Opiate Treatment Research Articles

Cost-effectiveness of Hepatitis C Virus Treatment Models for People Who Inject Drugs in Opioid Agonist Treatment Programs.

Many people who inject drugs in the United States have chronic hepatitis C virus (HCV). On-site treatment in opiate agonist treatment (OAT) programs addresses HCV treatment barriers, but few evidence-based models exist. We evaluated the cost-effectiveness of HCV treatment models for OAT patients using data from a randomized trial conducted in Bronx, New York. We used a decision analytic model to compare self-administered individual treatment (SIT), group treatment (GT), directly observed therapy (DOT), and no intervention for a simulated cohort with the same demographic characteristics of trial participants. We projected long-term outcomes using an established model of HCV disease progression and treatment (hepatitis C cost-effectiveness model: HEP-CE). Incremental cost-effectiveness ratios (ICERs) are reported in 2016 US$/quality-adjusted life years (QALY), discounted 3% annually, from the healthcare sector and societal perspectives. For those assigned to SIT, we projected 89% would ever achieve a sustained viral response (SVR), with 7.21 QALYs and a $245 500 lifetime cost, compared to 22% achieving SVR, with 5.49 QALYs and a $161 300 lifetime cost, with no intervention. GT was more efficient than SIT, resulting in 0.33 additional QALYs and a $14 100 lower lifetime cost per person, with an ICER of $34 300/QALY, compared to no intervention. DOT was slightly more effective and costly than GT, with an ICER > $100 000/QALY, compared to GT. In probabilistic sensitivity analyses, GT and DOT were preferred in 91% of simulations at a threshold of <$100 000/QALY; conclusions were similar from the societal perspective. All models were associated with high rates of achieving SVR, compared to standard care. GT and DOT treatment models should be considered as cost-effective alternatives to SIT.

The clinical efficacy of ultrasound-guided percutaneous microwave ablation for rib metastases with severe intractable pain: a preliminary clinical study.

Purpose: To retrospectively evaluate the clinical efficacy of ultrasound-guided percutaneous microwave ablation (US-PMWA) for patients with rib metastases that caused severe intractable pain.Materials and methods: From Jan 2016 to Apr 2018, 9 rib metastases from 7 solid tumor patients were treated with US-PMWA. The visual analogue scale (VAS), daily opiate intake doses, local tumor control and complications were recorded and analyzed.Results: The follow-up period ranged from 6 to 33 months (median: 16 months). The procedures were successfully performed in all of the patients by one ablation. The ablation power ranged from 30 to 60 W, and the ablation time was 610.0±317.5 s. The mean preablation VAS pain score was 8.1±0.7, whereas the mean VAS pain score at 72 h postablation was 3.3±0.5 (P<0.001). All of the patients needed to apply oral and/or intravenous injection opiates to relieve severe intractable pain before ablation, with daily opiate intake doses of 61.4±30.8 mg. After ablation, five patients did not need to apply any opiate treatments 72 h after ablation, and only two patients needed oral opiates (daily opiate intake doses: 30 mg and 20 mg). Recurrence was detected in three lesions at 6, 11 and 9 months after ablation, with the maximum diameter observed being more than 4 cm. All of the patients were alive during the follow-up period. No minor or major complications occurred.Conclusion: US-PMWA appears to be feasible, convenient, safe and effective in the palliative management of refractory pain caused by rib metastases. This treatment can improve the quality of life of patients and may also achieve promising local control of tumors.

Opioid Dependence and Health Care Utilization After Decompression and Fusion in Patients With Adult Degenerative Scoliosis.

