Coordination of oral anticoagulant care at hospital discharge (COACHeD): pilot randomised controlled trial.

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.

Application of natural language processing to predict final recommendation of Brazilian health technology assessment reports.

INTRODUCTION: Health technology assessment (HTA) plays a vital role in healthcare decision-making globally, necessitating the identification of key factors impacting evaluation outcomes due to the significant workload faced by HTA agencies. OBJECTIVES: The aim of this study was to predict the approval status of evaluations conducted by the Brazilian Committee for Health Technology Incorporation (CONITEC) using natural language processing (NLP). METHODS: Data encompassing CONITEC's official report summaries from 2012 to 2022. Textual data was tokenized for NLP analysis. Least Absolute Shrinkage and Selection Operator, logistic regression, support vector machine, random forest, neural network, and extreme gradient boosting (XGBoost), were evaluated for accuracy, area under the receiver operating characteristic curve (ROC AUC) score, precision, and recall. Cluster analysis using the k-modes algorithm categorized entries into two clusters (approved, rejected). RESULTS: The neural network model exhibited the highest accuracy metrics (precision at 0.815, accuracy at 0.769, ROC AUC at 0.871, and recall at 0.746), followed by XGBoost model. The lexical analysis uncovered linguistic markers, like references to international HTA agencies' experiences and government as demandant, potentially influencing CONITEC's decisions. Cluster and XGBoost analyses emphasized that approved evaluations mainly concerned drug assessments, often government-initiated, while non-approved ones frequently evaluated drugs, with the industry as the requester. CONCLUSIONS: NLP model can predict health technology incorporation outcomes, opening avenues for future research using HTA reports from other agencies. This model has the potential to enhance HTA system efficiency by offering initial insights and decision-making criteria, thereby benefiting healthcare experts.

Findings from a pragmatic cluster randomised controlled feasibility trial of a music and dance programme for community dwelling older adults.

INTRODUCTION: Functional decline, chronic illness, reduced quality of life and increased healthcare utilisation are common in older adults. Evidence suggests music and dance can support healthy ageing in older adults. This study explored the feasibility, potential for effect and cost effectiveness of the Music and Movement for Health (MMH) programme among community-dwelling older adults using a pragmatic cluster-randomised, controlled feasibility trial design. METHODS: Community-dwelling adults aged 65 years or older were recruited to seven clusters in the Mid-West region of Ireland. Clusters were block randomised to either the MMH intervention or control. Primary feasibility outcomes included recruitment, retention, adherence, fidelity, and safety. Secondary outcomes measured physical activity, physical and cognitive performance, and psychosocial well-being, along with healthcare utilisation were assessed at baseline and after 12 weeks. RESULTS: The study successfully met feasibility targets, with recruitment (n = 100), retention (91 %), adherence (71 %), data completeness (92 %) and intervention fidelity (21 out of 24) all meeting predetermined criteria. Both groups exhibited an increase in self-reported physical activity and improved physical function. Participants in the intervention group scored consistently better in psychosocial measures compared to the control group at follow-up. The health economic analysis confirmed the feasibility of the methodology employed and points to the potential cost-effectiveness of the MMH relative to the control or no organised programme. DISCUSSION AND IMPLICATIONS: The MMH intervention and study design were found to be feasible and acceptable with important findings to inform future evaluation of the clinical and cost-effectiveness of a definitive randomised controlled trial.

Lessons learned about development and assessment of feasibility of tools for health and rehabilitation services.

