Using ecological momentary assessments of negative affect and craving during residential opioid use disorder treatment to predict patients' relapse to substance use.

BACKGROUND: Negative affect (NA) and craving are often independently examined as precipitators of relapse among individuals with substance use disorders, including opioid use disorder (OUD). Recent ecological momentary assessment (EMA) research has revealed that NA and craving frequently co-occur within individuals. Yet we know little about the general patterns of, and variability in, within-person associations between NA and craving, as well as whether the nature and degree of within-person NA-craving coupling predicts post-treatment time-to-relapse. METHODS: Seventy-three patients (77 % male, Mage = 30.10, Range = 19-61) in residential treatment for OUD took part in a 12-day, 4× daily smartphone-based EMA study. Linear mixed-effects models tested within-person, day-level associations between self-reported NA and craving during treatment. The study used Person-specific slopes (i.e., average within-person NA-craving coupling for each participant) estimated from the mixed-effects model in survival analyses with Cox proportional hazards regression models to determine if between-person differences in the within-person coupling predicted post-treatment time-to-relapse (operationalized as the return to problematic use of any substance except tobacco), and whether this prediction was similar across patients' average levels of NA and craving intensity. The study monitored relapse through a combination of hair samples and reports from patients or alternative contacts via a voice response system twice a month for up to 120 days or more following discharge. RESULTS: Among the 61 participants with time-to-relapse data, those with stronger positive within-person NA-craving coupling on average during residential OUD treatment had a lower hazard of relapsing (slower time to relapse) post-treatment than participants with weaker NA-craving slopes. The significant association held after controlling for interindividual differences in age, sex, and average levels of NA and craving intensity. Average NA and craving intensity did not moderate the association between NA-craving coupling and time-to-relapse. CONCLUSIONS: Interindividual differences in average within-person, day-level NA-craving coupling during residential treatment predict OUD patients' post-treatment time-to-relapse.

Results of a Military Family Medicine Scholarly Activity Training Needs Assessment.

INTRODUCTION: Scholarly activity among family medicine physicians is an important element of military medical readiness, both in terms of required scholarship during training and ongoing scholarship to address ongoing and emergent operational medical threats. Most literature on barriers to scholarly activity are limited to training programs and lack an important element in overcoming barriers-their priority to physicians. This study seeks to address these gaps by identifying prioritized research training needs of military family medicine physicians at all levels of training and practice. MATERIALS AND METHODS: An institutional review board (IRB)-approved, cross-sectional, online survey was conducted from January 22, 2019, to February 7, 2020, using a modified version of the Hennessy-Hicks Training Needs Analysis Questionnaire. Respondents ranked their perceived level of skill and need for training for 20 literature-based elements of research success. They also self-identified research experience, level of training, and service membership. One-way analysis of variance to 95% CI was used to compare differences in self-reported research experience, number of peer-reviewed publications, number of external grants, and number of IRB protocols among services (Army, Navy, and Air Force), primary roles (resident, faculty, clinician, and leadership), and gender. Chi-squared tests were used to compare proportional differences, also to 95% CI. RESULTS: Of 124 respondents, most were members of the Air Force (46%), Navy (24%), or Army (13%), serving in clinician (40%) or faculty (32%) roles. Most respondents (67%) reported three or fewer publications and had never been a primary investigator or co-investigator on an external grant. Of the 34 respondents who identified as a faculty at some point in their career, 26 (77%) reported two or more peer-reviewed publications, and 20 (59%) had fewer than six publications. The faculty had significantly more research experience and peer-reviewed publications than residents, clinicians, or leaders (3.92 vs 2.19, 2.24, and 3.40, respectively, P < .001, η2 = 0.22; 5.11 vs 1.13, 2.12, and 4.33, respectively, P < .001, η2 = 0.25). Gender differences in priority ranking were found, but each gender identified the same top three training needs. Among the top 10 training needs for scholarly activity for military family medicine physicians, 7 may be addressed with specific training modules: (1) obtaining funding/grants for research, (2) accessing research resources (e.g., research administrators and other staff, information, equipment, money, and time), (3) establishing a relationship with research mentors, (4) undertaking health promotion studies, (5) designing a research study, (6) writing reports of your research studies, and (7) using technical equipment, including computer software, to find and organize published research or prepare manuscripts. CONCLUSIONS: Knowledge of military family medicine physicians' prioritized research training needs enables a focused approach to support an essential component of military medical readiness: primary care scholarship. Addressing these needs may begin with raising awareness of military primary care research network resources. Furthermore, a coordinated effort to develop specific training modules to address needs and ongoing research to identify, target training by audience need, and prioritize needs as they change over time are indicated to ensure that military family medicine physicians maintain and develop a flourishing culture of scholarly engagement.

