Implementation of an audit and feedback module targeting low-value clinical practices in a provincial trauma quality assurance program: a cost-effectiveness study.

BACKGROUND: Audit and Feedback (A&F) interventions based on quality indicators have been shown to lead to significant improvements in compliance with evidence-based care including de-adoption of low-value practices (LVPs). Our primary aim was to evaluate the cost-effectiveness of adding a hypothetical A&F module targeting LVPs for trauma admissions to an existing quality assurance intervention targeting high-value care and risk-adjusted outcomes. A secondary aim was to assess how certain A&F characteristics might influence its cost-effectiveness. METHODS: We conducted a cost-effectiveness analysis using a probabilistic static decision analytic model in the Québec trauma care continuum. We considered the Québec Ministry of Health perspective. Our economic evaluation compared a hypothetical scenario in which the A&F module targeting LVPs is implemented in a Canadian provincial trauma quality assurance program to a status quo scenario in which the A&F module is not implemented. In scenarios analyses we assessed the impact of A&F characteristics on its cost-effectiveness. Results are presented in terms of incremental costs per LVP avoided. RESULTS: Results suggest that the implementation of A&F module (Cost = $1,480,850; Number of LVPs = 6,005) is associated with higher costs and higher effectiveness compared to status quo (Cost = $1,124,661; Number of LVPs = 8,228). The A&F module would cost $160 per LVP avoided compared to status quo. The A&F module becomes more cost-effective with the addition of facilitation visits; more frequent evaluation; and when only high-volume trauma centers are considered. CONCLUSION: A&F module targeting LVPs is associated with higher costs and higher effectiveness than status quo and has the potential to be cost-effective if the decision-makers' willingness-to-pay is at least $160 per LVP avoided. This likely represents an underestimate of true ICER due to underestimated costs or missed opportunity costs. Results suggest that virtual facilitation visits, frequent evaluation, and implementing the module in high-volume centers can improve cost-effectiveness.

Integration of real-world evidence from different data sources in health technology assessment.

Real-world evidence (RWE) is being increasingly used by a wide range of stakeholders involved in the therapeutic product lifecycle but remains underutilized in the health technology assessment (HTA) process. RWE aims to fill the current evidence gaps, reduce the uncertainty around the benefits of medical technologies, and better understand the long-term impact of health technologies in real-world conditions. Despite the minimal use of RWE in some elements of HTA, there has been a larger push to further utilize RWE in the HTA processes. HTA bodies, as other stakeholders, work towards developing more robust means to leverage RWE from various data sources in the HTA processes. However, these agencies need to overcome important challenges before the broader incorporation of RWE into their routine practice. This paper aims to explore the extensive integration of RWE utilizing diverse sources of RWD. We discuss the utilization of RWE in HTA processes, considering aspects such as when, where, and how RWE can be effectively applied. Additionally, we seek the potential challenges and barriers associated with the utilization of different data sources.

Health Utilities Index Mark 3 scores for children and youth: Population norms for Canada based on cycles 5 (2016 and 2017) and 6 (2018 and 2019) of the Canadian Health Measures Survey.

Background: Utility scores are an important tool for evaluating health-related quality of life. Utility score norms have been published for Canadian adults, but no nationally representative utility score norms are available for children and youth. Data and methods: Health Utilities Index Mark 3 (HUI3) data from two recent cycles of the Canadian Health Measures Survey (i.e., 2016 and 2017, and 2018 and 2019) were used to provide utility score norms for children aged 6 to 11 years and adolescents aged 12 to 17 years. Children younger than 14 years answered the HUI3 under the supervision of an adult, while older children answered without supervision. Utility scores were reported as a weighted average (95% confidence intervals [CIs]) and median values (interquartile range). Utility scores were stratified by sociodemographic and medical characteristics of the child or adolescent. Regression analyses were used to identify predictors of utility scores. All results were weighted using sampling weights provided by Statistics Canada. Results: Among the 2,297,136 children aged 6 to 11 years and the 2,329,185 adolescents aged 12 to 17 years in the weighted sample, the average utility scores were 0.95 (95% CI: 0.94 to 0.95) and 0.89 (95% CI: 0.87 to 0.90), respectively. Approximately 60% of the children and 34% of the adolescents had a utility score of 1.00. Analyses identified several factors associated with utility scores (e.g., age, chronic condition and income levels), although differences were observed between children and adolescents. Interpretation: This study provides utility score estimates based on a nationally representative sample of Canadian children and youth. Further research examining the determinants of utility scores of children and adolescents is warranted.

