viral markers, diagnosis codes, and antiviral treatment for chronic hepatitis B and/or C. The cohort was randomly split into training and validation cohorts in a 7:3 ratio. Five popular machine learning methods, namely, logistic regression, ridge regression, AdaBoost, decision tree, and random forest, were performed and compared to find the best prediction model. RESULTS: A total of 124,006 patients with CVH with complete data were included to build the models. In the training cohort (n = 86,804; 6,821 HCC), ridge regression (area under the receiver operating characteristic curve [AUROC] 0.842), decision tree (0.952), and random forest (0.992) performed the best. In the validation cohort (n = 37,202; 2,875 HCC), ridge regression (AUROC 0.844) and random forest (0.837) maintained their accuracy, which was significantly higher than those of HCC risk scores: CU-HCC (0.672), GAG-HCC (0.745), REACH-B (0.671), PAGE-B (0.748), and REAL-B (0.712) scores. The low cut-off (0.07) of HCC ridge score (HCC-RS) achieved 90.0% sensitivity and 98.6% negative predictive value (NPV) in the validation cohort. The high cut-off (0.15) of HCC-RS achieved high specificity (90.0%) and NPV (95.6%); 31.1% of patients remained indeterminate. CONCLUSIONS: HCC-RS from the ridge regression machine learning model accurately predicted HCC in patients with CVH. These machine learning models may be developed as built-in functional keys or calculators in electronic health systems to reduce cancer mortality. LAY SUMMARY: Novel machine learning models generated accurate risk scores for hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis. HCC ridge score was consistently more accurate than existing HCC risk scores. These models may be incorporated into electronic medical health systems to develop appropriate cancer surveillance strategies and reduce cancer death.

Analysis of tumor response and clinical factors associated with vitiligo in patients receiving anti-programmed cell death-1 therapies for melanoma: A cross-sectional study.

BACKGROUND: Clinical factors associated with vitiligo in patients receiving anti-programmed cell death-1 (PD-1) remain unknown. OBJECTIVE: To better characterize the occurrence of vitiligo in patients receiving anti-PD-1. METHODS: The present single-center ambispective cohort study included patients with melanoma treated with anti-PD-1. Progression-free survival, overall survival, and objective tumor response were compared between patients with and those without vitiligo using Kaplan-Meier curves and the log-rank test. Demographic and clinical factors associated with vitiligo were evaluated using multivariate logistic regression. RESULTS: Of the 457 patients included in the study, vitiligo developed in 85 patients. The clinical presentation of vitiligo consisted of the presence of ovalar and multiple flecked white macules, mainly located on chronic sun-exposed areas. The presence of vitiligo was associated with a significant improvement in overall survival and progression-free survival (P < .001). A Cox proportional hazards model estimation demonstrated markedly improved survival in patients with vitiligo compared with those without vitiligo (aHR [overall survival], 0.20; 95% CI, 0.12-0.33; P < .001; and aHR [progression-free survival], 0.33; 95% CI, 0.23-0.47; P < .001). In the multivariate logistic regression analyses, men showed an independent increased risk of the development of vitiligo (odds ratio, 1.66). In contrast, the presence of pulmonary metastases was found to be an independent factor associated with a reduced risk of the development of vitiligo (odds ratio, 0.50). LIMITATIONS: Single-center ambispective cohort. CONCLUSION: Vitiligo in patients receiving anti-PD-1 for advanced melanoma is associated with a better outcome. A gender effect associated with the development of vitiligo will need further investigation.

Prevalence and Prognostic Significance of Frailty in Asian Patients With Heart Failure: Insights From ASIAN-HF.

