Is Abstinence from Alcohol and Smoking Associated with Less Anxiety and Depressive Symptoms Among People with HIV?

Achieving abstinence from alcohol, tobacco, or both may improve mental health, but is understudied in people with HIV (PWH). The St PETER HIV randomized clinical trial compared varenicline, cytisine, and nicotine replacement therapy on alcohol and smoking behavior among 400 PWH in Russia. The primary exposure was thirty-day point prevalence abstinence (PPA) from (1) alcohol, (2) smoking, (3) both, or (4) neither and was assessed at 1, 3, 6 and 12-months as were the study outcomes of anxiety (GAD-7) and depressive (CES-D) symptoms. The primary aim was to examine the association between smoking and/or alcohol abstinence and subsequent symptoms of depression and anxiety. Primary analysis used repeated measures generalized linear modeling to relate PPA with mental health scores across time. In secondary analyses, Kruskal-Wallis tests related PPA with mental health scores at each timepoint. Primary analyses did not identify significant differences in anxiety or depressive symptoms between exposure groups over time. Secondary analyses found CES-D scores across PPA categories were similar at 1-month (11, 10, 11, 11) and 6-months (10, 10, 11, 11) but differed at 3-months (9, 11, 10, 12; p = 0.035) and 12-months (10, 6, 11, 10; p = 0.019). GAD-7 scores did not vary across PPA categories at any time point. While abstinence was associated with fewer depressive symptoms at times, findings were not consistent during follow-up, perhaps reflecting intermittent relapse. PWH with polysubstance use and mental health comorbidity are complex, and larger samples with sustained abstinence would further elucidate effects of abstinence on mental health.

Healthcare Utilization Among Persons with HIV and Unhealthy Alcohol Use in St. Petersburg, Russia.

Few studies have examined the association between healthcare utilization and heavy alcohol use in Russia among persons with HIV (PWH), a group with high healthcare needs. This study analyzed the association between unhealthy alcohol use (defined as AUDIT score ≥ 8) and healthcare utilization among PWH with heavy alcohol use and daily smoking in St. Petersburg, Russia. This secondary analysis used data from a randomized controlled trial addressing alcohol use. The primary outcome was seeing an infectionist for HIV care in the past year. Outcomes were measured at baseline, 6 months, and 12 months. We assessed the association between unhealthy alcohol use and healthcare utilization outcomes with a repeated measures logistic regression model, controlling for relevant covariates. Nearly all (96.0%) participants had unhealthy alcohol use at baseline, and 90.0% had seen an infectionist for HIV care in the past year. In adjusted analyses, unhealthy alcohol use was associated with a 36% decrease in seeing an infectionist for HIV care (aOR = 0.64, 95% CI 0.43-0.95). Participants reported low levels of emergency department visits and hospitalizations. Understanding how to engage this population in alcohol use disorder treatment and HIV care is an important next step for improving health outcomes for this population.

Association of Alcohol Consumption With CD4 Recovery After Antiretroviral Therapy Initiation in St. Petersburg, Russia.

BACKGROUND: Delayed CD4 recovery after initiating antiretroviral therapy (ART) is a novel potential mechanism by which alcohol consumption leads to increased morbidity and mortality in people with HIV. We hypothesized that alcohol consumption at ART initiation is associated with slower CD4 recovery. METHODS: We retrospectively analyzed 2 pooled longitudinal alcohol/HIV cohorts (2014-2019) in St. Petersburg, Russia. Eligible participants initiated the first ART during parent studies; had alcohol consumption assessed by the blood biomarker, phosphatidylethanol (PEth), at the last research visit before ART initiation; and had ≥1 CD4 count measurement before and after initiating ART. Participants were stratified by low, moderate, and high PEth (<8, 8-80, and >80 ng/mL, respectively). We used random-effects piecewise linear regression models to estimate CD4 recovery, defined as CD4 count change per 30 days after ART initiation, by the alcohol group. RESULTS: Of 60 eligible participants, median age was 34 years and 28% were female. The median pre-ART PEth in the low, moderate, and high PEth groups were <8, 23, and 232 ng/mL, respectively. After starting ART, the CD4 count increased by 13.60 cells/mm3/mo (95% CI: 0.33 to 26.87) with low PEth, 0.93 cells/mm3/mo (95% CI: -6.18 to 8.04) with moderate PEth, and 2.33 cells/mm3/mo (95% CI: -3.44 to 8.09) with high PEth. CONCLUSIONS: Among Russians with HIV, we observed faster CD4 recovery after ART initiation in those with low alcohol consumption compared with those with moderate and high alcohol consumption, as assessed by PEth. This analysis provides further evidence for the possible value of alcohol reduction interventions for people with HIV who are initiating ART.

Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal.

Of the 12 million people who inject drugs worldwide, 13% live with HIV. Whether opioid use impacts HIV pathogenesis and latency is an outstanding question. To gain insight into whether opioid use influences the proviral landscape and latent HIV reservoir, we performed intact proviral DNA assays (IPDA) on peripheral blood mononuclear cells (PBMCs) from antiretroviral therapy (ART)-suppressed people living with HIV (PWH) with or without current opioid use. No differences were observed between PWH with and without opioid use in the frequency of HIV intact and defective proviral genomes. To evaluate the latent reservoir, we activated PBMCs from ART-suppressed PWH with or without opioid use and assessed the induction of HIV RNA. PWH using opioids had diminished responses to ex vivo HIV reactivation, suggesting a smaller reversible reservoir of HIV-1 latently infected cells. However, in vitro studies using primary CD4+ T cells treated with morphine showed no effect of opioids on HIV-1 infection, replication or latency establishment. The discrepancy in our results from in vitro and clinical samples suggests that while opioids may not directly impact HIV replication, latency and reactivation in CD4+ T cells, opioid use may indirectly shape the HIV reservoir in vivo by modulating general immune functions.

Food Insecurity and Transmission Risks Among People with HIV Who Use Substances.

Food insecurity (FI) impacts people with HIV (PWH) and those who use substances (i.e. drugs and alcohol). We evaluated the longitudinal association between FI and HIV transmission risks (unprotected sexual contacts and shared needles/syringes). Among 351 PWH who use substances in Russia, 51.6% reported FI and 37.0% past month injection drug use. The mean number of unprotected sexual contacts in the past 90 days was 13.4 (SD 30.1); 9.7% reported sharing needles/syringes in the past month. We did not find a significant association between mild/moderate FI (adjusted IRR = 0.87, 95% CI 0.47, 1.61) or severe FI (aIRR = 0.84, 95% CI 0.46, 1.54; global p = 0.85) and unprotected sexual contacts. We observed a significant association between severe FI and sharing needles/syringes in the past month (adjusted OR = 3.27, 95% CI 1.45, 7.39; p = 0.004), but not between mild/moderate FI and sharing needles/syringes in the past month (aOR = 1.40,95% CI 0.58, 3.38; p = 0.45). These findings suggest that severe FI could be a potential target for interventions to lower HIV transmission.

RESUMEN: La inseguridad alimentaria (IF) afecta a las personas que viven con VIH (PVV y a personas con abuso desustancias (.ej. drogas y alcohol). Evaluamos la asociación longitudinal entre la IF y los riesgos de transmisión del VIH (relaciones sexuales sin protección y agujas/jeringas compartidas). Entre 351 PVVcon abuso de sustancias en Rusia, el 51,6% reportó FI y el 37,0% consumió drogas intravenosas en el último mes. El promedio de contactos sexuales sin protección en los últimos 90 días fue de 13,4 (DE 30,1); el 9,7% informó haber compartido agujas/jeringas en el último mes. No encontramos una asociación significativa entre IF leve/moderada (IRR ajustada = 0,87, IC 95% = 0,47, 1,61) o IF grave (IRRa = 0,84, IC 95% = 0,46, 1,54; p global = 0,85) y relaciones sexuales sin protección. Observamos una asociación significativa entre IF grave y compartir agujas/jeringas en el último mes (OR ajustado = 3,27, IC 95% = 1,45, 7,39; p = 0,004), pero no entre IF leve/moderada y compartir agujas/jeringas en el último mes (ORa = 1,40, IC 95% = 0,58, 3,38; p = 0,45). Estos hallazgos sugieren que la IF grave podría ser un enfoque para intervenciones que buscan reducir la transmisión del VIH.

Posttraumatic Stress Symptoms and the Quality of Maternal-Child Interactions in Mothers of Preterm Infants.