Economic Evaluation of In-Hospital Clinical Practices in Acute Injury Care: A Systematic Review.

OBJECTIVES: Underuse of high-value clinical practices and overuse of low-value practices are major sources of inefficiencies in modern healthcare systems. To achieve value-based care, guidelines and recommendations should target both underuse and overuse and be supported by evidence from economic evaluations. We aimed to conduct a systematic review of the economic value of in-hospital clinical practices in acute injury care to advance knowledge on value-based care in this patient population. METHODS: Pairs of independent reviewers systematically searched MEDLINE, Embase, Web of Science, and Cochrane Central Register for full economic evaluations of in-hospital clinical practices in acute trauma care published from 2009 to 2019 (last updated on June 17, 2020). Results were converted into incremental net monetary benefit and were summarized with forest plots. The protocol was registered with PROSPERO (CRD42020164494). RESULTS: Of 33 910 unique citations, 75 studies met our inclusion criteria. We identified 62 cost-utility, 8 cost-effectiveness, and 5 cost-minimization studies. Values of incremental net monetary benefit ranged from international dollars -467 000 to international dollars 194 000. Of 114 clinical interventions evaluated (vs comparators), 56 were cost-effective. We identified 15 cost-effective interventions in emergency medicine, 6 in critical care medicine, and 35 in orthopedic medicine. A total of 58 studies were classified as high quality and 17 as moderate quality. From studies with a high level of evidence (randomized controlled trials), 4 interventions were clearly dominant and 8 were dominated. CONCLUSIONS: This research advances knowledge on value-based care for injury admissions. Results suggest that almost half of clinical interventions in acute injury care that have been studied may not be cost-effective.

A comparison of confounder selection and adjustment methods for estimating causal effects using large healthcare databases.

PURPOSE: Confounding adjustment is required to estimate the effect of an exposure on an outcome in observational studies. However, variable selection and unmeasured confounding are particularly challenging when analyzing large healthcare data. Machine learning methods may help address these challenges. The objective was to evaluate the capacity of such methods to select confounders and reduce unmeasured confounding bias. METHODS: A simulation study with known true effects was conducted. Completely synthetic and partially synthetic data incorporating real large healthcare data were generated. We compared Bayesian adjustment for confounding (BAC), generalized Bayesian causal effect estimation (GBCEE), Group Lasso and Doubly robust estimation, high-dimensional propensity score (hdPS), and scalable collaborative targeted maximum likelihood algorithms. For the hdPS, two adjustment approaches targeting the effect in the whole population were considered: Full matching and inverse probability weighting. RESULTS: In scenarios without hidden confounders, most methods were essentially unbiased. The bias and variance of the hdPS varied considerably according to the number of variables selected by the algorithm. In scenarios with hidden confounders, substantial bias reduction was achieved by using machine-learning methods to identify proxies as compared to adjusting only by observed confounders. hdPS and Group Lasso performed poorly in the partially synthetic simulation. BAC, GBCEE, and scalable collaborative-targeted maximum likelihood algorithms performed particularly well. CONCLUSIONS: Machine learning can help to identify measured confounders in large healthcare databases. They can also capitalize on proxies of unmeasured confounders to substantially reduce residual confounding bias.

Evidence of the Different Associations of Prognostic Factors With Censoring Across Treatment Groups and Impact on Censoring Weight Model Specification: The Example of Anticoagulation in Atrial Fibrillation.

