Mixed amphetamine salts-extended release (MAS-ER) as a behavioral treatment augmentation strategy for cocaine use disorder: A randomized clinical trial.

Psychosocial interventions remain the primary strategy for addressing cocaine use disorder (CUD), although many individuals do not benefit from these approaches. Amphetamine-based interventions have shown significant promise and may improve outcomes among individuals continuing to use cocaine in the context of behavioral interventions. One hundred forty-five adults (122 males) who used cocaine a minimum of 4 days in the prior month and met the criteria for a CUD enrolled in a two-stage intervention. All participants received a computer-delivered skills intervention and contingency management for reinforcing abstinence for a 1-month period. Participants demonstrating less than 3 weeks of abstinence in the first month were randomized to receive mixed amphetamine salts-extended release (MAS-ER) or placebo (80 mg/day) for 10 weeks under double-blind conditions. All participants continued with the behavioral intervention. The primary outcome was the proportion of individuals who achieved 3 consecutive weeks of abstinence as measured by urine toxicology confirmed self-report at the study end. The proportion of participants demonstrating 3 consecutive weeks of abstinence at study end did not differ between the medication groups: MAS-ER = 15.6% (7/45) and placebo = 12.2% (5/41). Participants who received MAS-ER reported greater reductions in the magnitude of wanting cocaine, although no group differences were noted in either the perceived improvement or the frequency of wanting cocaine. Retention rates were greater for both medication groups compared to behavioral responders. Overall, augmenting a behavioral intervention with MAS-ER did not significantly increase the abstinence rate among individuals continuing to use cocaine following a month of behavioral therapy alone. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Open label trial of lofexidine-assisted non-opioid induction onto naltrexone extended-release injection for opioid use disorder.

Background: Opioid use disorder (OUD) continues to be major public health problem in the US and innovative medication strategies are needed. The extended-release injectable formulation of naltrexone (ER-NTX), an opioid receptor antagonist, is an effective treatment for OUD, but the need for an opioid-free period during the induction phase of treatment is a barrier to treatment success, particularly in the outpatient setting. Lofexidine, an alpha-2-adrenergic agonist, is an effective treatment for opioid withdrawal.Objectives: To evaluate the feasibility, safety, and tolerability of lofexidine for facilitating induction onto ER-NTX in the management of OUD.Methods: In an open-label, uncontrolled, 10-week outpatient clinical trial, 20 adults (four women) with OUD were treated with a fixed-flexible dosing strategy (maximum 0.54 mg 4×/daily) of lofexidine for up to 10 days to manage opioid withdrawal prior to receiving ER-NTX. The COVID-19 pandemic resulted in a modification of the study methods after enrolling 10 participants who attended all visits in person. The second group of 10 participants attended most induction period visits remotely.Results: Overall, 10 of the 20 participants (50%) achieved the primary outcome by receiving the first ER-NTX injection. Rates of induction success did not differ by the presence of fentanyl or remote visit attendance, although the small sample size provided limited statistical power. Six out of 20 participants (30%) initiated on lofexidine required dose adjustments. There were no study-related serious adverse events.Conclusions: This study provides preliminary evidence supporting the feasibility of inducting individuals with OUD onto ER-NTX using lofexidine.

Secondary Analysis of Agreement Between Negative Timeline Follow Back Report and Negative Urine Toxicology in a Large Trial of Individuals with Opioid Use Disorder.

OBJECTIVES: Timeline follow-back (TLFB) is a self-report measure commonly used as a method of assessing historical drug use in both clinical and research settings. Our study considered rates of agreement between TLFB and an objective biological assay of opioid use. METHODS: We calculated the rates of agreement between negative report of opioid use for the most recent 8 days on TLFB and urine toxicology (UTOX) results in a large multisite opioid use disorder treatment trial. RESULTS: In total, 3986 assessments were provided by trial participants with both UTOX and TLFB during weeks 1 to 12, 2716 during weeks 13 to 24, and 325 at week 28. Rates of disagreement between negative TLFB and positive opioid UTOX were 2.33% of all assessments (21.68% of those with positive UTOX) over weeks 1 to 12, 2.06% of all assessment (25.00% of those with positive UTOX) over weeks 13 to 24, and 9.85% of all assessments (26.02% of those with positive UTOX) at week 28. CONCLUSIONS: Negative TLFB seems to be generally associated with negative results on urine toxicology.

