Objective Neighborhood-Level Disorder Versus Subjective Safety as Predictors of HIV Transmission Risk and Momentary Well-Being.

Mental health and HIV risk behavior have been studied with ecological momentary assessment (EMA), but this approach has not been combined with tracking of activity space (where people go and what they encounter there) in people with HIV and their social relations, who may be HIV+ or HIV-. Activity space represents a modifiable risk or protective factor for behavior related to health status and quality of life, in both clinical and nonclinical populations. We conducted an observational study with 286 participants (243 HIV+ and 43 HIV-), roughly matched for socioeconomic status and neighborhood of residence via three waves of snowball sampling. Each participant carried a smartphone for up to 4 weeks, making 5 randomly prompted entries and 1 end-of-day entry each day, plus self-initiated event-contingent entries for sexual activity and drug use. Responses to randomly prompted items provided subjective evaluations of the safety of the participant's current social and physical environment (the place they were and the people they were with). GPS-based location tracking-coupled with publicly available statistic indicating neighborhood-level physical disorder and socioeconomic disadvantage-provided an indicator of each participant's exposure to objective psychosocial hazard. We examined possible relationships of these objective and subjective environmental exposures with risky sexual and intravenous drug-use behavior, knowledge and utilization of antiretroviral treatment and prophylaxis, and momentary mental health (mood and stress, which relate to risky behavior and overall well-being). We found that both risky behavior and mental health were more related to participants' subjective evaluations of their activity space than to objective measures of neighborhood-level disorder, suggesting that, even within an objectively hazardous neighborhood, people who find a niche they perceive as socially and physically safe may engage in less risky behavior and have better well-being.Trial registration Clinicaltrials.gov Identifier NCT01571752.

Health Outcomes by Neighborhood (HON): Effects of Neighborhood, Social Instability, and Health Factors on 12-Month Trajectories of Substance-Use Disorder Symptoms.

BACKGROUND: Previous studies have shown that environment and health can influence drug use trajectories and the effects of substance use disorder (SUD) treatments. We hypothesized that trajectories of drug use-related problems, based on changes in DSM-5 symptoms, would vary by type(s) of drugs used, health factors, and neighborhood characteristics. METHODS: We assessed mental and physical health, stress, social instability, neighborhood characteristics (disorderliness and home value), and DSM-5 symptom counts at two study visits, 12 months apart, in a community sample (baseline N = 735) in Baltimore, MD. Three prominent categories of drug-use trajectory were identified with K-means cluster analysis of symptom counts: Persistent (4 or more symptoms at both visits or at Visit 2), Improved (decrease from 4 or more symptoms at Visit 1 to 3 or fewer symptoms at Visit 2), and Low-Stable (3 or fewer symptoms at both visits). Baseline health and neighborhood measures were tested as predictors of trajectory in mediation and moderation models. RESULTS: Among people with current opioid- and/or stimulant-use, odds of an Improved trajectory were (1) decreased with neighborhood disorder and social instability, or (2) increased with home value and social instability. Odds of a Low-Stable trajectory were decreased by social instability and stress but increased in those who were older or self-identified as white. CONCLUSIONS: Trajectories of drug use-related problems are influenced by sociodemographic variables, neighborhood factors, and health. Assessing DSM-5 symptom counts as an outcome measure may be valuable in monitoring or predicting long-term trajectories and treatment effectiveness.

Reward Responsiveness in Patients with Opioid Use Disorder on Opioid Agonist Treatment: Role of Comorbid Chronic Pain.

OBJECTIVE: Evidence suggests that blunted reward responsiveness may account for poor clinical outcomes in both opioid use disorder (OUD) and chronic pain. Understanding how individuals with OUD and comorbid chronic pain (OUD+CP) respond to rewards is, therefore, of clinical interest because it may reveal a potential point of behavioral intervention. METHODS: Patients with OUD (n = 28) and OUD+CP (n = 19) on opioid agonist treatment were compared on: 1) the Probabilistic Reward Task (an objective behavioral measure of reward response bias) and 2) ecological momentary assessment of affective responses to pleasurable events. RESULTS: Both the OUD and the OUD+CP groups evidenced an increase in reward response bias in the Probabilistic Reward Task. The rate of change in response bias across blocks was statistically significant in the OUD group (B = 0.06, standard error [SE] = 0.02, t = 3.92, P < 0.001, 95% confidence interval [CI]: 0.03 to 0.09) but not in the OUD+CP group (B = 0.03, SE = 0.02, t = 1.90, P = 0.07, 95% CI: -0.002 to 0.07). However, groups did not significantly differ in the rate of change in response bias across blocks (B = 0.03, SE = 0.02, t = 1.21, P = 0.23, 95% CI: -0.02 to 0.07). Groups did not significantly differ on state measures of reward responsiveness (P's ≥0.50). CONCLUSIONS: Overall, findings across objective and subjective measures were mixed, necessitating follow-up with a larger sample. The results suggest that although there is a reward response bias in patients with OUD+CP treated with opioid agonist treatment relative to patients with OUD without CP, it is modest and does not appear to translate into patients' responses to rewarding events as they unfold in daily life.

Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African-Americans with opioid use disorder.

Many patients with opioid use disorder do not have successful outcomes during treatment but the underlying reasons are not well understood. An OPRD1 variant (rs678849) was previously associated with methadone and buprenorphine efficacy in African-Americans with opioid use disorder. The objective of this study was to determine if the effect of rs678849 on opioid use disorder treatment outcome could be replicated in an independent population. Participants were recruited from African-American patients who had participated in previous studies of methadone or buprenorphine treatment at the outpatient treatment research clinic of the NIDA Intramural Research Program in Baltimore, MD, USA between 2000 and 2017. Rs678849 was genotyped retrospectively, and genotypes were compared with urine drug screen results from the previous studies for opioids other than the one prescribed for treatment. Genotypes were available for 24 methadone patients and 55 buprenorphine patients. After controlling for demographics, the effect of rs678849 genotype was significant in the buprenorphine treatment group (RR = 1.69, 95% confidence interval (CI) 1.59-1.79, p = 0.021). Buprenorphine patients with the C/C genotype were more likely to have opioid-positive drug screens than individuals with the C/T or T/T genotypes, replicating the original pharmacogenetic finding. The effect of genotype was not significant in the methadone group (p = 0.087). Thus, the genotype at rs678849 is associated with buprenorphine efficacy in African-Americans being treated for opioid use disorder. This replication suggests that rs678849 genotype may be a valuable pharmacogenetic marker for deciding which opioid use disorder medication to prescribe in this population.

Defining and Predicting Opioid and Cocaine Treatment Response.

Background: Treatment with methadone is effective in reducing heroin use, HIV risk, and death; however, not all patients respond to treatment. Better outcomes may emerge with personalized treatment based on factors that influence treatment courses. Objectives: To investigate psychosocial variables contributing to treatment response, using a comprehensive definition of treatment response. Methods: Seventy participants seeking treatment for heroin and cocaine addiction completed up to 40 weeks of daily methadone. At week 22, we administered a semi-structured interview for DSM-IV symptoms. We defined opioid treatment responders as people still enrolled at 22 weeks, not meeting past 30-day criteria for DSM-IV opioid abuse or dependence or DSM-5 opioid use disorder, and providing ≥75% opioid-negative urine samples in the 30 days prior to week 22. The same criteria were applied to assess cocaine treatment response. Results: Sample was 71% male, 41% White, and averaged 39.4 ± 7.9 years old. Opioid treatment response was more likely in participants who had been employed over the past 3 years (OR: 8.1, 95% CI: 1.2-55) and less likely in those who spent more time on hobbies (OR: 0.45, 95% CI: 0.23-0.88). Cocaine treatment response was more likely in participants who had a good relationship with their father (OR: 5.3, 95% CI: 1.2-24) and less likely if positive for hepatitis C (OR: 0.15, 95% CI: 0.03-0.75). Conclusions: Pretreatment characteristics differentially predict treatment response for heroin and cocaine use. Similar research in diverse patient groups may aid in the development of personalized treatment combining biologic treatment with targeted psychosocial interventions.

Using ecological momentary assessment to examine the relationship between craving and affect with opioid use in a clinical trial of clonidine as an adjunct medication to buprenorphine treatment.

