Substance use disparities by age, race, sex, and sexual orientation among persons living with HIV in the Southern U.S.

BACKGROUND: Alcohol and drug use is overrepresented among individuals living with Human Immunodeficiency Virus (HIV) and is associated with poor health outcomes. Determining the extent to which substance use differs between demographic profiles of people living with HIV (PLWH) would determine at-risk groups that would benefit from intervention. METHODS: Cross-sectional screening data (N = 1307, Mage = 42.7 years, 66% male, 86% African American, 39% sexual minority) was examined from an HIV clinic in the southern U.S. largely treating underserved and low-income patients. Age, gender, race/ethnicity, sexual orientation, and their interactions were entered as predictors of substance use and related impairment in a series of zero-inflated negative binomial regressions. RESULTS: African Americans reported more drug use (p = 0.004) and drug-related negative consequences (p = 0.003). Notably, alcohol-related negative consequences of African American heterosexuals were much higher at younger ages, compared to sexual minorities (regardless of race) and White heterosexuals of all age groups (p = 0.04). CONCLUSIONS: Among PLWH in the U.S. South, African Americans may be uniquely at-risk with for problems related to drug-related functional impairment. Specifically, young heterosexual African Americans are at high risk for alcohol-related impairment. Implications are discussed.

Low-Burden Universal Substance Use Screening in a Primary Care Clinic to Lower Implementation Barriers.

Universal substance use screening in primary care can proactively identify patients for intervention, though implementation is challenging. This project developed a strategy for universal low time- and labor-cost screening, brief intervention, and referral for treatment (SBIRT) in an HIV primary care clinic at an academic medical center in the Southeastern USA. Screening was implemented using a tablet computer that calculated results in real time and suggested motivational language for provider response. A brief intervention (BNI) was conducted by a trained professional as needed, preventing the need for all clinic providers to be competent in motivational interviewing (MI). More than 1868 patients were screened in 12 months, with an MI intervention conducted for 101 patients with higher risk use. Forty-four patients were referred for in-clinic treatment, compared to nine in the previous year. Computer-based, self-administered screening with real-time linkage to a BNI can allow recommended screening with low provider burden.

Users of cannabis-only are less likely to accept brief interventions than other substance use profiles in a sample of people living with HIV/AIDS.

BACKGROUND AND OBJECTIVES: Research has shown that people living with HIV/AIDS (PLWHA) engage in increased rates of substance use, which has a number of potential negative health outcomes. Increased legalization of cannabis is likely to further increase the availability and use of cannabis in this population. Efforts have been made to integrate screening and intervention resources as part of an individual's routine healthcare visits. Though brief approaches such as Screening and Brief Intervention (SBIRT) have shown promise in addressing alcohol use, results are mixed in addressing cannabis use. The present study investigated how individuals reporting cannabis use responded to an invitation to engage in a brief negotiated intervention (BNI). METHODS: PLWHA participated in a self-administered tablet computer-based version of SBIRT. Patients screened as having at-risk, high-risk, or dependent substance use (N = 331) were eligible to receive the BNI. Of these patients, 101 reported cannabis-only use, with or without alcohol. RESULTS: Binary logistic regressions controlling for Alcohol Use Disorders Identification Test and Drug Abuse Screening Test score and demographics, found that cannabis-only use was significantly related to declining the BNI. DISCUSSION AND CONCLUSIONS: Cannabis-only engagement predicts lower BNI acceptance rates than other substance use profiles; inappropriate screening tools may be one reason for this discrepancy. Implications and directions for future research are discussed. SCIENTIFIC SIGNIFICANCE: Findings are relevant in modifying SBIRT for cannabis use. To our knowledge, this is the first work to evaluate acceptance of brief interventions for cannabis as compared to other substances and brief intervention acceptance in a sample of PLWHA.

Fimepinostat (CUDC-907) in patients with relapsed/refractory diffuse large B cell and high-grade B-cell lymphoma: report of a phase 2 trial and exploratory biomarker analyses.