BACKGROUND: Given the dire need for health and rehabilitation services internationally, exacerbated during the COVID-19 pandemic, there is a critical need to develop tools to support service delivery. This need is palpable in the Global South where tools developed in Eurocentric contexts are not always adaptable, applicable, or relevant. It is for this reason that the researchers present three case studies of tool development using pilot and feasibility studies in South Africa and share the lessons learned from these studies. OBJECTIVES: To describe three case studies that developed new tools for health and rehabilitation services using pilot and feasibility studies. To synthesize lessons learned from these case studies on the development of tools. METHOD: The researchers describe three case studies that were developed. The case studies are summarized as follows: aims and objectives, context, problem, study design, findings, and what happened after the study. Thereafter, a qualitative cross-case analysis was conducted by the researchers to generate themes. FINDINGS: The case studies are described individually and followed by themes identified through cross-case analysis. DISCUSSION: The lessons learned are discussed. It is essential to develop new tools and protocols, motivated by the need for equitable and contextually relevant practices. Partnerships and collaboration with end-users are critical for success. A critical, scientific process is essential in developing new tools. Pilot and feasibility studies are invaluable in developing tools and assessing the feasibility of tools and implementation. The goal is to develop practical, usable tools and protocols. CONCLUSION: Through the lessons learned, the researchers are hopeful that the international health and rehabilitation professions will continue to strengthen the scientific development of contextually relevant tools and resources.

Economic evaluation of non-invasive liver tests for the diagnosis of liver fibrosis in chronic liver diseases: a systematic review protocol.

OBJECTIVE: The objective of this review is to determine the costs and benefits of non-invasive liver tests vs liver biopsy in patients with chronic liver diseases. INTRODUCTION: Hepatic diseases can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. In the past, liver biopsy was the only option for diagnosing fibrosis degree. Liver biopsy is an invasive procedure that depends on the sample size to be able to deliver an accurate diagnosis. In recent years, non-invasive liver tests have been increasingly used to estimate liver fibrosis degree; however, there is a lack of economic assessments of technology implementation outcomes. INCLUSION CRITERIA: This review will include partial (cost studies) and complete economic evaluation studies on hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease that compare non-invasive liver tests with liver biopsies. Studies published in English, French, Spanish, German, Italian, or Portuguese will be included. No date limits will be applied to the search. METHODS: This review will identify published and unpublished studies. Published studies will be identified using MEDLINE (PubMed), Cochrane Library (CENTRAL), Embase, Web of Science, Scopus, and LILACS. Sources of unpublished studies and gray literature will include sources from health technology assessment agencies, clinical practice guidelines, regulatory approvals, advisories and warnings, and clinical trial registries, as well as Google Scholar. Two independent reviewers will screen and assess studies, and extract and critically appraise the data. Data extracted from the included studies will be analyzed and summarized to address the review objective using narrative text, and the JBI dominance ranking matrix. REVIEW REGISTRATION: PROSPERO CRD42023404278.

Resource use and cost associated with computerized decision support system and usual care in managing patients with atrial fibrillation: analysis of IMPACT-AF randomized trial data.

BACKGROUND: IMPACT-AF is a prospective, randomized, cluster design trial comparing atrial fibrillation (AF) management with a computerized decision support system (CDS) to usual care (control) in the primary care setting of Nova Scotia, Canada. The objective of this analysis was to compare the resource use and costs between CDS and usual care groups. METHODS: Case costing data, 12-month self-administered questionnaires, and monthly diaries from IMPACT-AF were used in this analysis. Descriptive statistics were used to compare costs and resource use between groups. All costs are presented in 2021 Canadian dollars and cover the 12-month period of participation in the study. RESULTS: A total of 1,145 patients enrolled in the trial. Case costing data were available for 466 participants (41.1%), 12-month self-administered questionnaire data for 635 participants (56.0%) and monthly diary data for 223 participants (19.7%). Emergency department visits and hospitalizations comprised the most expensive component of AF care. Across all three datasets, there were no statistically significant differences in costs or resource use between CDS and usual care groups. CONCLUSIONS: Although there were no significant differences in resource use or costs among CDS and usual care groups in the IMPACT-AF trial, this study provides insight into the methodology and practical challenges of collecting economic data alongside a trial. REGISTRATION: Clinicaltrials.gov (registration number: NCT01927367, date of registration: 2013-08-20).

Prevalence of Pediatric Masked Hypertension and Risk of Subclinical Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m2.7 [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.

Robotic Lobectomy Is Cost-effective and Provides Comparable Health Utility Scores to Video-assisted Lobectomy: Early Results of the RAVAL Trial.

