Association of Syndemic Unhealthy Alcohol Use, Smoking, and Depressive Symptoms on Incident Cardiovascular Disease among Veterans With and Without HIV-Infection.

Unhealthy alcohol use, smoking, and depressive symptoms are risk factors for cardiovascular disease (CVD). Little is known about their co-occurrence - termed a syndemic, defined as the synergistic effect of two or more conditions-on CVD risk in people with HIV (PWH). We used data from 5621 CVD-free participants (51% PWH) in the Veteran's Aging Cohort Study-8, a prospective, observational study of veterans followed from 2002 to 2014 to assess the association between this syndemic and incident CVD by HIV status. Diagnostic codes identified cases of CVD (acute myocardial infarction, stroke, heart failure, peripheral artery disease, and coronary revascularization). Validated measures of alcohol use, smoking, and depressive symptoms were used. Baseline number of syndemic conditions was categorized (0, 1, ≥ 2 conditions). Multivariable Cox Proportional Hazards regressions estimated risk of the syndemic (≥ 2 conditions) on incident CVD by HIV-status. There were 1149 cases of incident CVD (52% PWH) during the follow-up (median 10.1 years). Of the total sample, 64% met our syndemic definition. The syndemic was associated with greater risk for incident CVD among PWH (Hazard Ratio [HR] 1.87 [1.47-2.38], p < 0.001) and HIV-negative veterans (HR 1.70 [1.35-2.13], p < 0.001), compared to HIV-negative with zero conditions. Among those with the syndemic, CVD risk was not statistically significantly higher among PWH vs. HIV-negative (HR 1.10 [0.89, 1.37], p = .38). Given the high prevalence of this syndemic combined with excess risk of CVD, these findings support linked-screening and treatment efforts.

Does Reducing Drinking in Patients with Unhealthy Alcohol Use Improve Pain Interference, Use of Other Substances, and Psychiatric Symptoms?

BACKGROUND: We aimed to investigate the impact of reducing drinking in patients with unhealthy alcohol use on improvement of chronic pain interference, substance use, and psychiatric symptoms. METHODS: We analyzed longitudinal data from 2003 to 2015 in the Veterans Aging Cohort Study, a prospective, multisite observational study of US veterans, by emulating a hypothetical randomized trial (a target trial). Alcohol use was assessed using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, and outcome conditions were assessed via validated survey items. Individuals were followed from the first time their AUDIT score was ≥ 8 (baseline), a threshold consistent with unhealthy alcohol use. We compared individuals who reduced drinking (AUDIT < 8) at the next follow-up visit with individuals who did not (AUDIT ≥ 8). We fit separate logistic regression models to estimate odds ratios for improvement of each condition 2 years postbaseline among individuals who had that condition at baseline: moderate or severe pain interference symptoms, tobacco smoking, cannabis use, cocaine use, depressive symptoms, and anxiety symptoms. Inverse probability weighting was used to account for potential selection bias and confounding. RESULTS: Adjusted 2-year odds ratios (95% confidence intervals) for associations between reducing drinking and improvement or resolution of each condition were as follows: 1.49 (0.91, 2.42) for pain interference symptoms, 1.57 (0.93, 2.63) for tobacco smoking, 1.65 (0.92, 2.95) for cannabis use, 1.83 (1.03, 3.27) for cocaine use, 1.11 (0.64, 1.92) for depressive symptoms, and 1.33 (0.80, 2.22) for anxiety symptoms. CONCLUSIONS: We found some evidence for improvement of pain interference symptoms and substance use after reducing drinking among US veterans with unhealthy alcohol use, but confidence intervals were wide.

Insights Provided by Depression Screening Regarding Pain, Anxiety, and Substance use in a Veteran Population.

