Opioid Maintenance Research Articles

Continuation in Treatment and Maintenance of Custody of Newborns After Delivery in Women With Opioid Use Disorder.

To identify variables associated with continuation in treatment and maintenance of custody after pregnancies in women with opioid use disorder (OUD). The medical records of pregnant women with documented OUD from 2011 to 2018 and with at least 6 months follow-up postpartum were retrospectively reviewed. Via multivariate analysis, women on opioid maintenance therapy (OMT) were more likely to continue in treatment and maintain custody, whereas women enrolled in a residential treatment program during pregnancy were less likely to continue in treatment or maintain custody. Women who continued in treatment were significantly more likely to maintain custody of their children than those who did not. Continuation in treatment and maintenance of custody were closely related. Care providers should attempt to improve both outcomes.

Hab-o Shefa, a Persian Medicine Compound for Maintenance Treatment of Opioid Dependence: Randomized Placebo-Controlled Clinical Trial.

Objectives: The major problem in maintenance treatment of opioid use disorder is craving and relapse. The utilization of herbal compounds and complementary therapy for treatment of disease and addiction has been widely expanding. Considering the significant effect of Hab-o Shefa in detoxification phase, this clinical trial has explored the influence of this compound on maintenance treatment of opioid-dependent patients. This product is made of four herbs, including Datura stramonium L., Rheum palmatum L., Zingiber officinale Roscoe, and Acacia senegal L. Design: The authors conducted a two-group parallel randomized double-blind clinical trial on 81 opioid-dependent patients within 12 weeks. After medically assisted detoxification, participants were assigned randomly to Hab-o Shefa (n = 41) and placebo (n = 40). Outcome measures included craving assessed by craving beliefs questionnaire, self-reported opioid use, and lapse (any opioid-positive urine test) according to urinalysis and addiction severity index-lite questionnaire, retention in treatment, and depression and anxiety scores on the Hamilton's anxiety and depression scales. Results: Forty-one participants completed the study for 12 weeks, 21 subjects in the drug group and 20 subjects in the placebo group. The rates of opioid-positive urine tests and self-reported opioid use were significantly lower in Hab-o Shefa group (f = 8.41, p = 0.001). Hab-o Shefa also indicated a significant superiority over placebo in the effect of treatment by time interaction for craving (f = 5.91, p = 0.001), depression (f = 3.40, p = 0.01), and anxiety (f = 2.58, p = 0.035). The retention time was 66.6 days for drug group and 59.6 days for placebo one. Although the causes for dropping out in two groups were different, there was no significant difference (p = 0.623). The side effects of the two groups were not significantly different. Conclusion: Results indicated that Hab-o Shefa could be useful for opioid maintenance treatment, and it can also be considered as a new promising drug for prevention of craving and relapse.

In a Rat Model of Opioid Maintenance, the G Protein–Biased Mu Opioid Receptor Agonist TRV130 Decreases Relapse to Oxycodone Seeking and Taking and Prevents Oxycodone-Induced Brain Hypoxia

BackgroundMaintenance treatment with opioid agonists (buprenorphine, methadone) is effective for opioid addiction but does not eliminate opioid use in all patients. We modeled maintenance treatment in rats that self-administered the prescription opioid oxycodone. The maintenance medication was either buprenorphine or the G protein–biased mu opioid receptor agonist TRV130. We then tested prevention of oxycodone seeking and taking during abstinence using a modified context-induced reinstatement procedure, a rat relapse model. MethodsWe trained rats to self-administer oxycodone (6 hours/day, 14 days) in context A; infusions were paired with discrete tone-light cues. We then implanted osmotic pumps containing buprenorphine or TRV130 (0, 3, 6, or 9 mg/kg/day) and performed 3 consecutive tests: lever pressing reinforced by oxycodone-associated discrete cues in nondrug context B (extinction responding), context-induced reinstatement of oxycodone seeking in context A, and reacquisition of oxycodone self-administration in context A. We also tested whether TRV130 maintenance would protect against acute oxycodone-induced decreases in nucleus accumbens oxygen levels. ResultsIn male rats, buprenorphine and TRV130 decreased extinction responding and reacquisition of oxycodone self-administration but had a weaker (nonsignificant) effect on context-induced reinstatement. In female rats, buprenorphine decreased responding in all 3 tests, while TRV130 decreased only extinction responding. In both sexes, TRV130 prevented acute brain hypoxia induced by moderate doses of oxycodone. ConclusionsTRV130 decreased oxycodone seeking and taking during abstinence in a partly sex-specific manner and prevented acute oxycodone-induced brain hypoxia. We propose that G protein–biased mu opioid receptor agonists, currently in development as analgesics, should be considered as relapse prevention maintenance treatment for opioid addiction.

