Economic Evaluations of CAR-T Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aims to systematically review evidence on the cost-effectiveness of chimeric antigen receptor (CAR)-T therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments and economic evaluations that compared costs and effects of CAR-T therapy in cancer patients were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US Dollars RESULTS: Our search yielded 1,809 records, 47 of which were included. The majority of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared to various standard-of-care chemotherapies. The incremental cost-effective ratio (ICER) for CAR-T therapies ranged from $9,424 to $4,124,105 per QALY in adults and from $20,784 to $243,177 per QALY in pediatric patients. ICERs were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness were uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Associations of preoperative anaemia with healthcare resource use and outcomes after colorectal surgery: a population-based cohort study.

BACKGROUND: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. METHODS: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged ≥18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin <130 g L-1 in males; <120 g L-1 in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. RESULTS: We included 54,286 patients, with mean 65.3 (range 18-102) years of age and 49.0% females, among which 21 264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04-1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04-4.66), MAEs (OR 1.14, 95% CI 1.03-1.27), LOS (RoM 1.08, 95% CI 1.07-1.10), and readmissions (OR 1.16, 95% CI 1.08-1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95-0.96). CONCLUSIONS: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders.

Turmeric has been gaining popularity as a treatment option for digestive disorders, although a rigorous synthesis of efficacy has not been conducted. This study aimed to summarize the evidence for the efficacy and safety of turmeric in the treatment of digestive disorders, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), dyspepsia, gastroesophageal reflux disease, and peptic ulcers. Literature searches were conducted in Medline, EMBASE, AMED, the Cochrane Central Register of Control Trials, and Dissertation Abstracts from inception to November 15, 2021. Dual independent screening of citations and full texts was conducted and studies meeting inclusion criteria were retained: randomized controlled trials (RCT) and comparative observational studies evaluating turmeric use in people of any age with one of the digestive disorders of interest. Extraction of relevant data and risk of bias assessments were performed by two reviewers independently. Meta-analysis was not conducted due to high heterogeneity. From 1136 citations screened, 26 eligible studies were retained. Most studies were assessed to have a high risk of bias, and many had methodological limitations. Descriptive summaries suggest that turmeric is safe, with possible efficacy in patients with IBD or IBS, but its effects were inconsistent for other conditions. The efficacy of turmeric in digestive disorders remains unclear due to the high risk of bias and methodological limitations of the included studies. Future studies should be designed to include larger sample sizes, use rigorous statistical methods, employ core outcome sets, and adhere to reporting guidance for RCTs of herbal interventions to facilitate more meaningful comparisons and robust conclusions.

Incremental net monetary benefit of using varenicline for smoking cessation: A systematic review and meta-analysis of economic evaluation studies.

AIMS: To conduct a systematic review and meta-analysis and pool the incremental net benefits (INBs) of varenicline compared with behaviour support with bupropion or nicotine replacement therapy (NRT), behaviour support alone and unaided cessation in adult smokers making a first-time attempt to quit. METHODS: A search for economic evaluation studies was conducted from inception to 30 September 2022, on PubMed, Embase, Cost-Effectiveness Analysis (CEA) Registry by Tufts Medical Centre, EconLit and the NHS Economic Evaluation Database (NHS EED). Eligible studies were included if they were (1) conducted among adults ages 18 years old and older who were smokers attempting to quit for the first time; (2) compared varenicline to behaviour support with bupropion or NRT, behaviour support alone and unaided cessation; and (3) performed a CEA or cost-utility analysis. The INBs were calculated and pooled across studies stratified by country income level and study perspective using the random-effects model. Statistical heterogeneity between studies was assessed using the I2 statistic and Cochrane Q statistic. RESULTS: Of the 1433 identified studies, 18 studies were included in our review. Our findings from healthcare system/payer perspective suggested that the use of varenicline is statistically significantly cost-effective compared with bupropion (pooled INB, $830.75 [95% confidence interval, $208.23, $1453.28]), NRTs ($636.16 [$192.48, $1079.84]) and unaided cessation ($4212.35 [$1755.79, $6668.92]) in high-income countries. Similarly, varenicline is also found to be cost-effective compared to bupropion ($2706.27 [$1284.44, $4128.11]), NRTs ($3310.01 [$1781.53, $4838.50]) and behavioural support alone ($5438.22 [$4105.99, $6770.46]) in low- and middle-income countries. CONCLUSION: Varenicline is cost-effective as a smoking cessation aid when compared with behavioural support with bupropion or nicotine replacement therapies and behavioural support alone in both high-income countries and low- and middle-income countries, from the healthcare system/payer perspective in adult smokers who attempt to quit for the first time.

