Search

Abstract Background Seniors with recurrent hospitalizations who are taking multiple medications including high-risk medications are at particular risk for serious adverse medication events. We will assess whether an expert Clinical Pharmacology and Toxicology (CPT) medication management intervention during hospitalization with follow-up post-discharge and communication with circle of care is feasible and can decrease drug therapy problems amongst this group. Methods The design is a pragmatic pilot randomized trial with 1:1 patient-level concealed randomization with blinded outcome assessment and data analysis. Participants will be adults 65 years and older admitted to internal medicine services for more than 2 days, who have had at least one other hospitalization in the prior year, taking five or more chronic medications including at least one high-risk medication. The CPT intervention identifies medication targets; completes consult, including priorities for improving prescribing negotiated with the patient; starts the care plan; ensures a detailed discharge medication reconciliation and circle-of-care communication; and sees the patient at least twice after hospital discharge via virtual visits to consolidate the care plan in the community. Control group receives usual care. Primary outcomes are feasibility — recruitment, retention, costs, and clinical — number of drug therapy problems improved, with secondary outcomes examining coordination of transitions in care, quality of life, and healthcare utilization and costs. Follow-up is to 3-month posthospital discharge. Discussion If results support feasibility of ramp-up and promising clinical outcomes, a follow-up definitive trial will be organized using a developing national platform and medication appropriateness network. Since the intervention allows a very scarce medical specialty expertise to be offered via virtual care, there is potential to improve the safety, outcomes, and cost of care widely. Trial registration number ClinicalTrials.gov identifier: NCT04077281.

BackgroundIn 2020, the Ministry of Health (MoH) in Ontario, Canada, introduced a virtual urgent care (VUC) pilot program to provide alternative access to urgent care services and reduce the need for in-person emergency department (ED) visits for patients with low acuity health concerns. ObjectiveThis study aims to compare the 30-day costs associated with VUC and in-person ED encounters from an MoH perspective. MethodsUsing administrative data from Ontario (the most populous province of Canada), a population-based, matched cohort study of Ontarians who used VUC services from December 2020 to September 2021 was conducted. As it was expected that VUC and in-person ED users would be different, two cohorts of VUC users were defined: (1) those who were promptly referred to an ED by a VUC provider and subsequently presented to an ED within 72 hours (these patients were matched to in-person ED users with any discharge disposition) and (2) those seen by a VUC provider with no referral to an in-person ED (these patients were matched to patients who presented in-person to the ED and were discharged home by the ED physician). Bootstrap techniques were used to compare the 30-day mean costs of VUC (operational costs to set up the VUC program plus health care expenditures) versus in-person ED care (health care expenditures) from an MoH perspective. All costs are expressed in Canadian dollars (a currency exchange rate of CAD $1=US $0.76 is applicable). ResultsWe matched 2129 patients who presented to an ED within 72 hours of VUC referral and 14,179 patients seen by a VUC provider without a referral to an ED. Our matched populations represented 99% (2129/2150) of eligible VUC patients referred to the ED by their VUC provider and 98% (14,179/14,498) of eligible VUC patients not referred to the ED by their VUC provider. Compared to matched in-person ED patients, 30-day costs per patient were significantly higher for the cohort of VUC patients who presented to an ED within 72 hours of VUC referral ($2805 vs $2299; difference of $506, 95% CI $139-$885) and significantly lower for the VUC cohort of patients who did not require ED referral ($907 vs $1270; difference of $362, 95% CI 284-$446). Overall, the absolute 30-day costs associated with the 2 VUC cohorts were $18.9 million (ie, $6.0 million + $12.9 million) versus $22.9 million ($4.9 million + $18.0 million) for the 2 in-person ED cohorts. ConclusionsThis costing evaluation supports the use of VUC as most complaints were addressed without referral to ED. Future research should evaluate targeted applications of VUC (eg, VUC models led by nurse practitioners or physician assistants with support from ED physicians) to inform future resource allocation and policy decisions.

Abstract Background Total knee arthroplasty is a common surgery for end-stage knee osteoarthritis. Partial knee arthroplasty is also a treatment option for patients with arthritis present in only one or two knee compartments. Partial knee arthroplasty can preserve the natural knee biomechanics, but these replacements may not last as long as total knee replacements. Robotic-assisted orthopedic techniques can help facilitate partial knee replacements, increasing accuracy and precision. This trial will investigate the feasibility and assess clinical outcomes for a larger definitive trial. Methods This is a protocol for an ongoing parallel randomized pilot trial of 64 patients with uni- or bicompartmental knee arthritis. Patients are randomized to either receive robot-assisted partial knee arthroplasty or manual total knee arthroplasty. The primary outcome of this pilot is investigating the feasibility of a larger trial. Secondary (clinical) outcomes include joint awareness, return to activities, knee function, patient global impression of change, persistent post-surgical pain, re-operations, resource utilization and cost-effectiveness, health-related quality of life, radiographic alignment, knee kinematics during walking gait, and complications up to 24 months post-surgery. Discussion The RoboKnees pilot study is the first step in determining the outcome of robot-assisted partial knee replacements. Conclusions from this study will be used to design future large-scale trials. This study will inform surgeons about the potential benefits of robot-assisted partial knee replacements. Trial registration This study was prospectively registered on clinicaltrials.gov (identifier: NCT04378049) on 4 May 2020, before the first patient was randomized.

Abstract Background Knee arthritis is a leading cause of limited function and long-term disability in older adults. Despite a technically successful total knee arthroplasty (TKA), around 20% of patients continue to have persisting pain with reduced function, and low quality of life. Many of them continue using opioids for pain control, which puts them at risk for potential long-term adverse effects such as dependence, overdose and risk of falls. Although persisting pain and opioid use after TKA have been recognised to be important issues, individual strategies to decrease their burden have limitations and multi-component interventions, despite their potential, have not been well studied. In this study, we propose a multi-component pathway including personalized pain management, facilitated by a pain management coordinator. The objectives of this pilot trial are to evaluate feasibility (recruitment, retention, and adherence), along with opioid-free pain control at 8 weeks after TKA. Methods This is a protocol for a multicentre pilot randomised controlled trial using a 2-arm parallel group design. Adult participants undergoing unilateral total knee arthroplasty will be considered for inclusion and randomised to control and intervention groups. Participants in the intervention group will receive support from a pain management coordinator who will facilitate a multicomponent pain management pathway including (1) preoperative education on pain and opioid use, (2) preoperative risk identification and mitigation, (3) personalized post-discharge analgesic prescriptions and (4) continued support for pain control and recovery up to 8 weeks post-op. Participants in the control group will undergo usual care. The primary outcomes of this pilot trial are to assess the feasibility of participant recruitment, retention, and adherence to the interventions, and key secondary outcomes are persisting pain and opioid use. Discussion The results of this trial will determine the feasibility of conducting a definitive trial for the implementation of a multicomponent pain pathway to improve pain control and reduce harms using a coordinated approach, while keeping an emphasis on patient centred care and shared decision making. Trial registration Prospectively registered in Clinicaltrials.gov (NCT04968132).

