Seonaid Nolan

The impact of methadone maintenance therapy on hepatitis C incidence among illicit drug users

AIMS To determine the relationship between methadone maintenance therapy (MMT) and hepatitis C (HCV) seroconversion among illicit drug users. DESIGN A generalized estimating equation model assuming a binomial distribution and a logit-link function was used to examine for a possible protective effect of MMT use on HCV incidence. SETTING Data from three prospective cohort studies of illicit drug users in Vancouver, Canada between 1996 and 2012. PARTICIPANTS A total of 1004 HCV antibody-negative illicit drug users stratified by exposure to MMT. MEASUREMENTS Baseline and semi-annual HCV antibody testing and standardized interviewer-administered questionnaire soliciting self-reported data relating to drug use patterns, risk behaviors, detailed socio-demographic data and status of active participation in an MMT program. FINDINGS One hundred and eighty-four HCV seroconversions were observed for an HCV incidence density of 6.32 [95% confidence interval (CI) = 5.44-7.31] per 100 person-years. After adjusting for potential confounders, MMT exposure was protective against HCV seroconversion [adjusted odds ratio (AOR) = 0.47; 95% CI = 0.29-0.76]. In subanalyses, a dose-response protective effect of increasing MMT exposure on HCV incidence (AOR = 0.87; 95% CI = 0.78-0.97) per increasing 6-month period exposed to MMT was observed. CONCLUSION Participation in methadone maintenance treatment appears to be highly protective against hepatitis C incidence among illicit drug users. There appears to be a dose-response protective effect of increasing methadone exposure on hepatitis C incidence.

Adherence and plasma HIV RNA response to antiretroviral therapy among HIV-seropositive injection drug users in a Canadian setting

Abstract HIV-positive individuals who use injection drugs (IDU) may have lower rates of adherence to highly active antiretroviral therapy (ART). However, previous studies of factors associated with adherence to ART among IDU have been limited primarily to samples drawn from clinical settings and in areas with financial barriers to healthcare.We evaluated patterns of ART adherence and rates of plasma HIV RNA response among a Canadian cohort of community-recruited IDU. Using data from a community-recruited cohort of antiretroviral-naive HIV-infected IDU, we investigated ART adherence patterns based on prescription refill compliance and factors associated with time to plasma HIV-1 RNA suppression (<500 copies/mL) using Cox proportional hazards regression in a setting with universal health care, including free ART. Between 1996 and 2008, 267 antiretroviral-naive HIV-infected IDU initiated ART and had a median of 51 months (inter-quartile range: 17–95 months) of follow-up. Overall, 81 (30.3%) were ≥95% adherent during the first year of HAART and 187 (70.0%) achieved HIV RNA suppression at least once over the study period, for an incidence-density of 34.5 (95% confidence interval [CI]: 29.8–39.9) per 100 person-years. The Kaplan-Meier cumulative plasma HIV RNA suppression rates at 12 months after the initiation of ART were 80.8% (95% CI: 71.2–88.7) for adherent and 28.9% (95% CI: 22.8–36.1) for non-adherent participants. While several socio-demographic characteristics and drug-using behaviours were identified as barriers to successful treatment in unadjusted analyses, the factor most strongly associated with time to HIV RNA suppression in multivariate analysis was adherence to ART of at least 95% (adjusted hazard ratio [AHR] = 6.0, 95% CI: 4.2–8.6, p<0.001). These results demonstrate low rates of adherence to ART among a community-recruited cohort of IDU and reinforce the importance of adherence as the key determinant of successful virological response to antiretroviral therapy.

Dose–response relationship between methadone dose and adherence to antiretroviral therapy among HIV‐positive people who use illicit opioids

BACKGROUND AND AIMS For HIV-positive individuals who use illicit opioids, engagement in methadone maintenance therapy (MMT) can contribute to improved HIV treatment outcomes. However, to our knowledge, the role of methadone dosing in adherence to antiretroviral therapy (ART) has not yet been investigated. We sought to examine the relationship between methadone dose and ART adherence among a cohort of people who use illicit opioids. DESIGN AND SETTING We used data from the AIDS Care Cohort to Evaluate Access to Survival Services (ACCESS) study, an ongoing prospective observational cohort of HIV-positive people who use illicit drugs in Vancouver, Canada, linked confidentially to comprehensive HIV treatment data in a setting of universal no-cost medical care, including medications. We evaluated the longitudinal relationship between methadone dose and the likelihood of ≥ 95% adherence to ART among ART-exposed participants during periods of engagement in MMT. PARTICIPANTS Two hundred and ninety-seven ART-exposed individuals on MMT were recruited between December 2005 and May 2013 and followed for a median of 42.1 months. MEASUREMENTS We measured methadone dose at ≥ 100 versus < 100 mg/day and the likelihood of ≥ 95% adherence to ART. FINDINGS In adjusted generalized estimating equation (GEE) analyses, MMT dose ≥ 100 mg/day was associated independently with optimal adherence to ART [adjusted odds ratio (AOR) = 1.38; 95% confidence interval (CI) = 1.08-1.77). In a subanalysis, we observed a dose-response relationship between increasing MMT dose and ART adherence (AOR = 1.06 per 20 mg/day increase, 95% CI = 1.00-1.12). CONCLUSION Among HIV-positive individuals in methadone maintenance therapy, those receiving higher doses of methadone (≥ 100 mg/day) are more likely to achieve ≥ 95% adherence to antiretroviral therapy than those receiving lower doses.

The impact of low-threshold methadone maintenance treatment on mortality in a Canadian setting

BACKGROUND Methadone maintenance therapy (MMT) is among the most effective treatment modalities available for the management of opioid use disorder. However, the effect of MMT on mortality, and optimal strategies for delivering methadone are less clear. This study sought to estimate the effect of low-threshold MMT and its association with all-cause mortality among persons who inject drugs (PWID) in a setting where methadone is widely available through primary care physicians and community pharmacies at no cost through the settings universal medical insurance plan. METHODS Between May, 1996 and December, 2011 data were collected as part of two prospective cohort studies of PWID in Vancouver, Canada, and were linked to the provincial vital statistics database to ascertain rates and causes of death. The association of MMT with all-cause mortality was estimated using multivariable extended Cox regression with time-dependent variables. RESULTS Of 2335 PWID providing 15027 person-years of observation, 511 deaths were observed for a mortality rate of 3.4 (95% Confidence Interval [CI]: 3.1-3.7) deaths per 100 person-years. After adjusting for potential confounders including age and HIV seropositivity, MMT enrolment was found to be associated with lower mortality (adjusted hazard ratio [AHR]=0.73, 95% CI: 0.61-0.88). CONCLUSIONS While observed all-cause mortality rates among PWID in this setting were high, participation in low-threshold MMT was significantly associated with improved survival. These findings add to the known benefits of providing low-threshold MMT on reducing the harms associated with injection drug use.

Alcohol use in opioid agonist treatment

Alcohol misuse among individuals receiving agonist treatment for an opioid use disorder is common and is associated with significant morbidity and mortality. At present, though substantial research highlights effective strategies for the screening, diagnosis and management of an alcohol or opioid use disorder individually, less is known about how best to care for those with a dual diagnosis especially since common treatments for opioid addiction may be contraindicated in a setting of alcohol use. This review summarizes existing research and characterizes the prevalence, clinical implications and management of alcohol misuse among individuals with opioid addiction. Furthermore, it highlights clinically relevant management strategies in need of future research to advance care for this unique, but important, patient population.

