Health System-Based Unhealthy Alcohol Use Screening and Treatment Comparing Demographically Matched Participants With and Without HIV.

BACKGROUND: Unhealthy alcohol use among persons living with HIV (PLWH) is linked to significant morbidity, and use of alcohol services may differ by HIV status. Our objective was to compare unhealthy alcohol use screening and treatment by HIV status in primary care. METHODS: Cohort study of adult (≥18 years) PLWH and HIV-uninfected participants frequency matched 20:1 to PLWH by age, sex, and race/ethnicity who were enrolled in a large integrated healthcare system in the United States, with information ascertained from an electronic health record. Outcomes included unhealthy alcohol screening, prevalence, provider-delivered brief interventions, and addiction specialty care visits. Other predictors included age, sex, race/ethnicity, neighborhood deprivation index, depression, smoking, substance use disorders, Charlson comorbidity index, prior outpatient visits, insurance type, and medical facility. Cox proportional hazards models were used to compute hazard ratios (HR) for the outcomes of time to unhealthy alcohol use screening and time to first addiction specialty visit. Poisson regression with robust standard errors was used to compute prevalence ratios (PR) for other outcomes. RESULTS: 11,235 PLWH and 227,320 HIV-uninfected participants were included. By 4.5 years after baseline, most participants were screened for unhealthy alcohol use (85% of PLWH and 93% of HIV-uninfected), but with a lower rate among PLWH (adjusted HR 0.84, 95% CI 0.82 to 0.85). PLWH were less likely, compared with HIV-uninfected participants, to report unhealthy drinking among those screened (adjusted PR 0.74, 95% CI 0.69 to 0.79), and among those who screened positive, less likely to receive brief interventions (adjusted PR 0.82, 95% CI 0.75 to 0.90), but more likely (adjusted HR 1.7, 95% CI 1.2 to 2.4) to have an addiction specialty visit within 1 year. CONCLUSIONS: Unhealthy alcohol use was lower in PLWH, but the treatment approach by HIV status differed. PLWH reporting unhealthy alcohol use received less brief interventions and more addiction specialty care than HIV-uninfected participants.

Effect of a Peer Health Coaching Intervention on Clinical Outcomes Among US Veterans With Cardiovascular Risks: The Vet-COACH Randomized Clinical Trial.

Importance: Although cardiovascular disease (CVD) is the leading cause of death in the US, CVD risk factors remain suboptimally controlled. Objective: To test the effectiveness of a home-visit, peer health coaching intervention to improve health outcomes for veterans with multiple CVD risks. Design, Setting, and Participants: This 2-group, unblinded randomized clinical trial, called Vet-COACH (Veteran Peer Coaches Optimizing and Advancing Cardiac Health), used a novel geographic-based method to recruit a racially diverse population of veterans with low income. These veterans were enrolled at the Seattle or American Lake Veterans Health Affairs primary care clinics in Washington state. Veterans with a diagnosis of hypertension with at least 1 blood pressure reading of 150/90 mm Hg or higher in the past year, and 1 other CVD risk factor (current smoker, overweight or obesity, and/or hyperlipidemia), who resided in Census tracts with the highest prevalence of hypertension were eligible to participate. Participants were randomized to the intervention group (n = 134) or control group (n = 130). An intention-to-treat analysis was performed from May 2017 to October 2021. Intervention: Participants in the intervention group received peer health coaching for 12 months with mandatory and optional educational materials, an automatic blood pressure monitor, a scale, a pill organizer, and healthy nutrition tools. Participants in the control group received usual care plus educational materials. Main Outcomes and Measures: The primary outcome was a change in systolic blood pressure (SBP) from baseline to 12-month follow-up. Secondary outcomes included change in health-related quality of life (HRQOL; measured using the 12-item Short Form survey's Mental Component Summary and Physical Component Summary scores), Framingham Risk Score, and overall CVD risk and health care use (hospitalizations, emergency department visits, and outpatient visits). Results: The 264 participants who were randomized (mean [SD] age of 60.6 [9.7] years) were predominantly male (229 [87%]) and 73 (28%) were Black individuals and 103 (44%) reported low annual income (<$40 000 per year). Seven peer health coaches were recruited. No difference was found in change in SBP between the intervention and control groups (-3.32 [95% CI, -6.88 to 0.23] mm Hg vs -0.40 [95% CI, -4.20 to 3.39] mm Hg; adjusted difference in differences, -2.05 [95% CI, -7.00 to 2.55] mm Hg; P = .40). Participants in the intervention vs control group reported greater improvements in mental HRQOL scores (2.19 [95% CI, 0.26-4.12] points vs -1.01 [95% CI, -2.91 to 0.88] points; adjusted difference in differences, 3.64 [95% CI, 0.66-6.63] points; P = .02). No difference was found in physical HRQOL scores, Framingham Risk Scores, and overall CVD risk or health care use. Conclusions and Relevance: This trial found that, although the peer health coaching program did not significantly decrease SBP, participants who received the intervention reported better mental HRQOL compared with the control group. The results suggest that a peer-support model that is integrated into primary care can create opportunities for well-being improvements beyond blood pressure control. Trial Registration: ClinicalTrials.gov Identifier: NCT02697422.