Objectives To evaluate whether a focused, expert medication management intervention is feasible and potentially effective in preventing anticoagulation-related adverse events for patients transitioning from hospital to home.Design Randomised, parallel design.Setting Medical wards at six hospital sites in southern Ontario, Canada.Participants Adults 18 years of age or older being discharged to home on an oral anticoagulant (OAC) to be taken for at least 4 weeks.Interventions Clinical pharmacologist-led intervention, including a detailed discharge medication management plan, a circle of care handover and early postdischarge virtual check-up visits to 1 month with 3-month follow-up. The control group received the usual care.Outcomes measures Primary outcomes were study feasibility outcomes (recruitment, retention and cost per patient). Secondary outcomes included adverse anticoagulant safety events composite, quality of transitional care, quality of life, anticoagulant knowledge, satisfaction with care, problems with medications and health resource utilisation.Results Extensive periods of restriction of recruitment plus difficulties accessing patients at the time of discharge negatively impacted feasibility, especially cost per patient recruited. Of 845 patients screened, 167 were eligible and 56 were randomised. The mean age (±SD) was 71.2±12.5 years, 42.9% females, with two lost to follow-up. Intervention patients were more likely to rate their ability to manage their OAC as improved (17/27 (63.0%) vs 7/22 (31.8%), OR 3.6 (95% CI 1.1 to 12.0)) and their continuity of care as improved (21/27 (77.8%) vs 2/22 (9.1%), OR 35.0 (95% CI 6.3 to 194.2)). Fewer intervention patients were taking one or more inappropriate medications (7 (22.5%) vs 15 (60%), OR 0.19 (95% CI 0.06 to 0.62)).Conclusion This pilot randomised controlled trial suggests that a transitional care intervention at hospital discharge for older adults taking OACs was well received and potentially effective for some surrogate outcomes, but overly costly to proceed to a definitive large trial.Trial registration number NCT02777047.

BackgroundParents or children's primary caregivers are a key influence on child weight as both decision makers and role models for eating patterns, physical activity, and other social behaviors. It is unknown whether caregivers' time preferences are associated with overweight or obesity in children. The primary objective was to estimate the association between parents' or caregivers' time preferences and children having overweight or obesity in Mexico.MethodsA cross-sectional study was conducted using a representative survey of the Mexican population. A multinomial logistic model was used to examine the association between parents' or caregivers' time preferences (patience and time consistency) and child overweight or obesity, adjusting for potential confounders.ResultsThe study included 9,102 children (mean age 10, 43% female) and 5,842 caregivers (mean age 37; 95% female). Intertemporal preference was strongly associated with increased odds of overweight or obesity in children. A medium patient caregiver had higher odds of having overweight (adjusted OR: 1.73; 95% CI: 1.19, 2.52). Similarly, having a caregiver with a present (OR: 2.52; 95% CI: 1.72, 3.70) or future bias (OR: 1.48; 95% CI: 1.11, 1.98) was associated with higher odds of obesity.ConclusionCaregivers' time preferences were associated with having overweight and obesity in children and should be considered when developing policies to reduce children's obesity status.

Objective The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain.Design Systematic review and network meta-analysis.Data sources EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021.Study selection Randomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks.Data extraction and synthesis Paired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings.Results Ninety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) −1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI −0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI −4.72 to 5.59).Conclusions Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain.PROSPERO registration number CRD42020185184.

Abstract Background Obesity is a chronic disease and is an established risk factor for other chronic diseases and mortality. Young adulthood is a period when people may be highly amenable to healthy behavior change, develop lifelong healthy behaviors, and when primary prevention of obesity may be feasible. Interventions in early adulthood have the potential for primary or primordial prevention (i.e., preventing risk factors before disease onset). The primary objective of this study is to determine the feasibility of a 6-month behavioral and educational intervention to promote healthy behaviors for obesity prevention among young adults. Methods This is the study protocol for a pilot randomized controlled trial. Young adults (age 18–29) attending McMaster University, Hamilton, Canada, will be recruited and randomized to either the intervention or control. The intervention will include individual motivational interviewing sessions (online or in-person) with a trained interviewer plus educational materials (based on Canada’s food guide and physical activity recommendations). The control group will receive educational materials only. The primary feasibility outcomes that will be evaluated as part of this pilot study include enrollment, retention (≥ 80%), data completion (≥ 80% of weights measured, and surveys completed), and participant satisfaction. Secondary clinical outcomes will include body mass index (BMI) change from baseline to 6 months, physical activity, nutrition risk, health-related quality of life mental health, and economic outcomes. Outcomes will be measured remotely using activity trackers, and online questionnaires at baseline and every 2 months. Risk stratification will be applied at baseline to identify participants at high risk of obesity (e.g., due to family or personal history). Exit questionnaires will collect data on how participants felt about the study and cost analysis will be conducted. Discussion Our pilot randomized controlled trial will evaluate the feasibility of an obesity prevention intervention in early adulthood and will inform future larger studies for obesity prevention. The results of this study have the potential to directly contribute to the primary prevention of several types of cancer by testing an intervention that could be scalable to public health, post-secondary education, or primary care settings. Trial registration https://clinicaltrials.gov/ct2/show/NCT05264740 . Registered on March 3, 2022.