Retrospective study. To identify factors associated with opioid dependence after surgery for adult degenerative scoliosis (ADSc). Opioid epidemic is of prodigious concern throughout the United States. Data was extracted using national MarketScan database (2000-2016). Opioid dependence was defined as continued opioid use or >10 opioid prescriptions for 1 year either before or 3 to 15 months after the procedure. Patients were segregated into four groups based on opioid dependence before and postsurgery: NDND (before nondependent who remain non-dependent), NDD (before nondependent who become dependent), DND (before dependent who become non-dependent) and DD (before dependent who remain dependent). Outcomes were discharge disposition, length of stay, complications, and healthcare resource utilization. Approximately, 35.82% (n = 268) of patients were identified to have opioid dependence before surgery and 28.34% (n = 212) were identified to have opioid dependence after surgery for ADSc. After surgical fusion for ADSc, patients were twice likely to become opioid independent than they were to become dependent (13.77% vs. 6.28%, OR: 2.191, 95% CI: 21.552-3.094; P < 0.0001). Before opioid dependence (RR: 14.841; 95% CI: 9.867, 22.323; P < 0.0001) was identified as a significant predictor of opioid dependence after surgery for ADSc. In our study, 57.9%, 6.28%, 13.77%, and 22.06% of patients were in groups NDND, NDD, DND, and DD respectively. DD and NDD were likely to incur 3.03 and 2.28 times respectively the overall costs compared with patients' ingroup NDND (P < 0.0001), at 3 to 15 months postsurgery (median $21648 for NDD; $40,975 for DD; and $ 13571 for NDND groups). Surgery for ADSc was not associated with increased likelihood of opioid dependence, especially in opioid naïve patients. Patients on regular opiate treatment before surgery were likely to remain on opiates after surgery. Patients who continued to be opioid dependent or become dependent after surgery incur significantly higher healthcare utilization at 3 and 3 to 15 months. 4.

Psychological distress mediated the effects of self-stigma on quality of life in opioid-dependent individuals: A cross-sectional study.

BackgroundBoth stigma and psychological distress affect quality of life (QOL). This study is an attempt to determine the effects of these two factors on QOL and to explore possible mediation effects between psychological distress and self-stigma in opioid-dependent individuals.MethodsThis cross-sectional study comprised 268 consecutive, treatment-seeking opioid-dependent individuals who were interviewed using the brief version of the World Health Organization Quality of Life instrument (WHOQOL-BREF), the Self-Stigma Scale-Short (SSS-S), the Chinese Health Questionnaire-12 (CHQ-12), and the Opiate Treatment Index (OTI). A series of regression models were constructed to determine if the SSS-S and CHQ-12 predict the WHOQOL-BREF scores. Moreover, a comparison of the potential mediation effects of psychological distress (as assessed by the CHQ-12) was made between the SSS-S and the WHOQOL-BREF using the Baron and Kenny procedure (including three separate regressions), along with the Sobel test.ResultsThe CHQ-12 score was predictive of the scores for the four domains and almost all facets of the WHOQOL-BREF except the item, “Dependence on medical aids.” Nonetheless, the SSS-S score predicted three of the four facets of the social QOL after adjustment of the CHQ-12 score. Psychological distress completely mediated the relation between self-stigma and the physical, psychological, and environmental domains, and partially mediated the relationship between self-stigma and social QOL (two-tailed Sobel test: p = 0.02 for each domain).ConclusionsPsychological distress has a significant impact on the QOL of treated opioid users. It appears to be a core element in reducing the negative effects of self-stigma on aspects of QOL.

The impact of opiate substitution treatment on mortality risk in drug addicts: a natural experiment study

Background Opiate substitution treatment (OST) is the main treatment for people addicted to heroin and other opioid drugs. However, there is limited information on how the delivery of this treatment affects mortality risk. Objectives To investigate the associations of mortality risk with periods during treatment and following cessation of treatment, medication type, co-prescription of other medication and dosing regimens during titration and detoxification. The trends with time of prescribed medication, dose and treatment duration were also explored. Design Prospective longitudinal observational study. Setting UK primary care between 1998 and 2014. Participants A total of 12,780 patients receiving methadone, buprenorphine or dihydrocodeine. Main outcome measures All-cause mortality relating to 657 deaths and drug-related poisoning relating to 113 deaths. Data sources Clinical Practice Research Datalink with linked information on cause of death from the Office for National Statistics. Results For both outcomes, the lowest mortality risk was observed after 4 weeks of treatment and the highest risk was observed in the first 4 weeks following cessation of treatment [e.g. for drug-related poisoning, incidence rate ratio (IRR) 8.15, 95% confidence interval (CI) 5.45 to 12.19]. There was evidence that the treatment period risks varied with OST medication. The largest difference in risk was for the first 4 weeks of treatment for both outcomes, with patients on buprenorphine being at lower risk than those on methadone (e.g. for drug-related poisoning, IRR 0.08, 95% CI 0.01 to 0.48). The co-prescription of benzodiazepines was associated with linearly increasing the risk of drug-related deaths by dose (IRR 2.02, 95% CI 1.66 to 2.47), whereas z-drugs (zolpidem, zopiclone and zaleplon) were associated with increased risk of both all-cause (IRR 1.83, 95% CI 1.59 to 2.12) and drug-related (IRR 3.31, 95% CI 2.45 to 4.47) mortality. There was weak evidence that higher initial and final doses were associated with increased all-cause mortality risk. In the first 4 weeks of treatment, the risk increased by 4% for each 5-mg increment in methadone dose (1-mg increase in buprenorphine) (hazard ratio 1.04, 95% CI 1.00 to 1.09). In the first 4 weeks after treatment ceased, a similar increment in final dose increased the risk by 3% (hazard ratio 1.03, 95% CI 0.99 to 1.07). There were too few deaths to evaluate the effects on drug-related poisoning. The proportion of OST patients receiving buprenorphine increased between 1998 and 2006. Median treatment duration was consistently shorter for buprenorphine than for methadone for each year studied (overall median duration of 48 and 106 days, respectively). Limitations As this was an observational study, the possibility remains of bias from unmeasured factors, which covariate adjustment and inverse probability weighting can eliminate only partially. Conclusions Using buprenorphine as an alternative to methadone may not reduce mortality overall despite resulting in lower IRRs from shorter treatment duration. Clinical guidance needs to consider strengthening warnings about the co-prescription of a range of drugs for OST patients. Future work Our analyses need to be replicated using other clinical data sets in the UK and in other countries. New interventions and trials are required to investigate improving the retention of OST patients in primary care. Funding The National Institute for Health Research Health Services and Delivery Research programme.