OBJECTIVE: The aim of this study was to determine if robotic-assisted lobectomy (RPL-4) is cost-effective and offers improved patient-reported health utility for patients with early-stage non-small cell lung cancer when compared with video-assisted thoracic surgery lobectomy (VATS-lobectomy). BACKGROUND: Barriers against the adoption of RPL-4 in publicly funded health care include the paucity of high-quality prospective trials and the perceived high cost of robotic surgery. METHODS: Patients were enrolled in a blinded, multicentered, randomized controlled trial in Canada, the United States, and France, and were randomized 1:1 to either RPL-4 or VATS-lobectomy. EuroQol 5 Dimension 5 Level (EQ-5D-5L) was administered at baseline and postoperative day 1; weeks 3, 7, 12; and months 6 and 12. Direct and indirect costs were tracked using standard methods. Seemingly Unrelated Regression was applied to estimate the cost effect, adjusting for baseline health utility. The incremental cost-effectiveness ratio was generated by 10,000 bootstrap samples with multivariate imputation by chained equations. RESULTS: Of 406 patients screened, 186 were randomized, and 164 analyzed after the final eligibility review (RPL-4: n=81; VATS-lobectomy: n=83). Twelve-month follow-up was completed by 94.51% (155/164) of participants. The median age was 68 (60-74). There were no significant differences in body mass index, comorbidity, pulmonary function, smoking status, baseline health utility, or tumor characteristics between arms. The mean 12-week health utility score was 0.85 (0.10) for RPL-4 and 0.80 (0.19) for VATS-lobectomy ( P =0.02). Significantly more lymph nodes were sampled [10 (8-13) vs 8 (5-10); P =0.003] in the RPL-4 arm. The incremental cost/quality-adjusted life year of RPL-4 was $14,925.62 (95% CI: $6843.69, $23,007.56) at 12 months. CONCLUSION: Early results of the RAVAL trial suggest that RPL-4 is cost-effective and associated with comparable short-term patient-reported health utility scores when compared with VATS-lobectomy.

Health Technology Reassessment: Addressing Uncertainty in Economic Evaluations of Oncology Drugs at Time of Reimbursement Using Long-Term Clinical Trial Data.

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.

Exploring the COVID-19 Pandemic's Impact on the Health Technology Assessment Process of the National Commission for the Incorporation of Technologies Into the Brazilian Health System.

OBJECTIVES: This study aimed to evaluate the impact of the COVID-19 pandemic on Brazilian health technology assessment processes based on public reports from the National Committee for Health Technology Incorporation (CONITEC). METHODS: This descriptive study analyzed CONITEC's official reports on Brazil available on its website between 2018 and 2021 that aimed to propose recommendations for technologies to be incorporated into its public healthcare system. We used descriptive statistics covering the number of technologies and number of reports about drugs per year, objective, type of technology, demanding sector, and outcome before 2018 to 2019 and during the COVID-19 pandemic (2020-2021). Furthermore, we used logistic regression to explore any association between the final decision labeled as "incorporated" and the emergence of the COVID-19 pandemic. RESULTS: A total of 278 reports were analyzed. Approximately 85% (136 of 278), 79% (220 of 278), and 45% of the reports (125 of 278) were about drugs, for incorporation, and requested by the government, respectively. Moreover, 74 of 130 (57%) and 56 of 148 decisions (38%) were "incorporated" before and during the pandemic, respectively. No significant association was noted between incorporated decisions and the arrival of the COVID-19 pandemic for all technologies (odds ratio 1.43; 95% CI 0.84-2.46; P = .192) and for drugs (odds ratio 1.43; 95% confidence interval 0.81-2.53; P = .223) while adjusting for the type of technology and demandant. CONCLUSIONS: The COVID-19 pandemic has brought many challenges, but it does not seem to have had a significant impact on the health technology assessment approval decisions of CONITEC in Brazil.

Identifying factors associated with high use of acute care in Canada: a population-based retrospective study.

