Explore the vast range of titles available.

Although costly, genome-wide sequencing (GWS) detects an extensive range of variants, enhancing our ability to diagnose and assess risk for an increasing number of diseases. In addition to detecting variants related to the indication for testing, GWS can detect secondary variants in BRCA1, BRCA2, and other genes for which early intervention may improve health. As the list of secondary findings grows, there is increased demand for surveillance and management by multiple specialists, adding pressure to constrained health care budgets. Secondary finding testing is actively debated because some consider it opportunistic screening for future health risks that may not manifest. Given the economic implications of secondary finding testing and follow-up and its unproven clinical utility, the objective is to assess the incremental cost-effectiveness of secondary finding ascertainment per case detected and per unit of improved clinical utility in families of children with unexplained suspected genetic conditions undergoing clinical GWS. Those undergoing trio genome or exome sequencing are eligible for the study. Positive secondary finding index cases will be matched to negative controls (1:2) based on age group, primary result(s) type, and clinical indication. During the 2-year study, 71 cases and 142 matched controls are expected. Health service use will be collected in patients and 1 adult family member every 6 months. The per-child and per-dyad total cost will be determined by multiplying use of each resource by a corresponding unit price and summing all cost items. Costs will be estimated from the public and societal payer perspectives. The mean cost per child and per dyad for secondary finding–positive and secondary finding–negative groups will be compared statistically. If important demographic differences are observed between groups, ordinary least-squares regression, log transformation, or other nonparametric technique will be used to compare adjusted mean costs. The ratio of the difference in mean cost to the secondary finding yield will be used to estimate incremental cost-effectiveness. In secondary analyses, effectiveness will be estimated using the number of clinical management changes due to secondary findings or the Clinician-Reported Genetic Testing Utility Index (C-GUIDE) score, a validated measure of clinical utility. Sensitivity analysis will be undertaken to assess the robustness of the findings to variation in key parameters. This study generates key evidence to inform clinical practice and funding allocation related to secondary finding testing. The inclusion of family members and a new measure of clinical utility represent important advancements in economic evaluation in genomics.

Purpose The purpose of the study is to estimate the EQ-5D-derived health utilities associated with selected chronic conditions (hypertension, heart disease, arthritis, asthma or COPD, cancer, diabetes, chronic back pain, and anxiety or depression) and to estimate minimally important differences (MID) based on the Commonwealth Fund Survey of Sicker Adults in Canada. Methods We used a cross-sectional survey of 3765 sick adults in Canada conducted in 2011 by the Commonwealth Fund. Health utilities were calculated for the entire sample and for each of the eight chronic health conditions. An ordinary least squares regression was used to estimate the utility decrement associated with these conditions with and without adjustment for socio-demographic factors. The MIDs were estimated using the anchor- and distribution based methods. Results The adjusted utility decrement varied from 0.028 (95 % confidence interval (CI) –0.049, –0.008) for diabetes to 0.124 (95 % CI –0.142, –0.105) for anxiety or depression. The anchor-based MID for the entire group was 0.044 (95 % CI 0.025, 0.062), and the distribution-based MID for the entire group was 0.091. The condition-specific MIDs using the distribution-based method ranged from 0.089 for cancer to 0.108 for asthma or COPD. Conclusions The MID estimated by the distribution-based method was larger than the MID estimated by the anchor-based method, indicating that the choice of method matters. The impact of arthritis, anxiety or depression, and chronic back pain on health utility was substantial, all exceeding or approximating the MID estimated using either anchor- or distribution-based methods.

