Is opioid substitution treatment beneficial if injecting behaviour continues?

Background

Opioid substitution treatment (OST) is recognised as an effective treatment for opioid dependence. Still, a subgroup of OST users continues to inject drugs. This study examines health risks and criminal activity in a population of needle exchange programme (NEP) participants by comparing those identified as current OST users to (i) those identified as former OST users and (ii) those with no OST experience.

Methods

This was a semi-annual cross-sectional study conducted from 2002 to 2011. NEP participants were interviewed in Oslo, Norway (n = 1760); 341 were identified as current OST users, 356 as former OST users and 1063 had no OST experience. The associations between OST status and health risk and criminal activity were assessed through univariate and multiple logistic regression analyses.

Results

Among NEP participants, those currently in OST had fewer non-fatal overdoses (OR = 0.5 [95% CI 0.3, 0.9]) compared to former OST users and those never in OST. Additionally, they were less likely to have injected frequently (OR = 0.4 [95% CI 0.3, 06]), to have used heroin daily or almost daily (OR = 0.3 [95% CI 0.2, 0.4]), and to have committed theft (OR = 0.6 [95% CI 0.4, 1.0]) and engaged in drug dealing (OR = 0.7 [95% CI 0.5, 0.9]) in the past month. Overall, there was a high level of polysubstance use and no group differences on this measure.

Conclusions

NEP participants who are currently in OST have substantially reduced health risks and criminal activity than other NEP participants. The high level of polysubstance use nevertheless poses a public health challenge.     

Self-perceived problem with alcohol use among opioid substitution treatment clients

Background and aim

Excessive alcohol use increases mortality and morbidity among opioid substitution therapy (OST) clients. Regular attendance for OST dosing presents key opportunities for screening and treatment. However, individuals' perception of their alcohol consumption as problematic or otherwise may impact their willingness to change. This study examines patterns of alcohol consumption among OST clients, perceptions of their own use and correlates of excess consumption.

Methods

Confidential, structured interviews were conducted with 264 clients of two Sydney OST clinics. Alcohol consumption was assessed using the Alcohol Use Disorders Identification Test (AUDIT); and illicit drug dependence with the Severity of Dependence Scale.

Results

Forty-one percent of the participants scored ≥ 8 on the AUDIT (‘AUDIT-positive’), indicating excessive alcohol use. The higher a participant's AUDIT score, the more likely they were to demonstrate insight into the potential problems associated with their drinking (linear trend, p < 0.01). However, only half of AUDIT-positive participants believed they drank too much and/or had a problem with alcohol. One-third had discussed their drinking with OST staff, and a similar proportion reported a history of alcohol treatment. AUDIT-positive participants were more likely than others to be classified as dependent on an illicit drug in the last six months (AOR = 1.76, 95% CI:1.00–3.09), report a history of alcohol treatment (AOR = 5.70, 95% CI:2.83–11.48) and believe it is safe to drink 4 + standard drinks in one session (AOR = 5.30, 95% CI:2.79–10.06).

Conclusions

OST clients with AUDIT scores ≥ 8 appear to underestimate the risks associated with their alcohol consumption. Regular assessments of alcohol use and targeted brief alcohol interventions may improve health outcomes among OST clients.     

Client incentives versus contracting and staff incentives: How care continuity interventions in substance abuse treatment can improve residential to outpatient transition

Interventions for improving transition from short-term residential to outpatient treatment were examined. Usual care (UC; n = 114) was referral to a preferred outpatient program with advance appointment optional. Client incentive (CI; n = 97) offered up to $100 in gift cards for intake and attendance during the first 30 days of treatment. Contracting with staff incentives (CSI; n = 49) consisted of meeting with an outpatient counselor prior to residential discharge, signing an attendance contract, receiving an appointment and payment to staff if clients attended. CSI significantly improved rates of successful transition (84%) and admission (74%) compared to UC (64% contact; 49% admitted). CI did not result in significantly improved outcomes (74%; 60%). CSI was likely mediated by the reliability (92 versus 52% in UC) and immediacy (1.0 versus 3.9 days) of appointment scheduling. This study supports use of CSI for improving rates of transition between residential and outpatient continuing care treatment.     

Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence

Opioid substitution treatment (OST) for opioid dependence may be limited by adverse events (AEs). Increasing the range of therapeutic options optimizes outcomes and facilitates patient management. An international, multi-center, two-phase study investigated the efficacy and safety of slow-release oral morphine (SROM) versus methadone in patients receiving methadone therapy for opioid dependence. In phase 1 (two way cross-over, 11 weeks each period) patients were randomized to SROM or methadone oral solution. In phase 2 (25 weeks), patients continued treatment with SROM (group A) or switched from methadone to SROM (group B). In total, 211 out of 276 completed phase 1 and 198 entered phase 2 (n = 95 group A, n = 103 group B). Treatment with both SROM and methadone was well tolerated. However, the mean QTc-interval associated with methadone was significantly longer than that under SROM. Higher treatment satisfaction, fewer cravings for heroin, and lower mental stress were reported with SROM. This study adds a significant further weight of evidence that SROM is an effective and well tolerated long-term maintenance treatment for opioid dependence with a beneficial risk profile compared to methadone regarding cardiac effects and supports its clinical utility.     

A cognitive behavioral smoking abstinence intervention for adults with chronic pain: A randomized controlled pilot trial

Current evidence suggests it may be difficult for patients with chronic pain to quit smoking and, based on previous formative work, a 7-session individual and group-based cognitive behavioral (CB) intervention was developed. The primary aim of this randomized controlled pilot trial was to test the hypothesis that abstinence at month 6 would be greater among patients with chronic pain who received the CB intervention compared to a control condition. Upon admission to a 3-week interdisciplinary pain treatment (IPT) program, patients were randomized to receive the CB intervention (n = 30) or the control condition (n = 30). The 7-day point prevalence of self-reported smoking status was assessed at week 3 (upon completion of the 3-week IPT program) and at month 6 in an intent-to-treat analysis. At week 3, 30% (n = 9) of patients in the CB condition were abstinent from smoking compared to 10% (n = 3) in the control group (P = .104). At month 6, 20% (n = 6) of patients who received the CB intervention were abstinent compared to none in the control group (P = .024). At week 3, a significant group by time interaction effect was found where the CB patients experienced greater improvements in self-efficacy from baseline compared to the control group (P = .002). A greater proportion of patients randomized to the CB group completed the IPT program (P = .052). The findings of this pilot trial suggest that integration of a CB-based smoking abstinence intervention into ongoing pain therapy may be an effective treatment for smokers with chronic pain.     

Referral for substance abuse treatment and depression improvement among patients with co-occurring disorders seeking behavioral health services in primary care

This study examined the relationship between substance treatment referrals and depression improvement among 2,373 participants with concurrent substance use and depressive disorders enrolled in an integrated behavioral health program. Three groups of substance treatment referral status were identified: accessed treatment (n = 780), declined treatment (n = 315), and no referral for treatment (n = 1278). The primary outcome is improvement in depressive symptoms (PHQ-9 < 10 or ≥ 50% reduction). Using propensity score adjustments, patients accessing substance treatment were significantly more likely to achieve depression improvement than those who declined receiving treatment services (hazard ratio (HR) = 1.82, 95% confidence interval (CI): 1.50–2.20, p < 0.001) and those without a referral for treatment (HR = 1.13, 95% CI: 1.03–1.25, p = 0.014). Each 1 week delay in initiating a referral was associated with a decreased likelihood of depression improvement (HR = 0.97, 95% CI: 0.96–0.98, p < 0.001). Study findings highlight the need of enhancing early treatment contact for co-occurring substance use disorders in primary care.     

Naltrexone with or without guanfacine for preventing relapse to opiate addiction in St.-Petersburg,Russia

Background

Stress is a key precipitant to discontinuing naltrexone and relapsing to opiate abuse. Alpha-2 adrenergic agonists like guanfacine may reduce stress induced craving and have reduced opiate relapse in small clinical trials.