Background: Frailty is common in patients with heart failure (HF) and can adversely impact outcomes. Objectives: This study examined the prevalence of frailty among Asian patients with HF, its association with 1-year outcomes, and if race-ethnicity, HF subtypes, and sex modify this relationship. Methods: In the multinational ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, a baseline frailty index (FI) was constructed using a cumulative deficits approach with 48 baseline variables, and patients were followed for the 1-year primary outcome of all-cause death or HF hospitalization. Results: Among 3,881 participants (age 61 ± 13 years, 27% female), the mean FI was 0.28 ± 0.11, and 69% were frail (FI >0.21). Higher FI was associated with older age, Malay ethnicity, and Southeast Asian residency. While comorbidities were more frequent in frail patients (by definition), body mass index was not different across frailty classes. Compared with FI class 1 (<0.21, nonfrail), FI class 2 (0.21-0.31) and FI class 3 (>0.31) had increased risk of the 1-year composite outcome (hazard ratios of 1.84 [95% confidence interval (CI): 1.42-2.38] and 4.51 [95% CI: 3.59-5.67], respectively), even after multivariable adjustment (adjusted hazard ratios of 1.49 [95% CI: 1.13-1.97] and 2.69 [95% CI: 2.06-3.50], respectively). Race-ethnicity modified the association of frailty with the composite outcome (P interaction = 0.0097), wherein the impact of frailty was strongest among Chinese patients. The association between frailty and outcomes did not differ between men and women (P interaction = 0.186) or for HF with reduced ejection fraction versus HF with preserved ejection fraction (P interaction = 0.094). Conclusions: Most Asian patients with HF are frail despite relatively young age. Our results reveal specific ethnic (Malay) and regional (Southeast Asia) predisposition to frailty and highlight its prognostic importance, especially in Chinese individuals. (ASIAN HF Registry, A Prospective Observational Study [ASIANHF]; NCT01633398).

Incidence of relapse following a new approach to simplifying and optimising acute malnutrition treatment in children aged 6-59 months: a prospective cohort in rural Northern Burkina Faso.

The present study aimed to determine the 3-month incidence of relapse and associated factors among children who recovered under the Optimising treatment for acute MAlnutrition (OptiMA) strategy, a MUAC-based protocol. A prospective cohort of children successfully treated for acute malnutrition was monitored between April 2017 and February 2018. Children were seen at home by community health workers (CHWs) every 2 weeks for 3 months. Relapse was defined as a child who had met OptiMA recovery criteria (MUAC ≥ 125 mm for two consecutive weeks) but subsequently had a MUAC < 125 mm at any home visit. Cumulative incidence and incidence rates per 100 child-months were estimated. Multivariable survival analysis was conducted using a shared frailty model with a random effect on health facilities to identify associated factors. Of the 640 children included, the overall 3-month cumulative incidence of relapse was 6⋅8 % (95 % CI 5⋅2, 8⋅8). Globally, the incidence rate of relapse was 2⋅5 (95 % CI 1⋅9, 3⋅3) per 100 child-months and 3⋅7 (95 % CI 1⋅9, 6⋅8) per 100 child-months among children admitted with a MUAC < 115 mm. Most (88⋅6 %) relapses were detected early when MUAC was between 120 and 124 mm. Relapse was positively associated with hospitalisation, with an adjusted hazard ratio (aHR) of 2⋅06 (95 % CI 1⋅01, 4⋅26) for children who had an inpatient stay at any point during treatment compared with children who did not. The incidence of relapse following recovery under OptiMA was relatively low in this context, but the lack of a standard relapse definition does not allow for comparison across settings Closer follow-up with caretakers whose children are admitted with MUAC < 115 mm or required hospitalisation during treatment should be considered in managing groups at high risk of relapse. Training caretakers to screen their children for relapse at home using MUAC could be more effective at detecting early relapse, and less costly, than home visits by CHWs.

Cardiovascular Manifestations From Therapeutic Radiation: A Multidisciplinary Expert Consensus Statement From the International Cardio-Oncology Society.

Radiation therapy is a cornerstone of cancer therapy, with >50% of patients undergoing therapeutic radiation. As a result of widespread use and improved survival, there is increasing focus on the potential long-term effects of ionizing radiation, especially cardiovascular toxicity. Radiation therapy can lead to atherosclerosis of the vasculature as well as valvular, myocardial, and pericardial dysfunction. We present a consensus statement from the International Cardio-Oncology Society based on general principles of radiotherapy delivery and cardiovascular risk assessment and risk mitigation in this population. Anatomical-based recommendations for cardiovascular management and follow-up are provided, and a priority is given to the early detection of atherosclerotic vascular disease on imaging to help guide preventive therapy. Unique management considerations in radiation-induced cardiovascular disease are also discussed. Recommendations are based on the most current literature and represent a unanimous consensus by the multidisciplinary expert panel.