Applied Biochemistry and Microbiology

Abstract Background The Car, Relax, Alone, Forget, Friends, Trouble (CRAFFT) scale is a widely used screening tool for early identification of alcohol and other drug use, and assessing the risk of substance use disorders in adolescents and young adults. Despite its broad use, translation into several languages, and validation in various settings, no study has yet confirmed the psychometric properties of a Moroccan version. The present research aims to adapt and validate the Moroccan Arabic dialect version of the CRAFFT scale among adolescents and young adults with alcohol and drug use disorder. Methods A total of 302 adolescents and young adults (mean age = 18.36 ± 2.36), including 161 males and 41 females, were recruited from a substance use treatment center in Fez City. Confirmatory Factor Analysis (CFA) was used to assess the factorial structure and model fit, while internal consistency was evaluated using the Kuder-Richardson Formula 20 (KR-20). Convergent validity was examined using gold standard measures, including the International Neuropsychiatric Interview (MINI) and the Hooked-on Nicotine Checklist (HONC). All statistical analyses were performed using JASP software (version 0.17). Results CFA revealed a one-factor structure with a good overall fit (χ²/df = 1.91, Root Mean Square Error of Approximation (RMSEA) = 0.06, Standardized Root Mean Square Residual (SRMR) = 0.03, Comparative Fit Index (CFI) = 0.98, Normed Fit Index (NFI) = 0.97. The model had strong reliability with a KR-20 coefficient of 0.80. Convergent validity was confirmed by a high and significant correlation with the MINI gold standard (r = 0.82, p < 0.001), while a low correlation with the HONC gold standard (r = 0.20, p < 0.001) confirmed the scale’s convergent validity. A cutoff score of 4 or higher on the CRAFFT was identified as optimal for balancing sensitivity (78.35%) and specificity (91.67%), achieving a Youden index of 0.70. Conclusion The psychometric properties of the Moroccan version of the CRAFFT confirm that it is a valid tool for screening the early detection of alcohol and drug use and for assessing the risk of substance use disorders in adolescents and young adults.

Abstract Background Efforts to scale up overdose education and naloxone distribution (OEND), an evidence-based practice for reducing opioid overdose mortality, was a major focus of the HEALing Communities Study (HCS). The aim of this analysis is to describe the qualitative perspectives of partner organizations regarding the impacts of implementing OEND in a state that used a naloxone “hub with many spokes” model for scaling up this strategy. Methods Small group (n = 20) and individual (n = 24) qualitative interviews were conducted with staff from 44 agencies in eight Kentucky counties that implemented OEND from April 2020 to June 2022. Interviews were conducted between 6 and 8 months after the end of the intervention. Initial deductive coding used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework, and then additional inductive sub-coding focused on passages within the OEND Effectiveness code. Thematic analysis was then utilized to identify themes regarding the impacts of implementing OEND. Results Participants identified multi-level impacts of implementing OEND. At the individual-level, participants described lives being saved, greater access to naloxone for individuals served by the agency, reduced stigma toward OEND by clients, and greater client-level self-efficacy to respond to overdoses. Organizational impacts included improved staff readiness for overdose response, enhanced clinical relationships between staff and clients, and reduced staff stigma. Participants described positive impacts on their organizational networks and clients’ social networks. Community-level impacts included greater overall access and reduced stigma toward OEND. Conclusions These qualitative data revealed that staff from agencies involved in a community-wide effort to scale up OEND perceived multi-level benefits, including saving lives, reducing stigma, improving naloxone access, and enhancing staff and client readiness, while strengthening organizational and community networks. Trial registration ClinicalTrials.gov, NCT04111939. Registered 30 September 2019, https://clinicaltrials.gov/ct2/show/NCT04111939

