Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry.

BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

Alcohol and drug use severity are independently associated with antiretroviral adherence in the current treatment era.

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.

Vaporized nicotine use among patients in HIV care who smoke tobacco: perceived health effects and effectiveness as a smoking cessation tool.

Evidence suggests adverse health effects from vaporized nicotine (VN) use, such as electronic "e" cigarettes, and limited efficacy to aid tobacco cessation. People with HIV (PWH) smoke tobacco at higher rates than the general population, with greater morbidity, highlighting the necessity of effective tobacco cessation tools. PWH may be more vulnerable to adverse effects of VN. Using semi-structured 1:1 interviews, we examined health beliefs regarding VN, patterns of use, and perceived effectiveness for tobacco cessation among PWH in HIV care at three geographically diverse U.S. sites. PWH (n = 24) had limited understanding of VN product content or health effects, presuming VN less harmful than tobacco cigarettes (TC). VN failed to adequately replicate the psychoactive effects or desired ritual of smoking TC. Concurrent TC use, and continuous VN use throughout the day, was common. Satiety using VN was elusive, and consumption quantity was difficult to track. VN had limited desirability and durability as a TC cessation tool among the interviewed PWH.

Individual and poly-substance use and condomless sex among HIV-uninfected adults reporting heterosexual sex in a multi-site cohort.

BACKGROUND: We analyzed the association between substance use (SU) and condomless sex (CS) among HIV-negative adults reporting heterosexual sex in the Seek, Test, Treat, and Retain (STTR) consortium. We describe the impact of SU as well as person/partner and context-related factors on CS, identifying combinations of factors that indicate the highest likelihood of CS. METHODS: We analyzed data from four US-based STTR studies to examine the effect of SU on CS using two SU exposures: 1) recent SU (within 3 months) and 2) SU before/during sex. Behavioral data were collected via 1:1 or self-administered computerized interviews. Adjusted individual-study, multivariable relative risk regression was used to examine the relationship between CS and SU. We also examined interactions with type of sex and partner HIV status. Pooled effect estimates were calculated using traditional fixed-effects meta-analysis. We analyzed data for recent SU (n = 6781; 82% men, median age = 33 years) and SU before/during sex (n = 2915; 69% men, median age = 40 years). RESULTS: For both exposure classifications, any SU other than cannabis increased the likelihood of CS relative to non-SU (8-16%, p-values< 0.001). In the recent SU group, however, polysubstance use did not increase the likelihood of CS compared to single-substance use. Cannabis use did not increase the likelihood of CS, regardless of frequency of use. Type of sex was associated with CS; those reporting vaginal and anal sex had a higher likelihood of CS compared to vaginal sex only for both exposure classifications (18-21%, p < 0.001). Recent SU increased likelihood of CS among those reporting vaginal sex only (9-10%, p < 0.001); results were similar for those reporting vaginal and anal sex (5-8%, p < 0.01). SU before/during sex increased the likelihood of CS among those reporting vaginal sex only (20%; p < 0.001) and among those reporting vaginal and anal sex (7%; p = 0.002). Single- and poly-SU before/during sex increased the likelihood of CS for those with exclusively HIV-negative partners (7-8%, p ≤ 0.02), and for those reporting HIV-negative and HIV-status unknown partners (9-13%, p ≤ 0.03). CONCLUSION: Except for cannabis, any SU increased the likelihood of CS. CS was associated with having perceived HIV-negative partners and with having had both anal/vaginal sex.

Patient acceptability and usability of a self-administered electronic patient-reported outcome assessment in HIV care: relationship with health behaviors and outcomes.