Inverse probability of censoring weights (IPCWs) may reduce selection bias due to informative censoring in longitudinal studies. However, in studies with an active comparator, the associations between predictors and censoring may differ across treatment groups. We used the clinical example of anticoagulation treatment with warfarin or a direct oral anticoagulant (DOAC) in atrial fibrillation to illustrate this. The cohort of individuals initiating an oral anticoagulant during 2010-2016 was identified from the Régie de l'assurance maladie du Québec (RAMQ) databases. The parameter of interest was the hazard ratio (HR) of the composite of stroke, major bleeding, myocardial infarction, or death associated with continuous use of warfarin versus DOACs. Two strategies for the specification of the model for estimation of censoring weights were explored: exposure-unstratified and exposure-stratified. The HR associated with continuous treatment with warfarin versus DOACs adjusted with exposure-stratified IPCWs was 1.26 (95% confidence interval: 1.20, 1.33). Using exposure-unstratified IPCWs, the HR differed by 15% in favor of DOACs (1.41, 95% confidence interval: 1.34, 1.48). Not accounting for the different associations between the predictors and informative censoring across exposure groups may lead to misspecification of censoring weights and biased estimate on comparative effectiveness and safety.

Development and Validation of an Instrument to Measure Health-Related Out-of-Pocket Costs: The Cost for Patients Questionnaire.

OBJECTIVE: The growth of healthcare spending is a major concern for insurers and governments but also for patients whose health problems may result in costs going beyond direct medical costs. To develop a comprehensive tool to measure direct and indirect costs of a health condition for patients and their families to various outpatient contexts. METHODS: We conducted a content and face validation including results of a systematic review to identify the items related to direct and indirect costs for patients or their families and an online Delphi to determine the cost items to retain. We conducted a pilot test-retest with 18 naive participants and analyzed data calculating intraclass correlation and kappa coefficients. RESULTS: An initial list of 34 items was established from the systematic review. Each round of the Delphi panel incorporated feedback from the previous round until a strong consensus was achieved. After 4 rounds of the Delphi to reach consensus on items to be included and wording, the questionnaire had a total of 32 cost items. For the test-retest, kappa coefficients ranged from -0.11 to 1.00 (median = 0.86), and intraclass correlation ranged from -0.02 to 0.99 (median = 0.62). CONCLUSIONS: A rigorous process of content and face development was implemented for the Cost for Patients Questionnaire, and this study allowed to set a list of cost elements to be considered from the patient's perspective. Additional research including a test-retest with a larger sample will be part of a subsequent validation strategy.

Age- and sex-specific Canadian utility norms, based on the 2013-2014 Canadian Community Health Survey.

BACKGROUND: Although many Canadian studies have provided disease-specific or patient group-specific utility scores, the utility score norms currently available for the general Canadian population are outdated. Canadian guideline recommendations for the economic evaluation of health technologies advocate for utilities reflecting those of the general population and for stratified analyses when results are heterogeneous; as such, there is also a need for age-, sex- and jurisdiction-specific utility score norms. METHODS: We used data from the 2013-2014 Canadian Community Health Survey. We used the Health Utilities Index Mark 3 to calculate utility scores. We estimated means (with 95% confidence intervals [CIs]) and medians (with interquartile ranges [IQRs]) for utility scores. In addition to Canadian-level measures, we stratified all utility score norms by respondents' age, sex, and province or territory of residence. We weighted respondents' answers and computed 95% CIs using sampling weights and bootstrap weights provided by Statistics Canada to extrapolate the study findings to the Canadian population. RESULTS: Respondents to the 2013-2014 Canadian Community Health Survey represented 30 014 589 community-dwelling Canadians 12 years of age and older (98% of the Canadian population); half of the respondents were female (50.6%), and the weighted average age was 44.8 (95% CI 44.7-44.9) years. The mean and median self-reported utility scores for Canadians were estimated at 0.863 (95% CI 0.861-0.865) and 0.927 (IQR 0.838-0.972), respectively. INTERPRETATION: This study provides utility score norms for several age-, sex-and jurisdiction-specific strata in Canada. These results will be useful for future cost-utility analyses and could serve as benchmark values for comparisons with future studies.

Regional variation in healthcare spending and mortality among senior high-cost healthcare users in Ontario, Canada: a retrospective matched cohort study.