OBJECTIVE: We sought to quantify the extent to which a depression screening instrument commonly used in primary care settings provides additional information regarding pain interference symptoms, anxiety, and substance use. METHODS: Veterans Aging Cohort Study (VACS) data collected from 2003 through 2015 was used to calculate odds ratios (OR) for associations between positive depression screening result cutoffs and clustering conditions. We assessed the test performance characteristics (likelihood ratio value, positive predictive value, and the percentage of individuals correctly classified) of a positive Patient Health Questionnaire (PHQ-9 & PHQ-2) depression screen for the identification of pain interference symptoms, anxiety, and substance use. RESULTS: A total 7731 participants were included in the analyses. The median age was 50 years. The PHQ-9 threshold of ≥20 was strongly associated with pain interference symptoms (OR 21.6, 95% CI 17.5-26.7) and anxiety (OR 72.1, 95% CI 52.8-99.0) and yielded likelihood ratio values of 7.5 for pain interference symptoms and 21.8 for anxiety and positive predictive values (PPV) of 84% and 95%, respectively. A PHQ-9 score of ≥10 still showed significant associations with pain interference symptoms (OR 6.1, 95% CI 5.4-6.9) and symptoms of anxiety (OR 11.3, 95% CI 9.7-13.1) and yet yielded lower likelihood ratio values (4.36 & 8.24, respectively). The PHQ-9 was less strongly associated with various forms of substance use. CONCLUSION: Depression screening provides substantial additional information regarding the likelihood of pain interference symptoms and anxiety and should trigger diagnostic assessments for these other conditions.

Association of Alcohol Screening Scores With Adverse Mental Health Conditions and Substance Use Among US Adults.

Importance: Alcohol screening may be associated with health outcomes that cluster with alcohol use (ie, alcohol-clustering conditions), including depression, anxiety, and use of tobacco, marijuana, and illicit drugs. Objective: To quantify the extent to which alcohol screening provides additional information regarding alcohol-clustering conditions and to compare 2 alcohol use screening tools commonly used for this purpose. Design, Setting, and Participants: This longitudinal cohort study used data from the Veterans Aging Cohort Study. Data were collected at 8 Veterans Health Administration facilities from 2003 through 2012. A total of 7510 participants were enrolled, completed a baseline survey, and were followed up. Veterans with HIV were matched with controls without HIV by age, race, sex, and site of care. Data were analyzed from January 2019 to December 2019. Exposures: The Alcohol Use Disorders Identification Test (AUDIT) and Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) were used to assess alcohol use, with 4 risk groups delineated for each test: score 0 to 7 (reference), score 8 to 15, score 16 to 19, and score 20 to 40 (maximum score) for the full AUDIT and score 0 to 3 (reference), score 4 to 5, score 6 to 7, and score 8 to 12 (maximum score) for the AUDIT-C. Main Outcomes and Measures: Alcohol-clustering conditions, including self-reported symptoms of depression and anxiety and use of tobacco, marijuana, cocaine, other stimulants, opioids, and injection drugs. Results: A total of 6431 US patients (6104 [95%] men; median age during survey years 2003-2004, 50 years [range, 28-86 years; interquartile range, 44-55 years]) receiving care in the Veterans Health Administration completed 1 or more follow-up surveys when the AUDIT was administered and were included in the present analyses. Of the male participants, 4271 (66%) were African American, 1498 (24%) were white, and 590 (9%) were Hispanic. The AUDIT and AUDIT-C scores were associated with each alcohol-clustering condition. In particular, an AUDIT score of 20 or higher (vs <8, the reference) was associated with symptoms of depression (odds ratio [OR], 8.37; 95% CI, 6.20-11.29) and anxiety (OR, 8.98; 95% CI, 6.39-12.60) and with self-reported use of tobacco (OR, 14.64; 95% CI, 8.94-23.98), marijuana (OR, 12.41; 95% CI, 8.61-17.90), crack or cocaine (OR, 39.47; 95% CI, 27.38-56.90), other stimulants (OR, 21.31; 95% CI, 12.73-35.67), and injection drugs (OR, 8.67; 95% CI, 5.32-14.13). An AUDIT score of 20 or higher yielded likelihood ratio (sensitivity / 1 - specificity) values greater than 3.5 for depression, anxiety, crack or cocaine use, and other stimulant use. Associations between AUDIT-C scores and alcohol-clustering conditions were more modest. Conclusions and Relevance: Alcohol screening can inform decisions about further screening and diagnostic assessment for alcohol-clustering conditions, particularly for depression, anxiety, crack or cocaine use, and other stimulant use. Future studies using clinical diagnoses rather than screening tools to assess alcohol-clustering conditions may be warranted.