Methods

This randomized, double blind double dummy placebo-controlled 6-month trial tested oral naltrexone with or without guanfacine for reducing stress and preventing opiate relapse. We randomized 301 patients to: naltrexone 50 mg/day + guanfacine 1 mg/day (n = 75) (N/G), naltrexone + guanfacine placebo (N/P) (n = 76), naltrexone placebo + guanfacine (n = 75) (P/G), and double placebo (n = 75) (P/P).

Results

Among the 75 patients in each group the percentage still retained on naltrexone treatment at six months was: N/G 26.7%, N/P 19.7% (p = 0.258 to N/G), P/G 6.7% (p < 0.05 to both N groups), and P/P 10.7% (p = 0.013 to N + G). Guanfacine reduced the severity of stress particularly at weeks 10 and 18. Adverse events (AE) were infrequent (4.7%) without group differences, with most common AEs: headache, poor appetite, insomnia, and dizziness.

Conclusions

Adding guanfacine to naltrexone did not improve treatment retention or opiate free urines, but it reduced both stress and craving at later time points in treatment, which may be related to stress-induced craving and the animal model of incubation of reinstatement. During treatment, HIV risk, anxiety, and depression reduced among all patients in treatment, regardless of group.     

Epidemiologic and clinical survey of victims of centipede stings admitted to Hospital Vital Brazil (São Paulo, Brazil)

We retrospectively analyzed 98 proven cases of centipede stings admitted to Hospital Vital Brazil, Butantan Institute, São Paulo, Brazil, between 1990 and 2007. Most stings occurred at the metropolitan area of São Paulo city (n = 94, 95.9%), in the domiciles of patients (n = 67, 68.4%), and during the warm-rainy season (n = 60, 61.2%). The mean age of the victims was 32.0 ± 18.8-years-old. Cryptops and Otostigmus genera were responsible for most cases. Around 86% of the patients sought medical care within 6 h after the sting. Both lower (56.1 %) and upper limbs (41.8 %) were most frequently bitten, especially the feet and hands (89.8%). The most frequent local clinical manifestations were pain (94.9%), erythema (44.9%) and edema (21.4%), and the latter was mainly observed in patients bitten by Otostigmus spp. Supportive treatment was used in only 28.6% of the patients, namely administration of local anesthesia (9.2%) and systemic analgesia (13.3%). No sequels or complications were observed in patients, and the prognostic was benign.     

Ameliorative effects of SLC22A2 gene polymorphism 808 G/T and cimetidine on cisplatin-induced nephrotoxicity in Chinese cancer patients

To investigate the roles of SLC22A2 gene polymorphism 808 G/T and cimetidine on cisplatin-induced nephrotoxicity, a total of 123 Chinese cancer patients treated with cisplatin alone (n = 55) or in combination with cimetidine (n = 68) were genotyped. The changes of serum creatinine (SCr), blood urea nitrogen (BUN) and cystatin C levels were used as biomarkers for the evaluation of cisplatin-induced nephrotoxicity. The changes of BUN and SCr levels showed no significant difference between groups divided by genotypes and treatments (P > 0.05). However, patients with mutant genotype (GT/TT) or with cimetidine treatment had smaller increase of the cystatin C levels compared to those with wild genotype (GG) or without cimetidine treatment (P < 0.05). In the non-cimetidine-treated group, the changes of cystatin C level in patients with mutant genotype (GT/TT) was significantly smaller than those with wild genotype (GG) (P = 0.043). In the wild type group, the cystatin C level change of patients without cimetidine treatment was significantly larger than those with cimetidine treatment (P = 0.007). These results suggested that SLC22A2 gene polymorphism 808 G/T and cimetidine could attenuate cisplatin nephrotoxicity in Chinese cancer patients. But the renoprotection mechanism of cimetidine might be damaged by the mutation.     