Abstract Background An estimated 84,181 people died due to opioid overdose in 2022 alone [1]. Mobile technologies may offer an additional pathway to provide support to people seeking recovery from opioid use disorder (OUD). To this end, we conducted a content analysis of opioid-related apps to determine to what extent apps exist that provide support to people seeking or in recovery from OUD. For apps specifically targeting OUD recovery, we identified the tools these apps offer to users seeking support in their recovery. Methods Our team conducted a content analysis of publicly available opioid-related apps identified via web-scraping in the Apple and Google app stores. Using a two-step qualitative coding process, we first identified which apps were meaningfully related to OUD recovery and second identified what tools, if any, these apps provided. Results Web-scraping identified 1,136 apps from the Apple App Store (n = 247) and Google Play (n = 889). Of those, 290 apps were specific to OUD recovery (65% of iOS apps, 35% of Android apps). Of those, 161 apps were included in our final analysis. The most common type of tools provided support for motivation (65.2%) and accountability (65.8%). Many apps (53%) also supported linkage to recovery support (e.g., meeting finder, telehealth). Surprisingly, fewer apps provided information about OUD recovery (43.5%) or tools for cravings (33.5%). 42.9% of apps had limited accessibility (e.g., paywalls, private invite). Conclusions Our results show a substantial increase in the number of apps designed to support OUD recovery. Nevertheless, there remains a need for apps that provide empirically supported information and tools. Furthermore, restrictions in accessibility (i.e., findability, cost, private) may limit the impact of available apps.

Abstract Background Translating innovative research advancements into commercially viable medical interventions presents well-known challenges. However, there is limited understanding of how specific patient, clinical, social, and legal complexities have further complicated and delayed the development of new and effective interventions for Opioid Use Disorder (OUD). We present the following case studies to provide introductory clinical, social, and business insights for researchers, medical professionals, and entrepreneurs who are considering or are currently developing medical. Methods Four small business recipients of National Institute on Drug Abuse (NIDA) small business grant funding collected a total of 416 customer discovery interviews during the 2021 National Institutes of Health (NIH) Innovation-Corps (I-Corps) program. Each business received funding to advance an OUD-specific innovation: therapeutics (2 companies), medical device (1 company), and Software as a Medical Device (SaMD) (1 company). Interview participants included stakeholders from a variety of disciplines of Substance Use Disorders (SUD) healthcare including clinicians, first responders, policymakers, relevant manufacturers, business partners, advocacy groups, regulatory agencies, and insurance companies. Results Agnostic to the type of product (therapeutic, device, or SaMD), several shared barriers were identified: (1) There is a lack of standardization across medical providers for managing patients with OUD, resulting in diverse implementation practices due to a fragmented healthcare policy; (2) Underlying Social Determinants of Health (SDOH) present unique challenges to medical care and contribute to poor outcomes in OUD; (3) Stigma thwarts adoption, implementation, and the development of innovative solutions; (4) Constantly evolving public health trends and legal policies impact development and access to OUD interventions. Conclusion It is critical for innovators to have early interactions with the full range of OUD stakeholders to identify and quantify true unmet needs and to properly position development programs for commercial success. The NIH I-Corps program provides a framework to educate researchers to support their product design and development plans to increase the probability of a commercially successful outcome to address the ongoing opioid epidemic.

Abstract Introduction Buprenorphine is an effective first-line treatment for opioid use disorder (OUD) that substantially reduces morbidity and mortality. For patients using illicitly-manufactured fentanyl (IMF), however, transitioning to buprenorphine can be challenging. Evidence is lacking for how best to make this transition in the outpatient setting. A shared decision-making (SDM) approach has been found to benefit patients with OUD but has not been studied for buprenorphine initiation. We sought to explore participants’ experiences with a SDM approach to buprenorphine initiation. Methods Participants were seeking care at a low barrier, telehealth buprenorphine clinic. Clinicians implemented a standardized SDM approach whereby they offered patients using IMF three options for buprenorphine initiation (traditional, low-dose, and QuickStart). They elicited patient goals and preferences and discussed the pros and cons of each method to come to a shared decision. Patients meeting study criteria were invited to participate in semi-structured qualitative interviews 1–2 weeks after the initial visit. Interviews focused on experiences with the clinical visit, suggestions for enhancing the treatment experience, and patient factors affecting the method they chose. Interviews were coded and analyzed using reflexive thematic analysis. Results Twenty participants completed interviews. Participants’ mean age was 33, they were 50% female, predominantly white (16 [80%]), and most had Medicaid insurance (19 [95%]). We identified three important themes. First, participants found SDM acceptable and a positive addition to their OUD treatment. They felt their opinion mattered and reported that SDM gave them important control over their care plan. Second, patient goals, preferences, and past experiences with buprenorphine-associated withdrawal impacted what type of buprenorphine initiation method they chose. Finally, participants had advice for clinicians to improve SDM counseling. Participant recommendations included ensuring patients are informed that withdrawal (or “feeling sick”) can occur with any initiation method, that buprenorphine will eventually “block” fentanyl effects once at a high enough dose, and that clinicians provide specific advice for tapering off fentanyl during a low dose initiation. Conclusions For patients with OUD using IMF, shared decision-making is an acceptable approach to buprenorphine initiation in the outpatient setting. It can enhance patient autonomy and lead to an individualized approach to OUD care.