Psychometric Evaluation of the Multidimensional Scale-Uremic Pruritus in Dialysis Patients (UP-Dial): Comparison in Hemodialysis and Peritoneal Dialysis Patients with Chronic Pruritus.

BACKGROUND: High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. OBJECTIVES: To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uremic Pruritus in Dialysis (UP-Dial) 14-item, by comparing hemodialysis and peritoneal dialysis modality. METHODS: This validation study used data from the Thai Renal Outcomes Research-Uremic Pruritus, a prospective, multicenter, longitudinal study. Data for this study were collected from February 1, 2019, to May 31, 2022. The adult sample of 226 hemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across hemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73 to 0.74) with global itching, a positively moderate correlation (0.33 to 0.58) with DLQI, PSQI, global fatigue, SSS-8, and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation: 0.84 to 0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05). CONCLUSIONS: The findings reaffirm good measurement properties of the UP-Dial 14-items in hemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.

Protocol for the ONLOOP trial: pragmatic randomized trial evaluating a province-wide system of personalized reminders for evidence-based surveillance tests in adult survivors of childhood cancer in Ontario.

BACKGROUND: Childhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time. METHODS: This is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP's impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants' consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later. The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed. DISCUSSION: The results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05832138.

Resource Use and Costs of Indwelling Pleural Catheters vs Pleurodesis for Malignant Pleural Effusions: A Population-based Study.

RATIONALE: Malignant pleural effusions (MPE) are associated with significant health service use and healthcare costs, but the current evidence is limited. OBJECTIVES: To compare 12-month post-procedure: (1) health service utilization, and (2) healthcare costs following indwelling pleural catheter (IPC) insertion with at-home drainage performed by homecare nursing services, versus in-hospital chemical pleurodesis. METHODS: We performed a retrospective population-based study on a cohort of adults with MPE who underwent IPC insertion or chemical pleurodesis between January 1, 2015 and December 31, 2019 using provincial health administrative data (Ontario, Canada). Patients were followed from the procedure date until death or until 12-month post-procedure. Inverse probability of treatment weighting (IPTW) was performed to adjust for imbalances in baseline characteristics. Differences in length of stay (LOS), readmissions, emergency department visits, home care visits, and healthcare costs were estimated using weighted regression analysis. RESULTS: Of 5,752 included individuals, 4432 (77%) underwent IPC insertion and 1320 (23%) had pleurodesis. In the weighted sample, individuals who received an IPC had fewer inpatient days (12.4 days vs 16 days, standardized mean difference 0.229), but a higher proportion of subsequent admissions for empyema (2.7% vs 1.1%, p=0.0002) compared to those undergoing pleurodesis. IPC individuals received more hours of nursing home care (41 hours vs 21.1 hours, standardized mean difference 0.671) but overall had lower average healthcare costs ($40,179 vs $46,640 per patient, standardized mean difference 0.177) than those receiving pleurodesis. CONCLUSIONS: IPCs with home nursing drainage are associated with reduced health resource use compared to pleurodesis in adults with MPE even after controlling for important baseline and clinical characteristics. Given that both procedures have similar health outcomes, our findings support the ongoing promotion of IPCs to increase outpatient management of patients with MPEs. Primary source of funding: TOHAMO Innovation Fund grant.