Brain glutamate and sleep efficiency associations following a ketogenic diet intervention in individuals with Alcohol Use Disorder.

Background: We previously showed that ketogenic diet (KD) was effective in curbing alcohol withdrawal and craving in individuals with alcohol use disorder (AUD). We hypothesized that the clinical benefits were due to improvements in sleep. To test this, we performed a secondary analysis on the KD trial data to (1) examine the effects of KD on total sleep time (TST) and sleep quality and (2) investigate the association between KD-induced alterations in cingulate glutamate concentration and changes in TST and sleep quality. Methods: AUD individuals undergoing alcohol detoxification were randomized to receive KD (n=19) or standard American diet (SA; n=14) for three weeks. TST was measured weekly by self-report, GENEActive sleep accelerometer, and X4 Sleep Profiler ambulatory device. Sleep quality was assessed using subjectively ratings of sleep depth and restedness and Sleep Profiler (Sleep Efficiency [%]). Weekly 1H magnetic resonance spectroscopy scans measured cingulate glutamate levels. Results: TST was lower in KD than SA and increased with effect of time. Sleep depth, restedness, and Sleep Efficiency improved with time, but exhibited no effect of diet. In KD and SA combined, week 1 cingulate glutamate levels correlated positively with Sleep Efficiency, but not with TST. Conclusions: Although cingulate glutamate levels correlated positively with Sleep Efficiency in week 1, KD-induced glutamate elevation did not produce significant sleep improvements. Rather, KD was associated with lower TST than SA. Given the well-established associations between sleep and alcohol relapse, longer follow up assessment of KD's impact on sleep in AUD is warranted.

Prefrontal cortical response to natural rewards and self-reported anhedonia are associated with greater craving among recently withdrawn patients in residential treatment for opioid use disorder.

Both anhedonia and craving are common among patients with opioid use disorder (OUD), and are associated with vulnerability to relapse. Although these constructs are theoretically linked relatively few studies have examined them together. In the current study, recently withdrawn patients (N = 71) in residential treatment for prescription OUD underwent a cue reactivity paradigm while being monitored with functional near-infrared spectroscopy (fNIRS). Patients also self-reported symptoms of anhedonia via the Snaith-Hamilton Pleasure Scale (SHAPS), while smartphone-based ecological momentary assessments (EMA) were used to measure craving levels. On average, lower right prefrontal cortex (PFC) activity in response to positive social stimuli was associated with higher craving (ß = - 2.87; S.E. = 1.23; p = 0.02). Self-reported anhedonia moderated the association between PFC activity and craving (ß = - 1.02; S.E. = 0.48; p = 0.04), such that patients with two or more anhedonic symptoms had a significant and stronger negative association between PFC activation to hedonically positive images and craving, compared to patients with fewer than two anhedonic symptoms, among whom the association was not significant. This finding provides evidence that higher levels of anhedonia among patients in residential treatment for OUD are associated with a stronger link between lower PFC response to positive social experiences and higher levels of craving, potentially increasing overall vulnerability to relapse.

Reregulation of cortisol levels and sleep in patients with prescription opioid use disorder during long-term residential treatment.