Association between Adult Attention Deficit/Hyperactivity Disorder and Intravenous Misuse of Opioid and Benzodiazepine in Patients under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study

Background: Intravenous misuse and attention-deficit/hyperactivity disorder (ADHD) are common in patients under opioid maintenance treatment (OMT), who often misuse benzodiazepine (BZD). Objectives: To explore the rate of adult ADHD among patients under OMT in Italy and whether screening positive for adult ADHD is associated with OMT and BZD misuse and emergency room (ER) admission because of misuse. Methods: We recruited 1,649 patients from 27 addiction units (AUs) in Italy and collected data on the self-reported rate of OMT intravenous misuse (prevalence, repeated misuse, main reason, temporal pattern in relation to AU access, experience), concurrent intravenous and intranasal BZD misuse (prevalence, type of misused BZD), ADHD and ER admissions because of misuse complications. Results: Screening positive for adult ADHD was found in 11.2% patients (ADHD+), with a significant gender difference (women: 15.3%, men: 10.3%). OMT misuse was reported by 24.4 and 18.5% patients during lifetime and in the previous 6 months respectively. BZD misuse was reported by 20.0 and 8.6% patients for intravenous and intranasal route respectively. Misuse was significantly more common in ADHD+ (OMT 27.4–33.1%, BZD 14.5–31.5%) than ADHD– group (OMT 17.4–23.3%, BZD 7.9–18.3%). The multivariate logistic regression model showed positive screening for ADHD to be significantly associated with intravenous OMT misuse in the previous 6 months, and intravenous/intranasal BZD misuse, independently of age, gender and route of previous heroin administration. Conclusions: Screening positive for adult ADHD was associated with OMT and BZD misuse. AU physicians and medical personnel should focus on OMT patient’s features that are associated with a higher likelihood of misuse, in particular ADHD.

Effects of Interim Buprenorphine Treatment for opioid use disorder among emerging adults

ObjectiveAlthough opioid maintenance is a first-line approach for treating opioid use disorder (OUD), suboptimal treatment outcomes have been reported among emerging adults (EAs; 18-25 years of age). In this secondary analysis, we compared treatment outcomes between EAs and older adults (OAs; ≥ 26 years of age) receiving low-barrier, technology-assisted Interim Buprenorphine Treatment (IBT) during waitlist delays to comprehensive opioid maintenance treatment. MethodParticipants were 35 individuals with OUD who received IBT consisting of 12-weeks of buprenorphine maintenance with bi-monthly clinic visits and technology-assisted monitoring. At monthly follow-up assessments, participants completed staff-observed urinalysis, the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), and Addiction Severity Index (ASI). ResultsAt study intake, EAs (n = 10) reported greater past-year intravenous drug use and greater employment, legal, and psychiatric severity (p’s < .05) compared to OAs (n = 25). Despite these initial differences, there were no significant differences in the percentages of urine specimens testing negative for illicit opioids between EA and OA participants at Study Week 4 (90 % vs. 88 %, p = .99), Week 8 (80 % vs. 76 %, p = .99) or Week 12 (60 % vs. 68 %, p = .71). Relative to their older peers, EAs also demonstrated significantly greater improvements on the BAI, BDI-II, and ASI Employment and Legal subscales (p’s < .05). ConclusionsDespite presenting with greater past-year intravenous drug use and psychosocial severity relative to OAs, EAs responded favorably to the IBT intervention.