Cardiovascular variability, sociodemographics, and biomarkers of disease: the MIDUS study.

Introduction: Like heart rate, blood pressure (BP) is not steady but varies over intervals as long as months to as short as consecutive cardiac cycles. This blood pressure variability (BPV) consists of regularly occurring oscillations as well as less well-organized changes and typically is computed as the standard deviation of multiple clinic visit-to-visit (VVV-BP) measures or from 24-h ambulatory BP recordings (ABPV). BP also varies on a beat-to-beat basis, quantified by methods that parse variation into discrete bins, e.g., low frequency (0.04-0.15 Hz, LF). However, beat-to-beat BPV requires continuous recordings that are not easily acquired. As a result, we know little about the relationship between LF-BPV and basic sociodemographic characteristics such as age, sex, and race and clinical conditions. Methods: We computed LF-BPV during an 11-min resting period in 2,118 participants in the Midlife in the US (MIDUS) study. Results: LF-BPV was negatively associated with age, greater in men than women, and unrelated to race or socioeconomic status. It was greater in participants with hypertension but unrelated to hyperlipidemia, hypertriglyceridemia, diabetes, elevated CRP, or obesity. LF-diastolic BPV (DBPV), but not-systolic BPV (SBPV), was negatively correlated with IL-6 and s-ICAM and positively correlated with urinary epinephrine and cortisol. Finally, LF-DBPV was negatively associated with mortality, an effect was rendered nonsignificant by adjustment by age but not other sociodemographic characteristics. Discussion: These findings, the first from a large, national sample, suggest that LF-BPV differs significantly from VVV-BP and ABPV. Confirming its relationship to sociodemographic risk factors and clinical outcomes requires further study with large and representative samples.

Culturally tailored digital therapeutic for substance use disorders with urban Indigenous people in the United States: A randomized controlled study.

INTRODUCTION: Indigenous people experience health disparities, including higher rates of substance use disorders (SUDs). Digital therapeutics are a growing platform for treatment services and have the potential to expand access to culturally responsive interventions for Indigenous people. As one of the first randomized controlled trials for SUDs for American Indian and Alaska Native (AI/AN) adults, the aim of this study was to pilot test the efficacy of a culturally tailored intervention among urban Indigenous adults. METHODS: The study used a randomized controlled parallel design of 12 weeks of treatment-as-usual (TAU) (n = 26) versus TAU + Therapeutic Education System-Native Version (TES-NAV) (n = 27) with follow-up assessments at end of treatment and week 24 in an urban outpatient addiction treatment program for Native American adults. TAU consisted of individual/group counseling and cultural activities. The TES-NAV arm comprised TAU + 26 self-directed culturally tailored digital skills-based modules grounded in the community reinforcement approach with contingency management for abstinence and module completion. Primary outcome was longest consecutive weeks of abstinence from drugs and heavy drinking measured using self-report (Timeline Followback) and urine alcohol and drug toxicology screen during 12 weeks of treatment. Secondary outcomes were percent days abstinence during and posttreatment, coping strategies, social connectedness, and substance use and sexual risk behaviors. RESULTS: The study enrolled fifty-three (52.8 % male) AI/AN adults seeking treatment for a SUD. Although the study did not detect a benefit of TAU+TES-NAV over TAU on the primary outcome (Median = 2 consecutive weeks of abstinence for both arms) at end of treatment (treatment effect: Z = -0.78, p = 0.437), TAU+TES-NAV participants did demonstrate significantly greater percent days of abstinence at the week 24 follow-up (69.3 % versus 49.0 % for TAU; t = 2.08, p = 0.045) and significantly greater change in social connectedness mean score, baseline to week 12 (Z = -2.66, p = 0.011), compared to TAU. The study detected no differences between treatment arms for coping strategies or risk behaviors. CONCLUSION: The addition of TES-NAV to TAU did not significantly improve consecutive weeks of abstinence from drugs or heavy drinking; however, several secondary findings suggest promise for a culturally tailored digital therapeutic SUD intervention among urban Indigenous people. CLINICAL TRIALS: GOV REGISTRATION: #NCT03363256.