OBJECTIVE: Research has demonstrated that hypothalamic-pituitary-adrenal (HPA) axis function and sleep patterns are dysregulated in patients diagnosed with opioid use disorder (OUD). It is unclear whether and/or when cortisol and sleep might re-regulate over time, and, whether re-regulation is associated with abstinence following discharge from residential treatment. The current study evaluated changes in sleep and basal cortisol levels in prescription OUD patients in residential treatment, and the association between these measures and treatment outcome following discharge. METHOD: As part of a larger study, 55 participants with prescription OUD provided two days of salivary cortisol samples and 12 consecutive nights of sleep actigraphy between days 19-30 of residential treatment (Time Point 1; TP1). Thirteen of the original 55 participants remained in residence and repeated the measures between days 60-72 (Time Point 2; TP2). Thirty-seven healthy controls (HC) provided baseline measures (TP1) of salivary cortisol and sleep. Treatment outcome data, abstinence vs relapse, were established at 120 days following discharge. RESULTS: Prescription OUD patients had higher cortisol levels and lower total sleep time (TST) than HC at TP1. At TP2, TST and cortisol levels no longer differed from HCs in the subgroup of patients who remained abstinent following discharge after TP2. Individuals whose cortisol and TST did not change from TP1 to TP2 were more likely to relapse following discharge from residential treatment. CONCLUSION: Re-regulation of TST and cortisol levels while in residential treatment was associated with better treatment outcome following discharge for prescription OUD patients.

Daily meaningfulness among patients with opioid use disorder: Examining the role of social experiences during residential treatment and links with post-treatment relapse.

BACKGROUND: A sense of meaningfulness is an important initial indicator of the successful treatment of addiction, and supports the larger recovery process. Most studies address meaningfulness as a static trait, and do not assess the extent to which meaningfulness might vary within an individual, or how it may vary in response to daily life events such as social experiences. METHODS: Ecological momentary assessment (EMA) was used to: 1) examine the amount of within-person variability in meaningfulness among patients in residential treatment for prescription opioid use disorder; 2) determine whether that variability was related to positive or negative social experiences on a daily basis; and 3) assess whether those day-to-day relationships were related to relapse at four months post-treatment. Participants (N = 73, 77% male, Mage = 30.10, Range = 19-61) completed smartphone-based assessments four times per day for 12 days. Associations among social experiences, meaningfulness, and relapse were examined using multilevel modeling. RESULTS: Between-person variability accounted for 52% (95% CI = 0.35, 0.67) of variance in end-of-day meaningfulness. End-of-day meaningfulness was higher on days when participants reported more positive social experiences (ß = 1.17, SE = 0.33, p < .05, ΔR2 = 0.041). On average, participants who relapsed within four months post-residential treatment exhibited greater within-day reactivity to negative social experiences (ß = -1.89, SE = 0.88, p < .05, ΔR2 = 0.024) during treatment than participants who remained abstinent. CONCLUSION: Individual differences in maintaining meaningfulness day by day when faced with negative social experiences may contribute to the risk of relapse in the early months following residential treatment.

Daily associations among craving, affect, and social interactions in the lives of patients during residential opioid use disorder treatment.

OBJECTIVE: This study captured the interrelationships among craving, negative affect, and positive and negative social exchanges in the daily lives of patients in residential treatment for opioid use disorders (OUDs). METHOD: Participants were 73 patients (77% male), age 19 to 61 (Mage = 30.10, SDage = 10.13) in residential treatment for OUD. Participants completed a smartphone-based survey 4 times per day for 12 consecutive days that measured positive and negative social exchanges (Test of Negative Social Exchange), negative affect (PA-NA scales), and craving (frequency and intensity). Within-person, day-level associations among daily positive and negative social exchanges, negative affect, and craving were examined using multilevel modeling. RESULTS: Daily negative social exchanges (M = 1.44, SD = 2.27) were much less frequent than positive social exchanges (M = 6.59, SD = 4.00) during residential treatment. Whereas negative social exchanges had a direct association with same-day craving (ß = 0.08; 95% CI = 0.01, 0.16, ΔR2 = 0.01), positive social exchanges related to craving indirectly via moderation of the within-person negative affect-craving link (ß = -0.01; 95% CI = -0.01, -0.001, ΔR2 = 0.002). Positive social exchanges decoupled the same-day linkage between negative affect and craving on days when individuals had at least four more positive social exchanges than usual. CONCLUSIONS: These results indicate that both negative affect and negative social exchanges are uniquely related to craving on a daily basis, and that extra positive social interactions can reduce the intraindividual coupling of negative affect and craving during residential treatment for OUD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Daily sleep quality affects drug craving, partially through indirect associations with positive affect, in patients in treatment for nonmedical use of prescription drugs.

