Predictors of alcohol and other drug treatment completion among young people accessing residential and community-based treatment: A retrospective analysis of routinely collected service data.

BACKGROUND AND AIMS: Young people accessing alcohol and other drug (AOD) treatment experience high rates of treatment disengagement, contributing to poorer outcomes. To improve outcomes, it is important to identify factors associated with treatment retention. This study measured the relationships between client characteristics, treatment characteristics, clinical severity measures and completion of treatment among young people. DESIGN, SETTING AND PARTICIPANTS: This study was a retrospective analysis of routinely collected data set in residential- and community-based AOD services in New South Wales, Australia. Routinely collected data from the Network of Alcohol and Other Drug Agencies' (NADA) database were used. Included individuals were aged 10-24 years and accessed treatment between 2012 and 2023 (n = 17 474). MEASUREMENTS: Variables included client-related characteristics, service characteristics and baseline measures of clinical severity [Kessler-10 (K10), EUROHIS-QoL, severity of dependence scale (SDS)]. Multivariable binary logistic regression models assessed the relationships between these characteristics and treatment completion. FINDINGS: Rates of treatment completion were highest among adolescents in community-based treatment (57%) and lowest among young adults in residential treatment (35%). Polysubstance use was negatively associated with treatment completion among adolescents [adjusted odds ratio (adjOR) = 0.71, P < 0.001] and adults (adjOR = 0.70, P < 0.001) in community-based treatment, and adolescents in residential treatment (adjOR = 0.62, P = 0.006), as was housing insecurity (adolescents in community treatment, adjOR = 0.61, P = 0.001; adults in community treatment, adjOR = 0.77, P = 0.002; adolescents in residential treatment, adjOR = 0.42, P = 0.005). Attending youth-specific services was associated with higher treatment completion rates among adults in community-based (adjOR = 1.81, P < 0.001) and residential treatment (adjOR = 1.72, P < 0.001). Varying correlates of treatment completion were identified throughout treatment groups, reflecting the differences in population and/or needs across contexts. CONCLUSIONS: In New South Wales, Australia, fewer than half of young people accessing alcohol and other drug treatment between 2012 and 2023 completed treatment, and completion rates were lower among those facing barriers such as polysubstance use and housing insecurity.

Shifting sands: Indigenous conceptions of health and place in fragile times.

Place and health are deeply interconnected for Indigenous people, and place-based services have been established to better meet people's needs. The meaning of place, however, remains difficult to define, an issue compounded by non-Indigenous settler attempts to erase people's association with place. This paper argues that we must understand place as something more than a geographical locality, and consider the histories, experiences and feelings that connect people to place in the south coast of New South Wales (NSW), Australia. The paper focuses on the role of Aboriginal Community Controlled Organisations (ACCOs) as place-based entities which deliver a range of health and social services to local Aboriginal communities across Australia. This study was undertaken during a period of crisis when places and people's capacity to remain connected to them was perilous due to the 2019/20 bushfires, named in the media as the Black Summer Bushfires. The experience of living through this disastrous period elevated the importance of ACCOs and their unique and deep engagement with the communities they serve.

Women and opioid use disorder treatment: A scoping review of experiences, use of patient-reported experience measures, and integration of person-centred care principles.

BACKGROUND: Patient-reported experience measures (PREMs) are an important aspect of assessing and improving women's experiences of person-centred care during treatment for Opioid Use Disorder (OUD). This scoping review aimed to 1) examine the extent, type, and characteristics of evidence regarding women's OUD treatment experiences, and 2) describe the extent to which PREMs and person-centred care principles are incorporated within research methods. METHODS: Following Joanna Briggs Institute guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), we conducted a scoping review to identify peer-reviewed articles on women's OUD treatment experiences. Data were extracted from 39 included studies and synthesised based on study design, method of assessment/analysis (including use of PREMs), key findings, and the integration of person-centred care principles. RESULTS: Analysis of included studies revealed a predominance of qualitative research focused on women's experiences of pharmacological OUD treatment (methadone and/or buprenorphine) in Western countries. Women in these studies reported predominantly negative or mixed experiences of treatment. Few studies used validated PREMs and there was a lack of direct assessment or focus on recognised person-centred care principles. However, common categories of outcomes/findings identified in results across studies broadly aligned with person-centred care principles (e.g., fast access to reliable healthcare, effective treatment by trusted professionals), emphasising their applicability to women's experiences of treatment. CONCLUSIONS: Although there has been an increased focus on women's experiences of treatment for OUD in recent years, results highlighted room for improvement regarding the systematic and comprehensive assessment of women's experiences across different contexts. Given the often negative or mixed experiences reported by women, an increased focus on assessing service provision through a person-centred care lens (including utilising PREMs) may allow for service improvements or adaptations targeted towards the needs and experiences of women.

