Lower buprenorphine elimination rate constant is associated with lower opioid use.

BACKGROUND: Opioid craving is suggested to correlate with the rate of reduction in buprenorphine (BUP) plasma levels. No studies explored Buprenorphine elimination rate constant (BUP EL.R) as a predictor of opioid use or retention in BUP treatment. METHODS: Analysis was performed using data from a randomized controlled trial of 141 adults with opioid use disorder (OUD) randomized to Incentivized Adherence and Abstinence monitoring (I-AAM; experimental (n = 70) and treatment-as-usual; control (n = 71). In the I-AAM, structured access to unsupervised BUP doses was provided up to 28 days contingent of adherence measured by Therapeutic Drug Monitoring and abstinence by Urinary Drug Screens (UDS). In contrast, the treatment-as-usual (control) provided unstructured access to unsupervised doses was provided for up to 14 days considering UDS results. The primary outcome was percentage negative UDS. The secondary outcome, retention in treatment, was continuous enrollment in the study and analysis was via intention-to-treat. Significant bivariate correlations with the outcomes were adjusted for group allocation. RESULTS: A significant negative correlation between BUP EL.R and percentage negative opioid screens (Pearson correlation coefficient - 0.57, p < 0.01) was found. After adjusting for trial group, BUP EL.R was shown to be an independent predictor of percentage negative opioid screens (Standardized Beta Coefficient - 0.57, 95% CI - 221.57 to - 97.44, R2 0.322). CONCLUSION: BUP EL.R predicted 32.2% of the variation in percentage negative opioid UDS and may serve as a potential promising tool in precision medicine of BUP treatment. Higher buprenorphine elimination is associated with higher positive opioid urine screens during treatment. TRIAL REGISTRATION: ISRCTN41645723 retrospectively registered on 15/11/2015.

Exploratory Economic Evaluation of Buprenorphine Treatment in Opioid Use Disorder.

BACKGROUND: Burden of opioid use disorder (OUD) is expressed in economic values or health metrics like Disability Adjusted Life Years (DALYs). Disability Weight (DW), a component of DALYs is estimated using economic methods or psychometric tools. Estimating DW at patient level using psychometric tools is an alternative to non-population specific DW overestimated by economic methods. Providing Medication Assisted Treatment (MAT) using buprenorphine/naloxone film (BUP/NX-F) for OUD is limited by financial constraints. AIM: To estimate the burden of OUD at patient level and explore the cost-benefit of two buprenorphine treatment interventions. METHODS: The present study was conducted alongside a randomized controlled trial of 141 adults with OUD stabilized on BUP/NX-F and randomized to BUP/NX-F with Incentivized Abstinence and Adherence Monitoring (experimental, n=70) and BUP/NX-F in usual care (control, n=71). The cost of illness was estimated applying a societal perspective. The Impairment Weight (IW) was estimated over a '0' to '1' scale, where '0' represents no impairment and '1' full impairment using the Work and Social Adjustment Scale (WSAS). RESULTS: Median (interquartile range) annual cost of OUD per participant was AED 498,171.1 (413,499.0 -635,725.3) and AED 538,694.4 (4,211,398.0 - 659,949.0) in the experimental and control groups, respectively (p=0.33). Illicit drug purchase represented 60 % of the annual cost of illness. At baseline, the mean Impairment Weight (IW) was 0.55 (SD 0.26) and 0.62 (SD 0.24) in the experimental and control groups, respectively. At end of the study, the IW was 0.26 (SD 0.28) representing 51% reduction in the experimental group compared to 0.42 (SD 0.33) in the control group representing a 27% reduction. Excluding imprisonment, the cost-benefit of treatment was not realized. In contrast, accounting for imprisonment, cost benefit expressed as a return-on-investment was established at 1.55 and 1.29 in the experimental and control groups, respectively. IMPLICATIONS FOR MENTAL HEALTH POLICY: Cost benefit analysis can serve as a simple and practical tool to evaluate the cost benefit of treatment interventions. Demonstrating the cost benefit of buprenorphine treatment has the potential to facilitate public funding and accessibility to opioid assisted treatment.

Stratified analyses of genome wide association study data reveal haplotypes for a candidate gene on chromosome 2 (KIAA1211L) is associated with opioid use in patients of Arabian descent.