OBJECTIVE: Sleep disturbance has been identified as a risk factor for relapse in addiction to a range of substances. The relationship between sleep quality and treatment outcome has received relatively little attention in research on nonmedical use of prescription drugs (NMUPD). This study examined the within-person association between sleep quality and craving in medically detoxified patients in residence for the treatment of NMUPD. METHOD: Participants (n=68) provided daily reports of their sleep quality, negative affect (NA), positive affect (PA), and craving for an average of 9.36 (SD=2.99) days. Within-person associations of sleep quality and craving were examined using multilevel modeling. Within-person mediation analyses were used to evaluate the mediating roles of NA and PA in the relationship between sleep quality and craving. RESULTS: Greater cravings were observed on days of lower than usual sleep quality (γ10=-0.10, p=0.003). Thirty-one percent of the overall association between sleep quality and craving was explained by PA, such that poorer sleep quality was associated with lower PA and, in turn, lower PA was associated with greater craving. No evidence emerged for an indirect association between sleep quality and craving through NA. CONCLUSIONS: Daily fluctuations in sleep quality were associated with fluctuations in craving, an association partially explained by the association between sleep quality and daily PA. These data encourage further research on the relationship between sleep, affect, and craving in NMUPD patients, as well as in patients with other substance use disorders.

An Initial Evaluation of a Comprehensive Continuing Care Intervention for Clients with Substance Use Disorders: My First Year of Recovery (MyFYR).

INTRODUCTION: Physician health programs (PHPs) generate high rates of sustained abstinence in addicted physicians, through a combination of formal treatment, self-help involvement, regular monitoring via random urine toxicology tests, and powerful incentives generated by the threat of losing one's medical license. Recently, Caron Treatment Centers developed a new continuing care intervention, "My First Year of Recovery" (MyFYR), which is modeled after PHPs but provides extended recovery support to a broader segment of those with substance use disorders. This paper presents initial outcome data from MyFYR. METHODS: MyFYR features frequent outcomes monitoring via urine toxicology tests, and also includes a web-based social platform to coordinate efforts of recovery coaches, family members, and others (e.g., employers, probation officers). Participants were the first 198 clients who enrolled in MyFYR after participating in residential treatment at Caron. Substance use outcomes were determined by a combination of urine toxicology tests, client self-report, and information from family members obtained during a 12-month period following entry into MyFYR. RESULTS: Clients in MyFYR provided 70% of scheduled urine samples, for an average of 16.4 urine samples per client. Only 4.1% of the samples tested positive for alcohol or any drug. As determined by urine toxicology and client and family reports, 54% of the participants had some use of alcohol or drugs during the follow-up. Of these relapsed clients, 70.1% were retained or re-engaged in MyFYR, and of these, half were able to re-establish abstinence of two months duration or more, as documented by urine toxicology. DISCUSSION: These initial results are extremely promising, as they document high rates of sustained participation in urine drug test monitoring and positive outcome in clients not under the threat of losing a professional license or incarceration.

Ecological momentary assessment of affect and craving in patients in treatment for prescription opioid dependence.

Low positive affect (PA) is likely to contribute to risk of relapse; however, it has received relatively little attention in clinical research. This study examined the associations among positive affect, negative affect (NA), and craving in medically withdrawn patients using ecological momentary assessment (EMA). Participants (n=73) provided reports of their PA, NA, and craving 4 times a day for an average of 10.47 (SD=3.80) days. Person- and day-level associations between PA, NA, and craving were examined using multilevel models. A significant interaction emerged between person- and day-level PA such that PA on the day level was negatively associated with craving for individuals experiencing low mean PA throughout the study. No significant interaction emerged between person- and day-level NA. The main effects for both person- and day-level NA were significant. Individuals experiencing high NA throughout the study experienced higher craving overall and on days when NA was higher than usual, craving was also higher. Results suggest that high person- and day-level NA may directly contribute to the risk for relapse via increased craving, whereas low day- level PA may contribute to risk for relapse among individuals exhibiting low person-level PA via increased craving on days with lower than average levels of PA for those individuals. Given that there is a paucity of research relating low PA to craving, continued investigation into how and when low PA creates risk for relapse is warranted.

Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

OBJECTIVES: There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. METHODS: Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. RESULTS: Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). CONCLUSIONS: These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.