Abstract Background Conducting research within a carceral health care context offers a unique view into the nature of drug use among arrestees with potential to identify and prevent drug use consequences. The purpose of this study was to characterize the nature and extent of drug use among first-time jail arrestees to inform detection and treatment. Methods This study utilized a naturalistic research design to collect de-identified urine drug screens (UDS), jail characteristics, and arrestee demographic variables among arrestees indicating drug use from 25 jails across the United States in 2023 through a confidential data sharing agreement with NaphCare, Inc. using its proprietary electronic health record operating system. Descriptive statistics were used to detail the features of the dataset, Pearson’s chi-square tests of independence were performed to statistically analyze associations between UDS results and jail characteristics and arrestee demographics, and significant chi-square test results were further investigated by examining standardized residuals to clarify the nature and significance of within-group differences in proportions. Results Of the 43,553 UDS cases comprising the final sample (28.8% of total arrestees), 74.8% (32,561) were positive for one or more drugs, and 25.2% of UDS cases were negative for all drugs. Among those who tested positive, 69.0% were positive for cannabis, 54.8% for stimulants, 29.6% for opioids, and 12.4% for sedatives. Arrestees were positive for multiple drugs half the time, with combinations of cannabis, stimulants, and opioids most common. Significant associations between drug use and both jail characteristics and arrestee demographics were found. Conclusions Though drug use is not a recent phenomenon, the lethality potential of the drugs being used today is relatively new. Arrestees with positive urine drug screens are at heightened risk of adverse outcome due to sudden cessation of substance use. Findings highlight the need for objective clinical data to guide acute treatment of individuals at risk of withdrawing while detained.

Abstract Background Deaths from opioid overdose have increased dramatically in the past decade. For individuals with opioid use disorder (OUD), agonist medications such as methadone and buprenorphine reduce opioid-related morbidity and mortality. Historically, the provision of buprenorphine treatment in office-based settings has relied on frequent in-person contact, likely influencing patients’ access to and retention in care. In response to the COVID-19 pandemic, providers of office-based buprenorphine treatment rapidly adapted their care processes, increasingly relying on telemedicine visits. To date, relatively few prior studies have combined patient and clinician perspectives to examine the implementation of telemedicine and related care adaptations, particularly in safety-net settings. Methods Qualitative methods were used to explore clinician and patient experiences with telemedicine in an office-based buprenorphine treatment clinic affiliated with an urban safety-net hospital. From this clinic, we conducted semi-structured interviews with 25 patients and 16 clinicians (including prescribers and non-prescribers). We coded all interview data and used a thematic analysis approach to understand how telemedicine impacted treatment quality and engagement in care, as well as preferences for using telemedicine moving forward. Results Five themes regarding the implementation of telemedicine and other COVID-19-related care adaptations arose from patient and clinician perspectives: (1) telemedicine integration precipitated openness to more flexibility in care practices, (2) concerns regarding telemedicine-related adaptations centered around safety and accountability, (3) telemedicine encounters required rapport and trust between patients and clinicians to facilitate open communication, (4) safety-net patient populations experienced unique challenges when using telemedicine, particularly in terms of the technology required and the need for privacy, and (5) there is an important role for telemedicine in office-based buprenorphine treatment moving forward, primarily through its use in hybrid models of care which integrate both in-person and virtual visits. Conclusions Telemedicine implementation within office-based buprenorphine treatment has the potential to improve patients’ engagement in care; however, our findings emphasize the need for tailored approaches to implementing telemedicine in office-based buprenorphine treatment, particularly within safety-net settings. Overall, this study supports the maintenance of changes to policy and practice that facilitate the use of telemedicine in office-based buprenorphine treatment beyond the COVID-19 public health emergency.

