Association Between Gabapentin Receipt for Any Indication and Alcohol Use Disorders Identification Test-Consumption Scores Among Clinical Subpopulations With and Without Alcohol Use Disorder.

BACKGROUND: Current medications for alcohol use disorder (AUD) have limited efficacy and utilization. Some clinical trials have shown efficacy for gabapentin among treatment-seeking individuals. The impact of gabapentin on alcohol consumption in a more general sample remains unknown. METHODS: We identified patients prescribed gabapentin for ≥180 consecutive days for any clinical indication other than substance use treatment between 2009 and 2015 in the Veterans Aging Cohort Study. We propensity-score matched each gabapentin-exposed patient with up to 5 unexposed patients. Multivariable difference-in-difference (DiD) linear regression models estimated the differential change in Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores during follow-up between exposed and unexposed patients, by baseline level of alcohol consumption and daily gabapentin dose. Analyses were stratified by AUD history. Clinically meaningful changes were a priori considered a DiD ≥1 point. RESULTS: Among patients with AUD, AUDIT-C scores decreased 0.39 points (95% confidence interval [CI] 0.05, 0.73) more among exposed than unexposed patients (p < 0.03). Potentially clinically meaningful differences were observed among those with AUD and exposed to ≥1,500 mg/d (DiD 0.77, 95% CI 0.15, 1.38, p < 0.02). No statistically significant effects were found among patients with AUD at doses lower than 1,500 mg/d or baseline AUDIT-C ≥4. Among patients without AUD, we found no overall difference in changes in AUDIT-C scores, nor in analyses stratified by baseline level of alcohol consumption. CONCLUSIONS: Patients exposed to doses of gabapentin consistent with those used in clinical trials, particularly those with AUD, experienced a greater decrease in AUDIT-C scores than matched unexposed patients

Reduction in Drinking was Associated With Improved Clinical Outcomes in Women With HIV Infection and Unhealthy Alcohol Use: Results From a Randomized Clinical Trial of Oral Naltrexone Versus Placebo

Background Alcohol consumption is associated with poor health outcomes in women living with HIV (WLWH), but whether medication can help to reduce drinking in non–treatment‐seeking women or whether reduction in drinking improves HIV outcomes is unclear. We conducted a randomized clinical trial (RCT) of daily oral naltrexone (50 mg) versus placebo in WLWH who met criteria for current unhealthy alcohol use. Methods WLWH with current unhealthy alcohol use (\u3e7 drinks/wk or \u3e3 drinks/occasion) were randomly assigned to daily oral naltrexone 50 mg (n = 96) or placebo (n = 98) for 4 months. Drinking outcomes, including the proportion of women who reduced ( Results The participants’ mean age was 48 years, 86% were African American, and 94% were receiving HIV antiretroviral therapy. Among all participants, 89% and 85% completed the 4‐month and 7‐month follow‐ups, respectively. Participants in both groups substantially reduced drinking over time. At 1 and 3 months, naltrexone was associated with a greater reduction in drinking (p \u3c 0.05), but the proportion who reduced/quit drinking at 4 months (52% vs. 45%, p = 0.36) or 7 months (64% in both groups) was not different. HIV viral suppression at follow‐up was significantly better in participants who reduced/quit drinking versus those continuing unhealthy alcohol use at 4 months (72% vs. 53%, p = 0.02) and 7 months (74% vs. 54%, p = 0.02). Conclusions Participating in an RCT to reduce drinking was associated with significant drinking reduction regardless of medication assignment, suggesting that nonmedication aspects of research study participation (e.g., repeated assessments and support from research staff) could be important interventions to help reduce drinking outside of research studies. Drinking reduction was associated with improved HIV viral suppression, providing evidence to support recommendations to avoid unhealthy alcohol use among WLWH

Age-associated gut dysbiosis, marked by loss of butyrogenic potential, correlates with altered plasma tryptophan metabolites in older people living with HIV.