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.

Health Utilities Index Mark 3 scores for major chronic conditions: Population norms for Canada based on the 2013 and 2014 Canadian Community Health Survey.

BACKGROUND: Utility scores are frequently used as preference weights when estimating quality-adjusted life years within cost-utility analyses or health-adjusted life expectancies. Though previous Canadian estimates for specific chronic conditions have been produced, these may no longer reflect current patient populations. DATA AND METHODS: Data from the 2013 and 2014 Canadian Community Health Survey were used to provide Canadian utility score norms for 17 chronic conditions. Utility scores were estimated using the Health Utilities Index Mark 3 instrument and were reported as weighted average (95% confidence intervals [95% CI]) values. In addition to age- and sex-stratified analyses, results were also stratified according to the number of reported chronic conditions (i.e., "none" to "five or more"). All results were weighted using sampling and bootstrapped weights provided by Statistics Canada. RESULTS: Utility scores were estimated for 123,654 (97.2%) respondents (weighted frequency = 29,337,370 [97.7%]). Of the chronic conditions that were examined, asthma had the least detrimental effect (weighted average utility score = 0.803 [95% CI: 0.795 to 0.811]) on respondents' utility scores, and Alzheimer's disease or any other dementia had the most detrimental effect (weighted average utility score = 0.374 [95% CI: 0.323 to 0.426]). Respondents who reported suffering from no chronic conditions had, on average, the highest utility scores (weighted average utility score = 0.928 [95% CI: 0.926 to 0.930]). Estimates dropped as a function of the number of reported chronic conditions. DISCUSSION: Utility scores differed between various chronic conditions and as a function of the number of reported chronic conditions. Results also highlighted several differences with previously published Canadian utility norms.

Head to head comparison of the propensity score and the high-dimensional propensity score matching methods.

BACKGROUND: Comparative performance of the traditional propensity score (PS) and high-dimensional propensity score (hdPS) methods in the adjustment for confounding by indication remains unclear. We aimed to identify which method provided the best adjustment for confounding by indication within the context of the risk of diabetes among patients exposed to moderate versus high potency statins. METHOD: A cohort of diabetes-free incident statins users was identified from the Quebec's publicly funded medico-administrative database (Full Cohort). We created two matched sub-cohorts by matching one patient initiated on a lower potency to one patient initiated on a high potency either on patients' PS or hdPS. Both methods' performance were compared by means of the absolute standardized differences (ASDD) regarding relevant characteristics and by means of the obtained measures of association. RESULTS: Eight out of the 18 examined characteristics were shown to be unbalanced within the Full Cohort. Although matching on either method achieved balance within all examined characteristic, matching on patients' hdPS created the most balanced sub-cohort. Measures of associations and confidence intervals obtained within the two matched sub-cohorts overlapped. CONCLUSION: Although ASDD suggest better matching with hdPS than with PS, measures of association were almost identical when adjusted for either method. Use of the hdPS method in adjusting for confounding by indication within future studies should be recommended due to its ability to identify confounding variables which may be unknown to the investigators.

Performance of the high-dimensional propensity score in adjusting for unmeasured confounders.

PURPOSE: High-dimensional propensity scores (hdPS) can adjust for measured confounders, but it remains unclear how well it can adjust for unmeasured confounders. Our goal was to identify if the hdPS method could adjust for confounders which were hidden to the hdPS algorithm. METHOD: The hdPS algorithm was used to estimate two hdPS; the first version (hdPS-1) was estimated using data provided by 6 data dimensions and the second version (hdPS-2) was estimated using data provided from only two of the 6 data dimensions. Two matched sub-cohorts were created by matching one patient initiated on a high-dose statin to one patient initiated on a low-dose statin based on either hdPS-1 (Matched hdPS Full Info Sub-Cohort) or hdPS-2 (Matched hdPS Hidden Info Sub-Cohort). Performances of both hdPS were compared by means of the absolute standardized differences (ASDD) regarding 18 characteristics (data on seven of the 18 characteristics were hidden to the hdPS algorithm when estimating the hdPS-2). RESULTS: Eight out of the 18 characteristics were shown to be unbalanced within the unmatched cohort. Matching on either hdPS achieved adequate balance (i.e., ASDD <0.1) on all 18 characteristics. CONCLUSION: Our results indicate that the hdPS method was able to adjust for hidden confounders supporting the claim that the hdPS method can adjust for at least some unmeasured confounders.

