Experiences of the HIV Cascade of Care Among Indigenous Peoples: A Systematic Review.

Indigenous leaders remain concerned that systemic oppression and culturally unsafe care impede Indigenous peoples living with HIV from accessing health services that make up the HIV cascade of care. We conducted a systematic review to assess the evidence related to experiences of the HIV care cascade among Indigenous peoples in Australia, Canada, New Zealand, and United States. We identified 93 qualitative and quantitative articles published between 1996 and 2017 reporting primary data on cascade outcomes disaggregated by Indigenous identity. Twelve involved data from Australia, 52 from Canada, 3 from New Zealand and 26 from United States. The majority dealt with HIV testing/diagnosis (50). Relatively few addressed post-diagnosis experiences: linkage (14); retention (20); treatment initiation (21); adherence (23); and viral suppression (24). With the HIV cascade of care increasingly the focus of global, national, and local HIV agendas, it is critical that culturally-safe care for Indigenous peoples is available at all stages.

Ethnicity and HIV vulnerabilities among men who have sex with men in China.

Ethnic affiliation can define sociocultural boundaries and contribute to the HIV vulnerabilities faced by men who have sex with men (MSM). This study investigated the influence of ethnic affiliation on HIV vulnerabilities among MSM in North China. Our study analyzed a cross-sectional survey of MSM (n = 398) in two major North China cities. We examined associations between ethnic affiliation and (a) HIV status, (b) sexual behaviors and experiences, and (c) substance use. Compared to ethnic majority Han MSM: MSM belonging to ethnic minority groups of South China had significantly greater odds of HIV infection (AOR: 7.40; 95% CI: 2.33-23.47) and experience of forced sex (AOR: 3.27; 95% CI: 1.12-9.52). Compared to ethnic majority Han MSM, Ethnic Hui MSM had significantly lower odds of condomless anal sex (AOR: 0.41; 95% CI: 0.21-0.82) and significantly greater odds of circumcision (AOR: 2.62; 95% CI: 1.24-5.51). HIV prevalence and riskier sexual behaviors among MSM in China appear to vary significantly by ethnic affiliation. Current epidemiological practices of aggregating all ethnic minority groups in China into a single category may be masking important interethnic differences in HIV risk, and precluding opportunities for more culturally appropriate interventions.

Population-Level Immune-Mediated Adaptation in HIV-1 Polymerase during the North American Epidemic.

UNLABELLED: Human leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n = 338) and modern (2001 to 2011; n = 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average ∼2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era. IMPORTANCE: HLA class I-restricted cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 that persist upon transmission may accumulate in circulation over time, potentially undermining host antiviral immunity to the transmitted viral strain. We studied >600 experimentally collected HIV-1 polymerase sequences linked to host HLA information dating back to 1979, along with phylogenetically reconstructed HIV-1 sequences dating back to the virus' introduction into North America. Overall, our results support the gradual spread of many-though not all-HIV-1 polymerase immune escape mutations in circulation over time. This is consistent with recent observations from other global regions, though the extent of polymorphism accumulation in North America appears to be lower than in populations with high seroprevalence, older epidemics, and/or limited HLA diversity. Importantly, the risk of acquiring an HIV-1 polymerase sequence at transmission that is substantially preadapted to one's HLA profile remains relatively low in North America, even in the present era.

The Cedar Project: mortality among young Indigenous people who use drugs in British Columbia.

BACKGROUND: Young Indigenous people, particularly those involved in the child welfare system, those entrenched in substance use and those living with HIV or hepatitis C, are dying prematurely. We report mortality rates among young Indigenous people who use drugs in British Columbia and explore predictors of mortality over time. METHODS: We analyzed data collected every 6 months between 2003 and 2014 by the Cedar Project, a prospective cohort study involving young Indigenous people who use illicit drugs in Vancouver and Prince George, BC. We calculated age-standardized mortality ratios using Indigenous and Canadian reference populations. We identified predictors of mortality using time-dependent Cox proportional hazard regression. RESULTS: Among 610 participants, 40 died between 2003 and 2014, yielding a mortality rate of 670 per 100 000 person-years. Young Indigenous people who used drugs were 12.9 (95% confidence interval [CI] 9.2-17.5) times more likely to die than all Canadians the same age and were 7.8 (95% CI 5.6-10.6) times more likely to die than Indigenous people with Status in BC. Young women and those using drugs by injection were most affected. The leading causes of death were overdose (n = 15 [38%]), illness (n = 11 [28%]) and suicide (n = 5 [12%]). Predictors of mortality included having hepatitis C at baseline (adjusted hazard ratio [HR] 2.76, 95% CI 1.47-5.16), previous attempted suicide (adjusted HR 1.88, 95% CI 1.01-3.50) and recent overdose (adjusted HR 2.85, 95% CI 1.00-8.09). INTERPRETATION: Young Indigenous people using drugs in BC are dying at an alarming rate, particularly young women and those using injection drugs. These deaths likely reflect complex intersections of historical and present-day injustices, substance use and barriers to care.