Abstract Background Public health experts currently agree that heated tobacco products (HTPs) pose a significant health risk for their consumers. The same concentrations and speed of delivery of nicotine found for HTPs and conventional combustion cigarettes make it necessary to consider the addictiveness of HTPs, and provide precise diagnostic instruments to serve as the basis for effective treatment plans. Therefore, the main objectives of this study were to design a questionnaire for HTPs addiction called “Heated Tobacco Products Addiction Questionnaire (HeaTPAQ)” and to examine its psychometric properties. Methods Adults from the general population of Lebanon (n = 754) were administered the HeatPAQ, along with the Fagerström test for nicotine dependence (FTND), the Caffeine Use Disorder Questionnaire, the Generalized Anxiety Disorder 7-item, and the Patient Health Questionnaire-9. We split the main sample into two subsamples; subsample 1 consisting of 33% of the participants used for the exploratory factor analysis (EFA) (n = 246; mean age 27.82 ± 9.38 years) and subsample 2 consisting of 67% of the participants used for the confirmatory factor analysis (CFA) (n = 508; mean age 27.81 ± 8.80 years). Results EFA then CFA analyses revealed a one-factor model consisting of 13 items with acceptable fit to the data. The HeaTPAQ reached excellent internal consistency coefficients, with both Cronbach’s α and McDonald’s ω values of 0.96. The one-dimensional structure of the HeaTPAQ was found to be invariant across sex groups. Convergent validity was demonstrated through significant positive correlation with FTND scores. Furthermore, HeaTPAQ scores correlated positively with measures of caffeine addiction, anxiety and depression, which suggests the adequate concurrent validity of the scale. Conclusion Findings suggest that the HeatPAQ is a specific, short and simple-to-use self-report questionnaire to assess HTPs addiction reliably and validly. Pending future studies confirming our results, we hope that the HeatPAQ will facilitate routine screening for HTPs addiction, which is an essential step towards appropriate prevention and intervention efforts and to inform policy makers.

Abstract Background Withdrawal prior to buprenorphine initiation may be intolerable or create barriers to therapy. We aim to update our previous systematic review on the efficacy and safety of buprenorphine initiation strategies that aim to omit prerequisite opioid withdrawal (POW). Methods We used the same search strategy for this update as in the original review with the modification of an additional term “low dose.” We searched Embase and Scopus from April 11, 2020 to August 1, 2024 with searches in Google Scholar and www.clinicaltrials.gov. A study was included if it described patients with opioid use disorder or chronic pain that transitioned from a full mu-opioid agonist to buprenorphine without preceding withdrawal and reported withdrawal during initiation as an outcome. Two investigators independently screened citations and articles for inclusion, collected data using a standardized data collection tool, and assessed study risk of bias. Results Forty-four articles met our inclusion criteria; 31 were case reports/series reporting 84 cases and 13 were single-arm observational studies reporting a total of 576 cases. These studies were added to the literature from our original systematic review, totaling 59 studies and 682 patients. Sublingual buprenorphine was the most common initial formulation, comprising 55% (376/682) of cases. In case reports/series, use of a validated scale to measure withdrawal was uncommon; validated scales were only used in 36% of patients. All other patients had withdrawal assessed in a manner not utilizing a validated scale. Approximately half of these patients experienced any level of withdrawal (57/106 = 54%). The specific outcome of “any level of withdrawal” was not consistently reported in single-arm observational studies. Eight studies reported on any level of withdrawal, which occurred in 41% (177/428) of initiation attempts; some patients experienced more than one initiation attempt. Thirteen patients in case reports/series and 37 patients in the single-arm observational studies reported clinically significant withdrawal (50/682 = 7%). 81% (451/555) of patients transitioned to buprenorphine. Conclusion The prevalence of buprenorphine dosing strategies that aim to omit POW has vastly increased over the past 4 years. While quality of evidence remains low, the increased quantity of publications and integration into health-system guidelines and protocols demonstrates the need for prospective, controlled studies. It is unknown how selection bias impacts current findings, further highlighting the need for prospective, randomized, controlled trials evaluating these dosing strategies.