Clinical and psychosocial outcomes by sex among individuals prescribed buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX) for opioid use disorder.

BACKGROUND AND OBJECTIVES: Limited research has explored sex differences in opioid use disorder medication (MOUD) treatment outcomes. The purpose of this study was to examine MOUD initiation onto buprenorphine-naloxone (BUP-NX) versus extended-release naltrexone (XR-NTX) by sex, and sex differences in clinical and psychosocial outcomes. METHODS: Using data from a 24-week open-label comparative effectiveness trial of BUP-NX or XR-NTX, this study examined MOUD initiation (i.e., receiving a minimum one XR-NTX injection or first BUP-NX dose) and 24-week self-report outcomes. We used regression models to estimate the probability of MOUD initiation failure among the intent-to-treat sample (N = 570), and the main and interaction effects of sex on outcomes of interest among the subsample of participants who successfully initiated MOUD (n = 474). RESULTS: In the intent-to-treat sample, the odds of treatment initiation failure were not significantly different by sex. In the subsample of successful MOUD initiates, the effect of treatment on employment at week 24 was significantly moderated by sex (p = .003); odds of employment were not significantly different among males by MOUD type; females randomized to XR-NTX versus BUP-NX had 4.63 times greater odds of employment (p < .001). Males had significantly lower odds of past 30-day exchanging sex for drugs versus females (adjusted odds ratios [aOR] = 0.10, p = .004), controlling for treatment and baseline outcomes. DISCUSSION AND CONCLUSIONS: Further research should explore how to integrate employment support into OUD treatment to improve patient outcomes, particularly among women. SCIENTIFIC SIGNIFICANCE: The current study addressed gaps in the literature by examining sex differences in MOUD initiation and diverse treatment outcomes in a large, national sample.

Homelessness and Treatment Outcomes Among Black Adults With Opioid Use Disorder: A Secondary Analysis of X:BOT.

OBJECTIVE: We sought to identify the sociodemographic and clinical characteristics associated with homelessnesss, and explore the relationship between homelessnesss and treatment outcomes among Black individuals. METHODS: This is a secondary analysis of the subgroup of Black participants (n = 73) enrolled in "X:BOT," a 24-week multisite randomized clinical trial comparing the effectiveness of extended-release naltrexone versus sublingual buprenorphine-naloxone (n = 570). Outcomes included medication initiation, return to extramedical use of opioids assessed by both self-report and urine toxicology, and engagement in medications for opioid use disorder (MOUD) treatment at 28 weeks postrandomization. Descriptive statistics were performed. RESULTS: Black participants were mostly unmarried and male, and about a third were aged 21-30 years. Among people experiencing homelessnesss, more were uninsured (45.5% [10/22] vs 19.6% [10/51]), unemployed (77.3% [17/22] vs 64.7% [33/51]), and reported alcohol (40.9% [9/22] vs 23.5% [12/51]) and sedative use (54.5% [12/22] vs 17.6% [9/51]) within the previous 30 days. Compared with housed Black individuals, a slightly higher proportion of Black individuals experiencing homelessnesss successfully initiated study medication (81.1% [18/22] vs 72.6% [37/51]); similar proportions returned to opioid use during the trial (68.2% [15/22] vs 68.6% [35/51]) and were engaged in MOUD at 28 weeks after trial entry (72.2% [13/18] vs 69.7% [23/33]) among participants located for follow-up. CONCLUSIONS: These descriptive results among Black patients participating in a trial of MOUD suggest that efficacious MOUD is possible despite homelessnesss with additional clinical supports such as those provided by a clinical trial.

