The Study to Assess Long-term Opioid Medication Effectiveness (SALOME) is a two-stage phase III, single site (Vancouver, Canada), randomized, double blind controlled trial designed to test if hydromorphone is as effective as diacetylmorphine for the treatment of long-term illicit opioid injection. Recruiting participants for clinical trials continues to be a challenge in medical and addiction research, with many studies not being able to reach the planned sample size in a timely manner. The aim of this study is to describe the recruitment strategies in SALOME, which offered appealing treatments but had limited clinic capacity and no guaranteed post-trial continuation of the treatments.
SALOME included chronic opioid-dependent, current illicit injection opioid users who had at least one previous episode of opioid maintenance treatment. Regulatory approvals were received in June 2011 and recruitment strategies were implemented over the next 5 months. Recruitment strategies included ongoing open communication with the community, a consistent and accessible team and participant-centered screening. All applicants completed a pre-screening checklist to assess prerequisites. Applicants meeting these prerequisites were later contacted to commence the screening process.
A total of 598 applications were received over the two-year recruitment period; 130 were received on the first day of recruitment. Of these applicants, 485 met prerequisites; however, many could not be found or were not reached before recruitment ended. For the 253 candidates who initiated the screening process, the average time lapse between application and screening date was 8.3 months (standard deviation [SD] = 4.44) and for the 202 randomized to the study, the average processing time from initial screen to randomization was 25.9 days (SD = 37.48; Median = 15.0).
As in prior trials offering injectable diacetylmorphine within a supervised model, recruiting participants for this study took longer than planned. The recruitment challenges overcome in SALOME were due to the high number of applicants compared with the limited number that could be randomized and treated. Our study emphasizes the value of integrating these strategies into clinical addiction research to overcome study-specific barriers.
Opioid dependency; Injectable diacetylmorphine; Injectable hydromorphone; Recruitment; Randomized clinical trial
The most widely used maintenance treatment for opioid dependency is substitution with long-acting oral opioids. Treatment with injectable diacetylmorphine provides an opportunity for patients to stabilize and possibly transition to oral treatment, if clinically indicated. The aim of this study was to explore outcomes of individuals that received injectable diacetylmorphine and voluntarily transitioned to oral methadone.
Design and methods
The North American Opiate Medication Initiative was a randomized controlled trial that compared the effectiveness of injectable diacetylmorphine (or hydromorphone) to oral methadone for long-term opioid-dependency. Treatment was provided for 12-months with an additional 3 months for transition and weaning. Participants were followed until 24-months from randomization. Among the participants randomized to injectable treatments, a sub-group voluntarily chose to transition to oral methadone (n = 16) during the treatment period. Illicit heroin use and treatment retention were assessed at 24-months for those voluntarily and involuntarily transitioning (n = 95) to oral methadone.
At 24-months, the group that voluntarily transitioned to oral methadone had higher odds of treatment retention (adjusted odds ratio = 5.55; 95% confidence interval [CI] = 1.11, 27.81; Chi-square = 4.33, df = 1, p-value = 0.037) than the involuntary transition group. At 24-months, the adjusted mean difference in prior 30 days of illicit heroin use for the voluntary, compared to the involuntary group was -5.58 (95% CI = -11.62, 0.47; t-value = -1.83, df = 97.4, p-value = 0.070).
Although the results of this study were based on small groups of self-selected (i.e., non-randomized) participants, our data underlines the critical importance of voluntary and patient-centered decision making. If we had continued offering treatment with diacetylmorphine, those retained to injectable medication may have sustained the achieved improvements in the first 12 months. Diversified opioid treatment should be available so patients and physicians can flexibly choose the best treatment at the time.
Clinical Trial Registration: NCT00175357
Opioid dependency; Diacetylmorphine, Injectable; Oral methadone; Opioid maintenance treatment
HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979–1989) and 382 modern (2000–2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a “consensus-like” founder virus, the median “background” frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were “pre-adapted” to the average host HLA profile was only ∼2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins.