OBJECTIVES: To determine demographic, socioeconomic, and clinical factors associated with being high-cost users (HCUs) in adult patients (≥ 18 years) who received acute care in Canada. RESEARCH DESIGN: We conducted a retrospective study among adults who had at least one encounter with acute care facilities each year from 2011 to 2014 using national linked data sets. We defined HCUs as patients on the top 10% of the highest acute care cost users in the province, where the care was provided. Risk factors associated with being HCUs were identified using multilevel logistic regression. Provincial variations of identified risk factors were examined using logistic regression. Sensitivity analyses were also performed to investigate the influences of using different metrics and different thresholds to define high system users, missing data, and the inclusion of interaction terms on the study results. RESULTS: Between 2011 and 2014, a total of 3,891,410 patients with 6,017,430 hospitalizations were included. Patients who were male [odds ratio (OR), 1.60; 95% confidence interval (CI) 1.59-1.61], with low incomes [OR 1.42; 95% CI 1.41-1.43), with higher comorbidity score (OR 1.41; 95% CI 1.40-1.41] and older [OR 1.18; 95% CI 1.17-1.18] were more likely to be acute care HCUs. Significant interactions existed between comorbidity score and age/sex/income status. Across provinces, the associations between socioeconomic factors and being HCUs has the largest variation. When using various high system users (HSUs) definitions, the impacts of living in rural area and being visible minority on the odds of being HSUs differ. CONCLUSIONS: A few demographic, socioeconomic, and clinical factors was associated with high acute care expenditures. The associations between included risk factors and being acute care HCUs vary across provinces and different definitions of high system users (HSUs).

Long-term Health Care Utilization and Associated Costs After Dialysis-Treated Acute Kidney Injury in Children.

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) is common among hospitalized children and is associated with increased hospital length of stay and costs. However, there are limited data on postdischarge health care utilization after AKI hospitalization. Our objectives were to evaluate health care utilization and physician follow-up patterns after dialysis-treated AKI in a pediatric population. STUDY DESIGN: Retrospective cohort study, using provincial health administrative databases. SETTING & PARTICIPANTS: All children (0-18 years) hospitalized between 1996 and 2017 in Ontario, Canada. Excluded individuals comprised non-Ontario residents; those with metabolic disorders or poisoning; and those who received dialysis or kidney transplant before admission, a kidney transplant by 104 days after discharge, or were receiving dialysis 76-104 days from dialysis start date. EXPOSURE: Episodes of dialysis-treated AKI, identified using validated health administrative codes. AKI survivors were matched to 4 hospitalized controls without dialysis-treated AKI by age, sex, and admission year. OUTCOME: Our primary outcome was postdischarge hospitalizations, emergency department visits, and outpatient physician visits. Secondary outcomes included outpatient visits by physician type and composite health care costs. ANALYTICAL APPROACH: Proportions with≥1 event and rates (per 1,000 person-years). Total and median composite health care costs. Adjusted rate ratios using negative binomial regression models. RESULTS: We included 1,688 pediatric dialysis-treated AKI survivors and 6,752 matched controls. Dialysis-treated AKI survivors had higher rehospitalization and emergency department visit rates during the analyzed follow-up periods (0-1, 0-5, and 0-10 years postdischarge, and throughout follow-up), and higher outpatient visit rates in the 0-1-year follow-up period. The overall adjusted rate ratio for rehospitalization was 1.46 (95% CI, 1.25-1.69; P<0.0001) and for outpatient visits was 1.16 (95% CI, 1.09-1.23; P=0.01). Dialysis-treated AKI survivors also had higher health care costs. Nephrologist follow-up was infrequent among dialysis-treated AKI survivors (18.6% by 1 year postdischarge). LIMITATIONS: Potential miscoding of study exposures or outcomes. Residual uncontrolled confounding. Data for health care costs and emergency department visits was unavailable before 2006 and 2001, respectively. CONCLUSIONS: Dialysis-treated AKI survivors had greater postdischarge health care utilization and costs versus hospitalized controls. Strategies are needed to improve follow-up care for children after dialysis-treated AKI to prevent long-term complications.

Health economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): a cost-effectiveness analysis.

