National Institute Of Drug Abuse Research Articles

Implementation of universal screening for substance use in pregnancy in a public healthcare system

ObjectiveScreening questionnaires are one option for identification of at-risk substance use and substance use disorder (SUD) during pregnancy. We report the experience of a single institution following universal implementation of a brief screening tool for self-reported substance use at the first prenatal encounter. Study DesignThis is a prospective implementation study evaluating screening for substance use in pregnancy in a large safety net healthcare system. Universal screening with the National Institute of Drug Abuse (NIDA) Quick screen V1.0 was integrated into the electronic medical record (EMR) and administered at the first point of contact with the healthcare system. SUD was identified initially with diagnosis within the EMR by a healthcare provider and was confirmed with toxicology (maternal or neonatal) results corroborating a pattern of substance use and maternal and neonatal ICD-10 codes for SUD. Patients identified with SUD were then classified as moderate or severe SUD based on criteria established by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V). We measured rates of NIDA implementation across different healthcare settings, evaluated NIDA concordance with ascertainment of SUD, and compared adverse pregnancy outcomes associated with moderate and severe SUD. ResultsFrom July 28,2021 through June 25, 2022, 14,634 unique pregnant individuals accessed care at ambulatory and acute care sites. Universal implementation of the NIDA Quick Screen identified at-risk substance use in 2,146 (14.7%) of those who accessed our system, or 17.1% of 12,550 screened across the system, with greater screen completion in ambulatory over acute care settings. SUD was identified in 256 (1.7%) of 14,634 individuals and moderate or severe SUD was identified in 184 (1.3%). Among those with moderate or severe SUD, 90 (48.9%) were NIDA positive, 22 (12.0%) NIDA negative and 72 (39.1%) unscreened. Of 94 individuals with NIDA discordance or who were unscreened 76 (81%) accessed initial care through an acute care setting. Of 96 individuals with opioid use disorder, 68 (70.8%) were treated with medication assisted therapy and 56 (58.3%) were screened with the NIDA Quick Screen. Among delivered individuals with available outcomes, those with moderate or severe SUD were less likely to seek prenatal care (71(76%) vs 9852(98%), <0.001)) and more likely to deliver before 37 weeks, (18(20%) vs 909(9%), RR(95%CI) 2.13(1.40,3.24)) compared to individuals without SUD. Neonates exposed to moderate or severe SUD were more likely to have birth weight <10th centile for gestational age (20(22%) vs 1147(12%), RR(95%CI) 1.92(1.29,2.85)) and require admission to the neonatal intensive care unit (NICU) (19(21%) vs 964(10%), RR(95%) 1.95 (1.30,2.93)). ConclusionUniversal screening was implemented across a large public healthcare system at a high rate, with higher rates of implementation in ambulatory settings. NIDA successfully identified at-risk substance use in 17% of the SUD cohort but failed to identify more than 50% of patients with moderate or severe SUD. Patients with moderate and severe SUD accessed care primarily through the ED and experienced higher rates of adverse obstetric and neonatal outcomes. Future efforts to identify, engage and retain this highest risk group are needed.

Lumbar epidural electrical stimulation enhances respiration in mice

Spinal cord epidural electrical stimulation (EES) has emerged as a novel approach to modulate and interrogate the neural circuit(s) underlying sensorimotor functions in the past few decades. Recent studies have revealed that cervical EES can regulate respiration in both human subjects and animal models. Furthermore, coupled cervical and lumbar stimulations significantly increased the rhythmic motor outputs in both the cervical and lumbar spinal cord. We hypothesize that the lumbar and cervical coupling is underpinned by cervico-lumbar synaptic connections, and thus, EES at level of the lumbar spinal cord alone may also facilitate respiration via the cervico-lumbar circuit. In this study, we applied EES to the dorsal surface of the lumbar spinal cord between levels 1 and 6 (L1-6) in anesthetized mice. We found that rostral lumbar (L1-2) EES at a stimulation intensity of 0.5 mA elicited significantly higher respiratory frequency, tidal volume, and minute ventilation responses compared to the other lumbar levels (L3-4 and L5-6) tested at intensities ranging from 0.1-1.0 mA. The increased respiratory activity elicited by lumbar stimulation persisted even after the stimulation ceased. Using the optimal stimulation parameters that we identified, we further investigated the underlying mechanism of the lumbar EES-induced respiratory response by examining the neuronal activation patterns. Using immunostaining, we detected c-fos signals, a marker of neuronal activity, in the cervical spinal cord and brainstem after EES at L1-2 using 0.5 mA at 30Hz. This indicates that focal lumbar stimulation elicits remote neuronal activation in cervical spinal cord and brainstem, regions that contain respiration-related neural circuits. These findings suggest that lumbar EES may facilitate respiration by recruiting paraspinal respiratory circuits and potentially supra-spinal respiratory central pattern generator(s). This study provides insights into the development of novel approaches to restore normal respiratory patterns for patients with respiratory disorders, particularly spinal cord injuries. This work was supported by The Louis and Harold Price Foundation, H &amp; H Evergreen Foundation, Jonathan and Susan Dolgen Foundation, the National Institute of Drug Abuse (R01DA047637), and the National Institute of Neurological Disorders and Stroke (UH3NS119772) in the National Institutes of Health. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial.

Cannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks. The aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial. Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS-UPDRS from baseline to final dose. Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS-UPDRS was reduced by 4.57 (95% CI, -8.11 to -1.03; P = 0.013) in CBD/THC group, and 2.77 (-4.92 to -0.61; P = 0.014) in placebo; the difference between groups was non-significant: -1.80 (-5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL. The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Retention and critical outcomes among new methadone maintenance patients following extended take-home reforms: a retrospective observational cohort study

Approximately 1800 opioid treatment programs (OTPs) in the US dispense methadone to upwards of 400,000 patients with opioid use disorder (OUD) annually, operating under longstanding highly restrictive guidelines. OTPs were granted novel flexibilities beginning March 15, 2020, allowing for reduced visit frequency and extended take-home doses to minimize COVID exposure with great variation across states and sites. We sought to use electronic health records to compare retention in treatment, opioid use, and adverse events among patients newly entering methadone maintenance in the post-reform period in comparison with year-ago, unexposed, controls. Retrospective observational cohort study across 9 OTPs, geographically dispersed, in the National Institute of Drug Abuse (NIDA) Clinical Trials Network. Newly enrolled patients between April 15 and October 14, 2020 (post-COVID, reform period) v. March 15-September 14, 2019 (pre-COVID, control period) were assessed. The primary outcome was 6-month retention. Secondary outcomes were opioid use and adverse events including emergency department visits, hospitalizations, and overdose. 821 individuals were newly admitted in the post-COVID and year-ago control periods, average age of 38.3 (SD 11.1), 58.9% male. The only difference across pre- and post-reform groups was the prevalence of psychostimulant use disorder (25.7% vs 32.9%, p=0.02). Retention was non-inferior (60.0% vs 60.1%) as were hazards of adverse events in the aggregate (X2 (1)=0.55, p=0.46) in the post-COVID period. However, rates of month-level opioid use were higher among post-COVID intakes compared to pre-COVID controls (64.8% vs 51.1%, p<0.001). Moderator analyses accounting for stimulant use and site-level variation in take-home schedules did not change findings. Policies allowing for extended take-home schedules were not associated with worse retention or adverse events despite slightly elevated rates of measured opioid use while in care. Relaxed guidelines were not associated with measurable increased harms and findings could inform future studies with prospective trials. USDHHSNIDACTNUG1DA013035-15.

HIV Prevention and Care Among Black Cisgender Sexual Minority Men and Transgender Women: Protocol for an HIV Status-Neutral Cohort Study Using an Observational-Implementation Hybrid Approach.

Black cisgender gay, bisexual, and other sexual minority men (SMM) and transgender women (TW) continue to be heavily affected by HIV. Further research is needed to better understand HIV prevention and care outcomes in this population. In particular, there is a need for research examining the impact of substance use and sleep health on HIV prevention and treatment outcomes among Black SMM and TW. This paper outlines the study methods being used in the recently launched follow-up study to the Neighborhoods and Networks (N2) study, which we refer to as N2 Part 2 (N2P2). N2P2 aims to address this gap in the literature, build off the findings of the original N2 study, and identify socioenvironmental determinants of health, including whether neighborhood and network factors mediate and moderate these relationships. Building on the N2 cohort study in Chicago from 2018 to 2022, N2P2 used a prospective longitudinal cohort design and an observational-implementation hybrid approach. With sustained high levels of community engagement, we aim to recruit a new sample of 600 Black SMM and TW participants residing in the Chicago metropolitan statistical area. Participants are asked to participate in 3 study visits across an 18-month study period (1 visit every 9 months). Four different forms of data are collected per wave: (1) an in-person survey, (2) biological specimen collection, (3) a daily remote ecological momentary assessment for 14 days after each study visit, and (4) data from electronic health records. These forms of data collection continue to assess neighborhood and network factors and specifically explore substance use, sleep, immune function, obesity, and the implementation of potential interventions that address relevant constructs (eg, alcohol use and pre-exposure prophylaxis adherence). The N2P2 study was funded in August 2021 by the National Institute of Drug Abuse (R01DA054553 and R21DA053156) and National Heart, Lung, and Blood Institute (R01HL160325). This study was launched in November 2022. Recruitment and enrollment for the first wave of data collection are currently ongoing. The N2P2 study is applying innovative methods to comprehensively explore the impacts of substance use and sleep health on HIV-related outcomes among an HIV status-neutral cohort of Black SMM and TW in Chicago. This study is applying an observational-implementation hybrid design to help us achieve findings that support rapid translation, a critical priority among populations such as Black SMM and TW that experience long-standing inequities with regard to HIV and other health-related outcomes. N2P2 will directly build off the findings that have resulted from the original N2 study among Black SMM and TW in Chicago. These findings provide a better understanding of multilevel (eg, individual, network, and neighborhood) factors that contribute to HIV-related outcomes and viral suppression among Black SMM and TW. DERR1-10.2196/48548.