Abstract Background Addiction Medicine training in Canada has evolved substantially in the last few years with the establishment of accreditation standards and several new fellowship programs. The novelty of these formal training programs, created in response to complex and ever-expanding clinical needs in Addiction Medicine, creates unique educational circumstances that must be understood to support future growth. This study characterizes the current state of these postgraduate training programs in Canada through the perspectives of Program Directors (PDs). Methods This study is a mixed methods study of 12 PDs. In Phase 1, participants completed a quantitative survey analyzed through descriptive statistics. In Phase 2, participants underwent a qualitative semi-structured interview that was coded with a thematic analysis approach. Mixing occurred both during the interim analysis between phases and during the interpretation stage. Results 28 trainees enrolled in a fellowship program in 2021–22 across 10 programs, and 27 trainees enrolled in 2022–23 across 11 programs. In each year, there were significantly fewer available spots than applications (31% and 29%, respectively). PDs identified a funding “bottleneck” as the most difficult and important challenge facing programs, with trainees supported by diverse and unstable funding sources. Qualitative analysis highlighted the need for sustainable funding models, flexibility toward alternative training pathways (shorter durations of training and re-entry from practice), and establishment of a national community of practice to support the co-creation of a robust addictions medical education infrastructure. Conclusion For Addiction Medicine training to meet workforce demands, PDs stressed that funding was the challenge of prime importance. Future studies should examine the perspectives of Addiction Medicine fellows, the clinical and research impacts of fellowship graduates, and the cost-effectiveness of fellowship funding models.

Abstract Background and aims Little is known regarding predictors of outcome in treatment of alcohol dependence via the internet and in primary care. The aim of the present study was to investigate the role of socio-demographic and clinical factors for outcomes in internet-based cognitive behavioral treatment (ICBT) added to treatment as usual (TAU) for alcohol dependence in primary care. Design Secondary analyses based on data from a randomized controlled trial in which participants were randomized to ICBT + TAU or to TAU only. Setting The study was conducted in collaboration with 14 primary care centers in Stockholm, Sweden. Participants The randomized trial included 264 adult primary care patients with alcohol dependence enrolled between September 2017 and November 2019. Interventions Patients in the parent trial were randomized to ICBT that was added to TAU (n = 132) or to TAU only (n = 132). ICBT was a 12-week intervention based on motivational interviewing, relapse prevention and behavioral self-control training. Measures Primary outcome was number of standard drinks last 30 days. Sociodemographic and clinical predictors were tested in separate models using linear mixed effects models. Findings Severity of dependence, assessed by ICD-10 criteria for alcohol dependence, was the only predictor for changes in alcohol consumption and the only moderator of the effect of treatment. Participants with severe dependence showed a larger reduction in alcohol consumption between baseline and 3-months follow-up compared to participants with moderate dependence. The patients with moderate dependence continued to reduce their alcohol consumption between 3- and 12-months follow-up, while patients with severe dependence did not. Conclusions Dependence severity predicted changes in alcohol consumption following treatment of alcohol dependence in primary care, with or without added ICBT. Dependence severity was also found to moderate the effect of treatment. The results suggest that treatment for both moderate and severe alcohol dependence is viable in primary care. Clinical trial registration: The study was approved by the Regional Ethics Board in Stockholm, no. 2016/1367–31/2. The study protocol was published in Trials 30 December 2019. The trial identifier is ISRCTN69957414, available at http://www.isrctn.com, assigned 7 June 2018, retrospectively registered.

Abstract Background The availability of the fellowships of Alcoholics Anonymous and Narcotics Anonymous in community settings is extensive and patients admitted to treatment programs for substance use disorder may therefore have previously attended meetings of these two Twelve Step (TS) programs. Data on such prior attendance and related clinical findings, however, are not typically available. They can, however, be relevant to how ensuing treatment is planned. We therefore undertook this study to ascertain the feasibility of evaluating how the level of TS attendance prior to treatment entry can be evaluated, and to determine clinically relevant findings that are associated with such attendance. Methods Over the course of 2022, 3,125 patients were admitted to a large urban multimodal United States-based treatment center. All patients were administered the structured interview-based Global Appraisal of Individual Needs upon admission. This instrument is employed to evaluate substance use, demographics, and related psychosocial variables. Clinically related variables were analyzed relative to whether given respondents have a history of any TS group attendance prior to admission. Results Distinctions were found between the 57.3% of respondents who had previously attended any TS meetings and the 42.6% who had not attended any meetings. Compared to respondents who had never attended TS meetings, those who had ever attended scored higher on emotional problems (p <.001, d = -0.58), and had more likely undergone previous SUD treatment (p <.001, d = 0.80). They were less likely to use substances in unsafe situations (p <.001, d = -0.55) and were less likely to express reluctance to remain abstinent (p <.001, d = -0.50). The 11% of respondents who considered themselves regular TS members reported a lower frequency of recent substance use (p <.001, d = -0.80) and were more likely to have attended intensive outpatient (p <.001, 0.46) and residential (p <.001, 0.44) treatment than patients who did not consider themselves regular attenders. Conclusions Examination of TS attendance prior to treatment admission is feasible. Findings can be clinically relevant for differential treatment planning and can also serve as a basis for further research into the role of TS participation in community settings.

Abstract Introduction In South Africa, community-oriented primary care teams work to re-engage out-of-care people with HIV (PWH) in treatment, many of whom have substance use (SU) concerns. SU stigma is high among these teams, limiting care engagement efforts. Integrating peer recovery coaches into community-oriented primary care teams could shift SU stigma and improve patients’ engagement in care. The peer role does not exist in SA and represents a workforce innovation. To enhance acceptability, feasibility, and appropriateness for the local context, we engaged multiple stakeholder groups to co-design a peer role for community-oriented primary care team integration. Methods We used a five-step human-centered design process: (i) semi-structured interviews with healthcare worker (n = 25) and patient (n = 15) stakeholders to identify priorities for the role; (ii) development of an initial role overview; (iii) six ideation workshops with healthcare worker (n = 12) and patient (n = 12) stakeholders to adapt this overview; (iv) refinement of the role prototype via four co-design workshops with healthcare worker (n = 7) and patient (n = 9) stakeholders; and (v) consultation with HIV and SU service leaders to assess the acceptability and feasibility of integrating this prototype into community-oriented primary care teams. Results Although all stakeholders viewed the peer role as acceptable, patients and healthcare worker identified different priorities. Patients prioritized the care experience through sharing of lived experience and confidential SU support. Healthcare worker prioritized clarification of the peer role, working conditions, and processes to limit any impact on the community-oriented primary care team. A personal history of SU, minimum 1 year in SU recovery, and strong community knowledge were considered role prerequisites by all stakeholders. Through the iterative process, stakeholders clarified their preferences for peer session structure, location, and content and expanded proposed components of peer training to include therapeutic and professional work practice competencies. Service leaders endorsed the prototype after the addition of peer integration training for community-oriented primary care teams and peer mentoring to address community and team dynamics. Conclusion Stakeholder engagement in an iterative design process has been integral to co-designing a peer role that multiple stakeholder groups consider acceptable and that community-oriented primary care teams are willing to implement. This offers a methodological framework for other teams designing SU workforce innovations.