Time to develop severe acute malnutrition and its predictors among children living with HIV in the era of test and treat strategies at South Gondar hospitals, northwest, Ethiopia, 2021: a multicentre retrospective cohort study

Background Although severe acute malnutrition is a major public issue among HIV infected children, there is no prior evidence in Ethiopia. Hence, this study aims to assess the time to develop severe acute malnutrition and its predictors among children living with human immunodeficiency virus in Ethiopia, 2012. Methods An institution based retrospective cohort study was conducted in South Gondar hospitals among 363 HIV infected children from February 10, 2014, to January 7, 2021. Epi-data version 3.1 was used to enter data, which was then exported to STATA version 14 for analysis. Besides, WHO (World Health Organization) Anthro Plus software was used to assess the nutritional status of the children. A standardized data extraction tool was used to collect the data. The Kaplan Meier survival curve was used to estimate the median survival time. The Cox-proportional hazard model assumption was checked via the Schoenfeld residual ph test and a stph plot. Bivariable and multivariable Cox proportional hazard models were employed at 95% confidence intervals (CI). A variable having a p-value < 0.05 was considered a statistically significant predictor of severe acute malnutrition. Results A total of 363 children living with HIV, 97 (26.72%) developed severe acute malnutrition during the follow-up period. The overall incidence rate was 5.4 (95% CI: 4.7–5.9) person per year with a total of 21, 492 months or 1791 years of observation. Moreover, the median survival time was 126 months. Treatment failure [AHR =3.4 (95% CI: 2.05–5.75)], CD4 count below threshold [AHR =2.5 (95% CI: 1.64–3.95)], and WHO stage III & IV [AHR =2.9 (95% CI: 1.74–4.73)] were all significant predictors of severe acute malnutrition. Conclusion The time to develop severe acute malnutrition was found to be very low. Treatment failure, CD4 count below threshold, and WHO stage III were all significant predictors of severe acute malnutrition. Hence, emphasizing those predictor variables is essential for preventing and controlling the occurrence of severe acute malnutrition among HIV infected children.

Pigmentary abnormality without significant drusen as a risk factor for late age-related macular degeneration

We investigated the incidence and risk factors of late age-related macular degeneration (AMD) in the fellow eye (FE) without significant drusen of patients with unilateral exudative macular neovascularization (MNV). In this retrospective study, 241 eligible patients who were followed-up for more than 3 years were enrolled. We analyzed the incidence and hazard ratios (HRs) of late AMD in the FE according to demographic and ophthalmologic variables. Hypopigmentation on color fundus photography (CFP) corresponds to shallow irregular RPE elevation (SIRE), so-called “double-layer sign” and/or “attenuation or disruption of RPE and/or ellipsoid zone” on OCT. The 5-year incidence of FE exudative MNV conversion was 8.6%. The 5-year incidence of FE exudative MNV of large hypopigmentation (≥ 0.5 disc area; DA) and small hypopigmentation (< 0.5 DA) on CFP, and SIRE (≥ 1000 µm) and small RPE elevation (< 1000 µm) on OCT were 36.2%, 14.2%, 55.0%, and 15.6%, respectively. The multivariate Cox proportional hazard model revealed that large hypopigmentation, small hypopigmentation, SIRE, and small RPE elevation showed HRs of 23.230, 8.037, 132.589, and 41.823 for FE exudative MNV occurrence, respectively. Hypopigmentation on CFP and SIRE on OCT could represent the same lesion. Even small hypopigmentation and small RPE elevation were significant risk factors for progression to exudative MNV.

MicroRNAs as biomarkers for prostate cancer prognosis: a systematic review and a systematic reanalysis of public data

Background Reliable prognostic biomarkers to distinguish indolent from aggressive prostate cancer (PCa) are lacking. Many studies investigated microRNAs (miRs) as PCa prognostic biomarkers, often reporting inconsistent findings. We present a systematic review of these; also systematic reanalysis of public miR-profile datasets to identify tissue-derived miRs prognostic of biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Methods Independent PubMed searches were performed for relevant articles from January 2007 to December 2019. For the review, 128 studies were included. Pooled-hazard-ratios (HRs) for miRs in multiple studies were calculated using a random-effects model (REM). For the reanalysis, five studies were included and Cox proportional-hazard models, testing miR association with BCR, performed for miRs profiled in all. Results Systematic review identified 120 miRs as prognostic. Five (let-7b-5p, miR-145-5p, miR152-3p, miR-195-5p, miR-224-5p) were consistently associated with progression in multiple cohorts/studies. In the reanalysis, ten (let-7a-5p, miR-148a-3p, miR-203a-3p, miR-26b-5p, miR30a-3p, miR-30c-5p, miR-30e-3p, miR-374a-5p, miR-425-3p, miR-582-5p) were significantly prognostic of BCR. Of these, miR-148a-3p (HR = 0.80/95% CI = 0.68-0.94) and miR-582-5p (HR = 0.73/95% CI = 0.61-0.87) were also reported in prior publication(s) in the review. Conclusions Fifteen miRs were consistently associated with disease progression in multiple publications or datasets. Further research into their biological roles is warranted to support investigations into their performance as prognostic PCa biomarkers.