0676 Sleep medication prescribing among patients receiving opioid use disorder treatment with comorbid insomnia

Abstract Introduction People initiating treatment for opioid use disorder (OUD) report insomnia to be a high priority, and insomnia is associated with compromised OUD treatment outcomes. However, insomnia treatments have yet to be investigated in the OUD clinical setting. Knowledge of prescribing patterns for sleep medications among OUD treatment patients is an essential first step to advance therapeutic development at the insomnia-OUD comorbidity. This retrospective cohort study used administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases (2006-2016) to investigate the prevalence of insomnia medication prescriptions among patients in OUD treatment with buprenorphine. In doing so, we assess sex differences in prescription receipt within this unique patient population, given the known sex-based disparities in insomnia among other adult populations. Methods We included people aged 12-64 years with diagnoses of insomnia and OUD initiating buprenorphine during the study timeframe. The primary outcome was receipt of insomnia medication prescription within 60 days of buprenorphine start, encompassing benzodiazepines, Z-drugs, or non-sedative/hypnotic insomnia medications (e.g., hydroxyzine, trazodone, and mirtazapine). Descriptive analyses present prescription prevalence for the total sample as well as separately for males and females. Lastly, associations between sex and insomnia medication prescription receipt were estimated using Poisson regression models. Results Our sample included 9,510 individuals (female n=4,637; male n=4,873) initiating buprenorphine for OUD who also had insomnia, of whom 6,569 (69.1%) received benzodiazepines, 3,891 (40.9%) Z-drugs, and 8,441 (88.8%) non-sedative/hypnotic medications. Poisson regression models, adjusting for sex differences in psychiatric comorbidities, found female sex to be associated with a slightly increased likelihood of prescription receipt: benzodiazepines (risk ratio [RR], RR=1.17 [1.11-1.23]), Z-drugs (RR=1.26 [1.18-1.34]), and non-sedative/hypnotic insomnia medication (RR=1.07, [1.02-1.12]). Conclusion Sleep medications are commonly being prescribed to individuals with insomnia in OUD treatment, especially females. These findings juxtapose the known increased overdose risk with benzodiazepine use and lack of efficacy data for these pharmacologic insomnia treatments in this growing patient population in the opioid crisis. Support (if any) National institute of Drug Abuse: K23 DA053507 (CEM), UG1DA050207 (FGM). National Institutes of Health: R25 MH112473-01 (HP), T32 DA015035 (KYX), R21 DA044744 (RAG and LJB). National Center for Advancing Translational Sciences: UL1 TR002345 (Washington University), UL1TR002649 (Virginia Commonwealth University)

0330 Blinded Verses Open-Label Hypnotic Tapering for Hypnotic Discontinuation: A Randomized Clinical Trial

Abstract Introduction Many patients have difficulties achieving hypnotic discontinuation due to anxiety that arises when they knowingly reduce their hypnotic dose or withhold it entirely. This study is testing a blinded tapering approach designed to reduce patients’ anxiety during the hypnotic tapering process. Methods Thus far, a sample of 44 (M age = 59.1±14.1 yrs.; 61.4% women) users of benzodiazepine (BZD) or newer generation benzodiazepine receptor agonists (BZRA) have enrolled in this trial and completed a 3-month post-tapering follow-up. Following baseline assessments that included completion of the insomnia severity index (ISI), these enrollees completed 4 sessions of cognitive behavioral insomnia therapy (CBTI). Subsequently they were randomized to one of two 10-week, tapering protocols wherein their medication dosage was reduced by 25% every two weeks either in a blinded or open-label manner. Medication usage was assessed and ISI scores were obtained at the end of the tapering phase and at a 3-month follow-up. Results A linear mixed model analysis showed only an effect for time in study on ISI scores with both tapering groups showing a significant (F = 36.89; p = .0001) decline in these scores from baseline through the 3-month follow-up. By the 3-month follow-up, a slightly, albeit non-significantly, higher proportion of the blinded tapering group (76.2%) were no longer using their BZD/BZRA hypnotics than in the open label group (60.9%). However, there was a significantly higher BZD/BZRA discontinuation rate by the 3-month follow-up among those who achieved ISI score-determined insomnia remission than among unremitted participants both for the sample as a whole (85% vs. 54.2%; p = .05) and for the open label group (88.9% vs. 42.9%; p = .0397) considered separately. This difference between remitted and unremitted participants was not seen in the blinded tapering group. Conclusion Early findings in this trial suggest a slight advantage to blinded over open label hypnotic tapering in achieving hypnotic discontinuation. Moreover, insomnia remission may not be essential for hypnotic discontinuation when blinded tapering is conducted. Support (if any) National Institute of Drug Abuse, Grant # 1R01DA047341-01A1