OBJECTIVE: The purpose of this study was to examine associations between maternal trauma exposure, posttraumatic stress symptoms, and directly observed maternal-child interactions among a diverse cohort of mother-preterm infant dyads at 12-month corrected age. METHODS: We conducted a retrospective cohort study. Maternal trauma exposure and posttraumatic stress symptoms were measured using the Modified Posttraumatic Stress Disorder Symptom Scale at baseline and 6 and 12 months. The primary outcome was directly observed maternal-child interactions at 12-month corrected age using the Coding Interactive Behavior Manual. We used linear regression models to estimate the associations between trauma exposure, posttraumatic stress symptoms (and symptom clusters), and observer-rated maternal-child interactions. RESULTS: Among the 236 participants, 89 (37.7%) self-reported as Black and 98 (41.5%) as Latina; mean gestational age of the infants was 31.6 weeks (SD 2.6). Mothers with posttraumatic stress symptoms demonstrated greater maternal sensitivity (ß = 0.32; 95% confidence interval [CI], 0.06-0.58; standardized effect size = 0.39) and greater dyadic reciprocity (ß = 0.39; 95% CI, 0.04-0.73; standardized effect size = 0.36) compared with those not exposed to trauma; however, we did not observe significant differences between trauma-exposed but asymptomatic women and those not exposed to trauma. Across symptom clusters, differences in maternal sensitivity and dyadic reciprocity were most pronounced for mothers with avoidance and re-experiencing symptoms, but not hyperarousal symptoms. CONCLUSION: Maternal posttraumatic stress symptoms seem to be associated with the quality of maternal-child interactions at age 1 year among a cohort of urban, mother-preterm infant dyads. These findings have implications for strength-based intervention development.

Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use: A Randomized Clinical Trial.

Importance: Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions. Objective: To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT. Design, Setting, and Participants: This 4-group randomized, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrollment. Data were analyzed from May 2021 through June 2022. Interventions: Participants received alcohol and tobacco counseling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4). Main Outcomes and Measures: The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months. Results: Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking. Conclusions and Relevance: This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behavior change rates were high in all groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02797587.

Impact of illicit opioid use on markers of monocyte activation and systemic inflammation in people living with HIV.

INTRODUCTION: We hypothesize that illicit opioid use increases bacterial translocation from the gut, which intensifies systemic inflammation. OBJECTIVE: To investigate the association between opioid use and plasma soluble CD14 [sCD14], interleukin-6 [IL-6] and D-dimer in people living with HIV (PLWH). METHODS: We analyzed data from the Russia ARCH study-an observational cohort of 351 ART-naive PLWH in St. Petersburg, Russia. Plasma levels of sCD14 (primary outcome), IL-6 and D-dimer (secondary outcomes) were evaluated at baseline, 12, and 24 months. Participants were categorized into three groups based on illicit opioid use: current, prior, and never opioid use. Linear mixed effects models were used to evaluate associations. RESULTS: Compared to never opioid use, sCD14 levels were significantly higher for participants with current opioid use (AMD = 197.8 ng/ml [11.4, 384.2], p = 0.04). IL-6 levels were also higher for participants with current vs. never opioid use (ARM = 2.10 [1.56, 2.83], p <0.001). D-dimer levels were higher for current (ARM = 1.95 [1.43, 2.64], p <0.001) and prior (ARM = 1.57 [1.17, 2.09], p = 0.004) compared to never opioid use. CONCLUSIONS: Among PLWH, current opioid use compared to never use is associated with increased monocyte activation and systemic inflammation.

Stigma and ART initiation among people with HIV and a lifetime history of illicit drug use in Saint-Petersburg, Russia-A prospective cohort analysis.