Evaluation of Pharmacological Treatments for Acute Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness and safety of pharmacological treatments for acute urticaria remain unclear. OBJECTIVE: To systematically review and meta-analyze the efficacy and safety of pharmacological treatments for acute urticaria in emergency department (ED) and non-ED settings. METHODS: We searched electronic databases and gray literature up to July 8, 2023, without language restrictions. Randomized clinical trials (RCTs) relating to pharmacological interventions in patients with acute urticaria, regardless of age, were eligible for inclusion. The relevant outcomes of interest were the treatment efficacy and safety profiles. The results are presented as standardized mean differences (SMDs) or odds ratios (ORs). RESULTS: We identified 8 RCTs comprising 680 patients. Regarding the ED setting (2 trials, n = 118), intramuscular first-generation H1-antihistamine (fgAH) was more efficacious in decreasing pruritus symptoms (SMD, -0.38; 95% confidence interval [CI], -0.75 to -0.02) but had higher sedative effects than H2-blockers. With comparable pruritus symptom improvement (2 trials, n = 295), intravenous second-generation H1-antihistamine (sgAH) had favorable clinical outcomes compared with intravenous fgAH in the ED setting with a lower risk of return to any ED/clinic (OR, 0.31; 95% CI, 0.12-0.83) and lower risk of any adverse event (OR, 0.24; 95% CI, 0.09-0.63). The efficacy of adjunctive therapy with a short course of systemic glucocorticosteroids in ED and non-ED settings remains unclear. No serious concerns regarding the safety profiles were observed in any of the treatment comparisons. CONCLUSIONS: H1-antihistamine is a crucial and effective component of acute urticaria treatment, and intravenous sgAH is preferred as an initial treatment option.

Balancing risks of recurrent venous thromboembolism and bleeding with extended anticoagulation: a decision analysis.

Background: A decision to stop or continue anticoagulation after 3 months of anticoagulation for venous thromboembolism (VTE) should be made by weighing individual risks of recurrence and bleeding. Objectives: To determine the optimal ratio of recurrence risk reduction to increase the risk of bleeding in terms of maximizing quality-adjusted life years (QALYs) gained. Methods: Using a microsimulation model, outcomes within 5 years were simulated after assigning extended treatment if absolute recurrence risk reduction outweighed absolute increase in clinically relevant bleeding risk (International Society on Thrombosis and Haemostasis definition), weighted by a certain ratio. Data were simulated based on the Bleeding Risk Study, a prospective cohort including patients after ≥3 months of anticoagulation for unprovoked VTE or provoked VTE with history of VTE. The VTE-PREDICT risk score was used to estimate 5-year risks of recurrent VTE and clinically relevant bleeding. Results: Among 10,000 individuals (mean age, 60.2 years, 36% female), the ratio of 0.90 (95% CI, 0.51-3.40; ie, bleeding is considered 0.90 the severity of recurrent VTE), with 99% of patients assigned extended anticoagulation, was considered optimal and resulted in 93 (95% CI, -23 to 203) additional QALYs compared with the least favorable ratio (5.10, 0% extended anticoagulation). At the optimal ratio, treatment based on VTE-PREDICT yielded 44 (95% CI, -69 to 157) additional QALYs versus standard of care. Conclusion: With the current evidence, the optimal ratio between relevant bleeding risk and absolute recurrence risk reduction remains uncertain. Our results confirm that clinical equipoise exists regarding the decision to stop or continue anticoagulation after initial VTE treatment, emphasizing the importance of shared decision-making.

Potentially Inappropriate Prescribing in Long-Term Care and its Relationship With Probable Delirium.

OBJECTIVES: This study examined potentially inappropriate prescribing (PIP) of medication and its association with probable delirium among long-term care (LTC) residents in Ontario, Canada. DESIGN: Population-based cross-sectional study using provincial health administrative data, including LTC assessment data via the Resident Assessment Instrument-Minimum Dataset version 2.0 (RAI-MDS 2.0). SETTING AND PARTICIPANTS: LTC residents in Ontario between January 1, 2016, and December 31, 2019. METHODS: We used residents' first RAI-MDS 2.0 assessment in the study period as the index assessment. Probable delirium was identified via the delirium Clinical Assessment Protocol. Medication use in the 2 weeks preceding assessment was captured using medication claims data. PIP was measured using the STOPP/START criteria and 2015 Beers criteria, with residents classified as having 0, 1, 2, or 3+ instances of PIP. Relationships between PIP and probable delirium was assessed via bivariate and multivariable logistic regression models. RESULTS: The study population included 171,190 LTC residents (mean age 84.5 years, 66.8% female, 62.9% with dementia). More than half (51.8%) of residents had 1+ instances of PIP and 21% had 3+ instances of PIP according to the STOPP/START criteria; PIP prevalence was slightly lower when assessed using Beers criteria (36.5% with 1+, 11.1% with 3+). Overall, 3.7% of residents had probable delirium. The prevalence of probable delirium increased as the number of instances of PIP increased, with residents with 3+ instances of STOPP/START PIP being 1.66 times more likely (95% CI 1.56-1.77) to have probable delirium compared to those with no instances of PIP. Similar findings were observed when PIP was measured using the Beers criteria. Central nervous system (CNS)-related PIP criteria showed a stronger association with probable delirium than non-CNS-related PIP criteria. CONCLUSIONS AND IMPLICATIONS: This population-based study highlighted that PIP was highly prevalent in long-term care residents and was associated with an increased prevalence of probable delirium.