Ventral and dorsal cervical spinal cord electrical epidural stimulation facilitated respiration differently in the presence of opioids in human via different neural circuits

Opioid overdose is one of the leading causes of overdose related deaths in the United States of America, accounting for 70.6% of overdose fatalities in 2019 alone. A leading cause of death among opioid overdoses is respiratory depression. Epidural electrical stimulation (EES) emerges as a novel approach of facilitating rhythmic motor activities such as locomotion and respiration. Previous studies conducted in humans and rodent models demonstrated respiratory augmentations induced by EES delivered to the dorsal cervical spinal cord. Importantly, EES at the dorsal cervical spinal cord opposes opioid-induced respiratory depression in human. To reveal the mechanism underpins how cervical EES modulate the respiratory neural circuit, we conducted this comparative study between dorsal cervical EES to the ventral EES in patients with opioid-induced respiratory suppression or depression. We hypothesize that the ventral cervical EES activates the local motor neuronal pools while the dorsal EES recruits both sensory and motor cervical circuits as well as accesses supraspinal structures such as medulla. We recruited and consented 25 patients who underwent anterior (ventral) cervical spinal cord surgery and compared the effect of ventral cervical EES to to the effect of dorsal cervical ESS in a dataset that we collected from 18 patients undergoing cervical spinal surgery. In the 25 patients, the EES was deliver to the ventral surface of spinal cord ranging from cervical level 3 to 7 (C3 to C7) for no more than 90 seconds at the optimal intensity ranging from 0.5 mA to 5 mA with stimulation frequencies 5 Hz or 30 Hz. In both the dorsal and ventral EES groups, the subjects were anesthetized with low dose or high dose remifentanil that partially or completely depressed voluntary respiration. We observed three main differences between the dorsal and ventral cervical EEST in regulating respiration in the presence of remifentanil. First, dorsal cervical EES induced the resetting of inspiratory rhythm while ventral cervical EES did not. Second, dorsal but not ventral cervical EES induced longer lasting respiratory modulation after the stimulation stopped. Third, dorsal cervical EES induced both frequency and amplitude changes of respiration while ventral cervical EES modulated the amplitude of the respiration more significantly. These observations suggest that the dorsal and ventral cervical EES facilitate respiration via different neural circuits. This work was supported by the National Institute of Drug Abuse in the National Institutes of Health: R01 DA047637, Louis and Harold Price Foundation, H &amp; H Evergreen Foundation, and J. Yang Family Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of clinical, comorbid, and social determinants of health on brain ageing in people with and without HIV: a retrospective case-control study.

Neuroimaging reveals structural brain changes linked with HIV infection and related neurocognitive disorders; however, group-level comparisons between people with HIV and people without HIV do not account for within-group heterogeneity. The aim of this study was to quantify the effects of comorbidities such as cardiovascular disease and adverse social determinants of health on brain ageing in people with HIV and people without HIV. In this retrospective case-control study, people with HIV from Washington University in St Louis, MO, USA, and people without HIV identified through community organisations or the Research Participant Registry were clinically characterised and underwent 3-Tesla T1-weighted MRI between Dec 3, 2008, and Oct 4, 2022. Exclusion criteria were established by a combination of self-reports and medical records. DeepBrainNet, a publicly available machine learning algorithm, was applied to estimate brain-predicted age from MRI for people with HIV and people without HIV. The brain-age gap, defined as the difference between brain-predicted age and true chronological age, was modelled as a function of clinical, comorbid, and social factors by use of linear regression. Variables were first examined singly for associations with brain-age gap, then combined into multivariate models with best-subsets variable selection. In people with HIV (mean age 44·8 years [SD 15·5]; 78% [296 of 379] male; 69% [260] Black; 78% [295] undetectable viral load), brain-age gap was associated with Framingham cardiovascular risk score (p=0·0034), detectable viral load (>50 copies per mL; p=0·0023), and hepatitis C co-infection (p=0·0065). After variable selection, the final model for people with HIV retained Framingham score, hepatitis C, and added unemployment (p=0·0015). Educational achievement assayed by reading proficiency was linked with reduced brain-age gap (p=0·016) for people without HIV but not for people with HIV, indicating a potential resilience factor. When people with HIV and people without HIV were modelled jointly, selection resulted in a model containing cardiovascular risk (p=0·0039), hepatitis C (p=0·037), Area Deprivation Index (p=0·033), and unemployment (p=0·00010). Male sex (p=0·078) and alcohol use history (p=0·090) were also included in the model but were not individually significant. Our findings indicate that comorbid and social determinants of health are associated with brain ageing in people with HIV, alongside traditional HIV metrics such as viral load and CD4 cell count, suggesting the need for a broadened clinical perspective on healthy ageing with HIV, with additional focus on comorbidities, lifestyle changes, and social factors. National Institute of Mental Health, National Institute of Nursing Research, and National Institute of Drug Abuse.