PURPOSE: We sought to compare the cost-effectiveness of probiotics and usual care with usual care without probiotics in mechanically ventilated, intensive care unit patients alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT). METHODS: We conducted a health economic evaluation alongside the PROSPECT randomized control trial (October 2013-March 2019). We adopted a public healthcare payer's perspective. Forty-four intensive care units in three countries (Canada/USA/Saudi Arabia) with adult critically ill, mechanically ventilated patients (N = 2,650) were included. Interventions were probiotics (Lactobacillus rhamnosus GG) vs placebo administered enterally twice daily. We collected healthcare resource use and estimated unit costs in 2019 United States dollars (USD) over a time horizon from randomization to hospital discharge/death. We calculated incremental cost-effectiveness ratios (ICERs) comparing probiotics vs usual care. The primary outcome was incremental cost per ventilator-associated pneumonia (VAP) event averted; secondary outcomes were costs per Clostridioides difficile-associated diarrhea (CDAD), antibiotic-associated diarrhea (AAD), and mortality averted. Uncertainty was investigated using nonparametric bootstrapping and sensitivity analyses. RESULTS: Mean (standard deviation [SD]) cost per patient was USD 66,914 (91,098) for patients randomized to probiotics, with a median [interquartile range (IQR)] of USD 42,947 [22,239 to 76,205]. By comparison, for those not receiving probiotics, mean (SD) cost per patient was USD 62,701 (78,676) (median [IQR], USD 41,102 [23,170 to 75,140]; incremental cost, USD 4,213; 95% confidence interval [CI], -2,269 to 10,708). Incremental cost-effectiveness ratios for VAP or AAD events averted, probiotics were dominated by usual care (more expensive, with similar effectiveness). The ICERs were USD 1,473,400 per CDAD event averted (95% CI, undefined) and USD 396,764 per death averted (95% CI, undefined). Cost-effectiveness acceptability curves reveal that probiotics were not cost-effective across wide ranges of plausible willingness-to-pay thresholds. Sensitivity analyses did not change the conclusions. CONCLUSIONS: Probiotics for VAP prevention among critically ill patients were not cost-effective. Study registration data www. CLINICALTRIALS: gov (NCT01782755); registered 4 February 2013.

RéSUMé: OBJECTIF: Nous avons cherché à comparer le rapport coût-efficacité d'un traitement avec probiotiques ajoutés aux soins habituels avec des soins habituels prodigués sans probiotiques chez les patients des soins intensifs sous ventilation mécanique dans le cadre de l'étude PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial). MéTHODE: Nous avons réalisé une évaluation de l'économie de la santé parallèlement à l'étude randomisée contrôlée PROSPECT (octobre 2013-mars 2019). Nous avons adopté le point de vue d'un payeur public de services de santé. Quarante-quatre unités de soins intensifs dans trois pays (Canada/États-Unis/Arabie saoudite) prenant soin de patients adultes gravement malades sous ventilation mécanique (n = 2650) ont été inclus. Les interventions ont été les suivantes : probiotiques (Lactobacillus rhamnosus GG) vs placebo administrés par voie entérale deux fois par jour. Nous avons recueilli les données concernant l'utilisation des ressources en soins de santé et estimé les coûts unitaires en dollars américains (USD) de 2019 sur un horizon temporel allant de la randomisation au congé de l'hôpital / décès. Nous avons calculé des rapports coût-efficacité différentiels (RCED) en comparant les probiotiques vs les soins habituels. Le critère d'évaluation principal était le coût différentiel par événement évité de pneumonie associée au ventilateur (PAV); les critères d'évaluation secondaires étaient les coûts par diarrhée associée au Clostridioides difficile (DACD), diarrhée associée aux antibiotiques (DAA) et mortalité évitées. L'incertitude a été étudiée à l'aide d'analyses d'amorçage et de sensibilité non paramétriques. RéSULTATS: Le coût moyen (écart type [ÉT]) par patient était de 66 914 (91 098) USD pour les patients randomisés au groupe probiotiques, avec une médiane [écart interquartile (ÉIQ)] de 42 947 USD [22 239 à 76 205]. En comparaison, pour ceux ne recevant pas de probiotiques, le coût moyen (ÉT) par patient était de 62 701 USD (78 676) (médiane [ÉIQ], 41 102 USD [23 170 à 75 140]; coût différentiel, 4213 USD; intervalle de confiance [IC] à 95%, -2269 à 10 708). En matière de rapports coût-efficacité différentiels pour les événements de PAV ou DAA évités, les probiotiques étaient dominés par les soins habituels (plus coûteux, avec une efficacité similaire). Les RCED étaient de 1 473 400 USD par événement de DACD évitée (IC 95 %, non défini) et de 396 764 USD par décès évité (IC 95 %, non défini). Les courbes d'acceptabilité coût-efficacité révèlent que les probiotiques n'étaient pas rentables dans de larges gammes de seuils plausibles de volonté de payer. Les analyses de sensibilité n'ont pas modifié les conclusions. CONCLUSION: Les probiotiques utilisés pour prévenir la PAV chez les patients gravement malades n'étaient pas rentables. Enregistrement de l'étude : www.clinicaltrials.gov (NCT01782755); enregistrée le 4 février 2013.