Association of Syndemic Unhealthy Alcohol Use, Cigarette Use, and Depression With All-Cause Mortality Among Adults Living With and Without HIV Infection: Veterans Aging Cohort Study.

BACKGROUND: The prevalence and risk of concurrent unhealthy drinking, cigarette use, and depression on mortality among persons living with HIV (PLWH) is unclear. This study applied a syndemic framework to assess whether these co-occurring conditions increase mortality and whether such risk is differential by HIV status. METHODS: We evaluated 6721 participants (49.8% PLWH) without baseline cancer from the Veterans Aging Cohort Study, a prospective, observational cohort of PLWH and matched uninfected veterans enrolled in 2002 and followed through 2015. Multivariable Cox proportional hazards regressions estimated risk of a syndemic score (number of conditions: that is, unhealthy drinking, cigarette use, and depressive symptoms) on all-cause mortality by HIV status, adjusting for demographic, health status, and HIV-related factors. RESULTS: Fewer than 10% of participants had no conditions; 25.6% had 1, 51.0% had 2, and 15.0% had all 3. There were 1747 deaths (61.9% PLWH) during the median follow-up (11.4 years). Overall, age-adjusted mortality rates/1000 person-years increased with a greater number of conditions: (0: 12.0; 1: 21.2; 2: 30.4; 3: 36.3). For 3 conditions, the adjusted hazard ratio of mortality was 36% higher among PLWH compared with uninfected participants with 3 conditions (95% confidence interval, 1.07-1.72; P = .013), after adjusting for health status and HIV disease progression. Among PLWH and uninfected participants, mortality risk persisted after adjustment for time-updated health status. CONCLUSIONS: Syndemic unhealthy drinking, cigarette use, and depression are common and are associated with higher mortality risk among PLWH, underscoring the need to screen for and treat these conditions.

High-dose prescribed opioids are associated with increased risk of heroin use among United States military veterans.

Despite evidence linking increased risk of opioid use disorder with specific opioid-prescribing patterns, the relationship between these patterns and heroin use is less understood. This study aimed to determine whether dose and duration of opioid prescriptions predict subsequent heroin use in United States veterans. We analyzed data from 2002 to 2012 from the Veterans Aging Cohort Study, a prospective cohort study. We used inverse probability of censoring weighted Cox regression to examine the relationship between self-reported past year heroin use and 2 primary predictors: (1) prior receipt of a high-dose opioid prescription (≥90 mg morphine equivalent daily dose), and (2) prior receipt of a long-term opioid prescription (≥90 days). Heroin use was ascertained using most recent value of time-updated self-reported past year heroin use. Models were adjusted for HIV and hepatitis C virus infection status, sociodemographics, pain interference, posttraumatic stress disorder, depression, and use of marijuana, cocaine, methamphetamines, and unhealthy alcohol use. In the final model, prior receipt of a high-dose opioid prescription was associated with past year heroin use (adjusted hazard ratio use = 2.54, 95% confidence interval: 1.26-5.10), whereas long-term opioid receipt was not (adjusted hazard ratio = 1.09, 95% confidence interval: 0.75-1.57). Patients receiving high-dose opioid prescriptions should be monitored for heroin use. These findings support current national guidelines recommending against prescribing high-dose opioids for treating pain.

Predictors of timely opioid agonist treatment initiation among veterans with and without HIV.

BACKGROUND: Opioid use disorder (OUD) is prevalent among people with HIV (PWH). Opioid agonist therapy (OAT) is the most effective treatment for OUD and is associated with improved health outcomes, but is often not initiated. To inform clinical practice, we identified factors predictive of OAT initiation among patients with and without HIV. METHODS: We identified 19,698 new clinical encounters of OUD between 2000 and 2012 in the Veterans Aging Cohort Study (VACS), a national observational cohort of PWH and matched uninfected controls. Mixed effects models examined factors predictive of OAT initiation within 30-days of a new OUD clinical encounter. RESULTS: 4.9% of both PWH and uninfected patients initiated OAT within 30 days of a new OUD clinical encounter. In adjusted models, participants with a psychiatric diagnosis (aOR = 0.54, 95% CI 0.47 - 0.62), PWH (aOR = 0.79, 95% CI 0.68-0.92), and rural residence (aOR = 0.56, 95% CI 0.39-0.78) had a lower likelihood of any OAT initiation, while African-American patients (aOR = 1.60, 95% CI 1.34-1.92), those with an alcohol related diagnosis (aOR = 1.76, 95% CI 1.48-2.08), diagnosis year 2005-2008 relative to 2000-2004 (aOR = 1.24, 95% CI 1.05-1.45), and patients with HCV (aOR = 1.50, 95% CI 1.27-1.77) had a greater likelihood of initiating any OAT within 30 days. Predictive factors were similar in the total sample and PWH only models. CONCLUSIONS: PWH were less likely to receive timely OAT initiation than demographically similar uninfected patients. Given the health benefits of such treatment, the low rate of OAT initiation warrants focused efforts in both PWH and uninfected populations.