Effects on substance use outcomes in adolescents receiving motivational interviewing for smoking cessation during psychiatric hospitalization

The purpose of this study was to compare substance involvement among psychiatrically hospitalized adolescent smokers who had received motivational interviewing (MI) versus brief advice (BA) for smoking cessation. One hundred and ninety-one (191) adolescent smokers (62.3% female; 15.4 years of age) were randomly assigned to MI (n = 116) or BA (n = 75). All patients were assessed at baseline, immediately after hospitalization, and at 1-, 3-, 6-, 9-, and 12-month follow-ups. Rates of substance use in the MI condition during follow-up increased from a low of 8.2% (SD = 18.5) to a high of 15.4% (SD = 30.0) substance use days, whereas in BA, substance use days increased from a low of 8.4% (SD = 20.8) to a high of 21.4% (SD = 35.2). The results of this study suggest that MI, relative to BA, for smoking cessation was associated with better substance use outcomes during the first 6 months following psychiatric hospitalization among adolescents. This finding is consistent with previous studies that have shown that smoking cessation does not have a detrimental effect on substance abuse treatment outcomes among youth.     

Rewarding early abstinence in Veterans Health Administration addiction clinics

This study investigates the addition of a contingency management (CM) intervention to Veterans Health Administration substance use disorders treatment on during- and post-treatment outcomes for Veterans diagnosed with alcohol dependence only (n = 191) or stimulant dependence (n = 139). Participants were randomly assigned to 8 weeks of usual care or usual care plus CM. Follow-up assessments occurred at 2, 6 and 12 months. In the alcohol dependent subgroup, CM participants submitted significantly more negative samples (13 versus 11 samples, Cohen's d = 0.54), were retained significantly longer (7 versus 6 weeks, d = 0.47), achieved significantly longer median durations of abstinence (16 versus 9 consecutive visits; median difference = 7, 95% CI = 4–8), and submitted significantly more negative samples at follow-ups (unstandardized effect size = 0.669, se = 0.2483) compared to usual care participants. Intervention effects were non-significant for the stimulant dependent subgroup. The study provides support for the effectiveness of CM interventions for alcohol dependent patients.     

Feasibility of buprenorphine and methadone maintenance programmes among users of home made opioids in Ukraine

BackgroundOpioid substitution therapy (OST) in the Ukraine was not provided until 2004. Methadone maintenance therapy only became available in May 2008. Injecting drug users in Ukraine are predominantly injecting self-made opioid solution (‘Shirka’). A feasibility study on buprenorphine and methadone maintenance treatment was conducted in 2008.MethodsA total of 331 opioid dependent patients were given buprenorphine (n = 191) or methadone (n = 140) as a substitute, and a survey of substance use, HIV transmission risks, and legal and social status was conducted at baseline and at six months follow-up.ResultsIllegal substance use, illegal activities, incomes and HIV related transmission risks were highly reduced, whereas employment rates and psychiatric problems improved. Retention was comparatively high among the patients in buprenorphine (84.8%) and in methadone maintenance treatment (85.0%) after six months of treatment.ConclusionThese data show the successful implementation of OST in the Ukraine among drug users who were predominantly injectors of self-made opioid solutions. Continuing scale-up of OST in the Ukraine is therefore both feasible and highly recommended.     

Feasibility and impact of brief interventions for frequent cannabis users in Canada

Cannabis use is prevalent among young people, and frequent users are at an elevated risk for health problems. Availability and effectiveness of conventional treatment are limited, and brief interventions (BIs) may present viable alternatives. One hundred thirty-four young high-frequency cannabis users from among university students were randomized to either an oral (C-O; n = 25) or a written experimental cannabis BI (C-W; n = 47) intervention group, or to either an oral (H-O; n = 25) or written health BI (H-W; n = 37) control group. Three-month follow-up assessments based on repeated measures analysis of variance techniques found a decrease in the mean number of cannabis use days in the total sample (p = 0.024), reduced deep inhalation/breathholding use in the C-O group (p = 0.003), reduced driving after cannabis use in the C-W group (p = 0.02), and a significant reduction in deep inhalation/breathholding in the C-O group (p = 0.011) compared with controls. Feasibility and short-term impact of the BIs were demonstrated, yet more research is needed.     

