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).

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.

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.

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.

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.

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.

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.

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.

Anxiety sensitivity, controllability, and experiential avoidance and their relation to drug of choice and addiction severity in a residential sample of substance-abusing veterans.

The aim of the present study was to evaluate anxiety-related psychological risk factors (e.g., anxiety sensitivity, perceived uncontrollability, emotional avoidance) and their relation to drug of choice and addiction severity in an inpatient residential substance abuse population. Fully detoxified veterans (N=94) meeting criteria for Axis I substance abuse disorders were enrolled in a 28-day residential substance abuse treatment program and completed the following measures at intake and discharge: Anxiety Sensitivity Index, Body Sensations Questionnaire (BSQ), Acceptance and Action Questionnaire (AAQ), Beck Depression Inventory (BDI; intake only), and the Anxiety Control Questionnaire (ACQ). Consistent with the expectation, veterans who reported more distress over bodily sensations (anxiety sensitivity, BSQ) and depressive symptoms (BDI) were more likely to avoid experiencing negative affect (AAQ) and perceived themselves as lacking in control (ACQ). Further, extent of avoidance, and to a lesser extent, controllability, discriminated between participants as a function of primary and comorbid diagnostic status, whereas anxiety sensitivity did not. No relation was found between anxiety sensitivity and drug of choice, and relations between assessed psychological factors and domains of addiction severity were mixed. Findings suggest that heightened bodily sensitivity, emotional avoidance, and perceived uncontrollability are common sequelae of patients seeking residential substance abuse treatment, but they do not contribute uniquely to drug of choice and measures of addiction severity. Theoretical and treatment implications are discussed with particular emphasis on approaches that may increase coping with untoward bodily cues, decrease avoidance of negative affect, and improve patient's sense of personal control over their responses and the environment.

Administrative, clinical, and ethical issues surrounding the use of waiting lists in the delivery of mental health services.

The waiting list is commonly used in the delivery of mental health services. Despite their prevalence, their design and management are generally not standardized; rather, they take place on an ad hoc basis as a response to undesirable circumstances. The formulation and management of a waiting list initially appear to be simple, straightforward, and benign. However, on close examination, waiting lists are complicated, and implementation involves pervasive costs and benefits. This article delineates the costs and benefits involved in the use of waiting lists. It outlines administrative, clinical, and ethical issues intrinsic in the use of waiting lists and provides recommendations aimed at assisting in their design and management. While recommendations encompassing the range of possible unique situations are impractical, guidelines for consideration of important variables are provided.

A brief telephone intervention targeting treatment engagement from a substance abuse program wait list.

This study compares three brief participant-initiated telephone interventions aimed at enhancing treatment engagement of individuals on a substance abuse treatment wait list. Policies requiring that wait list members call at least every other week in order to remain eligible for treatment remained in place for the standard and enhanced conditions but not for the voluntary condition. The standard condition was a minimal intervention, providing information on the program. The enhanced condition focused on client motivation for treatment and recovery. If individuals in the voluntary condition called, they were provided information about current wait list number and approximate remaining wait time. The rate of treatment engagement was the same among treatment conditions. The best predictor of engagement was the number of calls placed to the program while waiting. Treatment condition was a positive predictor of call frequency; presence of a comorbid psychiatric diagnosis was a negative predictor. The article also discusses future directions.

Somatic dysfunction during carisoprodol cessation: evidence for a carisoprodol withdrawal syndrome.

Carisoprodol is a commonly used skeletal muscle relaxant with potential for abuse because of its active metabolite, meprobamate, and several reports have suggested that patients abruptly stopping intake of carisoprodol may have a withdrawal syndrome. The authors studied changes in the occurrence of somatic dysfunctions in five patients during an 8-day period following discontinuation from large doses of carisoprodol. Results showed that the number of somatic dysfunctions changed significantly during the withdrawal period. Each patient had an increase in the number of somatic dysfunctions during the first 3 days after cessation of carisoprodol with return to at or near baseline by the eighth day. This was reflected statistically in a significant-within-subjects effect for time. Results of supplemental analyses revealed a significant component of the effect and a trend for the quadratic component to be significant. Increases in the number of somatic dysfunctions during carisoprodol discontinuation support the existence of a carisoprodol withdrawal syndrome.

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.

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.