Duration of opioid prescriptions predicts incident nonmedical use of prescription opioids among U.S. veterans receiving medical care.

BACKGROUND/AIMS: Although nonmedical use of prescription opioids (NMUPO) is a public health problem, few studies have examined the new-onset NMUPO in clinical populations. We estimated NMUPO incidence among veterans in medical care who had received prescription opioid medication and examined correlates of new-onset NMUPO. DESIGN: Prospective cohort study. SETTING: Veterans Health Administration primary care and infectious disease clinics in Atlanta, Baltimore, Bronx, Houston, Los Angeles, Manhattan, Pittsburgh, and Washington, DC. PARTICIPANTS: Patients enrolled in the Veterans Aging Cohort Study wave 3 (2005-2007) who received prescription opioids in the previous year and without lifetime NMUPO were followed at waves 4 and 5 (2008-2011). MEASUREMENTS: Cox proportional hazards regression was used to examine the relationship between duration of prescription opioid receipt and incident NMUPO, adjusting for demographics, alcohol and tobacco use, substance use disorders, psychiatric and medical diagnoses, and medication-related characteristics. FINDINGS: Among eligible participants (n = 815), the median age was 52 (IQR = 47-58) and 498 (59.8%) were Black; 122 (15.0%) reported new-onset NMUPO, for an incidence rate of 5.0 per 100 person-years. In a multivariable Cox model, compared to <30 days, receipt of prescription opioids for 30-180 days (adjusted hazard ratio [AHR] = 1.65 95% CI: 1.06, 2.58) or >180 days (AHR = 1.99, 95% CI: 1.21, 3.29) was associated with incident NMUPO. CONCLUSIONS: Duration of prescription opioid receipt is a risk factor for incident NMUPO among veterans receiving medical care. Providers who prescribe opioids should monitor for NMUPO, especially among those with a longer duration of opioid therapy.

National Trends in Hospitalizations for Opioid Poisonings Among Children and Adolescents, 1997 to 2012.

Importance: National data show a parallel relationship between recent trends in opioid prescribing practices and hospitalizations for opioid poisonings in adults. No similar estimates exist describing hospitalizations for opioid poisonings in children and adolescents. Objective: To describe the incidence and characteristics of hospitalizations attributed to opioid poisonings in children and adolescents. Design, Setting, and Participants: Retrospective analysis of serial cross-sectional data from a nationally representative sample of US pediatric hospital discharge records collected every 3 years from January 1, 1997, through December 31, 2012. The Kids' Inpatient Database was used to identify 13 052 discharge records for patients aged 1 to 19 years who were hospitalized for opioid poisonings. Data were analyzed within the collection time frame. Main Outcomes and Measures: Poisonings attributed to prescription opioids were identified by codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. In adolescents aged 15 to 19 years, poisonings attributed to heroin were also identified. Census estimates were used to calculate incidence per 100 000 population. The Cochran-Armitage test for trend was used to assess for changes in incidence over time. Results: From 1997 to 2012, a total of 13 052 (95% CI, 12 500-13 604) hospitalizations for prescription opioid poisonings were identified. The annual incidence of hospitalizations for opioid poisonings per 100 000 children aged 1 to 19 years rose from 1.40 (95% CI, 1.24-1.56) to 3.71 (95% CI, 3.44-3.98), an increase of 165% (P for trend, <.001). Among children 1 to 4 years of age, the incidence increased from 0.86 (95% CI, 0.60-1.12) to 2.62 (95% CI, 2.17-3.08), an increase of 205% (P for trend, <.001). For adolescents aged 15 to 19 years, the incidence increased from 3.69 (95% CI, 3.20-4.17) to 10.17 (95% CI, 9.48-10.85), an increase of 176% (P for trend, <.001). In this age group, poisonings from heroin increased from 0.96 (95% CI, 0.75-1.18) to 2.51 (95% CI, 2.21-2.80), an increase of 161% (P for trend, <.001); poisonings involving methadone increased from 0.10 (95% CI, 0.03-0.16) to 1.05 (95% CI, 0.87-1.23), an increase of 950% (P for trend, <.001). Conclusions and Relevance: During the course of 16 years, hospitalizations attributed to opioid poisonings rose nearly 2-fold in the pediatric population. Hospitalizations increased across all age groups, yet young children and older adolescents were most vulnerable to the risks of opioid exposure. Mitigating these risks will require comprehensive strategies that target opioid storage, packaging, and misuse.