Background: Not much is known about the burden of palmoplantar pustulosis (PPP). Objectives: To document the burden of PPP in Canada, and to compare with psoriasis vulgaris (PV). Methods: Adult Canadians (excluding the province of Quebec) hospitalized or visiting an emergency department (ED) or hospital-/community-based clinic between April 1, 2007, and March 31, 2020, with a diagnostic code indicating PPP (ICD-10-CA: L40.3) or PV (ICD10-CA: L40.9 or L40.0) were identified using Canadian administrative data. 10-year prevalent- and 3-year incident-based approaches were conducted. Costs were determined when the most responsible diagnosis (MRD) for the admission was PPP or PV (MRD costs) and for all reasons (all-cause costs). Results: In the prevalence analysis, the 10-year mean (standard deviation [SD]) and MRD costs were $544 ($1874) for PPP and $222 ($1828) for PV (P

Background: Not much is known about the burden of generalized pustular psoriasis (GPP). Objectives: To document the burden of GPP in Canada and to compare it with psoriasis vulgaris (PV). Methods: National data were used to identify Canadian adult patients with GPP or PV hospitalized or visiting an emergency department (ED) or hospital-/community-based clinic between April 1, 2007, and March 31, 2020. Analyses of 10-year prevalence and 3-year incidence were conducted. Costs were determined when the most responsible diagnosis (MRD) was GPP or PV (MRD costs) and for all reasons (all-cause costs). Results: In the prevalence analysis, 10-year mean (SD) MRD costs were $2393 ($11,410) for patients with GPP and $222 ($1828) for those with PV (P

The evidence base to support reimbursement decision making for oncology drugs is often based on short-term follow-up trial data, and attempts to address this uncertainty are not typically undertaken once a reimbursement decision is made. To address this gap, we sought to conduct a reassessment of an oncology drug (pembrolizumab) for patients with advanced melanoma which was approved based on interim data with a median 7.9 months of follow-up and for which long-term data have since been published. We developed a three-health-state partitioned survival model based on the phase 3 KEYNOTE-006 clinical trial data using patient-level data reconstruction techniques based on an interim analysis. We used a standard survival analysis and parametric curve fitting techniques to extrapolate beyond the trial follow-up time, and the model structure and inputs were derived from the literature. Five-year long-term follow-up data from the trial were then used to re-evaluate the cost-effectiveness of pembrolizumab versus ipilimumab for treatment of advanced melanoma. The best fitting parametric curves and corresponding survival extrapolations for reconstructed interim data and long-term data reconstructed from KEYNOTE-006 were different. An analysis of the 5 year long-term follow-up data generated a base case incremental cost-effectiveness ratio (ICER) that was 28% higher than the ICER based on interim trial data. Our findings suggest that there may be a trade-off between certainty and the ICER. Conducting health technology re-assessments of certain oncology products on the basis of longer-term data availability, especially for those health technology adoption decisions made based on immature clinical data, may be of value to decision makers.

Pancreatic cancer has an annual incidence of 2/10,000 in Canada, with a one-year mortality rate greater than 80%. In the absence of a cost-effectiveness analysis in Canada, this study’s objective was to assess the cost-effectiveness of olaparib versus a placebo in adult patients with deleterious or suspected deleterious BRCA metastatic pancreatic adenocarcinoma, who did not show any progression for at least 16 weeks with first-line platinum-based chemotherapy. A partitioned survival model with a 5-year time horizon was adopted to estimate the costs and effectiveness. All of the costs were extracted from the public payer’s available resources, effectiveness data were obtained from the POLO trial, and Canadian studies were used for utility inputs. Probabilistic sensitivity analyses and scenario analyses were performed. The total costs of olaparib and the placebo over five years were CAD 179,477 and CAD 68,569, with overall quality-adjusted life-years (QALYs) of 1.70 and 1.36, respectively. The incremental cost-effectiveness ratio (ICER) of the olaparib group compared with the placebo was CAD 329,517 per QALY. With a commonly cited willingness to pay (WTP) threshold of CAD 50,000 per QALY, the drug does not achieve acceptable cost-effectiveness mainly due to the high price of the medication and insufficient impact on the overall survival of patients with metastatic pancreatic cancer.

Abstract Background Pediatric obesity management can be successful, but some families discontinue care prematurely (i.e., attrition), limiting treatment impact. Attrition is often a consequence of barriers and constraints that limit families’ access to obesity management. Family Navigation (FN) can improve access, satisfaction with care, and treatment outcomes in diverse areas of healthcare. To help our team prepare for a future effectiveness trial, the objectives of our randomized feasibility study are to (i) explore children’s and caregivers’ acceptability of FN and (ii) examine attrition, measures of study rigor and conduct, and responses to FN + Usual Care vs Usual Care by collecting clinical, health services, and health economic data. Methods In our 2.5-year study, 108 6–17-year-olds with obesity and their caregivers will be randomized (1:1) to FN + Usual Care or Usual Care after they enroll in obesity management clinics in Calgary and Mississauga, Canada. Our Stakeholder Steering Committee and research team will use Experience-Based Co-Design to design and refine our FN intervention to reduce families’ barriers to care, maximizing the intervention dose families receive. FN will be delivered by a navigator at each site who will use logistical and relational strategies to enhance access to care, supplementing obesity management. Usual Care will be offered similarly at both clinics, adhering to expert guidelines. At enrollment, families will complete a multidisciplinary assessment, then meet regularly with a multidisciplinary team of clinicians for obesity management. Over 12 months, both FN and Usual Care will be delivered virtually and/or in-person, pandemic permitting. Data will be collected at 0, 3, 6, and 12 months post-baseline. We will explore child and caregiver perceptions of FN acceptability as well as evaluate attrition, recruitment, enrolment, randomization, and protocol integrity against pre-set success thresholds. Data on clinical, health services, and health economic outcomes will be collected using established protocols. Qualitative data analysis will apply thematic analysis; quantitative data analysis will be descriptive. Discussion Our trial will assess the feasibility of FN to address attrition in managing pediatric obesity. Study data will inform a future effectiveness trial, which will be designed to test whether FN reduces attrition. Trial registration This trial was registered prospectively at ClinicalTrials.gov (# NCT05403658 ; first posted: June 3, 2022).

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019–2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran’s Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ.

Abstract Background Oral anticoagulants (OACs) are commonly prescribed, have well-documented benefits for important clinical outcomes but have serious harms as well. Rates of OAC-related adverse events including thromboembolic and hemorrhagic events are especially high shortly after hospital discharge. Expert OAC management involving virtual care is a research priority given its potential to reach remote communities in a more feasible, timely, and less costly way than in-person care. Our objective is to test whether a focused, expert medication management intervention using a mix of in-person consultation and virtual care follow-up, is feasible and effective in preventing anticoagulation-related adverse events, for patients transitioning from hospital to home. Methods and analysis A randomized, parallel, multicenter design enrolling consenting adult patients or the caregivers of cognitively impaired patients about to be discharged from medical wards with a discharge prescription for an OAC. The interdisciplinary multimodal intervention is led by a clinical pharmacologist and includes a detailed discharge medication reconciliation and management plan focused on oral anticoagulants at hospital discharge; a circle of care handover and coordination with patient, hospital team and community providers; and early post-discharge follow-up virtual medication check-up visits at 24 h, 1 week, and 1 month. The control group will receive usual care plus encouragement to use the Thrombosis Canada website. The primary feasibility outcomes include recruitment rate, participant retention rates, trial resources management, and the secondary clinical outcomes include adverse anticoagulant safety events composite (AASE), coordination and continuity of care, medication-related problems, quality of life, and healthcare resource utilization. Follow-up is 3 months. Discussion This pilot RCT tests whether there is sufficient feasibility and merit in coordinating oral anticoagulant care early post-hospital discharge to warrant a full sized RCT. Trial registration NCT02777047.

