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Objective: It is unknown whether computer-generated, patient-tailored feedback leads to improvements in glycemic control in people with type 2 diabetes.Research Design and Methods: We recruited people with type 2 diabetes aged ≥ 40 years with a glycated hemoglobin (A1C) ≥ 7%, living in Hamilton, Canada, who were enrolled in a community-based program (Diabetes Hamilton) that provided regular evidence-based information and listings of community resources designed to facilitate diabetes self-management. After completing a questionnaire, participants were randomly allocated to either receive or not receive periodic computer-generated, evidence-based feedback on the basis of their questionnaire responses and designed to facilitate improved glycemic control and diabetes self-management. The primary outcome was a change in A1C after 1 year.Results: A total of 465 participants (50% women, mean age 62 years, and mean A1C 7.83%) were randomly assigned, and 12-month A1C values were available in 96% of all participants, at which time the A1C level had decreased by an absolute amount of 0.24 and 0.15% in the intervention and control groups, respectively. The difference in A1C reduction for the intervention versus control group was 0.09% (95% CI -0.08 to 0.26; P = 0.3). No between-group differences in measures of quality of life, diabetes self-management behaviors, or clinical outcomes were observed.Conclusions: Providing computer-generated tailored feedback to registrants of a generic, community-based program that supports diabetes self-management does not lead to lower A1C levels or a better quality of life than participation in the community-based program (augmented by periodic A1C testing) alone. [ABSTRACT FROM AUTHOR]

Objective: Previous reviews of the effect of oral antidiabetic (OAD) agents on A1C levels summarized studies with varying designs and methodological approaches. Using predetermined methodological criteria, we evaluated the effect of OAD agents on A1C levels.Research Design and Methods: The Excerpta Medica (EMBASE), the Medical Literature Analysis and Retrieval System Online (MEDLINE), and the Cochrane Central Register of Controlled Trials databases were searched from 1980 through May 2008. Reference lists from systematic reviews, meta-analyses, and clinical practice guidelines were also reviewed. Two evaluators independently selected and reviewed eligible studies.Results: A total of 61 trials reporting 103 comparisons met the selection criteria, which included 26,367 study participants, 15,760 randomized to an intervention drug(s), and 10,607 randomized to placebo. Most OAD agents lowered A1C levels by 0.5-1.25%, whereas thiazolidinediones and sulfonylureas lowered A1C levels by approximately 1.0-1.25%. By meta-regression, a 1% higher baseline A1C level predicted a 0.5 (95% CI 0.1-0.9) greater reduction in A1C levels after 6 months of OAD agent therapy. No clear effect of diabetes duration on the change in A1C with therapy was noted.Conclusions: The benefit of initiating an OAD agent is most apparent within the first 4 to 6 months, with A1C levels unlikely to fall more than 1.5% on average. Pretreated A1C levels have a modest effect on the fall of A1C levels in response to treatment. [ABSTRACT FROM AUTHOR]

Context: Trials comparing higher vs lower levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury or acute respiratory distress syndrome (ARDS) have been underpowered to detect small but potentially important effects on mortality or to explore subgroup differences.Objectives: To evaluate the association of higher vs lower PEEP with patient-important outcomes in adults with acute lung injury or ARDS who are receiving ventilation with low tidal volumes and to investigate whether these associations differ across prespecified subgroups.Data Sources: Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (1996-January 2010) plus a hand search of conference proceedings (2004-January 2010).Study Selection: Two reviewers independently screened articles to identify studies randomly assigning adults with acute lung injury or ARDS to treatment with higher vs lower PEEP (with low tidal volume ventilation) and also reporting mortality.Data Extraction: Data from 2299 individual patients in 3 trials were analyzed using uniform outcome definitions. Prespecified effect modifiers were tested using multivariable hierarchical regression, adjusting for important prognostic factors and clustering effects.Results: There were 374 hospital deaths in 1136 patients (32.9%) assigned to treatment with higher PEEP and 409 hospital deaths in 1163 patients (35.2%) assigned to lower PEEP (adjusted relative risk [RR], 0.94; 95% confidence interval [CI], 0.86-1.04; P = .25). Treatment effects varied with the presence or absence of ARDS, defined by a value of 200 mm Hg or less for the ratio of partial pressure of oxygen to fraction of inspired oxygen concentration (P = .02 for interaction). In patients with ARDS (n = 1892), there were 324 hospital deaths (34.1%) in the higher PEEP group and 368 (39.1%) in the lower PEEP group (adjusted RR, 0.90; 95% CI, 0.81-1.00; P = .049); in patients without ARDS (n = 404), there were 50 hospital deaths (27.2%) in the higher PEEP group and 44 (19.4%) in the lower PEEP group (adjusted RR, 1.37; 95% CI, 0.98-1.92; P = .07). Rates of pneumothorax and vasopressor use were similar.Conclusions: Treatment with higher vs lower levels of PEEP was not associated with improved hospital survival. However, higher levels were associated with improved survival among the subgroup of patients with ARDS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to determine the information that pregnant women report receiving when being counseled about weight gain and the risks of inappropriate gain. STUDY DESIGN: With the use of a self-administered questionnaire at prenatal clinics in Hamilton, Ontario, Canada, a cross-sectional survey was conducted of women who had had at least 1 prenatal visit, who could read English, and who had a live singleton gestation. RESULTS: Three hundred ten women completed the survey, which was a 93.6% response rate. Although 28.5% (95% confidence interval, 23.5-33.6%) reported that their health care provider had made a recommendation about how much weight they should gain, only 12.0% (95% confidence interval, 8-16.1%) of the women reported having achieved the recommended weight gain in accordance with the 2009 guidelines. One quarter of the women reported being told that there were risks with inappropriate gain. CONCLUSION: Despite the recent 2009 publication of the gestational weight gain guidelines, only 12% of women reported being counseled correctly, which suggests an urgent need for improved patient education. [ABSTRACT FROM AUTHOR]

