Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. Objective: To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. Design, Setting, and Participants: The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Interventions: Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Main Outcomes and Measures: Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. Results: A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. Conclusions and Relevance: In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT04762537.

Healthcare utilisation and costs associated with adherence to antipsychotics among people living with HIV/AIDS and schizophrenia: a population-based cohort study in British Columbia, Canada.

OBJECTIVES: Non-adherence to antipsychotics is the greatest obstacle to treating schizophrenia. We assessed the economic and clinical impacts of adherence to antipsychotics among people living with HIV/AIDS (PLWH) and schizophrenia in British Columbia, Canada. DESIGN AND SETTING: A population-based cohort study in British Columbia, Canada. METHODS: Eligible PLWH were enrolled in the Seek and Treat for Optimal Prevention HIV/AIDS population-based cohort during 2001-2016, diagnosed with schizophrenia, on antipsychotics for ≥1 day, and followed for ≥1 year from schizophrenia diagnosis date or 1 January 2001, whichever occurred last. PRIMARY AND SECONDARY OUTCOME MEASURES: A two-part model assessed the marginal effect of adherence on healthcare costs (in 2016 Canadian dollar), while logistic regression examined the effect on virological failure, and generalised linear mixed models examined the effect on hospital readmissions within 30 days and length of hospital stay. RESULTS: Among 726 PLWH with schizophrenia, ≥80% adherence to antipsychotics increased from 25% (50/198) in 2001 to 41% (225/554) in 2016. In most years, we observed no difference in adherence to antipsychotics among those who used only injectables, only non-injectables, and a combination of both, or among those who have ever consumed typical/first-generation antipsychotics and who consumed only atypical/second-generation antipsychotics. Overall healthcare costs were higher in the non-adherent group ($C2185), driven by the average annual hospitalisation costs ($C5517), particularly among women ($C8806) and people who ever injected drugs (PWID) ($C5985). Non-adherent individuals also experienced higher hospital readmissions (adjusted odds ratio (aOR) 1.48, 95% CI 1.23 to 1.77), and longer hospital stays (adjusted mean ratio 1.23, 95% CI 1.13 to 1.35) in comparison to adherent individuals. We found no difference in virological failure by adherence groups, except when we stratified by gender where the aOR for women was 2.48 (95% CI 1.06 to 5.82). CONCLUSIONS: Our results showed that implementing strategies and interventions to increase antipsychotic adherence, particularly among women and PWID, will be critical in addressing this public health challenge.

Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): A stepped wedge hybrid type 1 effectiveness-implementation study.

BACKGROUND: Extended-release injectable naltrexone (XR-NTX) is an effective treatment for opioid use disorder (OUD), but initiation remains a barrier to implementation. Standard practice requires a 10- to 15-day inpatient admission prior to XR-NTX initiation and involves a methadone or buprenorphine taper followed by a 7- to 10-day washout, as recommended in the Prescribing Information for XR-NTX. A 5- to 7-day rapid induction approach was developed that utilizes low-dose oral naltrexone and non-opioid medications. METHODS: The CTN-0097 Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT) study was a hybrid type I effectiveness-implementation trial that compared the effectiveness of the standard procedure (SP) to the rapid procedure (RP) for XR-NTX initiation across six community inpatient addiction treatment units, and evaluated the implementation process. Sites were randomized to RP every 14 weeks in an optimized stepped wedge design. Participants (target recruitment = 450) received the procedure (SP or RP) that the site was implementing at time of admission. The hypothesis was RP will be non-inferior to SP on proportion of inpatients who receive XR-NTX, with a shorter admission time for RP. Superiority testing of RP was planned if the null hypothesis of inferiority of RP to SP was rejected. DISCUSSION: If RP for XR-NTX initiation is shown to be effective, the shorter inpatient stay could make XR-NTX more feasible and have an important public health impact expanding access to OUD pharmacotherapy. Further, a better understanding of facilitators and barriers to RP implementation can help with future translatability and uptake to other community programs. TRIAL REGISTRATION: NCT04762537 Registered February 21, 2021.

A province-wide HIV initiative to accelerate initiation of treatment-as-prevention and virologic suppression in British Columbia, Canada: a population-based cohort study.