BACKGROUND: In a recent clinical trial (NCT00295308), we demonstrated that clonidine decreased the association between opioid craving and moderate levels of stress and affect in patients receiving buprenorphine-based opioid agonist therapy. OBJECTIVES: To examine the relationship between illicit opioid use and craving and affect during the evaluation of clonidine as an adjunct medication in buprenorphine treatment for opioid use disorder. Secondarily, to examine whether those relationships are driven by within- or between-participant factors. METHODS: This was a secondary data analysis from our original trial. Participants (N = 108, female: n = 23, male n = 85) receiving buprenorphine were randomized to receive adjunct clonidine or placebo. Participants used portable electronic devices to rate stress, mood, and craving via ecological momentary assessment (EMA) four times randomly each day. To associate the EMA data with illicit opioid use, each EMA report was linked to participants' next urine drug screen (thrice weekly). We used generalized linear mixed models to examine the interaction between treatment group and illicit opioid use, as well as to decompose the analysis into within- and between-participant effects. RESULTS: Craving for opioids and cocaine was increased when participants were using illicit opioids; this effect was greater in the clonidine group. For affect, mood was poorer during periods preceding opioid-positive urines than opioid-negative urines for clonidine-treated participants, whereas there was no difference for placebo participants. CONCLUSION: This secondary analysis provides evidence that for participants maintained on opioid agonist therapy, clonidine minimized the behavioral impact of moderate levels of negative affect and craving.

Sex differences in daily life stress and craving in opioid-dependent patients.

BACKGROUND: Responses to stress and drug craving differ between men and women. Differences in the momentary experience of stress in relation to craving are less well-understood. OBJECTIVES: Using ecological momentary assessment (EMA), we examined sex differences in real-time in two areas: (1) causes and contexts associated with stress, and (2) the extent to which stress and drug cues are associated with craving. METHODS: Outpatients on opioid-agonist treatment (135 males, 47 females) reported stress, craving, and behavior on smartphones for 16 weeks. They initiated an entry each time they felt more stressed than usual (stress event) and made randomly prompted entries 3 times/day. In stress-event entries, they identified the causes and context (location, activity, companions), and rated stress and craving severity. RESULTS: The causes reported for stress events did not differ significantly by sex. Women reported arguing and being in a store more often during stress events, and men reported working more often during stress events, compared to base rates (assessed via random prompts). Women showed a greater increase in opioid craving as a function of stress (p < 0.0001) and had higher stress ratings in the presence of both stress and drug cues relative to men (p < 0.01). Similar effects were found for cocaine craving in men (p < 0.0001). CONCLUSION: EMA methods provide evidence based on real-time activities and moods that opioid-dependent men and women experience similar contexts and causes for stress but differ in stress- and cue-induced craving. These findings support sex-based tailoring of treatment, but because not all participants conformed to the overall pattern of sex differences, any such tailoring should also consider person-level differences.

A Cross-Sectional Online Survey of HIV Pre-Exposure Prophylaxis Adoption Among Primary Care Physicians.

BACKGROUND: Among health care providers, prescription of HIV pre-exposure prophylaxis (PrEP) has been low. Little is known specifically about primary care physicians (PCPs) with regard to PrEP awareness and adoption (i.e., prescription or referral), and factors associated with adoption. OBJECTIVE: To assess PrEP awareness, PrEP adoption, and factors associated with adoption among PCPs. DESIGN: Cross-sectional online survey conducted in April and May 2015. RESPONDENTS: Members of a national professional organization for academic primary care physicians (n = 266). MAIN MEASURES: PrEP awareness, PrEP adoption (ever prescribed or referred a patient for PrEP [yes/no]), provider and practice characteristics, and self-rated knowledge, attitudes, and beliefs associated with adoption. KEY RESULTS: The survey response rate was 8.6 % (266/2093). Ninety-three percent of respondents reported prior awareness of PrEP. Of these, 34.9 % reported PrEP adoption. In multivariable analysis of provider and practice characteristics, compared with non-adopters, adopters were more likely to provide care to more than 50 HIV-positive patients (vs. 0, aOR = 6.82, 95 % CI 2.06-22.52). Compared with non-adopters, adopters were also more likely to report excellent, very good, or good self-rated PrEP knowledge (15.1 %, 33.7 %, 30.2 % vs. 2.5 %, 18.1 %, 23.8 %, respectively; p < 0.001) and to perceive PrEP as extremely safe (35.1 % vs. 10.7 %; p = 0.002). Compared with non-adopters, adopters were less likely to perceive PrEP as being moderately likely to increase risk behaviors ("risk compensation") (12.8 % vs. 28.8 %, p = 0.02). CONCLUSIONS: While most respondents were aware of PrEP, only one-third of PrEP-aware PCPs reported adoption. Adopters were more likely to have experience providing HIV care and to perceive PrEP as extremely safe, and were less likely to perceive PrEP use as leading to risk compensation. To enhance PCP adoption of PrEP, educational efforts targeting PCPs without HIV care experience should be considered, as well as training those with HIV care experience to be PrEP "clinical champions". Concerns about safety and risk compensation must also be addressed.