Upon HIV transmission, many – though not all – immune escape mutations selected in the previous host will revert to the consensus residue. The persistence of certain escape mutations following transmission has led to concerns that these could gradually accumulate in circulating HIV sequences over time, thereby undermining host antiviral immune potential as the epidemic progresses. As certain immune-driven mutations reduce viral fitness, their spread through the population could also have consequences for the average replication capacity and/or protein function of circulating HIV sequences. Here, we characterized HIV sequences, linked to host immunogenetic information, from patients enrolled in historic (1979–1989) and modern (2000–2011) HIV cohorts from four key cities in the North American epidemic. We reconstructed the epidemic's ancestral (founder) HIV sequence and assessed the subsequent extent to which known HIV immune escape mutations have spread in the population. Our data support the gradual spread of many - though not all - immune escape mutations in HIV sequences over time, but to an extent that is unlikely to have major immediate immunologic consequences for the North American epidemic. Notably, in vitro assessments of ancestral and patient-derived HIV sequences suggested functional implications of ongoing HIV evolution for certain viral proteins.
Little is known about HIV infection and the related vulnerabilities of young people living in resource-scarce, post-emergency transit camps that are now home to thousands of Internally Displaced Persons (IDPs) following two decades of war in northern Uganda. The objective of this analysis was to assess the prevalence and correlates of HIV infection among young people living in post-conflict transition in Gulu District, northern Uganda.
In 2010, a cross-sectional demographic and behavioural survey was conducted in two of Gulu District’s sub-counties with 384 purposively selected transit camp residents aged 15 to 29 years. Biological specimens were collected for rapid HIV testing in the field and confirmatory laboratory testing. Multivariable logistic regression identified independent determinants of HIV infection.
HIV prevalence was alarmingly high at 12.8% (95% CI: 9.6%, 16.5%). The strongest determinant of HIV infection among young people was a non-consensual sexual debut (adjusted odds ratio [AOR], 9.88; 95% CI: 1.70–18.06). Residing in Awach sub-county (AOR, 2.93; 95% CI: 1.28–6.68), experiencing STI symptoms in the previous 12 months (AOR, 2.36; 95% CI: 1.43–6.17), and practicing dry sex (AOR, 2.31; 95% CI: 1.04–5.13) were other key determinants of HIV infection.
Study findings contribute to filling an important gap in epidemiological evidence and are useful for planning public health interventions in northern Uganda that effectively target young people in post-conflict transition and support them in the resettlement process. Findings serve to recommend reaching beyond traditional prevention programming in a way more effectively beneficial to young people in post-conflict settings by developing population-specific responses sensitive to local contexts and sufficient to address the underlying causes of the complex risk factors influencing the spread of HIV.
The North American Opiate Medication Initiative (NAOMI) clinical trial compared the effectiveness of injectable diacetylmorphine (DAM) or hydromorphone (HDM) to oral methadone maintenance treatment (MMT). This study aimed to determine participants’ perceptions of treatment delivered in NAOMI.
A qualitative sub-study was conducted with 29 participants (12 female): 18 (62.1%) received injectable DAM or HDM and 11 (37.9%) received MMT. A phenomenological theoretical framework was used. Semi-structured interviews were audio-recorded and transcribed verbatim. A thematic analysis was used over successive phases and was driven by the semantic meanings of the data.
Participants receiving injectable medications suggested that the supervised delivery model was stringent but provided valuable stability to their lives. Females discussed the adjustment required for the clinical setting, while males focused on the challenging clinic schedule and its impact on employment abilities. Participants receiving MMT described disappointment with being randomized to this treatment; however, positive aspects, including the quick titration time and availability of auxiliary services, were also discussed.