Introduction In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults.Methods and analysis We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups.Ethics and dissemination Critical Care Cycling to improve Lower Extremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations.Trial registration number NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).

Purpose: Paget's disease of bone (PDB) is a focal metabolic bone disorder characterized by an increased bone remodeling. Fifteen to 40 % of PDB patients have a familial form with an autosomal dominant inheritance. Disease-causing mutations of the SQSTM1 gene have been linked to PDB in about 40 % of families whereas genes linked to the remaining families are unknown. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in unrelated patient non-carriers of a SQSTM1 mutation. The current clinical practice guidelines still recommend the measure of serum total alkaline phosphatase (sALP) for PDB screening. In unrelated individual non-carriers of SQSTM1 mutations, we previously developed a genetic test combining male sex with five genetic markers (rs499345, rs5742915, rs2458413, rs3018362, rs2234968), giving rise to an area under the curve (AUC) for PDB phenotype of 0.73 (0.69; 0.77). A combination of male sex with total calcium corrected for albumin and Procollagen type I N-terminal propeptide (P1NP), had an AUC of 0.82 (0.73; 0.92). Combining both genetic and biochemical tests increased the AUC to 0.89 (0.83; 0.95). Objective: This study aimed at estimating the performance of our previous test of PDB, in families not linked to SQSTM1 mutations with disease-causing genes yet unknown, and at developing a new algorithm if the performance is not satisfactory. Methods: We genotyped the five SNPs cited above, and measured calcium corrected for albumin and P1NP in 181 relatives, with PDB or not, from 19 PDB families not linked to SQSTM1 mutations. Bivariate and multivariate logistic regression models including male sex were fitted to search for a molecular test that could best detect PDB in these families. A receiving operating characteristics analysis was done to establish a cut-off point for continuous variables. Results: Logistic regression estimates of our previous molecular test gave rise to a high sensitivity of 78 %, 97 % and 88 % for the genetic, biochemical, and combined test but the specificity was very low, 35 %, 11 % and 21 %, respectively. This poor specificity persisted even when the cut-off point was changed. We then generated in these families, new logistic regression estimates but on the same parameters as mentioned above, giving rise to an AUC of 0.65 (0.55; 0.75) for the genetic test, of 0.84 (0.74; 0.94) for the biochemical test, and 0.89 (0.82; 0.96) for the combination test, the latter having a sensitivity of 96 % and specificity of 57 %. By comparison serum P1NP alone gave rise to an AUC of 0.84 (0.73; 0.94), with a sensitivity of 71 % and a specificity of 79 %. Conclusion: In PDB families not linked to SQSTM1 mutations, the estimates of our previous molecular test gave rise to a poor specificity. Using new estimates, the biochemical and combined tests have similar predictive abilities than our former test. Serum P1NP is a bone marker of interest for the screening for PDB in families not linked to SQSTM1 mutations.

Abstract Rationale To inform future policies, the study objectives were to determine to what extent the policies included in the 5‐year Plan of Action for the Prevention of Obesity in Children and Adolescents—proposed by Pan American Health Organization (PAHO) and signed by 19 Latin America countries in 2014—have been implemented and evaluated. Methods A scoping review of the Governmental websites for Latin American countries and a literature review was conducted to identify whether policies have been implemented and evaluated. Key information was abstracted. Results The review identified 115 PAHO policies/interventions implemented (43% implemented after signing the proposed plan in 2014). Nearly all (18/19) countries implemented food guidelines or school feeding programs, but fiscal and marketing policies were less commonly implemented (6/19). Through the review, 44 evaluations of PAHO policies were identified of which 23% were qualitative and 77% quantitative. The results of these evaluations were in general positive (e.g., decrease in sugar‐sweetened beverages consumption following tax implementation) but no studies evaluated the outcome of reduced obesity. Conclusions PAHO recommended policies have been implemented to various degrees in Latin America since 2014 and more research is required to understand their impacts on child and adolescent obesity.

IntroductionIn response to the COVID-19 pandemic, the Ontario Ministry of Health introduced a pilot program of 14 virtual urgent care (VUC) initiatives across the province to encourage physical distancing and provision of care by telephone and video-enabled visits. The implementation of the VUC pilot is currently being evaluated by an external academic team. The objective of this study was to understand patient experiences with VUC to determine barriers and facilitators to optimal virtual care as it rapidly expands during the current pandemic and beyond.MethodThe qualitative component of the evaluation used one-on-one telephone interviews with patients, families, providers, and program administrators as the main method of data collection. Patient and family participants were invited to participate by the triage nurse after their VUC visit. Data analysis, using thematic analysis, occurred in conjunction with data collection to monitor emerging themes and areas for further exploration.ResultsBetween April and October 2021, we completed 14 patient and/or family interviews from a representative cross-section of 6 pilot sites. Participants had a range of presenting complaints including infection, injury, medication side effects, and abdominal pain. The vast majority of participants were female (90%), and 70% were VUC patients themselves. Our analysis identified three key themes in the data which characterise patient and family member experience with VUC: a) emphasis on access to the ED; b) efficiency and quality of care; c) obtaining reassurance and next steps.ConclusionVirtual care options are valued by patients and families; however, the nature of care needed by those accessing VUC and who can best provide that care needs to be evaluated to position it for sustainability. Understanding how virtual care performs from both a provider and patient perspective during the current crisis has implications for designing alternative care options beyond the COVID-19 pandemic.

Abstract The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. (“GUIDED”), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian “GAPP-MDD” RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).