BACKGROUND: In 2010, HIV treatment as prevention (TasP), encompassing widespread HIV testing and immediate initiation of free antiretroviral treatment (ART), was piloted under the Seek and Treat for Optimal Prevention of HIV/AIDS initiative (STOP) in British Columbia, Canada. We compared the time from HIV diagnosis to treatment initiation, and from treatment initiation to first virologic suppression, before (2005-2009) and after (2010-2016) the implementation of STOP. METHODS: In this population-based cohort study, we used longitudinal data of all people living with an HIV diagnosis in BC from 1996 to 2017. We included those aged 18 years or older who had never received ART and had received an HIV diagnosis in the 2005-2016 period. We defined the virologic suppression date as the first date of at least 2 consecutive test results within 4 months with a viral load of less than 200 copies/mL. Negative binomial regression models assessed the effect of STOP on the time to ART initiation and suppression, adjusting for confounders. All p values were 2-sided, and we set the significance level at 0.05. RESULTS: Participants who received an HIV diagnosis before STOP (n = 1601) were statistically different from those with a diagnosis after STOP (n = 1700); 81% versus 84% were men (p = 0.0187), 30% versus 15% had ever injected drugs (p < 0.0001), and 27% versus 49% had 350 CD4 cells/µL or more at diagnosis (p < 0.0001). The STOP initiative was associated with a 64% shorter time from diagnosis to treatment (adjusted mean ratio 0.36, 95% confidence interval [CI] 0.34-0.39) and a 21% shorter time from treatment to suppression (adjusted mean ratio 0.79, 95% CI 0.73-0.85). INTERPRETATION: In a population with universal health coverage, a TasP intervention was associated with shorter times from HIV diagnosis to treatment initiation, and from treatment initiation to viral suppression. Our results show accelerating progress toward the United Nations' 90-90-90 target of people with HIV who have a diagnosis, those who are on antiretroviral therapy and those who are virologically suppressed, and support the global expansion of TasP to accelerate the control of HIV/AIDS.

Disparities in multimorbidity and mortality among people living with and without HIV across British Columbia's health regions: a population-based cohort study.

OBJECTIVES: Longer survival has increased the likelihood of antiretroviral-treated people living with HIV (PLWH) developing age-associated comorbidities. We compared the burden of multimorbidity and all-cause mortality across HIV status in British Columbia (BC), and assessed the longitudinal effect of multimorbidity on all-cause mortality among PLWH. METHODS: Antiretroviral-treated PLWH aged ≥19 years and 1:4 age-sex-matched HIV-negative individuals from a population-based cohort were followed for ≥1 year during 2001-2012. Diagnoses of seven age-associated comorbidities were identified from provincial administrative databases and grouped into 0, 1, 2, and ≥3 comorbidities. Multimorbidity prevalence and age-standardized mortality rates (ASMRs) in both populations were stratified by BC's health regions. Marginal structural models were used to estimate the effect of multimorbidity on mortality among PLWH, adjusted for time-varying confounders affected by prior multimorbidity. RESULTS: Among 8031 PLWH and 32,124 HIV-negative individuals, 25% versus 11% developed multimorbidity, and 23.53 deaths/1000 person-years (95% confidence interval [95% CI]: 22.02-25.13) versus 3.04 (2.81-3.29) were observed, respectively. PLWH in Northern region had the highest ASMR, but those in South Vancouver Island experienced the greatest difference in mortality compared with HIV-negative individuals. Among PLWH, compared with those with zero comorbidities, adjusted hazard ratios for those with 1, 2, and ≥3 comorbidities were 3.36 (95% CI: 2.86-3.95), 6.92 (5.75-8.33), and 12.87 (10.45-15.85), respectively. CONCLUSION: PLWH across BC's health regions experience excess multimorbidity and associated mortality. We highlight health disparities which are key when planning the distribution of healthcare resources across BC, and provide evidence for improved HIV care models integrating prevention and management of chronic diseases.

RéSUMé: OBJECTIF: Les nouvelles thérapeutiques antirétrovirales (ARV) ont permis une plus longue espérance de vie aux personnes porteuses du VIH. Cependant, le vieillissement augmente la probabilité de développer des comorbidités au sein même de la population des personnes vivant avec le VIH (PVVIH) qui suivent des traitements ARV. On a comparé le fardeau de la multimorbidité et mortalité, toutes causes confondues, lié au statut VIH à travers la Colombie-Britannique. On a aussi évalué l'effet longitudinal de la multimorbidité sur la mortalité, toutes causes confondues, parmi les PVVIH. MéTHODES: L'étude comprit des PVVIH suivant un traitement ARV âgés de ≥19 ans et un groupe témoin séronégatif (4 témoins par PVVIH) comparable en termes d'âge et de sexe, tous provenant d'une cohorte de surveillance continue d'au moins 1 an sur une période allant de 2001 à 2012. Des diagnostics de sept comorbidités liées à l'âge ont été identifiés à partir des bases de données administratives provinciales et regroupés en 0, 1, 2 et ≥3 comorbidités. La prévalence de la multimorbidité et les taux de mortalité normalisés selon l'âge (TMNA) dans les deux populations ont été stratifiés selon les régions sociosanitaires de la Colombie-Britannique. Des modèles structurels marginaux ont été utilisés pour estimer l'effet de la multimorbidité sur la mortalité chez les PVVIH, ajustant pour les facteurs de confusion variables affectés par une multimorbidité antérieure. RéSULTATS: Parmi 8 031 PVVIH et 32 124 personnes séronégatives pour le VIH, 25 % contre 11 % ont développé une multimorbidité et 23,53 décès pour 1 000 personnes-années (intervalle de confiance à 95 % [IC à 95 %]: 22,02­25,13) contre 3,04 (2,81­3,29) ont été observés, respectivement. Les PVVIH de la région septentrionale avaient le TMNA le plus élevé, alors que ceux du sud de l'île de Vancouver ont connu la plus grande différence de mortalité par rapport aux personnes séronégatives. Parmi les PVVIH, les personnes atteintes de 1, 2 et ≥3 comorbidités avaient respectivement 3,36 (IC à 95 %: 2,86­3,95), 6,92 (5,75­8,33) et 12,87 (10,45­15,85) fois plus la probabilité de mourir que les personnes sans comorbidités. CONCLUSION: Les PVVIH des régions sociosanitaires de la Colombie-Britannique connaissent une multimorbidité excessive et la surmortalité s'y associant. Notre étude souligne les disparités-clés en matière de santé qu'il faut prendre en compte lors de la planification de la distribution des ressources de soins de santé à travers la Colombie-Britannique. Elle fournit aussi des preuves pour des modèles de soins du VIH améliorés, y intégrant la prévention et la gestion des maladies chroniques.