Cocaine use disorder patients develop distinct patterns of regulation of acth secretion by a vasopressin agonist and oxytocin: Report on a laboratory study.

Background: : Oxytocin and Vasopressin systems in the brain sustain adaptation to stressors. Cocaine being a stressor, it may alter brain homeostatic function. This dysregulation may entrench cocaine use disorder. Method: : This is a human laboratory study of the effects of intranasal desmopressin (a Vasopressin 1b receptor agonist) and oxytocin on ACTH secretion in cocaine use disorder patients versus a control group. It consisted of two endocrine challenges performed on consecutive days. On day 1, the effect of intranasal desmopressin (80 IU) on ACTH secretion was measured. On day 2, a pre-treatment with intranasal oxytocin (24 IU) preceded intranasal desmopressin to monitor its effect on desmopressin-induced ACTH secretion. We hypothesized that the effect of intranasal oxytocin in controls would differ from the effect in cocaine use disorder patients. Results: : Forty-three patients were included in this study: 14 controls and 29 cocaine use disorder patients. Significant differences were noted in the direction of change of ACTH secretion between the two groups. In cocaine use disorder patients, overall ACTH secretion was on average 2.7 pg/ml/min higher after intranasal desmopressin than after intranasal oxytocin/desmopressin (t292 = 2.91, p = 0.004). The opposite was observed in controls: overall ACTH secretion averaged 3.3 pg/ml/min less after intranasal desmopressin than after intranasal oxytocin/desmopressin (t292 = -2.35, p = 0.02). Conclusion: : Intranasal oxytocin and desmopressin revealed a pattern of ACTH secretion in cocaine use disorder patients that is distinct from a non-addicted control group. (ClinicalTrial.gov00255357, 10/2014).

Cerebrovascular Phenotype in Fabry Disease Patients Assessed by Ultrasound.

OBJECTIVES: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with variable phenotypes, including neurological symptoms. These can be influenced by vascular impairment. Extracranial and transcranial vascular sonography is an effective and noninvasive method for measuring arterial structures and blood flow. The study aims to investigate cerebrovascular phenotype characteristics in FD patients compared to controls using neurosonology. METHODS: This is a single-center, cross-sectional study of 130 subjects-65 patients (38 females), with genetically confirmed FD, and 65 sex- and age-matched controls. Using ultrasonography, we measured structural and hemodynamic parameters, including distal common carotid artery intima-media thickness, inner vertebral artery diameter, resting blood flow velocity, pulsatility index, and cerebral vasoreactivity (CVR) in the middle cerebral artery. To assess differences between FD and controls and to identify factors influencing investigated outcomes, unadjusted and adjusted regression analyses were performed. RESULTS: In comparison to sex- and age-matched controls, FD patients displayed significantly increased carotid artery intima-media thickness (observed FD 0.69 ± 0.13 mm versus controls 0.63 ± 0.12 mm; Padj = .0014), vertebral artery diameter (observed FD 3.59 ± 0.35 mm versus controls 3.38 ± 0.33 mm; Padj = .0002), middle cerebral artery pulsatility index (observed FD 0.98 ± 0.19 versus controls 0.87 ± 0.11; Padj < .0001), and significantly decreased CVR (observed FD 1.21 ± 0.49 versus controls 1.35 ± 0.38; Padj = .0409), when adjusted by age, BMI, and sex. Additionally, FD patients had significantly more variable CVR (0.48 ± 0.25 versus 0.21 ± 0.14; Padj < .0001). CONCLUSIONS: Our results suggest the presence of multiple vascular abnormalities and changes in hemodynamic parameters of cerebral arteries in patients with FD.