Aripiprazole for cocaine abstinence: a randomized-controlled trial with ecological momentary assessment.

Aripiprazole blocks psychostimulant seeking in a rat model of relapse. However, in humans, it may increase ongoing use. We tested aripiprazole specifically for relapse prevention. Methadone-maintained outpatients who were abstinent from cocaine in weeks 11-12 were randomized to double-blind aripiprazole (15 mg daily) or placebo in weeks 13-27 after 12 weeks of contingency management. Participants reported craving through ecological momentary assessment. We stopped the trial because very few (18/41) participants fulfilled the abstinence criterion. The results suggested that aripiprazole delayed lapse [hazard ratio (HR)=0.45, 95% confidence interval (CI)=0.14-1.42, P=0.17] and relapse (HR=0.31, 95% CI=0.07-1.27, P=0.10), but the effects did not reach statistical significance. Unexpectedly, the proportion of participants reporting cocaine craving was higher in the aripiprazole group (Fisher's exact P=0.026), although the frequency of craving was similar in the aripiprazole and placebo groups (1.89 vs. 1.16%, reffect=0.43, 95% CI=-0.08-0.76). The results suggest that in recently abstinent cocaine users, aripiprazole might delay relapse, but might also slightly increase craving. Difficulty in trial implementation underscores the fact that initial abstinence from cocaine is not a trivial hurdle.

Real-time assessment of alcohol drinking and drug use in opioid-dependent polydrug users.

We investigated relationships between drinking, other drug use, and drug craving, using ecological momentary assessment (EMA), in a sample of polydrug users who were not heavy drinkers. In a prospective longitudinal cohort study, 114 heroin and cocaine users on methadone-maintenance treatment carried handheld electronic diaries during waking hours and were screened for drug and alcohol use for up to 25 weeks. Individuals who fulfilled the Diagnostic and Statistical Manual of Mental Disorders criteria for alcohol abuse or dependence were excluded. Participants responded to 2-5 random prompts per day to report on their moods, cravings, and activities and initiated entries when they used or acutely craved heroin or cocaine. Drinking alcohol was assessed in both types of entries. Breath alcohol was measured three times weekly. Participants reported drinking alcohol in 1.6% of random-prompt entries, 3.7% of event-contingent entries when craving cocaine and/or heroin, and 11.6% of event-contingent entries when using cocaine and/or heroin. Alcohol drinking was also associated with higher craving ratings and prestudy alcohol use. More drinking was detected by ambulatory self-report than by in-clinic breath testing. Even though we had screened out heavy drinkers from our sample of polydrug users, drinking was associated with heroin and cocaine craving and actual use.

Cardiac complications of unwitting co-injection of quinine/quinidine with heroin in an intravenous drug user.

Adulterants "cut into" street heroin are common and often not detected by standard urine toxicology screening; however, their unwitting co-injection may have clinical consequences. We report a case of accelerated atrioventricular junctional arrhythmia that we determined to have been caused by quinine/quinidine cut into heroin. While identification and discontinuation of the offending agent helps confirm the diagnosis and is the treatment of choice, this is often complicated by the individual's dependence on the street drug in which the adulterant is mixed. This case highlights the need for clinicians to be aware of common adulterants, to know how to test for them, and to consider them as possible causes of medical complications in individuals who use drugs.

Intra-individual variability and stability of affect and craving among individuals receiving medication treatment for opioid use disorder.