Background: Hemagglutinin (HA)-inhibiting antibodies contribute to the immune defense against influenza infection. However, there are insufficient data on the extent of correlation between vaccine-elicited HA antibodies and protection in children against different influenza strains, particularly when comparing live attenuated influenza vaccines (LAIV) versus inactivated influenza vaccines (IIV)., Methods: We measured postvaccination hemagglutination-inhibition (HAI) titers in 3-15-year-old participants of a cluster-randomized controlled trial of trivalent LAIV(3) versus IIV(3) in Canadian Hutterite colonies. We assessed HAI titers as predictors of symptomatic, reverse transcription polymerase chain reaction (RT-PCR)-confirmed influenza over 3 influenza seasons using Cox proportional hazards regression models with vaccine type as a covariate., Results: For each log2 unit increase in postvaccination HAI against A/H1N1 in 2013-2014, A/H3N2 2014-2015, and B/Yamagata in 2013-2014 (each the predominant circulating strain for the respective influenza season), the reduction in the risk of confirmed influenza was equal to 29.6% (95% confidence interval [CI], 17.1%-39.5%), 34.8% (95% CI, 17.2%-47.9%), and 31.8% (95% CI, 23.8%-38.5%), respectively. No reduction in the risk of influenza was observed with B/Yamagata-specific HAI titers in 2012-2013, which was dominated by a mixture of Yamagata and Victoria strains. Despite the overall lower HAI titers in the LAIV3 group, both H1N1 and H3N2 HAI titers were associated with protection against subtype matched influenza., Conclusions: Both LAIV3- and IIV3-elicited HA antibodies are associated with protection against influenza infection in seasons when the vaccine strains match the circulating influenza strain subtypes, supporting the use of HAI as a correlate of protection for both vaccine types in children., Competing Interests: Potential conflicts of interest. M. S. M. has received honoraria from Seqirus, Sanofi, and Grifols; research funding from Providence Therapeutics and Pfizer; and is cofounder of Aeroimmune, Inc. M. L. reports funding from World Health Organization, Medical Research Council UK, and CIHR; advisory board membership for GSK, Pfizer, Medicago, Merk, Seqirus, Sanofi, and Novavax; and data safety monitoring committee membership for CanSino Biologics and PATH. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Objectives: Preterm birth (PTB) affects ~10% of births worldwide; however, most literature focused on short-term clinical outcomes, with much less focus on long-term socioeconomic outcomes after PTB. We examined associations between PTB and individuals' income, employment, and educational outcomes during early adulthood., Methods: We conducted a population-level matched cohort study including all live births in Canada between 1990 and 1996, followed until 2018. Outcomes included Employment income per year in 2018 CAD and employment between ages 18 and 28 years, postsecondary education enrollment (18-22 years), and maximum educational attainment at age 22-27 years. Mean differences and risk ratios (RR) and differences (RD) were estimated using generalized estimating equation regression models for economic outcomes and multinomial logistic regression models for educational outcomes., Results: Of 2.4 million births, 7% were born preterm (0.3%, 0.6%, 0.8%, and 5.4% born extremely preterm (24-27 weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), and late preterm (34-36 weeks) respectively). After matching on baseline characteristics (e.g., sex, province of birth, and parental demographics) and adjusting for age and period effects, preterm-born individuals, on average, had $958 CAD less employment income per year (95% CI: $854-$1062), 6% lower income per year, than term-born individuals, and were 2.13% less likely to be employed (1.98-2.29%). PTB was also negatively associated with university enrollment (RR 0.93 (0.91-0.94) and graduation with a university degree (RR 0.95 (0.94-0.97)). Mean income differences for those born 24-27 weeks were -$5,463 CAD per year (17% lower), and adjusted RR were 0.55 for university enrollment and graduation., Conclusion: In this population-based study, preterm birth was associated with lower economic and educational achievements at least until the late twenties. The associations were stronger with decreasing GA at birth. Policymakers, clinicians, and parents should be aware that the socioeconomic impact of PTB is not limited to the early neonatal period but extends into adulthood., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ahmed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Decreased severe respiratory illness was observed during the first 2 years of the COVID-19 pandemic, with a relatively smaller decrease among children with medical complexity (CMC) compared to non-CMC. We extended this analysis to the third pandemic year (April 1, 2022, to March 31, 2023) when pandemic public health measures were loosened. A population-based repeated cross-sectional study evaluated respiratory hospitalizations among CMC and non-CMC (<18 years) in Ontario, Canada. Among the 67,517 CMC and 3,006,504 non-CMC in Ontario, there were more CMC respiratory hospitalizations compared with the expected prepandemic levels (n = 3145 hospitalizations, corresponding to rate ratio [RR], 1.20; 95% confidence interval [CI], 1.16-1.25) with an even larger relative increase among non-CMC (n = 6653, RR, 1.36; 95% CI, 1.34-1.38). Increased intensive care unit admissions for respiratory illness were also observed (CMC: RR, 1.44; 95% CI, 1.31-1.59; non-CMC: RR, 2.02; 95% CI, 1.89-2.16). Understanding respiratory surge drivers may provide insights to protect at-risk children from respiratory morbidity., (© 2024 Society of Hospital Medicine.)

Objective: To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections., Design: Multi-centre observational cohort study using data from 2009 to 2018 clinical records., Setting: Canadian children's hospitals (7) and community hospitals (3)., Patients: Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections., Interventions: Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation., Main Outcome Measures: Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates., Results: Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018., Conclusions: Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes., Competing Interests: Competing interests: PJG has received grants from the Canadian Institutes of Health Research (CIHR), the PSI Foundation and The Hospital for Sick Children. He has received non-financial support from the EBMLive Steering Committee (expenses reimbursed to attend conferences) and the CIHR Institute of Human Development, Child and Youth Health (as a member of the institute advisory board, expenses reimbursed to attend meetings), is a member of the CMAJ Open and BMJ Evidence-Based Medicine Editorial Board. OD was supported by a Chercheur Boursier Clinicien Award, from the Fonds de recherche du Québec – Santé. PP has received grants from the Hospital for Sick Children Foundation and CIHR. The other authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: This study aimed to compare the effects of the combination of rivaroxaban and aspirin with aspirin alone on health-related quality of life in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial., Methods and Results: Health-related quality of life assessed using the EQ-5D-3L. The treatment effects on health utility and EQ visual analogue scale (EQ VAS) scores were compared between rivaroxaban plus aspirin and aspirin alone in terms of adjusted mean difference in change from baseline and odds ratio of having deterioration events. Nine thousand forty-nine (98.9%) and 6916 (75.5%) completed the EQ-5D-3L at baseline and at final visit, respectively. Nine thousand twenty-eight (98.9%) and 6887 (76.3%) completed the EQ-5D-3L at baseline and final visit, respectively. Mean (standard deviation) health utility and EQ VAS scores at baseline were 0.871 (0.141) and 76.0 (15.3), respectively, for the rivaroxaban plus aspirin group, compared with 0.873 (0.139) and 75.8 (15.1) for the aspirin group. Adjusted mean difference in change from baseline utility was -0.002 [95% confidence interval (CI), -0.006, 0.002, P = 0.30] between the combination therapy group and the aspirin group. The odds ratio (95% CI) of experiencing deterioration in health utility was 1.01 (95% CI, 0.93, 1.10, P = 0.81) between the two groups. Adjusted mean difference in change from baseline EQ VAS was 0.02 (95% CI, -0.43, 0.47, P = 0.93) between the two groups., Conclusion: This analysis of the COMPASS trial demonstrated that the quality of life of patients was similar between the rivaroxaban plus aspirin group and the aspirin alone group., Registration: Trial registration number: ClinicalTrials.gov number (NCT01776424). Trial protocol and statistical analysis plan: https://www.nejm.org/doi/full/10.1056/NEJMoa1709118#APPNEJMoa1709118PRO., Competing Interests: Conflict of interest: F.X. is a member of the EuroQol Group, the developer of the EQ-5D. J.B. has received fees for event adjudication from Bayer AG. E.M. discloses that she is an employee of Bayer AG. D.L.B. discloses the following relationships—advisory board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado BioSciences, and Stasys; board of directors: Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; chair: Inaugural Chair and American Heart Association Quality Oversight Committee; consultant: Broadview Ventures and Hims; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (deputy editor), NCDR-ACTION Registry Steering Committee (chair), VA CART Research and Publications Committee (chair); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (Editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; Unfunded Research: FlowCo, and Takeda., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Discrete choice experiments including a duration attribute (DCEd) represent a promising candidate method for valuing health-related quality-of-life instruments. However, it has not been established that DCEd can produce similar results as composite time trade-off (cTTO) or EuroQol Valuation Technology (EQ-VT) valuations of the EQ-5D-5L instrument. This study provides a direct comparison between cTTO and EQ-VT, and DCEd valuation methods., Methods: An EQ-VT study was conducted in Trinidad and Tobago to value the EQ-5D-5L. 1079 respondents each completed 10 cTTO tasks and 12 discrete choice experiments tasks without a duration attribute. A separate sample of 970 respondents each completed 18 split-triplet DCEd tasks. Several regression models were applied to the EQ-VT data, and the DCEd data were analyzed using mixed logit models with an exponential discount rate. The estimated values were compared using scatterplots and Bland-Altman plots., Results: The ordering of dimensions was identical in level 5 for cTTO/EQ-VT and DCEd models, with pain/discomfort being the most important dimension and usual activities being least important. cTTO/EQ-VT models produced a value for state 55555 ranging between -0.52 and -0.69, whereas this was -0.543 for the nonlinear mixed logit model for the DCEd data. Scatterplots and Bland-Altman plots suggested excellent agreement between cTTO/EQ-VT and DCEd-based estimates., Conclusions: CTTO/EQ-VT and DCEd valuations produce similar results when correcting DCEd for nonlinear time preferences. The ordering of importance of the dimensions and scale are identical, suggesting that the 2 methods measure the same construct and produce similar results., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Influenza vaccination may protect through the humoral immune response, cellular immune response, or possibly both. Immunity after vaccination can be mediated through antibodies that may be detected by the rise of serum hemagglutination inhibition (HAI) titers. Our objective was to investigate the proportion of protection against influenza mediated through antibodies by measuring the rise of HAI titer (indirect effect) compared to that induced through other immune mechanisms (direct effect) for influenza A and B., Methods: We analysed data from a cluster randomized trial conducted during the 2008-2009 season in which Canadian Hutterite children were vaccinated against influenza. We used inverse probability weighting to calculate the indirect and direct effect of vaccination against influenza A/H3N2 and influenza B/Brisbane using HAI titres and overall vaccine efficacy., Results: We included data on 617 children from 46 Hutterite colonies, aged between 3 and 15 years who were vaccinated with either inactivated trivalent influenza vaccine or hepatitis A vaccine. Vaccine efficacy was 63 % for influenza A (H3N2) and 28 % for influenza B. The hazard ratio for protection against influenza A/H3N2 due to an indirect effect of vaccination was 0.96 (95 % confidence interval (CI) of 0.00 to 2.89) while for the direct effect it was 0.38 (95 % CI of 0.00 to 5.47). The hazard ratio for influenza B indirect effect was 0.75 (95 % CI of 0.07 to 1) and for the direct effect 0.96 (95 % CI of 0.00 to 12.02). In contrast, repeating the analysis using microneutralization in a subgroup of 488 children revealed that the protective effect for vaccination for A/H3N2 was entirely mediated by antibodies but only for 13 % for influenza B., Conclusions: Although vaccination provided higher protective effectiveness against influenza A than B, most of the influenza A vaccine efficacy likely occurred through antibodies other than what could be detected by HAI titres. In contrast, for influenza B, while the HAI titres appeared to mediate most of the vaccine effectiveness, this was not confirmed by microneutralization analysis., Competing Interests: Declaration of competing interest Dr. Loeb reports grant support from the Canadian Institutes of Health Research and WHO; receipt of an in-kind supply of vaccines from Sanofi; consulting fees for participation on advisory boards for Medicago, Novavax, Janssen, Pfizer, GSK, Merck, Sanofi, and Seqirus; and participation on a data and safety monitoring board for CanSino Biologics., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The purpose of this study was to determine the reliability of anthropometric measurements between two trained anthropometrists working in a team and one trained anthropometrist working with a child's parent/caregiver in a primary health care setting. Study Design: An observational study to determine measurement reliability was conducted in a primary care child research network in Canada. In total, 120 children 0-5 years old had their anthropometric measurement taken twice by two trained anthropometrists working in a team and twice by one trained anthropometrist working with a child's parent/caregiver. Inter- and intra-observer reliability was calculated using the technical error of measurement (TEM), relative TEM (%TEM), and the coefficient of reliability (R). Results: The %TEM values for length/height and weight were <2%, and the R coefficient values were >0.99, indicating a high degree of inter- and intra-observer reliability. The TEM values demonstrated a high degree of reliability for inter- and intra-observer measurement of length/height in comparison with other anthropometric measurement parameters. However, there was greater variation seen in the length measurement for children 0 to <2 years of age and in arm circumference measurement across both age-groups. Conclusion(s): This study suggests that anthropometric measurement taken by one trained anthropometrist with the assistance of a parent/caregiver is reliable. These findings provide evidence to support inclusion of a child's parent/caregiver with anthropometric measurement collection in clinical setting(s) to enhance feasibility and efficiency and reduce the research costs of including a second trained anthropometrist.