Treatment with injectable DAM (or HDM) is preferred by participants and considered effective in reducing the burden of opioid dependency. Engaging patients in research regarding their perceptions of treatment provides a comprehensive assessment of treatment needs and barriers.
Clinical trial registration
Opioid dependency; Diacetylmorphine; Injectable; Oral methadone; Opioid maintenance treatment; Qualitative methods
Thousands of former child soldiers who were abducted during the prolonged conflict in northern Uganda have returned to their home communities. Programmes that facilitate their successful reintegration continue to face a number of challenges. Although there is increasing knowledge of the dynamics of HIV infection during conflict, far less is known about its prevalence and implications for population health in the post-conflict period. This study investigated the effects of abduction on the prevalence of HIV and HIV-risk behaviours among young people in Gulu District, northern Uganda. An understanding of abduction experiences and HIV-risk behaviours is vital to both the development of effective reintegration programming for former child soldiers and the design of appropriate HIV prevention interventions for all young people.
In 2010, we conducted a cross-sectional study of 2 sub-counties in Gulu District. A demographic and behavioural survey was interview-administered to a purposively selected sample of 384 transit camp residents aged 15–29. Biological specimens were collected for HIV rapid testing in the field and confirmatory laboratory testing. Descriptive statistics were used to describe characteristics of abduction. Additionally, a gender-stratified bivariate analysis compared abductees’ and non-abductees’ HIV risk profiles.
Of the 384 participants, 107 (28%) were former child soldiers (61% were young men and 39% were young women). The median age of participants was 20 and median age at abduction was 13. HIV prevalence was similar among former abductees and non-abductees (12% vs. 13%; p = 0.824), with no differences observed by gender. With respect to differences in HIV vulnerability, our bivariate analysis identified greater risky sexual behaviours in the past year for former abductees than non-abductees, but there were no differences between the two groups’ survival/livelihood activities and food insufficiency experiences, both overall and by gender. The analysis further revealed that young northern Ugandans in general are in desperate need of education, skills development, and support for victims of sexual violence.
This study persuasively demonstrates that all young people in northern Ugandan have been similarly affected by HIV infection during war and displacement. Post-conflict programme planners must therefore abandon rudimentary targeting practices based on abductees as a high-profile category. Instead, they must develop evidence-based HIV interventions that are commensurate with young people’s specific needs. As such programmes will be less stigmatizing, more oriented to self-selection, and more inclusive, they will effectively reach the most vulnerable young people in northern Uganda.
Child soldiers; HIV/AIDS; Post-conflict programming; Young people; Northern Uganda
Factors associated with HCV incidence among young Aboriginal people in Canada are still not well understood. We sought to estimate time to HCV infection and the relative hazard of risk factors associated HCV infection among young Aboriginal people who use injection drugs in two Canadian cities.
The Cedar Project is a prospective cohort study involving young Aboriginal people in Vancouver and Prince George, British Columbia, who use illicit drugs. Participants’ venous blood samples were drawn and tested for HCV antibodies. Analysis was restricted to participants who use used injection drugs at enrolment or any of follow up visit. Cox proportional hazards regression was used to identify independent predictors of time to HCV seroconversion.
In total, 45 out of 148 participants seroconverted over the study period. Incidence of HCV infection was 26.3 per 100 person-years (95% Confidence Interval [CI]: 16.3, 46.1) among participants who reported using injection drugs for two years or less, 14.4 per 100 person-years (95% CI: 7.7, 28.9) among participants who had been using injection drugs for between two and five years, and 5.1 per 100 person-years (95% CI: 2.6,10.9) among participants who had been using injection drugs for over five years. Independent associations with HCV seroconversion were involvement in sex work in the last six months (Adjusted Hazard Ratio (AHR): 1.59; 95% CI: 1.05, 2.42) compared to no involvement, having been using injection drugs for less than two years (AHR: 4.14; 95% CI: 1.91, 8.94) and for between two and five years (AHR: 2.12; 95%CI: 0.94, 4.77) compared to over five years, daily cocaine injection in the last six months (AHR: 2.47; 95% CI: 1.51, 4.05) compared to less than daily, and sharing intravenous needles in the last six months (AHR: 2.56; 95% CI: 1.47, 4.49) compared to not sharing.