Impact of Buprenorphine Dosage on the Occurrence of Relapses in Patients with Opioid Dependence

Objectives: Buprenorphine (BUP) is used in opioid maintenance treatment (OMT) for opioid-dependent patients. Previous real-world evidence suggests that many patients receive lower BUP dosage than recommended, with 38% of patients receiving <6 mg BUP per day. The goal of this research is to evaluate the impact of BUP dosage on the risk of relapses in the real world. Methods: This study was based on German claims data of 4 million patients. Patients identified by International Classification of Diseases, 10th Edition F11.2 (opioid dependence) between 2011 and 2012 and at least one BUP prescription were selected for this study (n = 364) and followed up over 4 years. Patients were assigned to 6 dosage groups, with <6 mg/day serving as low dosage/reference category. The impact of dosage on the occurrence of relapses (indicated by treatment interruption of >3 months without OMT prescription or hospital admissions) was examined using multivariate logistic regression. Age, gender, comorbidities, fixed/variable dosing, and up-dosing were used as covariates. Results: Results showed a protective effect of higher BUP as higher BUP dosages were significantly associated with a lower risk of relapse. Using low dosage (<6 mg/day) as the reference category, ORs were 0.40 (95% CI 0.19–0.87) at 6–<8 mg/day, 0.28 (0.15–0.56) at 8–<10 mg/day, 0.26 (0.10–0.67) at 10–<12 mg/day, 0.40 (0.18–0.92) at 12–<16 mg/day, and 0.18 (0.09–0.37) at ≥16 mg/day. No covariate showed a significant effect on the probability of relapse. Conclusions: The present study used a large German health claims dataset to confirm that higher BUP dosages are a protective factor for avoiding relapses in opioid-dependent patients, thus highlighting the importance of adequate BUP dosing in relapse prevention.

Buprenorphine\u2013cannabis interaction in patients undergoing opioid maintenance therapy

Buprenorphine is a partial μ-opioid agonist widely used for opioid maintenance therapy (OMT). It is mainly metabolized to pharmacologically active norbuprenorphine by the cytochrome P450 (CYP) isozyme 3A4. This may give rise to drug–drug interactions under combinations with inhibitors or inducers of CYP3A4. Cannabis is a potential inhibitor of CYP3A4, and there is a large degree of concomitant cannabis use among OMT patients. We performed a retrospective analysis on liver healthy OMT patients substituted with buprenorphine, either with (n = 15) or without (n = 17) concomitant use of cannabis. Patients with additional illicit drugs or medications affecting CYP3A were excluded. Measured blood concentrations of buprenorphine and norbuprenorphine were compared between the two groups. Cannabis users and non-users received similar doses, but users had 2.7-fold higher concentrations of buprenorphine (p < 0.01) and 1.4-fold for norbuprenorphine (1.4-fold, p = 0.07). Moreover, the metabolite-to-parent drug ratio was 0.98 in non-users and 0.38 in users (p = 0.02). Female gender did not produce significant effects. These findings indicate that cannabis use decreases the formation of norbuprenorphine and elevates buprenorphine and norbuprenorphine concentrations in blood most probably by inhibition of CYP3A4. The pharmacokinetic interaction may give rise to enhanced or altered opioid activity and risk of intoxications. Physicians should inform patients about this risk and supervise cannabis users by regular control of buprenorphine blood levels, i.e., by therapeutic drug monitoring.