Community-based screening and triage connecting First Nations children and youth to local supports: a cross-sectional study.

BACKGROUND: First Nations children in Canada experience health inequities. We aimed to determine whether a self-report health app identified children's needs for support earlier in their illness than would typically occur. METHODS: Children (aged 8 to 18 yr) were recruited from a rural First Nation community. Children completed the Aaniish Naa Gegii: the Children's Health and Well-being Measure (ACHWM) and then met with a local mental health worker who determined their risk status. ACHWM Emotional Quadrant Scores (EQS) were compared between 3 groups of children: healthy peers (HP) who were not at risk, those with newly identified needs (NIN) who were at risk and not previously identified, and a typical treatment (TT) group who were at risk and already receiving support. RESULTS: We included 227 children (57.1% girls), and the mean age was 12.9 (standard deviation [SD] 2.9) years. The 134 children in the HP group had a mean EQS of 80.1 (SD 11.25), the 35 children in the NIN group had a mean EQS of 67.2 (SD 13.27) and the 58 children in the TT group had a mean EQS of 66.2 (SD 16.30). The HP group had significantly better EQS than the NIN and TT groups (p < 0.001). The EQS did not differ between the NIN and TT groups (p = 0.8). INTERPRETATION: The ACHWM screening process identified needs for support among 35 children, and the associated triage process connected them to local services; the similarity of EQS in the NIN and TT groups highlights the value of community screening to optimize access to services. Future research will examine the impact of this process over the subsequent year in these groups.

Pandemic Effect on Healthcare Use and Death in Adults with Epilepsy: A Population Study.

OBJECTIVES: We conducted a population-based study using Ontario health administrative data to describe trends in healthcare utilization and mortality in adults with epilepsy during the first pandemic year (March 2020-March 2021) compared to historical data (2016-2019). We also investigated if changes in outpatient visits and diagnostic testing during the first pandemic year were associated with increased risk for hospitalizations, emergency department (ED) visits, or death. METHODS: Projected monthly visit rates (per 100,000 people) for outpatient visits, electroencephalography, magnetic resonance, computed tomography, all-cause ED visits, hospitalizations, and mortality were calculated based on historical data by fitting monthly time series autoregressive integrated moving-average models. Two-way interactions were calculated using Quasi-Poisson models. RESULTS: In adults with epilepsy during the first quarter of the pandemic, we demonstrated a reduction in all-cause outpatient visits, diagnostic testing, ED visits and hospitalizations, and a temporary increase in mortality (observed rates of 355.8 vs projected 308.8, 95% CI: 276.3-345.1). By the end of the year, outpatient visits increased (85,535.4 vs 76,620.6, 95% CI: 71,546.9-82,059.4), and most of the diagnostic test rates returned to the projected. The increase in the rate of all-cause mortality during the pandemic, compared to pre-pandemic, was greater during months with the lower frequency of diagnostic tests than months with higher frequency (interaction p-values <.0001). CONCLUSION: We described the impact of the pandemic on healthcare utilization and mortality in adults with epilepsy during the first year. We demonstrated that access to relevant diagnostic testing is likely important for this population while planning restrictions on non-urgent health services.

Non-Adherence to COPD Medications and its Association with Adverse Events: A Longitudinal Population Based Cohort Study of Older Adults.