Preexposure Prophylaxis for HIV Prevention in a Large Integrated Health Care System: Adherence, Renal Safety, and Discontinuation.

BACKGROUND: Placebo-controlled and open-label studies have demonstrated the safety and efficacy of daily oral preexposure prophylaxis (PrEP) in preventing HIV infection, but data are limited on real-world PrEP use. METHODS: We conducted a cohort study from July 2012 through June 2015 of Kaiser Permanente Northern California members initiating PrEP. We assessed pharmacy refill adherence and discontinuation, decreases in estimated glomerular filtration rate (eGFR), and sexually transmitted infection (STI)/HIV incidence. RESULTS: Overall, 972 individuals initiated PrEP, accumulating 850 person-years of PrEP use. Mean adherence was 92% overall. Black race/ethnicity [adjusted risk ratio (aRR) 3.0; 95% confidence interval: 1.7 to 5.1, P < 0.001], higher copayments (aRR 2.0; 1.2 to 3.3, P = 0.005), and smoking (aRR 1.6; 1.1 to 2.3, P = 0.025) were associated with <80% adherence. PrEP was discontinued by 219 (22.5%); female sex (aRR 2.6; 1.5 to 4.6, P < 0.001) and drug/alcohol abuse (aRR 1.8; 1.3 to 2.6, P = 0.002) were associated with discontinuation. Among 909 with follow-up creatinine testing, 141 (15.5%) had an eGFR <70 mL·min·1.73 m and 5 (0.6%) stopped PrEP because of low eGFR. Quarterly STI positivity was high and increased over time for rectal chlamydia (P < 0.001) and urethral gonorrhea (P = 0.012). No HIV seroconversions occurred during PrEP use; however, 2 occurred in individuals who discontinued PrEP after losing insurance coverage. CONCLUSIONS: PrEP adherence was high in clinical practice, consistent with the lack of HIV seroconversions during PrEP use. Discontinuation because of renal toxicity was rare. STI screening every 6 months, as recommended by current guidelines, may be inadequate. Strategies are needed to increase PrEP access during gaps in insurance coverage.

Opiate recidivism in a drug-treatment program: comparison of hair and urine data.

The objective of this preliminary study was to determine whether hair can be used as an adjunct specimen for the monitoring of opiate use in a drug-treatment program. Subjects (n = 10) initiating clinical therapy for opiate addiction were monitored for up to 17 weeks with hair and urinalysis. Questionnaires were administered weekly to document hair cuts and chemical treatments. Hair specimens were collected weekly by cutting at the scalp and segmented into 1-cm lengths prior to analysis. Codeine (COD), morphine (MOR), and 6-monoacetylmorphine (6-MAM) concentrations in hair were measured by liquid chromatography-mass spectrometry (LC-MS) [limit of detection (LOD): 20 pg/mg for COD and 6-MAM; 50 pg/mg MOR]. Urine specimens were analyzed by semiquantitative radioimmunoassay (25-ng/mL cutoff) and LC-MS for codeine (COD), morphine (MOR), morphine-3beta-glucuronide (M3G), morphine-6 beta-glucuronide (M6G), and 6-monoacetylmorphine (6-MAM). The LOD and limit of quantitation (LOQ) in urine for COD, M3G, M6G, and 6-MAM were 10 ng/mL and 25 ng/mL for MOR. Interpretation of the segmental hair data in this study was complex and generally was not in agreement with urine data in most cases. Evaluation of hair data suggested that 6 of 10 subjects discontinued opiate use by the end of the study, whereas 3 of 10 appeared to have reduced their use. One subject appeared not to have used opiates throughout the entire study. In contrast, evaluation of urine data suggested that only 4 of 10 subjects significantly reduced use, and 6 of 10 continued drug use on at least an intermittent basis. Urine appeared to be a more sensitive indicator of changes in the pattern(s) of drug use during the course of clinical drug treatment.

Centralspindlin and chromosomal passenger complex behavior during normal and Rappaport furrow specification in echinoderm embryos.