Purpose To systematically assess patterns and temporal changes in the measurement and valuation of childhood health utilities and associations between methodological factors. Methods Studies reporting childhood health utilities using direct or indirect valuation methods, published by June 2017, were identified through PubMed, Embase, Web of Science, PsycINFO, EconLit, CINAHL, Cochrane Library and PEDE. The following were explored: patterns in tariff application; linear trends in numbers of studies/samples and paediatric cost–utility analyses (CUAs) and associations between them; changes in proportions of studies/samples within characteristic-based categories over pre-specified periods; impact of National Institute for Health and Care Excellence (NICE) guidance on primary UK research and associations between valuation method, age and methodological factors. Results 335 studies with 3974 samples covering all ICD-10 chapters, 23 valuation methods, 12 respondent types and 42 countries were identified by systematic review. 34.0% of samples using indirect methods compatible with childhood applied childhood-derived tariffs. There was no association between numbers of studies/samples and numbers of CUAs. Compared to 1990–2008, 2009–June 2017 saw a significant fall in the proportion of studies using case series; significant compositional changes across ICD-10 chapters and significantly higher sample proportions using childhood-specific and adult-specific indirect valuation methods, and based on pre-adolescents, self-assessment, self-administration and experienced health states. NICE guidance was weakly effective in promoting reference methods. Associations between valuation method, age and methodological factors were significant. Conclusion 1990–2017 witnessed significant changes in primary research on childhood health utilities. Health technology assessment agencies should note the equivocal effect of methodological guidance on primary research.

Background: Timing to surgery for acute cholecystitis remains variable, ranging from early (< 7 d) to delayed surgery (> 7 d). Accelerated surgery may result in better outcomes owing to reduced exposure to hypercoagulable and inflammatory states. We sought to determine the feasibility of a trial comparing accelerated surgery with standard care among patients with calculous acute cholecystitis. Methods: We conducted a multicentre pilot randomized controlled trial. We randomly assigned adult patients with acute cholecystitis to receive accelerated surgery (i.e., goal of surgery within 6 hours of diagnosis) or standard care. The primary feasibility outcome included recruitment of 60 patients, randomly assigning the equivalent of 1 patient per site per month, and 95% follow-up at 90 days. Results: Sixty patients (mean age 61.7, standard deviation [SD] 13.5, yr; 27 [45%] female) were randomly assigned to accelerated surgery (n = 31) or standard care (n = 29) from December 2019 to December 2021, with 2 recruitment pauses due to the COVID-19 pandemic. The median time from diagnosis to surgery was 5.8 (interquartile range [IQR] 4.4-11.1) hours in the accelerated care arm and 20.3 (IQR 6.8-26.8) hours in the standard care arm. Across 4 sites, 4.6 patients per month were randomly assigned. All patients completed the 90-day follow up. Conclusion: In our pilot trial, we found that accelerated cholecystectomy was achievable. These results show the feasibility of a trial comparing accelerated and standard care among patients requiring surgery for acute cholecystitis and support a definitive trial. Trial registration: ClinicalTrials.gov, no. NCT04033822. Contexte: Le delai d'intervention pour la cholecystite aigue reste variable, allant de bref (< 7 j) a long (> 7 j). Une intervention rapide donnerait de meilleurs resultats en raison du risque moindre d'hypercoagulabilite et d'inflammation. Nous avons voulu verifier la possibilite de proceder a un essai comparatif entre chirurgie acceleree et soins standard aupres de personnes presentant une cholecystite aigue lithiasique. Methodes: Nous avons effectue une etude pilote randomisee et controlee multicentrique. Nous avons assigne aleatoirement des cas de cholecystite aigue a une chirurgie acceleree (chirurgie realisee dans les 6 heures suivant le diagnostic) ou aux soins standard. Le parametre de faisabilite principal incluait le recrutement de 60 cas que nous avons assignes aleatoirement a l'equivalent de 1 cas par site par mois, et un suivi de 95% au bout de 90 jours. Resultats: Nous avons ainsi assigne aleatoirement 60 cas (age moyen 61,7, ecart type (ET) 13,5 ans; 27 [45%] femmes) a une chirurgie acceleree (n = 31) ou aux soins standard (n = 29) entre decembre 2019 et decembre 2021, incluant 2 pauses dues a la pandemie de COVID-19. Le delai median entre le diagnostic et la chirurgie a ete de 5,8 (ecart interquartile [EI] 4,4-11,1) heures pour le groupe soumis a l'intervention acceleree et de 20,3 (EI 6,8-26,8) heures dans le groupe soumis aux soins standard. Dans 4 sites, 4,6 cas par mois ont ete assignes aleatoirement. Tous les cas ont pu etre suivis sur une periode de 90 jours. Conclusion: Notre etude pilote a demontre qu'il est possible de proceder a une cholecystectomie acceleree. Ces resultats confirment la faisabilite d'un essai comparatif entre soins acceleres et soins standard prodigues a des personnes qui doivent etre operees pour une cholecystite aigue et appuient la realisation d'un essai concluant. Numero d'enregistrement de la recherche: ClinicalTrials. gov, no NCT04033822.