Affect and craving are dynamic processes that are clinically relevant in opioid use disorder (OUD) treatment, and can be quantified in terms of intra-individual variability and stability. The purpose of the present analysis was to explore associations between opioid use and variability and stability of affect and craving among individuals receiving medication treatment for OUD (MOUD). Adults (N = 224) with OUD in outpatient methadone or buprenorphine treatment completed ecological momentary assessment (EMA) prompts assessing positive affect, negative affect, opioid craving, and opioid use. Dynamic structural equation modeling (DSEM) was used to quantify person-level indices of magnitude and stability of change. Beta regression was used to examine associations between intra-individual variability and stability and proportion of opioid-use days, when controlling for overall intensity of affect and craving. Results suggested that greater magnitude of craving variability was associated with opioid use on a greater proportion of days, particularly among individuals with lower average craving. Low average positive affect was also associated with higher proportion of days of use. Individuals who experience substantial craving variability in the context of lower average craving may be particularly vulnerable to opioid use during treatment. Ongoing assessment of craving may be useful in identifying treatment needs. Examining correlates of intra-individual variability and stability in MOUD treatment remains a relevant direction for future work.

Being at work improves stress, craving, and mood for people with opioid use disorder: Ecological momentary assessment during a randomized trial of experimental employment in a contingency-management-based therapeutic workplace.

Employment problems are common among people with substance use disorders (SUDs), and improving vocational functioning is an important aspect of SUD treatment. More detailed understanding of the psychosocial benefits of employment may help refine vocational interventions for people with SUDs. Here, we used ecological momentary assessment to measure possible affective improvements associated with work. Participants (n = 161) with opioid use disorder were randomized to work (job-skills training) in a contingency-management-based Therapeutic Workplace either immediately or after a waitlist delay. Throughout, participants responded via smartphone to randomly scheduled questionnaires. In linear mixed models comparing responses made at work vs. all other locations, being at work was associated with: less stress, less craving for opioids and cocaine, less negative mood, more positive mood, and more flow-like states. Some of these differences were also observed on workdays vs. non-workdays outside of work hours. These results indicate that benefits associated with work may not be restricted to being actually in the workplace; however, randomization did not reveal clear changes coinciding with the onset of work access. Overall, in contrast to work-associated negative moods measured by experience-sampling in the general population, Therapeutic Workplace participants experienced several types of affective improvements associated with work.

Craving mediates the association between momentary pain and illicit opioid use during treatment for opioid-use disorder: an ecological momentary assessment study.

AIM: To assess the role of momentary pain on opioid craving and illicit opioid use among individuals receiving opioid agonist treatment. DESIGN: Observational study using ecological momentary assessment. SETTING: The National Institute of Drug Abuse Intramural Research Program in the United States. PARTICIPANTS: Fifty-six adults who qualified for opioid agonist treatment. MEASUREMENTS: Participants completed randomly prompted assessments of pain severity, stress, negative mood, opioid craving and illicit opioid use for a mean of 66 days [standard deviation (SD) = 27]. Urine samples were collected two to three times/week throughout. FINDINGS: Almost 70% of participants reported moderate average pain severity in the past 24 hours at intake and 35% of participants reported chronic pain. There were no significant differences in percent of opioid-positive urine samples (P = 0.73) and average level of opioid craving during the study period (P = 0.91) among opioid agonist treatment only patients versus opioid agonist treatment patients with chronic pain. However, momentary pain severity significantly predicted concurrent opioid craving [B = 0.02, 95% confidence interval (CI) = 0.01, 0.04], over and above stress and negative mood. Momentary opioid craving, in turn, significantly predicted illicit opioid use that was assessed in the next moment [odds ratio (OR) = 1.72, 95% CI = 1.12, 2.64), while controlling for autocorrelation and the effects of pain, negative mood and stress. Momentary opioid craving significantly mediated the prospective association between momentary pain and illicit opioid use (95% CI = 0.003, 0.032). Exploratory analysis revealed that momentary pain severity also significantly moderated the momentary association between stress and opioid craving (B = 0.02, 95% CI = 0.00, 0.04), such that when momentary pain severity increased, the association between the two intensified. CONCLUSIONS: Among people receiving opioid agonist treatment, momentary pain appears to be indirectly associated with illicit opioid use via momentary opioid craving.

I feel good? Anhedonia might not mean "without pleasure" for people treated for opioid use disorder.