The effects of buprenorphine/naloxone maintenance treatment on sexual dysfunction, sleep and weight in opioid use disorder patients

Opioid use disorder is a growing social problem. Different agents are used in the treatment of this disorder. One of these agents is buprenorphine / naloxone combination that includes buprenorphine and naloxone in a ratio of 4:1. Although used successfully in opiate maintenance treatment, buprenorphine / naloxone could have some side effects that might affect the treatment. The present study aimed to examine the effects of buprenorphine /naloxone opiate maintenance treatment on sexual dysfunction, sleep and bodyweight in patients diagnosed with opioid use disorder and to draw the attention of clinicians to the adverse effects of the treatment. The study group included 107 inpatients who were diagnosed based on The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and received treatment for opioid use disorder. On admission to the hospital and at the end of the 4th month, a Sociodemographic and Clinical Data Form, the Pittsburgh Sleep Quality Index (PSQI) and the Arizona Sexual Life Scale (ASEX) were applied to all patients. Patients were weighed, and their weight was recorded on the day of admission to the hospital and at the end of the 4th month. The data recorded at the beginning and during the treatment of the same group were compared. The mean age of 107 patients was 24.55 ± 4.27. Overall ASEX scores were 12.98 ± 4.33 before treatment and 15.03 ± 6.61 at 4 months (p < 0.001). The mean patient bodyweight was 63.86 ± 8.78 kg before the treatment and 68.49 ± 8.65 kg at the 4th month of the treatment (p < 0.001). Total PSQI scores were 8.87 ± 3.53 before the treatment and 6.85 ± 3.29 at the 4th month of the treatment (p < 0.001). The study findings demonstrated that after 4 months of buprenorphine /naloxone treatment, total ASEX scores and bodyweight of the patients increased and total PSQI scores decreased. These results demonstrated that sexual problems and bodyweight of the patients increased after the buprenorphine /naloxone treatment and sleep-related problems decreased, albeit still prevalent. These potential side effects should be included with other information about buprenorphine that is given to patients as they may influence interest in starting or continuing treatment.

Exploring the experiences of staff working at an opiate assisted treatment clinic: An interpretive descriptive study