Background Childhood illness can impose significant costs and health strains on family members, but these are not routinely captured by pediatric economic evaluations. This review investigated how family “spillover effects” related to costs and health outcomes are considered in pediatric cost-utility analyses (CUAs). Methods We reviewed pediatric CUAs published between 2000 and 2015 using the Tufts Medical Center Cost-effectiveness Analysis (CEA) Registry and the Pediatric Economic Database Evaluation (PEDE) Registry. We selected studies conducted from the societal perspective and included in both registries. We investigated how frequently family spillover was incorporated into analyses, and how the inclusion of spillover health effects and costs changed CUA results. Results We found 142 pediatric CUAs meeting inclusion criteria. Of those, 105 (72%) considered either family spillover costs ( n  = 98 time costs, n  = 33 out-of-pocket costs, n  = 2 caregiver healthcare costs) or health outcomes ( n  = 15). Twenty-four studies included 43 pairs of incremental cost-effectiveness ratios (ICERs) with and without spillover. In 19 pairs of ICERs, adding spillover changed the ICER enough to cross a common cost-effectiveness threshold (i.e., $50,000/QALY, $100,000/QALY, $150,000/QALY; values are in 2016 US$). Incorporating spillover generally made interventions more cost-effective ( n  = 18; 42%), or did not change CUA results enough to cross a threshold ( n  = 24; 56%). Including family spillover reduced ICERs by 31% ($40,000/QALY) on average. Conclusion Most pediatric CUAs conducted from a societal perspective include family costs but fewer include family health effects. Inclusion of family spillover effects tends to make CUA results more favorable. Future pediatric CUAs should aim to more fully incorporate the family burden of illness.

Purpose Whole-exome (WES) and whole-genome sequencing (WGS) increase the diagnostic yield in autism spectrum disorder (ASD) compared to chromosomal microarray (CMA), but there have been no comprehensive cost analyses. The objective was to perform such an assessment of CMA, WES, and WGS and compare the incremental cost per additional positive finding in hypothetical testing scenarios. Methods Five-year patient and program costs were estimated from an institutional perspective. WES and WGS estimates were based on HiSeq 2500 with an additional WGS estimate for HiSeq X platforms. Parameter uncertainty was assessed with probabilistic and deterministic sensitivity analysis. Results The cost per ASD sample was CAD$1,655 (95% CI: 1,611; 1,699) for WES, CAD$2,851 (95% CI: 2,750; 2,956) for WGS on HiSeq X, and CAD$5,519 (95% CI: 5,244; 5,785) on HiSeq 2500, compared to CAD$744 (95% CI 714, 773) for CMA. The incremental cost was over CAD$25,000 per additional positive finding if CMA was replaced by newer technology. Conclusion While costs for WES and WGS remain high, future reductions in material and equipment costs, and increased understanding of newly discovered variants and variants of unknown significance will lead to improved value.