Does Adding Adverse Pregnancy Outcomes Improve the Framingham Cardiovascular Risk Score in Women? Data from the Tehran Lipid and Glucose Study

Background Limited and conflicting evidence is available regarding the predictive value of adding adverse pregnancy outcomes (APOs) to established cardiovascular disease (CVD) risk factors. Hence, the objective of this study was to determine whether adding APOs to the Framingham risk score improves the prediction of CVD events in women. Methods and Results Out of 5413 women who participated in the Tehran Lipid and Glucose Study, 4013 women met the eligibility criteria included for the present study. The exposure and the outcome variables were collected based on the standard protocol. Cox proportional hazard model was used to evaluate the association of APOs and CVDs. The variant of C‐statistic for survivals and reclassification of subjects into Framingham risk score categories after adding APOs was reported. Out of the 4013 eligible subjects, a total of 1484 (36.98%) women reported 1 APO, while 395 (9.84%) of the cases reported multiple APOs. Univariate proportional hazard Cox models showed the significant relations between CVD events and APOs. The enhanced model had a higher C‐statistic indicating more acceptable discrimination as well as a slight improvement in discrimination (C‐statistic differences: 0.0053). Moreover, we observed a greater risk of experiencing a CVD event in women with a history of multiple APOs compared with cases with only 1 APO (1 APO: hazard ratio [HR] = 1.22; 2 APOs: HR; 1.94; ≥3 APOs: HR = 2.48). Conclusions Beyond the established risk factors, re‐estimated CVDs risk by adding APOs to the Framingham risk score may improve the accurate risk estimation of CVD. Further observational studies are needed to confirm our findings.

Clustering-based COPD Subtypes Have Distinct Longitudinal Outcomes and Multi-omics Biomarkers

Introduction: Chronic obstructive pulmonary disease (COPD) can progress across several domains, complicating the identification of the determinants of disease progression. In our previous work, we applied k-means clustering to spirometric and chest radiologic measures to identify four COPD-related subtypes: "Relatively resistant smokers (RRS)", "mild upper lobe predominant emphysema (ULE)", "airway-predominant disease (AD)", and "severe emphysema (SE)". In the current study, we examined longitudinal spirometric and radiologic emphysema changes and prospective risks of COPD exacerbations, incident comorbidities, and mortality of these clusters. We also compared their associations to protein and transcriptomic biomarkers. Methods: We included 8,266 non-Hispanic white and African-American smokers from the COPDGene study. We used linear regression to investigate associations to five-year prospective changes in spirometric and radiologic measures and to plasma protein and blood gene expression levels. We used Cox-proportional hazard modeling to test for associations to prospective exacerbations, comorbidities, and mortality. Results: The RRS, ULE, AD, and SE clusters represented 39%, 15%, 26%, and 20% of the studied cohort at baseline, respectively. The SE cluster had the greatest 5-year FEV1 and emphysema progression, and the highest risks of exacerbations, cardiovascular disease (CVD), and mortality. The AD cluster had the highest diabetes risk. After adjustments, only the ULE and AD clusters had elevated CVD mortality risks, while only the ULE cluster had the highest cancer-related mortality risk. These clusters also demonstrated differential protein and gene expression biomarker associations. Conclusion: COPD k-means subtypes demonstrate varying rates of disease progression, prospective comorbidities, mortality, and associations to proteomic and transcriptomic biomarkers.

Effects of Reversal Technique for Neuromuscular Paralysis on Time to Recovery of Bowel Function after Craniotomy

Background Non-depolarizing neuromuscular blockade can be reversed with neostigmine/glycopyrrolate or sugammadex. We test the hypothesis that sugammadex is associated with earlier postoperative recovery of bowel function (first bowel movement, BM). Methods In adult patients undergoing craniotomy from 2016 to 2019, we identified time of first postoperative BM after receiving neostigmine/glycopyrrolate or sugammadex to reverse neuromuscular blockade. Logistic and proportional hazard regression, with and without inverse probability of treatment weighting (IPTW), were used to assess whether sugammadex is associated with earlier recovery of bowel function. Results Seven hundred and thirty-one patients underwent craniotomy, 323 (44.2%) received neostigmine/glycopyrrolate, and 408 (55.8%) sugammadex. From logistic regression analysis, the proportion of patients having a BM within the first 24 and 48 hours was higher in sugammadex group (unadjusted OR [95% CI]) 1.79 [1.16 to 2.77] P = .009; and 1.45 [1.08 to 1.94] P = .014; IPTW adjusted OR [95% CI]) 1.58 [.95, 2.61] P = .078; and 1.38 [.95 to 2.02] P = .095 for 24 and 48 h, respectively). From proportional hazards regression, sugammadex was associated with improved bowel function recovery (unadjusted hazard ratio (HR) [95% CI] 1.35 [1.08, 1.68], P = .008; IPTW adjusted HR 1.29 [.97 to 1.71], P = .076). Conclusion Patients undergoing craniotomy who had neuromuscular blockade reversed with sugammadex may have earlier recovered bowel function compared to patients reversed with neostigmine/glycopyrrolate.

Reduced Incidence of Stroke in Patients with Gout Using Benzbromarone

Gout is strongly associated with the incidence of atherosclerotic events, including stroke and myocardial infarction. Considering the increased prevalence of stroke in the population with gout, the aim of this study was to evaluate the effects of benzbromarone, a uricosuric agent, on the incidence of stroke in the population with gout. We used data from the Taiwanese National Health Insurance Registration Database (NHIRD). The benzbromarone user cohort included 15,143 patients; each patient was age- and sex-matched with one non-user randomly selected from the population with gout. Cox proportional hazard regression analysis was conducted to estimate the effects of benzbromarone on the incidence of stroke in the population with gout. The incidence of stroke was significantly lower in benzbromarone users than in benzbromarone non-users. The HR for the incidence of stroke was lower in male benzbromarone users than in non-users. An analysis of three age groups (<40, 40–59, and ≥60 years) indicated that the HRs in those aged 40–59 years and ≥60 years were significantly lower among benzbromarone users than non-users. In the population with gout, the incidence of stroke was lower in benzbromarone users than in benzbromarone non-users.