The Alcohol Use Disorders Identification Test (AUDIT): Exploring the Factor Structure and Cutoff Thresholds in a Representative Post-Conflict Population in Northern Uganda.

AIMS: Despite increased use of the Alcohol Use Disorders Identification Test (AUDIT) in sub-Saharan Africa, few studies have assessed its underlying conceptual framework, and none have done so in post-conflict settings. Further, significant inconsistencies exist between definitions used for problematic consumption. Such is the case in Uganda, facing one of the highest per-capita alcohol consumption levels regionally, which is thought to be hindering rebuilding in the North after two decades of civil war. This study explores the impact of varying designation cutoff thresholds in the AUDIT as well as its conceptual factor structure in a representative sample of the population. METHODS: In all, 1720 Cango Lyec Project participants completed socio-economic and mental health questionnaires, provided blood samples and took the AUDIT. Participant characteristics and consumption designations were compared at AUDIT summary score thresholds of ≥3, ≥5 and ≥8. Confirmatory factor analyses (CFA) explored one-, two- and three-factor level models overall and by sex with relative and absolute fit indicators. RESULTS: There were no significant differences in participant demographic characteristics between thresholds. At higher cutoffs, the test increased in specificity to identify those with hazardous drinking, disordered drinking and suffering from alcohol-related harms. All conceptual models indicated good fit, with three-factor models superior overall and within both sexes. CONCLUSION: In Northern Uganda, a three-factor AUDIT model best explores alcohol use in the population and is appropriate for use in both sexes. Lower cutoff thresholds are recommended to identify those with potentially disordered drinking to best plan effective interventions and treatments. SHORT SUMMARY: A CFA of the AUDIT showed good fit for one-, two, and three-factor models overall and by sex in a representative sample in post-conflict Northern Uganda. A three-plus total AUDIT cutoff score is suggested to screen for hazardous drinking in this or similar populations.

The Role of Gender in Suicidal Ideation among Long-term Opioid Users.

OBJECTIVE: This study aims to examine factors associated with suicidal ideation among people with opioid dependence and to explore whether these factors are gender-specific. METHODS: Cross-sectional data were collected among long-term opioid-dependent individuals ( n = 176; 46.0% women). Lifetime histories of suicidal ideation were measured using the Composite International Diagnostic Interview, and additional data were collected regarding sociodemographic characteristics, drug use, health, and adverse life events. Multivariable logistic regression was used to determine the relationships between these variables and suicidal ideation for the full study sample and separately for women and men to explore the potential role of gender. RESULTS: A total of 43.8% ( n = 77) of participants reported a lifetime history of suicidal ideation. Among those with suicidal ideation, 49.3% were women and the overall average age of first ideation was 19.82 years (SD, 11.66 years). Results from multivariable analyses showed that a history of depression, anxiety, and childhood emotional neglect and the number of lifetime traumatic events were significantly associated with higher odds of suicidal ideation. The gender-based analysis suggested that histories of depression and anxiety remained independently associated with lifetime suicidal ideation among women, whereas for men, childhood emotional neglect and the number of lifetime potentially traumatic events were independently associated with lifetime suicidal ideation. CONCLUSIONS: This study offers a critical first step to understanding factors associated with suicidal ideation among long-term opioid-dependent men and women and the potential importance of gender-sensitive approaches for suicidal behavior interventions. These data inform further research and clinical opportunities aiming to better respond to the psychological health needs of this population.

Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic.

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.