This study contributes to the limited body of research addressing HCV infection among Aboriginal people in Canada. The HCV incidence rate among Cedar Project participants who were new initiates of injection drug use underscores an urgent need for HCV and injection prevention and safety strategies aimed at supporting young people surviving injection drug use and sex work in both cities. Young people must be afforded the opportunity to provide leadership and input in the development of prevention programming.
Although diacetylmorphine has been proven to be more effective than methadone maintenance treatment for opioid dependence, its direct costs are higher. We compared the cost-effectiveness of diacetylmorphine and methadone maintenance treatment for chronic opioid dependence refractory to treatment.
We constructed a semi-Markov cohort model using data from the North American Opiate Medication Initiative trial, supplemented with administrative data for the province of British Columbia and other published data, to capture the chronic, recurrent nature of opioid dependence. We calculated incremental cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-, 10-year and lifetime horizons.
Diacetylmorphine was found to be a dominant strategy over methadone maintenance treatment in each of the time horizons. Over a lifetime horizon, our model showed that people receiving methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average (95% credibility interval [CI] 6.91–8.01) and generated a societal cost of $1.14 million (95% CI $736 800–$1.78 million). Those who received diacetylmorphine gained 7.92 discounted QALYs on average (95% CI 7.32–8.53) and generated a societal cost of $1.10 million (95% CI $724 100–$1.71 million). Cost savings in the diacetylmorphine cohort were realized primarily because of reductions in the costs related to criminal activity. Probabilistic sensitivity analysis showed that the probability of diacetylmorphine being cost-effective at a willingness-to-pay threshold of $0 per QALY gained was 76%; the probability was 95% at a threshold of $100 000 per QALY gained. Results were confirmed over a range of sensitivity analyses.
Using mathematical modelling to extrapolate results from the North American Opiate Medication Initiative, we found that diacetylmorphine may be more effective and less costly than methadone among people with chronic opioid dependence refractory to treatment.
Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT.
Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months).
A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period.
After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes.
Sex work; opioid dependence; substitution treatment
Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST). In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes.
Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone vs. injectable diacetylmorphine over 12 months. A small sub-group of patients received injectable hydromorphone on a double blind basis with diacetylmorphine. The Client Satisfaction Questionnaire (CSQ-8) was used to measure satisfaction with treatment. CSQ-8 scores, as well as retention and response to treatment, did not differ between those receiving hydromorphone and diacetylmorphine at 3 or 12 months assessments; therefore, these two groups were analyzed together as the 'injectable' treatment group.
A total of 232 (92%) and 237 (94%) participants completed the CSQ-8 at 3 and 12 months, respectively. Participants in both groups were highly satisfied with treatment. Independent of treatment group, participants satisfied with treatment at 3 months were more likely to be retained at 12 months. Multivariate analysis indicated that satisfaction was greater among those randomized to the injection group after controlling for treatment effectiveness. Participants who were retained, responded to treatment, and had fewer psychological symptoms were more satisfied with treatment. Finally, open-ended comments were made by 149 (60.3%) participants; concerns about the randomization process and the study ending were most commonly reported by participants receiving the oral and injectable medications, respectively.
The higher satisfaction among those receiving medically prescribed injectable diacetylmorphine (or hydromorphone) supports current evidence regarding the attractiveness of this treatment for long-term, opioid-dependent individuals not benefiting sufficiently from other treatments. In addition, the measurement of treatment satisfaction provides valuable information about participants at risk of relapse and in need of additional services.