OBJECTIVE: To determine the association between non-adherence to long term chronic obstructive pulmonary disease (COPD) medications and COPD related emergency department (ED) visits and hospitalizations in patients with incident COPD, utilizing time varying measures of adherence as well as accounting for time-varying confounding impacted by prior adherence. STUDY DESIGN AND SETTING: We conducted a population-based retrospective cohort study between 2007-2017 among individuals aged 66 years and older with incident COPD using multiple linked administrative health databases from the province of Ontario, Canada. Adherence to COPD medications was measured using time varying proportion of days covered based on insurance claims for medications dispensed at community pharmacies. The parametric g-formula was used to assess the association between time-varying adherence (in the last 90-days) to COPD medications and risk of COPD related hospitalizations and ED visits while accounting for time varying confounding by COPD severity. RESULTS: Overall, 60,251 individuals with incident COPD were included; mean age was 76 (SD 7) and 59% were male. Mean adherence over the entire follow-up was 23% (SD 0.3). There were 7,248 (12%) COPD related ED visits (2.8 events per 100 person years [PY]) and 9,188 (15%) COPD related hospitalizations (3.5 events per 100 PY). Compared to those with 0% 90-day adherence, those with adherence between 1-33% had a 19% decreased risk of COPD related ED visits (adjusted risk ratio[aRR]:0.81, 95% confidence interval [CI]:0.78-0.83), those with adherence between 34%-67% had a 18% decreased risk (aRR: 0.82, 95% CI: 0.77-0.85) while those with 68%-100% 90-day adherence had a 63% increased risk of COPD related ED visits (aRR: 1.63, 95% CI: 1.47-1.78). Nearly identical results were obtained for COPD specific hospitalizations. CONCLUSION: After accounting for time varying confounding by COPD severity, the highest time varying 90-days adherence was associated with an increased risk of both COPD related ED visits and hospitalizations compared to the lowest adherence categories. Differences in COPD severity between adherence categories, perception of need for medication management in the higher adherence categories, and potential residual confounding makes it difficult to disentangle the independent effects of adherence from the severity of the condition itself.

Service-level barriers to and facilitators of accessibility to treatment for problematic alcohol use: a scoping review.

Introduction: Services to treat problematic alcohol use (PAU) should be highly accessible to optimize treatment engagement. We conducted a scoping review to map characteristics of services for the treatment of PAU that have been reported in the literature to be barriers to or facilitators of access to treatment from the perspective of individuals with PAU. Methods: A protocol was developed a priori, registered, and published. We searched MEDLINE®, Embase, the Cochrane Library, and additional grey literature sources from 2010 to April 2022 to identify primary qualitative research and surveys of adults with current or past PAU requiring treatment that were designed to identify modifiable characteristics of PAU treatment services (including psychosocial and pharmacologic interventions) that were perceived to be barriers to or facilitators of access to treatment. Studies of concurrent PAU and other substance use disorders were excluded. Study selection was performed by multiple review team members. Emergent barriers were coded and mapped to the accessibility dimensions of the Levesque framework of healthcare access, then descriptively summarized. Results: One-hundred-and-nine included studies reported an extensive array of unique service-level barriers that could act alone or together to prevent treatment accessibility. These included but were not limited to lack of an obvious entry point, complexity of the care pathway, high financial cost, unacceptably long wait times, lack of geographically accessible treatment, inconvenient appointment hours, poor cultural/demographic sensitivity, lack of anonymity/privacy, lack of services to treat concurrent PAU and mental health problems. Discussion: Barriers generally aligned with recent reviews of the substance use disorder literature. Ranking of barriers may be explored in a future discrete choice experiment of PAU service users. The rich qualitative findings of this review may support the design of new or modification of existing services for people with PAU to improve accessibility. Systematic Review Registration: Open Science Framework doi: 10.17605/OSF.IO/S849R.

Cost-effectiveness of postoperative imaging surveillance strategies for nonfunctional pituitary adenomas after resection with curative intent.