Anhedonia is usually defined as partial or total loss of the capacity for pleasure. People with anhedonia in the context of major depressive disorder may have an unexpected capacity for event-related mood brightening, observable when mood is assessed dynamically (with smartphone-based ecological momentary assessment [EMA]) rather than only statically via questionnaire. We used EMA to monitor mood and pleasant events for 4 weeks in 54 people being treated with opioid agonist medication for opioid-use disorder (OUD), which is also associated with anhedonia, said to manifest especially as loss of pleasure from nondrug reward. We compared OUD patients' EMA reports with those of 47 demographically similar controls. Background positive mood was lower in OUD patients than in controls, as we hypothesized (Cohen ds = .85 to 1.32, 95% CIs [.66, 1.55]), although, contrary to our hypothesis, background negative mood was also lower (ds = .82 to .85, 95% CIs [.73, .94]). As hypothesized, instances of nondrug pleasure were as frequent in OUD patients as in controls-and were not rated much less pleasurable (d = .18, 95% CI [-.03, .35]). Event-related mood brightening occurred in both abstinent and nonabstinent OUD patients (ds = .18 to .37, CIs [-.01, .57]) and controls (ds = .04 to .60, CIs [-.17, .79]), brightening before each event began earlier for controls than OUD patients, but faded similarly postevent across groups. Our findings add to the evidence that anhedonia does not rule out reactive mood brightening, which, for people with OUD being treated on opioid agonist medication, can be elicited by nondrug activities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Quality of life during a randomized trial of a therapeutic-workplace intervention for opioid use disorder: Web-based mobile assessments reveal effects of drug abstinence and access to paid work.

Background: Employment and improved quality of life (QOL) are, separately, valued outcomes of substance use disorder (SUD) treatment. It is also important to understand QOL changes caused by employment itself; therefore, we assessed QOL during a randomized trial of a contingency-management-based Therapeutic Workplace for people with opioid use disorder. Methods: For 12 weeks, participants (n = 61) responded to QOL questionnaires in a mobile web app accessed with study-issued smartphones. At enrollment, participants were randomized to work in the Therapeutic Workplace immediately (immediate work group, IWG) or after a 3-week waitlist delay (delayed work group, DWG). Once both groups could work, wage-resetting contingencies were introduced for their opiate- and cocaine-urinalysis. Data were analyzed by (1) access to work with and without contingencies and (2) overall urinalysis-verified opiate- and cocaine-abstinence. Results: DWG and/or IWG reported improvements in several QOL areas (sleep, transportation, recreation); however, they also reported increased money-related difficulties and less time spent with friends/family. These changes did not coincide with DWG's work access, but some (more sleep, money-related difficulties) coincided with the urinalysis contingencies. Greater opiate- and/or cocaine-abstinence was also associated with several improvements: sleep, paying bills, time spent with friends/family, and exercising. Surprisingly, intermediate cocaine abstinence was associated with reductions in work-capacity satisfaction and recreation. Conclusions: Participants reported complex QOL differences during their experimental employment and associated with drug abstinence. Future work should help participants address issues that may be relevant to employment generally (e.g., time with friends/family) or contingency management specifically (e.g., money-related issues for non-abstinent participants).

Beyond abstinence and relapse II: momentary relationships between stress, craving, and lapse within clusters of patients with similar patterns of drug use.

RATIONALE: Given that many patients being treated for opioid-use disorder continue to use drugs, identifying clusters of patients who share similar patterns of use might provide insight into the disorder, the processes that affect it, and ways that treatment can be personalized. OBJECTIVES AND METHODS: We applied hierarchical clustering to identify patterns of opioid and cocaine use in 309 participants being treated with methadone or buprenorphine (in a buprenorphine-naloxone formulation) for up to 16 weeks. A smartphone app was used to assess stress and craving at three random times per day over the course of the study. RESULTS: Five basic patterns of use were identified: frequent opioid use, frequent cocaine use, frequent dual use (opioids and cocaine), sporadic use, and infrequent use. These patterns were differentially associated with medication (methadone vs. buprenorphine), race, age, drug-use history, drug-related problems prior to the study, stress-coping strategies, specific triggers of use events, and levels of cue exposure, craving, and negative mood. Craving tended to increase before use in all except those who used sporadically. Craving was sharply higher during the 90 min following moderate-to-severe stress in those with frequent use, but only moderately higher in those with infrequent or sporadic use. CONCLUSIONS: People who share similar patterns of drug-use during treatment also tend to share similarities with respect to psychological processes that surround instances of use, such as stress-induced craving. Cluster analysis combined with smartphone-based experience sampling provides an effective strategy for studying how drug use is related to personal and environmental factors.