BACKGROUND: HIV-positive people who inject drugs (PWID) are stigmatized and face more challenges in accessing ART. The natural course of stigma and its role on ART initiation in this population is unclear. We examined 1] whether HIV stigma changes over time and 2] whether HIV and substance use stigma are associated with ART initiation in a prospective cohort of HIV-positive PWID in St. Petersburg, Russia. METHODS: We used data from 165 HIV-positive PWID who were ART-naïve at enrollment andgeneralized estimating equations to assess changes in HIV stigma between baseline, 12- and 24-month study visits. Logistic regression estimated associations of HIV stigma and substance use stigma with ART initiation. All models were adjusted for gender, age, CD4 count, duration of HIV diagnosis, recent (past 30-day) drug use and depressive symptoms. RESULTS: Participants characteristics were the following: median age of 34 (Q1; Q3: 30; 37) years; 30% female; 28% with CD4 count <350; 44% reported recent drug use. During the study period, 31% initiated ART and the median time between HIV diagnosis and ART initiation was 8.5 years (Q1; Q3: 4.68; 13.61). HIV stigma scores decreased yearly by 0.57 (95% CI -1.36, 0.22). More than half (27/47 [57.4%]) of participants who were eligible for ART initiation per local ART guidelines did not initiate therapy. Total HIV stigma and substance use stigma scores were not associated with ART initiation (AOR 0.99, 95%CI 0.94-1.04; AOR 1.01, 95%CI 0.96-1.05, respectively). CONCLUSION: In this Russian cohort of HIV-positive, ART-naïve PWID, stigma did not change over time and was not associated with ART initiation. Addressing stigma alone is unlikely to increase ART initiation rates in this population. Reducing further existing structural barriers, e.g., by promoting equal access to ART and the value of substance-use treatment for ART treatment success should complement stigma-reduction approaches.

Disparities in Utilization of Ambulatory Cholecystectomy: Results From Three States.

BACKGROUND: Inpatient cholecystectomy is associated with higher cost and morbidity relative to ambulatory cholecystectomy, yet the latter may be underutilized by minority and underinsured patients. The purpose of this study was to examine the effects of race, income, and insurance status on receipt of and outcomes following ambulatory cholecystectomy. MATERIALS AND METHODS: Retrospective observational cohort study of patients 18-89 undergoing cholecystectomy for benign indications in Florida, Iowa, and New York, 2011-2014 using administrative databases. The primary outcome of interest was odds of having ambulatory cholecystectomy; secondary outcomes included intraoperative and postoperative complications, and 30-day unplanned admissions following ambulatory cholecystectomy. RESULTS: Among 321,335 cholecystectomies, 190,734 (59.4%) were ambulatory and 130,601 (40.6%) were inpatient. Adjusting for age, sex, insurance, income, residential location, and comorbidities, the odds of undergoing ambulatory versus inpatient cholecystectomy were significantly lower in black (aOR = 0.71, 95% CI [0.69, 0.73], P< 0.001) and Hispanic (aOR = 0.71, 95% CI [0.69, 0.72], P< 0.001) patients compared to white patients, and significantly lower in Medicare (aOR = 0.77, 95% CI [0.75, 0.80] P < 0.001), Medicaid (aOR = 0.56, 95% CI [0.54, 0.57], P< 0.001) and uninsured/self-pay (aOR = 0.28, 95% CI [0.27, 0.28], P< 0.001) patients relative to privately insured patients. Patients with Medicaid and those classified as self-pay/uninsured had higher odds of postoperative complications and unplanned admission as did patients with Medicare compared to privately insured individuals. CONCLUSIONS: Racial and ethnic minorities and the underinsured have a higher likelihood of receiving inpatient as compared to ambulatory cholecystectomy. The higher incidence of postoperative complications in these patients may be associated with unequal access to ambulatory surgery.

Epidemiological and Clinical Observations of Gonococcal Infections in Women and Prevention Strategies.

Neisseria gonorrhoeae is rapidly developing antimicrobial resistance. There is an urgent need for an effective gonococcal vaccine. In this study we examined epidemiological and clinical factors associated with gonorrhea in a cohort of women exposed to men with gonococcal urethritis attending the National Center for STD Control clinic in Nanjing, China, to understand the natural history and the risk factors for gonorrhea in this vulnerable population. This analysis will help identify the best target populations for vaccination, which is essential information for the development of vaccine strategies. We observed that 75% of the women in our cohort yielded a N. gonorrhoeae positive culture (infected women) and reported multiple sexual exposures to their infected partner. Infected women were younger than exposed but uninfected women. Contrary to the general belief that gonorrhea is asymptomatic in most women, 68% of the infected women acknowledged symptoms during their STD clinic visit, and overt inflammatory responses were detected upon medical examination in 88% of subjects. Other sexually transmitted infections were detected in 85% of subjects. This study confirmed that N. gonorrhoeae infections are underdiagnosed in women and, consequentially, untreated. Thus, our analysis reinforces the need to establish strategies for gonococcal prevention through the determination of the target population for a gonococcal vaccine.

The Hepatitis C Continuum of Care Among HIV-Positive Persons with Heavy Alcohol Use in St. Petersburg, Russia.

