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.

Challenges to Conducting Contingency Management Treatment for Substance Use Disorders: Practice Recommendations for Clinicians.

A growing empirical literature supports contingency management (CM) as an efficacious treatment for substance use disorders, especially when reinforcers are immediate, frequent, and of sufficient magnitude on escalating schedules. However, in real world-practice, CM is often conducted in ways that are inconsistent with research protocols. One reason for these inconsistencies may be due to pragmatic challenges inherent in conducting CM. In this article, we described an outpatient CM treatment program for drug use disorders and several specific challenges associated with adherence to CM parameters from research protocols. Finally, we propose possible solutions for these challenges and discuss implications for practice.

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).

Pre-Implementation Review of Contracts, Prompts, and Reinforcement in SUD Continuing Care.

The Contracts, Prompts, and Reinforcement (CPR) intervention has demonstrated an ability to increase the duration of continuing care participation following substance use disorder (SUD) treatment, resulting in improved treatment outcome. The current project was a qualitative pre-implementation study aimed at identifying barriers and facilitators to implementation of CPR using an evidence-based quality improvement (EBQI) approach. Formative evaluations were conducted with staff from residential SUD treatment programs across three VA sites, and key informant interviews were completed with opinion and program leaders. Data were analyzed using a grounded theory approach, which identified barriers and facilitators to implementation. Fidelity measures were developed for each of the core CPR components, and the research-focused treatment manual was rewritten to facilitate future implementation efforts with the design and content of the documents shaped by the findings of the qualitative analyses. Overall, data suggested that clinicians and administrators are receptive to the core components of CPR.

Paranoid personality disorder in the United States: the role of race, illicit drug use, and income.

Differential rates of schizophrenia and paranoia symptoms have been found for Black and White individuals. Paranoid personality disorder shares symptoms with schizophrenia, yet has received minimal attention with regard to potential racial differences. In a sample consisting of 180 substance use disorder treatment-seeking individuals, the association between the diagnosis of paranoid personality disorder and the variables of race, cannabis use disorder, and income were examined. Results extended previous findings to paranoid personality disorder, supporting the hypothesis that Black individuals would be diagnosed with higher rates of paranoid personality disorder. Cannabis use disorder status and income did not predict paranoid personality disorder diagnoses.

The effect of continuous positive air pressure (CPAP) on nightmares in patients with posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA).

OBJECTIVES: Post-Traumatic Stress Disorder (PTSD) is increasingly prevalent among Veterans characterized by recurrent nightmare and disrupted sleep. Veterans with PTSD also have a high prevalence of obstructive sleep apnea (OSA) and untreated OSA worsens the sleep-related symptoms of PTSD. In our study, we hypothesized that among PTSD-afflicted Veterans with OSA, CPAP therapy may reduce the frequency of nightmares and a better CPAP compliance may be associated with increased symptom improvement. METHODS: We retrospectively reviewed medical records to identify OSA patients treated in a VA medical center who also carried a diagnosis of PTSD (n = 69). Data about patient characteristics and polysomnographic findings were extracted. Repeated-measures t-tests were performed, comparing mean nightmare frequency and Epworth sleepiness score (ESS) before and after CPAP treatment. Multiple linear regressions were done to identify factors predicting CPAP compliance. A logistic regression analysis was also done to estimate the odds of subjective improvement in PTSD symptoms with CPAP. RESULTS: CPAP therapy reduced the mean ESS from 14.62 to 8.52 (p < 0.001) and the mean number of nightmares per week from 10.32 to 5.26 (p < 0.01). Reduced nightmare frequency after CPAP treatment was best predicted by CPAP compliance (p < 0.001). Every 10% increase in CPAP compliance almost doubled the odds of benefitting by CPAP (odds ratio = 1.92, 95% CI = 1.47-2.5). CONCLUSIONS: In Veterans with PTSD and OSA, CPAP therapy reduces PTSD-associated nightmares and improves overall PTSD symptoms. We recommend that all PTSD patients should be screened clinically for symptoms of OSA and receive CPAP treatment whenever possible to improve PTSD symptoms.

Interaction with both ZNRF3 and LGR4 is required for the signalling activity of R-spondin.