ClinicalTrials.gov Identifier: NCT00175357
Studies suggest that Aboriginal people in Canada are over-represented among people using injection drugs. The factors associated with transitioning to the use of injection drugs among young Aboriginal people in Canada are not well understood.
The Cedar Project is a prospective cohort study (2003–2007) involving young Aboriginal people in Vancouver and Prince George, British Columbia, who use illicit drugs. Participants’ venous blood samples were tested for antibodies to HIV and the hepatitis C virus, and drug use was confirmed using saliva screens. The primary outcomes were use of injection drugs at baseline and tranisition to injection drug use in the six months before each follow-up interview.
Of 605 participants, 335 (55.4%) reported using injection drugs at baseline. Young people who used injection drugs tended to be older than those who did not, female and in a relationship. Participants who injected drugs were also more likely than those who did not to have been denied shelter because of their drug use, to have been incarcerated, to have a mental illness and to have been involved in sex work. Transition to injection drug use occurred among 39 (14.4%) participants, yielding a crude incidence rate of 19.8% and an incidence density of 11.5 participants per 100 person-years. In unadjusted analysis, transition to injection drug use was associated with being female (odds ratio [OR] 1.98, 95% confidence interval (CI) 1.06–3.72), involved in sex work (OR 3.35, 95% CI 1.75–6.40), having a history of sexually transmitted infection (OR 2.01, 95% CI 1.07–3.78) and using drugs with sex-work clients (OR 2.51, 95% CI 1.19–5.32). In adjusted analysis, transition to injection drug use remained associated with involvement in sex work (adjusted OR 3.94, 95% CI 1.45–10.71).
The initiation rate for injection drug use of 11.5 participants per 100 person-years among participants in the Cedar Project is distressing. Young Aboriginal women in our study were twice as likely to inject drugs as men, and participants who injected drugs at baseline were more than twice as likely as those who did not to be involved in sex work.
Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting.
Methods and Findings
We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options.
We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.
We sought to estimate the prevalence and incidence of hepatitis C virus (HCV) infection among Aboriginal young people who use drugs and to identify risk factors associated with HCV infection in this population.
The Cedar Project is a longitudinal study involving Aboriginal young people living in Vancouver and Prince George, British Columbia. Eligibility criteria include age from 14 to 30 years and self-reported use (smoking or injection) of illicit drugs (e.g., crystal methamphetamine, crack cocaine, heroin or other opiates, and cocaine) at least once in the month before enrolment. At each visit, participants completed a detailed questionnaire administered by an Aboriginal interviewer. For this analysis, we included information for 512 participants who were recruited between September 2003 and April 2005.
Among the 512 participants, the prevalence of HCV infection was 34.8% (95% confidence interval [CI] 30.6%–38.9%); the rates were similar in Prince George and Vancouver (34.5% and 35.0% respectively, p = 0.37). Among those who reported the use of injection drugs at baseline (n = 286), the prevalence of HCV infection was 59.4% (95% CI 53.8%–65.1%); the rate in this group was slightly higher in Prince George than in Vancouver (62.4% v. 57.1% respectively, p = 0.37). The prevalence was 3.5% among participants who reported smoking drugs (n = 226). In the multivariate logistic regression analysis, factors significantly associated with HCV infection among participants who used injection drugs included daily injection of opiates (adjusted odds ratio [OR] 2.7, 95% CI 1.0–7.4), reuse of syringes (adjusted OR 2.4, 95% CI 1.3–4.4), having at least 1 parent who attended residential school (adjusted OR 1.9, 95% CI 1.1–3.4), female sex (adjusted OR 1.9, 95% CI 1.1–3.4) and duration of injection drug use (per year) (adjusted OR 1.4, 95% CI 1.3–1.5). The crude incidence rate of HCV infection was 10.6% and the incidence density estimate was 9.9 per 100 person-years in this cohort.
The prevalence of HCV infection was elevated among Aboriginal young people living in Prince George and Vancouver who use drugs. Culturally based prevention, treatment and harm-reduction programs are urgently needed in this population.