The chromosomal passenger (CPC) and Centralspindlin complexes are essential for organizing the anaphase central spindle and providing cues that position the cytokinetic furrow between daughter nuclei. However, echinoderm zygotes are also capable of forming "Rappaport furrows" between asters positioned back-to-back without intervening chromosomes. To understand how these complexes contribute to normal and Rappaport furrow formation, we studied the localization patterns of Survivin and mitotic-kinesin-like-protein1 (MKLP1), members respectively of the CPC and the Centralspindlin complex, and the effect of CPC inhibition on cleavage in mono- and binucleate echinoderm zygotes. In zygotes, Survivin initially localized to metaphase chromosomes, upon anaphase onset relocalized to the central spindle and then, together with MKLP1 spread towards the equatorial cortex in an Aurora-dependent manner. Inhibition of Aurora kinase activity resulted in disruption of central spindle organization and furrow regression, although astral microtubule elongation and furrow initiation were normal. In binucleate cells containing two parallel spindles MKLP1 and Survivin localized to the plane of the former metaphase plate, but were not observed in the secondary cleavage plane formed between unrelated spindle poles, except when chromosomes were abnormally present there. However, the secondary furrow was sensitive to Aurora inhibition, indicating that Aurora kinase may still contribute to furrow ingression without chromosomes nearby. Our results provide insights that reconcile classic micromanipulation studies with current molecular understanding of furrow specification in animal cells.

Mutual dependence of Mob1 and the chromosomal passenger complex for localization during mitosis.

The spatial and temporal coordination of chromosome segregation with cytokinesis is essential to ensure that each daughter cell receives the correct complement of chromosomal and cytoplasmic material. In yeast, mitotic exit and cytokinesis are coordinated by signaling cascades whose terminal components include a nuclear Dbf2-related family kinase and a noncatalytic subunit, Mps one binding (Mob) 1. There are five human Mob1 isoforms, all of which display redundant localization patterns at the spindle poles and kinetochores in early mitosis, and the spindle midzone during cytokinesis. Mob1 shares similar localization patterns to Polo-like kinase (Plk1) and the chromosomal passenger complex (CPC), and although depletion of Plk1 resulted in a loss of Mob1 from the spindle poles, Mob1 recruitment to kinetochores was unaffected. Conversely, disruption of CPC signaling resulted in a loss of Mob1 from kinetochores without disrupting recruitment to the spindle poles. In Mob1-depleted cells, the relocalization of the CPC and mitotic kinesin-like protein (MKLP) 2 to the spindle midzone was delayed during early anaphase, and as a consequence, the midzone recruitment of MKLP1 also was affected. Together, these results suggest that Mob1 and the other mammalian orthologues of the mitotic exit network regulate mitotic progression by facilitating the timely mobilization of the CPC to the spindle midzone.

Aortic valve thrombus presenting as a non-ST elevation myocardial infarction.

Thrombosis of prosthetic heart valves is well known; however it rarely occurs on native heart valves. To our knowledge there are no reports of native aortic valve thrombus in the absence of blood dyscrasia or prior valve pathology. We describe a patient who presented with a non-ST segment elevation myocardial infarction (NSTEMI) caused by a large aortic valve thrombus.

Reactive oxygen species modulate Anopheles gambiae immunity against bacteria and Plasmodium.

The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. Strains of An. gambiae with higher systemic levels of ROS survive a bacterial challenge better, whereas reduction of ROS by dietary administration of antioxidants significantly decreases survival, indicating that ROS are required to mount effective antibacterial responses. Expression of several ROS detoxification enzymes increases in the midgut and fat body after a blood meal. Furthermore, expression of several of these enzymes increases to even higher levels when mosquitoes are fed a Plasmodium berghei-infected meal, indicating that the oxidative stress after a blood meal is exacerbated by Plasmodium infection. Paradoxically, a complete lack of induction of catalase mRNA and lower catalase activity were observed in P. berghei-infected midguts. This suppression of midgut catalase expression is a specific response to ookinete midgut invasion and is expected to lead to higher local levels of hydrogen peroxide. Further reduction of catalase expression by double-stranded RNA-mediated gene silencing promoted parasite clearance by a lytic mechanism and reduced infection significantly. High mosquito mortality is often observed after P. berghei infection. Death appears to result in part from excess production of ROS, as mortality can be decreased by oral administration of uric acid, a strong antioxidant. We conclude that ROS modulate An. gambiae immunity and that the mosquito response to P. berghei involves a local reduction of detoxification of hydrogen peroxide in the midgut that contributes to limit Plasmodium infection through a lytic mechanism.

The role of reactive oxygen species on Plasmodium melanotic encapsulation in Anopheles gambiae.

Malaria transmission depends on the competence of some Anopheles mosquitoes to sustain Plasmodium development (susceptibility). A genetically selected refractory strain of Anopheles gambiae blocks Plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. Morphological and microarray mRNA expression analysis suggest that the refractory and susceptible strains have broad physiological differences, which are related to the production and detoxification of reactive oxygen species. Physiological studies corroborate that the refractory strain is in a chronic state of oxidative stress, which is exacerbated by blood feeding, resulting in increased steady-state levels of reactive oxygen species, which favor melanization of parasites as well as Sephadex beads.