Excess burden of age-associated comorbidities among people living with HIV in British Columbia, Canada: a population-based cohort study.

OBJECTIVES: As people living with HIV (PLWH) live longer, morbidity and mortality from non-AIDS comorbidities have emerged as major concerns. Our objective was to compare prevalence trends and age at diagnosis of nine chronic age-associated comorbidities between individuals living with and without HIV. DESIGN AND SETTING: This population-based cohort study used longitudinal cohort data from all diagnosed antiretroviral-treated PLWH and 1:4 age-sex-matched HIV-negative individuals in British Columbia, Canada. PARTICIPANTS: The study included 8031 antiretroviral-treated PLWH and 32 124 HIV-negative controls (median age 40 years, 82% men). Eligible participants were ≥19 years old and followed for ≥1 year during 2000 to 2012. PRIMARY AND SECONDARY OUTCOME MEASURES: The presence of non-AIDS-defining cancers, diabetes, osteoarthritis, hypertension, Alzheimer's and/or non-HIV-related dementia, cardiovascular, kidney, liver and lung diseases were identified from provincial administrative databases. Beta regression assessed annual age-sex-standardised prevalence trends and Kruskal-Wallis tests compared the age at diagnosis of comorbidities stratified by rate of healthcare encounters. RESULTS: Across study period, the prevalence of all chronic age-associated comorbidities, except hypertension, were higher among PLWH compared with their community-based HIV-negative counterparts; as much as 10 times higher for liver diseases (25.3% vs 2.1%, p value<0.0001). On stratification by healthcare encounter rates, PLWH experienced most chronic age-associated significantly earlier than HIV-negative controls, as early as 21 years earlier for Alzheimer's and/or dementia. CONCLUSIONS: PLWH experienced higher prevalence and earlier age at diagnosis of non-AIDS comorbidities than their HIV-negative controls. These results stress the need for optimised screening for comorbidities at earlier ages among PLWH, and a comprehensive HIV care model that integrates prevention and treatment of chronic age-associated conditions. Additionally, the robust methodology developed in this study, which addresses concerns on the use of administrative health data to measure prevalence and incidence, is reproducible to other settings.

The uptake of family screening in hypertrophic cardiomyopathy and an online video intervention to facilitate family communication.

BACKGROUND: Individuals with hypertrophic cardiomyopathy (HCM), even when asymptomatic, are at-risk for sudden cardiac death and stroke from arrhythmias, making it imperative to identify individuals affected by this familial disorder. Consensus guidelines recommend that first-degree relatives (FDRs) of a person with HCM undergo serial cardiovascular evaluations. METHODS: We determined the uptake of family screening in patients with HCM and developed an online video intervention to facilitate family communication and screening. Family screening and genetic testing data were collected through a prospective quality improvement initiative, a standardized clinical assessment and management plan (SCAMP), utilized in an established cardiovascular genetics clinic. Patients were prescribed an online video if screening of their FDRs was incomplete and a pilot study on video utilization and family communication was conducted. RESULTS: Two-hundred and sixteen probands with HCM were enrolled in SCAMP Phase I and 190 were enrolled in SCAMP Phase II. In both phases, probands reported that 51% of FDRs had been screened (382/749 in Phase I, 258/504 in Phase II). Twenty patients participated in a pilot study on video utilization and family communication. Nine participants reported watching the video and six participants reported sharing the video with relatives; however only one participant reported sharing the video with relatives who were not yet aware of the diagnosis of HCM in the family. CONCLUSION: Despite care in a specialized cardiovascular genetics clinic, approximately one half of FDRs of patients with HCM remained unscreened. Online interventions and videos may serve as supplemental tools for patients communicating genetic risk information to relatives.