The North American Opiate Medication Initiative (NAOMI) is a randomized controlled trial evaluating the feasibility and effectiveness of heroin-assisted treatment (HAT) in the Canadian context. Our objective is to analyze the profile of the NAOMI participant cohort in the context of illicit opioid use in Canada and to evaluate its comparability with patient profiles of European HAT studies. Recruitment began in February 2005 and ended in March 2007. Inclusion criteria included opioid dependence, 5 or more years of opioid use, regular opioid injection, and at least two previous opiate addiction treatment attempts. Standardized assessment instruments such as the European Addiction Severity Index and the Maudsley Addiction Profile were employed. A total of 251 individuals were randomized from Vancouver, BC (192, 76.5%), and Montreal, Quebec (59, 23.5%); 38.5% were female, the mean age was 39.7 years (SD:8.6), and participants had injected drugs for 16.5 years (SD:9.9), on average. In the prior month, heroin was used a mean of 26.5 days (SD:7.4) and cocaine 16 days (SD;12.6). Vancouver had significantly more patients residing in unstable housing (88.5 vs. 22%; p < 0.001) and higher use of smoked crack cocaine (16.9 days vs. 2.3 days in the prior month; p < 0.001), while a significantly higher proportion of Montreal participants reported needle sharing in the prior 6 months (25% vs. 3.7%; p < 0.001). In many respects, the patient cohort was similar to the European trials; however, NAOMI had a higher proportion of female participants and participants residing in unstable housing. This study suggests that the NAOMI study successfully recruited participants with a profile indicated for HAT. It also raises concern about the high levels of crack cocaine use and social marginalization.
Heroin dependence; Injection Drug Use; Substitution treatment; Cocaine abuse; Opioid-related disorders; Treatment refusals
This study compared two methods of booking elective surgery – booking from wait lists and pre-booking surgery dates at the time of decision to operate – in terms of cancellations of elective procedures and time to surgery.
The authors conducted simulation experiments with group randomized design, in which the unit of allocation was the hospital and the units of analysis were both the hospital and the patient.
In the case of pre-booking, cancellation of high-priority elective procedures was only one-third as likely as it was in the case of booking from wait lists (odds ratio 0.35; 95% confidence interval 0.18–0.68). After adjustment for hospital and patient factors, the weekly likelihood that patients on the wait list had their operation was about 20% higher for medium-priority procedures (OR 1.21; CI 1.18–1.24) after pre-booking surgery dates.
The findings suggest that redesigning booking processes may improve the performance of surgical services.
Opioid addiction is a chronic, relapsing disease and remains a major public health challenge. Despite important expansions of access to conventional treatments, there are still significant proportions of affected individuals who remain outside the reach of the current treatment system and who contribute disproportionately to health care and criminal justice costs as well as to public disorder associated with drug addiction.
The NAOMI study is a Phase III randomized clinical trial comparing injectable heroin maintenance to oral methadone. The study has ethics board approval at its Montréal and Vancouver sites, as well as from the University of Toronto, the New York Academy of Medicine and Johns Hopkins University.
The main objective of the NAOMI Study is to determine whether the closely supervised provision of injectable, pharmaceutical-grade opioid agonist is more effective than methadone alone in recruiting, retaining, and benefiting chronic, opioid-dependent, injection drug users who are resistant to current standard treatment options.
The case study submitted chronicles the challenges of getting a heroin assisted treatment trial up and running in North America. It describes: a brief background on opioid addiction; current standard therapies for opioid addiction; why there is/was a need for a heroin assisted treatment trial; a description of heroin assisted treatment; the beginnings of creating the NAOMI study in North America; what is the NAOMI study; the science and politics of the NAOMI study; getting NAOMI started in Canada; various requirements and restrictions in getting the study up and running; recruitment into the study; working with the media; a status report on the study; and a brief conclusion from the authors' perspectives.