Abstract Background In 2007–2012 the Mexican government launched the National HIV program and there was a major change in HIV policies implemented in 2013–2018, when efforts focused on prevention, increase in early diagnosis and timely treatment. Still, late HIV diagnosis is a major concern in Mexico due to its association with the development of AIDS development and mortality. Thus, the objectives of this study were to identify the determinants of late HIV diagnosis (i.e. CD4 count less than 200 cells/mm3) in Mexico from 2008 to 2017 and to evaluate the impact of the 2013–2017 National HIV program. Methods Using patient level data from the SALVAR database, which includes 64% of the population receiving HIV care in Mexico, an adjusted logistic model was conducted. Main study outcomes were HIV late diagnosis which was defined as CD4 count less than 200 cells/mm3 at diagnosis. Results The study included 106,830 individuals newly diagnosed with HIV and treated in Mexican public health facilities between 2008 and 2017 (mean age: 33 years old, 80% male). HIV late diagnosis decreased from 45 to 43% (P

Precision medicine in oncology poses unique challenges to the generation of clinical and economic evidence used for cost-effectiveness analyses that can inform health technology assessment. The conduct of randomized controlled trials for biomarker-specific therapies targeted towards small populations has limitations in regard to feasibility, timeliness, and cost. These limitations result in associated challenges for groups involved in the generation of economic evidence to inform treatment-related decision making, including the Committee of Economic Analysis (CEA) at the Canadian Cancer Trials Group (CCTG). We provide a high-level description and vision about the new paradigm of clinical trial design, generation of economic evidence, and novel approaches to economic evaluations necessary in the space of precision medicine in oncology in Canada. The CEA’s previous approach to precision medicine, including master protocol designs and single-arm studies, is reviewed. Methods and approaches currently under consideration by the CEA and national collaborators, such as the role of real-world and clinical trial evidence in enabling life-cycle assessment of therapies, are explored. Finally, future initiatives being planned in the space of precision medicine at CCTG, such as the incorporation of correlative studies to identify and test high-performing biomarkers in trials, are discussed.

Objective In response to the COVID-19 pandemic, Sunnybrook Health Sciences Centre launched the first virtual emergency department (VED) in Toronto, Ontario. The objective of this pilot project was to leverage linked administrative data to describe the healthcare utilization of VED patients compared to matched patients who attended an ED in person. Approach Evaluation of the VED program was supported by the ICES Applied Health Research Question Program, which is funded by the Ontario Ministry of Health to answer questions directly related to Ontario healthcare policy, planning, or practice. VED visit records from December 2020 to May 2021 were linked with Ontario administrative data. VED patients with low acuity complaints were matched 1:1 with in-person ED comparators according to visit date, presenting complaint, and a propensity score that incorporated age, sex, comorbidities, and other important potential confounders. The primary outcomes were healthcare utilization within 7 days and all-cause mortality within 30 days. Results Of the 609 eligible patients discharged from the VED, 600 (98.5%) were successfully matched to a comparator. Mean (SD) age was 43.0 (21.1) and 64.1% were female. In-person ED revisits and hospitalizations were similar for VED and comparator patients at 72 hours (ED: 12.1% vs. 11.3%; Δ 0.8%, 95%: -2.8, 4.5%; hospitalization: 1.2% vs. 1.5%; Δ 0.3%, 95%: -0.7, 1.4%,) and 7 days (ED: 16.1% vs. 14.4%; Δ 1.7, 95%: -2.4, 5.7%; hospitalization: 1.7% vs. 1.8%; Δ 0.2%, 95%: -0.1, 1.4%) following the index visit. The number of patients visiting a primary care provider within 7 days was also similar between groups (36.7% vs. 32.4%; Δ 4.3, 95%: -1.1, 9.8%). No patients died within 30 days. Conclusion/Implications VED patients and their matched comparators had similar healthcare utilization in the 7 days following their index ED visit. Methodology from this study will inform a province-wide evaluation of VED programs across Ontario.

ABSTRACTBackground Total knee arthroplasties are the second most common surgery in Canada. Most patients recover well, but 20% or more still suffer from persistent pain and opioid use. Though opioids are an important part of perioperative pain management, their potential for long-term adverse effects is well recognized. Limiting opioids may be insufficient to overcome the issue of opioid overuse. Pain and opioid use are highly linked, so an effective alternative needs to address both issues.Objectives The principal objective of this pilot trial is to assess the feasibility. The clinical objectives are to determine the effects of a multicomponent care pathway on opioid-free pain control, persisting pain and opioid use, functional knee outcomes, quality of life, and return to function.Methods We will include adult patients scheduled for primary elective total knee arthroplasty. Patients in the intervention group will undergo a multicomponent intervention pathway that will be facilitated by an intervention coordinator linking each patient and their surgical/ perioperative team. The interventional pathway will include (1) preoperative education on pain and opioid use, (2) preoperative risk identification and mitigation using cognitive behavioral skills, (3) personalized postdischarge analgesic prescriptions, and (4) continued support for pain control and recovery up to 8 weeks. Patients in the control group will receive the usual care at their institution.Discussion The overarching goal is to implement and evaluate a coordinated approach to clinical care to improve pain control and reduce harms, with an emphasis on patient-centered care and shared decision making.Trial Registration Number: NCT04968132 (informed consent/ research ethics board statement).

Abstract Background The secondary fracture prevention gap in the osteoporosis field has been previously described as a ‘crisis’. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1–2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures. Methods This retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017). BMD assessment and use of osteoporosis therapies following index fracture were also characterized. Results Among 115,776 patients with an index fragility fracture, 17.8% incurred a second fragility fracture. Median time between index and second fracture occurring at any site was 555 days (interquartile range: 236–955). For each index fracture site examined, median time from index to second fracture was 3 years post index fracture. Conclusions This cohort of Canadian patients aged > 65 years who experienced a fragility fracture at any site are at imminent risk of experiencing subsequent fracture within the next 2 years and should be proactively assessed and treated.