We assessed acceptability/usability of tablet-based patient-reported outcome (PRO) assessments among patients in HIV care, and relationships with health outcomes using a modified Acceptability E-Scale (AES) within a self-administered PRO assessment. Using multivariable linear regression, we measured associations between patient characteristics and continuous combined AES score. Among 786 patients (median age=48; 91% male; 49% white; 17% Spanish-speaking) overall mean score was 26/30 points (SD: 4.4). Mean scores per dimension (max 5, 1=lowest acceptability, 5=highest): ease of use 4.7, understandability 4.7, time burden 4.3, overall satisfaction 4.3, helpfulness describing symptoms/behaviors 4.2, and enjoyability 3.8. Higher overall score was associated with race/ethnicity (+1.3 points/African-American patients (95%CI:0.3-2.3); +1.6 points/Latino patients (95%CI:0.9-2.3) compared to white patients). Patients completing PROs in Spanish scored +2.4 points on average (95%CI:1.6-3.3). Higher acceptability was associated with better quality of life (0.3 points (95%CI:0.2-0.5)) and adherence (0.4 points (95%CI:0.2-0.6)). Lower acceptability was associated with: higher depression symptoms (-0.9 points (95%CI:-1.4 to -0.4)); recent illicit opioid use (-2.0 points (95%CI:-3.9 to -0.2)); multiple recent sex partners (-0.8 points (95%CI:-1.5 to -0.1)). While patients endorsing depression symptoms, recent opioid use, condomless sex, or multiple sex partners found PROs less acceptable, overall, patients found the assessments highly acceptable and easy to use.

Anemia risk factors among people living with HIV across the United States in the current treatment era: a clinical cohort study.

BACKGROUND: Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking. METHODS: Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site. RESULTS: This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR. CONCLUSION: Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.

A Comparison of Adherence Timeframes Using Missed Dose Items and Their Associations with Viral Load in Routine Clinical Care: Is Longer Better?

Questions remain regarding optimal timeframes for asking about adherence in clinical care. We compared 4-, 7-, 14-, 30-, and 60-day timeframe missed dose items with viral load levels among 1099 patients on antiretroviral therapy in routine care. We conducted logistic and linear regression analyses examining associations between different timeframes and viral load using Bayesian model averaging (BMA). We conducted sensitivity analyses with subgroups at increased risk for suboptimal adherence (e.g. patients with depression, substance use). The 14-day timeframe had the largest mean difference in adherence levels among those with detectable and undetectable viral loads. BMA estimates suggested the 14-day timeframe was strongest overall and for most subgroups although findings differed somewhat for hazardous alcohol users and those with current depression. Adherence measured by all missed dose timeframes correlated with viral load. Adherence calculated from intermediate timeframes (e.g. 14-day) appeared best able to capture adherence behavior as measured by viral load.

Lessons learned from the design and implementation of myocardial infarction adjudication tailored for HIV clinical cohorts.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol?

BACKGROUND: Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage. OBJECTIVES: To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 µg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 µg (DRSP/EE30). METHODS: Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current). RESULTS: The study included 238 683 drospirenone and 193,495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) vs. levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41). CONCLUSIONS: We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected.

Benzodiazepines and elderly drivers: a comparison of pharmacoepidemiological study designs.

PURPOSE: Contradictory results were published from two studies in the late 1990s about the effects of long half-life benzodiazepine use on the risk of motor vehicle crashes (MVCs) in the elderly. The use of different study designs could explain the differences observed in these studies. METHODS: The results of an unmatched case-control study were compared to those of a case-crossover study using the same prescription claims database to determine whether the current use of benzodiazepines increased the risk of MVCs. RESULTS: There were 5579 cases and 12 911 controls identified between the years 1990 and 1993 in the province of Quebec, Canada. The case-control approach demonstrated an increased rate of injurious MVC associated with the current use of long-acting benzodiazepines [odds ratio (OR) 1.45; 95% confidence interval (CI): 1.12-1.88]. The case-crossover approach applied to all cases did not show any association [OR 0.99; 95%CI: 0.83-1.19]. However, among the cases restricted to subjects with four or less prescriptions filled in the previous year, corresponding more to transient exposures, the OR was elevated [OR 1.53; 95%CI: 1.08-2.16]. CONCLUSIONS: Differences in study design and analysis may explain some of the discrepancies in previous results. Both study designs provide evidence that long-acting benzodiazepines appear to be associated with an increased risk of MVC.

Furosemide use and hospitalization for benign prostatic hyperplasia.