Prediction of stress and drug craving ninety minutes in the future with passively collected GPS data.

Just-in-time adaptive interventions (JITAIs), typically smartphone apps, learn to deliver therapeutic content when users need it. The challenge is to "push" content at algorithmically chosen moments without making users trigger it with effortful input. We trained a randomForest algorithm to predict heroin craving, cocaine craving, or stress (reported via smartphone app 3x/day) 90 min into the future, using 16 weeks of field data from 189 outpatients being treated for opioid-use disorder. We used only one form of continuous input (along with person-level demographic data), collected passively: an indicator of environmental exposures along the past 5 h of movement, as assessed by GPS. Our models achieved excellent overall accuracy-as high as 0.93 by the end of 16 weeks of tailoring-but this was driven mostly by correct predictions of absence. For predictions of presence, "believability" (positive predictive value, PPV) usually peaked in the high 0.70s toward the end of the 16 weeks. When the prediction target was more rare, PPV was lower. Our findings complement those of other investigators who use machine learning with more broadly based "digital phenotyping" inputs to predict or detect mental and behavioral events. When target events are comparatively subtle, like stress or drug craving, accurate detection or prediction probably needs effortful input from users, not passive monitoring alone. We discuss ways in which accuracy is difficult to achieve or even assess, and warn that high overall accuracy (including high specificity) can mask the abundance of false alarms that low PPV reveals.

Beyond abstinence and relapse: cluster analysis of drug-use patterns during treatment as an outcome measure for clinical trials.

RATIONALE: Many people being treated for opioid use disorder continue to use drugs during treatment. This use occurs in patterns that rarely conform to well-defined cycles of abstinence and relapse. Systematic identification and evaluation of these patterns could enhance analysis of clinical trials and provide insight into drug use. OBJECTIVES: To evaluate such an approach, we analyzed patterns of opioid and cocaine use from three randomized clinical trials of contingency management in methadone-treated participants. METHODS: Sequences of drug test results were analyzed with unsupervised machine-learning techniques, including hierarchical clustering of categorical results (i.e., whether any samples were positive during each week) and K-means longitudinal clustering of quantitative results (i.e., the proportion positive each week). The sensitivity of cluster membership as an experimental outcome was assessed based on the effects of contingency management. External validation of clusters was based on drug craving and other symptoms of substance use disorder. RESULTS: In each clinical trial, we identified four clusters of use patterns, which can be described as opioid use, cocaine use, dual use (opioid and cocaine), and partial/complete abstinence. Different clustering techniques produced substantially similar classifications of individual participants, with strong above-chance agreement. Contingency management increased membership in clusters with lower levels of drug use and fewer symptoms of substance use disorder. CONCLUSIONS: Cluster analysis provides person-level output that is more interpretable and actionable than traditional outcome measures, providing a concrete answer to the question of what clinicians can tell patients about the success rates of new treatments.

Preferences for implementation of HIV pre-exposure prophylaxis (PrEP): Results from a survey of primary care providers.

Primary care physicians (PCPs) are critical for promoting HIV prevention by prescribing pre-exposure prophylaxis (PrEP). Yet, there are limited data regarding PCP's preferred approaches for PrEP implementation. In 2015, we conducted an online survey of PCPs' PrEP prescribing and implementation. Participants were general internists recruited from a national professional organization. We examined provider and practice characteristics and perceived implementation barriers and facilitators associated with preferred models for PrEP implementation. Among 240 participants, the majority (85%) favored integrating PrEP into primary care, either by training all providers ("all trained") (42%) or having an onsite PrEP specialist ("on-site specialist") (43%). Only 15% preferred referring patients out of the practice to a specialist ("refer out"). Compared to those who preferred to "refer out," participants who preferred the "all trained" model were more likely to spend most of their time delivering direct patient care and to practice in the Northeast. Compared to participants who preferred the "refer out" or on-site specialist" models, PCPs preferring the all trained model were less likely to perceive lack of clinic PrEP guidelines/protocols as a barrier to PrEP. Most PCPs favored integrating PrEP into primary care by either training all providers or having an on-site specialist. Time devoted to clinical care and geography may influence preferences for PrEP implementation. Establishing clinic-specific PrEP protocols may promote on-site PrEP implementation. Future studies should focus on evaluating the effectiveness of different PrEP implementation models on PrEP delivery.