Reducing sexual risk and promoting acceptance of men who have sex with men living with HIV in India: Outcomes and process evaluation of a pilot randomised multi-level intervention

ABSTRACT

HIV-positive men who have sex with men (HIV+MSM) in India need culturally-relevant interventions to promote safer sex. We tested a multi-level intervention among HIV+MSM that targeted individual, interpersonal, and community factors, based on the Social-Personal and Social Ecological Models. We conducted a 2?×?2 factorial RCT with 119 HIV+MSM randomised to receive either an individual-level intervention (ILI) using motivational interviewing to promote safer sex, a community-level intervention (CLI) to strengthen community norms toward safer sex and reduce stigma among MSM communities, a multi-level intervention combining the individual- and community-level interventions (ILI?+?CLI), or standard-of-care control. Participants completed pre- and post-intervention assessments of a composite sexual risk score and a process evaluation to assess fidelity and satisfaction. Out of the 119 HIV+MSM, 106 (89.0%) completed pre- and post-intervention assessments. Generalised Estimating Equation models showed that both CLI (Incidence Rate Ratio [IRR]?=?.67, 95% CI .47 to .96) and ILI?+?CLI (IRR?=?.66, 95% CI .48 to .91) groups had a statistically significant decrease in sexual risk compared to the standard-of-care. The interventions had high levels of fidelity and satisfaction. This pilot RCT demonstrated feasibility and potential effectiveness of a multi-level intervention that addresses individual, interpersonal and community-level contributors of sexual risk among HIV+MSM.     

Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.     

Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.