This study describes the self-reported prevalence of hepatitis C virus (HCV) coinfection and the HCV care continuum among persons enrolled in the St PETER HIV Study, a randomized controlled trial of medications for smoking and alcohol cessation in HIV-positive heavy drinkers and smokers in St. Petersburg, Russia. Baseline health questionnaire data were used to calculate proportions and 95% confidence intervals for self-reported steps along the HCV continuum of care. The cohort included 399 HIV-positive persons, of whom 387 [97.0% (95% CI 95.3-98.7%)] reported a prior HCV test and 315 [78.9% (95% CI 74.9-82.9%)] reported a prior diagnosis of HCV. Among those reporting a diagnosis of HCV, 43 [13.7% (95% CI 9.9-17.4%)] had received treatment for HCV, and 31 [9.8% (95% CI 6.6-13.1%)] had been cured. Despite frequent HCV testing in this HIV-positive Russian cohort, the proportion reporting prior effective HCV treatment was strikingly low. Increased efforts are needed to scale-up HCV treatment among HIV-positive Russians in St. Petersburg.

Effect of Family Navigation on Diagnostic Ascertainment Among Children at Risk for Autism: A Randomized Clinical Trial From DBPNet.

Importance: Early identification of autism spectrum disorder (ASD) is associated with improved cognitive and behavioral outcomes. Targeted strategies are needed to support equitable access to diagnostic services to ensure that children from low-income and racial/ethnic minority families receive the benefits of early ASD identification and treatment. Objective: To test the efficacy of family navigation (FN), an individually tailored, culturally informed care management strategy, to increase the likelihood of achieving diagnostic ascertainment among young children at risk for ASD. Design, Setting, and Participants: This randomized clinical trial of 249 families of children aged 15 to 27 months who had positive screening results for possible ASD was conducted in 11 urban primary care sites in 3 cities. Data collection occurred from February 24, 2015, through November 5, 2018. Statistical analysis was performed on an intent-to-treat basis from November 5, 2018, to July 27, 2020. Interventions: Families were randomized to FN or conventional care management (CCM). Families receiving FN were assigned a navigator who conducted community-based outreach to families to address structural barriers to care and support engagement in recommended services. Families receiving CCM were assigned to a care manager, who did limited telephone outreach. Families received FN or CCM after positive initial screening results and for 100 days after diagnostic ascertainment. Main Outcomes and Measures: The primary outcome, diagnostic ascertainment, was measured as the number of days from randomization to completion of the child's clinical developmental evaluation, when a diagnosis of ASD or other developmental disorder was determined. Results: Among 250 families randomized, 249 were included in the primary analysis (174 boys [69.9%]; mean [SD] age, 22.0 [3.5] months; 205 [82.3%] publicly insured; 233 [93.6%] non-White). Children who received FN had a greater likelihood of reaching diagnostic ascertainment over the course of 1 year (FN, 108 of 126 [85.7%]; CCM, 94 of 123 [76.4%]; unadjusted hazard ratio [HR], 1.39 [95% CI, 1.05-1.84]). Site (Boston, New Haven, and Philadelphia) and ethnicity (Hispanic vs non-Hispanic) moderated the effect of FN (treatment × site interaction; P = .03; Boston: HR, 2.07 [95% CI, 1.31-3.26]; New Haven: HR, 1.91 [95% CI, 0.94-3.89]; and Philadelphia: HR, 0.91 [95% CI, 0.60-1.37]) (treatment × ethnicity interaction; P < .001; Hispanic families: HR, 2.81 [95% CI, 2.23-3.54] vs non-Hispanic families: HR, 1.49 [95% CI, 1.45-1.53]). The magnitude of FN's effect was significantly greater among Hispanic families than among non-Hispanic families (diagnostic ascertainment among Hispanic families: FN, 90.9% [30 of 33], and CCM, 53.3% [16 of 30]; vs non-Hispanic families: FN, 89.7% [35 of 39], and CCM, 77.5% [31 of 40]). Conclusions and Relevance: Family navigation improved the likelihood of diagnostic ascertainment among children from racial/ethnic minority, low-income families who were detected as at risk for ASD in primary care. Results suggest differential effects of FN by site and ethnicity. Trial Registration: ClinicalTrials.gov Identifier: NCT02359084.

Improving Family Navigation for Children With Autism: A Comparison of Two Pilot Randomized Controlled Trials.