Trajectories of depression among patients in treatment for opioid use disorder: A growth mixture model secondary analysis of the XBOT trial.

BACKGROUND AND OBJECTIVES: To inform clinical practice, we identified subgroups of adults based on levels of depression symptomatology over time during opioid use disorder (OUD) treatment. METHODS: Participants were 474 adults in a 24-week treatment trial for OUD. Depression symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAM-D) at nine-time points. This was a secondary analysis of the Clinical Trials Network Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (XBOT) trial using a growth mixture model. RESULTS: Three distinct depression trajectories were identified: Class 1 High Recurring-10% with high HAM-D with initial partial reductions (of HAM-D across time), Class 2 Persistently High-5% with persistently high HAM-D, and Class 3 Low Declining-85% of the participants, with low HAM-D with early sustained reductions. The majority (low declining) had levels of depression that improved in the first 4 weeks and then stabilized across the treatment period. In contrast, 15% (high recurring and persistently high) had high initial levels that were more variable across time. The persistently high class had higher rates of opioid relapse. DISCUSSION AND CONCLUSIONS: In this OUD sample, most depressive symptomatology was mild and improved after medication treatment for opioid use disorder (MOUD). Smaller subgroups had higher depressive symptoms that persisted or recurred after the initiation of MOUD. Depressive symptoms should be followed in patients initiating treatment for OUD, and when persistent, should prompt further evaluation and consideration of antidepressant treatment. SCIENTIFIC SIGNIFICANCE: This study is the first to identify three distinct depression trajectories among a large clinical sample of individuals in MOUD treatment.

Patient Characteristics Associated with Opioid Abstinence after Participation in a Trial of Buprenorphine versus Injectable Naltrexone.

Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful treatment outcomes.

Polysubstance use before and during treatment with medication for opioid use disorder: Prevalence and association with treatment outcomes.

OBJECTIVE: Polysubstance use may complicate treatment outcomes for individuals who use opioids. This research aimed to examine the prevalence of polysubstance use in an opioid use disorder treatment trial population and polysubstance use's association with opioid relapse and craving. METHODS: This study is a secondary data analysis of individuals with opioid use disorder who received at least one dose of medication (n = 474) as part of a 24-week, multi-site, open label, randomized Clinical Trials Network study (CTN0051, X:BOT) comparing the effectiveness of extended-release naltrexone versus buprenorphine. Models examined pretreatment polysubstance use and polysubstance use during the initial 4 weeks of treatment on outcomes of relapse by week 24 of the treatment trial and opioid craving. RESULTS: Polysubstance use was generally not associated with treatment outcomes of opioid relapse and craving. Proportion of days of pretreatment sedative use was associated with increased likelihood of opioid relapse (OR: 1.01, 95 % CI: 1.00-1.02). Proportion of days of cocaine use during the initial 4 weeks of treatment was associated with increased likelihood of opioid relapse (OR: 1.05, 95 % CI: 1.01-1.09) but this effect was no longer significant once the potential of confounding by opioid use was considered. Sedative use during initial 4 weeks of treatment was associated with increased opioid craving (b: 0.77, 95 % CI: 0.01-1.52). The study found no other significant relationships. CONCLUSIONS: In the current study population, polysubstance use was only marginally associated with 24-week treatment outcomes.

Methamphetamine/amphetamine use over time among persons with opioid use disorders treated with buprenorphine/naloxone versus extended-release naltrexone.

BACKGROUND: Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use. METHODS: Secondary analysis of data from a multi-site, open-label, randomized controlled trial of XR-NTX versus BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX v. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use. RESULTS: Among the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects (OR=0.50; p = 0.051). In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time. CONCLUSION: In this sample of treated OUD patients, nearly a fifth of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02032433).

