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

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

Reply to Ruan et al. (2017): Non-medical use of prescription opioids is associated with heroin initiation among US veterans.

We thank Ruan and colleagues for their letter and appreciate their comments regarding our recent study, which demonstrated an independent association between non-medical use of prescription opioids (NMUPO) and heroin initiation among US veterans

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 Veterans 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

Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

etuximab, an anti-EGFR monoclonal antibody (mAb), is approved for advanced head and neck squamous cell carcinoma (HNSCC) but benefits a minority. An established tumor-intrinsic resistance mechanism is cross-talk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways. Dual pathway inhibition may overcome cetuximab resistance. This Phase I study evaluated the combination of cetuximab and ficlatuzumab, an anti-HGF mAb, in patients with recurrent/metastatic HNSCC. The primary objective was to establish the recommended Phase II dose (RP2D). Secondary objectives included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Mechanistic tumor-intrinsic and immune biomarkers were explored. Thirteen patients enrolled with no dose-limiting toxicities observed at any dose tier. Three evaluable patients were treated at Tier 1 and nine at Tier 2, which was determined to be the RP2D (cetuximab 500 mg/m2 and ficlatuzumab 20 mg/kg every 2 weeks). Median PFS and OS were 5.4 (90% CI = 1.9–11.4) and 8.9 (90% CI = 2.7–15.2) months, respectively, with a confirmed ORR of 2 of 12 (17%; 90% CI = 6–40%). High circulating soluble cMet levels correlated with poor survival. An increase in peripheral T cells, particularly the CD8+ subset, was associated with treatment response whereas progression was associated with expansion of a distinct myeloid population. This well-tolerated combination demonstrated promising activity in cetuximab-resistant, advanced HNSCC

Trajectories of Self-Reported Opioid Use Among Patients With HIV Engaged in Care: Results From a National Cohort Study.

BACKGROUND: No prior studies have characterized long-term patterns of opioid use regardless of source or reason for use among patients with HIV (PWH). We sought to identify trajectories of self-reported opioid use and their correlates among a national sample of PWH engaged in care. SETTING: Veterans Aging Cohort Study, a prospective cohort including PWH receiving care at 8 US Veterans Health Administration (VA) sites. METHODS: Between 2002 and 2018, we assessed past year opioid use frequency based on self-reported "prescription painkillers" and/or heroin use at baseline and follow-up. We used group-based trajectory models to identify opioid use trajectories and multinomial logistic regression to determine baseline factors independently associated with escalating opioid use compared to stable, infrequent use. RESULTS: Among 3702 PWH, we identified 4 opioid use trajectories: (1) no lifetime use (25%); (2) stable, infrequent use (58%); (3) escalating use (7%); and (4) de-escalating use (11%). In bivariate analysis, anxiety; pain interference; prescribed opioids, benzodiazepines and gabapentinoids; and marijuana use were associated with escalating opioid group membership compared to stable, infrequent use. In multivariable analysis, illness severity, pain interference, receipt of prescribed benzodiazepine medications, and marijuana use were associated with escalating opioid group membership compared to stable, infrequent use. CONCLUSION: Among PWH engaged in VA care, 1 in 15 reported escalating opioid use. Future research is needed to understand the impact of psychoactive medications and marijuana use on opioid use and whether enhanced uptake of evidence-based treatment of pain and psychiatric symptoms can prevent escalating use among PWH

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

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