OBJECTIVE: Family navigation (FN), a care management strategy, helps families overcome systems and person-level barriers to care. We previously demonstrated FN's feasibility, acceptability, and potential efficacy for increasing access and reducing time to autism-related diagnostic services among low-income, minority children. In this paper, we describe modifications to FN in response to concerns raised in our first pilot randomized controlled trial (RCT), and then assess these modifications in a second pilot RCT. METHODS: An advisory group recommended modifications to recruitment procedures and study conditions. Forty parent-child dyad participants with autism-related concerns were randomized to receive modified usual care (UC) or modified FN. We compared whether the first and second pilot RCTs differed in: participant enrollment, satisfaction with clinical care, and timely completion of the diagnostic assessment. RESULTS: Recruitment improved under the modified protocol with significantly fewer potentially eligible families refusing (19.5% vs 4.8%, P < .05) or being excluded from study enrollment (43.6% vs 0%, P < .01). Comparing the first and second pilot RCTs, regardless of study arm, families in the second pilot were more likely to complete diagnostic assessment (UC: hazard ratio [HR] 3.41, 95% confidence intervals [CI 1.20, 9.68]; FN: HR 2.64, 95% CI [1.31, 5.30]) and report greater satisfaction with clinical care. In the second pilot, compared to UC, FN continued increase the likelihood of completing the diagnostic assessment (HR: 2.57; 95% CI [1.22, 5.40]). CONCLUSIONS: Easy-to-implement system-level enhancements improved study recruitment, satisfaction with care, and completion of a diagnostic assessment. With enhancement, FN continued to confer benefits to families.

Association between alcohol use and inflammatory biomarkers over time among younger adults with HIV-The Russia ARCH Observational Study.

BACKGROUND: Biomarkers of monocyte activation (soluble CD14 [sCD14]), inflammation (interleukin-6 [IL-6]), and altered coagulation (D-dimer) are associated with increased mortality risk in people with HIV. The objective of the Russia Alcohol Research Collaboration on HIV/AIDS (ARCH) study was to evaluate the association between heavy alcohol use and inflammatory biomarkers over time. METHODS: The study sought antiretroviral therapy naive participants with HIV (n = 350) and assessed them at baseline, 12 and 24 months. Linear mixed effects models were used to determine whether heavy drinking (self-report augmented by phosphatidylethanol [PEth], an alcohol biomarker) was longitudinally associated with IL-6, sCD14 and D-dimer adjusting for potential confounders (e.g., demographics, HIV factors, comorbid conditions). RESULTS: Participants' baseline characteristics were as follows: 71% male; mean age of 34 years; 87% self-reported hepatitis C; and 86% current smokers. Mean log10 (HIV RNA) was 4.3 copies/mL. Heavy alcohol use, based on National Institute of Alcohol Abuse and Alcoholism risky drinking criteria and PEth (versus non-heavy alcohol use) was associated with higher sCD14 (adjusted mean difference 125 ng/mL [95% CI: 42, 209]), IL-6 (ratio of means 1.35 [95% CI: 1.17, 1.55] pg/mL), and D-dimer (ratio of means 1.20 [95% CI: 1.06, 1.37] ug/mL) across the two-year follow-up. CONCLUSION: Among HIV+ adults, current heavy alcohol use is associated with higher sCD14, IL-6 and D-dimer over time. Since these biomarkers are associated with mortality, interventions to mitigate effects of heavy drinking on these immune processes merit consideration.

Opportunity Lost? Diagnostic Laparoscopy in Patients with Pancreatic Cancer in the National Surgical Quality Improvement Program Database.

BACKGROUND: Routine preoperative staging in pancreas cancer is controversial. We sought to evaluate the rates of diagnostic laparoscopy (DLAP) for pancreatic cancer. METHODS: We queried the National Surgical Quality Improvement Program for patients with pancreas cancer (2005-2013) and compared groups who underwent DLAP, exploratory laparotomy (XLAP), pancreas resection (RSXN) or therapeutic bypass (THBP). We compared demographics, comorbidities, postoperative complications, 30-day mortality (Chi-square P < 0.05) and trends over time (R2 0-1). RESULTS: We identified 17,138 patients (RSXN 81.8%, XLAP 16.5%, THBP 8.2%, and DLAP 12.9%), with some having multiple CPT codes. Only 10.3% (n = 1432) of RSXN patients underwent DLAP prior to resection. XLAP occurred in 49.5% of non-RSXN patients, of whom 67.1% had no other operation. The percentage of patients undergoing RSXN increased 20.3% over time (R2 0.81), while DLAP decreased 52.6% (R2 0.92). XLAP patients without other operations decreased from 4.2 to 2.4%, although not linearly (R2 0.31). Only 10.3% of XLAP had a diagnostic laparoscopy as well, leaving nearly 90% of these patients with an exploratory laparotomy without RSXN or THBP. DISCUSSION: Diagnostic laparoscopy for pancreas malignancy is becoming less common but could benefit a subset of patients who undergo open exploration without resection or therapeutic bypass.