Results and conclusion
As this is a case study, there are no specific results or main findings listed. The case study focuses on: the background of the study; what it took to get the study started in Canada; the unique requirements and conditions of getting a site, and the study, approved; working with the media; recruitment into the study; a brief status report on the study; and a brief conclusion from the authors' perspectives.
ClinicalTrials.gov registration number: NCT00175357
Since the initial Swiss heroin-assisted treatment (HAT) study conducted in the mid-1990s, several other jurisdictions in Europe and North America have implemented HAT trials. All of these studies embrace the same goal—investigating the utility of medical heroin prescribing for problematic opioid users—yet are distinct in various key details. This paper briefly reviews (initiated or completed) studies and their main parameters, including primary research objectives, design, target populations, outcome measures, current status and—where available—key results. We conclude this overview with some final observations on a decade of intensive HAT research in the jurisdictions examined, including the suggestion that there is a mounting onus on the realm of politics to translate the—largely positive—data from completed HAT science into corresponding policy and programming in order to expand effective treatment options for the high-risk population of illicit opioid users.
Heroin-assisted treatment; Science; Politics; Opioid dependence; Clinical trials
Progressive Audiologic Tinnitus Management (PATM) is based on the premise that tinnitus is managed most efficiently using a hierarchy of clinical services that address different levels of need. PATM includes five levels of management: (a) triage; (b) audiologic evaluation; (c) group education; (d) tinnitus evaluation; and (e) individualized management. This article provides an overview of PATM and focuses on the procedures that make up the Level 2 Audiologic Evaluation. The evaluation is conducted to assess the potential need for medical, audiologic (hearing loss, tinnitus, hyperacusis), and/or mental health services. The Tinnitus Handicap Inventory, Hearing Handicap Inventory, and Tinnitus and Hearing Survey are used to differentiate effects of tinnitus and hearing loss. If indicated, patients are interviewed with the Tinnitus-Impact Screening Interview. Patients requiring amplification receive hearing aids. Often, management of hearing loss at Level 2 addresses any problems that were attributed to the tinnitus, which obviates further tinnitus-specific intervention.
auditory; hearing disorders; hearing aids; intervention; assessment; rehabilitation; tinnitus
Management of tinnitus generally involves educational counseling, stress reduction, and/or the use of therapeutic sound. This article focuses on therapeutic sound, which can involve three objectives: (a) producing a sense of relief from tinnitus-associated stress (using soothing sound); (b) passively diverting attention away from tinnitus by reducing contrast between tinnitus and the acoustic environment (using background sound); and (c) actively diverting attention away from tinnitus (using interesting sound). Each of these goals can be accomplished using three different types of sound—broadly categorized as environmental sound, music, and speech—resulting in nine combinations of uses of sound and types of sound to manage tinnitus. The authors explain the uses and types of sound, how they can be combined, and how the different combinations are used with Progressive Audiologic Tinnitus Management. They also describe how sound is used with other sound-based methods of tinnitus management (Tinnitus Masking, Tinnitus Retraining Therapy, and Neuromonics).
auditory; hearing disorders; intervention; outcomes; rehabilitation; tinnitus
Recent reports have suggested that Aboriginal and American Indian people are at elevated risk of HIV infection. We undertook the present study to compare socio-demographic and risk variables between Aboriginal and non-Aboriginal young (aged 13 – 24 years) injection drug users (IDUs) and characterize the burden of HIV infection among young Aboriginal IDUs.
We compared socio-demographic and risk variables between Aboriginal and non-Aboriginal young IDUs. Data were collected through the Vancouver Injection Drug Users Study (VIDUS). Semi-annually, participants have completed an interviewer-administered questionnaire and have undergone serologic testing for HIV and Hepatitis C (HCV).