Background: Maternal-perinatal interventions delivered during pregnancy or childbirth have unique characteristics that impact the health-related quality of life (HRQoL) of the mother, fetus, and newborn child. However, maternal-perinatal cost-utility analyses (CUAs) often only consider either maternal or child health outcomes. Challenges include, but are not limited to, measuring fetal, newborn, and infant health outcomes, and assessing their impact on maternal HRQoL. It is also important to recognize the impact of maternal-perinatal health on family members' HRQoL (i.e., family spillover effects) and to incorporate these effects in maternal-perinatal CUAs., Objective: The aim was to systematically review the methods used to include health outcomes of pregnant women, fetuses, and children and to incorporate family spillover effects in maternal-perinatal CUAs., Methods: A literature search was conducted in Medline, Embase, EconLit, Cochrane Collection, Cumulative Index to Nursing and Allied Health Literature (CINAHL), International Network of Agencies for Health Technology Assessment (INAHTA), and the Pediatric Economic Database Evaluation (PEDE) databases from inception to 2020 to identify maternal-perinatal CUAs that included health outcomes for pregnant women, fetuses, and/or children. The search was updated to December 2022 using PEDE. Data describing how the health outcomes of mothers, fetuses, and children were measured, incorporated, and reported along with the data on family spillover effects were extracted., Results: Out of 174 maternal-perinatal CUAs identified, 62 considered the health outcomes of pregnant women, and children. Among the 54 quality-adjusted life year (QALY)-based CUAs, 12 included fetal health outcomes, the impact of fetal loss on mothers' HRQoL, and the impact of neonatal demise on mothers' HRQoL. Four studies considered fetal health outcomes and the effects of fetal loss on mothers' HRQoL. One study included fetal health outcomes and the impact of neonatal demise on maternal HRQoL. Furthermore, six studies considered the impact of neonatal demise on maternal HRQoL, while four included fetal health outcomes. One study included the impact of fetal loss on maternal HRQoL. The remaining 26 only included the health outcomes of pregnant women and children. Among the eight disability-adjusted life year (DALY)-based CUAs, two measured fetal health outcomes. Out of 174 studies, only one study included family spillover effects. The most common measurement approach was to measure the health outcomes of pregnant women and children separately. Various approaches were used to assess fetal losses in terms of QALYs or DALYs and their impact on HRQoL of mothers. The most common integration approach was to sum the QALYs or DALYs for pregnant women and children. Most studies reported combined QALYs and incremental QALYs, or DALYs and incremental DALYs, at the family level for pregnant women and children., Conclusions: Approximately one-third of maternal-perinatal CUAs included the health outcomes of pregnant women, fetuses, and/or children. Future CUAs of maternal-perinatal interventions, conducted from a societal perspective, should aim to incorporate health outcomes for mothers, fetuses, and children when appropriate. The various approaches used within these CUAs highlight the need for standardized measurement and integration methods, potentially leading to rigorous and standardized inclusion practices, providing higher-quality evidence to better inform decision-makers about the costs and benefits of maternal-perinatal interventions. Health Technology Assessment agencies may consider providing guidance for interventions affecting future lives in future updates., (© 2024. The Author(s).)

Purpose: The 2016 EQ-5D-3L value set for Trinidad and Tobago (T&T) allows for the calculation of EQ-5D-5L values via the crosswalk algorithm. The 2016 value set was based on methods predating the EQ-VT protocol, now considered the gold standard for developing EQ-5D value sets. Furthermore, direct elicitation of EQ-5D-5L is preferred over crosswalked values. This study aimed to produce an EQ-5D-5L value set for T&T., Methods: A representative sample (age, sex, geography) of adults each completed 10 composite Time Trade-Off (cTTO) tasks and 12 Discrete Choice Experiment (DCE) tasks in face-to-face interviews. The cTTO data were analyzed using a Tobit model that corrects for heteroskedasticity. DCE data were analyzed using a mixed logit model. The cTTO and DCE data were combined in hybrid models., Results: One thousand and seventy-nine adults completed the valuation interviews. Among the modelling approaches that were explored, the hybrid heteroskedastic Tobit model produced all internally consistent, statistically significant coefficients, and performed best in terms of out-of-sample predictivity for single states. Compared to the existing EQ-5D-5L crosswalk set, the new value set had a higher number of negative values (236 or 7.6% versus 21 or 0.7%). The mean absolute difference was 0.157 and the correlation coefficient between the two sets was 0.879., Conclusion: This study provides a value set for the EQ-5D-5L for T&T using the EQ-VT protocol. We recommend this value set for QALY computations relating to T&T., (© 2024. The Author(s).)