Evaluation of the Architect tacrolimus assay in kidney,liver, and heart transplant recipients

The narrow therapeutic range of tacrolimus requires therapeutic drug monitoring to prevent transplant rejection and to minimize nephrotoxicity. The aim of this study was to evaluate the analytical performance of the tacrolimus chemiluminescent microparticle immunoassay (CMIA) in everyday practice comparatively with other methods. CMIA imprecision and accuracy were tested using low, medium, and high concentrations in control samples. The limits of quantification (LOQ) of CMIA and antibody-conjugated magnetic immunoassay (ACMIA) were evaluated using negative whole-blood samples containing 0.4–5.7 ng/ml of tacrolimus from a stock solution. CMIA was compared with ACMIA, enzyme multiplied immunoassay (EMIT), and liquid chromatography–tandem mass spectrometry (LC–MS/MS), using 176 samples from recipients (135 men and 41 women) of heart (n = 19), kidney (n = 107), or liver (n = 50) transplants. CMIA total precision was 5.7%, 3.7% and 3.6% with the low-, medium-, and high-concentration controls, respectively; corresponding values for accuracy were 98%, 104%, and 104%. LOQ was 0.5 (95%CI, 0.22–1.38) with CMIA and 2.5 ng/ml with ACMIA. Linear regression results were as follows: CMIA = 1.2LC–MS/MS + 0.14 (r = 0.98); CMIA = 0.93EMIT + 0.36 (r = 0.975); CMIA = 1.15ACMIA − 0.25 (r = 0.988); and, for tacrolimus concentrations in the 1–15 ng/ml range, of special interest as many transplant recipients are given low-dose tacrolimus, CMIA = 1.05LC–MS/MS + 0.38 (r = 0.94). Two patients had falsely elevated tacrolimus concentrations due to interference in the ACMIA assay; one was a renal transplant recipient who stopped her treatment and had tacrolimus concentrations of 12.5 ng/ml by ACMIA and <0.5 ng/ml by CMIA; the other was an HIV-positive renal transplant recipient whose tacrolimus concentrations by ACMIA were 1.8–43.7-fold those by CMIA. Such interferences with ACMIA, which may be related to endogenous antibodies in the plasma, are likely to negatively impact patient care. In conclusion, the tacrolimus CMIA assay is suitable for routine laboratory use and does not suffer from the interferences seen with ACMIA in some patients.     

Criminal justice referral and incentives in outpatient substance abuse treatment

A substantial number of substance abusers entering outpatient psychosocial counseling treatment are referred from the criminal justice (CJ) system. This secondary analysis of previously published findings from a large (N = 415) multi-site trial of a prize-based abstinence incentive intervention ( Petry et al., 2005) examined the influence of CJ referral on usual care outcomes and response to the incentive procedure. CJ referrals (n = 138) were more likely than those not CJ referred (n = 277) to provide stimulant negative urine samples whether missing samples were counted as positive (50 versus 41%, p = .016) or as missing (96 versus 91%, p < .001). A significant interaction term was found only for percentage of treatment completers (p = .027). However, on that retention variable, and three additional drug use measures, significant incentive effects were confined to participants who entered treatment without referral from the criminal justice system. The study suggests that abstinence incentives should be offered as a first priority to stimulant users entering treatment without criminal justice referral. However, incentives can be considered for use with CJ-referred stimulant users based on the observation that best outcomes were obtained in CJ referrals who also received the abstinence incentive program.     

"Should I stay or should I go?" Coming off methadone and buprenorphine treatment

Background

This study aimed to investigate patient perspectives regarding coming off maintenance opioid substitution treatment (OST). The study explored previous experiences, current interest and concerns about stopping treatment, and perceptions of how and when coming off treatment should be supported.

Methods

A cross-sectional survey was used. Participants were 145 patients receiving OST at public opioid treatment clinics in Sydney, Australia.