A needs assessment of the number of comprehensive addiction care physicians required in a Canadian setting

Objective:Medical professionals adequately trained to prevent and treat substance use disorders are in short supply in most areas of the world. Whereas physician training in addiction medicine can improve patient and public health outcomes, the coverage estimates have not been established. We estimated the extent of the need for medical professionals skilled in addiction medicine in a Canadian setting. Methods:We used Monte-Carlo simulations to generate medians and 95% credibility intervals for the burden of alcohol and drug use harms, including morbidity and mortality, in British Columbia, by geographic health region. We obtained prevalence estimates for the models from the Medical Services Plan billing, the Discharge Abstract Database data, and the government surveillance data. We calculated a provider availability index (PAI), a ratio of the size of the labor force per 1000 affected individuals, for each geographic health region, using the number of American Board of Addiction Medicine certified physicians in each area. Results:Depending on the data source used for population estimates, the availability of specialized addiction care providers varied across geographic health regions. For drug-related harms, we found the highest PAI of 23.72 certified physicians per 1000 affected individuals, when using the Medical Services Plan and Discharge Abstract Database data. Drawing on the surveillance data, the drug-related PAI dropped to 0.46. The alcohol-related PAI ranged between 0.10 and 86.96 providers, depending on data source used for population estimates. Conclusions:Our conservative estimates highlight the need to invest in healthcare provider training and to develop innovative approaches for more rural health regions.

Risk factors associated with benzodiazepine use among people who inject drugs in an urban Canadian setting.

BACKGROUND Though known to have abuse potential, benzodiazepine medications remain widely prescribed. Furthermore, issues related to benzodiazepine use by people who inject drugs (PWID) remain to be fully characterized. We therefore sought to examine the prevalence of and risk factors associated with benzodiazepine use in a street-involved urban population. METHODS Between May 1996 and November 2013, data were derived from two open prospective cohort studies in Vancouver, Canada, restricted to PWID. Multivariable logistic regression with generalized estimating equations (GEE) was used to determine factors independently associated with benzodiazepine use. RESULTS Over the study period, 2806 individuals were recruited, including 949 (34%) women. Of these, 1080 (38.5%) participants reported benzodiazepine use at least once during the study period. In the multivariable analysis, Caucasian ethnicity, ≥ daily heroin injection, ≥ daily cocaine injection, non-fatal overdose, incarceration, syringe sharing, and unsafe sex were all independently associated with benzodiazepine use. Conversely, older age, homelessness, and ≥ daily crack smoking were negatively associated with benzodiazepine use. CONCLUSIONS Use of benzodiazepines was common in this urban setting and was associated with several markers of addiction severity and significant health and social vulnerabilities including syringe sharing and unsafe sex. These findings underscore the need to promote treatment for benzodiazepine use, safer benzodiazepine prescribing, including greater recognition of the limited indications for evidence-based use of this medication class.

Awareness, Possession, and Use of Take-Home Naloxone Among Illicit Drug Users, Vancouver, British Columbia, 2014-2015:

Objectives: Although take-home naloxone (THN) programs are integral in strategies to prevent overdose deaths among opioid users, the uptake of THN among people who use drugs (PWUD) (including non-opioid users) is unknown. The objectives of this study were to determine awareness, possession, and use of THN among PWUD in Vancouver, Canada, and identify barriers to adopting this strategy. Methods: From December 1, 2014, to May 29, 2015, participants in 2 prospective cohort studies of PWUD in Vancouver completed a standardized questionnaire, which asked about awareness, possession, and use of THN; sociodemographic characteristics; and drug use patterns. We conducted multivariable logistic regression analyses to determine factors independently associated with awareness and possession of THN. Results: Of 1137 PWUD, 727 (64%) reported at least 1 previous overdose ever, and 220 (19%) had witnessed an overdose in the previous 6 months. Although 769 (68%) participants overall reported awareness of THN, only 88 of 392 (22%) opioid users had a THN kit, 18 (20%) of whom had previously administered naloxone. Factors that were positively associated with awareness of THN included witnessing an overdose in the previous 6 months (adjusted odds ratio [aOR] = 2.23; 95% confidence interval [CI], 1.49-3.34; P < .001), possession of THN (aOR = 1.85; 95% CI, 1.11-3.06; P = .02), younger age (aOR = 1.02; 95% CI, 1.01-1.04; P = .003), white race (aOR = 1.67; 95% CI, 1.27-2.19; P < .001), hepatitis C infection (aOR = 1.63; 95% CI, 1.13-2.36; P = .01), residing in Vancouver’s Downtown Eastside neighborhood (aOR = 1.93; 95% CI, 1.47-2.53; P < .001), and at least daily heroin injection (aOR = 1.69; 95% CI, 1.09-2.62; P < .02). Conclusion: Efforts to improve knowledge of and participation in the THN program may contribute to reduced opioid overdose mortality in Vancouver.