Background: Imbalance in tryptophan (TRP) metabolism and its neuroactive metabolites, serotonin and kynurenine (KYN), is a known pathogenic mechanism underlying neurocognitive impairment. Gut microbiota plays an important role in TRP metabolism, and the production of these neuroactive molecules affects neurocognitive function. Although both HIV infection and normal aging independently induce gut dysbiosis and influence TRP metabolism, their interactive effects on compositional/functional changes in gut microbiota and consequent alterations in TRP metabolites remain largely undetermined. Methods: Older people living with HIV infection (PLWH, aged 50–70 years, n = 22) were enrolled in this cross-sectional pilot study. Metagenomic analysis of fecal microbiome using 16S Ribosomal ribonucleic acid gene sequencing and metabolomics analysis of plasma using mass spectrometry with a reverse-phase iquid chromatography tandem mass spectrometry were performed. Statistical analyses included the univariate linear regression and Spearman correlation analyses. Results: Age-associated changes in plasma levels of key neuroactive TRP metabolites, serotonin and KYN, were seen in PLWH. Specifically, we observed age-dependent decreases in serotonin and increases in KYN and KYN-to-TRP ratio, indicative of dysfunctional TRP metabolism. Furthermore, the gut dysbiosis seen in older PLWH is characterized by a reduction of Firmicutes/Bacteroidetes ratio and butyrate-producing microbial families Lachnospiraceae and Lactobacillaceae. Of importance, correspondent with gut dysbiosis, increasing age was significantly associated with decreased plasma butyrate levels, which in turn correlated positively with serotonin and negatively with KYN/TRP ratio. Conclusions: Age-dependent gut microbial dysbiosis distinguished by a decrease in butyrogenic potential is a key pathogenic feature associated with the shift in TRP metabolism from serotonin to KYN in older PLWH

Epigenetic mechanisms underlying HIV-infection induced susceptibility of CD4+ T cells to enhanced activation-induced FasL expression and cell death.

Background: Chronic immune activation and CD4+ T cell depletion are significant pathogenic features of HIV infection. Expression of Fas ligand (FasL), a key mediator of activation-induced cell death in T cells, is elevated in people living with HIV-1 infection (PLWH). However, the epigenetic mechanisms underlying the enhanced induction of FasL expression in CD4+ T lymphocytes in PLWH are not completely elucidated. Hence, the current work examined the effect of HIV infection on FasL promoter-associated histone modifications and transcriptional regulation in CD4+ T lymphocytes in PLWH. Method: Flow cytometric analysis was performed to examine the Fas-FasL expression on total CD4+ T cells and naïve/memory CD4+ T cell subsets. Epigenetic FasL promoter histone modifications were investigated by chromatin immunoprecipitation-quantitative real-time polymerase chain reaction analysis using freshly isolated total CD4+ T lymphocytes from HIV-1 infected and noninfected individuals. Results: All naïve/memory CD4+ T cell subsets from PLWH showed markedly greater frequency of FasL expression. Notably, examination of functional outcome of FasL/Fas co-expression demonstrated the preferential susceptibility of Tcm and Tem subsets to activation-induced apoptosis. Importantly, these CD4+ T cells collectively demonstrated a distinct FasL promoter histone profile involving a coordinated cross-talk between histone H3 modifications leading to enhanced FasL gene expression. Specifically, levels of transcriptionally permissive histone H3K4-trimethylation (H3K4Me3) and histone H3K9-acetylation (H3K9Ac) were increased, with a concomitant decrease in the repressive H3K9-trimethylation (H3K9Me3). Conclusion: The present work demonstrates that epigenetic mechanisms involving promoter-histone modifications regulate transcriptional competence and FasL expression in CD4+ T cells from PLWH and render them susceptible to activation-induced cell death

A conceptual analysis of SBIRT implementation alongside the continuum of PrEP awareness: domains of fit and feasibility.

Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a supplementary intervention that can be incorporated into the Pre-Exposure Prophylaxis (PrEP) Care Continuum, complementing initiatives and endeavors focused on Human Immunodeficiency Virus (HIV) prevention in clinical care and community-based work. Referencing the Transtheoretical Model of Change and the PrEP Awareness Continuum, this conceptual analysis highlights how SBIRT amplifies ongoing HIV prevention initiatives and presents a distinct chance to address identified gaps. SBIRT\u27s mechanisms show promise of fit and feasibility through (a) implementing universal Screening (S), (b) administering a Brief Intervention (BI) grounded in motivational interviewing aimed at assisting individuals in recognizing the significance of PrEP in their lives, (c) providing an affirming and supportive Referral to Treatment (RT) to access clinical PrEP care, and (d) employing client-centered and destigmatized approaches. SBIRT is uniquely positioned to help address the complex challenges facing PrEP awareness and initiation efforts. Adapting the SBIRT model to integrate and amplify HIV prevention efforts merits further examination

Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania

SummaryThis study was part of a larger cross-sectional survey that was evaluating tuberculosis (TB) infection in humans, livestock and wildlife in the Serengeti ecosystem in Tanzania. The study aimed at evaluating the genetic diversity of Mycobacterium tuberculosis isolates from TB patients attending health facilities in the Serengeti ecosystem. DNA was extracted from 214 sputum cultures obtained from consecutively enrolled newly diagnosed untreated TB patients aged ≥18 years. Spacer oligonucleotide typing (spoligotyping) and Mycobacterium Interspersed Repetitive Units and Variable Number Tandem Repeat (MIRU-VNTR) were used to genotype M. tuberculosis to establish the circulating lineages. Of the214 M. tuberculosis isolates genotyped, 55 (25.7%) belonged to the Central Asian (CAS) family, 52 (24.3%) were T family (an ill-defined family), 38 (17.8%) belonged to the Latin American Mediterranean (LAM) family, 25 (11.7%) to the East-African Indian (EAI) family, 25 (11.7%) comprised of different unassigned (‘Serengeti’) strain families, while 8 (3.7%) belonged to the Beijing family. A minority group that included Haarlem, X, U and S altogether accounted for 11 (5.2%) of all genotypes. MIRU-VNTR typing produced diverse patterns within and between families indicative of unlinked transmission chains. We conclude that, in the Serengeti ecosystem only a few successful families predominate namely CAS, T, LAM and EAI families. Other types found in lower prevalence are Beijing, Haarlem, X, S and MANU. The Haarlem, EAI_Somalia, LAM3 and S/convergent and X2 subfamilies found in this study were not reported in previous studies in Tanzania

Importance of effective collaboration between health professionals for the facilitation of optimal community diabetes care

Diabetes places a significant burden on the individuals concerned, their families and society as a whole. The debilitating sequelae of diabetes can be limited or prevented altogether through strict glycaemic control. Despite the seemingly uncomplicated nature of the disorder, effective management can be elusive, as the impact of having to deal with diabetes on a daily basis can be profound and appropriate professional support is not always readily available. As the roles of general practitioners (GPs) and allied health professionals have evolved, a major issue now facing all is that of developing and maintaining effective collaborative relationships for the facilitation of optimal community diabetes care. Using a simple survey methodology, the present exploratory study investigated the referral patterns of GPs to diabetic educators (DEs) working for a community health service in an Australian town, and reasons for referral and non-referral in order to identify factors that contribute to a sound and sustainable collaborative relationship.The results provide some evidence that GPs and DEs in this town do work collaboratively towards achieving client-centred goals and highlight the need to inform GPs who are new to communities, such as this one, of the available DE services. Most importantly, the study identified that there are many opportunities to strengthen collaboration so as to facilitate optimal community diabetes care. This information is valuable, because there is limited empirical evidence either nationally or internationally about the process of collaboration between health professionals in the management of chronic diseases, such as diabetes