"The Cango Lyec Project - Healing the Elephant": HIV related vulnerabilities of post-conflict affected populations aged 13-49 years living in three Mid-Northern Uganda districts.

BACKGROUND: The protracted war between the Government of Uganda and the Lord's Resistance Army in Northern Uganda (1996-2006) resulted in widespread atrocities, destruction of health infrastructure and services, weakening the social and economic fabric of the affected populations, internal displacement and death. Despite grave concerns that increased spread of HIV/AIDS may be devastating to post conflict Northern Uganda, empirical epidemiological data describing the legacy of the war on HIV infection are scarce. METHODS: The 'Cango Lyec' Project is an open cohort study involving conflict-affected populations living in three districts of Gulu, Nwoya and Amuru in mid-northern Uganda. Between November 2011 and July 2012, 8 study communities randomly selected out of 32, were mapped and house-to-house census conducted to enumerate the entire community population. Consenting participants aged 13-49 years were enrolled and interviewer-administered data were collected on trauma, depression and socio-demographic-behavioural characteristics, in the local Luo language. Venous blood was taken for HIV and syphilis serology. Multivariable logistic regression was used to determine factors associated with HIV prevalence at baseline. RESULTS: A total of 2954 participants were eligible, of whom 2449 were enrolled. Among 2388 participants with known HIV status, HIV prevalence was 12.2% (95%CI: 10.8-13.8), higher in females (14.6%) than males (8.5%, p < 0.001), higher in Gulu (15.2%) than Nwoya (11.6%, p < 0.001) and Amuru (7.5%, p = 0.006) districts. In this post-conflict period, HIV infection was significantly associated with war trauma experiences (Adj. OR = 2.50; 95%CI: 1.31-4.79), the psychiatric problems of PTSD (Adj. OR = 1.44; 95%CI: 1.06-1.96), Major Depressive Disorder (Adj. OR = 1.89; 95%CI: 1.28-2.80) and suicidal ideation (Adj. OR = 1.87; 95%CI: 1.34-2.61). Other HIV related vulnerabilities included older age, being married, separated, divorced or widowed, residing in an urban district, ulcerative sexually transmitted infections, and staying in a female headed household. There was no evidence in this study to suggest that people with a history of abduction were more likely to be HIV positive. CONCLUSIONS: HIV prevalence in this post conflict-affected population is high and is significantly associated with age, trauma, depression, history of ulcerative STIs, and residing in more urban districts. Evidence-based HIV/STI prevention programs and culturally safe, gender and trauma-informed are urgently needed.

Factors Associated with Perceived Abuse in the Health Care System Among Long-Term Opioid Users: A Cross-Sectional Study.

BACKGROUND: Opioid-dependence is a chronic relapsing disorder. Histories of physical, sexual, and emotional abuse are prevalent among long-term opioid users. While perceived abuse in health care has been linked to histories of abuse in other populations it has not been investigated among long-term opioid users. OBJECTIVE: To determine factors associated with perceived abuse in health care among a sample of long-term opioid users. METHODS: Gender Matters in the Health of Long-Term Opioid Users (GeMa) was a descriptive cross-sectional study. Participants (n = 175) answered questions on health, drug use, treatment history, and victimization. A multivariable model of perceived abuse in health care was built using logistic regression. RESULTS: Half of participants (n = 88) reported perceived abuse in health care in lifetime with no gender differences. Histories of abuse, physical, and psychological health problems, and health care access were more prevalent among those reporting perceived abuse in health care compared to those not reporting such experiences. Multivariable analysis showed that more methadone maintenance treatment attempts in life, prescribed psychiatric medication in life, and having higher childhood emotional abuse scores were independently associated with perceived abuse in health care. Among all childhood neglect and abuse types measured, emotional abuse was the only significant predictor. CONCLUSIONS: A high prevalence of lifetime perceived abuse in health care (50%) was reported, along with extremely high childhood abuse and neglect scores. Consideration of these variables by health care and service providers is extremely important to improving patient perceptions of care, and ultimately health and treatment outcomes among opioid-dependent people.

Heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addiction†.