Appraisals by Health Technology Assessment Agencies of Economic Evaluations Submitted as Part of Reimbursement Dossiers for Oncology Treatments: Evidence from Canada, the UK, and Australia.

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.

The impact of OHIP+ pharmacare on use and costs of public drug plans among children and youth in Ontario: a time-series analysis.

BACKGROUND: In 2018, Ontario implemented a pharmacare program (Ontario Health Insurance Plan Plus [OHIP+]) to provide children and youth younger than 25 years with full coverage for prescription medications in the provincial formulary. We aimed to assess the use of public drug plans and costs of publicly covered prescriptions before and after the program's implementation and modification. METHODS: We conducted a population-based, interrupted time-series analysis using data on prescription drug claims, from the Canadian Institute for Health Information's National Prescription Drug Utilization Information System, for people younger than 25 years from January 2016 to October 2019 in Ontario, using British Columbia as the control. We assessed changes in the level and trend of publicly covered prescriptions and expenditures after the introduction of OHIP+ in January 2018 and after program modifications in April 2019. We also assessed plan use and expenditures for publicly covered prescriptions for diabetes and asthma. RESULTS: Publicly covered prescriptions in Ontario increased by 290%, from 756 per 1000 people before OHIP+ to 2952 per 1000 (p < 0.001) after its implementation. After program modification, prescriptions decreased by 52% to 1421 per 1000 (p < 0.001). Similarly, total public drug expenditures increased by 254%, from $379 million in 2017 to $839 million in 2018, then reduced by 49% to $204 million in 2019. Monthly public plan expenditures increased by $115.94 (95% confidence interval [CI] $100.93 to $130.94) post-OHIP+ implementation and decreased by $99.97 (95% CI -$119.79 to -$80.15) per person per month after April 2019. INTERPRETATION: Adopting OHIP+ increased use of public drug plans and expenditures for publicly funded prescription medicines, and the program modification was associated with decreases in both outcomes. This study's findings can inform the national pharmacare debate; future research should investigate associations with health outcomes.

Exploring comparative assessment of adiposity measures during pregnancy and postpartum.