Importance: Preterm birth (PTB) has been associated with lower income in adulthood, but associations with intergenerational income mobility and the role of family socioeconomic status (SES) as modifying factor are unclear., Objectives: To assess whether the association between PTB and income differs according to family SES at birth and to assess the association between PTB and intergenerational income mobility., Design, Setting, and Participants: This study comprised a matched cohort of live births in Canada between January 1, 1990, and December 31, 1996, with follow-up until December 31, 2018. Statistical analysis was performed between May 2023 and March 2024., Exposure: Preterm birth, defined as birth between 24 and 37 weeks' gestational age (with gestational age subcategories of 34-36, 32-33, 28-31, and 24-27 weeks) vs early and full term births (gestational age, 37-41 weeks)., Main Outcomes and Measures: Associations between PTB and annual adulthood income in 2018 Canadian dollars were assessed overall (current exhange rate: $1 = CAD $1.37) and stratified by family income quintiles, using generalized estimating equation regression models. Associations between PTB and percentile rank change (ie, difference between the rank of individuals and their parents in the income distribution within their respective generations) and upward or downward mobility (based on income quintile) were assessed using linear and multinomial logistic regressions, respectively., Results: Of 1.6 million included births (51.1% boys and 48.9% girls), 6.9% infants were born preterm (5.4% born at 34-36 weeks, 0.7% born at 32-33 weeks, 0.5% born at 28-31 weeks, and 0.2% born at 24-27 weeks). After matching on baseline characteristics (eg, sex, province of birth, and parental demographics) and adjusting for age and period effects, PTB was associated with lower annual income (mean difference, CAD -$687 [95% CI, -$788 to -$586]; 3% lower per year), and the differences were greater among those belonging to families in the lowest family SES quintile (mean difference, CAD -$807 [95% CI, -$998 to -$617]; 5% lower per year). Preterm birth was also associated with lower upward mobility and higher downward mobility, particularly for those born earlier than 31 weeks' gestational age (24-27 weeks: mean difference in percentile rank change, -8.7 percentile points [95% CI, -10.5 to -6.8 percentile points])., Conclusions and Relevance: In this population-based matched cohort study, PTB was associated with lower adulthood income, lower upward social mobility, and higher downward mobility, with greater differences among those belonging to economically disadvantaged families. Interventions to optimize socioeconomic outcomes of preterm-born individuals would need to define target population considering SES.

Social determinants of health are important in designing effective interventions for hepatitis B virus (HBV) infection. This systematic review characterises equity-oriented, social determinants of health-focused HBV interventions, and describes their effectiveness in terms of the prevention, care, or treatment of HBV in high-income countries. We searched electronic databases for central concepts of 'HBV', 'equity', 'social determinants of health', 'intervention', and 'Organization for Economic Co-operation and Development (OECD) countries'. Screening and data abstraction were conducted independently by two reviewers. Data were abstracted from 66 studies; articles with a comparative study design (n=36) were included in the narrative synthesis, highlighting social determinants of health domains of interventions, HBV-relevant health outcomes, and extra-health social determinants of health effects (ie, those effects that extend beyond health outcomes). Synthesis aligned with six emergent themes corresponding to HBV prevention and care: knowledge and education, diagnosis and screening, immunisation, care initiation, engagement with clinical care and treatment, and upstream prevention. Studies presented a heterogeneous array of HBV-relevant health outcomes. Most interventions were tailored for social determinants of health domains of race, ethnicity, culture, and language; drug use; and socioeconomic status. Across the themes, at least two-thirds of interventions showed comparative effectiveness for addressing HBV. Extra-health social determinants of health outcomes were observed for two studies. Considerable diversity in population-level approaches was observed regarding intervention goals and effectiveness; most interventions were effective at enhancing the prevention, care, or treatment of HBV., Competing Interests: Declaration of interests WWLW has received research support from the Canadian Liver Foundation. JJF has received research support from AbbVie, Eiger, Gilead, GlaxoSmithKline, Janssen, and Roche and consulting fees from AbbVie, Arbutus, Gilead, Janssen, Roche, and Vir outside of the current work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Valuing child health is critical to assessing the value of healthcare interventions for children. However, there remain important methodological and normative issues. This qualitative study aimed to understand the views of Canadian stakeholders on these issues., Methods: Stakeholders from health technology assessment (HTA) agencies, pharmaceutical industry representatives, healthcare providers, and academic researchers/scholars were invited to attend an online interview. Semi-structured interviews were designed to focus on: (1) comparing the 3-level and 5-level versions of the EQ-5D-Y; (2) source of preferences for valuation (adults vs. children); (3) perspective of valuation tasks; and (4) methods for valuation (discrete choice experiment [DCE] and its variants versus time trade-off [TTO]). Participants were probed to consider HTA guidelines, cognitive capacity, and potential ethical concerns. All interviews were recorded and transcribed verbatim. Framework analysis with the incidence density method was used to analyze the data., Results: Fifteen interviews were conducted between May and September 2022. 66.7% (N = 10) of participants had experience with economic evaluations, and 86.7% (N = 13) were parents. Eleven participants preferred the EQ-5D-Y-5L. 12 participants suggested that adolescents should be directly involved in child health valuation from their own perspective. The participants were split on the ethical concerns. Eight participants did not think that there was ethical concern. 11 participants preferred DCE to TTO. Among the DCE variants, 6 participants preferred the DCE with duration to the DCE with death., Conclusions: Most Canadian stakeholders supported eliciting the preferences of adolescents directly from their own perspective for child health valuation. DCE was preferred if adolescents are directly involved., (© 2024. The Author(s).)

Importance: Children requiring care in a pediatric intensive care unit (PICU) are known to have increased risk of subsequent mortality. Children with severe neurologic impairment (SNI)-who carry neurologic or genetic diagnoses with functional impairments and medical complexity-are frequently admitted to PICUs. Although recurrent PICU critical illness episodes (PICU-CIEs) are assumed to indicate a poor prognosis, the association between recurrent PICU-CIEs and mortality in this patient population is poorly understood., Objective: To assess the association between number of recent PICU-CIEs and survival among children with severe neurologic impairment., Design, Setting, and Participants: This population-based retrospective cohort study used health administrative data from April 1, 2002, to March 31, 2020, on 4774 children born between 2002 and 2019 with an SNI diagnosis code in an Ontario, Canada, hospital record before 16 years of age and a first PICU-CIE from 2002 to 2019. Data were analyzed from November 2021 to June 2023., Exposure: Pediatric intensive care unit critical illness episodes (excluding brief postoperative PICU admissions)., Main Outcome and Measures: One-year survival conditioned on the number and severity (length of stay >15 days or use of invasive mechanical ventilation) of PICU-CIEs in the preceding year., Results: In Ontario, 4774 children with SNI (mean [SD] age, 2.1 [3.6] months; 2636 [55.2%] <1 year of age; 2613 boys [54.7%]) were discharged alive between 2002 and 2019 after their first PICU-CIE. Ten-year survival after the initial episode was 81% (95% CI, 79%-82%) for children younger than 1 year of age and 84% (95% CI, 82%-86%) for children 1 year of age or older; the age-stratified curves converged by 15 years after the initial episode at 79% survival (95% CI, 78%-81% for children <1 year and 95% CI, 75%-84% for children ≥1 year). Adjusted for age category and demographic factors, the presence of nonneurologic complex chronic conditions (adjusted hazard ratio [AHR], 1.70 [95% CI, 1.43-2.02]) and medical technology assistance (AHR, 2.32 [95% CI, 1.92-2.81]) were associated with increased mortality. Conditional 1-year mortality was less than 20% regardless of number or severity of recent PICU-CIEs. Among children with high-risk PICU-CIEs, 1-year conditional survival decreased from 90% (95% CI, 89%-91%) after the first PICU-CIE to 81% (95% CI, 77%-86%) after the fourth PICU-CIE., Conclusions and Relevance: This cohort study of children with SNI demonstrated a modest dose-dependent association between PICU-CIEs and short-term mortality. These data did not support the conventional wisdom that recurrent PICU admissions are associated with subsequent high mortality risk.

Objective: In Canada, population norms are only available for 2 provinces, Alberta and Quebec. The objective of this study was to derive the population norms for the EQ-5D-5L based on a representative sample of the Canadian general population., Methods: Data from the Canadian EQ-5D-5L valuation study, a cross-sectional study, were used. A quota sampling method was used to recruit a representative sample of the Canadian general population in terms of age, sex, and education. EQ-5D-5L utilities and EQ VAS were summarized using descriptive statistics and the impact of demographic characteristics on the EQ-5D-5L utilities was evaluated using statistical hypothesis testing and Tobit regression., Results: 1207 eligible participants were included in the analysis. Pain/discomfort (53.1%) was the most frequently reported domain with any problem, and self-care (7.6%) domain was the least. The mean (standard deviation [SD]) EQ-5D-5L utility was 0.864 (0.121) and the mean (SD) EQ VAS was 82.3 (14.23). The highest mean EQ-5D-5L utility was 0.881 in age group 25-34 while the lowest was 0.839 in age group 55-64. Participants who had full-time employment, were married, a higher annual household income and no chronic health conditions had significantly higher EQ-5D-5L utilities., Conclusion: This article reports the first Canadian population norms for the EQ-5D-5L and can be used as population references for economic evaluations and clinical research., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Severe respiratory disease declined during the COVID-19 pandemic, partially due to decreased circulation of respiratory pathogens. However, the outcomes of children with higher risk have not been described using population-based data., Objective: To compare respiratory-related hospitalizations, intensive care unit (ICU) admissions, and mortality during the pandemic vs prepandemic, among children with medical complexity (CMC) and without medical complexity (non-CMC)., Design, Setting, and Participants: This population-based repeated cross-sectional study used Canadian health administrative data of children aged younger than 18 years in community and pediatric hospitals during a pandemic period (April 1, 2020, to February 28, 2022) compared with a 3-year prepandemic period (April 1, 2017, to March 31, 2020). The pandemic period was analyzed separately for year 1 (April 1, 2020, to March 31, 2021) and year 2 (April 1, 2021, to February 28, 2022). Statistical analysis was performed from October 2022 to April 2023., Main Outcomes and Measures: Respiratory-related hospitalizations, ICU admissions, and mortality before and during the pandemic among CMC and non-CMC., Results: A total of 139 078 respiratory hospitalizations (29 461 respiratory hospitalizations for CMC and 109 617 for non-CMC) occurred during the study period. Among CMC, there were fewer respiratory hospitalizations in both 2020 (rate ratio [RR], 0.44 [95% CI, 0.42-0.46]) and 2021 (RR, 0.55 [95% CI, 0.51-0.62]) compared with the prepandemic period. Among non-CMC, there was an even larger relative reduction in respiratory hospitalizations in 2020 (RR, 0.18 [95% CI, 0.17-0.19]) and a similar reduction in 2021 (RR, 0.55 [95% CI, 0.54-0.56]), compared with the prepandemic period. Reductions in ICU admissions for respiratory illness followed a similar pattern for CMC (2020: RR, 0.56 [95% CI, 0.53-0.59]; 2021: RR, 0.66 [95% CI, 0.63-0.70]) and non-CMC (2020: RR, 0.22 [95% CI, 0.20-0.24]; RR, 0.65 [95% CI, 0.61-0.69]). In-hospital mortality for these conditions decreased among CMC in both 2020 (RR, 0.63 [95% CI, 0.51-0.77]) and 2021 (RR, 0.72 [95% CI, 0.59-0.87])., Conclusions and Relevance: This cross-sectional study found a substantial decrease in severe respiratory disease resulting in hospitalizations, ICU admissions, and mortality during the first 2 years of the pandemic compared with the 3 prepandemic years. These findings suggest that future evaluations of the effect of public health interventions aimed at reducing circulating respiratory pathogens during nonpandemic periods of increased respiratory illness may be warranted.

Autistic children experience high rates of anxiety. Insistence on sameness behaviour (IS) is a core feature of autism that appears correlated with anxiety severity. The objective of this study was to examine the longitudinal relations between anxiety and IS in autistic children using a developmental cascade model. A longitudinal cohort of 421 autistic children was followed between 4 and 11 years of age. Anxiety was quantified using items from the Anxiety Problems subscale of the Child Behavior Checklist; sameness behaviours were measured using the Repetitive Behavior Scale-Revised, Ritualistic/sameness subscale (both parent-report measures). Structural equation modelling was used to examine the longitudinal and directional associations between anxiety and IS at four time-points, through cross-lagged panel models (CLPM) with and without a random-intercepts component (RI-CLPM). Both the CLPM and the RI-CLPM had good fit. Significant directional associations were detected whereby elevated or increasing IS preceded elevated or increasing anxiety symptoms 1-2 years later, respectively. Stable baseline tendencies towards anxiety and IS as between-person traits (intercepts) were strongly associated (standardized estimate = 0.69, p < 0.001). The magnitude of the cross-sectional associations between anxiety and IS appeared to lessen with age. IS and anxiety symptoms in autism are closely related. They appear to be shared traits that mirror each other particularly in younger children. Increasing IS may be a sign of emerging future anxiety. Interventions that target IS to reduce or prevent anxiety amongst school-aged autistic children merit further study., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Importance: Orbital cellulitis with subperiosteal or orbital abscess can result in serious morbidity and mortality in children. Objective volume criterion measurement on cross-sectional imaging is a useful clinical tool to identify patients with abscess who may require surgical drainage., Objective: To determine the predictive value of abscess volume and the optimal volume cut-point for surgical intervention., Design: We conducted an observational cohort study using medical records from children hospitalized between 2009 and 2018., Setting: Multicentre study using data from 6 children's hospitals., Participants: Children were included if they were between 2 months and 18 years of age and hospitalized for an orbital infection with an abscess confirmed on cross-sectional imaging., Exposure: Subperiosteal or orbital abscess volume., Main Outcome and Measures: The primary outcome was surgical intervention, defined as subperiosteal and/or orbital abscess drainage. Multivariable logistic regression was performed to assess the association of abscess volume with surgery. To determine the optimal abscess volume cut-point, receiver operating characteristic (ROC) analysis was performed using the Youden Index to optimize sensitivity and specificity., Results: Of the 150 participants (mean [SD] age, 8.5 [4.5] years), 68 (45.3%) underwent surgical intervention. On multivariable analysis, larger abscess volume and non-medial abscess location were associated with surgical intervention (abscess volume: adjusted odds ratio [aOR], 1.46; 95% CI, 1.11-1.93; abscess location: aOR, 3.46; 95% CI, 1.4-8.58). ROC analysis demonstrated an optimal abscess volume cut-point of 1.18 mL [AUC: 0.75 (95% CI 0.67-0.83) sensitivity: 66%; specificity: 79%]. CONCLUSIONS AND RELEVANCE: In this multicentre cohort study of 150 children with subperiosteal or orbital abscess, larger abscess volume and non-medial abscess location were significant predictors of surgical intervention. Children with abscesses >1.18 mL should be considered for surgery., Competing Interests: Declaration of competing interest PJG has received grants from the Canadian Institutes of Health Research (CIHR), the PSI Foundation, and The Hospital for Sick Children. He has received nonfinancial support from the EBMLive Steering Committee (expenses reimbursed to attend conferences) and the CIHRInstitute of Human Development, Child and Youth Health (as a member of the institute advisory board, expenses reimbursed to attend meetings). He is a member of the CMAJ Open and BMJ Evidence Based Medicine Editorial Board. PCP has received grants from the Hospital for Sick ChildrenFoundation (SP05-602), Canadian Institutes of Health Research (FRN # 115059), and non-financial support for an investigator-initiated trial for which Mead Johnson Nutrition provides non-financial support (Fer-In-Sol® liquid iron supplement) (2011–2017). OD was supported by a Chercheur Boursier Clinicien Award, from the Fonds de recherche du Québec – Santé. GW has received grants from the Canadian Institutes of Health Research and the Hamilton Health SciencesFoundation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Discrete choice experiments (DCE) are increasingly being conducted using online panels. However, the comparability of such DCE-based preferences to traditional modes of data collection (e.g., in-person) is not well established. In this study, supervised, face-to-face DCE was compared with its unsupervised, online facsimile on face validity, respondent behavior, and modeled preferences., Methods: Data from face-to-face and online EQ-5D-5L health state valuation studies were compared, in which each used the same experimental design and quota sampling procedure. Respondents completed 7 binary DCE tasks comparing 2 EQ-5D-5L health states presented side by side (health states A and B). Data face validity was assessed by comparing preference patterns as a function of the severity difference between 2 health states within a task. The prevalence of potentially suspicious choice patterns (i.e., all As, all Bs, and alternating As/Bs) was compared between studies. Preference data were modeled using multinomial logit regression and compared based on dimensional contribution to overall scale and importance ranking of dimension-levels., Results: One thousand five Online respondents and 1,099 face-to-face screened (F2F S ) respondents were included in the main comparison of DCE tasks. Online respondents reported more problems on all EQ-5D dimensions except for Mobility. The face validity of the data was similar between comparators. Online respondents had a greater prevalence of potentially suspicious DCE choice patterns ([Online]: 5.3% [F2F S ] 2.9%, P  = 0.005). When modeled, the relative contribution of each EQ-5D dimension differed between modes of administration. Online respondents weighed Mobility more importantly and Anxiety/Depression less importantly., Discussion: Although assessments of face validity were similar between Online and F2F S , modeled preferences differed. Future analyses are needed to clarify whether differences are attributable to preference or data quality variation between modes of data collection.

Purpose: Advanced genomic and genetic testing technologies are quickly diffusing into clinical practice, but standardized approaches to assessing their clinical utility are limited. Previous work developed and generated preliminary evidence of validity for a novel outcome measure, the Clinician-reported Genetic testing Utility InDEx (C-GUIDE). C-GUIDE is a 17-item measure that captures the utility of genetic testing from the providers' perspective. Preliminary evidence of its inter-rater reliability was obtained through a clinical vignette study. The purpose of this study was to further assess its inter-rater reliability using actual clinical cases., Methods: One genetic counselor and one medical geneticist independently completed C-GUIDE Version 1.1 after genetic test results were disclosed to a shared set of 42 patients. Raters also completed a case description questionnaire, including information about the patient's age, indication for testing, and type of test performed. Inter-rater reliability was assessed by comparing the raters' C-GUIDE scores using ANOVA to generate intra-class correlation coefficients (ICCs), absolute agreement, and mixed repeated measures ANOVA., Findings: Of the 42 patients studied, the most common indications for testing were hearing loss (n = 18) and craniosynostosis (n = 11), and the most common tests ordered were gene panels (n = 20) and microarrays (n = 10). Test results were diagnostic or partially diagnostic for 11 patients, potentially diagnostic for 14 patients, or nondiagnostic for 17 patients. The overall ICC was 0.95 (95% CI, 0.89-0.97) and absolute agreement was acceptable (>70%) for 15 individual items. Inter-rater agreement was excellent (ICC > 0.90) for 8 items, good (ICC = 0.75-0.89) for 3 items, moderate (ICC = 0.50-0.74) for 4 items and poor (ICC < 0.50) for 2 items. Absolute agreement was unacceptable (<70%), and rater agreement was fair (ICC = 0.40-0.59) for 2 items. For the global rating, the ICC was 0.62 (95% CI, 0.39-0.77), and the absolute agreement was 61.9%., Implications: Rater instructions for item completion have been modified to improve consistency of item interpretation. Although further assessments of reliability are warranted after modifications, these findings provide additional tentative evidence of C-GUIDE's inter-rater reliability and suggest that it may be useful as a strategy for measuring the value of genetic testing, as perceived by genetics providers., Competing Interests: Declaration of Competing Interest Dr Hayeems is supported by the Canada Research Chair in Genomics and Health Policy (Tier 2); and is a member of the Ontario Genetics Advisory Committee and the Provincial Genetics Advisory Committee. Dr Meyn received an honorarium for review of the National Institutes of Health intramural program; holds a patent for PhenoTips software; is a member of the Directors Committee of the National Organization for Rare Disease Centers of Excellence (USA); and has 1% stock ownership in Gene42. Dr Ungar is supported by the Canada Research Chair in Economic Evaluation and Technology Assessment in Child Health; and is the Chair of the Ontario Genetics Advisory Committee. The authors have indicated that they have no other conflicts of interest regarding the content of this article. The Canadian Institutes of Health Research did not have any role in the study design, collection, analysis and interpretation of data, or in the writing and decision to submit the manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Health utilities from value sets for the EQ-5D-5L are commonly used in economic evaluations. We examined whether modeling spatial correlation among health states could improve the precision of the value sets., Methods: Using data from 7 EQ-5D-5L valuation studies, we compared the predictive precision of the published linear model, a recently proposed cross-attribute level effects (CALE) model, and 2 Bayesian models with spatial correlation. Predictive precision was quantified through the root mean squared error (RMSE) for out-of-sample predictions of state-level mean utilities on omitting individual states, as well as omitting blocks of states., Results: In all 7 countries, on omitting single health states, Bayesian models with spatial correlation improved upon the published linear model: the RMSEs for the originally published models, 0.050, 0.051, 0.060, 0.061, 0.039, 0.050, and 0.087 for Canada, China, Germany, Indonesia, Japan, Korea, and the Netherlands, respectively, could be reduced to 0.043, 0.042, 0.051, 0.054, 0.037, 0.037, and 0.085, respectively. On omitting blocks of health states, Bayesian models with spatial correlation led to smaller RMSEs in 3 countries, while the CALE model led to smaller RMSEs in the remaining 4 countries., Discussion: Bayesian models incorporating spatial correlation and CALE models are promising for improving the precision of value sets for the EQ-5D-5L. The differential performance of the Bayesian models on omitting single states versus blocks of states suggests that designing valuation studies to capture more health states may further improve precision. We suggest that Bayesian and CALE models be considered as candidates when creating value sets and that alternative designs be explored; this is vital as the prediction errors in value sets need to be smaller than the minimal important difference of the instrument., Highlights: The accuracy of value sets of multi-attribute utility instruments is typically of the same order of magnitude as the instrument's minimal important difference and would benefit from improvement.Bayesian models with spatial correlation have been shown to improve value set accuracy in isolated cases.We showed that Bayesian approaches with spatial correlation improved predictive precision in 7 EQ-5D-5L valuation studies.We recommend that Bayesian models incorporating spatial correlation be considered when creating value sets and have provided code for fitting them.

Background: The objective of this study was to estimate the economic burden attributable to laboratory-confirmed Lyme disease (LD) in Ontario, Canada and assess health outcomes associated with LD., Method: We conducted a cohort study using laboratory-confirmed LD cases accrued between 2006 and 2018. The exposed cohort was matched 1:3 to the unexposed cohort using a combination of hard and propensity score matching. We used phase-of-care costing methods to calculate attributable costs for four phases of illness: pre-diagnosis, acute care, post-acute care, and continuing care in 2018 Canadian dollars. We used ICD-10-CA and OHIP billing codes to identify emergency department visits, physician billings and hospitalizations related to LD sequelae to assess health outcomes., Results: A total of 2,808 cases were identified with a mean age of 46.5 (20.7) years and 44% female. Within 30-days, 404 (14.3%) cases required an ED visit and 63 (2.4%) cases required hospitalization. The mean (95% CI) total costs for LD cases in pre-diagnosis, acute, and post-acute care phases were $209 ($181, 238), $1,084 ($956, $1,212), and $1,714 ($1,499, $1,927), respectively. The highest mean attributable 10-day cost was $275 ($231, $319) during acute care. At 1-year post-infection, LD increased the relative risk of nerve palsies by 62 (20, 197), and polyneuropathy by 24 (3.0, 190). LD resulted in 16 Lyme meningitis events vs. 0 events in the unexposed., Conclusion: Individuals with laboratory-confirmed LD have increased healthcare resource use pre-diagnosis and up to six months post-diagnosis, and were more likely to seek healthcare services related to LD sequelae., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mac et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The present study examines various activities of social participation (i.e., church or religious activities; educational or cultural activities; service club or fraternal organization activities; neighbourhood, community, or professional association activities; volunteer or charity work; and recreational activities) as contributing factors to successful aging. Successful aging in this study includes the following: adequate social support, no limitations with respect to Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs), no mental illness in the preceding year, no serious cognitive decline or pain that prevents activity, as well as high levels of happiness, and self-reports of good physical health, mental health, and successful aging. Methods: The Canadian Longitudinal Study on Aging (CLSA) is a large, national, longitudinal study on aging. A secondary analysis of the baseline (i.e., 2011-2015) and Time 2 (i.e., 2015-2018) data of the CLSA was conducted on a sample of 7623 older adults who were defined as "aging successfully" at baseline and were aged 60+ at Time 2. Binary logistic regression analyses were employed to examine the association between engaging in various social participation activities at baseline and aging successfully at Time 2. Results: In a subsample (n = 7623) of the Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort who were aging successfully at baseline, the prevalence of successful aging at Time 2 was significantly higher among the participants who participated in volunteer or charity work and recreational activities compared to those who were not involved in these activities. After adjusting for 22 potential factors, the results of the binary logistic regression analyses reported that participants who, at baseline, participated in volunteer or charity work and recreational activities had higher age-sex-adjusted odds of achieving successful aging (volunteer or charity work: aOR = 1.17, 95% CI: 1.04, 1.33; recreational activities: aOR = 1.15, 95% CI: 1.00, 1.32). Conclusions: Among six types of social participation activities, people who participated in volunteer or charity work and recreational activities were more likely to achieve successful aging than their counterparts who did not engage in these activities. If these associations are found to be causal, policies and interventions encouraging older adults to participate in volunteer or charity work and recreational activities may support older adults to achieve successful aging in later life.