Evaluation of Physician Assistants' Self-Reported Attitudes and Behaviors After Completion of a Hospital-Wide Multidisciplinary Communication Skills Training Workshop.

Physician's assistants (PA) are an integral part of hospital teams. To the best of our knowledge, this is the first study to examine the effects of a multidisciplinary hospital-wide communication skills training (CST) workshop on PAs. From November 2017 to November 2019, all participants in the CST workshop were sent a web-based retrospective pre-post survey to measure self-reported attitudes and behaviors related to communicating with patients, CST, and specific skills taught. PA responses were analyzed alone and were compared to non-PAs. Non-PAs were physicians and 1 nurse practitioner. In total, 258 PA and 333 non-PA participants were surveyed for an overall response rate of 25%. Among PAs, in 9 out of 10 domains measured, there was a significant change in self-reported attitudes and behaviors toward communicating with patients, CST, and skills taught (P < .05). Similar to other providers, PAs experienced positive changes in these self-reported attitudes and behaviors after CST, however, there were some significant differences found when comparing PAs and non-PAs in the covariate analysis.

Durable Viral Suppression Among People with HIV and Problem Substance Use in the Era of Universal Antiretroviral Treatment.

This study explored factors associated with durable viral suppression (DVS) among two groups of people living with HIV (PLWH) and problem substance use in the context of universal antiretroviral treatment initiation. Participants (N = 99) were recruited between 2014-2017 from public sexual health clinics [SHC] and a hospital detoxification unit [detox]). DVS (NYC HIV surveillance registry) was defined as two consecutive viral load tests ≤ 200 copies/mL, ≤ 90 days apart, with all other viral loads suppressed over 12 or 18 months. Detox participants were significantly older, with more unstable housing/employment, substance use severity, and longer-term HIV vs. SHC participants. Older age, opioid and stimulant use disorder were significantly associated with lower odds of DVS, while fulltime employment and stable housing were significantly associated with higher odds of DVS at 12-month follow-up. Patterns held at 18-month follow-up. Co-located substance use and HIV services, funding for supportive housing, and collaborative patient-provider relationships could improve DVS among populations with the syndemic of problem substance use, poverty, and long-term HIV.

Enhancing the tropism of bacteria via genetically programmed biosensors.

Engineered bacteria for therapeutic applications would benefit from control mechanisms that confine the growth of the bacteria within specific tissues or regions in the body. Here we show that the tropism of engineered bacteria can be enhanced by coupling bacterial growth with genetic circuits that sense oxygen, pH or lactate through the control of the expression of essential genes. Bacteria that were engineered with pH or oxygen sensors showed preferential growth in physiologically relevant acidic or oxygen conditions, and reduced growth outside the permissive environments when orally delivered to mice. In syngeneic mice bearing subcutaneous tumours, bacteria engineered with both hypoxia and lactate biosensors coupled through an AND gate showed increased tumour specificity. The multiplexing of genetic circuits may be more broadly applicable for enhancing the localization of bacteria to specified niches.

Multiomics subtyping for clinically prognostic cancer subtypes and personalized therapy: A systematic review and meta-analysis.

PURPOSE: Multiomics cancer subtyping is becoming increasingly popular for directing state-of-the-art therapeutics. However, these methods have never been systematically assessed for their ability to capture cancer prognosis for identified subtypes, which is essential to effectively treat patients. METHODS: We systematically searched PubMed, The Cancer Genome Atlas, and Pan-Cancer Atlas for multiomics cancer subtyping studies from 2010 through 2019. Studies comprising at least 50 patients and examining survival were included. Pooled Cox and logistic mixed-effects models were used to compare the ability of multiomics subtyping methods to identify clinically prognostic subtypes, and a structural equation model was used to examine causal paths underlying subtyping method and mortality. RESULTS: A total of 31 studies comprising 10,848 unique patients across 32 cancers were analyzed. Latent-variable subtyping was significantly associated with overall survival (adjusted hazard ratio, 2.81; 95% CI, 1.16-6.83; P = .023) and vital status (1 year adjusted odds ratio, 4.71; 95% CI, 1.34-16.49; P = .015; 5 year adjusted odds ratio, 7.69; 95% CI, 1.83-32.29; P = .005); latent-variable-identified subtypes had greater associations with mortality across models (adjusted hazard ratio, 1.19; 95% CI, 1.01-1.42; P = .050). Our structural equation model confirmed the path from subtyping method through multiomics subtype (߈ = 0.66; P = .048) on survival (߈ = 0.37; P = .008). CONCLUSION: Multiomics methods have different abilities to define clinically prognostic cancer subtypes, which should be considered before administration of personalized therapy; preliminary evidence suggests that latent-variable methods better identify clinically prognostic biomarkers and subtypes.