Background: There is a lack of data on the burden of patients hospitalized with aortic stenosis (AS) in Canada. The primary study objective was to document the index and 1-year costs of hospitalized patients with AS in Canada. Secondary objectives were to explore results by treatment modality and Canadian provinces. Methods: Hospitalized patients with a most responsible diagnosis (MRD) of AS during fiscal year 2014/2015 were identified using Canadian administrative databases. Costs were calculated for the index admission and for up to 1 year. For our secondary analyses, patients were classified according to the intervention received: surgical aortic valve replacement (SAVR), SAVR with coronary artery bypass graft, or transfemoral or transapical transcatheter aortic valve implantation. Hospitalized AS patients who did not undergo SAVR or transcatheter aortic valve implantation were classified as the untreated group. The data were also analyzed by Canadian provinces. Results: During fiscal year 2014/15, a total of 7217 Canadians were hospitalized with an MRD of AS. The mean (standard deviation) age of our population was 74.2 (11.5) years, and 39% were female. The 1-year hospital costs associated with an MRD of AS in Canada were calculated at $393 million. Our secondary analyses suggest that patient demographics (mean age ranging from 69 to 82 years) and outcomes (median length of stay ranging from 6 to 12 days) differ among treatment modalities and Canadian provinces. Conclusions: AS hospitalizations result in a significant cost burden in Canada. Future research is needed to better understand variation among treatment modalities and Canadian provinces. Résumé: Contexte: Les données sur le fardeau associé aux hospitalisations pour sténose aortique (SA) au Canada sont fragmentaires. L’étude avait pour principal objectif de déterminer le coût de référence et le coût d’une année d’hospitalisations pour SA au Canada. Les objectifs secondaires consistaient à étudier les résultats selon les modalités thérapeutiques ainsi que par province canadienne. Méthodologie: Les patients hospitalisés pour un diagnostic principal de SA pendant l’exercice financier 2014-2015 ont été répertoriés à partir de bases de données administratives canadiennes. Les coûts ont été calculés pour l’admission de référence et pour une période maximale d’un an. Pour nos analyses secondaires, les patients ont été classés selon l’intervention reçue : chirurgie de remplacement valvulaire aortique, chirurgie de remplacement valvulaire aortique avec pontage aortocoronarien, ou implantation valulaire aortique par chathéter par voie transfémorale ou transapicale. Les patients hospitalisés pour SA n’ayant subi aucune chirurgie de remplacement valvulaire aortique ni aucune implantation valvulaire aortique par cathéter ont été classés non traités. Résultats: Pendant l’exercice financier 2014-2015, un total de 7 217 Canadiens ont été hospitalisés pour un diagnostic principal de SA. L’âge moyen (écart-type) de notre population était de 74,2 (11,5) ans; 39 % étaient des femmes. Les coûts des hospitalisations pour SA comme diagnostic principal pour une année au Canada ont été calculés à 393 millions de dollars. Nos analyses secondaires laissent croire que les données démographiques des patients (âge moyen variant de 69 à 82 ans) et les issues (durée médiane des séjours variant de 6 à 12 jours) diffèrent selon les modalités thérapeutiques et les provinces canadiennes. Conclusions: Les hospitalisations pour SA constituent un important fardeau financier au Canada. D’autres recherches sont nécessaires pour mieux comprendre les variations en fonction des modalités thérapeutiques et des provinces canadiennes.

Abstract Background Recent studies are lacking reports on mortality after non-hip fractures in adults aged > 65. Methods This retrospective, matched-cohort study used de-identified health services data from the publicly funded healthcare system in Ontario, Canada, contained in the ICES Data Repository. Patients aged 66 years and older with an index fragility fracture occurring at any osteoporotic site between 2011 and 2015 were identified from acute hospital admissions, emergency and ambulatory care using International Classification of Diseases (ICD)-10 codes and data were analyzed until 2017. Thus, follow-up ranged from 2 years to 6 years. Patients were excluded if they presented with an index fracture occurring at a non-osteoporotic fracture site, their index fracture was associated with a trauma code, or they experienced a previous fracture within 5 years prior to their index fracture. This fracture cohort was matched 1:1 to controls within a non-fracture cohort by date, sex, age, geography and comorbidities. All-cause mortality risk was assessed. Results The survival probability for up to 6 years post-fracture was significantly reduced for the fracture cohort vs matched non-fracture controls (p 65 years, a fragility fracture occurring at any site was associated with reduced survival for up to 6 years post-fracture. The greatest reduction in survival occurred within the first-year post-fracture, where mortality risk more than doubled and deaths were observed in 1 in 11 women and 1 in 7 men following a non-hip fracture and in 1 in 5 women and 1 in 3 men following a hip fracture.

BackgroundWearable continuous monitoring biosensor technologies have the potential to transform postoperative care with early detection of impending clinical deterioration. ObjectiveOur aim was to validate the accuracy of Cloud DX Vitaliti continuous vital signs monitor (CVSM) continuous noninvasive blood pressure (cNIBP) measurements in postsurgical patients. A secondary aim was to examine user acceptance of the Vitaliti CVSM with respect to comfort, ease of application, sustainability of positioning, and aesthetics. MethodsIncluded participants were ≥18 years old and recovering from surgery in a cardiac intensive care unit (ICU). We targeted a maximum recruitment of 80 participants for verification and acceptance testing. We also oversampled to minimize the effect of unforeseen interruptions and other challenges to the study. Validation procedures were according to the International Standards Organization (ISO) 81060-2:2018 standards for wearable, cuffless blood pressure (BP) measuring devices. Baseline BP was determined from the gold-standard ICU arterial catheter. The Vitaliti CVSM was calibrated against the reference arterial catheter. In static (seated in bed) and supine positions, 3 cNIBP measurements, each 30 seconds, were taken for each patient with the Vitaliti CVSM and an invasive arterial catheter. At the conclusion of each test session, captured cNIBP measurements were extracted using MediCollector BEDSIDE data extraction software, and Vitaliti CVSM measurements were extracted to a secure laptop through a cable connection. The errors of these determinations were calculated. Participants were interviewed about device acceptability. ResultsThe validation analysis included data for 20 patients. The average times from calibration to first measurement in the static position and to first measurement in the supine position were 133.85 seconds (2 minutes 14 seconds) and 535.15 seconds (8 minutes 55 seconds), respectively. The overall mean errors of determination for the static position were –0.621 (SD 4.640) mm Hg for systolic blood pressure (SBP) and 0.457 (SD 1.675) mm Hg for diastolic blood pressure (DBP). Errors of determination were slightly higher for the supine position, at 2.722 (SD 5.207) mm Hg for SBP and 2.650 (SD 3.221) mm Hg for DBP. The majority rated the Vitaliti CVSM as comfortable. This study was limited to evaluation of the device during a very short validation period after calibration (ie, that commenced within 2 minutes after calibration and lasted for a short duration of time). ConclusionsWe found that the Cloud DX’s Vitaliti CVSM demonstrated cNIBP measurement in compliance with ISO 81060-2:2018 standards in the context of evaluation that commenced within 2 minutes of device calibration; this device was also well-received by patients in a postsurgical ICU setting. Future studies will examine the accuracy of the Vitaliti CVSM in ambulatory contexts, with attention to assessment over a longer duration and the impact of excessive patient motion on data artifacts and signal quality. Trial RegistrationClinicalTrials.gov NCT03493867; https://clinicaltrials.gov/ct2/show/NCT03493867

Injection drug use poses a public health challenge. Clinical experience indicates that people who inject drugs (PWID) are hospitalized frequently for infectious diseases, but little is known about outcomes when admitted. Charts were identified from local hospitals between 2013–2018 using consultation lists and hospital record searches. Included individuals injected drugs in the past six months and presented with infection. Charts were accessed using the hospital information system, undergoing primary and secondary reviews using Research Electronic Data Capture (REDCap). The Wilcoxon rank-sum test was used for comparisons between outcome categories. Categorical data were summarized as count and frequency, and compared using Fisher’s exact test. Of 240 individuals, 33% were admitted to the intensive care unit, 36% underwent surgery, 12% left against medical advice (AMA), and 9% died. Infectious diagnoses included bacteremia (31%), abscess (29%), endocarditis (29%), cellulitis (20%), sepsis (10%), osteomyelitis (9%), septic arthritis (8%), pneumonia (7%), discitis (2%), meningitis/encephalitis (2%), or other (7%). Sixty-six percent had stable housing and 60% had a family physician. Fifty-four percent of patient-initiated discharges were seen in the emergency department within 30 days and 29% were readmitted. PWID are at risk for infections. Understanding their healthcare trajectory is essential to improve their care.