Background: Timing to surgery for acute cholecystitis remains variable, ranging from early (<7 d) to delayed surgery (> 7 d). Accelerated surgery may result in better outcomes owing to reduced exposure to hypercoagulable and inflammatory states. We sought to determine the feasibility of a trial comparing accelerated surgery with standard care among patients with calculous acute cholecystitis. Methods: We conducted a multicentre pilot randomized controlled trial. We randomly assigned adult patients with acute cholecystitis to receive accelerated surgery (i.e., goal of surgery within 6 hours of diagnosis) or standard care. The primary feasibility outcome included recruitment of 60 patients, randomly assigning the equivalent of 1 patient per site per month, and 95% follow-up at 90 days. Results: Sixty patients (mean age 61.7, standard deviation [SD] 13.5, yr; 27 [45%] female) were randomly assigned to accelerated surgery (n = 31) or standard care (n = 29) from December 2019 to December 2021, with 2 recruitment pauses due to the COVID-19 pandemic. The median time from diagnosis to surgery was 5.8 (interquartile range [IQR] 4.4-11.1) hours in the accelerated care arm and 20.3 (IQR 6.8-26.8) hours in the standard care arm. Across 4 sites, 4.6 patients per month were randomly assigned. All patients completed the 90-day follow up. Conclusion: In our pilot trial, we found that accelerated cholecystectomy was achievable. These results show the feasibility of a trial comparing accelerated and standard care among patients requiring surgery for acute cholecystitis and support a definitive trial. Trial registration: ClinicalTrials.gov, no. NCT04033822. Contexte : Le d lai d'intervention pour la chol cystite aigu reste variable, allant de bref (< 7 j) long (> 7 j). Une intervention rapide donnerait de meilleurs r sultats en raison du risque moindre d'hypercoagulabilit et d'infammation. Nous avons voulu v rifer la possibilit de proc der un essai comparatif entre chirurgie acc l r e et soins standard aupr s de personnes pr sentant une chol cystite aigu lithiasique. M thodes : Nous avons effectu une tude pilote randomis e et contr l e multicentrique. Nous avons assign al atoirement des cas de chol cystite aigu une chirurgie acc l r e (chirurgie r alis e dans les 6 heures suivant le diagnostic) ou aux soins standard. Le param tre de faisabilit principal incluait le recrutement de 60 cas que nous avons assign s al atoirement l' quivalent de 1 cas par site par mois, et un suivi de 95% au bout de 90 jours. R sultats : Nous avons ainsi assign al atoirement 60 cas ( ge moyen 61,7, cart type (ET) 13,5 ans; 27 [45%] femmes) une chirurgie acc l r e (n = 31) ou aux soins standard (n = 29) entre d cembre 2019 et d cembre 2021, incluant 2 pauses dues la pand mie de COVID-19. Le d lai m dian entre le diagnostic et la chirurgie a t de 5,8 ( cart interquartile [EI] 4,4-11,1) heures pour le groupe soumis l'intervention acc l r e et de 20,3 (EI 6,8-26,8) heures dans le groupe soumis aux soins standard. Dans 4 sites, 4,6 cas par mois ont t assign s al atoirement. Tous les cas ont pu tre suivis sur une p riode de 90 jours. Conclusion : Notre tude pilote a d montr qu'il est possible de proc der une chol cystectomie acc l r e. Ces r sultats confirment la faisabilit d'un essai comparatif entre soins acc l r s et soins standard prodigu s des personnes qui doivent tre op r es pour une chol cystite aigu et appuient la r alisation d'un essai concluant. Num ro d'enregistrement de la recherche : ClinicalTrials. gov, no NCT04033822.