HIV-infected individuals who use alcohol and other drugs, and virologic suppression

ABSTRACT People living with HIV (PLWH) on antiretroviral therapy (ART) who use substances were examined to (a) describe those with virologic control and (b) determine which substance use-factors are associated with lack of virologic control. Participants were adult PLWH taking ART with either past 12-month DSM-IV substance dependence or past 30-day alcohol or illicit drug use. Substance use factors included number of DSM-IV alcohol or drug dependence criteria and past 30-day specific substance use. Associations with HIV viral load (HVL) (<200 vs. ≥200 copies/mL) were tested using logistic regression models. Multivariable analyses adjusted for age, sex, homelessness and anxiety or depression. Participants (n = 202) were median age 50 years, 66% male, 51% African American and 75% self-reported ≥90% past 30-day ART adherence. Though HVL suppression (HVL <200 copies/mL) was achieved in 78% (158/202), past 30-day substance use was common among this group: 77% cigarette use; 51% heavy alcohol use; 50% marijuana; 27% cocaine; 16% heroin; and 15% illicit prescription opioid use. After adjusting for covariates, specific substance use was not associated with a detectable HVL, however number of past 12-month DSM-IV drug dependence criteria was (adjusted odds ratio = 1.23 for each additional criterion, 95% CI: 1.04–1.46). Three-quarters of a substance-using cohort of PLWH receiving ART had virologic control and ≥90% ART adherence. Substance dependence criteria (particularly drug dependence), not specifically substance use, were associated with lack of virologic control. Optimal HIV outcomes can be achieved by individuals who use alcohol or drugs and addressing symptoms of substance dependence may improve HIV-related outcomes.

Will This Hospitalized Patient Develop Severe Alcohol Withdrawal Syndrome?: The Rational Clinical Examination Systematic Review.

Importance Although severe alcohol withdrawal syndrome (SAWS) is associated with substantial morbidity and mortality, most at-risk patients will not develop this syndrome. Predicting its occurrence is important because the mortality rate is high when untreated. Objective To assess the accuracy and predictive value of symptoms and signs for identifying hospitalized patients at risk of SAWS, defined as delirium tremens, withdrawal seizure, or clinically diagnosed severe withdrawal. Data Sources MEDLINE and EMBASE (1946-January 2018) were searched for articles investigating symptoms and signs predictive of SAWS in adults. Reference lists of retrieved articles were also searched. Study Selection Original studies that were included compared symptoms, signs, and risk assessment tools among patients who developed SAWS and patients who did not. Data Extraction and Synthesis Data were extracted and used to calculate likelihood ratios (LRs), sensitivity, and specificity. A meta-analysis was performed to calculate summary LR. Results Of 530 identified studies, 14 high-quality studies that included 71 295 patients and 1355 relevant cases of SAWS (1051 cases), seizure (53 cases), or delirium tremens (251 cases) were analyzed. A history of delirium tremens (LR, 2.9 [95% CI 1.7-5.2]) and baseline systolic blood pressure 140 mm Hg or higher (LR, 1.7 [95% CI, 1.3-2.3) were associated with an increased likelihood of SAWS. No single symptom or sign was associated with exclusion of SAWS. Six high-quality studies evaluated combinations of clinical findings and were useful for identifying patients in acute care facilities at high risk of developing SAWS. Of these combinations, the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was most useful, with an LR of 174 (95% CI, 43-696; specificity, 0.93) when patients had 4 or more individual findings and an LR of 0.07 (95% CI, 0.02-0.26; sensitivity, 0.99) when there were 3 or fewer findings. Conclusions and Relevance Assessment tools that use a combination of symptoms and signs are useful for identifying patients at risk of developing severe alcohol withdrawal syndrome. Most studies of these tools were not fully validated, limiting their generalizability.