BACKGROUND: Genome Wide Association Studies (GWAS) have been conducted to identify genes and pathways involved in development of opioid use disorder. This study extends the first GWAS of substance use disorder (SUD) patients from the United Arab Emirates (UAE) by stratifying the study group based on opioid use, which is the most common substance of use in this cohort. METHODS: The GWAS cohort consisted of 512 (262 case, 250 controls) male participants from the UAE. The samples were genotyped using the Illumina Omni5 Exome system. Data was stratified according to opioid use using PLINK. Haplotype analysis was conducted using Haploview 4.2. RESULTS: Two main associations were identified in this study. Firstly, two SNPs on chromosome 7 were associated with opioid use disorder, rs118129027 (p-value = 1.23 × 10 - 8) and rs74477937 (p-value = 1.48 × 10 - 8). This has been reported in Alblooshi et al. (Am J Med Genet B Neuropsychiatr Genet 180(1):68-79, 2019). Secondly, haplotypes on chromosome 2 which mapped to the KIAA1211L locus were identified in association with opioid use. Five SNPs in high linkage disequilibrium (LD) (rs2280142, rs6542837, rs12712037, rs10175560, rs11900524) were arranged into haplotypes. Two haplotypes GAGCG and AGTTA were associated with opioid use disorders (p-value 3.26 × 10- 8 and 7.16 × 10- 7, respectively). CONCLUSION: This is the first GWAS to identify candidate genes associated with opioid use disorder in participants from the UAE. The lack of other genetic data of Arabian descent opioid use patients has hindered replication of the findings. Nevertheless, the outcomes implicate new pathways in opioid use disorder that requires further research to assess the role of the identified genes in the development of opioid use disorder.

A case-control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE).

Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p-value = 6.24 × 10-8 ), rs74477937 (p-value = 8.56 × 10-8 ) and rs78707086 (p-value = 8.55 × 10-8 ) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta-analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.

The frequency of DRD2 rs1076560 and OPRM1 rs1799971 in substance use disorder patients from the United Arab Emirates.

BACKGROUND: Dopaminergic and opioid systems are involved in mediating drug reward and reinforcement of various types of substances including psychoactive compounds. Genes of both systems have been candidate for investigation for associations with substance use disorder (SUD) in various populations. This study is the first study to determine the allele frequency and the genetic association of the DRD2 rs1076560 SNP and OPRM1 rs1799971 SNP variants in clinically diagnosed patients with SUD from the United Arab Emirates (UAE). METHODS: A cross-sectional case-control cohort that consisted of 512 male subjects was studied. Two hundred and fifty patients with SUD receiving treatment at the UAE National Rehabilitation Center were compared to 262 controls with no prior history of mental health and SUD. DNA from each subject was extracted and genotyped using the TaqMan ® SNP genotyping assay. RESULTS: There were no significant associations observed for DRD2 rs1076560 SNP, OPRM1 rs1799971 SNP, and combined genotypes of both SNPs in the SUD group. CONCLUSION: Further research is required with refinements to the criteria of the clinical phenotypes. Genetic studies have to be expanded to include other variants of the gene, the interaction with other genes, and possible epigenetic relationships.

Physicians' experiences of SBIRT training and implementation for SUD management in primary care in the UAE: a qualitative study.

AimThe objective of this paper is to present a qualitative study of introducing substance misuse screening using the Screening Brief Intervention and Referral to Treatment (SBIRT) model, in primary care in Abu Dhabi. BACKGROUND: Substance misuse in the UAE is an increasing problem. However religious beliefs and fear of legal consequences have prevented this topic from being openly discussed, risk levels identified through screening and treatment options offered. METHODS: A controlled trial was undertaken which included a qualitative process study which is reported here. Qualitative interviews with primary care physicians from two intervention clinics were undertaken to explore their views, experiences and attitudes towards substance misuse management in their clinic. Physicians were trained on SBIRT and on the research project process and documentation. At completion of the project, 10 months after the training, physicians (n=17) were invited to participate in an interview to explore their experiences of training and implementation of SBIRT. Interviews were recorded and transcribed. Inductive thematic coding was applied.FindingsIn total, 11 physicians were interviewed and three main themes emerged: (1) The SBIRT screening project, (2) cultural issues and (3) patient follow-up. Findings revealed a general willingness toward the concept of screening and delivering brief interventions in primary care although increased workload and uncertainties about remuneration for the service may be a barrier to future implementation. There was a perceived problem of substance misuse that was not currently being met and a strong perception that patients were not willing to reveal substance use due cultural barriers and fear of police involvement. In conclusion this qualitative process evaluation provided essential insight into implementing SBIRT in the Middle East. In conclusion, despite physician willingness and a clinical need for a substance misuse care pathway, the reluctance among patients to admit to substance use in this culture needs to be addressed to enable successful implementation.

Developing substance misuse services in United Arab Emirates: the National Rehabilitation Centre experience.

In 2001 a directive was issued to establish the National Rehabilitation Centre (NRC) to deal with the growing problem of substance misuse in the United Arab Emirates. The NRC has achieved many goals as a treatment and rehabilitation facility as well as a drug and alcohol demand reduction response centre. It is now working towards being an international centre of excellence.

National Rehabilitation Center programme performance measures in the United Arab Emirates, 2013.