OBJECTIVE: The aim of this study was to determine an optimal follow-up imaging surveillance strategy in terms of cost-effectiveness after resection of nonfunctioning pituitary adenomas with curative intent. METHODS: An individual-level state-transition microsimulation model was used to simulate costs and outcomes associated with three postoperative imaging strategies over a lifetime time horizon: 1) annual MRI surveillance, 2) tapered MRI surveillance (annual surveillance for 5 years followed by surveillance every 2 years), and 3) personalized surveillance (annual surveillance for 5 years followed by surveillance every 2 years when MRI shows remnant disease/postoperative changes, and surveillance at 7, 10, and 15 years for disease-free MRI). Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually. Model outcomes included lifetime costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, annual surveillance yielded higher costs and lower health effects (QALYs) compared with the tapered and personalized surveillance strategies (dominated). Personalized surveillance demonstrated an additional 0.1 QALY at additional cost ($1298) compared with tapered surveillance (7.7 QALYs at a cost of $12,862). The ICER was $11,793/QALY. The optimal decision was most sensitive to the probability of postoperative changes on MRI after surgery and MRI cost. Accounting for parameter uncertainty, personalized surveillance had a higher probability of being a cost-effective surveillance option compared with the alternative strategies at 79%. CONCLUSIONS: Using standard cost-effectiveness thresholds in the US ($100,000/QALY), personalized surveillance that accounted for remnant disease or postoperative changes on MRI was cost-effective compared with alternative surveillance strategies.

Nurse practitioner and physician end-of-life home visits and end-of-life outcomes.

OBJECTIVES: Physicians and nurse practitioners (NPs) play critical roles in supporting palliative and end-of-life care in the community. We examined healthcare outcomes among patients who received home visits from physicians and NPs in the 90 days before death. METHODS: We conducted a retrospective cohort study using linked data of adult home care users in Ontario, Canada, who died between 1 January 2018 and 31 December 2019. Healthcare outcomes included medications for pain and symptom management, emergency department (ED) visits, hospitalisations and a community-based death. We compared the characteristics of and outcomes in decedents who received a home visit from an NP, physician and both to those who did not receive a home visit. RESULTS: Half (56.9%) of adult decedents in Ontario did not receive a home visit from a provider in the last 90 days of life; 34.5% received at least one visit from a physician, 3.8% from an NP and 4.9% from both. Compared with those without any visits, having at least one home visit reduced the odds of hospitalisation and ED visits, and increased the odds of receiving medications for pain and symptom management and achieving a community-based death. Observed effects were larger in patients who received at least one visit from both. CONCLUSIONS: Beyond home care, receiving home visits from primary care providers near the end of life may be associated with better outcomes that are aligned with patients' preferences-emphasising the importance of NPs and physicians' role in supporting people near the end of life.

Long-term cognitive impairment after probable delirium in long-term care residents: A population-based retrospective cohort study.

BACKGROUND: The impact of delirium on cognition has not been well-studied in long-term care (LTC) residents. This study examined changes in cognition 1 year after a probable delirium episode among LTC residents, compared to LTC residents without probable delirium. We also evaluated whether the relationship between probable delirium and cognitive change differed according to a diagnosis of dementia. METHODS: We conducted a population-based retrospective cohort study using linked health administrative data. The study population included adults aged 65+ residing in LTC in Ontario, Canada and assessed via the Resident Assessment Instrument-Minimum Dataset between January 1, 2016 and December 31, 2018. Probable delirium was ascertained via the delirium Clinical Assessment Protocol on the index assessment. Cognition was measured quarterly using the Cognitive Performance Scale (range 0-6, higher values indicate greater impairment). Cognitive decline up to 1 year after index was evaluated using multivariable proportional odds regression models. RESULTS: Of 92,005 LTC residents, 2816 (3.1%) had probable delirium at index. Residents with probable delirium had an increased odds of cognitive decline compared to those without probable delirium, with adjusted odds ratios of 1.64 (95% confidence interval [CI] 1.35-1.99), 1.56 (95% CI 1.34-1.85), 1.57 (95% CI 1.32-1.86) and 1.50 (95% CI 1.25-1.80) after 1-3, 4-6, 7-9, and 10-12 months of follow-up. Residents with probable delirium and a comorbid dementia diagnosis had the highest adjusted odds of cognitive decline (adjusted odds ratio 5.57, 95% CI 4.79-6.48) compared to those without probable delirium or dementia. Residents with probable delirium were also more likely to die within 1 year than those without probable delirium (52.5% vs. 23.4%). CONCLUSIONS: Probable delirium is associated with increased mortality and worsened cognition in LTC residents that is sustained months after the probable delirium episode. Efforts to prevent delirium in this population may help limit these adverse effects.

Rapid Access Addiction Medicine Clinics for People With Problematic Opioid Use.