Systematic review of treatment completion rates and correlates among young people accessing alcohol and other drug treatment.

BACKGROUND AND AIMS: Treatment completion is associated with improved alcohol and other drug (AOD) treatment outcomes. Unfortunately, treatment disengagement is common, particularly among young people. We reviewed and synthesised research on AOD treatment completion and/or early disengagement among young people. METHODS: We conducted a systematic review and meta-analysis of studies reporting on completion rates and/or early disengagement from psychosocial AOD treatment among adolescents and young adults. An overall estimated treatment completion rate was calculated using inverse-variance random effects meta-analysis, and random-effects meta-regression was used to identify between-study level moderators of completion rate. We completed a narrative review summarising literature on early treatment disengagement and within-study level correlates of treatment completion. Study quality was assessed using the EPHPP. RESULTS: Of the 6158 studies screened, we retained 410 for full text review and included 98 studies in the review. Treatment completion rates were reported in 88 studies, and early disengagement rates were reported in 13. The estimated overall treatment completion rate was 59 % (95 % CI=57-61 %), with experimental studies reporting higher rates of completion than observational studies. There was limited evidence for demographic or substance-related correlates of treatment completion. Contingency management was associated with increased completion rates, as was family-based intervention. CONCLUSIONS: Disengagement from AOD treatment among youth populations is common and contributes to poor treatment outcomes. Existing research has yielded little consensus on the factors associated with treatment completion. The use of contingency management strategies and involving family/social supports in treatment were identified as potential avenues for promoting ongoing treatment engagement.

Patterns of substance use recovery following residential treatment: A repeated measures latent profile analysis.

INTRODUCTION: Ongoing improvement to residential treatment for substance use disorders is critical as it typically targets people with the highest need. Assessing multiple recovery indicators, such as cravings and mental health, at intake and following discharge is important in evaluating treatment effectiveness. To refine services, research should explore whether there are subgroups of individuals with different patterns of recovery following treatment. METHODS: Participants (n = 554) were attending Australian Salvation Army residential treatment services for substance use issues. Data were collected by surveys at intake and 3-month post-discharge ('early recovery'). Recovery indicators were cravings, confidence to resist substance use and the Depression, Anxiety and Stress Scale. Subgroups of individuals based on these recovery indicators ('profiles') were identified using repeated measures latent profile analysis. RESULTS: Five profiles were identified, three profiles improved over time (81.4%) and two (18.6%) deteriorated across all indicators. These two profiles had the poorest mental health and addiction scores at intake and reported shorter time in treatment compared to the three profiles showing improvement. There were no demographic or substance type differences between profiles. DISCUSSION AND CONCLUSIONS: By considering initial severity and multiple recovery indicators at early recovery, this study suggests that individuals at-risk of poor early recovery can be identified at intake. This opens opportunities for tailored treatment approaches to address both mental health and substance use, thereby potentially improving treatment outcomes and reducing the risk of relapse.

A phase 3 randomised double-blind placebo-controlled trial of mirtazapine as a pharmacotherapy for methamphetamine use disorder: a study protocol for the Tina Trial.

BACKGROUND: There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. METHODS: This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. DISCUSSION: This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial.

BACKGROUND: Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke. METHODS: We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed. FINDINGS: 3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (9·8%) of 1569 patients allocated to colchicine and usual care and 185 (11·7%) of 1575 patients allocated to usual care alone (incidence rates 3·32 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68-1·05, p=0·12). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<0·05 for all timepoints). The rates of serious adverse events were similar in both groups. INTERPRETATION: Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials. FUNDING: Health Research Board Ireland, Deutsche Forschungsgemeinschaft (German Research Foundation), and Fonds Wetenschappelijk Onderzoek Vlaanderen (Research Foundation Flanders), Belgium.

Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial.