&lt;p&gt;An Inverse Relationship Between Alcohol and Heroin Use in Heroin Users Post Detoxification&lt;/p&gt;

BackgroundGiven that fewer than 50% of countries provide Opioid Agonist Maintenance Therapies (OAMT), it is important to assess whether other substances act as a substitute for heroin in recovering heroin users who receive detoxification models of treatment. There is a dearth of prospective studies from low-and-middle-income countries evaluating these patterns of substance use.Methods300 heroin users from the Gauteng province of South Africa were assessed on entry into inpatient detoxification and then followed-up 3 and 9 months after leaving treatment. Treatment consisted of 1 week of detoxification followed by 6–8 weeks of psychosocial therapy. We measured the overall changes in the prevalence of heroin, alcohol and other drug use at baseline and postrehabilitation. Comparison of these outcomes at enrolment, 3 months and 9 months was performed by a Generalised Estimating Equation (GEE) with the outcome as the dependent variable, observation point as the independent variable, and participant as the repeated measure. Injecting status and treatment completion were included as covariates. We also measured the individual pathways between heroin and alcohol use in the 210 participants that were seen at all three timepoints.ResultsOf the original cohort, 252 (84.0%) were re-interviewed at 3 months and 225 (75.0%) at 9 months. From baseline to 3 months, the proportion of past month heroin users decreased significantly to 65.5%; however, during this time, the proportion of past month alcohol users increased from 16.3% to 55.2% (p<0.0001). When assessing the pathways between heroin and alcohol use at an individual level, 55.4% (n-97) of those who were past month alcohol abstinent prior to rehabilitation were using alcohol at 3 months. From 3 to 9 months the proportion of heroin users increased to 72.4% (p<0.0001), and during this time, the proportion of alcohol users decreased.ConclusionAfter detoxification, a significant reduction in heroin use was observed with a concomitant increase in alcohol consumption. Under these circumstances, alcohol may have acted as a substitute for heroin in the short term. The initial reduction in heroin use 3 months postrehabilitation was followed by increased consumption 6 months later. This observation supports the need for interventions to prevent, monitor and treat high levels of alcohol use in heroin users post detoxification. The provision of OAMT is a necessary consideration to address both the risk of increased alcohol intake as well as the decline in heroin abstinence rates.

Opioid and Polydrug Use Among Patients in Opioid Maintenance Treatment.

PurposeOpioid maintenance treatment reduces a person’s use of heroin. However, frequent substance use in treatment is a problem.AimTo examine the association between opioid maintenance treatment and opioid/polydrug use, and whether social factors, adverse experiences, social resources, and quality of life are associated with opioid/polydrug use during the first 12 months in treatment.Patients and MethodsForty-seven participants from treatment units in Bergen, Norway participated in five waves of data collection. Every third month, a structured face-to-face interview collected self-reported data on sociodemographic characteristics, opioid/polydrug use, participants’ social resources or adverse experiences, and quality of life. Data were collected as part of KVARUS, the National Quality Register for Substance Abuse Treatment. A multilevel binary logistic regression analysis was conducted to examine the association of opioid/polydrug use and time in current treatment. The analysis included regressions of opioid/polydrug use on time-invariant baseline adverse experiences and social resources, and time-varying reports of quality of life.ResultsThere was a significant negative association between time in treatment and use of opioids, b =−0.89, SE = 0.19, p = <0.01. Furthermore, a negative association of age at substance use on polydrug use was found, b =−0.40, SE =0.19, p = 0.03. A higher overall quality of life was significantly associated with lower odds of opioid use during opioid maintenance treatment, b = −0.62, SE = 0.23, p = < 0.01. Social dimensions, participants’ adverse experiences, and social resources were not associated with polydrug or opioid use.ConclusionOpioid maintenance treatment is associated with lowered opioid use, but to a lesser degree with polydrug use. Our findings add quality of life as an important factor that should be given particular attention because it can offer insight to aspects that can affect the patients’ opioid use.

Aerobic Exercise Interventions for Patients in Opioid Maintenance Treatment: A Systematic Review.

