Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda : a prospective interventional open-label cohort study

Funding: We acknowledge the funding support from the Government of the Republic of Uganda through the Makerere University Research and Innovations Fund (Mak-RIF).Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.Publisher PDFPeer reviewe

Relationship between maternal and/or newborn cholesterol levels and neonatal septicemia: protocol for a Ugandan cohort of mother-newborn pairs.

BACKGROUND: Many aspects of microbial dissemination appear to vary with host cholesterol levels. Since neonatal septicemia remains a leading cause of newborn admissions and mortality in resource-limited settings, the contribution of abnormal cholesterol levels in maternal and/or newborn blood to the risk of neonatal septicemia and outcome requires elucidation. We aim to determine a relationship between maternal serum and neonatal cord blood cholesterol levels and neonatal septicemia. METHODS: This will be a mother-newborn pair cohort study. Approximately 353 pregnant women who are eligible and consent to participate in the study will have blood drawn for a lipid profile. Upon delivery, we will analyse the cord blood cholesterol of their newborns and follow them for 28 days to determine whether the infants develop clinical signs and symptoms suggestive of neonatal septicemia. Relative risk will be used to determine the association between cholesterol and newborn septicemia. Poisson regression will be used to estimate the relative risk (with 95% confidence intervals) of developing septicemia. DISCUSSION: Findings from our study will contribute evidence to support the inclusion of lipid profile screening for pregnant women and newborns. Our study will determine whether newborns with abnormal cholesterol or those born to mothers with abnormal cholesterol will require rigorous follow-up in neonatal clinics

HIV pre-exposure prophylaxis uptake, retention and adherence among female sex workers in sub-Saharan Africa: a systematic review

Objective To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA).Design Systematic review and meta-analysis.Data sources We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022.Eligibility criteria for studies Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA.Data extraction and synthesis Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention.Results Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26).Conclusions A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs.PROSPERO registration number CRD42020219363

Use of hydrodynamic forces to engineer cartilaginous tissues resembling the non-uniform structure and function of meniscus

The aim of this study was to demonstrate that differences in the local composition of bi-zonal fibrocartilaginous tissues result in different local biomechanical properties in compression and tension. Bovine articular chondrocytes were loaded into hyaluronan-based meshes (HYAFF((R))-11) and cultured for 4 weeks in mixed flask, a rotary Cell Culture System (RCCS), or statically. Resulting tissues were assessed histologically, immunohistochemically, by scanning electron microscopy and mechanically in different regions. Local mechanical analyses in compression and tension were performed by indentation-type scanning force microscopy and by tensile tests on punched out concentric rings, respectively. Tissues cultured in mixed flask or RCCS displayed an outer region positively stained for versican and type I collagen. and an inner region positively stained for glycosaminoglycans and types I and II collagen. The outer fibrocartilaginous capsule included bundles (up to 2 mu m diameter) of collagen fibers and was stiffer in tension (up to 3.6-fold higher elastic modulus), whereas the inner region was stiffer in compression (up to 3.8-fold higher elastic modulus). Instead, molecule distribution and mechanical properties were similar in the outer and inner regions of statically grown tissues. In conclusion, exposure of articular chondrocyte-based constructs to hydrodynamic flow generated tissues with locally different composition and mechanical properties, resembling some aspects of the complex structure and function of the outer and inner zones of native meniscus. (c) 2006 Elsevier Ltd. All rights reserved

PCR arrays identify metallothionein-3 as a highly hypoxia-inducible gene in human adipocytes

Hypoxia-signalling pathway PCR arrays were used to examine the integrated response of human adipocytes to low O2 tension. Incubation of adipocytes in 1% O2 for 24 h resulted in no change in the expression of 63 of the 84 genes on the arrays, a reduction in expression of 9 genes (including uncoupling protein 2) and increased expression of 12 genes. Substantial increases (>10-fold) in leptin, angiopoietin-like protein 4, VEGF and GLUT-1 mRNA levels were observed. The expression of one gene, metallothionein-3 (MT-3), was dramatically (>600-fold) and rapidly (by 60 min) increased by hypoxia. MT-3 gene expression was also substantially induced by hypoxia mimetics (CoCl2, desferrioxamine, dimethyloxalylglycine), indicating transcriptional regulation through HIF-1. Hypoxia additionally induced MT-3 expression in preadipocytes, and MT-3 mRNA was detected in human (obese) subcutaneous and omental adipose tissue. MT-3 is a highly hypoxia-inducible gene in human adipocytes; the protein may protect adipocytes from hypoxic damage

Presence of sporophylls in floating kelp rafts of Macrocystis spp.(Phaeophyceae) along the Chilean Pacific Coast

Some species of macroalgae continue to live for extended periods of time after detachment and may even maintain reproductive structures, yet very little is known about this process. Here, we describe the presence of sporophylls (with sporogenous tissues) on floating kelp rafts of Macrocystis spp. along the coast of Chile. Surveys were conducted at nine sites (18-50&deg; S) during austral summer 2002, and floating kelp rafts were seen and collected at seven of these nine sites (between 22 and 50&deg; S). Fifteen (26.8%) of the 56 samples had sporophylls, indicating maintenance of sporophylls after detachment. Some of the kelp sporophytes with reproductive blades showed signs of having been afloat for long periods (indicated by the large size of attached stalked barnacles). Additionally, experiments showed that floating kelps released viable zoospores. To understand the reproductive dynamics of floating kelps, we compared these results with information from attached populations of Macrocystis spp. at nearby coastal sites. In general, attached kelp had higher proportions of sporophylls than floating rafts, suggesting that detachment may negatively affect reproductive status. Nevertheless, floating kelps remained functionally reproductive, suggesting that zoospores may be dispersed via floating rafts. Published reports on other macroalgae indicate that some species (Lessoniaceae, Fucaceae, and Sargassaceae) are fertile and probably release zoospores or zygotes while floating or drifting in ocean currents. Because dispersal distances achieved by spores of most macroalgae are relatively short, release of spores from floating algae may be an alternative mechanism of long-distance dispersal