To date over 1500 Vancouver IDU have been enrolled and followed, among whom 291 were aged 24 years and younger. Of the 291 young injectors, 80 (27%) were Aboriginal. In comparison to non-Aboriginal youth, Aboriginal youth were more likely to test seropositive for either HIV (20% vs 7%, p=< 0.001) or Hepatitis C virus (HCV) (66% vs 38%, p =< 0.001), be involved in sex work and live in the city's IDU epi-centre at baseline. After 48 months of follow-up, Aboriginal youth experienced significantly higher HIV seroconversion rates than non-Aboriginal youth, 27.8 per ppy (95% CI: 13.4–42.2) vs. 7.0 per ppy (95% CI: 2.3–11.8) respectively (log-rank p = 0.005) and the incidence density over the entire follow-up period was 12.6 per 100 pyrs (CI: 6.49–21.96) and 3.9 per 100 pyrs (CI: 1.8–7.3) respectively.
These findings demonstrate that culturally relevant, evidence based prevention programs are urgently required to prevent HIV infection among Aboriginal youth.
OBJECTIVES: Few prospective studies are available on the relationship between incarceration and HIV risk among injection drug users (IDUs). The authors evaluated self-reported rates of syringe sharing and incarceration among a cohort of IDUs. METHODS: This study analyzed syringe lending by HIV-infected IDUs and syringe borrowing by HIV-negative IDUs among participants enrolled in the Vancouver Injection Drug Users Study (VIDUS). Since serial measures for each individual were available, variables potentially associated with each outcome (syringe lending and borrowing) were evaluated using generalized estimating equations for binary outcomes. RESULTS: The study sample consisted of 1,475 IDUs who were enrolled into the VIDUS cohort from May 1996 through May 2002. At baseline, 1,123 (76%) reported a history of incarceration since they first began injecting drugs. Of these individuals, 351 (31%) reported at baseline that they had injected drugs while incarcerated. Among 318 baseline HIV-infected IDUs, having been incarcerated in the six months prior to each interview remained independently associated with syringe lending during the same period (adjusted odds ratio [OR]=1.33; 95% confidence interval [CI] 1.06, 1.69; p=0.015). Similarly, among the 1,157 baseline HIV-negative IDUs, having been incarcerated in the six months prior to each interview remained independently associated with reporting syringe borrowing during the same period (adjusted OR=1.26; 95% CI 1.12, 1.44; p<0.001). CONCLUSIONS: Incarceration was independently associated with risky needle sharing for HIV-infected and HIV-negative IDUs. This evidence of HIV risk behavior should reinforce public health concerns about the high rates of incarceration among IDUs.
Estimated and potential medical costs of treating patients infected with human immunodeficiency virus (HIV) in urban areas of high HIV prevalence have not been well defined. We estimated the total medical cost of HIV disease among injection drug users in Vancouver, British Columbia, Canada, assuming stable and increasing HIV prevalence. Total medical costs were estimated by multiplying the average lifetime medical cost per person by the number of HIV-infected individuals. We assumed the cost of each HIV infection to be $150,000 (Canadian), based on empirical data, and HIV prevalence estimates were derived from the Vancouver Injection Drug Users Study (VIDUS) and external data sources. By use of Monte Carlo simulation methodology, we performed sensitivity analyses to estimate total medical cost, assuming the HIV prevalence remained stable at 31% and under a scenario in which the prevalence rose to 50%. Expected medical expenditures based on current HIV prevalence levels were estimated as $215,852,613. If prevalence rises to 50% as reported in other urban centers, the median estimated medical cost would be approximately $348,935,865. This represents a difference in the total costs between the two scenarios of $133,083,253. Health planners should consider that predicted medical expenditures related to the HIV epidemic among injection drug users in our setting may cost an estimated $215,852,613. If funding cannot be found for appropriate prevention interventions and the prevalence rises to 50%, a further $133,083,253 may be required.
AIDS; Cost; Health care; HIV; Injection drug use