Baseline- and treatment-associated pain in the X:BOT comparative effectiveness study of extended-release naltrexone versus buprenorphine-naloxone for OUD.

Chronic pain is highly prevalent among patients with opioid use disorder (OUD). However, little is known about how pharmacological treatments for OUD, for example, extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX), affect pain. To begin addressing this question, we performed a secondary analysis of pain data on a large prospective 24-week, open-label, randomized-controlled comparative effectiveness trial of XR-NTX versus BUP-NX (X:BOT trial). Participants' pain status was measured by the EuroQol (EQ-5D). Based on their responses to the pain question at baseline, participants were dichotomized into "Pain" versus "No Pain" categories. Participant's pain status was evaluated every 4 weeks. A mixed effects longitudinal logistic regression model was fitted to examine the differential effect of XR-NTX versus BUP-NX on pain, modelling pain at all available follow-up assessments, adjusted for age, sex, and baseline pain. A total of 474 individuals who were successfully inducted onto their assigned medications were included in this analysis. Among participants endorsing pain at baseline, substantial reductions in pain were observed over the course of the study in both treatment groups. Howecver reduction in pain was slightly greater in the group treated with XR-NTX than the one treated with BUP-NX (OR = 1.60 [95% CI: 1.07-2.40], P = 0.023). Future research using instruments and design specifically focused on pain could extend the present observations and evaluate their clinical significance.

Intranasal oxytocin may improve odds of abstinence in cocaine-dependent patients: results from a preliminary study.

Background: Oxytocin (OT) treatment in drug addiction studies have suggested potential therapeutic benefits. There is a paucity of clinical trial studies of oxytocin in cocaine use disorders. Method: This was a 6-week randomized, double-blind, outpatient clinical trial study investigating the effect of daily Intranasal Oxytocin (24 IU) on cocaine use by cocaine use disorder patients. After a 7-day inpatient abstinence induction stage, patients were randomized to intranasal oxytocin or intranasal placebo. During the outpatient phase, cocaine use disorder patients were required to present themselves to the research staff 3 times a week for witnessed randomized medication administration, to provide a urine sample for qualitative toxicology, and complete mandatory assessments, including the Time-Line-Follow Back. For the interim days, patients were given an "at-home" bottle that was weighed at each clinic visit to monitor compliance. Results: Neither administration of Intranasal placebo (n = 11) or Oxytocin (n = 15) induced at least 3 weeks of continuous abstinence. However, from week 3, the odds of weekly abstinence increased from 4.61 (95% CI = 1.05, 20.3) to 15.0 (CI = 1.18, 190.2) by week 6 for the Intranasal Oxytocin group (t = 2.12, p = 0.037), though there was no significant group difference overall in the odds of abstinence over time (F1,69 = 1.73, p = 0.19). More patients on Intranasal Oxytocin dropped out (p = 0.0005). Conclusions: Intranasal Oxytocin increased the odds of weekly abstinence in Cocaine patients after 2 weeks compared to PBO, but was associated with a higher dropout rate. (ClinicalTrials.gov 02,255,357, 10/2014).