Objectives: Most juvenile idiopathic arthritis (JIA) biologic disease-modifying antirheumatic drugs (bDMARDs) trials used an open-label run-in period followed by randomized medication withdrawal. We used data from the run-in period of 4 bDMARD trials to 1) delineate early response trajectory to bDMARDs and 2) identify predictors of early response., Methods: Data from the first 16 weeks of 4 bDMARD trials were used. The primary outcome was the American College of Rheumatology (ACR) Pediatric 50 (Pedi 50) response criteria: clinically significant response defined as ACR Pedi 50 or greater. The secondary outcome was the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) minimal disease activity state. Response transition rates and predictors were modeled using an inhomogeneous Markov multistate model., Results: Five hundred thirty-two participants (70% receiving methotrexate, 41% prednisone) were included. By month 4, the probability of attaining ACR Pedi 50 or greater was 0.698. If ACR Pedi 50 or more was not achieved by month 1, the probability of achieving it by month 4 was 0.60. If ACR Pedi 50 or more was not achieved by month 3, the probability of achieving this by month 4 was 0.31. Age at diagnosis, disease duration, baseline rheumatoid factor, and active joint counts predicted ACR and cJADAS state transitions, adjusted for concomitant treatment., Conclusions: No response ACR Pedi 50 or more by month 1 after treatment was associated with a 0.60 probability of responding by month 4, but not responding by month 3 was associated with a 0.31 probability of response by month 4. Baseline disease duration, rheumatoid factor, and active joint counts predicted early treatment response (ACR and cJADAS10 states)., (© 2022 American College of Rheumatology.)

Objectives: No previous study has examined the management of hospitalized children with orbital cellulitis at both children's and community hospitals across multiple sites in Canada. We describe variation and trends over time in diagnostic testing and imaging, adjunctive agents, empiric antibiotics, and surgical intervention in children hospitalized with orbital cellulitis., Patients and Methods: Multicenter cohort study of 1579 children aged 2 months to 18 years with orbital cellulitis infections admitted to 10 hospitals from 2009 to 2018. We assessed hospital-level variation in the use of diagnostic tests, imaging, antibiotics, adjunctive agents, surgical intervention, and clinical outcomes using X2, Mann-Whitney U, and Kruskal-Wallis tests. The association between clinical management and length of stay was evaluated with median regression analysis with hospital as a fixed effect., Results: There were significant differences between children's hospitals in usage of C-reactive protein tests (P < .001), computed tomography scans (P = .004), MRI scans (P = .003), intranasal decongestants (P < .001), intranasal corticosteroids (P < .001), intranasal saline spray (P < .001), and systemic corticosteroids (P < .001). Children's hospital patients had significantly longer length of hospital stay compared with community hospitals (P = .001). After adjustment, diagnostic testing, imaging, and subspecialty consults were associated with longer median length of hospital stay at children's hospitals. From 2009 to 2018, C-reactive protein test usage increased from 28.8% to 73.5% (P < .001), whereas erythrocyte sedimentation rate decreased from 31.5% to 14.1% (P < .001)., Conclusions: There was significant variation in diagnostic test usage and treatments, and increases in test usage and medical intervention rates over time despite minimal changes in surgical interventions and length of stay., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Young children are often accompanied by their parent/caregiver when attending primary healthcare visits, where clinical procedures such as anthropometric measurements are conducted. Parents are not typically involved in their child's anthropometric measurement collection, and there are no recommendations for parental involvement during visits. The objective of this study was to describe parents' experiences with being involved in their child's anthropometric measurements., Methods: A 10-question survey comprised of scaled and open-ended questions was self-administered to participants after child anthropometric measurement collection including length/height, weight, head, arm, and waist circumference. Survey data were analyzed using a general inductive approach and thematic analysis. Surveys were collected in participating TARGet Kids! primary care practice sites in Toronto, Canada. Survey respondents included 30 parents of children < 2 years of age, and 30 parents of children 2-5 years of age., Results: 76% of parents with children aged < 2 years and 93% of those with children aged 2-5 years rated their overall experience in being involved in their child's anthropometric measurement as enjoyable or thoroughly enjoyable. Analysis of open-ended survey questions revealed five themes: [1] parent interest in child growth; [2] ease of anthropometric measurement; [3] extended clinic visit; [4] child discomfort; and [5] interest in participating in research., Conclusion: Parents reported a high degree of enjoyment in being involved in their child's anthropometric measurements. Parent participation in anthropometric measurement may improve parental satisfaction with children's primary healthcare. Future research may include assessing the reliability of measurements taken with the support of a parent/caregiver., (© 2023. The Author(s).)

Background: In eliciting utilities to value multiattribute utility instruments, discrete choice experiments (DCEs) administered online are less costly than interviewer-facilitated time tradeoff (TTO) tasks. DCEs capture utilities on a latent scale and are often coupled with a small number of TTO tasks to anchor utilities to the interval scale. Given the costly nature of TTO data, design strategies that maximize value set precision per TTO response are critical., Methods: Under simplifying assumptions, we expressed the mean square prediction error (MSE) of the final value set as a function of the number J of TTO-valued health states and the variance V J of the states' latent utilities. We hypothesized that even when these assumptions do not hold, the MSE 1) decreases as V J increases while holding J fixed and 2) decreases as J increases while holding V J fixed. We used simulation to examine whether there was empirical support for our hypotheses a) assuming an underlying linear relationship between TTO and DCE utilities and b) using published results from the Dutch, US, and Indonesian EQ-5D-5L valuation studies., Results: Simulation set (a) supported the hypotheses, as did simulations parameterized using valuation data from Indonesia, which showed a linear relationship between TTO and DCE utilities. The US and Dutch valuation data showed nonlinear relationships between TTO and DCE utilities and did not support the hypotheses. Specifically, for fixed J , smaller values of V J reduced rather than increased the MSE., Conclusions: Given that, in practice, the underlying relationship between TTO and DCE utilities may be nonlinear, health states for TTO valuation should be placed evenly across the latent utility scale to avoid systematic bias in some regions of the scale., Highlights: Valuation studies may feature a large number of respondents completing discrete choice tasks online, with a smaller number of respondents completing time tradeoff (TTO) tasks to anchor the discrete choice utilities to an interval scale.We show that having each TTO respondent complete multiple tasks rather than a single task improves value set precision.Keeping the total number of TTO respondents and the number of tasks per respondent fixed, having 20 health states directly valued through TTO leads to better predictive precision than valuing 10 health states directly.If DCE latent utilities and TTO utilities follow a perfect linear relationship, choosing the TTO states to be valued by weighting on the 2 ends of the latent utility scale leads to better predictive precision than choosing states evenly across the latent utility scale.Conversely, if DCE latent utilities and TTO utilities do not follow a linear relationship, choosing the states to be valued using TTO evenly across the latent utility scale leads to better predictive precision than weighted selection does.In the context of valuation of the EQ-5D-Y-3L, we recommend valuing 20 or more health states using TTO and placing them evenly across the latent utility scale.