Non-medical use of prescription opioids is associated with heroin initiation among US veterans: a prospective cohort study.

AIMS: To estimate the influence of non-medical use of prescription opioids (NMUPO) on heroin initiation among US veterans receiving medical care. DESIGN: Using a multivariable Cox regression model, we analyzed data from a prospective, multi-site, observational study of HIV-infected and an age/race/site-matched control group of HIV-uninfected veterans in care in the United States. Approximately annual behavioral assessments were conducted and contained self-reported measures of NMUPO and heroin use. SETTING: Veterans Health Administration (VHA) infectious disease and primary care clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh and Washington, DC. PARTICIPANTS: A total of 3396 HIV-infected and uninfected patients enrolled into the Veterans Aging Cohort Study who reported no life-time NMUPO or heroin use, had no opioid use disorder diagnoses at baseline and who were followed between 2002 and 2012. MEASUREMENTS: The primary outcome measure was self-reported incident heroin use and the primary exposure of interest was new-onset NMUPO. Our final model was adjusted for socio-demographics, pain interference, prior diagnoses of post-traumatic stress disorder and/or depression and self-reported other substance use. FINDINGS: Using a multivariable Cox regression model, we found that non-medical use of prescription opioids NMUPO was associated positively and independently with heroin initiation [adjusted hazard ratio (AHR) = 5.43, 95% confidence interval (CI) = 4.01, 7.35]. CONCLUSIONS: New-onset non-medical use of prescription opioids (NMUPO) is a strong risk factor for heroin initiation among HIV-infected and uninfected veterans in the United States who reported no previous history of NMUPO or illicit opioid use.

Preserved memory function during bispectral index-guided anesthesia with sevoflurane for major orthopedic surgery.

BACKGROUND: Memory function under anesthesia is undesired but may arise from light hypnosis as well as stress-enhanced learning during surgery. The bispectral index (BIS, Aspect Medical Systems, Norwood, MA) is a monitor of hypnotic state that can help to avoid light hypnosis (i.e., BIS above 60). This study tested the hypothesis that BIS-guided anesthesia maintaining BIS 50-60 reduces the likelihood of memory function under anesthesia. METHODS: After obtaining informed consent, 128 patients scheduled for joint replacement surgery under general anesthesia with sevoflurane were randomly assigned to BIS-guided anesthesia, titrating drugs to BIS 50-60 (BIS group), or a standard practice group in which BIS was recorded but did not guide drug administration. After induction, all patients were repeatedly played a list of 15 words. After recovery from anesthesia, all were interviewed about recall and completed a recognition memory test containing the presented words (targets, 33.3%) and new words (distractors). Preoperatively, patients filled out a stress questionnaire (Spielberger State-Trait Anxiety Inventory). RESULTS: BIS values above 60 were recorded in both groups, but no patient recalled the presented words postoperatively. Only patients in the BIS group selected targets more often than distractors (37.1% vs. 31.5% hit rate, P = 0.001). Target hit rates correlated poorly to stress scores (P > 0.9), but were associated with the amount of fentanyl received preoperatively (P = 0.01) and pain management technique (P < 0.01). CONCLUSIONS: BIS titration to BIS 50-60 does not necessarily curb memory function under anesthesia when BIS values higher than 60 occur. Preoperative analgesia attenuated the likelihood of memory function under anesthesia.