Opioids and restless legs syndrome: a double-edged sword.

Opioids and restless legs syndrome: a double-edged sword.

0683 Smoking and Perceived Stress: Examining Associations with Subjective Symptoms of Obstructive Sleep Apnea through Parallel Mediation Analyses

Abstract Introduction Cigarette smoking is known to have a negative effect on individuals’ sleep quality. Specifically, evidence shows that smoking can exacerbate sleep disorders such as obstructive sleep apnea (OSA) by increasing irritation and inflammation of the upper respiratory conducts. Furthermore, previous research highlights a complex bidirectional positive association between cigarette smoking and perceived stress. Sleep quality may be an important aspect intervening in the association between smoking and perceived stress, given that individuals who report high stress also report more sleeping issues and increased risk for OSA. Further research is needed to elucidate the impact of smoking and OSA on perceived stress. Methods The present cross-sectional survey of N=459 (75.8% female; 60.3% non-Hispanic White) current smokers and non-smokers investigated the associations between smoking status and perceived stress through the indirect effects of subjective OSA symptoms. A parallel mediation analysis using PROCESS Macro Model 4 was conducted with three mediators: risk for OSA based on subjective symptoms (assessed using the STOP portion of the STOP-BANG questionnaire), average sleep propensity (evaluated using the Epworth Sleepiness Scale), and overall subjective sleep quality (assessed with the Pittsburgh Sleep Quality Index). Race, sex, employment, and income were added to the model as covariates. Results Analyses supported a significant indirect effect of risk for OSA based on subjective symptoms (B = -0.55, 95% CI [-1.07, -0.09]) and overall subjective sleep quality (B = -1.39, 95% CI [-2.16, -0.74]) on the relationship between smoking status and perceived stress. However, average sleep propensity was not found to mediate this association (B = -0.09, 95% CI [-0.45, 0.21]). The direct effect of smoking status on perceived stress was also not statistically significant (B = 0.06, t = 0.09, p = 0.93). Conclusion Findings illustrate that smokers tend to be at greater risk for OSA and overall report worse sleep quality, which in turn increases their reported levels of perceived stress. Further research is necessary to understand possible demographics-based differences behind these findings as well as potential clinical implications. Support (If Any) This project was financially supported by the National Institute of Drug Abuse (R01DA046096-02S1).

Evidence of Intact Corticostriatal and Altered Subcortical-striatal Resting-state Functional Connectivity in Chronic Pain

Highly relevant to both pain and reward, corticostriatal circuits are important for understanding chronic pain. Previous research has demonstrated importance of the nucleus accumbens (NAcc) - medial prefrontal cortex (MPFC) circuit in predicting localized pain chronification in chronic back pain (CBP). The aims of our study were to extend prior evidence of brain reward/value circuit alterations to new cohorts of chronic pain patients and further evaluate activity within reward/value networks in chronic pain. As outlined in our pre-registered plan on the Open Science Framework (OSF, https://osf.io/cj9u8), we hypothesized that resting-state brain reward circuits (i.e., fMRI-indicated NAcc-MPFC resting-state functional connectivity [rsFC] measurements) are altered in patients with fibromyalgia (FM). In a first study, we examined corticostriatal rsFC strength of the NAcc-MPFC circuit in patients with FM (N=17) compared to healthy controls (HC, N=17). Robust NAcc-MPFC functional connectivity was found among patients with FM and HCs, but no significant group differences were observed, indicating intact NAcc-MPFC rsFC in FM. Because previous resting-state studies in patients with CBP involved a pain-monitoring/rating task, in a second study, we compared our results from FM and HC cohorts to a separate cohort of patients with CBP (publicly available dataset, N=31) during resting-state fMRI with no rating task. We again found no significant group differences in NAcc-MPFC rsFC. In a third study, we conducted an expanded analysis of NAcc rsFC to mesolimbic (i.e., subcortical) circuit regions in chronic pain. We found reduced rsFC of the right NAcc with mesolimbic circuit regions (putamen, thalamus, and ventral pallidum) in FM vs. HC, and additional NAcc-mesolimbic alterations across FM and CBP vs. HC groups. Together, our results expand upon prior observed alterations in brain reward circuits, providing novel evidence of intact corticostriatal but altered subcortical-striatal circuits in chronic pain. This project was funded by the National Institutes of Health, National Institute of Drug Abuse (NIDA), K99/R00 DA040154 (awarded to K.T.M.), K24 NS126781 (awarded to S.C.M.), and the Redlich Pain Research Endowment (S.C.M.). Data used in this project from the Open Pain Project (OPP; Principal Investigator: A. Vania Apkarian, PhD, Northwestern University) was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Drug Abuse (NIDA).

Acute to Chronic Pain Signatures Program (a2CPS): Implementation of Remote Training for a Multisite Observation Study During COVID-19

Chronic pain produces the largest non-fatal burden of disease, yet our understanding of factors that contribute to the transition from acute chronic pain are poorly understood. The Acute to Chronic Pain Signatures Program (A2CPS) is a longitudinal, multi-site observational study to identify biomarkers (individual or biosignature combinations) that predict susceptibility or resilience to the development of chronic pain after surgery (knee replacement or thoracotomy). Due to the COVID-19 pandemic, however, travel between sites was restricted just as the study was preparing to begin enrollment. Here, we present multiple training protocol adaptations that were successfully implemented to facilitate remote research-related training. The A2CPS consortium includes 2 Multisite Clinical Centers (MCCs, 10 recruitment sites), a Clinical Coordinating Center (CCC), a Data Integration and Resource Center (DIRC), 3 Omics Data Generation Centers, and representation from the NIH Pain Consortium, Common Fund, and National Institute of Drug Abuse. The A2CPS is collecting candidate and exploratory biomarkers including pain, fatigue, function, sleep, psychosocial factors, quantitative sensory testing (QST), genomics, proteomics, metabolomics, lipidomics, and brain imaging. The CCC adapted the A2CPS training and evaluation techniques for certifying the MCCs to ensure competency with recruitment, assessments (surveys, QST, function), and data entry across clinical sites using a combination of virtual training sessions, standardized quantitative measurements, video demonstrations, and reliability assessments. Staff at data collection sites have been successfully certified in all psychophysical assessments (QST, function). This included use of stop watches and metronomes to ensure standard application rates, completion of application-rate and inter-rater-reliability worksheets at each clinical site, designation of site-specific master examiners, training rubrics and video demonstration to verify competency was harmonized across sites. Adaptation of training protocols to a remote format enabled initiation of subject enrollment while maintaining documented standards with high data completion rates for surveys and assessments. The A2CPS Consortium is supported by the National Institutes of Health Common Fund, which is managed by the OD/Office of Strategic Coordination (OSC). Consortium components include: Clinical Coordinating Center (UO1NS077179), Data Integration and Resource Center (UO1NS077352), Omics Data Generation Centers (U54DA049116, U54DA049115, U54DA09113), and Multisite Clinical Centers: MCC 1 (UM1NS112874) and MCC 2 (UM1NS118922). Postdoctoral support for GB provided by the National Institutes of Neurological Disease and Stroke (NINDS) of the NIH under Award Number U24NS112873-03S2.

MHealth Intervention to Improve Treatment Outcomes Among People With HIV Who Use Cocaine: Protocol for a Pilot Randomized Controlled Trial

BackgroundAntiretroviral therapy is effective in reducing HIV-related morbidity, mortality, and transmission among people with HIV. However, adherence and persistence to antiretroviral therapy are crucial for successful HIV treatment outcomes. People with HIV who use cocaine have poor access to HIV services and lower retention in care.ObjectiveThe primary goal of this paper is to provide a detailed description of a mobile health intervention. This study is designed to improve medication adherence among people with HIV who use cocaine. A secondary goal is to list the important challenges and adaptations incorporated in the study design.MethodsThis study, titled Project SMART, used a wireless technology–based intervention, including cellular-enabled electronic pillboxes called TowerView Health and smartphones, to provide reminders and feedback on adherence behavior. The intervention design was based on the theoretical frameworks provided by the self-determination theory and the Motivation Technology Model. The 12-week pilot randomized controlled trial with four arms provided three types of feedback: automated feedback, automated+clinician feedback, and automated feedback+social network feedback.ResultsThe study was funded by the National Institute of Drug Abuse (R21DA039842) on August 1, 2016. The institutional review board for the study was approved by Yale University on March 21, 2017. Data collection lasted from June 2017 to January 2020. The final enrollment was 71 participants, of whom 57 (80%) completed the study. The data are currently undergoing analysis, and the manuscript is being developed for publication in early 2022.ConclusionsImplementing complex mobile health interventions for high-risk and marginalized populations with multicomponent interventions poses certain challenges, such as finding companies with adequate technology for clients and financial stability and minimizing the research-related burden for the study population. Conducting feasibility studies is important to recognize these challenges and the opportunity to address these challenges with solutions while keeping the design of a randomized controlled trial as true as possible.Trial RegistrationClinicaltrials.gov NCT04418076; https://clinicaltrials.gov/ct2/show/NCT04418076International Registered Report Identifier (IRRID)DERR1-10.2196/28332

Prevalence and Screening of Tobacco and Substance Abuse among patients visiting Emergency Department

Aim: To prevalence and screening of tobacco and substance abuse among patients visiting emergency. Methods: This is a cross-sectional study conducted in the emergency department of Usman Memorial Hospital, Karachi during the period of Jan, 2020 to June, 2021. In the 18 months of study, we included patients visiting to our emergency department due to any acute complaint who is older than 18 years of age. All the participants were to be asked National Institute of Drug Abuse (NIDA) quick screen and tobacco addiction screening was done by CAGE questionnaire. Data was collected and analyzed using SPSS version 2. Results: During the 18 months’ time, we received 642 patients matching our inclusion criteria for this study. Out of these 371(59.4%) participants agreed to participate in the study whereas the 40.6% refused to enter the study. Out of these there were 242(65.2%) males and 129(34.7%) females in the study sample. All these participants were asked the single screen question for drug use and 178(47.9%) of the participants have used an illegal drug or prescription drugs for non-medical reason. Among the total 194 participants who smoke currently there were 146(75.2%) participants with positive CAGE modified results suggests nicotine dependence. Conclusion: The above study suggests that substance abuse/misuse of prescription drugs and nicotine dependence is common in our population and awareness regarding smoking cessation and drugs use is needed. Screening of individuals at emergency department is an efficient method for identifying severe cases and provide them proper medical help. Keywords: Tobacco, Nicotine, Smoking.

Prospective Prediction of Lapses in Opioid Use Disorder: Protocol for a Personal Sensing Study.

BackgroundSuccessful long-term recovery from opioid use disorder (OUD) requires continuous lapse risk monitoring and appropriate use and adaptation of recovery-supportive behaviors as lapse risk changes. Available treatments often fail to support long-term recovery by failing to account for the dynamic nature of long-term recovery.ObjectiveThe aim of this protocol paper is to describe research that aims to develop a highly contextualized lapse risk prediction model that forecasts the ongoing probability of lapse.MethodsThe participants will include 480 US adults in their first year of recovery from OUD. Participants will report lapses and provide data relevant to lapse risk for a year with a digital therapeutic smartphone app through both self-report and passive personal sensing methods (eg, cellular communications and geolocation). The lapse risk prediction model will be developed using contemporary rigorous machine learning methods that optimize prediction in new data.ResultsThe National Institute of Drug Abuse funded this project (R01DA047315) on July 18, 2019 with a funding period from August 1, 2019 to June 30, 2024. The University of Wisconsin-Madison Health Sciences Institutional Review Board approved this project on July 9, 2019. Pilot enrollment began on April 16, 2021. Full enrollment began in September 2021.ConclusionsThe model that will be developed in this project could support long-term recovery from OUD—for example, by enabling just-in-time interventions within digital therapeutics.International Registered Report Identifier (IRRID)DERR1-10.2196/29563

612. Empowering Patients with Addiction to Self-Administer Parenteral Antibiotics at Home: A Pilot Project

Abstract Background Nearly 20% of people in the United States use drugs each year. People who use drugs (PWUD) are predisposed to complex infections that require long term intravenous (IV) antibiotics. A frequent clinical quandary in PWUD is safe administration of extended IV antibiotics. Current standard of care is IV antibiotic administration in skilled nursing facilities. In this system, PWUD frequently do not finish antibiotic therapy, resulting in avoidable complications of untreated infections and increased healthcare utilization. We present a pilot study of ten patients with a history of addiction who required long-term IV antibiotics to evaluate the feasibility of self administered outpatient parenteral antibiotic therapy (S-OPAT) for PWUD. Methods Ten patients who had a history of mild addiction and stable housing, social support and transportation were enrolled at Parkland Health and Hospital System to complete S-OPAT. We extracted demographic, drug use, clinical and access to care variables and patients were followed with weekly clinical appointments. Addiction severity was defined using the National Institute of Drug Abuse (NIDA) -Modified ASSIST Score. We completed post-intervention surveys to evaluate the impact of the intervention on provider-patient trust. Results A total of 10 patients were enrolled in S-OPAT (Table 1). The patients were 48 years old on average, all were male and seven were Hispanic. All patients had stimulant use disorder and no patients had commercial insurance. Treated infections were bone/ joint and skin/soft tissue in origin. All patients completed their antibiotic course, nearly all appointments were attended (96%) and there were no 30-day hospital readmissions (Table 2). More than two-third of patients experienced improvement in addiction severity with progress in multiple psychosocial factors including housing instability, social support and legal problems (Figure 1; Table 2). Table 1. Demographic, substance use and clinical variables among people who use drugs enrolled in the pilot project for S-OPAT (N=10). Table 2. Clinical, drug use and psychosocial outcomes among people who use drugs and received S-OPAT (N=10). Addiction severity was defined using the National Institute of Drug Abuse (NIDA) -Modified ASSIST Score. Figure 1. Progression of addiction severity before and after completion of self-administered outpatient parenteral antibiotic therapy pilot among patients with a history of drug use (N=10). Addiction severity was defined using the National Institute of Drug Abuse (NIDA) -Modified ASSIST Score. Conclusion We demonstrate that PWUD can successfully complete S-OPAT with simultaneous improvement in addiction severity and psychosocial factors. We hope to create a framework for the patient-centered administration of extended courses of antibiotics for PWUD and to advocate for the expansion of individualized approaches to extended courses of IV antibiotics for PWUD. Disclosures All Authors: No reported disclosures