Timing to surgery for acute cholecystitis remains variable, ranging from early (< 7 d) to delayed surgery (> 7 d). Accelerated surgery may result in better outcomes owing to reduced exposure to hypercoagulable and inflammatory states. We sought to determine the feasibility of a trial comparing accelerated surgery with standard care among patients with calculous acute cholecystitis. We conducted a multicentre pilot randomized controlled trial. We randomly assigned adult patients with acute cholecystitis to receive accelerated surgery (i.e., goal of surgery within 6 hours of diagnosis) or standard care. The primary feasibility outcome included recruitment of 60 patients, randomly assigning the equivalent of 1 patient per site per month, and 95% follow-up at 90 days. Sixty patients (mean age 61.7, standard deviation [SD] 13.5, yr; 27 [45%] female) were randomly assigned to accelerated surgery (n = 31) or standard care (n = 29) from December 2019 to December 2021, with 2 recruitment pauses due to the COVID-19 pandemic. The median time from diagnosis to surgery was 5.8 (interquartile range [IQR] 4.4–11.1) hours in the accelerated care arm and 20.3 (IQR 6.8–26.8) hours in the standard care arm. Across 4 sites, 4.6 patients per month were randomly assigned. All patients completed the 90-day follow up. In our pilot trial, we found that accelerated cholecystectomy was achievable. These results show the feasibility of a trial comparing accelerated and standard care among patients requiring surgery for acute cholecystitis and support a definitive trial. ClinicalTrials.gov, no. NCT04033822. Le délai d’intervention pour la cholécystite aiguë reste variable, allant de bref (< 7 j) à long (> 7 j). Une intervention rapide donnerait de meilleurs résultats en raison du risque moindre d’hypercoagulabilité et d’inflammation. Nous avons voulu vérifier la possibilité de procéder à un essai comparatif entre chirurgie accélérée et soins standard auprès de personnes présentant une cholécystite aiguë lithiasique. Nous avons effectué une étude pilote randomisée et contrôlée multicentrique. Nous avons assigné aléatoirement des cas de cholécystite aiguë à une chirurgie accélérée (chirurgie réalisée dans les 6 heures suivant le diagnostic) ou aux soins standard. Le paramètre de faisabilité principal incluait le recrutement de 60 cas que nous avons assignés aléatoirement à l’équivalent de 1 cas par site par mois, et un suivi de 95 % au bout de 90 jours. Nous avons ainsi assigné aléatoirement 60 cas (âge moyen 61,7, écart type (ET) 13,5 ans; 27 [45 %] femmes) à une chirurgie accélérée (n = 31) ou aux soins standard (n = 29) entre décembre 2019 et décembre 2021, incluant 2 pauses dues à la pandémie de COVID-19. Le délai médian entre le diagnostic et la chirurgie a été de 5,8 (écart interquartile [EI] 4,4–11,1) heures pour le groupe soumis à l’intervention accélérée et de 20,3 (EI 6,8–26,8) heures dans le groupe soumis aux soins standard. Dans 4 sites, 4,6 cas par mois ont été assignés aléatoirement. Tous les cas ont pu être suivis sur une période de 90 jours. Notre étude pilote a démontré qu’il est possible de procéder à une cholécystectomie accélérée. Ces résultats confirment la faisabilité d’un essai comparatif entre soins accélérés et soins standard prodigués à des personnes qui doivent être opérées pour une cholécystite aiguë et appuient la réalisation d’un essai concluant. ClinicalTrials.gov, no NCT04033822.

This study measured resource utilization and costs for pre-school autism spectrum disorder (ASD)-related services in community-based sectors from multiple payer perspectives in two Canadian provinces, Nova Scotia (NS) and New Brunswick (NB), during the 12 months prior to and following the start of early intensive behavioural intervention (EIBI). The results indicate significant differences between NB and NS in utilization of services and costs to families, public sector and society. Differences can be attributed to variation in EIBI delivery models and may also be influenced by differences in diagnostic assessment practices. The study results provide resource utilization rates and costs which could be used in future economic evaluations and to inform policy making to improve outcomes for children with ASD.

The clinical use of whole-genome sequencing (WGS) is expected to alter pediatric medical management. The study aimed to describe the type and cost of healthcare activities following pediatric WGS compared to chromosome microarray (CMA). Healthcare activities prompted by WGS and CMA were ascertained for 101 children with developmental delay over 1 year. Activities following receipt of non-diagnostic CMA were compared to WGS diagnostic and non-diagnostic results. Activities were costed in 2016 Canadian dollars (CDN). Ongoing care accounted for 88.6% of post-test activities. The mean number of lab tests was greater following CMA than WGS (0.55 vs. 0.09; p = 0.007). The mean number of specialist visits was greater following WGS than CMA (0.41 vs. 0; p = 0.016). WGS results (diagnostic vs. non-diagnostic) modified the effect of test type on mean number of activities (p < 0.001). The cost of activities prompted by diagnostic WGS exceeded $557CDN for 10% of cases. In complex pediatric care, CMA prompted additional diagnostic investigations while WGS prompted tailored care guided by genotypic variants. Costs for prompted activities were low for the majority and constitute a small proportion of total test costs. Optimal use of WGS depends on robust evaluation of downstream care and cost consequences.