Importance: New approaches are needed to provide care for individuals with problematic opioid use (POU). Rapid access addiction medicine (RAAM) clinics offer a flexible, low-barrier, rapid access care model for this population. Objective: To assess the associations of RAAM clinics with emergency department (ED) visits, hospitalizations, and mortality for people with POU. Design, Setting, and Participants: A retrospective cohort study involving a matched control group was performed using health administrative data from Ontario, Canada. Anonymized data from 4 Ontario RAAM clinics (cities of Ottawa, Toronto, Oshawa, and Sudbury) were linked with health administrative data. Analyses were performed on a cohort of individuals who received care at participating RAAM clinics and geographically matched controls who did not receive care at a RAAM clinic. All visits occurred between October 2, 2017, and October 30, 2019, and data analyses were completed in spring 2023. A propensity score-matching approach was used to balance confounding factors between groups, with adjustment for covariates that remained imbalanced after matching. Exposures: Individuals who initiated care through the RAAM model (including assessment, pharmacotherapy, brief counseling, harm reduction, triage to appropriate level of care, navigation to community services and primary care, and related care) were compared with individuals who did not receive care through the RAAM model. Main Outcomes and Measures: The primary outcome was a composite measure of ED visits for any reason, hospitalization for any reason, and all-cause mortality (all measured up to 30 days after index date). Outcomes up to 90 days after index date, as well as outcomes looking at opioid-related ED visits and hospitalizations, were also assessed. Results: In analyses of the sample of 876 patients formed using propensity score matching, 440 in the RAAM group (mean [SD] age, 36.5 [12.6] years; 276 [62.7%] male) and 436 in the control group (mean [SD] age, 36.8 [13.8] years; 258 [59.2%] male), the pooled odds ratio (OR) for the primary, 30-day composite outcome of all-cause ED visit, hospitalization, or mortality favored the RAAM model (OR, 0.68; 95% CI, 0.50-0.92). Analysis of the same outcome for opioid-related reasons only also favored the RAAM intervention (OR, 0.47; 95% CI, 0.29-0.76). Findings for the individual events of hospitalization, ED visit, and mortality at both 30-day and 90-day follow-up also favored the RAAM model, with comparisons reaching statistical significance in most cases. Conclusions and Relevance: In this cohort study of individuals with POU, RAAM clinics were associated with reductions in ED visits, hospitalizations, and mortality. These findings provide valuable evidence toward a broadened adoption of the RAAM model in other regions of North America and beyond.

Applying the Theoretical Domains Framework to identify police, fire, and paramedic preferences for accessing mental health care in a First Responder Operational Stress Injury Clinic: a qualitative study. / Application du cadre Theoretical Domains Framework pour cerner les préférences des policiers, des pompiers et des ambulanciers en matière d'accès aux soins de santé mentale dans une clinique de traitement des blessures de stress opérationnel pour les premiers répondants : une étude qualitative.

INTRODUCTION: First responders and other public safety personnel (PSP; e.g. correctional workers, firefighters, paramedics, police, public safety communicators) are often exposed to events that have the potential to be psychologically traumatizing. Such exposures may contribute to poor mental health outcomes and a greater need to seek mental health care. However, a theoretically driven, structured qualitative study of barriers and facilitators of help-seeking behaviours has not yet been undertaken in this population. This study used the Theoretical Domains Framework (TDF) to identify and better understand critical barriers and facilitators of help-seeking and accessing mental health care for a planned First Responder Operational Stress Injury (OSI) clinic. METHODS: We conducted face-to-face, one-on-one semistructured interviews with 24 first responders (11 firefighters, five paramedics, and eight police officers), recruited using purposive and snowball sampling. Interviews were analyzed using deductive content analysis. The TDF guided study design, interview content, data collection, and analysis. RESULTS: The most reported barriers included concerns regarding confidentiality, lack of trust, cultural competency of clinicians, lack of clarity about the availability and accessibility of services, and stigma within first responder organizations. Key themes influencing help-seeking were classified into six of the TDF's 14 theoretical domains: environmental context and resources; knowledge; social influences; social/professional role and identity; emotion; and beliefs about consequences. CONCLUSION: The results identified key actions that can be utilized to tailor interventions to encourage attendance at a First Responder OSI Clinic. Such approaches include providing transparency around confidentiality, policies to ensure greater cultural competency in all clinic staff, and clear descriptions of how to access care; routinely involving families; and addressing stigma.