Background:Opioid maintenance treatment (OMT) is the standard for treatment of opioid use disorder, but some individuals on OMT experience disrupted sleep, heightened sensitivity to pain, and continued relapse to non-medical opioid use. An adjunctive treatment that has potential to address these shortcomings of OMT is aerobic exercise.Objective:The aim of the present review was to identify and evaluate components of aerobic exercise interventions targeting OMT patients.Methods:For this PROSPERO-registered review (ID CRD42020139626), studies were identified via electronic bibliographic databases, funded research (NIH RePORTER) and clinical trials databases (ClinicalTrials.gov), and reference sections of relevant manuscripts. Studies that evaluated the effects of an aerobic exercise intervention using a comparison condition or pretest-posttest design in adult OMT patients were included.Results:Of 2971 unique records, three primary studies and one supplemental manuscript comprised the final sample. All studies were randomized trials involving supervised exercise interventions enrolling small samples of middle-aged OMT patients. Exercise interventions included a variety of aerobic and non-aerobic activities (e.g. flexibility exercises), and none controlled the dose of aerobic exercise. Few studies used objective measures of physical activity or cardiorespiratory fitness and there were no significant effects of adjunctive exercise on substance use outcomes, but tests of the latter were likely underpowered.Conclusions:Though early in the accumulation of evidence, interventions targeting aerobic exercise for OMT patients appear feasible, acceptable to patients, and beneficial. Longer-term studies that employ larger samples, include assessments of behavioral and biological mechanisms of change, more rigorous measurement of physical activity, and controlled doses of aerobic activity are warranted.

678: Comparison of Opioid Maintenance Therapy (OMT) on prenatal and postnatal growth effects

678: Comparison of Opioid Maintenance Therapy (OMT) on prenatal and postnatal growth effects

The evolution of addiction treatment and harm reduction programs in Iran: a chaotic response or a synergistic diversity?

Iran has 2.1 and 1.8% of its 15-64-year-old population living with illicit substance and opioid use disorders, respectively. To address these problems, Iran has been developing a large and multi-modality addiction treatment system, spanning the time before and after the Islamic Revolution. Iran's current drug treatment scene is a combination of services, ranging from medical/harm reduction services to punitive/criminal justice programs. Included in this array of services are drop-in centers providing low-threshold harm reduction services, such as distribution of sterile needles and syringes; opioid maintenance treatment clinics providing methadone, buprenorphine and opium tincture; and abstinence-based residential centers. We will review the evolution of this system in four phases. In 1980, Iran's revolutionary government shut down all voluntary treatment programs and replaced them with residential correctional programs. The first shift in the addiction treatment policies came 15years later after facing the negative consequences. Addiction is viewed as a disease, and new voluntary treatment centers offering non-agonist medications and psychosocial services were established. With an increased number of people who inject drugs and HIV/AIDS epidemics, in the second shift an extensive move towards harm reduction strategies and opioid-maintenance programs has been implemented to reduce HIV-related high-risk behavior. The emergence of a methamphetamine use crisis creating an increased number of socially marginalized addicted people resulted in public and political demands for stricter policies and ended in the third shift starting in 2010, with extended compulsory court-based residential programs. Currently, there is a new shift towards reducing the severity of criminal penalties for drug use/sales and promoting proposals for opium legalization. Iran's evolutionary experience in developing a large addiction treatment program in a complex combination of medical/harm reduction and punitive/criminal justice addiction treatment can be examined in its political, clinical and pragmatic context.

It is just that people treat you like a human being: The meaning of dignity for patients with substance use disorders.