BACKGROUND: Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown. METHODS: This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms. RESULTS: Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was -2.2% (95% CI, -7.8% to 3.5%) in people with HT (HI: -4.7% [95% CI, -10.8% to 1.4%]; PH: 6.1% [95% CI, -8.5% to 20.6%]) and -0.9% (95% CI, -2.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3-6) was 11.5% (95% CI, -0.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, -6.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and -2.6% (95% CI, -7.1% to 1.8%) in people without HT. CONCLUSIONS: We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH. REGISTRATION: URL: http://www.clinicaltrials.gov; Unique identifier: NCT03148457.

Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown. Objective: To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation. Design, Setting, and Participants: Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis. Intervention: Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke. Main Outcomes and Measures: The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined. Results: A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters. Conclusions and Relevance: The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03148457.

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year data from the ETNA-AF-Europe study.

BACKGROUND: To assess long-term effectiveness and safety of edoxaban in Europe. METHODS AND RESULTS: ETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively. Median (interquartile range) age of the 13,164 patients was 75.0 (68.0-80.0) years; CHA2DS2-VASc and HAS-BLED scores were 3.0 (2.0-4.0) and 2.0 (1.0-2.0), respectively. Follow-up duration was 3.98 (3.21-4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%). CONCLUSIONS: In European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics.

An International, Multidisciplinary Consensus Set of Patient-Centered Outcome Measures for Substance-Related and Addictive Disorders.

Background: In 1990, the United States' Institute of Medicine promoted the principles of outcomes monitoring in the alcohol and other drugs treatment field to improve the evidence synthesis and quality of research. While various national outcome measures have been developed and employed, no global consensus on standard measurement has been agreed for addiction. It is thus timely to build an international consensus. Convened by the International Consortium for Health Outcomes Measurement (ICHOM), an international, multi-disciplinary working group reviewed the existing literature and reached consensus for a globally applicable minimum set of outcome measures for people who seek treatment for addiction. Methods: To this end, 26 addiction experts from 11 countries and 5 continents, including people with lived experience (n = 5; 19%), convened over 16 months (December 2018-March 2020) to develop recommendations for a minimum set of outcome measures. A structured, consensus-building, modified Delphi process was employed. Evidence-based proposals for the minimum set of measures were generated and discussed across eight videoconferences and in a subsequent structured online consultation. The resulting set was reviewed by 123 professionals and 34 people with lived experience internationally. Results: The final consensus-based recommendation includes alcohol, substance, and tobacco use disorders, as well as gambling and gaming disorders in people aged 12 years and older. Recommended outcome domains are frequency and quantity of addictive disorders, symptom burden, health-related quality of life, global functioning, psychosocial functioning, and overall physical and mental health and wellbeing. Standard case-mix (moderator) variables and measurement time points are also recommended. Conclusions: Use of consistent and meaningful outcome measurement facilitates carer-patient relations, shared decision-making, service improvement, benchmarking, and evidence synthesis for the evaluation of addiction treatment services and the dissemination of best practices. The consensus set of recommended outcomes is freely available for adoption in healthcare settings globally.

An exploration of organizational climate in community-based opiate prescribing services; a mixed methods study.

INTRODUCTION: Assessing the internal dynamics of organizations has been shown to provide information that can help planners and policymakers improve service delivery. A good organizational climate, which in this study incorporates mission clarity, team cohesion, staff autonomy, communication, levels of stress, and openness to change has been shown to be of particular importance. Still, there is a dearth of evidence in this area, and while relationships between organizational factors have been identified, little is known about the mechanisms that might underpin these relationships, and there is little understanding of how to address deficits once they are identified. The objective of this study was to identify relationships between program factors that influence organizational climate and to explore which mechanisms might underpin these relationships. METHODS: This paper reports on a cross-sectional, concurrent, mixed-methods study design, across twelve discrete community-based prescribing service providers (organizations) in Ireland. Data was obtained using a staff survey [n = 132] which utilized measurements of organizational readiness to change and one-to-one interviews [n = 12]. Quantitative data was analyzed using multivariate linear regression modeling which assessed relationships between variables, while interviews were analyzed using an abductive approach, both types of data were synthesized at the interpretation stage. RESULTS: A range of interdependent factors were considered to affect the climate of organizations. Surveys identified that specific types of resources, such as physical infrastructure, training, and staffing resources were important for supporting a good organizational climate, while programs with greater needs had a poorer climate. Opportunities for professional growth, the skill sets of staff, and having access to e-communication were also significant. Interviewees reported that rigid organizational hierarchies and bureaucracy, philosophical views of addiction, stress, and staff turnover were influenced by the provision of fewer resources. Interdependent factors such as leadership, supervision, staff relationships, and collective training, also thought to be influenced by resources, were considered to positively influence programs. Resources were not the only challenge identified, and practices within programs and how existing resources are used were also thought to contribute both positively and negatively to the internal dynamics of services. CONCLUSION: Key findings in this study identified that the organization of effective services is influenced by a range of specific factors, some of which can be addressed without additional resources. Overall, staff views of organizations can provide us with valuable information to support service improvement. Using a mixed methods approach can not only identify where relationships between organizational variables exist but can also help us to understand the mechanisms that underpin these relationships and, importantly, how to address deficits once they are identified. In order to improve how substance misuse services work, the need for a long-term systemic approach to program development, which incorporates some of the findings from this study, is required.

Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: An individual participant and summary-level data meta-analysis of 11 prospective studies.

INTRODUCTION: Inflammation is an emerging target for secondary prevention after stroke and randomised trials of anti-inflammatory therapies are ongoing. Fibrinogen, a putative pro-inflammatory marker, is associated with first stroke, but its association with major adverse cardiovascular events (MACE) after stroke is unclear. MATERIALS AND METHODS: We did a systematic review investigating the association between fibrinogen and post-stroke vascular recurrence. Authors were invited to provide individual-participant data (IPD) and where available we did within-study multivariable analyses with adjustment for cardiovascular risk factors and medications. Adjusted summary-level data was extracted from published reports from studies that did not provide IPD. We pooled risk ratios (RR) by random-effects meta-analysis by comparing supra-median with sub-median fibrinogen levels and performed pre-specified subgroup analysis according to timing of phlebotomy after the index event. RESULTS: Eleven studies were included (14,002 patients, 42,800 follow-up years), of which seven provided IPD. Fibrinogen was associated with recurrent MACE on unadjusted (RR 1.35, 95% CI 1.17-1.57, supra-median vs sub-median) and adjusted models (RR 1.21, 95% CI 1.06-1.38). Fibrinogen was associated with recurrent stroke on univariate analysis (RR 1.19, 95% CI 1.03-1.39), but not after adjustment (RR 1.11, 95% CI 0.94-1.31). The association with recurrent MACE was consistently observed in patients with post-acute (⩾14 days) fibrinogen measures (RR 1.29, 95% CI 1.16-1.45), but not in those with early phlebotomy (<14 days) (RR 0.98, 95% CI 0.82-1.18) (Pinteraction = 0.01). Similar associations were observed for recurrent stroke. DISCUSSION AND CONCLUSION: Fibrinogen was independently associated with recurrence after stroke, but the association was modified by timing of phlebotomy. Fibrinogen measurements might be useful to identify patients who are more likely to derive benefit from anti-inflammatory therapies after stroke.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

SMART Family and Friends: Feasibility and outcomes of a video-conference delivered intervention for families impacted by another's methamphetamine use.

INTRODUCTION: Families affected by another's substance use, including methamphetamine, experience harms to their mental and physical health. Yet, research has paid little attention to support and service needs of this population. This pilot study examines the feasibility and outcomes of SMART Family and Friends, a video-conference-delivered mutual-support group targeting families affected by another's methamphetamine use. METHODS: Recruitment for this study occurred between March-October 2021 via the SMART Recovery Australia website. Participants were English-speaking Australian residents, ≥18 years, affected by another's methamphetamine use, interested in participating in a manualised eight-module group delivered via video-conferencing. Feasibility was evaluated by attendance rates, participant satisfaction, fidelity ratings, and semi-structured interviews. Measures of distress, quality of life, and family functioning assessed outcomes at baseline and one-month post-treatment conclusion. RESULTS: Forty-three participants commenced SMART Family and Friends groups. 84 % (n = 36) completed ≥4 modules, 67 % (n = 29) completed ≥6, and 42 % (n = 18) completed all 8 modules. Participant satisfaction (M = 4.32, SD = 0.66, out of 5) and facilitator fidelity (>94 % for all modules) were high. A within-group analysis, without comparison condition demonstrated significant improvements in psychological distress (d = 0.38), family impact (d = 0.64), family strain symptoms (d = 0.48), and total family burden (d = 0.69) post-treatment. Qualitative findings illustrated the benefits and challenges of the video-conference-delivered group, as well as recommendations for improvement. CONCLUSIONS: Results provide initial support for the feasibility and positive outcomes of the SMART Family and Friends program. These findings demonstrate the successful provision of a mutual-support group for affected families delivered via video-conferencing, and merit further sufficiently powered randomised-control-trials to evaluate efficacy.