R-spondin proteins sensitize cells to Wnt signalling and act as potent stem cell growth factors. Various membrane proteins have been proposed as potential receptors of R-spondin, including LGR4/5, membrane E3 ubiquitin ligases ZNRF3/RNF43 and several others proteins. Here, we show that R-spondin interacts with ZNRF3/RNF43 and LGR4 through distinct motifs. Both LGR4 and ZNRF3 binding motifs are required for R-spondin-induced LGR4/ZNRF3 interaction, membrane clearance of ZNRF3 and activation of Wnt signalling. Importantly, Wnt-inhibitory activity of ZNRF3, but not of a ZNRF3 mutant with reduced affinity to R-spondin, can be strongly suppressed by R-spondin, suggesting that R-spondin primarily functions by binding and inhibiting ZNRF3. Together, our results support a dual receptor model of R-spondin action, where LGR4/5 serve as the engagement receptor whereas ZNRF3/RNF43 function as the effector receptor.

Contracting, prompting and reinforcing substance use disorder continuing care.

The contracting, prompting and reinforcing (CPR) aftercare intervention has improved treatment adherence and outcomes in a number of clinical trials. In multisite randomized clinical trial 92 graduates of two intensive substance use disorder programs who received CPR were compared to 91 who received standard treatment (STX). The CPR group evidenced increased frequency of aftercare group therapy attendance and near significant findings suggested that more CPR than STX participants completed 3 months (76 vs. 64%), 6 months (48 vs. 35%), and 9 months (35 vs. 22%) of aftercare. However, the groups did not differ on the majority of attendance measures and had similar abstinence rates at the 3-month (67% CPR vs. 71% STX), 6-month (52% CPR vs. 51% STX), and 12-month (the primary outcome measure; 48% CPR vs. 49% STX) follow-up points. Exploratory analyses suggest that CPR might be more effective among participants not required to attend aftercare. The incremental capital and labor cost of CPR compared to STX was $98.25 per participant.

Contingency management for patients with cooccurring disorders: evaluation of a case study and recommendations for practitioners.

Research indicates that contingency management (CM) has potential to improve a number of outcomes (e.g. substance use, treatment attendance, quality of life) among individuals with substance use and cooccurring disorders. However, multiple factors must be considered on a case-by-case basis in order to promote optimal treatment effects. The present study describes an individualized CM protocol for a US Veteran with substance dependence and cooccurring severe mental illness. CM targeted attendance at outpatient appointments and appropriate use of hospital resources. Effects of CM were assessed by comparing the 3-month baseline and CM periods. The CM intervention marginally reduced unnecessary hospital admissions, resulting in cost savings to the medical center of over $5,000 in three months for this individual. However, CM did not affect outpatient attendance. Several complications arose, highlighting challenges in using CM in populations with substance use and cooccurring disorders. Practical suggestions are offered for maximizing the effects of CM.

Unrecognized physical illness prompting psychiatric admission.

BACKGROUND: We assessed factors that might contribute to clinicians erroneously attributing medically based changes in a patient's mental status to psychiatric illness. METHODS: Records of 1340 patients admitted to a VA hospital psychiatric unit and 613 to a public hospital psychiatric unit from 2001 to 2007 were reviewed. Cases admitted because of an unrecognized medical disorder underwent further analysis of the preadmission assessment and documented history of mental illness. RESULTS: Of 1340 patients whose records were reviewed, 55 (2.8%) had a medical disorder that caused their symptoms. Compared with patients admitted to medical units, patients inappropriately admitted to psychiatric units had lower rates of completion of medical histories, physical examinations, cognitive assessments, indicated laboratory and/or radiologic studies, and treatment of abnormal vital signs (P < .001 in each case). Among patients admitted to psychiatric units, 85.5% had a history of mental illness vs 30.9% of comparable admissions to medical units (Chi2(1) = 35.85; P < .001). CONCLUSIONS: Key assessment procedures are less likely to be performed in patients with mental status changes who are admitted to psychiatric units than in comparable patients admitted to medical units. Symptoms of patients with a history of mental illness are more likely to be attributed to psychiatric illness than are those of patients without such a history.

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.

Inappropriate psychiatric admission of elderly patients with unrecognized delirium.