Fimepinostat (CUDC-907), a first-in-class oral small-molecule inhibitor of histone deacetylase and phosphatidylinositol 3-kinase, demonstrated efficacy in a phase 1 study of patients with relapsed/refractory (R/R) diffuse large and high-grade B-cell lymphomas (DLBCL/HGBL), particularly those with increased MYC protein expression and/or MYC gene rearrangement/copy number gain (MYC-altered disease). Therefore, a phase 2 study of fimepinostat was conducted in this patient population with 66 eligible patients treated. The primary end-point of overall response (OR) rate for patients with MYC-IHC ≥40% (n = 46) was 15%. Subsequently, exploratory pooled analyses were performed including patients treated on both the phase 1 and 2 studies based upon the presence of MYC-altered disease as well as a biomarker identified by Virtual Inference of Protein activity by Enriched Regulon analysis (VIPER). For these patients with MYC-altered disease (n = 63), the overall response (OR) rate was 22% with seven responding patients remaining on treatment for approximately two years or longer, and VIPER yielded a three-protein biomarker classification with positive and negative predictive values of ≥85%. Prolonged durations of response were achieved by patients with MYC-altered R/R DLBCL/HGBL treated with single-agent fimepinostat. Combination therapies and/or biomarker-based patient selection strategies may lead to higher response rates in future clinical trials.

CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial.

CUDC-907 is a first-in-class, oral small molecule inhibitor of both HDAC (class I and II) and PI3K (class Iα, ß, and δ) enzymes, with demonstrated anti-tumor activity in multiple pre-clinical models, including MYC-driven ones. In this report, we present the safety and preliminary activity results of CUDC-907, with and without rituximab, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), with a particular focus on those with MYC-altered disease. Thirty-seven DLBCL patients were enrolled, 14 with confirmed MYC-altered disease. Twenty-five patients received monotherapy treatment, and 12 received the combination of CUDC-907 with rituximab. CUDC-907 monotherapy and combination demonstrated similar safety profiles consisting primarily of Grade 1/2 hematologic and gastrointestinal events. The most frequently reported Grade ≥3 treatment-related events were thrombocytopenia, neutropenia, diarrhea, fatigue, and anemia. Eleven responses (5 complete responses and 6 partial responses) were reported, for a response rate of 37% (11 out of 30) in evaluable patients [30% (11 out of 37) including all patients]. The objective response rate in evaluable MYC-altered DLBCL patients was 64% (7 out of 11; 4 complete responses and 3 partial responses), while it was 29% (2 out of 7) in MYC unaltered, and 17% (2 out of 12) in those with unknown MYC status. Median duration of response was 11.2 months overall; 13.6 months in MYC-altered patients, 6.0 months in MYC unaltered, and 7.8 months in those with MYC status unknown. The tolerable safety profile and encouraging evidence of durable anti-tumor activity, particularly in MYC-altered patients, support the continued development of CUDC-907 in these populations of high unmet need. (clinicaltrials.gov identifier: 01742988).

A flexible and fully integrated system for amplification, detection and genotyping of genomic DNA targets based on microfluidic oligonucleotide arrays.

A strategy allowing for amplification, detection and genotyping of different genomic DNA targets in a single reaction container is described. The method makes use of primer-directed solution-phase amplification with integrated labeling in a closed, microfluidic oligonucleotide array. Selective array probes allow for subsequent detection and genotyping of generated amplicons by hybridization. The array contains up to 15,624 programmable features that can be designed, de novo synthesized and tested within 24 hours using an automated benchtop microarray synthesizer. This enables rapid prototyping and adaptation of the system to newly emerging targets such as pathogenic bacterial or viral subtypes. The system was evaluated by amplifying and detecting different loci of viral (HPV), bacterial (Bacillus sp.) and eukaryotic (human) genomes. Multiplex PCR and semi-quantitative detection with excellent detection limits of <100 target copies is hereby demonstrated. The high automation grade of the system reduces contamination risk and workload and should enhance safety and reproducibility.

Psychometric evaluation of the National Opinion Research Center DSM-IV Screen for Gambling Problems (NODS).

The present study examined the reliability, validity, and clinical utility of a brief self-report measure of gambling behavior, the National Opinion Research Center DSM-IV Screen for Gambling Problems (NODS). Participants were 157 consecutively enrolled male military veterans taking part in substance use disorder treatment. The NODS displayed good internal consistency. Concurrent and discriminant validity were demonstrated by comparing scores on the NODS to scores on the South Oaks Gambling Screen and to a measure of medical problems, respectively. Overall, the NODS appears to be a reliable, valid, and clinically useful measure of gambling problems among patients in substance use disorder treatment programs.

War-related mental health problems of today's veterans: new clinical awareness.

1. Veterans of the military conflicts in Iraq and Afghanistan may have been exposed to significant psychological stressors, resulting in mental and emotional disorders. 2. Posttraumatic stress disorder (PTSD) is characterized by symptoms in three domains: reexperiencing the trauma, avoiding stimuli associated with the trauma, and symptoms of increased autonomic arousal. 3. Treatment of PTSD often requires both psychological and pharmacological interventions. 4. In addition to PTSD, other mental disorders may be precipitated or worsened by exposure to combat, including depression, anxiety, psychosis, and substance abuse.