BACKGROUND & AIMS: Excessive adiposity in pregnancy is associated with an altered cardiometabolic profile and adverse maternal and offspring outcomes. Pre-pregnancy body mass index (pBMI) is a proxy measure for adiposity that is most often used in clinical settings; however, it may not identify at-risk pregnancies caused by adiposity-related cardiometabolic dysfunction. The challenge is that validated direct adiposity measures are limited due to the dynamic nature of pregnancy. This exploratory analysis aimed to, 1) evaluate longitudinal changes in % body fat (BF) and the agreement between skinfold thickness (SFT) and bioelectrical impedance analysis (BIA) across pregnancy and in postpartum; 2) compare the discrimination power of SFT, BIA, and pBMI regarding adiposity status; and 3) assess agreement between SFT and BIA with dual-energy X-ray absorptiometry (DXA) in the postpartum. METHODS: Participants enrolled in the Be Healthy in Pregnancy (BHIP) RCT (NCT01693510) had demographic data and pBMI collected at enrollment and adiposity measured at 12-17, 26-28, and 36-38 weeks gestation by BIA (%BF) and SFT (sum and %BF), and also by DXA at 6 months postpartum. Agreement between methods was assessed by Bland Altman plots and McNemar's test and C-statistic for discriminative power. RESULTS: In 181 women with mean pBMI of 25.1 kg/m2 (min: 17.4 kg/m2, max: 39.6 kg/m2) and age 31.6 (SD: 4.0 yr), maternal adiposity increased significantly (p < 0.001) across pregnancy when measured by the sum of SFT or %BF by BIA, but not %BF by SFT. In early pregnancy, BF by BIA and SFT showed good agreement, with BIA values 1.8% greater than SFT, but low agreement in late pregnancy, with BIA values 7.1% greater than SFT. However, in the postpartum, agreement was similar to early pregnancy, and both BIA and SFT demonstrated good agreement with DXA. By pBMI, 45.5% of participants were categorized as overweight/obese, compared to 66.5% by BIA (p < 0.0001) and 54.5% by SFT (p < 0.0001). CONCLUSIONS: In comparison to SFT and BIA, the results suggest that pBMI is less sensitive in identifying participants with excessive adiposity, limiting its use as a screening tool for adiposity-related adverse outcomes in pregnancy. It would be preferable to use a direct measure of adiposity to screen for at-risk pregnancies. Both %BF by BIA and sum of SFT can quantify the change in adiposity across pregnancy and in the postpartum and thus could be adopted as clinical practice tools. Future research efforts should further refine and validate adiposity techniques for use, particularly in mid and late pregnancy. CLINICAL TRIAL: The BHIP clinical trial (NCT01693510). REGISTRATION SITE: https://clinicaltrials.gov/ct2/show/NCT01693510.

RAVAL trial: Protocol of an international, multi-centered, blinded, randomized controlled trial comparing robotic-assisted versus video-assisted lobectomy for early-stage lung cancer.

BACKGROUND: Retrospective data demonstrates that robotic-assisted thoracoscopic surgery provides many benefits, such as decreased postoperative pain, lower mortality, shorter length of stay, shorter chest tube duration, and reductions in the incidence of common postoperative pulmonary complications, when compared to video-assisted thoracoscopic surgery. Despite the potential benefits of robotic surgery, there are two major barriers against its widespread adoption in thoracic surgery: lack of high-quality prospective data, and the perceived higher cost of it. Therefore, in the face of these barriers, a prospective randomized controlled trial comparing robotic- to video-assisted thoracoscopic surgery is needed. The RAVAL trial is a two-phase, international, multi-centered, blinded, parallel, randomized controlled trial that is comparing robotic- to video-assisted lobectomy for early-stage non-small cell lung cancer that has been enrolling patients since 2016. METHODS: The RAVAL trial will be conducted in two phases: Phase A will enroll 186 early-stage non-small cell lung cancer patients who are candidates for minimally invasive pulmonary lobectomy; while Phase B will continue to recruit until 592 patients are enrolled. After consent, participants will be randomized in a 1:1 ratio to either robotic- or video-assisted lobectomy, and blinded to the type of surgery they are allocated to. Health-related quality of life questionnaires will be administered at baseline, postoperative day 1, weeks 3, 7, 12, months 6, 12, 18, 24, and years 3, 4, 5. The primary objective of the RAVAL trial is to determine the difference in patient-reported health-related quality of life outcomes between the robotic- and video-assisted lobectomy groups at 12 weeks. Secondary objectives include determining the differences in cost-effectiveness, and in the 5-year survival data between the two arms. The results of the primary objective will be reported once Phase A has completed accrual and the 12-month follow-ups are completed. The results of the secondary objectives will be reported once Phase B has completed accrual and the 5-year follow-ups are completed. DISCUSSION: If successfully completed, the RAVAL Trial will have studied patient-reported outcomes, cost-effectiveness, and survival of robotic- versus video-assisted lobectomy in a prospective, randomized, blinded fashion in an international setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02617186. Registered 22-September-2015. https://clinicaltrials.gov/ct2/show/NCT02617186.

Telephone Administration of the Automated Self-Administered 24-hour Dietary Assessment in Older Adults: Lessons Learned.