There have been many advances in harm reduction over the past three decades. One of the newest approaches is the provision of medical grade heroin to people with opiate addiction, known as opiate assisted treatment (OAT). There is one clinic in North America which provides this service. The goal of this study was to uncover how clinic staff provide care to those who attend this clinic, their perspectives on how the clinic program impacted them and their patients, and their opinions about the program itself. This was a qualitative study with an interpretive descriptive methodology underpinned by critical social theory. Convenience sampling yielded 22 participants – 18 nurses, two social workers and two peer support workers. Thematic analysis was undertaken to identify recurring, converging and contradictory patterns of interaction, key concepts and emerging themes. The study location was the OAT clinic located in the downtown eastside of Vancouver, BC. The findings were organized around the following six themes: from chaos to stability, it's not all roses, a little preparation would be good, putting the patient at the centre, the stigma hasn't gone away, and the clinic is life transforming. Taken together, these themes indicate the complexities of working in this environment. The findings can guide clinic staff, including nurses, in how they provide care to patients with addiction problems and also provide direction for policy makers on harm reduction planning. Contribution of the paperWhat is already known about the topic?•Opiate Assisted Treatment is an effective harm reduction approach to care and there is only one clinic offering this treatment approach in North America.•There is limited research on opiate assisted treatment clinics; research is primarily conducted in Europe.•Staff working in clinics that provide opiate assisted treatment are primarily concerned about overdoses and the diversion of heroin.What does this paper add?•Staff working in clinics that offer opiate assisted treatment engage in complex and challenging care, which is also very rewarding.•Patient outcomes in opiate assisted treatment clinics are positively impacted by the approach of staff.•This novel work establishes the importance of attending to the effects of educational preparation, power dynamics, and physical space on staff working at opiate assisted treatment clinics, for developing successful harm reduction programs.

INTEGRATING HEPATITIS C CARE FOR AT RISK GROUPS: FINDINGS FROM A MULTI-CENTRE OBSERVATIONAL STUDY IN PRIMARY AND COMMUNITY CARE

Introduction: Hepatitis C HCV infection is a major cause of chronic liver disease and death. In the EU, primary care is increasingly providing long-term care for people who inject drugs PWID, many of whom are infected with HCV. Although the barriers to HCV care in this population are well understood, real world solutions remain relatively unstudied. The ‘HepLink’ project aims to address this gap by developing an integrated model of HCV care and evaluating its feasibility and acceptability among PWID attending at four primary care / community-based sites. Methods: The integrated model of care comprises: education of primary and community care professionals on recent developments in HCV diagnosis and treatment and academic detailing on the ‘HepLink’ project, clinical support/outreach by a HCV trained nurse to primary care and community sites, and enhanced community-based HCV evaluation of patients including on-site Fibroscan to stage liver disease, blood borne virus testing/vaccination, HCV and harm reduction education. Practices/clinical sites in Dublin, London, Bucharest and Seville were recruited from the professional networks of consortium members. Patients were eligible to participate if aged over 18 years, on opiate substitutions treatment or at risk of HCV, and attending the practice/service for any reason during the recruitment period. Data on patient demographics and HCV care processes were collected on participating patients at baseline. Results: Twenty-seven practices/services Dublin n=14, London n=1, Seville n=3 and Bucharest n=9 are currently participating. A total of 452 patients have been recruited across the four sites Dublin n=135; London n=39, Seville n=109; Bucharest n=169 and baseline data has been collected on 438 patients. The 'HepLink’ model of care is currently being delivered at the four sites, tailored according to local primary care organisation and population need. To date, 53 GPs have received HCV education/academic detailing, 18 practices/services have received nurse specialist liaison; and 20 practices/services have delivered enhanced community-based HCV evaluation. Discussion: To address the growing burden of HCV-related liver disease among PWID, an integrated model of HCV care comprising education and training, clinical support / outreach and improved access to assessment has been developed and its feasibility / acceptability established in a real-world setting. Conclusions: Our research findings will determine the feasibility and acceptability of an integrated model of care for engaging and retaining PWID in the continuum of HCV care. Lessons learned: Lessons learned from the study can be incorporated into national and European guidelines and strategies for HCV. In addition, with health systems promoting ‘integrated care’ as a solution to many of the challenges facing healthcare today, this project provides valuable real-world insights on how such a model of care may be operationalised. Limitations: As a pre-post feasibility study, 'HepLink' does not employ a controlled trial design and lacks the scientific rigour of a RCT which could definitively determine effectiveness of the intervention. Suggestions for future research: This feasibility study can provide the key parameters for the design of a future cluster RCT.

HCV seroconversion in a cohort of people who use drugs followed in a mobile harm reduction unit in Madrid: Breaking barriers for HCV elimination