The aim of this study was to measure the performance of the National Rehabilitation Center (NRC) programme and the services it provides. A 6-point tool was developed based on international standards with appropriate performance measures. The elements of the tool were applied to the electronic data files for 2013. The results showed that there were some operational, quality and data system issues. Some items were easily accessible, e.g. capacity, waiting time, family involvement. Others were difficult to sort and find and some were not available in the electronic system and had to be retrieved from other sources, e.g. programme effectiveness. There was a high no-show rate for appointments (46%) and readmission rate (52%) and most families did not attend family sessions (72%). This was a valuable exercise which identified gaps in operations and records. The findings were shared with the different teams to help improve the quality of data and services and the tool will be used for annual performance evaluations.

The pattern of substance use disorder in the United Arab Emirates in 2015: results of a National Rehabilitation Centre cohort study.

BACKGROUND: Substance use disorder (SUD) is a global problem with no boundaries, which also afflicts individuals from countries of the Arabian Peninsula. Data from this region is limited. In an effort to develop targeted prevention and intervention initiatives in the United Arab Emirates (UAE), it was necessary to identify the nature of substance use by describing the characteristics of those using different substances. Consequently, this study in the UAE was conceived to describe the pattern of SUD in a first-ever cohort that was systematically recruited from the country's National Rehabilitation Centre (NRC) in Abu Dhabi. METHODS: Two hundred and fifty male patients were recruited from the NRC. Information on substance use was collected using a questionnaire that was completed at an interview with patients who consented to participate. The questionnaire was based on information that the study was designed to capture. It was reviewed by members of institutional ethics committees and approved prior to use. Two hundred and fifty male subjects from the Emirates Family Registry (EFR) were used as a comparison group. RESULTS: In the cohort studied, SUD correlated with smoking and marital status. Poly-substance users formed the majority of the cohort (84.4 %) with various combinations of substances identified across different age groups. Opioid and alcohol were the most common substances used. The use of pharmaceutical opioids, primarily Tramadol (67.2 % of opioid users), was higher among the youngest age group studied (<30 years old), while older opioid users (≥30 years old) commonly used illicit opioids (Heroin). The use of prescribed medication for non-medical use also included Pregabalin (mean of 8.3 capsules ± 0.5 per day), Procyclidin (6.1 tablets + 0.6 per day) and Carisoprodol (4.2 tablets ± 0.4 per day) and was again highest in the age group below 30 years. CONCLUSION: This 2015 study highlights the importance of examining the pattern of poly-substance use in a population in order to develop targeted prevention programs to arrest the prevailing trends. It has drawn attention to the rise in use of prescription medication in the UAE, in particular among younger patients (<30 years), and continuing use of illicit opioid amongst males above 30 years. Specific prevention and intervention strategies, targeting differences between these distinct demographic profiles will capture a large subset of sufferers.

Adolescents' perception of substance use and factors influencing its use: a qualitative study in Abu Dhabi.

OBJECTIVE: The objective of this article is to gain a deeper understanding of the attitudes and perceptions of adolescents in the United Arab Emirates regarding substance and to identify factors that, in their view, may influence the risk of substance use and suggest possible interventions. DESIGN: This was a qualitative study that used a focus group approach. SETTING: The study was carried out in Abu Dhabi, United Arab Emirates. PARTICIPANTS: Male and female teenagers aged 13-18 years residing in the emirate of Abu Dhabi. MAIN OUTCOME MEASURES: Adolescents' awareness of substance use, patterns of use and associated harm; Adolescents' perceptions about the factors associated with substance use. RESULTS: Six focus groups were carried out, and a total of 41 adolescents (20 males and 21 females) participated. Data analysis identified three main themes: (1) adolescents' awareness of substance use and associated harm; (2) gender role and image and (3) perceived factors affecting substance use among adolescents. Knowledge of substances and related consequences of use varied between groups but was compatible with participants' age and school years. Factors that participants believed influenced substance use were classified into: (1) parent-adolescent relationship, (2) peer pressure, (3) substance accessibility, (4) religiosity and (5) others. Many factors were believed to increase the risk of substance use among adolescents such as peer pressure, inadequate knowledge of the harmful consequences of drug use, family-related factors (e.g. low monitoring and poor parent-adolescents relationship), affordability and availability of substances, boredom and affluence. On the other hand, religiosity was as a shield against substance use, especially alcohol. Other identified protective factors included carrying out schools- and communities-based educational campaigns, enhancing social workers' ability to raise awareness and detect early signs of addiction and implementing CCTV systems in schools. CONCLUSIONS: The study was successful in exploring adolescents' awareness of substances and associated harm to health from their use. Also, it identifies a number of risk and protective factors based on the perceptions of a group of adolescents residing in the United Arab Emirates. Such factors can guide the planning, designing and implementing of prevention programmes that focus on raising awareness about the harms of substance use. The study findings would suggest that multifactorial prevention programmes that address social norms, gender role and image, and incorporate drug policy, religion, family and school would be more effective and may have better protective outcomes.