Abstract Background Health TAPESTRY (Health Teams Advancing Patient Experience: STRengthening qualitY) aims to help people stay healthier for longer where they live by providing person-focused care through the integration of four key program components: (1) trained volunteers who visit clients in their homes, (2) an interprofessional primary health care team, (3) use of technology to collect and share information, and (4) improved connections to community health and social services. The initial randomized controlled trial of Health TAPESTRY found promising results in terms of health care use and patient outcomes, indicating a shift from reactive to preventive care. The trial was based on one clinical academic center, thus limiting generalizability. The study objectives are (1) to test reproducibility of the established effectiveness of Health TAPESTRY on physical activity and hospitalizations, (2) to test the feasibility of, and understand the contributing factors to, the implementation of Health TAPESTRY in six diverse communities across Ontario, Canada, and (3) to determine the value for money of implementing Health TAPESTRY. Methods This planned study is a pragmatic parallel randomized controlled trial with a delayed intervention for control participants at 6 months. This trial will simultaneously assess effectiveness and implementation in a real-world setting (type II hybrid) in six diverse communities across Ontario. Participants 70 years of age and older will be randomized into the Health TAPESTRY intervention or the control group (usual care). Intervention clients will receive an individualized plan of care from an interprofessional care team. The plan will be based on a client’s goals and current health risks identified through volunteer visits. The study’s outcomes are mapped onto the RE-AIM framework, with levels of physical activity and number of hospitalizations as the co-primary outcomes. The main analysis will be a comparison at 6 months. Discussion It is important to evaluate the effectiveness and implementation of Health TAPESTRY in multiple communities prior to scaling or widespread adoption. Trial registration ClinicalTrials.gov NCT03397836 . Registered on 12 January 2018

Abstract Background In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection. Methods The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries. Results A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate. Conclusion This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.

Abstract Background Senior high cost health care users (HCU) are a priority for many governments. Little research has addressed regional variation of HCU incidence and outcomes, especially among incident HCU. This study describes the regional variation in healthcare costs and mortality across Ontario’s health planning districts [Local Health Integration Networks (LHIN)] among senior incident HCU and non-HCU and explores the relationship between healthcare spending and mortality. Methods We conducted a retrospective population-based matched cohort study of incident senior HCU defined as Ontarians aged ≥66 years in the top 5% most costly healthcare users in fiscal year (FY) 2013. We matched HCU to non-HCU (1:3) based on age, sex and LHIN. Primary outcomes were LHIN-based variation in costs (total and 12 cost components) and mortality during FY2013 as measured by variance estimates derived from multi-level models. Outcomes were risk-adjusted for age, sex, ADGs, and low-income status. In a cost-mortality analysis by LHIN, risk-adjusted random effects for total costs and mortality were graphically presented together in a cost-mortality plane to identify low and high performers. Results We studied 175,847 incident HCU and 527,541 matched non-HCU. On average, 94 out of 1000 seniors per LHIN were HCU (CV = 4.6%). The mean total costs for HCU in FY2013 were 12 times higher that of non-HCU ($29,779 vs. $2472 respectively), whereas all-cause mortality was 13.6 times greater (103.9 vs. 7.5 per 1000 seniors). Regional variation in costs and mortality was lower in senior HCU compared with non-HCU. We identified greater variability in accessing the healthcare system, but, once the patient entered the system, variation in costs was low. The traditional drivers of costs and mortality that we adjusted for played little role in driving the observed variation in HCUs’ outcomes. We identified LHINs that had high mortality rates despite elevated healthcare expenditures and those that achieved lower mortality at lower costs. Some LHINs achieved low mortality at excessively high costs. Conclusions Risk-adjusted allocation of healthcare resources to seniors in Ontario is overall similar across health districts, more so for HCU than non-HCU. Identified important variation in the cost-mortality relationship across LHINs needs to be further explored.

BackgroundKnowledge of HIV drug resistance informs the choice of regimens and ensures that the most efficacious options are selected. In January 2014, a policy change to routine resistance testing was implemented in Ontario, Canada. The objective of this study was to investigate the policy change impact of routine resistance testing in people with HIV in Ontario, Canada since January 2014.MethodsWe used data on people with HIV living in Ontario from administrative databases of the Institute for Clinical Evaluative Sciences (ICES) and Public Health Ontario (PHO), and ran ordinary least squares (OLS) models of interrupted time series to measure the levels and trends of 2-year mortality, 2-year hospitalizations and 2-year emergency department visits before (2005-2013) and after the policy change (2014-2017). Outcomes were collected in biannual periods, generating 18 periods before the intervention and 8 periods after. We included a control series of people who did not receive a resistance test within 3 months of HIV diagnosis.ResultsData included 12,996 people with HIV, of which 8881 (68.3%) were diagnosed between 2005 and 2013, and 4115 (31.7%) were diagnosed between 2014 and 2017. Policy change to routine resistance testing within 3 months of HIV diagnosis led to a decreasing trend in 2-year mortality of 0.8% every six months compared to the control group. No significant differences in hospitalizations or emergency department visits were noted.InterpretationThe policy of routine resistance testing within three months of diagnosis is beneficial at the population level.

Background: Propensity score (PS) methods are frequently used within economic evaluations based on nonrandomized data to adjust for measured confounders, but many researchers omit the fact that they cannot adjust for unmeasured confounders. Objective: To illustrate how confounding due to unmeasured confounders can bias an economic evaluation despite PS matching. Methods: We used data from a previously published nonrandomized study to select a prematched population consisting of 121 patients (46.5%) who received endovascular aneurysm repair (EVAR) and 139 patients (53.5%) who received open surgical repair (OSR), in which sufficient data regarding eight measured confounders were available. One-to-one PS matching was used within this population to select two PS-matched subpopulations. The Matched PS-Smoking Excluded Subpopulation was selected by matching patients using a PS model that omitted patients’ smoking status (one of the measured confounders), whereas the Matched PS-Smoking Included Subpopulation was selected by matching patients using a PS model that included all eight measured confounders. Incremental cost-effectiveness ratios (ICERs) were assessed within both subpopulations. Results: Both subpopulations were composed of two different sets of 164 patients. Balance within the Matched PS-Smoking Excluded Subpopulation was achieved on all confounders except for patients’ smoking status, whereas balance within the Matched PS-Smoking Included Subpopulation was achieved on all confounders. Results indicated that the ICER of EVAR over OSR differed between both subpopulations; the ICER was estimated at $157,909 per life-year gained (LYG) within the Matched PS-Smoking Excluded Subpopulation, while it was estimated at $235,074 per LYG within the Matched PS-Smoking Included Subpopulation. Discussion: Although effective in controlling for measured confounding, PS matching may not adjust for unmeasured confounders that may bias the results of an economic evaluation based on nonrandomized data.