Results

Sixty-two percent reported high interest in coming off treatment in the next 6 months. High interest was associated with having discussed coming off treatment with a greater number of categories of people (OR = 1.72), not citing concern about heroin relapse (OR = 3.18), and shorter duration of current treatment episode (OR = 0.99). Seventy-one percent reported previous withdrawal attempts and 23% had achieved opioid abstinence for ≥3 months following a previous withdrawal attempt. Attempts most commonly involved jumping off (59%), and doctor-controlled (52%) or self-controlled (48%) gradual reduction. For future attempts respondents were most interested in doctor-controlled (68%) or self-controlled (41%) gradual reduction. Concerns regarding coming off treatment included withdrawal discomfort (68%), increased pain (50%), and relapse to heroin use (48%).

Conclusion

While some patients may require lifetime maintenance, the issue of coming off treatment is important to many patients and should be discussed regularly throughout treatment and where appropriate supported by a menu of clinical options.     

Leaving buprenorphine treatment: Patients' reasons for cessation of care

Many opioid-dependent patients leave treatment prematurely. This study is a planned secondary analysis from a randomized trial of counseling for African Americans (N = 297) entering buprenorphine treatment at one of two outpatient programs. This study examines: (1) whether patients’ initial treatment duration intentions prospectively predict retention; and (2) patients’ reasons for leaving treatment. Participants were queried about their treatment duration intentions at treatment entry, and their reasons for leaving treatment at 6-month follow-up. At baseline, 28.0% reported wanting to stay in buprenorphine treatment less than 6 months, while 42.1% actually left buprenorphine treatment within 6 months. However, participants intending short-term buprenorphine at the outset were not at elevated risk of early treatment discontinuation (OR = 1.15; p = .65). Participants attributed treatment cessation predominantly to conflicts with staff, involuntary discharge, and perceived inflexibility of the program. Future research should examine patient-centered models of buprenorphine treatment that could improve retention.     

In vitro activity of S-(3,4-dichlorobenzyl)isothiourea hydrochloride and novel structurally related compounds against multidrug-resistant bacteria, including Pseudomonas aeruginosa and Burkholderia cepacia complex

The aim of this study was to establish the antimicrobial activities of S-(3,4-dichlorobenzyl)isothiourea hydrochloride (A22) and a series of structurally related compounds against multidrug-resistant (MDR) bacteria. The minimum inhibitory concentrations (MICs) of 21 compounds were determined against 18 strains of pathogenic bacteria in addition to Pseudomonas aeruginosa (n = 19) and Burkholderia cepacia complex (BCC) (n = 20) isolated from the sputa of cystic fibrosis patients. Selected compounds were tested against further isolates, including P. aeruginosa (n = 100), BCC (n = 12) and Stenotrophomonas maltophilia (n = 19). The interaction of S-(4-chlorobenzyl)isothiourea hydrochloride (C2) in combination with conventional antimicrobials was examined against 10 P. aeruginosa strains. Selected compounds were also tested against Enterobacteriaceae producing NDM-1 carbapenemase (n = 64) and meticillin-resistant Staphylococcus aureus (MRSA) (n = 37). Of the 21 compounds, 14 showed antimicrobial activity that was generally more pronounced against Gram-negative bacteria. Against P. aeruginosa, the most active compound was C2 [MIC for 50% of the organisms (MIC₅₀) = 32 μg/mL]. This compound was also the most active against BCC, with all isolates inhibited by 64 μg/mL. For all ten strains of P. aeruginosa subjected to combination testing with C2 and conventional antimicrobials, a bactericidal effect was achieved with at least one combination. C2 and A22 both showed strong activity [MIC for 90% of the organisms (MIC₉₀) = 4 μg/mL] against Enterobacteriaceae that produced NDM-1 carbapenemase. Finally, S-(4-chlorobenzyl)-N-(2,4-dichlorophenyl)isothiourea hydrochloride showed good activity (MIC₉₀ = 8 μg/mL) against MRSA. This work establishes the activity of isothiourea derivatives against a broad range of clinically important MDR bacteria.