'Selling their souls?' Nurses' understanding of addiction and recovery in acute hospital settings.

BACKGROUND: Nursing disciplines do not currently have a shared understanding of addiction or recovery to address their contribution to their patients' needs. Recent developments of addiction nursing models, alongside an international move to standardise language, is slow to be reflected in nurses' perceptions in acute hospital settings. AIM: To explore nurses' understanding of addiction and recovery in acute general hospitals. METHODS: A qualitative study with semi-structured open-ended questions informed by a prior literature review was undertaken with nurses working in an acute general hospital in Dublin, Ireland. RESULTS: The identified themes were the knowledge of addiction, including physical and psychological needs, and the understanding of recovery, patient-centred services and the impact of the individual's environment. CONCLUSION: Standardising language for addiction and recovery and improving addiction education will give nurses a better understanding of the chronic nature of substance use and the importance of this in providing high-quality health care.

Cognitive remediation in residential substance use treatment: A randomized stepped-wedge trial.

ABSTRACTExecutive dysfunction is common in individuals with substance use disorder (SUD) and presents a barrier to treatment engagement. The study aimed to investigate the effectiveness of cognitive remediation (CR) for improving executive functioning and treatment retention in patients with SUD, using a stepped-wedge cluster randomized controlled trial. The sample included 527 adults enrolled across ten residential SUD treatment providers in NSW, Australia. The intervention consisted of 12 hours of CR delivered over six weeks in a group format. The comparator was treatment-as-usual (TAU). Primary outcomes included self-reported executive functioning and proportion of treatment completed (PoTC), measured as the number of days in treatment divided by the planned treatment duration. Intention-to-treat analysis did not find significant differences for self-reported executive functioning (mean difference = -2.49, 95%CI [-5.07, 0.09], p = .059) or PoTC (adjusted mean ratio = 1.09, 95%CI [0.88, 1.36], p = .442). Due to high dropout from the intention-to-treat sample (56%) a post-hoc analysis was conducted using a per-protocol approach, in which CR was associated with improved self-reported executive functioning (mean difference = -3.33, 95%CI [-6.10, -0.57], p = .019) and improved likelihood of treatment graduation (adjusted odds ratio = 2.43, 95%CI [1.43, 4.11], p < .001). More research is required to develop a CR approach that results in service-wide treatment effectiveness.

Separation of Lipoproteins for Quantitative Analysis of 14C-Labeled Lipid-Soluble Compounds by Accelerator Mass Spectrometry.

To date, 14C tracer studies using accelerator mass spectrometry (AMS) have not yet resolved lipid-soluble analytes into individual lipoprotein density subclasses. The objective of this work was to develop a reliable method for lipoprotein separation and quantitative recovery for biokinetic modeling purposes. The novel method developed provides the means for use of small volumes (10-200 µL) of frozen plasma as a starting material for continuous isopycnic lipoprotein separation within a carbon- and pH-stable analyte matrix, which, following post-separation fraction clean up, created samples suitable for highly accurate 14C/12C isotope ratio determinations by AMS. Manual aspiration achieved 99.2 ± 0.41% recovery of [5-14CH3]-(2R, 4'R, 8'R)-α-tocopherol contained within 25 µL plasma recovered in triacylglycerol rich lipoproteins (TRL = Chylomicrons + VLDL), LDL, HDL, and infranatant (INF) from each of 10 different sampling times for one male and one female subject, n = 20 total samples. Small sample volumes of previously frozen plasma and high analyte recoveries make this an attractive method for AMS studies using newer, smaller footprint AMS equipment to develop genuine tracer analyses of lipophilic nutrients or compounds in all human age ranges.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis

BACKGROUND AND OBJECTIVES: Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. METHODS: Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after loge transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. RESULTS: IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, p = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, p = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, p = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per loge unit increase for MACE (LAA, RR 1.26 [1.06-1.50], p = 0.009; SVO, RR 1.22 [1.01-1.47], p = 0.04; UND, RR 1.18 [1.04-1.34], p = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], p = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). DISCUSSION: Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.