Patients who suffer from substance use disorder (SUD) might receive services from different service providers in an opioid maintenance treatment programme (OMT) and have a widespread and complex need for nursing. Literature reveals that prejudices against people with SUD exist. There is a lack of studies exploring patients with SUD experiences of preserving their dignity in the encounter with healthcare staff. The aim of the study was to gain insight into the meaning of dignity for patients with SUD. The research design was descriptive and interpretative. In the interpretation of qualitative in-depth interviews with six patients, a hermeneutical approach based on Gadamer (Truth and method, Sheed & Ward, London, UK, 1989) was used. Analysis resulted in three mains themes about the meaning of dignity: (a) The material dimension. (b) To be respected by others. (c) The inner experience. Factors enhancing dignity in the encounters were as follows: (a) Being respected and acknowledged. (b) Being cared for. (c) Knowledge and persistent relation. Factors depriving dignity were as follows: (a) Stigma and prejudice. (b) Insufficient relations and lack of confirmation. (c) Experiencing disrespectful/patronising attitudes and lack of knowledge. The material dimension of dignity containing an aesthetically aspect was important for these patients. Dignity was also experienced as strongly connected to respect. Dignity can be enhanced by treating patients with SUD with understanding and respect, and dignity can be inhibited through stigmatization of patients with SUD, as well as by caregivers' lack of knowledge. The study clarifies a need for more knowledge about SUD among healthcare staff, as well as promotes ethical awareness in encounters with patients regardless of their background.

Quality of life and well-being from the perspective of patients on opioid agonist maintenance treatment: study protocol for a systematic review of qualitative research and a scoping review of measures

BackgroundOpioid agonist maintenance treatment (OAMT) is a first-line treatment for heroin dependence, but its effectiveness has been assessed primarily through clinical outcomes with a limited attention to patient perspectives. Despite the increased use of patient reported outcome measures their patient-centeredness is highly questionable. This is the protocol of a systematic review of qualitative research on how OAMT users construct the meaning of their quality of life and well-being and a scoping review of instruments that measure these domains.MethodsWe will conduct a systematic review of qualitative research exploring the views of quality of life of patients on OAMT (registration number CRD42018086490). According pre-specified eligibility criteria, we will include studies from a comprehensive search of bibliographical databases from their inception. We will extract data from included studies and assess their risk of bias with the CASP appraisal criteria, and will implement a thematic analysis to generate a set of interpretative analytical themes ascertaining their confidence using the CERQual approach. We will implement similar methods to conduct a scoping review to assess to what extent the existing measures of these domains were focused on user’s views, assessing their validity using the COSMIN methodology, and summarizing their characteristics and level of patient centeredness.ConclusionThe findings from the reviews will contribute to obtain a genuine understanding of the perspective from users on OAMT regarding their perception of well-being and quality of life and will likely lead to greater patient centeredness when assessing such variables, which in turn may contribute to a more patient-centered care.

Opioid use disorder in Germany: healthcare costs of patients in opioid maintenance treatment

BackgroundOpioid Use Disorder (OUD) is a substance use disorder with a chronic course associated with comorbid mental and somatic disorders, a high burden of psychosocial problems and opioid maintenance treatment (OMT) as a standard treatment. In the US, OUD imposes a significant economic burden on society, with annual societal costs estimated at over 55 billion dollars. Surprisingly, in Europe and especially in Germany, there is currently no detailed information on the healthcare costs of patients with OUD. The goal of the present research is to gather cost information about OUD patients in OMT with a focus on maintenance medication and relapses.MethodsWe analysed health claims data of four million persons covered by statutory health insurance in Germany, applying a cost-of-illness approach and aimed at examining the direct costs of OMT patients in Germany. Patients with an ICD-10 code F11.2 and at least one claim of an OMT medication were stratified into the treatment groups buprenorphine, methadone or levomethadone, based on the first prescription in each of the follow-up years. Costs were stratified for years with and without relapses. Group comparisons were performed with ANOVA.ResultsWe analysed 3165 patient years, the total annual sickness funds costs were on average 7470 € per year and patient. Comparing costs of levomethadone (8400 €, SD: 11,080 €), methadone (7090 €, SD: 10,900 €) and buprenorphine (6670 €, SD: 7430 €) revealed significant lower costs of buprenorphine compared to levomethadone (p < 0.0001). In years with relapses, costs were higher than in years without relapses (8178 € vs 7409 €; SD: 11,622, resp. 10,378 €). In years with relapses, hospital costs were the major cost driver.ConclusionsThe present study shows the costs of OUD patients in OMT for the first time with a German dataset. Healthcare costs for patients with an OUD in OMT are associated with more than two times the cost of an average German patients. Preventing relapses might have significant impact on costs. Patients in different OMT were dissimilar which may have affected the cost differences.