BACKGROUND: Supervised injectable heroin (SIH) treatment has emerged over the past 15 years as an intensive treatment for entrenched heroin users who have not responded to standard treatments such as oral methadone maintenance treatment (MMT) or residential rehabilitation. AIMS: To synthesise published findings for treatment with SIH for refractory heroin-dependence through systematic review and meta-analysis, and to examine the political and scientific response to these findings. METHOD: Randomised controlled trials (RCTs) of SIH treatment were identified through database searching, and random effects pooled efficacy was estimated for SIH treatment. Methodological quality was assessed according to criteria set out by the Cochrane Collaboration. RESULTS: Six RCTs met the inclusion criteria for analysis. Across the trials, SIH treatment improved treatment outcome, i.e. greater reduction in the use of illicit 'street' heroin in patients receiving SIH treatment compared with control groups (most often receiving MMT). CONCLUSIONS: SIH is found to be an effective way of treating heroin dependence refractory to standard treatment. SIH may be less safe than MMT and therefore requires more clinical attention to manage greater safety issues. This intensive intervention is for a patient population previously considered unresponsive to treatment. Inclusion of this low-volume, high-intensity treatment can now improve the impact of comprehensive healthcare provision.

The Cedar Project: resilience in the face of HIV vulnerability within a cohort study involving young Indigenous people who use drugs in three Canadian cities.

BACKGROUND: Indigenous scholars have long argued that it is critical for researchers to identify factors related to cultural connectedness that may protect against HIV and hepatitis C infection and buffer the effects of historical and lifetime trauma among young Indigenous peoples. To our knowledge, no previous epidemiological studies have explored the effect of historical and lifetime traumas, cultural connectedness, and risk factors on resilience among young, urban Indigenous people who use drugs. METHODS: This study explored risk and protective factors associated with resilience among participants of the Cedar Project, a cohort study involving young Indigenous peoples who use illicit drugs in three cities in British Columbia, Canada. We utilized the Connor-Davidson Resilience Scale to measure resilience, the Childhood Trauma Questionnaire to measure childhood maltreatment, and the Symptom-Checklist 90-Revised to measure psychological distress among study participants. Multivariate linear mixed effects models (LME) estimated the effect of study variables on mean change in resilience scores between 2011-2012. RESULTS: Among 191 participants, 92 % had experienced any form of childhood maltreatment, 48 % had a parent who attended residential school, and 71 % had been in foster care. The overall mean resilience score was 62.04, with no differences between the young men and women (p = 0.871). Adjusted factors associated with higher mean resilience scores included having grown up in a family that often/always lived by traditional culture (B = 7.70, p = 0.004) and had often/always spoken their traditional language at home (B = 10.52, p < 0.001). Currently knowing how to speak a traditional language (B = 13.06, p = 0.001), currently often or always living by traditional culture (B = 6.50, p = 0.025), and having recently sought drug/alcohol treatment (B = 4.84, p = 0.036) were also significantly associated with higher mean resilience scores. Adjusted factors associated with diminished mean resilience scores included severe childhood emotional neglect (B = -13.34, p = 0.001), smoking crack daily (B = -5.42, p = 0.044), having been sexual assaulted (B = 14.42, p = 0.041), and blackout drinking (B = -6.19, p = 0.027). CONCLUSIONS: Young people in this study have faced multiple complex challenges to their strength. However, cultural foundations continue to function as buffers that protect young Indigenous people from severe health outcomes, including vulnerability to HIV and HCV infection.

The mobilization of nurse-client therapeutic relationships in injectable opioid agonist treatment: Autonomy, advocacy and action.

INTRODUCTION: Injectable opioid agonist treatment (iOAT) is an evidence-based treatment that serves an important minority of people with opioid use disorder who require specialized care. Unique to iOAT care is the consistency with which clients access treatment (up to three times daily), a condition that creates repeated opportunities for health care engagement. To date, no study has examined therapeutic relationships in this life saving, nurse-led treatment that can have lasting implications in the equitable delivery of other forms of addictions care. METHODS: This study used grounded theory to generate a dynamic framework for therapeutic relationship building in iOAT. Researchers collected semi-structured interviews from registered nurses working in iOAT sites (n=24) form January 2020 through June 2022. The study analyzed collected data through a constant comparative analysis; explored through open, axial, and selective coding; and assessed in a conditional relationship matrix. The team reviewed key findings with stakeholders through formalized processes of engagement to confirm saturation of coding categories. Throughout data collection and analysis, researchers integrated feedback from additional knowledge users and member checking. Reported findings adhered to the COREQ1 standardized checklist. RESULTS: We identified five interrelated categories that created a distinct culture of care for iOAT nurses: Ways of Knowing, Personal Investment, Leveraging Empathy, Finding Flexibility, and Collaborating to Overcome. Through creating a safe, nonjudgmental environment, nurses establish therapeutic relationships that build trust to identify client needs outside of medication administration. In turn, nurses participate in team-based problem solving to advocate for client needs. If nurses cannot find flexibility within and outside of the health care system to improve client engagement, tensions can arise and therapeutic relationships can be strained. CONCLUSIONS: Therapeutic relationships are an integral part of building and maintaining trust with a population that has been precariously involved with other forms of health care. Nurses make a substantial effort to create a safe and nonjudgmental environment to manifest a culture of care that bridges client needs and program access. Without the expansion of access to iOAT programs and their embedded services, nurses are limited in their ability to provide individualized care for clients with diverse needs.