Cost effectiveness of 'on demand' HIV pre-exposure prophylaxis for non-injection drug-using men who have sex with men in Canada.

BACKGROUND: Recent trials report the efficacy of continuous tenofovir-based pre-exposure prophylaxis (PrEP) for prevention of HIV infection. The cost effectiveness of 'on demand' PrEP for non-injection drug-using men who have sex with men at high risk of HIV acquisition has not been evaluated. OBJECTIVE: To conduct an economic evaluation of the societal costs of HIV in Canada and evaluate the potential benefits of this PrEP strategy. METHODS: Direct HIV costs comprised outpatient, inpatient and emergency department costs, psychosocial costs and antiretroviral costs. Resource consumption estimates were derived from the Centre Hospitalier de l'Université de Montréal HIV cohort. Estimates of indirect costs included employment rate and work absenteeism. Costs for 'on demand' PrEP were modelled after an ongoing clinical trial. Cost-effectiveness analysis compared costs of 'on demand' PrEP to prevent one infection with lifetime costs of one HIV infection. Benefits were presented in terms of life-years and quality-adjusted life-years. RESULTS: The average annual direct cost of one HIV infection was $16,109 in the least expensive antiretroviral regimen scenario and $24,056 in the most expensive scenario. The total indirect cost was $11,550 per year. Total costs for the first year of HIV infection ranged from $27,410 to $35,358. Undiscounted lifetime costs ranged from $1,439,984 ($662,295 discounted at 3% and $448,901 at 5%) to $1,482,502 ($690,075 at 3% and $485,806 at 5%). The annual cost of PrEP was $12,001 per participant, and $621,390 per infection prevented. The PrEP strategy was cost-saving in all scenarios for undiscounted and 3% discounting rates. At 5% discounting rates, the strategy is largely cost-effective: according to least and most expensive scenarios, incremental cost-effectiveness ratios ranged from $60,311 to $47,407 per quality-adjusted life-year. CONCLUSION: This 'on demand' PrEP strategy ranges from cost-saving to largely cost-effective. The authors believe it represents an important public health strategy for the prevention of HIV transmission.

HISTORIQUE: De récents essais rendent compte de l'efficacité d'une prophylaxie préexposition continue à base de ténofovir (PrEP) pour prévenir l'infection par le VIH. La rentabilité de la PrEP sur demande n'a pas été évaluée chez les hommes qui ne consomment pas de drogues injectables, mais qui ont des relations sexuelles avec d'autres hommes très susceptibles de contracter le VIH. OBJECTIF: Réaliser une évaluation économique des coûts du VIH pour la société au Canada et évaluer les avantages potentiels de cette stratégie de PrEP. MÉTHODOLOGIE: Les coûts directs du VIH incluaient les coûts des rendez-vous ambulatoires, des séjours hospitaliers et des visites à l'urgence, les coûts psychosociaux et les coûts des antirétroviraux. L'évaluation de la consommation des ressources était dérivée de la cohorte de VIH du Centre hospitalier de l'Université de Montréal. Les évaluations des coûts indirects incluaient le taux d'emploi et l'absentéisme au travail. Les coûts de la PrEP sur demande reprenaient le modèle d'un essai clinique en cours. L'analyse de rentabilité reposait sur une comparaison des coûts de la PrEP sur demande pour prévenir une infection avec les coûts de traitement à vie d'une infection par le VIH. Les avantages étaient présentés d'après les années de vie et les années de vie pondérées par la qualité. RÉSULTATS: Le coût direct annuel moyen d'une infection par le VIH s'élevait à 16 109 $ d'après le scénario de posologie antirétrovirale le moins coûteux, et à 24 056 $ d'après le scénario le plus coûteux. Le coût indirect total s'élevait à 11 550 $ par année. Les coûts totaux pour la première année d'infection par le VIH oscillaient entre 27 410 $ et 35 358 $. Les coûts de traitement à vie non actualisés variaient entre 1 439 984 $ (662 295 $ actualisés à 3 % et 448 901 $, à 5 %) et 1 482 502 $ (690 075 $ à 3 % et 485 806 $ à 5 %). Le coût annuel de la PrEP était de 12 001 $ par participant, et de 621 390 $ par infection prévenue. La stratégie de PrEP était économique dans tous les scénarios non actualisés et actualisés à 3 %. Dans les scénarios actualisés à 5 %, la stratégie était largement rentable. En effet, selon les scénarios le moins et le plus coûteux, le rapport coût-efficacité différentiel se situait entre 60 311 $ et 47 407 $ par année de vie pondérée par la qualité. CONCLUSION: Cette stratégie de PrEP sur demande se situe quelque part entre la production d'économies et une rentabilité substantielle. Les auteurs sont d'avis qu'elle représente une importante stratégie de santé publique pour prévenir la transmission du VIH.