Clinical Effectiveness of Decision Support for Prescribing Opioids for Chronic Noncancer Pain: A Prospective Cohort Study

ObjectivesThis prospective cohort study examines the clinical effectiveness of electronic medical record clinical decision support (EMR CDS) for opioid prescribing. MethodsData analysis included primary care patients with chronic opioid therapy for noncancer pain seen within an integrated health delivery system in Louisiana between January 2017 and October 2018. EMR CDS incorporated an opioid health maintenance tool to display the status of risk mitigation, and the medication order embedded the morphine equivalent daily dose (MEDD) calculator and a hyperlink to the Louisiana pharmacy drug monitoring program. Outcome measures included change in the average MEDD and rates of opioid risk mitigation, hospitalization, and emergency department use. ResultsAmong 14 221 patients, 9% had prescriptions with an average MEDD ≥90 mg. There were no significant changes in MEDD after EMR CDS implementation. Increasing age, Charlson Comorbidity Index score, female sex, black non-Hispanic race, non-opioid pain medication co-prescriptions, and specialty referrals were associated with a lower odds of MEDD ≥90 (high-dose threshold). Medicare or self-pay, substance abuse history, and pain agreements were associated with increased odds of prescribing above this high-dose threshold. After incorporation of EMR CDS, patients had higher rates of urine drug screens (17% vs 7%) and naloxone prescriptions (3% vs 1%, all P < .001). In addition, specialty referrals to physical or occupational therapy, orthopedics, neurology, and psychiatry or psychology increased in the postintervention period. Although emergency department use decreased (rate ratio 0.92; 95% confidence interval 0.89-0.95), hospitalization rates did not change. ConclusionsEMR CDS improved adherence to opioid risk mitigation strategies. Further research examining which practice redesign interventions effectively reduce high-dose opioid prescribing is needed.

Incidence and predictors of drug overdoses among a cohort of >10,000 patients treated for substance use disorder

BackgroundDrug overdoses remain a significant public health burden throughout the world. This study assessed the incidence and predictors of non-fatal and fatal drug overdoses among patients with an opioid use, treated for drug use disorders (DUD) at public treatment centers in Denmark. MethodsA consecutive cohort of patients (n = 11,199) were tracked from date of first registered enrollment between the year 2000 and 2010 to first registered drug overdose, death or December 31st 2010, whichever occurred first. Competing-risks regression models were fitted to estimate the sub hazard ratios (SHRs) of non-fatal and fatal drug overdoses and confounding risk factors. ResultsA total of 3186 (28%) patients experienced a non-fatal drug overdose during follow-up, and 572 (6%) died from an overdose. Use of benzodiazepines (SHR: 1.15 95% CI 1.03, 1.28) was significantly associated with non-fatal overdose. Intravenous drug use and previous hospitalization for a non-fatal overdose increased the risk of later non-fatal (SHR: 1.57 95% CI 1.42, 1.73) and fatal overdoses (SHR: 1.43 95% CI 1.12, 1.82). ConclusionsPatients who use opioids remain at risk of overdoses for a long time after discharge from drug treatment. Besides relevant monitoring and psychosocial support in opioid maintenance treatment, there is a need for informing and educating opioid users in risk factors and preventive measures in settings where they are often difficult to access for traditional treatment services.

Higher Social Rejection Sensitivity in Opioid-Dependent Patients Is Related to Smaller Insula Gray Matter Volume: A Voxel-Based Morphometric Study.