Liver fibrosis and accelerated immune dysfunction (immunosenescence) among HIV-infected Russians with heavy alcohol consumption - an observational cross-sectional study.

BACKGROUND: The multifactorial mechanisms driving negative health outcomes among risky drinkers with HIV may include immunosenescence. Immunosenescence, aging of the immune system, may be accentuated in HIV and leads to poor outcomes. The liver regulates innate immunity and adaptive immune tolerance. HIV-infected people have high prevalence of liver-related comorbidities. We hypothesize that advanced liver fibrosis/cirrhosis is associated with alterations in T-cell subsets consistent with immunosenescence. METHODS: ART-naïve people with HIV with a recent history of heavy drinking were recruited into a clinical trial of zinc supplementation. Flow cytometry was used to characterize T-cell subsets. The two primary dependent variables were CD8+ and CD4+ T-cells expressing CD28-CD57+ (senescent cell phenotype). Secondary dependent variables were CD8+ and CD4+ T-cells expressing CD45RO + CD45RA- (memory phenotype), CD45RO-CD45RA+ (naïve phenotype), and the naïve phenotype to memory phenotype T-cell ratio (lower ratios associated with immunosenescence). Advanced liver fibrosis/cirrhosis was defined as FIB-4 > 3.25, APRI≥1.5, or Fibroscan measurement ≥10.5 kPa. Analyses were conducted using multiple linear regression adjusted for potential confounders. RESULTS: Mean age was 34 years; 25% female; 88% hepatitis C. Those with advanced liver fibrosis/cirrhosis (N = 25) had higher HIV-1 RNA and more hepatitis C. Advanced liver fibrosis/cirrhosis was not significantly associated with primary or secondary outcomes in adjusted analyses. CONCLUSIONS: Advanced liver fibrosis/cirrhosis was not significantly associated with these senescent T-cell phenotypes in this exploratory study of recent drinkers with HIV. Future studies should assess whether liver fibrosis among those with HIV viral suppression and more advanced, longstanding liver disease is associated with changes in these and other potentially senescent T-cell subsets.

Engaging Mothers With Depressive Symptoms in Care: Results of a Randomized Controlled Trial in Head Start.

OBJECTIVE: The authors sought to determine whether a multicomponent, community-based program for preventing maternal depression also promotes engagement with mental health services for individuals with persistent symptoms. METHODS: Mothers of children enrolled in Head Start were randomly assigned between February 2011 and May 2016 to Problem-Solving Education (PSE) (N=111) or usual services (N=119) and assessed every two months for 12 months. RESULTS: Among 230 participants, 66% were Hispanic; 223 participants were included in the analysis. For all PSE participants, engagement with specialty mental health services increased from approximately 10% to 21% between two and 12 months. The PSE group was more likely than the control group to be engaged in specialty services at 12 months (adjusted odds ratio [AOR]=2.36, 95% confidence interval [CI]=1.07-5.20), and the rate of engagement with specialty services over time (treatment × time interaction) favored PSE (p=.016). Among PSE participants with persistent depressive symptoms over the follow-up period, engagement with specialty services increased from 12% (two months) to approximately 46% (12 months), whereas among control group participants, engagement fluctuated between 24% and 33%, without a clear trajectory pattern. At 12 months, PSE participants with persistent symptoms were more likely to engage with specialty care compared with their counterparts in the control group (AOR=6.95, CI=1.50-32.19). The treatment × time interaction was significant for the persistently symptomatic subgroup (p=.029) but not for the episodically symptomatic or the asymptomatic subgroups. CONCLUSIONS: Embedding mental health programs in Head Start is a promising strategy to engage parents with depressive symptoms in care, especially those with persistent symptoms.

Alcohol Consumption and Bone Mineral Density in People with HIV and Substance Use Disorder: A Prospective Cohort Study.

