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Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized. [ABSTRACT FROM AUTHOR]

The plethora of pharmacologic treatments used for periorificial dermatitis (POD) makes clinical decision‐making challenging. The objectives of this review were to assess the efficacy and safety of pharmacological interventions for POD in children and adults. The search was performed on 2 February 2021 and included seven databases and trial registries, with no date or language restrictions Study selection, data extraction and risk of bias assessments were performed independently and in duplicate by two authors, in accordance with a prespecified protocol. Meta‐analyses were performed and reported in accordance with PRISMA guidelines. Where meta‐analysis was not possible, a narrative synthesis was performed and reported in accordance with SWiM guidelines. The certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Eleven studies representing 733 participants were included. Oral tetracycline may improve physician‐reported severity of POD from day 20 onwards (low certainty evidence). Adverse effects may include abdominal discomfort, facial dryness and pruritus. Pimecrolimus cream may improve physician‐reported severity slightly after 4 weeks of treatment (MD −0.49, 95% CI −1.02 to 0.04, n = 164, low certainty evidence). Adverse effects may include erythema, herpes simplex virus infection, burning and pruritus. Azelaic acid gel may result in no change in either physician‐ or patient‐reported severity after 6 weeks of treatment. The evidence is very uncertain about the effect of praziquantel ointment on physician‐reported severity and skin‐related quality of life after 4 weeks of treatment. The evidence is also very uncertain about the effect of topical clindamycin/benzoyl peroxide on physician‐reported severity. The body of evidence to inform treatment of POD currently consists of low and very low certainty evidence for important outcomes. Well‐designed trials are needed to further investigate treatment options. Data are required for children and from low‐middle income countries to improve external validity. Future trials should also include adequate post‐treatment follow‐up and standardized outcome measures. [ABSTRACT FROM AUTHOR]

Background. Neonates of extremely low birthweight (ELBW; <1 000 g) have the highest neonatal mortality in South Africa (SA). Objective. To describe the morbidity and mortality of ELBW neonates treated at a tertiary hospital in SA. Methods. This was a retrospective cohort study including all live-born ELBW neonates treated at Tygerberg Hospital between 1 January and 31 December 2016. Data were extrapolated from a prospectively collected neonatal database and patient records. Multiple logistic regression and survival analysis were performed to identify risk factors of mortality. Results. The sample included 256 neonates. The following morbidities were recorded: respiratory distress syndrome (83.2%); bronchopulmonary dysplasia (8.2%); intraventricular haemorrhage (34.5%); periventricular leukomalacia (0.6%); necrotising enterocolitis (10.5%); and retinopathy of prematurity (31.2%). The survival-to-discharge rate was 63.3%. Cause of death was documented as extreme prematurity in 41% of the inpatient deaths. Birthweight was a significant predictor of mortality (hazard ratio 0.99; 95% confidence interval 0.992 - 0.999). Of the 162 neonates who survived until discharge, 11 died following discharge. Conclusion. Morbidity and mortality rates remain high among ELBW neonates. To improve survival, resources need to be allocated to neonatal resuscitation, surfactant therapy and increasing availability of intensive-care beds. [ABSTRACT FROM AUTHOR]

Ethanol exposure alters signal transduction through the adenylyl cyclase (AC) system. To elucidate the basis for this effect, we investigated the AC system in peripheral lymphocytes from abstinent alcoholic men ( n= 22), actively drinking alcoholic men ( n= 41), and nonalcoholic control men ( n= 16). Immunoblot analysis of lymphocyte membranes from abstinent alcoholics demonstrated a 3.0-fold increase in the level of Gi2α protein ( p < 0.05) compared with controls. However, levels of Gi2α protein were similar in both groups. Abstinent alcoholics had a 2.9-fold increase in Gi2α mRNA ( p < 0.001) and a 2.7-fold increase in G2α mRNA ( p < 0.03) compared with lymphocytes from control subjects. Actively drinking alcoholics, in contrast, had unaltered G2α protein, Gi2α protein, and Gi2α mRNA levels compared with control subjects, but did have a 1.8-fold increase ( p < 0.01) in Gi2α mRNA. Consistent with enhanced Gi2α expression, lymphocyte membranes from abstinent alcoholics had decreased basal, prostaglandin E1-, guanosine 5′-0-(3-thiotriphosphate)-γS-, and forskolin-stimulated AC activity compared with both controls and actively drinking alcoholics ( p < 0.05). We conclude that lymphocyte AC is reduced during abstinence from alcohol and enhanced expression of the inhibitory G-protein, Gi2α, may account for this change. [ABSTRACT FROM AUTHOR]

The adenylyl cyclase signal transduction system, a ubiquitous second messenger system, has been identified as a potential marker for genetic risk of alcohol and drug dependence. Using the polymerase chain reaction (PCR) to amplify exon 13 of the Gsα gene, two alleles were distinguished by denaturing gradient gel electrophoresis. One allele, designed A, contained the previously published C in the codon for asparagine 371, while the second allele, designated A, contains a C-T transition that conserves the asparagine residue at codon 371. The neutral polymorphism eliminates a Fok I restriction enzyme cleavage site, allowing use of restriction fragment length polymorphisms of PCR products to determine allelic frequency in 235 subjects with alcohol and/or drug dependence and in 85 control subjects. Since allele frequencies differ significantly by race, comparisons between affected individuals and controls were conducted separately for white and black groups. Within race, there were no significant differences in the frequency of the A allele among alcoholics, subjects dependent on cocaine or opioids, subjects dependent on these drugs and alcohol, and controls. We conclude that there is no association between alcohol and/or drug dependence and alleles of an exon 13 polymorphism of the Gsα gene in either black or white individuals. [ABSTRACT FROM AUTHOR]