Background. St. Joseph’s Health System has implemented an integrated comprehensive care bundle care (ICC) program with the hopes that it would improve patients’ care while reducing overall costs. The aim of this analysis was to evaluate the performance of the ICC program within patients admitted with chronic pulmonary obstructive disease (COPD). Methods. We conducted a retrospective observational cohort study comparing ICC patients to non-ICC patients admitted to St. Joseph’s Healthcare Hamilton for COPD being discharged with support services between June 2012 and March 2015, using administrative data. Confounding adjustment was achieved through the use of propensity score matching. Medical resource utilizations during the initial hospitalization and within the 60 days following discharge were compared using regression models. Results. All 76 patients who entered the ICC program (100.0%) were matched 1 : 1 to 76 eligible non-ICC patients (28.4%). Length of stay (6.47 [7.29] versus 9.55 [10.21] days) and resource intensity weights (1.16 [0.80] versus 1.64 [1.69]) were lower in the ICC group within the initial hospitalization but, while favoring the ICC program, healthcare resource use tended not to differ statistically following discharge. Interpretation. The ICC program was able to reduce initial medical resource utilization without increasing subsequent medical resource use.

Introduction Early exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT.Methods and analysis 60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0–4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients' muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1–2 patients per month per centre, (2) protocol violation rate 80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics.Ethics and dissemination Each participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors.Trial registration number NCT02377830; Pre-results.

Background. This paper presents unpublished clinical and economic data associated with open surgical repair (OSR) in low risk (LR) patients and how it compares with EVAR and OSR in high risk (HR) patients with an AAA > 5.5 cm. Design. Data from a 1-year prospective observational study was used to compare EVAR in HR patients versus OSR in HR and LR patients. Results. Between 2003 and 2005, 140 patients were treated with EVAR and 195 with OSR (HR: 52; LR: 143). The 1-year mortality rate with EVAR was statistically lower than HR OSR patients and comparable to LR OSR patients. One-year health-related quality of life was lower in the EVAR patients compared to OSR patients. EVAR was cost-effective compared to OSR HR but not when compared to OSR LR patients. Conclusions. Despite a similar clinical effectiveness, these results suggest that, at the current price, EVAR is more expensive than open repair for low risk patients.

BackgroundBayesian hierarchical models have been proposed to combine evidence from different types of study designs. However, when combining evidence from randomised and non-randomised controlled studies, imbalances in patient characteristics between study arms may bias the results. The objective of this study was to assess the performance of a proposed Bayesian approach to adjust for imbalances in patient level covariates when combining evidence from both types of study designs.Methodology/principal findingsSimulation techniques, in which the truth is known, were used to generate sets of data for randomised and non-randomised studies. Covariate imbalances between study arms were introduced in the non-randomised studies. The performance of the Bayesian hierarchical model adjusted for imbalances was assessed in terms of bias. The data were also modelled using three other Bayesian approaches for synthesising evidence from randomised and non-randomised studies. The simulations considered six scenarios aimed at assessing the sensitivity of the results to changes in the impact of the imbalances and the relative number and size of studies of each type. For all six scenarios considered, the Bayesian hierarchical model adjusted for differences within studies gave results that were unbiased and closest to the true value compared to the other models.Conclusions/significanceWhere informed health care decision making requires the synthesis of evidence from randomised and non-randomised study designs, the proposed hierarchical Bayesian method adjusted for differences in patient characteristics between study arms may facilitate the optimal use of all available evidence leading to unbiased results compared to unadjusted analyses.

Objectives. The objectives of this study were to elicit health utility scores for moderate Alzheimer's disease (AD) using members of the general public. Methods. Five-hundred Canadians were chosen randomly to participate in a telephone interview. The EQ-5D was administered to estimate the health utility score for respondents' current health status (i.e., no AD) and for a hypothetical moderate AD health state. Regression analyses were conducted to explain the perceived utility decrement associated with AD. Results. The mean age of the respondents was 51 years, 60% were female, and 42% knew someone with AD. Respondents' mean EQ-5D scores for their current health status and a hypothetical moderate AD were 0.873 (SD: 0.138) and 0.638 (SD: 0.194), respectively (P

Abstract Background Lack of evidence about the long-term economic benefits of interventions targeting underserved perinatal populations can hamper decision making regarding funding. To optimize the quality of future research, we examined what methods and costs have been used to assess the value of interventions targeting pregnant people and/or new parents who have poor access to healthcare. Methods We conducted a scoping review using methods described by Arksey and O’Malley. We conducted systematic searches in eight databases and web-searches for grey literature. Two researchers independently screened results to determine eligibility for inclusion. We included economic evaluations and cost analyses of interventions targeting pregnant people and/or new parents from underserved populations in twenty high income countries. We extracted and tabulated data from included publications regarding the study setting, population, intervention, study methods, types of costs included, and data sources for costs. Results Final searches were completed in May 2024. We identified 103 eligible publications describing a range of interventions, most commonly home visiting programs (n = 19), smoking cessation interventions (n = 19), prenatal care (n = 11), perinatal mental health interventions (n = 11), and substance use treatment (n = 10), serving 36 distinct underserved populations. A quarter of the publications (n = 25) reported cost analyses only, while 77 were economic evaluations. Most publications (n = 82) considered health care costs, 45 considered other societal costs, and 14 considered only program costs. Only a third (n = 36) of the 103 included studies considered long-term costs that occurred more than one year after the birth (for interventions occurring only in pregnancy) or after the end of the intervention. Conclusions A broad range of interventions targeting pregnant people and/or new parents from underserved populations have the potential to reduce health inequities in their offspring. Economic evaluations of such interventions are often at risk of underestimating the long-term benefits of these interventions because they do not consider downstream societal costs. Our consolidated list of downstream and long-term costs from existing research can inform future economic analyses of interventions targeting poorly served pregnant people and new parents. Comprehensively quantifying the downstream and long-term benefits of such interventions is needed to inform decision making that will improve health equity.