Patterns, temporal trends and methodological associations in the measurement and valuation of childhood health utilities

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 3,974 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/adolescent-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 methods

A Microcosting and Cost-Consequence Analysis of Genomic Testing Strategies in Autism Spectrum Disorder

Produced by Technology Assessment at SickKids, Hospital for Sick Children.The primary objective of this study is to estimate costs associated with Chromosomal microarray analysis (CMA), whole exome sequencing (WES) and whole genome sequencing (WGS) tests for a targeted patient population consisting of children with ASD from an institutional payer perspective over 5 years. The secondary objective is to compare the incremental costs and diagnostic yields of CMA, WES and WGS in hypothetical clinical testing scenarios in a cost-consequence analysis.Supported by a Large-Scale Applied Research Project grant from Genome Canada and the Ontario Genomics Institute

Chronic ischemic lesions and presence of patent foramen ovale in young adults with embolic stroke of undetermined source - Results of the Young ESUS Patient Registry.

BACKGROUND Chronic ischemic lesions (CIL) are frequent findings in patients with acute ischemic stroke, but their phenotypes and relevance in young adults with embolic stroke of undetermined source (Y-ESUS) remains uncertain. We aimed to compare Y-ESUS patients with CIL to those without CIL and assessed the association of CIL and its phenotypes with the presence of patent foramen ovale (PFO). METHODS This prospective longitudinal, multicenter cohort study enrolled consecutive patients 50 years and younger with ESUS from 10/2017 to 10/2019 in 41 stroke research centers in 13 countries. Local investigators adjudicated presence and phenotypes of CIL on routine brain imaging (either MRI or CT). RESULTS Overall, 535 patients were enrolled (mean age 40.4 (SD 7.3) years, 238 (44%) female). CIL were present in 76/534 (14.2%) patients with a median count CIL count of 1.0 (IQR: 1 to 2), 42/76 (55%) had at least one cortical phenotype and 38/76 (50%) at least one non-cortical phenotype. Y-ESUS with CIL were less often female (32% vs 47% in non-CIL Y-ESUS), were older (mean 43 vs 40 years), had more often hypertension (42% vs 19%), diabetes (17% vs 7%), and hyperlipidemia (34% vs 18%). CIL Y-ESUS were independently associated with lower stroke recurrence (RR 0.17 (0.05-0.61). In Y-ESUS with PFO, CIL were less frequent in probable pathogenic PFO than with probable non-pathogenic PFO (6.1% vs 30% P<0.001). CONCLUSIONS One in seven Y-ESUS patients has additional CIL. CIL were associated with several vascular risk factors, lower probability of a pathogenic PFO and lower stroke recurrence

Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage.

BACKGROUND Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.)