OBJECTIVES: To explore factors that might contribute to misattribution of mental status changes to psychiatric illness when an elderly patient actually has a delirium (mental status changes due to a medical condition). METHODS: Records of 900 elderly patients referred to a Veterans Affairs psychiatric inpatient unit and 413 to an inpatient psychiatric team at a public hospital from 2001 to 2007 were reviewed. Cases referred because of symptoms secondary to an unrecognized delirium underwent further analysis of preadmission assessments. Comparisons were made to elderly patients with delirium appropriately admitted to medical units. RESULTS: Thirty (2.3%) of the patients referred to psychiatric units were found to have a physical disorder requiring medical intervention within twelve hours. Compared to 30 delirious patients admitted to medical units, those inappropriately referred to psychiatric units had significantly lower rates of adequate medical histories, physical examinations, cognitive assessments, and laboratory/radiological studies. Among patients with delirium referred to psychiatric units, 66.7% had a history of mental illness, versus 26.7% of comparable admissions to medical units (chi (7) = 60.00, P < 0.001). CONCLUSIONS: Our findings suggest that elderly patients with delirium admitted to psychiatric units are less likely to undergo complete diagnostic assessments than delirious elderly patients admitted to medical units. Symptoms of delirium appear more likely to be incorrectly attributed to psychiatric illness in patients with a history of mental illness than in patients without such a history. Possible explanations for these findings and suggestions for addressing these issues are offered.

Using vouchers to increase continuing care participation in veterans: does magnitude matter?

The present study examined the comparative effects of adding contingency management (CM) schedules to an existing substance abuse continuing care program, with the goal of increasing attendance. We retrospectively examined the attendance of 135 veterans enrolled in one of three CM programs and a quasi-control condition of 55 veterans. Results indicated that participants enrolled in the two higher magnitude CM voucher programs increased both continuing care attendance and length of participation. Findings support the use of CM to increase continuing care attendance among veterans with substance use disorders, and suggest that voucher magnitude and bonuses both had a positive impact.

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.

Relation between cognitive testing performance and pattern of substance use in males at treatment entry.

This study examined the frequency and pattern of cognitive impairment in individuals entering substance use disorder treatment and additionally examined the relation between pattern of cognitive impairment and type of substance(s) used: alcohol (n = 116), cocaine (n = 49), alcohol/cocaine (n = 76), and alcohol/multiple substance (n = 54). The Cognistat, a screening measure of cognitive functioning, and the Addiction Severity Index were given to male veterans at the time of entering 3- to 4-week residential/day drug treatment. The most prominent areas of impairment were memory (37% of the total sample) and similarities or abstract concept formation (21% of the total sample). Moderate or greater severity of impairment was noted on at least one Cognistat scale in 35% of the participants. Results indicated no significant differences in the patterns of cognitive domain impairment between groups based on type(s) of substances used at the time of entering treatment. Multiple substance use was significantly related to greater levels of psychiatric problems as identified by the Alcohol Severity Index. Given the rate of impairment in memory and verbal abstract reasoning noted, it is suggested that cognitive screening be a standard consideration in residential substance use disorder treatment to assist in treatment selection and delivery that is optimized to provide maximal benefit to patients.

Characteristics of psychotic patients with foreign accent syndrome.

The authors describe three patients with foreign accent syndrome during psychotic episodes which resolve with improvement of psychotic symptoms. Psychotic symptoms were worse during the times patients had foreign accents, suggesting a relationship between the presence of the accent and the severity of the psychosis.

Affective modulation of pain in substance-dependent veterans.

OBJECTIVE: Prior work suggests that positive affect inhibits pain while negative affect facilitates it. The current study sought to determine whether: 1) affective modulation of pain extends to a patient population; 2) cocaine and alcohol dependence influences the pattern of modulation; and 3) affective modulation of pain is mediated by changes in arm temperature. DESIGN: Thirty-seven participants with and without substance dependence (14 alcohol, 13 cocaine, 10 none) attended three experimental sessions intended to induce emotions (negative, neutral, positive) by picture-viewing. Following emotion-induction, participants were asked to submerge their arm in 33 degrees F water and keep it there until they reached tolerance. During submersion, pain ratings were made on a mechanical visual analog scale (M-VAS). OUTCOME MEASURES: Latency from submersion to first movement of the M-VAS (pain threshold) and latency to arm removal (pain tolerance) were measured. Arm temperature and manipulation checks for emotion-induction (corrugator electromyogram, heart rate, skin conductance, self-report) were also recorded. RESULTS: Manipulation checks confirmed that targeted affective states were achieved. Pain threshold and tolerance were higher after viewing pleasant pictures than after unpleasant ones. Although arm temperature did vary based on the affect induced, analyses suggested that temperature did not influence pain outcomes. CONCLUSIONS: Affect modulates pain perception in patients and does not appear to be mediated by changes in arm temperature. Additionally, pain modulation was not significantly influenced by cocaine or alcohol dependence. These data are encouraging, because they suggest that nonpharmacological methods of pain modulation may be effective in substance-dependent individuals.