Development of a Patient-Reported Experience Measure Tool for Ambulatory Patients With Acute Unexpected Needs: The APEX Questionnaire.

Background: The aim of this study was to develop a patient-reported experience measure (PREM) for comparing the experience of care received by ambulatory patients with acute unexpected needs presenting in emergency departments (EDs), walk-in clinics, and primary care practices. Methods: The Ambulatory Patient EXperience (APEX) questionnaire was developed using a 5-phase mixed-methods approach. The questionnaire was pretested by asking potential users to rate its clarity, usefulness, redundancy, content and face validities, and discrimination on a 9-point scale (1 = strongly disagree to 9 = strongly agree). The pre-final version was then tested in a pilot study. Results: The final questionnaire is composed of 61 questions divided into 7 sections. In the pretest (n = 25), median responses were 8 and above for all dimensions assessed. In the pilot study, 63 participants were enrolled. Adjusted results show that access, cleanliness, and feeling treated with respect and dignity by nurses and physicians were significantly better in the clinics than in the ED. Conclusion: We developed a questionnaire to assess and compare experience of ambulatory care in different clinical settings.

Integration of primary contact physiotherapists in the emergency department for individuals presenting with minor musculoskeletal disorders: Protocol for an economic evaluation.

OBJECTIVES: 1) To compare the average cost of an emergency department (ED) visit for various minor musculoskeletal disorders between two models of care (physiotherapist and ED physician or ED physician alone); 2) To evaluate the incremental cost-effectiveness ratio (ICER) of these two models of care over a 3-month period post-initial visit; and 3) To estimate the ICER of three ED models of care (physiotherapist and ED physician, ED physician alone, physiotherapist alone) over a two-year period. METHODS: Obj.1: The costs incurred by participants in the two groups during their ED visit will be calculated using the Time-Driven Activity-Based Costing (TDABC) method. These costs will be compared using generalized linear models. Obj. 2: The ICER of the two models will be evaluated over three months via a cost-utility analysis that will combine costs and effectiveness data (quality-adjusted life years) using both Health system and Societal perspectives (patient + health system costs). Obj. 3: The 2-year ICER of the three above-mentioned models will be estimated using a mathematical model including a decision tree (0-3 months post-visit) and a Markov model (3-24 months post-visit), also using both Health system and Societal perspectives. Data to answer the three objectives will come from data collected during a randomized clinical trial (n = 78, CHU de Québec)which will be supplemented with data obtained via some of the CHU de Québec administrative databases (nominative data; SIURGE (ED management software), Cristal-Net (patient electronic record), and the ED's pharmacy transactions directory; administrative data: drug costs repository), the literature, and public cost repositories. CONCLUSION: This study will help to determine which model of care is most efficient for the management of individuals who come to the ED with minor musculoskeletal disorders. The increased involvement of various health professionals in the management of patients in the ED paves the way for the development of new avenues of practice and more efficient organization of services.