Changes in daily dose in open-label compared to double-blind: The role of clients' expectations in injectable opioid agonist treatment.

Introduction: Though double-blind studies have indicated that hydromorphone and diacetylmorphine produce similar effects when administered through injectable opioid agonist treatment (iOAT) programs, participant preference may influence some aspects of medication dispensation such as dose. Methods:  This is a retrospective longitudinal analysis. Participants (n = 131) were previously enrolled in a double-blind clinical trial for iOAT who continued to receive treatment in an open-label follow up study. Data included medication dispensation records from 2012 to 2020. Using linear regression and paired t-tests, average daily dose totals of hydromorphone and diacetylmorphine were examined comparatively between double-blind and open-label periods. A subgroup analysis explored dose difference by preference using the proxy, blinding guess, a variable used to facilitate the measurement of treatment masking during the clinical trial by asking which medication the participant thought they received. Results: During the open-label period, participants prescribed diacetylmorphine received 49.5 mg less than during the double-blind period (95% CI -12.6,-86.4). Participants receiving hydromorphone did not see a significant dose decrease. Participants who guessed they received hydromorphone during the clinical trial, but learned they were on diacetylmorphine during the open-label period, saw a decrease in total daily dose of 78.3 mg less (95% CI -134.3,-22.4) during the open-label period. Conclusion: If client preference is considered in the treatment of chronic opioid use disorder, clients may be able to better moderate their dose to suit their individual needs. Together with their healthcare providers, clients can participate in their treatment trajectories collaboratively to optimize client outcomes and promote person-centered treatment options.

Provider experiences with relaxing restrictions on take-home medications for opioid use disorder during the COVID-19 pandemic: A qualitative systematic review.

BACKGROUND: Historical restrictions on take-home medications for opioid use disorder have generated considerable debate. The COVID-19 pandemic shifted the perceived risks and benefits of daily clinic attendance and led to widespread policy reform, creating an unprecedented opportunity to explore the impact of more flexible prescribing. We conducted a qualitative systematic review to synthesize the evidence on providers' experiences with relaxing restrictions on take-home doses of medications prescribed for opioid use disorder during the COVID-19 pandemic. METHODS: The protocol for this systematic review was registered in PROSPERO (CRD42022360589; https://www.crd.york.ac.uk/prospero/). From Sept.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, the Cochrane Register of Controlled Trials, and the grey literature from 2020 onward. Studies were eligible for inclusion if they used qualitative methods to investigate providers' experiences with relaxed restrictions on take-home medications for opioid use disorder during the COVID-19 pandemic. We appraised study quality using the CASP qualitative checklist and used thematic synthesis and GRADE-CERQual to synthesize the results. RESULTS: We retrieved 13 articles representing 11 studies. Six were conducted in the United States and most focused on changes to methadone treatment. Providers' experiences with increased flexibilities around take-homes were broadly positive, despite widespread initial concern over client safety and the potential for medication misuse. For a small number of providers, concerns about diversion were a specific manifestation of more general unease with loss of control over clients and the treatment process. Most providers appreciated increased flexibilities and described them as enabling more individualized, person-centered care. CONCLUSION: Our findings support the continuation of flexibilities around take-homes and demonstrate that regulations and policies that reduce flexibility around take-homes conflict with person-centered approaches to care. Stronger guidance and support from professional regulatory agencies may help increase uptake of flexibilities around take-homes.