Automated Self-Administered 24-hour Dietary Assessment (ASA24) is an economical method of estimating dietary intake as nutrient analysis is automated, but its use in older adults is limited. The purpose of this work was to guide dietitians and future researchers on how to use the ASA24 with older adults, considering potential barriers encountered and strategies used to support completion based on our experience using this tool in a pilot clinical trial. ASA24 was completed by phone interview with 39 older adults. Challenges included: recalling food intake in detail, recording frequent eating occasions and complicated recipes, and general problems with communication. Strategies to support collection included making morning phone calls and suggesting that seniors write down the food consumed. Phone interviews were acceptable to older adults, but sufficient time was required. Dietitians and future researchers can use these findings to obtain dietary intake data from this hard-to-reach group.

The MoveStrong program for promoting balance and functional strength training and adequate protein intake in pre-frail older adults: A pilot randomized controlled trial.

BACKGROUND: Balance and functional strength training can improve muscle strength and physical functioning outcomes and decrease the risk of falls in older adults. To maximize the benefits of strength training, adequate protein intake is also important. However, the number of older individuals that consume enough protein or routinely engage in strength training remains low at less than 5% and even lower for activities that challenge balance. Our primary aim was to assess the feasibility of implementing a model (MoveStrong) of service delivery to teach older adults about balance and functional strength training and methods to increase protein intake. METHODS: This study was a closed cohort stepped wedge randomized controlled trial. We recruited individuals ≥60 years considered pre-frail or frail with at least one chronic condition who were not currently engaging in regular strength training from Northern (rural) and Southern (urban) Ontario sites in Canada. The primary outcome was feasibility of implementation, defined by recruitment, retention, and adherence, and safety (defined by monitoring adverse events). We also reported participants' and providers' experience with MoveStrong, adaptations to the model based on participant's and provider's experience, and program fidelity. RESULTS: We recruited 44 participants to the study and the average adherence rate was 72% with a retention of 71%. The program had a high-fidelity score. One person experienced a fall-related injury during exercise, while two other participants reported pain during certain activities. Five individuals experienced injuries or health problems that were not related to the program. Suggestions for future trials include modifying some exercises, exploring volunteer assistance, increasing the diversity of participants enrolled, and considering a different study design. CONCLUSIONS: Our pilot trial demonstrates the feasibility of recruitment and adherence for a larger multisite RCT of balance and functional strength training with attention to protein intake in pre-frail and frail older adults.

Standardized Assessment of Global activities in the Elderly scale in adult cardiac surgery patients.

BACKGROUND: Different instruments have been used to assess ability to perform everyday functional activities, such as activities of daily living (ADL) and instrumental activities of daily living (IADL). No measures of functional activity have been validated in cardiac surgery. We assessed the reliability and validity of the Standardized Assessment of Global activities in the Elderly (SAGE) scale. METHODS: We undertook an observational sub-study of VISION Cardiac Surgery. Patients were assessed post-discharge after cardiac surgery using SAGE and comparator measures to determine convergent validity. A blinded independent assessor administered SAGE by phone within 7 days to determine test-retest reliability. We sought to demonstrate a correlation of ≥0.5 between SAGE and each corresponding measure. We also sought to define the SAGE score corresponding to severe functional disability, defined using the World Health Organisation Disability Assessment Schedule (WHODAS). RESULTS: There were 152 patients included. Inter-rater reliability was excellent (intra-class correlation coefficient=0.99; 95% confidence interval [CI], 0.98-0.99). Convergent validity was evident, ranging from adequate for the overall SAGE score (0.54; 95% CI, 0.42-0.65) to very good for the SAGE mobility sub-score (0.80; 95% CI, 0.73-0.85). SAGE was initially poorly correlated with the IADL index (-0.24) but increased to -0.60 after post-hoc adjustment of SAGE scoring. A SAGE score ≥7 was associated with severe functional disability and occurred in 42/152 (27.6%) of patients. CONCLUSION: These results demonstrate the reliability and validity of the SAGE scale as a measure of global function in patients discharged home after cardiac surgery. CLINICAL TRIAL REGISTRATION: NCT01842568.