Opioid-dependent patients are highly sensitized to negative social feedback, and increased social rejection sensitivity was linked to adverse treatment outcome, but its neurobiological underpinnings have not been understood yet. The present study investigated gray matter (GM) volume differences between 19 opioid maintenance treatment (OMT) patients and 20 healthy controls using magnetic resonance imaging and voxel-based morphometry. Associations of GM volumes with subjective feelings of exclusion and inclusion during a social ostracism (Cyberball) paradigm, with rejection sensitivity, social interaction anxiety and social phobia were explored. OMT patients displayed smaller GM volume in the bilateral insula and inferior frontal gyri. Psychometric and task data showed that patients reported significantly higher rejection sensitivity, social anxiety and social phobia scores and felt more excluded and less included during the social ostracism paradigm. Smaller GM volume in the insula was associated with higher subjective exclusion, lower subjective inclusion and higher rejection sensitivity, social anxiety and social phobia scores. Findings indicate that structural deficits in emotion- and anxiety-processing brain regions in OMT patients are associated with increased social rejection sensitivity. As social rejection is a potential trigger for relapse, patients might benefit from therapeutic strategies that promote social integration.

The Impact of Hepatitis C Virus Infection on Buprenorphine Dose in Pregnancy.

Buprenorphine (BUP) is commonly used for opioid maintenance therapy in pregnancy. Our goal was to determine whether liver dysfunction related to hepatitis C virus (HCV) infection impacts BUP dosing requirements in pregnancy. This was a retrospective cohort study of pregnant women with antenatal exposure to BUP to compare dosing between individuals positive versus negative for HCV infection. Spearman correlation tests were used to assess the relationship between BUP dose and HCV status. HCV infection was present in 103 (39%) of the patients. Patients with HCV infection required lower dose increases of BUP throughout pregnancy (p = 0.02). HCV viral load was positively correlated with the liver enzymes aspartate transaminase (r = 0.30, p = 0.003) and alanine transaminase (r = 0.25, p = 0.01). There was a negative correlation between HCV viral load and BUP dose during the second trimester (r = -0.27, p = 0.01) and third trimester (r = -0.20, p = 0.04). Women with HCV infection required less of an increase in BUP dose throughout pregnancy compared with women without HCV infection. Severity of HCV infection, as measured by viral load and liver enzymes, was also associated with BUP dosing.

Harm reduction drug policy in Israel: what has been accomplished and what still needs to be done?

The leading formal drug policy in Israel is the traditional approach of abstinence, probation, and punitive measures based on three main pillars: Enforcement, Treatment and Rehabilitation, and Prevention. However, under the treatment pillar, Israel has adopted a number of harm reduction services, focused mostly on people who use heroin and people who inject drugs. These include Methadone Maintenance Treatment, Buprenorphine Maintenance Treatment, and Needle and Syringe Exchange Programs. More specialized services are designated mostly for people who use drugs, who frequent the largest open drug scene in Tel-Aviv. These include a health clinic, an emergency apartment for female addict sex-workers, and a ‘First Step’ center. Even so, the harm reduction approach has remained controversial, stigmatized, and is considered a sub-category for total-abstinence treatment in Israel. This paper follows the evolution of harm reduction interventions in Israel among people who use drugs and sheds light on the lack of a comprehensive, well-planned, formal national harm reduction drug policy. Additionally, this article expresses concern over the uncertain future of Israel’s comprehensive and balanced drug treatment policies caused by the structural changes in abolishing the Israel Anti-Drug Authority, the statutory authority and central body in Israel that promoted and coordinated all national policies related to treatment and harm reduction.ConclusionsAlthough it is a major challenge to translate worldwide evidence and research findings into action and social change, recommendations are offered to implement a comprehensive harm reduction drug policy led by a multidisciplinary group of policy-makers across all areas of drug policy. These focus on expanding and developing more services for Opioid Maintenance Therapy patients and people who inject drugs as well as a national effort to reduce high levels of stigma and discrimination against them, encompassing other common substances and focusing on populations such as adolescents and young adults that engage in other types of substance use such as cannabis, amphetamine-type stimulants, and hallucinogens.