The impact of relaxing restrictions on take-home doses during the COVID-19 pandemic on program effectiveness and client experiences in opioid agonist treatment: a mixed methods systematic review.

BACKGROUND: The COVID-19 pandemic led to an unprecedented relaxation of restrictions on take-home doses in opioid agonist treatment (OAT). We conducted a mixed methods systematic review to explore the impact of these changes on program effectiveness and client experiences in OAT. METHODS: The protocol for this review was registered in PROSPERO (CRD42022352310). From Aug.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, Cochrane Register of Controlled Trials, and the grey literature. We included studies reporting quantitative measures of retention in treatment, illicit substance use, overdose, client health, quality of life, or treatment satisfaction or using qualitative methods to examine client experiences with take-home doses during the pandemic. We critically appraised studies using the Mixed Methods Appraisal Tool. We synthesized quantitative data using vote-counting by direction of effect and presented the results in harvest plots. Qualitative data were analyzed using thematic synthesis. We used a convergent segregated approach to integrate quantitative and qualitative findings. RESULTS: Forty studies were included. Most were from North America (23/40) or the United Kingdom (9/40). The quantitative synthesis was limited by potential for confounding, but suggested an association between take-home doses and increased retention in treatment. There was no evidence of an association between take-home doses and illicit substance use or overdose. Qualitative findings indicated that take-home doses reduced clients' exposure to unregulated substances and stigma and minimized work/treatment conflicts. Though some clients reported challenges with managing their medication, the dominant narrative was one of appreciation, reduced anxiety, and a renewed sense of agency and identity. The integrated analysis suggested reduced treatment burden as an explanation for improved retention and revealed variation in individual relationships between take-home doses and illicit substance use. We identified a critical gap in quantitative measures of patient-important outcomes. CONCLUSION: The relaxation of restrictions on take-home doses was associated with improved client experience and retention in OAT. We found no evidence of an association with illicit substance use or overdose, despite the expansion of take-home doses to previously ineligible groups. Including patient-important outcome measures in policy, program development, and treatment planning is essential to ensuring that decisions around take-home doses accurately reflect their value to clients.

The Impact of Injectable Opioid Agonist Treatment (iOAT) on Involvement in Criminalized Activities: A Secondary Analysis from a Clinical Trial in Vancouver, BC.

Purpose: A significant portion of the economic consequences of untreated Opioid Use Disorder (OUD) relate to individuals' involvement in the criminal justice system. The present study uncovers if treatment with iOAT is related to the number of criminal charges amongst participants, what type of crime participants were involved in, and the frequency with which participants were victims of crime. This study contributes to the body of research on the effectiveness of iOAT reducing criminal involvement. Patients and Methods: This is a secondary analysis of police record data obtained from the Vancouver Police Department over a three-year period during the Study to Assess Longer-term Opioid Medication Effectiveness clinical trial. The data was obtained from participants (N = 192) enrolled in the trial through a release of information form. Results: During the three-year period, most charges (45.6%) were property offences, and 25.5% of participants were victims of crime. Participants with no treatment prior to randomization into the SALOME trial were 2.61 (95% CI = 1.64-4.14) more likely to have been charged with a crime than during the iOAT state. Conclusion: IOAT can reduce individuals' involvement with the criminal justice system and is thus a crucial part of the continuum of care. Addiction should be conceptualized as a healthcare rather than criminal issue.

The Cedar Project: Racism and its impacts on health and wellbeing among young Indigenous people who use drugs in Prince George and Vancouver, BC.