OBJECTIVE: Recent studies have shown that furosemide may have anti-inflammatory properties. We explored whether exposure to furosemide would reduce the risk of being hospitalized with prostatism, a marker of benign prostatic hyperplasia. METHODS: Using record linkage and the computerized health insurance databases of the province of Québec, Canada, we identified a cohort of men 65 years of age and older within which we conducted a case-control study. Cases were individuals hospitalized with prostatism (ICD-9 code 600) between January 1991 and June 1993, with the index date taken as the date of hospitalisation. Controls were those not having experienced the event during the study period, with an index date selected randomly during their follow-up. Cases and controls were required to have at least 2 (1/2) years of health coverage prior to index date in order to identify risk factors for benign prostatic hyperplasia and establish baseline medical history. We assessed the subjects' exposure to furosemide and various other diuretics in the period 180 to 900 days preceding the index date. Logistic regression was used to evaluate the association between the use of furosemide and hospitalization for prostatism, adjusting for potential confounders. RESULTS: The cohort included 8,814 subjects, of which 231 were cases and 8,583 controls. The rate of hospitalization for prostatism was lower for users of furosemide compared to non-users (adjusted rate ratio 0.49; 95% CI: 0.25-0.95). There was no association with the use of thiazide or potassium sparing diuretics (adjusted rate ratio 0.95; 95% CI: 0.65-1.37). Results suggestive of a protective effect associated with corticosteroid use were observed (adjusted rate ratio 0.64; 95% CI: 0.44-0.93). CONCLUSIONS: This study supports the hypothesis that furosemide can reduce the risk of hospitalization for prostatism, a marker of benign prostatic hyperplasia.

Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease.

CONTEXT: Recent reports suggest an increasing occurrence and severity of Clostridium difficile-associated disease. We assessed whether the use of gastric acid-suppressive agents is associated with an increased risk in the community. OBJECTIVE: To determine whether the use of gastric acid-suppressive agents increases the risk of C difficile-associated disease in a community population. DESIGN, SETTING, AND PATIENTS: We conducted 2 population-based case-control studies using the United Kingdom General Practice Research Database (GPRD). In the first study, we identified all 1672 cases of C difficile recorded between 1994 and 2004 among all patients registered for at least 2 years in each practice. Each case was matched to 10 controls on calendar time and the general practice. In the second study, a subset of these cases defined as community-acquired, that is, not hospitalized in the prior year, were matched on practice and age with controls also not hospitalized in the prior year. MAIN OUTCOME MEASURES: The incidence of C difficile and risk associated with gastric acid-suppressive agent use. RESULTS: The incidence of C difficile in patients diagnosed by their general practitioners in the General Practice Research Database increased from less than 1 case per 100,000 in 1994 to 22 per 100,000 in 2004. The adjusted rate ratio of C difficile-associated disease with current use of proton pump inhibitors was 2.9 (95% confidence interval [CI], 2.4-3.4) and with H2-receptor antagonists the rate ratio was 2.0 (95% CI, 1.6-2.7). An elevated rate was also found with the use of nonsteroidal anti-inflammatory drugs (rate ratio, 1.3; 95% CI, 1.2-1.5). CONCLUSIONS: The use of acid-suppressive therapy, particularly proton pump inhibitors, is associated with an increased risk of community-acquired C difficile. The unexpected increase in risk with nonsteroidal anti-inflammatory drug use should be investigated further.

Macrolide therapy for Chlamydia pneumoniae in the secondary prevention of coronary artery disease: a meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: As recent studies have shown that antibiotic therapy to eradicate Chlamydia pneumoniae may be beneficial in the secondary prevention of coronary artery disease, and studies to date may have lacked statistical power, we conducted a meta-analysis of randomized controlled trials to determine the role of antibiotic therapy in this patient population. DESIGN: Systematic review and meta-analysis of randomized controlled trials. PATIENTS: A total of 12,032 patients from nine studies. MEASUREMENTS AND MAIN RESULTS: We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and abstracts of conference proceedings to identify pertinent studies. The random effects model was used to estimate a pooled relative risk. Heterogeneity was assessed using the bootstrap version of the Q statistic with 1000 replications. In total, we reviewed nine randomized controlled trials enrolling 12,032 patients; six enrolled patients with acute coronary syndrome, two enrolled patients with stable coronary artery disease, and one enrolled a mixed population. Compared with placebo, macrolide therapy was not associated with a significant reduction in any coronary event (relative risk [RR] 0.98, 95% confidence interval [CI] 0.88-1.08), myocardial infarction or angina (RR 0.89, 95% CI 0.68-1.16), or overall mortality (RR 0.95, 95% CI 0.81-1.12). CONCLUSION: Our results do not support routine use of antichlamydial therapy for secondary prevention of coronary events.