BACKGROUND: People living with HIV (PLWH) commonly have low bone mineral density (BMD) (low bone mass and osteoporosis) and are at high risk for fractures. Fractures and low BMD are significant causes of morbidity and mortality, increasingly relevant as PLWH age. Alcohol use is common among PLWH and known to affect bone health. The association between alcohol use and changes in BMD among PLWH is not well understood. METHODS: We conducted a 3.5-year prospective cohort study of 250 PLWH with substance use disorder or ever injection drug use. Annual alcohol consumption was measured as a mean of grams per day of alcohol, mean number of heavy drinking days per month, mean number of days abstinent per month, and any heavy drinking, using the 30-day Timeline Followback method twice each year. The primary outcome was annual change in BMD measured each year by dual energy X-ray absorptiometry in grams per square centimeter (g/cm2 ) at the femoral neck. Additional dependent variables included annual change in total hip and lumbar spine BMD, >6% annual decrease in BMD at any site, and incident fractures in the past year. Regression models adjusted for relevant covariates. RESULTS: The median age of participants was 50 years. The median duration of HIV infection was 16.5 years and the mean time since antiretroviral therapy initiation was 12.3 years. At study entry, 67% of participants met criteria for low BMD (46% low bone mass, 21% osteoporosis). Median follow-up was 24 months. We found no significant associations between any measure of alcohol consumption and changes in BMD (g/cm2 ) at the femoral neck (adjusted ß for g/d of alcohol = -0.0032, p = 0.7487), total hip, or lumbar spine. There was no significant association between any measure of alcohol consumption and >6% annual decrease in BMD at any site, or incident fractures. CONCLUSIONS: In this sample of PLWH and substance use disorders or ever injection drug use, we detected no association between any of the alcohol measures used in the study and changes in BMD or incident fractures.

The effect of statin use and intensity on stroke and myocardial infarction after carotid endarterectomy.

OBJECTIVE: Statin use in patients with cerebrovascular disease undergoing carotid endarterectomy (CEA) has been advocated for prevention of stroke and cardiovascular events. However, the effect of statin therapy on long-term outcomes after CEA still needs to be delineated. METHODS: OptumLabs Data Warehouse, a comprehensive, longitudinal, real-world dataset with deidentified lives across claims and clinical information, was used to analyze the rates of stroke, myocardial infarction (MI), and statin use after CEA. Both duration and intensity of statin therapy were investigated. RESULTS: There were 21,277 patients who underwent CEA from 2004 to 2014. The average age was 70 years, and 59.4% were male. The average Elixhauser index score was 4.2. Follow-up was a median of 2.4 years (range, 0.2-10.0 years). Long-term statin use was observed in 57.4%. Statin distribution included atorvastatin 35%, simvastatin 35%, pravastatin 11%, rosuvastatin 10%, and lovastatin 7%. The 30- and 90-day stroke rates were 1.3% and 2.2%, and the MI rates were 0.5% and 1.1%, respectively. Postoperative statin use was associated with a lower perioperative stroke rate at 30 days (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.61-0.98; P = .036) and 90 days (OR, 0.75; 95% CI, 0.62-0.90; P = .002). Postoperative statin use did not show a protective effect on 30-day or 90-day MI rates (OR, 1.01; 95% CI, 0.69-1.46; P = .975) or 90-day MI rates (OR, 0.85; 95% CI, 0.66-1.11; P = .213). High-intensity statin use when compared with standard therapy did not affect 30-day stroke outcomes (OR, 0.96; 95% CI, 0.60-1.5; P = .847) or 90-day stroke outcomes (OR, 1.06; 95% CI, 0.74-1.5; P = .762); or 30-day MI (OR, 0.81; 95% CI, 0.39-1.68; P = .576) or 90-day MI (OR, 1.25; 95% CI, 0.79-1.96; P = .339). Statin use was independently protective against long-term stroke (hazard ratio, 0.82; 95% CI, 0.75-0.91; P < .001) and MI (hazard ratio, 0.83; 95% CI, 0.75-.92; P < .001). CONCLUSIONS: Postoperative statin use among patients undergoing CEA was associated with a decreased risk of stroke at 30 and 90 days, as well as a long-term protective effect against MI and stroke. High-intensity statin use compared with standard use did not show an effect on outcomes of stroke or MI at 30 and 90-days after CEA.