Prevalence and incidence of Paget's disease of bone: Temporal trend over 20 years in the province of Quebec, Canada.

BACKGROUND: Paget's disease of bone (PDB) is a focal bone disorder characterized by an increased bone remodeling and an anarchic bone structure. A decline of prevalence and incidence of PDB has been observed in some countries. No epidemiological data are available on PDB in Canada. AIMS: We aimed at examining the evolution of the prevalence and incidence of PDB in Quebec (Canada) by analyzing health administrative databases. METHODS: PDB case definition relied on one or more hospitalizations, or one or more physician-billing claims with a diagnosis code of PDB. To identify incident cases, a 'run-in' period of four years (1996-1999) was used to exclude prevalent cases. For each fiscal year from 2000 to 2001 to 2019-2020 (population size 2,914,480), crude age and sex-specific prevalence and incidence rates of PDB among individuals aged ≥55 years were determined, and sex-specific rates were also standardized to the 2011 age structure of the Quebec population. Generalized linear regressions were used to test for linear changes in standardized prevalence and incidence rates. RESULTS: Over the study period, standardized prevalence of PDB has remained stable in Quebec, from 0.44 % in 2000/2001 to 0.43 % in 2019/2020 (mean change -0.002, p-value = 0.0935). For the 2019-2020 fiscal year, 13,165 men and women had been diagnosed with PDB and prevalence of PDB increased with age. Standardized incidence of PDB has decreased over time from 0.77/1000 in 2000/2001 to 0.28/1000 in 2019-2020 (mean change -0.228/year, p-value<0.0001), the incidence decreasing from 0.82/1000 to 0.37/1000 in men and from 0.76/1000 to 0.22/1000 in women, respectively. This decrease was observed in all age categories. CONCLUSION: With the exception of a slight increase in PDB prevalence up to 0.55 % in years 2005 to 2007, the prevalence of PDB has remained stable in Quebec over the past 20 years, 13,160 men and women being currently diagnosed with PDB. The incidence has decreased over time. Our results support the epidemiological changes of PDB reported in other countries.

The use of early neuromuscular blockage in acute respiratory distress syndrome: A systematic review and meta-analyses of randomized clinical trials.

BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) as defined by the Berlin definition has an approximate mortality rate of 40% and no curative treatment. Mutliple therapies have been studied to reduce mortality but only neuromuscular blocking agents show potential benefits on mortality and other complications of ARDS. OBJECTIVE: This review aimed to investigate the efficacy of neuromuscular blockers in ARDS METHODS: Medline, Embase, Cochrane Central and Web of Science were queried on October 1st, 2021. Randomized clinical trials comparing neuromuscular blockers to any comparator in treating ARDS were included. Primary outcome was mortality. Secondary outcomes were ventilator-free days, intensive care (ICU) length of stay (LOS) and complications. Results between sedation levels were examined with a Bayesian Network for Meta-analysis method. RESULTS: We included 6 trials compiling a total of 1557 patients. Neuromuscular blockers compared to any comparator in treating ARDS showed a reduction in mortality (RR 0.79 [95% CI, 0.62 to 0.99]). No difference in ventilator-free days (MD 0.68 [95% CI, -0.50 to 1.85]) or ICU LOS (MD 0.77 [95% CI, -2.99 to 4.54]) were found. A Bayesian Network Meta-analysis yielded no difference in mortality when using light sedation compared to heavy sedation in ARDS. (OR 0.58 [95% CrI, 0.07 to 4.46].) CONCLUSION: Neuromuscular blockers safely reduce mortality. Light sedation potentially has a similar impact on mortality as heavy sedation that carries some burden. A non-inferiority trial comparing both sedation levels may be warranted considering the added value of light sedation.

Molecular test of Paget's disease of bone in families not linked to SQSTM1 gene mutations.

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.

Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF, and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of OACs is associated with a decreased incidence of dementia in patients with NVAF. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia. METHODS: Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline. RESULTS: The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80-0.89), but not in younger patients (HR 0.99, 95% CI 0.90-1.10). DISCUSSION: In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia.