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GWAS-identified genetic variants associated with medication-assisted treatment outcomes in patients with opioid use disorder: a systematic review and meta-analysis protocol.

ABSTRACT: BACKGROUND:The burden of opioid use disorder (OUD) has been increasing in North America. Administration of medication-assisted treatments (MATs) for OUD on an individual-dose basis has been shown to affect patient responses to treatment, proving to be, on occasion, dangerous. A genetic basis has been identified for some MAT responses in a candidate gene context, but consensus has not been reached for any genome-wide significant associations. This systematic review aims to identify and assess any genetic variants associated with MAT patient outcomes at genome-wide significance. METHODS:The databases searched by the authors will be: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog, GWAS Central, and NIH Database of Genotypes and Phenotypes. A title and abstract screening, full-text screening, data extraction, and quality assessment will be completed in duplicate for each study via Covidence. Treatment outcomes of interest include continued opioid use or abstinence during treatment or at follow-up, time to relapse, treatment retention rates, opioid overdose, other substance use, comorbid psychiatric disorders, risk taking behaviors, MAT plasma concentrations, and mortality rates. Analysis methods applied, if appropriate, will include random effects meta-analysis with pooled odds ratios for all outcomes. Subgroup analyses will also be implemented, when possible. DISCUSSION:This systematic review can hopefully inform the direction of future research, aiding in the development of a safer and more patient-centered treatment. It will be able to highlight genome-wide significant variants that are replicable and associated with MAT patient outcomes. SYSTEMATIC REVIEW REGISTRATION:This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration ID CRD42020169121).

SUBMITTER: Chawar C

PROVIDER: S-EPMC7466496 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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GWAS-identified genetic variants associated with medication-assisted treatment outcomes in patients with opioid use disorder: a systematic review and meta-analysis protocol.

Chawar Caroul C Hillmer Alannah A Sanger Stephanie S D'Elia Alessia A Panesar Balpreet B Guan Lucy L Xie Dave Xiaofei DX Bansal Nandini N Abdullah Aamna A Kapczinski Flavio F Pare Guillaume G Thabane Lehana L Samaan Zainab Z

Systematic reviews 20200901 1

<h4>Background</h4>The burden of opioid use disorder (OUD) has been increasing in North America. Administration of medication-assisted treatments (MATs) for OUD on an individual-dose basis has been shown to affect patient responses to treatment, proving to be, on occasion, dangerous. A genetic basis has been identified for some MAT responses in a candidate gene context, but consensus has not been reached for any genome-wide significant associations. This systematic review aims to identify and as ...[more]

PMID: 32873330

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Project description:IntroductionIllicit opioid use has become a national crisis in Canada, with over 65?000 people seeking treatment for opioid use disorder (OUD) in Ontario and British Columbia alone. Medication-assisted treatment (MAT) is a common treatment for OUD. There is substantial variability in treatment outcomes used to evaluate effectiveness of MAT, making it difficult to establish clinically and scientifically relevant treatment effect. Furthermore, patients are often excluded from the process of determining these outcomes. The primary objective of this review is to examine outcomes currently used to measure MAT effectiveness and to identify patient-relevant outcomes to enhance effectiveness of treatment options. This review refers to patient-important outcomes as those outcomes patients consider important to or markers of treatment success.Methods and analysisMEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, National Institutes for Health Clinical Trials Registry and WHO International Clinical Trials Registry Platform databases will be searched. We will search databases from inception to the date the search is ran. Studies of interest include those evaluating the effectiveness of MAT for patients with OUD, with or without consultation with patients regarding what they consider to be important as an indicator of treatment success. Results will be analysed using thematic analysis and qualitative analysis where possible. This will result in comprehensive synthesis of all outcomes and measures found related to OUD treatment effectiveness.Ethics and disseminationWe are collaborating with Canadian Addiction Treatment Centres which provide MAT to patients with OUD who will participate in disseminating study results. Dissemination strategies will involve sharing study results through workshops, presentations, peer-reviewed publications, study reports, community presentations and resources in primary care settings.Prospero registration numberCRD42018095553.

Project description:Background: Opioids accounted for 75% of drug overdoses in the United States in 2020, with rural states particularly impacted by the opioid crisis. While medication assisted treatment (MAT) with Suboxone remains one of the more efficacious treatments for opioid use disorder (OUD), approximately 40% of people receiving Suboxone for outpatient MAT for OUD (MOUD) relapse within the first 6 months of treatment. We developed the smartphone app-based intervention OptiMAT as an adjunctive intervention to improve MOUD outcomes. The aims of this study are to (1) evaluate the efficacy of adjunctive OptiMAT use in reducing opioid misuse among people receiving MOUD; and (2) evaluate the role of specific OpitMAT features in reducing opioid misuse, including the use of GPS-driven just-in-time intervention. Methods: We will conduct a two-arm, single-blind, randomized controlled trial of adults receiving outpatient MOUD in the greater Little Rock AR area. Participants are English-speaking adults ages 18 or older recently enrolled in outpatient MOUD at one of our participating study clinics. Participants will be allocated via 1:1 randomized block design to (1) MOUD with adjunctive use of OptiMAT (MOUD+OptiMAT) or (2) MOUD without OptiMAT (MOUD-only). Our blinded research statistician will evaluate differences between the two groups in opioid misuse (as determined by quantitative urinalysis conducted by clinical lab staff blinded to group membership) during the 6-months following study enrolment. Secondary analyses will evaluate if OptiMAT-usage patterns within the MOUD+OptiMAT group predict opioid misuse or continued abstinence. Discussion: This study will test if adjunctive use of OptiMAT improve MOUD outcomes. Study findings could lead to expansion of OptiMAT into rural clinical settings, and the identification of OptiMAT features which best predict positive clinical outcome could lead to refinement of this and similar smartphone appbased interventions. Trial registration: ClinicalTrials.gov identifier: NCT05336188, registered March 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05336188.

Project description:BackgroundPatients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes.ObjectivesThis systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.MethodsDatabases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively.ResultsOur search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10-7. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese.LimitationsThe limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.ConclusionThe results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.

Project description:BACKGROUND:Social functioning (SF), the ability to engage with life and fulfill roles may be a salient "patient important outcome" in addiction treatment. It is not known if medication-assisted treatment (MAT) impacts SF in opioid use disorder (OUD). There is a growing evidence to suggest that men and women are impacted differently by OUD. This study is the largest to date to study sex differences in OUD and explore associations between MAT and SF. METHODS:Data were collected from 2736 participants with OUD, enrolled in MAT for varying lengths of time, in outpatient clinics across Ontario. SF was defined according to the Maudsley Addiction Profile's domains of (1) employment, (2) criminal activity, and (3) interpersonal conflict. Using logistic regression analysis, we examined sociodemographic and clinical factors associated with domains of SF. RESULTS:There were 1544 men (56%) and 1192 women (44%) in this study, and ages varied from 17 to 76 years for men and 18 to 69 years for women. At study entry, participants had been on MAT for a median of 2 years. Compared to men, women reported more psychological (mean MAP score 14/40, SD = 9.55, versus 11/40, SD = 8.64; p < 0.001) and physical symptoms (mean MAP score 17/40, SD = 7.70 versus 14/40, SD = 7.74; p < 0.001). More women reported unemployment(74% versus 58%; p < 0.0001) and interpersonal conflict (46% versus 35%; p < 0.0001). Men were more likely than women to report criminal activity (11%, versus 8%; p = 0.001). Psychological symptoms increased the risk of worse SF, across domains, for men and for women. Every year on MAT was associated with a 7% increase in the odds of women engaging with criminal activity (OR = 1.07, 95% CI 1.02, 1.12, p = 0.006). CONCLUSIONS:Men and women had different SF profiles and psychological symptoms scores while on MAT. The length of time on MAT increased the risk of criminal activity in women, and overall, duration of MAT was not associated with improvement in SF. This may suggest that MAT alone may not support continual improvements in SF in OUD.

Project description:ImportanceIn the literature on opioid use disorder (OUD), opioid abstinence is used as an outcome measure for individuals receiving medication-assisted treatment (MAT), without consideration of patient-reported goals (PRGs).ObjectivesTo identify common PRGs for youths receiving MAT for OUD and assess whether these patients achieve their stated goals.Design, setting, and participantsThis prospective cohort study examined data from 152 individuals aged 16 to 25 years (noninclusive) recruited between May 22, 2018, and March 11, 2020, from 45 outpatient MAT clinics in the Pharmacogenetics of Opioid Substitution Treatment Response study. Youths receiving MAT for OUD were included and were followed up for 3 months.ExposuresMedication-assisted treatment for OUD.Main outcomes and measuresThe frequency of each PRG; the success of goal attainment, compared between those who reported specific PRGs and those who did not; and associations between reporting certain goals and achieving them.ResultsAmong the 152 youths in the study, 82 were male (53.9%), and the mean (SD) age was 22.8 (1.8) years. Ten overarching goals were identified, with the most common being to taper the dose of or stop MAT (96 [63.2%]), avoid use of recreational substances (71 [46.7%]), manage OUD symptoms (25 [16.4%]), live a normal life (14 [9.2%]), improve mental health (11 [7.2%]), and gain employment (8 [5.3%]). Overall, individuals who reported PRGs had similar odds of achieving them as those who did not for the goals of taper dose of or stop MAT (OR, 1.98; 95% CI, 0.88-4.46; P = .10), avoid recreational substances (OR, 1.34; 95% CI, 0.65-2.74; P = .43), manage OUD symptoms (β coefficient, -0.93; 95% CI, -4.24 to 2.38; P = .58), and improve mental health (β coefficient, -0.76; 95% CI, -6.31 to 4.78; P = .79). Furthermore, multivariable logistic regression showed that goals to taper the dose of or stop MAT (odds ratio, 1.90; 95% CI, 0.78-4.63; P = .16) or avoid recreational substances (odds ratio, 1.27; 95% CI, 0.60-2.67; P = .53) were not associated with achieving these respective outcomes.Conclusions and relevanceThis study suggests that youths have highly variable PRGs regarding MAT for OUD and that reporting a goal may not mean one is at higher odds of achieving it. There is a need to develop treatment plans that effectively incorporate PRGs. In addition, the finding that most youths aim to minimize or stop their MAT dose warrants the creation of a tapering protocol to guide clinicians. Because a diagnosis of OUD has substantial psychosocial implications in this population, clinicians must ensure that these dimensions of care are part of routine clinical practice.

Project description:BackgroundAs Colorado ranked among the top nationally in non-medical use of opioids, a pilot medication for opioid use disorder (MOUD) program was developed to increase the number of NPs and PAs providing MOUD in order to bring this evidence- based treatment to 2 counties showing disproportionally high opioid overdose deaths. Over the first 18 months, the MOUD Pilot Program led to 15 new health care providers receiving MOUD waiver training and 1005 patients receiving MOUD from the 3 participating organizations. Here we evaluate patient centered clinical and functional outcomes of the pilot MOUD program implemented in 2 rural counties severely affected by the opioid crisis.MethodsUnder state-funded law (Colorado Senate Bill 17-074), three rural agencies submitted de-identified patient-level data at baseline (N = 1005) and after 6 months of treatment (N = 190, 25%) between December 2017 and January 2020. The Addiction Severity Index, PhQ9 and GAD-7 with McNemar-Bowker, and Wilcoxon Signed Rank tests analysis were used to measure patient outcomes across after participation in the program. .ResultsPatients in treatment reported using less heroin (52.1% vs 20.4%), opioids (22.3% vs 11.0%), and alcohol (28.6% vs 13.1%, all P < 0.01). Patients reported improved health (53.4% vs. 68.2%, P = 0.04), less frequency of disability (8.69 vs. 6.51, P = 0.02), symptoms (29.8% vs 21.3%), pain (67.5% to 53.6), worry (45.3% vs 62.3%), anxiety (49.7% vs 23.2%), depression (54.1% vs 23.3%, all P < 0.02) after treatment.ConclusionsThis study shows decreased substance use, improved physical and mental health, and reduced symptoms after 6 months of MOUD. Although more research on retention and long-term effects is needed, data shows improved health outcomes after 6 months of MOUD. Lessons learned from implementing this pilot program informed program expansion into other rural areas in need to address some of Colorado' major public health crises.

Project description:OBJECTIVES:To assess interest in, concerns about and knowledge of long-acting reversible contraceptives (LARC) among women in medication-assisted treatment (MAT) for opioid use disorder who were at risk for unintended pregnancy. STUDY DESIGN:Women in MAT completed a survey on contraceptive use, attitudes and knowledge, including LARC methods, as part of eligibility screening for an ongoing trial evaluating family planning interventions for this population. RESULTS:Eighty-three women at risk for unintended pregnancy completed the survey, and a subset of 51 completed supplemental questions about implants. All participants had heard of IUDs and 75/83 (90%) had heard of implants, but only 34/83 (41%) and 14/51 (27%) reported being likely to use IUDs and implants, respectively. Thirty-five women reported they were unlikely to use IUDs, with 29/35 (83%) citing unspecified "other reasons" for this position and 24/35 (69%) endorsing concerns about side effects. Seventeen women reported they were unlikely to use implants, with 8/17 (47%) citing "other reasons" and 9/17 (53%) and 10/17 (59%) reporting concerns about insertion and removal, respectively. Participants reported they knew "a little" about LARCs, but only their knowledge of implants was limited. Only 50/83 (60%) participants were aware of the superior effectiveness of IUDs and 26/51 (51%) were aware of the superior effectiveness of implants relative to other reversible methods. CONCLUSIONS:Participants reported relatively low interest in LARCs. Many women had unspecified reasons for not using LARCs. Participants also lacked information about LARC safety and effectiveness, especially with regard to implants. IMPLICATIONS:Women in medication-assisted treatment for opioid use disorder are at high risk of unintended pregnancy, yet contraceptive use is low and use of less effective methods is common. Women in MAT may benefit from efforts to increase knowledge about implants and assuage concerns about their insertion and removal as well as more general efforts to improve knowledge about the relative efficacy of LARCs. Many women in MAT endorsed unspecified "other reasons" for not using LARCs, which should be explored further.

Project description:BackgroundOpioid use disorder (OUD) is a public health crisis with more than 2 million people living with OUD in the United States. Medication-assisted treatment (MAT) is an evidence-based approach for the treatment of OUD that relies on a combination of behavioral therapy and medication. Less than half of those living with OUD are accessing this treatment. Mobile technology can enhance the treatment of chronic diseases in readily accessible and cost-effective ways through self-monitoring and support.ObjectiveThe aim of this study is to describe the adaptation of a mobile platform for patients undergoing treatment for OUD and preliminary pilot testing results.MethodsOur study was conducted with patient and provider participants at the University of Virginia MAT clinic and was approved by the institutional review board. The formative phase included semistructured interviews to understand the needs of patients with OUD, providers' perspectives, and opportunities for MAT support via a mobile app. A second round of formative interviews used mock-ups of app features to collect feedback on feature function and desirability. Formative participants' input from 16 interviews then informed the development of a functional smartphone app. Patient participants (n=25) and provider participants (n=3) were enrolled in a 6-month pilot study of the completed platform. Patient app use and usability interviews, including a system usability score and open-ended questions, were completed 1 month into the pilot study. Open-ended responses were analyzed for prevalent themes.ResultsFormative interviews resulted in the development of a mobile app, named HOPE, which includes both evidence-based and participant-suggested features. The features included daily prompts for monitoring mood, stress, treatment adherence, and substance use; patient tracking of goals, reminders, and triggering or encouraging experiences; informational resources; an anonymous community board to share support with other patients; and secure messaging for communication between patients and providers. All patient participants engaged with at least one app feature during their first month of pilot study participation, and the daily self-monitoring prompts were the most used. Patients and providers reported high levels of system usability (mean 86.9, SD 10.2 and mean 83.3, SD 12.8, respectively). Qualitative analysis of open-ended usability questions highlighted the value of self-monitoring, access to support through the app, and perceived improvement in connection to care and communication for both patient and provider participants.ConclusionsThe use of the HOPE program by pilot participants, high usability scoring, and positive perceptions from 1-month interviews indicate successful program development. By engaging with end users and eliciting feedback throughout the development process, we were able to create an app and a web portal that was highly usable and acceptable to study participants. Further work is needed to understand the program's effect on clinical outcomes, patient linkage, and engagement in care.

Project description:Objective: Opioid use disorder (OUD) is a notable concern in the United States (US) and strongly associated with mortality. There is a high prevalence of OUD in patients with posttraumatic stress disorder (PTSD) and the mortality associated with OUD may be exacerbated in patients with PTSD. Medication-assisted treatment (MAT) for OUD has become standard of care for OUD and has been shown to reduce mortality. However, there has been little study of MAT and mortality in patients with PTSD and OUD. Methods: We conducted a retrospective cohort study in U.S. veterans who had newly engaged in PTSD treatment, were diagnosed with OUD and were provided MAT for at least one day between 2004 and 2013. We assessed mortality for one year following the index diagnosis date. We calculated all-cause mortality as well as death by external cause, overdose plus suicide, overdose, and suicide rates per 100,000. We used hazard ratios (HR) and 95% confidence intervals (CI) to compare death rates between patients with high versus low adherence to MAT. We evaluated the impact of high versus low exposure to general substance abuse care. We considered a confidence interval that did not cross one to be significant. Results: A total of 5,901 patients met inclusion criteria. Most patients were men and the average age was 43.3 years (SD = 13.8). The all-cause mortality rate was 1,370 per 100,000 patients. High adherence to MAT resulted in a non-significant, decreased risk for death due to all-cause (HR = 0.73, 95% CI [0.47, 1.13]), external cause (HR = 0.71, 95% CI [0.38, 1.35]), and overdose or suicide (HR = 0.66, 95% CI [0.33, 1.35]). Patients with high exposure (≥ 60 days) to general substance abuse care were significantly less likely to die due to external cause (HR = 0.39, 95% CI [0.18, 0.85]) and overdose or suicide (HR = 0.31, 95% CI [0.12, 0.77]). Conclusions: In patients with PTSD and OUD, improved adherence to MAT and greater exposure to general substance abuse care may result in lower mortality. Studies with longer follow-up and larger sample sizes to assess the impact of MAT on suicide are needed to confirm our findings.

Dataset Information

GWAS-identified genetic variants associated with medication-assisted treatment outcomes in patients with opioid use disorder: a systematic review and meta-analysis protocol.

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GWAS-identified genetic variants associated with medication-assisted treatment outcomes in patients with opioid use disorder: a systematic review and meta-analysis protocol.

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