Racism continues to drive health disparities between Indigenous and non-Indigenous peoples in Canada. This study focuses on racism experienced by young Indigenous people who have used drugs in British Columbia (BC), and predictors of interpersonal racism. Cedar Project is a community-governed cohort study involving young Indigenous people who use drugs in Vancouver and Prince George, BC. This cross-sectional study included data collected between August 2015-October 2016. The Measure of Indigenous Racism Experiences (MIRE) scale was used to assess experiences of interpersonal racism across 9 unique settings on a 5-point Likert scale, collapsing responses into three categories (none/low/high). Multinomial logistic regression models were used to examine associations between key variables and interpersonal racism. Among 321 participants, 79% (n = 255) experienced racism in at least one setting. Thirty two percent (n = 102) experienced high interpersonal racism from police, governmental agencies (child 'welfare', health personnel), and in public settings. Ever having a child apprehended (AOR:2.76, 95%CI:1.14-6.65), probable post-traumatic stress (AOR:2.64; 95%CI:1.08-6.46), trying to quit substances (AOR:3.69; 95%CI:1.04-13.06), leaving emergency room without receiving treatment (AOR:3.05; 95%CI:1.22-7.64), and having a traditional language spoken at home while growing up (AOR:2.86; 95%CI:1.90-6.90) were associated with high interpersonal racism. Among women, experiencing high interpersonal racism was more likely if they lived in Prince George (AOR:3.94; 95%CI:1.07-14.50), ever had a child apprehended (AOR:5.09; 95%CI:1.50-17.30), and had probable post-traumatic stress (AOR:5.21; 95%CI:1.43-18.95). Addressing racism experienced by Indigenous peoples requires immediate structural systemic, and interpersonal anti-racist reforms.

Cango Lyec (Healing the Elephant): HIV Prevalence and Vulnerabilities Among Adolescent Girls and Young Women in Postconflict Northern Uganda.

OBJECTIVES: Adolescent girls and young women younger than 25 years (AGYW) account for disproportionate HIV infections in sub-Saharan Africa. Impacts of war in Northern Uganda continue to affect HIV-related health and wellbeing of young people postconflict. Prevalence and incidence of HIV infection were estimated, and factors associated with HIV prevalence among sexually active AGYW in Northern Uganda were investigated. METHODS: Cango Lyec is a cohort involving conflict-affected populations in Northern Uganda. Nine randomly selected communities in Gulu, Nwoya, and Amuru districts were mapped. House-to-house census was conducted. Consenting participants aged 13-49 years were enrolled over 3 study rounds (2011-2015), of whom 533 were AGYW and had ever had sex. Data were collected on trauma, depression, and sociodemographic-behavioral characteristics. Venous blood was taken for HIV and syphilis serology. Multivariable logistic regression determined baseline factors associated with HIV prevalence. RESULTS: HIV prevalence among AGYW was 9.7% (95% CI: 7.3 to 12.6). AGYW living in Gulu (adjusted risk ratio, aRR: 2.48; 95% CI: 1.12 to 5.51) or Nwoya (aRR: 2.65; 95% CI: 1.03 to 6.83) were more likely than in Amuru to be living with HIV. Having self-reported genital ulcers (aRR: 1.93; 95% CI: 0.97 to 3.85) or active syphilis (aRR: 3.79; 95% CI: 2.35 to 6.12) was associated with increased risk of HIV infection. The likelihood of HIV was higher for those who experienced sexual violence in the context of war (aRR: 2.37; 95% CI: 1.21 to 4.62) and/or probable depression (aRR: 1.95; 95% CI: 1.08 to 3.54). HIV incidence was 8.9 per 1000 person-years. CONCLUSION: Ongoing legacies of war, especially gender violence and trauma, contribute to HIV vulnerability among sexually active AGYW. Wholistic approaches integrating HIV prevention with culturally safe initiatives promoting sexual and mental health in Northern Uganda are essential.

Diacetylmorphine versus methadone for the treatment of opioid addiction.

BACKGROUND: Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence. METHODS: In an open-label, phase 3, randomized, controlled trial in Canada, we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment. Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction (including at least one methadone treatment) were randomly assigned to receive methadone (111 patients) or diacetylmorphine (115 patients). The primary outcomes, assessed at 12 months, were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index. RESULTS: The primary outcomes were determined in 95.2% of the participants. On the basis of an intention-to-treat analysis, the rate of retention in addiction treatment in the diacetylmorphine group was 87.8%, as compared with 54.1% in the methadone group (rate ratio for retention, 1.62; 95% confidence interval [CI], 1.35 to 1.95; P<0.001). The reduction in rates of illicit-drug use or other illegal activity was 67.0% in the diacetylmorphine group and 47.7% in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; P=0.004). The most common serious adverse events associated with diacetylmorphine injections were overdoses (in 10 patients) and seizures (in 6 patients). CONCLUSIONS: Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.)

Cost-effectiveness of diacetylmorphine versus methadone for chronic opioid dependence refractory to treatment.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.