Prescription drug misuse during pandemic

Prescription drug misuse is when someone takes a medication inappropriately. The prescription drug misuse is not an uncommon issue but the use of prescription drugs has significantly increased during the covid 19 pandemic. The major factors that has contributed to the increased dependence to prescription drug use during the pandemic is the increased paranoia about the virus and the drug dependency of the substance abusers. The context of the study is the increased use of prescription drugs among young adults and case reports of violence attributed by drug use. The main aim of the study is to identify the trend of prescription drug use among young adults and the factors that contribute to the misuse. The study primarily focused on young adults and recorded the responses using the questionnaire. The methodology for the proposed study was through online interaction with the participants in the form of survey through google forms. The data collection method included literature review of published articles pertaining to the topic, newspaper articles and websites. The data collection was primarily through google forms and participants response are analyzed for arriving into conclusion. Further-more data from published article, journals, data published in websites like the National Health Portal, National Institute of Health (NIH)- National Institute of Drug Abuse (NIDA), World Health Organization (WHO). Both primary and secondary data is used for data collection. An age group between 20-30 was collected. This age group was selected due to the possibility that most utilization of prescription drugs would be contributed by these groups. Mostly randomized sampling was carried out due to the limitation of collecting data one to one considering the pandemic situations. After analyzing the results, it is inferred that there is a significant increase in use of prescription drugs during the pandemic time and the study also found a trend of alarming concern of buying prescription drug without it being prescribed by the medical practitioner which hence is a serious case of social concern.

Exposure to Negative Weight Talk From Family Members Is Associated With Weight Bias Internalization in Children

ObjectivesFrequent exposure to negative familial weight talk (NFWT), such as teasing or critical comments about weight from family members, may contribute to weight bias internalization (WBI) in children. WBI entails applying negative weight-based stereotypes to oneself and results in self-devaluation. Higher levels of WBI are linked to adverse outcomes, such as low self-esteem and disordered eating. We examined the association between NFWT exposure and WBI in a diverse sample of children from the Greater Boston Area. MethodsBaseline data on 137 parent-child dyads were analyzed. Children, 9–14yo, completed six items measuring NFWT frequency on a 6-point Likert scale (“never” to “almost every day”) from parents, siblings, and other household family members. Responses were converted to times in the past 3 months, summed, and dichotomized as < 9 times vs. ≥9 times. Children completed the WBI Scale–Modified indicating their agreement with applying negative weight-based statements to themselves on a 6-point Likert scale (“strongly disagree” to “strongly agree”). Responses were averaged and the mean WBI score was dichotomized as “low” (<3.0) versus “moderate-high” (≥3.0). ResultsOver half (52%) of the children were girls and 30% had overweight/obesity (BMI > 85th percentile). Half of the parents were non-Hispanic white. The mean child WBI score was 2.1 (SD = 0.9) and 15% had moderate-high levels of WBI. The median NFWT frequency was 0 (IQR = 6.0) and 25% reported NFWT ≥ 9 times. Children exposed to NFWT ≥ 9 times were 8.2 times more likely to have moderate-high levels of WBI than children exposed to NFWT < 9 times in the past 3 months (prevalence ratio = 8.2, 95%CI = 3.4 to 20.0, P < 0.001, by log binomial regression adjusted for child weight and parent race/ethnicity). ConclusionsFamily members appear to be a salient source of weight stigma in children. Exposure to NFWT as little as 3 times per month was significantly associated with moderate-high levels of WBI in this diverse sample of children. More research is needed to understand the impact of NFWT on child WBI, such as differences across racial/ethnic groups, by source (i.e., parents versus siblings), and across the lifespan. Funding SourcesNational Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Drug Abuse of the National Institutes of Health.

“What is vaping?“ 10-years of Youth Questions Regarding Electronic Nicotine Delivery Systems

ABSTRACT The increasing popularity of electronic nicotine delivery systems (ENDS) and the relationship of adolescent ENDS use to tobacco consumption in adulthood underscore the importance of effective prevention education. Prevention messaging relevant to youth curiosity about ENDS may serve to improve tobacco control strategies. ENDS-related questions were extracted from 10 years of transcripts of the National Institute of Drug Abuse’s Chat Day initiative, where youth engage anonymously with substance use experts. A content analysis of youth questions was completed to identify the concerns of youth and document changing ENDS nomenclature. Analysis revealed 10 topics depicting youth curiosity about ENDS and documented the changing terms youth use to refer to ENDS. These topics inform youth-focused prevention curricula by identifying content areas that resonate with youth concerns.