Objectives: In cost-effectiveness analysis of health technologies, health state utilities are needed. They are often elicited with a composite time trade-off (cTTO) method, particularly for the widely used EQ-5D-5L. Unfortunately, cTTO discriminatory power is hindered by (1) respondents' nontrading (NT) of time for quality, (2) censoring of utilities at -1, and (3) poor correlation of negative utilities with state severity. We investigated whether modifying cTTO can mitigate these effects., Methods: We interviewed online 478 students (February to April, 2021) who each valued the same 10 EQ-5D-5L health states in 1 of 3 arms. Arm A used a standard cTTO, expanded with 2 questions to explore reasons for NT and censoring. Arms B and C used a time trade-off with modified alternatives offered to overcome loss aversion, to unify the tasks for positive and negative utilities, and to enable eliciting utilities < -1., Results: In arms B and C, we observed less NT than in A (respectively, 4% and 4% vs 10%), more strictly negative utilities (38% and 40% vs 25%), and more utilities ≤ -1 (18% and 30% vs 10%). The average utility of state 55555 dropped to -2.15 and -2.52 from -0.53. Enabling finer trades in arm A reduced NT by 70%. Arms B and C yielded an intuitive association between negative utilities and state severity. These arms were considered more difficult and resulted in more inconsistencies., Conclusions: The discriminatory power of cTTO can be improved, but it may require increasing the difficulty of the task. The standard cTTO may overestimate the utilities, especially of severe states., (Copyright © 2022 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Health Utilities Preschool (HuPS) was developed to fill the need for a generic preference-based measure (GPM) applicable in early childhood. A GPM has all the properties for higher-order summary measures, such as quality-adjusted life-years, required to inform important policy decisions regarding health and healthcare services., Methods: Development was in accordance with published standards for a GPM, statistical procedures, and modeling. HuPS incorporates key components of 2 existing measurement systems: Health Status Classification System for Preschool Children and Health Utilities Index Mark 3 (HUI3). The study included a series of 4 measurement surveys: definitional, adaptational, quantificational, and evaluational health-related quality of life (HRQL). HuPS measurements were evaluated for reliability, validity, interpretability, and acceptability., Results: Definitional measurements identified 8 Health Status Classification System for Preschool Children attributes in common with HUI3 (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain and discomfort), making the HUI3 scoring equation commensurate with HuPS health states. Adaptational measurements informed the content of attribute-level descriptions (n = 35). Quantificational measurements determined level scoring coefficients. HRQL scoring inter-rater reliability (intraclass correlation coefficient = 0.79) was excellent. Continuity of HRQL scoring with HUI3 was reliable (intraclass correlation coefficient = 0.80, P < .001) and valid (mean absolute difference = 0.016, P = .396)., Conclusions: HuPS is an acceptable, reliable, and valid GPM. HRQL scoring is continuous with HUI3. Continuity expands the applicability of GPM (HUI3) scoring to include subjects as young as 2 years of age. Widespread applications of HuPS would inform important health policy and management decisions as HUI3 does for older subjects., (Copyright © 2022 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Children with autism spectrum disorder (ASD) receive a wide range of services., Aims: To examine the association between behavioural services received by children with ASD between ages 2 and 5 years and outcomes during primary school years., Methods: A total of 414 preschool-aged children diagnosed with ASD were enrolled at five Canadian sites and were assessed within four months of diagnosis (T1), six months later (T2), 12 months later (T3), at school entry (T4), and then annually (T5-T8) to 11 years of age. The association between the receipt of behavioural services during T1 to T3 and T8 outcomes related to adaptive behaviour and behavioural problems was modelled using linear regressions adjusted for immigrant status, family income, child's age at diagnosis, site, sex assigned at birth, and baseline (T1) outcome., Results: Children who received behavioural services during at least one time period from T1 to T3 did not have significantly different outcomes at T8 than children who did not receive any behavioural services., Implications: Pre-school use of behavioural services was not found to affect outcomes during later childhood. Numerous challenges accompany studies of the association between pre-school service use and later outcomes in a heterogeneous ASD sample. Recommendations for study design are provided., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Bayesian adaptive designs for clinical trials have gained popularity in the recent years due to the flexibility and efficiency that they offer. We consider the scenario where the outcome of interest comprises events with relatively low risk of occurrence and different case definitions resulting in varying control group risk assumptions. This is a scenario that occurs frequently for infectious diseases in global health research., Methods: We propose a Bayesian adaptive design that incorporates different case definitions of the outcome of interest that vary in stringency. A set of stopping rules are proposed where superiority and futility may be concluded with respect to different outcome definitions and therefore maintain a realistic probability of stopping in trials with low event rates. Through a simulation study, a variety of stopping rules and design configurations are compared., Results: The simulation results are provided in an interactive web application that allows the user to explore and compare the design operating characteristics for a variety of assumptions and design parameters with respect to different outcome definitions. The results for select simulation scenarios are provided in the article., Discussion: Bayesian adaptive designs offer the potential for maximizing the information learned from the data collected through clinical trials. The proposed design enables monitoring and utilizing multiple composite outcomes based on rare events to optimize the trial design operating characteristics.

Background: Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) have considerable overlap, supporting the need for a dimensional framework that examines neurodevelopmental domains which cross traditional diagnostic boundaries. In the following study, we use factor analysis to deconstruct the ASD-ADHD phenotype into its underlying phenotypic domains and test for measurement invariance across adaptive functioning, age, gender and ASD/ADHD clinical diagnoses., Methods: Participants included children and youth (aged 3-20 years) with a clinical diagnosis of ASD (n = 727) or ADHD (n = 770) for a total of 1,497 participants. Parents of these children completed the Social Communication Questionnaire (SCQ), a measure of autism symptoms, and the Strengths and Weaknesses of ADHD and Normal Behaviour (SWAN) questionnaire, a measure of ADHD symptoms. An exploratory factor analysis (EFA) was performed on combined SCQ and SWAN items. This was followed by a confirmatory factor analysis (CFA) and tests of measurement invariance., Results: EFA revealed a four-factor solution (inattention, hyperactivity/impulsivity, social-communication, and restricted, repetitive, behaviours and interests (RRBI)) and a CFA confirmed good model fit. This solution also showed good model fit across subgroups of interest., Conclusions: Our study shows that a combined ASD-ADHD phenotype is characterized by two latent ASD domains (social communication and RRBIs) and two latent ADHD domains (inattention and hyperactivity/impulsivity). We established measurement invariance of the derived measurement model across adaptive functioning, age, gender and ASD/ADHD diagnoses., (© 2022 Association for Child and Adolescent Mental Health.)

Genome sequencing (GS) outperforms other rare disease diagnostics, but standardized approaches to assessing its clinical utility are limited. This study assessed the validity of the Clinician-reported Genetic testing Utility InDEx (C-GUIDE), a novel tool for assessing the utility of genetic testing from a clinician's perspective, for GS. C-GUIDE ratings were completed for patients who received GS results. For each patient, total C-GUIDE and single item global scores were calculated. Construct validity was assessed using linear regression to determine the association between C-GUIDE total and global item scores and measure the effects of potential explanatory variables. Ratings were completed for 67 pediatric and 36 adult patients. GS indications were neurological for 70.9% and results were diagnostic for 28.2%. When the C-GUIDE assessed primary (PV), secondary (SV), and pharmacogenomic (PGx) variants, on average, a one unit increase in the global item score was associated with an increase of 7.3 in the C-GUIDE score (p < 0.05). Diagnostic results were associated with an increase in C-GUIDE score of 5.0 compared to non-diagnostic results (p < 0.05) and an increase of one SV was associated with an increase of 2.5 (p < 0.05). For children, decreased age of one year was associated with an increase in C-GUIDE score of 0.3 (p < 0.05). Findings provide evidence that C-GUIDE measures the construct of clinical utility in pediatric and adult rare disease populations and is sensitive to changes in utility related to variant type. Quantifying the clinical utility of GS using C-GUIDE can inform efforts to optimize its use in patient care., (© 2022. The Author(s).)