Background and aimsHarm reduction strategies have been shown to decrease the incidence of human immunodeficiency virus (HIV) infection in people who inject drugs (PWID), but the results have been inconsistent when it comes to prevention of hepatitis C virus (HCV) infection. We aimed to examine the rate of HCV seroconversion among people who use drugs (PWUD) followed at a mobile harm reduction unit (MHRU) to evaluate if a low-threshold methadone substitution program (LTMSP) is associated with a low HCV seroconversion rate and subsequently identify barriers for elimination.Materials and methodsA cohort of PWUD have been followed at a MRHU in Madrid between 2013 and 2016. Individuals who were negative for HCV antibodies at baseline and who had at least one retest for HCV antibodies were eligible. Kaplan-Meier methods were employed to estimate the global incidence density.ResultsDuring the study period, 946 PWUD were screened for HCV at least once. At baseline 127 PWUD were negative for HCV antibodies and had at least one follow-up HCV antibodies test. The baseline HCV prevalence was 33%. After a median 0.89 (IQR 0.3–1.5) years of follow-up and 135 person-years of risk for HCV infection, 28 subjects seroconverted. The incidence density for HCV seroconversion for this sample was 20.7 cases (95% CI: 14.3–29.7) per 100 person-years. Injecting drugs in the last year was strongly associated to HCV seroconversion (AHR 15.5, 95%CI 4.3–55.8, p < 0.001). Methadone status was not associated to HCV seroconversion.ConclusionsA high incidence of HCV infection was found among PWUD at a MHRU in Madrid. In this setting opiate substitutive treatment (OST) as a LTMSP does not appear to protect against HCV seroconversion.

Increased Methamphetamine Use among Persons Who Inject Drugs in Hai Phong, Vietnam, and the Association with Injection and Sexual Risk Behaviors

ABSTRACTMethamphetamine use has increased significantly in Southeast Asia in the last 5–10 years, but there is little research on risk behaviors associated with the increase in this region. We evaluate injection and sexual risk behaviors associated with current methamphetamine use among heterosexual persons who inject drugs (PWID) in Hai Phong, Vietnam. We recruited 1336 PWID and assessed associations between methamphetamine use, injection and sexual risk behaviors, stratified by HIV serostatus. There were several statistically significant associations between methamphetamine use and sexual risk behaviors among HIV-positive PWID, but we did not find any associations between methamphetamine use and injection risk behaviors. Methamphetamine may increase the likelihood of PWID transmitting HIV to non-injecting primary sexual partners, as it can reduce ART adherence and can lead to weakening of the immune system and increased HIV viral loads. All participants were injecting heroin, and methamphetamine use may interfere with opiate use treatment. Public health efforts should focus on the large increase in methamphetamine use and the associated sexual risk behaviors. Emphasis on sexual risk behavior, particularly among those who are HIV-positive, in conjunction with continued monitoring of ART adherence and HIV viral loads, is critical.

Methadone Maintenance Treatment: A 15-year Retrospective Study in Split-Dalmatia County, Croatia.

The aim of this retrospective study is to use existing epidemiological data on patients in methadone maintenance treatment in Split-Dalmatia County from 2001 to 2015 to evaluate the substitution treatment system and policy of opiate addicts treatment, the epidemiological trend, and risk of overdose mortality. In addition, we would like to highlight the problem of poor control of methadone therapy and thus the possibility of selling methadone. The result is a greater number of deaths caused by methadone in people who were not in methadone therapy. The research included data collected from 3189 patients who had been in the drug abuse treatment program in Split-Dalmatia County during 2001-2015 and data gathered from autopsy examinations of patients in Split-Dalmatia County with emphasis on data for 186 overdosed patients during research period. The total number of patients in the methadone treatment program in Split-Dalmatia County during the research period, except in 2005 and 2006, has been stable, while the number of new opiate patients, being in first-time treatment, decreased by 62.5%. The number of addicts who were in a long-term maintenance program has increased by 198%, whereas the number of addicts who were in a short-term detoxification treatment has decreased by 96.4%. According to results obtained from performed autopsies, 186 death cases were determined as overdoses. Methadone was found in 56 of those cases and was declared as the cause of death in 39 cases (70%). Of the total number of autopsied patients with diagnosed methadone overdose, only 23 (59%) had been recorded to receive methadone therapy in Public Health Institute of Split-Dalmatia County database. The results of this study show the favorable epidemiological trend because of the decreasing number of new opiate patients in treatment. The retention of opiate patients in substitution therapy indicates the effectiveness of methadone maintenance programs. Our research did not determine any influence of methadone substitution therapy on an increasing risk of specific (overdose) mortality.

Incidence and spontaneous clearance of hepatitis C virus (HCV) in people who inject drugs at the Stockholm Needle Exchange-Importance for HCV elimination.

The major transmission route for hepatitis C virus (HCV) is through sharing of unsterile injection equipment among people who inject drugs (PWID). The WHO strategy for HCV elimination by 2030 proposes increased efforts to treat PWID populations that drive the HCV epidemic. Among participants in the Stockholm needle exchange programme (NEP), the HCV prevalence is 60%. We aimed to study HCV incidence, spontaneous HCV clearance rate, and predictors associated with new HCV infections and reinfections in NEP participants. All 2320 patients enrolled in the programme between 8 April 2013 and 23 September 2016 were tested for HCV at baseline, and responded to a questionnaire regarding sociodemographic data and injection risk behaviour. Tests for HCV were repeated at an interval of 3-6months. The anti-HCV prevalence in the NEP participants at baseline was 77%, and the prevalence of HCV RNA was 57%. 24% of the anti-HCV positive were HCV RNA negative with a spontaneously cleared HCV infection. The overall HCV incidence rate was 22/100 PY. The HCV incidence rate in the HCV naive group was 26/100 PY, and in the spontaneously cleared group 19/100. Although there were no significant differences in becoming HCV infected between the two groups (31% vs 29%), the rate of spontaneous HCV clearance was significantly lower in the HCV naive group, 20% vs 44%, (P<0.05). A high HCV incidence rate was noted among the PWID indicating that treatment needs to be scaled up in conjunction with harm reduction measures to achieve HCV elimination goals set by WHO. This includes high coverage needle exchange programmes and effective addiction treatment for substance users, including opiate substitution treatment.

Death Ambivalence and Treatment Seeking: Suicidality in Opiate Addiction

Rates of suicide and opiate overdose have recently skyrocketed in the United States. In light of impulsivity and impaired motivation common in people with substance use disorders, suicidality is common in addiction. Chart review surveys indicate two primary suicidal populations that are important to distinguish for clinical practice and healthcare policy. One group is heavily composed of people with SUDs, in whom chronic compulsive use fosters a numb ambivalence about death (low death intentionality). Many of these individuals with opiate use disorder (OUD) exaggerate suicidality to get prompt psychiatric care to treat the OUD. The second group is composed of those who have co-morbid psychiatric disorders and/or chronic pain who have a higher intent to die consistent with traditionally understood suicide risk factors. We contend that easier access to outpatient opiate agonist treatment would avoid unnecessary hospitalizations for death-ambivalent OUD patients, and for OUD patients in either group. First line treatment with an opioid agonist has high potential to effectively treat suicidal ideation as a secondary benefit.

Intérêt de la mise à disposition de la naloxone auprès des usagers de drogues pour le traitement d’urgence de surdosage d’opioïdes

Over the course of these last decades, we observed a change on opioid use with the marketing of opiate maintenance treatment, an increase of opioids used for pain management and recent concerns have arisen around the use of synthetic opioid. The World Health Organization (WHO) reports around 70,000 people opioid overdose death each year. In France, according to the DRAMES program (fatalities in relation with abuse of licit or illicit drugs) of the French addictovigilance network, most of deaths are related to opioids overdose (especially methadone, following by heroin, buprenorphine and opioid used for pain management). Opioid overdose is treatable with naloxone, an opioid antagonist which rapidly reverses the effects of opioids. In recent years, a number of programs around the world have shown that it is feasible to provide naloxone to people likely to witness an opioid overdose. In 2014, the WHO published recommendations for this provision and the need to train users and their entourage in the management of opioid overdose. In this context, in July 2016, French drug agency has granted a temporary authorization for use of a naloxone nasal spray Nalscue®. Because different opioids can be used and because each opioid has specific characteristics (pharmacodynamics, pharmacokinetics, galenic form…), the risk of overdose may differ from one opioid to another and it may be necessary, depending on the clinical context, to use larger and repeated doses of naloxone.

Hepatitis C virus prevention and care for drug injectors: the French approach

After France removed hepatitis C treatment reimbursement restrictions on 25 May 2016, an expert report presented recommendations, which focused on vulnerable groups including people who inject drugs (PWID). This commentary presents the key points of the chapter with a particular focus on policy.Thanks to the official lifting of restrictions based on disease stage and to the excellent efficacy and tolerance of the new DAA (Direct-Acting Antivirals) among PWID, the main issue is to improve the HCV care cascade. In France, many HCV-infected PWID, especially active/current PWID, remain undiagnosed and unlinked to care. Our challenge is to improve HCV screening by point of care testing (POCT), outreach methods with mobile teams, rapid tests, FibroScan, etc. and to provide PWID with appropriate services in all the settings they attend, such as drug treatment or harm reduction services, social services, prisons, etc. Another important issue is the prevention of reinfection through comprehensive and long-term follow-up.The report recommends a new national policy: testing and treating PWID as a priority, since this is the best way to eliminate HCV infection. It requires a global strategy consisting of combined and long-term interventions: prevention, outreach, screening, DAA, drug treatment programs including opiate substitution treatment (OST) and various harm reduction programs, including needle exchange programs (NEP). Ideally, these services should be delivered in the same place with an integrated approach. This should lead to meeting the national objective set by the government of eliminating hepatitis C by 2025.

Oral morphine protocol evaluation for the treatment of vaso-occlusive crisis in paediatric sickle cell patients.

Vaso-occlusive crisis (VOC) is one of the most frequent causes of emergency visit and admission in children with sickle cell disease (SCD). This study aimed to evaluate whether the implementation of a protocol promoting the use of oral morphine as a primary intervention has led to improved care of SCD. We performed a retrospective chart review of patients with SCD who presented to the emergency department (ED) and hematology outpatient clinic (HOC) with VOC, in the year pre and postimplementation of the protocol. The primary outcome was the hospitalization rate. The protocol resulted in a significant 43% reduction of hospitalization rate (95% confidence interval [CI] -53.0, 26.5). Results also showed a 35% increase in the use of oral morphine as first-line opiate treatment (95% CI 17.9, 45.2), a 28% increase in the use of pain scales (95% CI 17.3, 43.2) and a 30% net increase in patients eventually not requiring intravenous (IV) line placement (95% CI 16.0, 39.9). While we did observe an overall decrease in length of stay in ED of -55 min (95% CI -100.6, -12.0), there was a nonsignificant decrease of 7 minutes (95% CI -26, 3) in the opiate administration time. This study validates the use of our oral morphine protocol for the treatment of VOC by significantly reducing the admission rate and decreasing the number of IVs.

Predicting health-related quality of life (EQ-5D-5\xa0L) and capability wellbeing (ICECAP-A) in the context of opiate dependence using routine clinical outcome measures: CORE-OM, LDQ and TOP

BackgroundEconomic evaluation normally requires information to be collected on outcome improvement using utility values. This is often not collected during the treatment of substance use disorders making cost-effectiveness evaluations of therapy difficult. One potential solution is the use of mapping to generate utility values from clinical measures. This study develops and evaluates mapping algorithms that could be used to predict the EuroQol-5D (EQ-5D-5 L) and the ICEpop CAPability measure for Adults (ICECAP-A) from the three commonly used clinical measures; the CORE-OM, the LDQ and the TOP measures.MethodsModels were estimated using pilot trial data of heroin users in opiate substitution treatment. In the trial the EQ-5D-5 L, ICECAP-A, CORE-OM, LDQ and TOP were administered at baseline, three and twelve month time intervals. Mapping was conducted using estimation and validation datasets. The normal estimation dataset, which comprised of baseline sample data, used ordinary least squares (OLS) and tobit regression methods. Data from the baseline and three month time periods were combined to create a pooled estimation dataset. Cluster and mixed regression methods were used to map from this dataset. Predictive accuracy of the models was assessed using the root mean square error (RMSE) and the mean absolute error (MAE). Algorithms were validated using sample data from the follow-up time periods.ResultsMapping algorithms can be used to predict the ICECAP-A and the EQ-5D-5 L in the context of opiate dependence. Although both measures can be predicted, the ICECAP-A was better predicted by the clinical measures. There were no advantages of pooling the data. There were 6 chosen mapping algorithms, which had MAE scores ranging from 0.100 to 0.138 and RMSE scores ranging from 0.134 to 0.178.ConclusionIt is possible to predict the scores of the ICECAP-A and the EQ-5D-5 L with the use of mapping. In the context of opiate dependence, these algorithms provide the possibility of generating utility values from clinical measures and thus enabling economic evaluation of alternative therapy options.Trial registrationISRCTN22608399. Date of registration: 27/04/2012. Date of first randomisation: 14/08/2012.

The impact of employment on perceived recovery from opiate dependence

Purpose Less than 15 per cent of people starting opiate substitution treatment (OST) in England are employed, but few gain employment during treatment. Increasingly punitive approaches have been tried to encourage individuals with substance dependence into employment in the hope of facilitating recovery. It is not clear which factors are associated with the successful maintenance of employment whilst receiving OST, and whether this group can be said to be “in recovery”. The paper aims to discuss these issues. Design/methodology/approach A cross-sectional study of the OST population in one English region was conducted between January and April 2017. Measures of physical health, employment patterns, drug use, mental health, recovery capital, and dependence severity were administered to 55 employed and 55 unemployed clients. Findings Those in employment had higher levels of “recovery capital”, better physical and mental health, fewer drug problems, and less severe dependence, despite reporting heroin use at a similar level. Three variables were significantly associated with employment: longest period of employment (OR=1.01, p=0.003); number of chronic medical conditions (OR=0.44, p=0.011); and number of days of psychological problems in the last month (OR=0.95, p=0.031). Practical implications These results suggest that abstinence may not be required in order to maintain stable employment when OST is in place. Different treatment strategies are required for clients receiving OST already in employment compared with those who are unemployed. Originality/value This is the first UK study to the author’s knowledge to focus on people receiving OST who are also in employment.

Heteromerization of \u03bc-opioid receptor and cholecystokinin B receptor through the third transmembrane domain of the \u03bc-opioid receptor contributes to the anti-opioid effects of cholecystokinin octapeptide

Activation of the cholecystokinin type B receptor (CCKBR) by cholecystokinin octapeptide (CCK-8) inhibits opioid analgesia. Chronic opiate treatment leads to an increase in the CCK-8 concentration and thus enhances the antagonism of CCK-8 against opioid analgesia; the underlying molecular mechanisms remain of great interest. In the present study, we validated the colocalization of the μ-opioid receptor (MOR) and CCKBR in pain signal transmission-related spinal cord dorsal horn and dorsal root ganglion neurons of rats. Co-immunoprecipitation (Co-IP) and fluorescence lifetime-imaging-microscopy-based fluorescence resonance energy transfer (FLIM-FRET) assays showed that MOR heteromerized with CCKBR directly in transfected HEK293 cells. Combined with MOR mutant construction, the third transmembrane domain of MOR (TM3MOR) was demonstrated to participate in heteromerization with CCKBR. Receptor ligand binding, ERK phosphorylation and cAMP assays showed that MOR heteromerization with CCKBR weakened the activity of MOR. A cell-penetrating interfering peptide consisting of TM3MOR and TAT (a transactivator of HIV-1) sequences from the N terminal to the C terminal disrupted the MOR–CCKBR interaction and restored the activity of MOR in transfected HEK293 cells. Furthermore, intrathecal application of the TM3MOR-TAT peptide alleviated CCK-8-injection-induced antagonism to morphine analgesia in rats. These results suggest a new molecular mechanism for CCK-8 antagonism to opioid analgesia in terms of G-protein-coupled receptor (GPCR) interaction through direct heteromerization. Our study may provide a potential strategy for pain management with opioid analgesics.

Risky Sexual Behavior Among Individuals Receiving Buprenorphine/Naloxone Opiate Dependency Treatment: HIV Prevention Trials Network (HPTN) 058.

Understanding the role of opiate dependency treatment in risky sexual behavior could help optimize interventions for people who inject drugs (PWID). We evaluated whether long-term medication-assisted treatment (LT-MAT) of opiate dependency with buprenorphine/naloxone influenced risky sexual behavior among HIV-uninfected PWID and identified predictors of risky sexual behavior. We used data from HPTN 058, a randomized controlled trial of LT-MAT vs. short-term medication-assisted treatment among PWID in China and Thailand. We evaluated associations between randomized opiate dependency treatment group and self-reported risky sexual behaviors within the past month: condomless sex with primary partner, condomless sex with nonprimary partner, multiple partners, and more than 3 sexual acts. We used generalized estimating equations to conduct intention-to-treat, as-treated, and exploratory analyses of these associations. Of 1250 participants included in the analysis, 92% were male, with median age of 34 years (interquartile range 28-39). At baseline, referring to the past month, 36% of participants reported condomless sex with primary partner, 4% reported condomless sex with nonprimary partner, 6% reported multiple sex partners, and 30% reported more than 3 sexual acts. Risky sexual behaviors did not differ significantly between treatment groups at any point. Significant predictors (P < 0.05) of condomless sex with nonprimary partner were history of incarceration and noninjection drug use. Number of needle-sharing partners, noninjection drug use, and higher income were predictors for multiple sexual partners. LT-MAT did not significantly modify risky sexual behavior among HIV-uninfected PWID. Interventions that reduce sexual risk should target PWID with history of incarceration, alcohol use, and needle sharing.