Creating a Multiply Imputed Value Set for the EQ-5D-5L in Canada: State-Level Misspecification Terms Are Needed to Characterize Parameter Uncertainty Correctly.

BACKGROUND: Parameter uncertainty in EQ-5D-5L value sets often exceeds the instrument's minimum important difference, yet this is routinely ignored. Multiple imputation (MI) accounts for parameter uncertainty in the value set; however, no valuation study has implemented this methodology. Our objective was to create a Canadian MI value set for the EQ-5D-5L, thus enabling users to account for parameter uncertainty in the value set. METHODS: Using the Canadian EQ-5D-5L valuation study (N = 1,073), we first refit the original model followed by models with state-level misspecification. Models were compared based on the adequacy of 95% credible interval (CrI) coverage for out-of-sample predictions. Using the best-fitting model, we took 100 draws from the posterior distribution to create 100 imputed value sets. We examined how much the standard error of the estimated mean health utilities increased after accounting for parameter uncertainty in the value set by using the MI and original value sets to score 2 data sets: 1) a sample of 1,208 individuals from the Canadian general public and 2) a sample of 401 women with breast cancer. RESULTS: The selected model with state-level misspecification outperformed the original model (95% CrI coverage: 94.2% v. 11.6%). We observed wider standard errors for the estimated mean utilities on using the MI value set for both the Canadian general public (MI: 0.0091; original: 0.0035) and patients with breast cancer (MI: 0.0169; original: 0.0066). DISCUSSION AND CONCLUSIONS: We provide 1) the first MI value sets for the EQ-5D-5L and 2) code to construct MI value sets while accounting for state-level model misspecification. Our study suggests that ignoring parameter uncertainty in value sets leads to falsely narrow SEs. HIGHLIGHTS: Value sets for health state utility instruments are estimated subject to parameter uncertainty; this parameter uncertainty may exceed the minimum important difference of the instrument, yet it is not fully captured using current methods.This study creates the first multiply imputed value set for a multiattribute utility instrument, the EQ-5D-5L, to fully capture this parameter uncertainty.We apply the multiply imputed value set to 2 data sets from 1) the Canadian general public and 2) women with invasive breast cancer.Scoring the EQ-5D-5L using a multiply imputed value set led to wider standard error estimates, suggesting that the current practice of ignoring parameter uncertainty in the value set leads to falsely low standard errors.Our work will be of interest to methodologists and developers of the EQ-5D-5L and users of the EQ-5D-5L, such as health economists, researchers, and policy makers.

Association of empiric antibiotic selection and clinical outcomes in hospitalised children with severe orbital infections: a retrospective cohort study.

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.

Understanding Canadian stakeholders' views on measuring and valuing health for children and adolescents: a qualitative study.

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.

Recurrent Intensive Care Episodes and Mortality Among Children With Severe Neurologic Impairment.

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.

Disease activity trajectories in juvenile dermatomyositis from childhood to adulthood.

OBJECTIVES: To assess whether there are identifiable subgroups of disease activity trajectory in a population of juvenile dermatomyositis (JDM) patients-followed throughout childhood and into adulthood-and determine factors that predict those trajectory groupings. METHODS: This is a retrospective, longitudinal inception cohort of patients with idiopathic inflammatory myopathies, largely JDM. We sought to identify baseline factors that predict membership into different groups (latent classes) of disease activity trajectory. RESULTS: A total of 172 patients (64% females), with median age at diagnosis of 7.7 years, were analyzed. We studied 4,725 visits (1,471 patient-years). We identified 3 latent classes of longitudinal disease activity, as measured by the modified disease activity score (DASm), with distinct class trajectories predicted by DASm at baseline, and by the changes of DASm from either baseline to 3 months or baseline to 6 months (early response to therapy). In the analysis in which DASm at baseline and the changes of DASm from baseline to 6 months are included as predictors, Class 1 (10%) has persistently high disease activity, Class 2 (34%) is characterized by moderate disease activity, and Class 3 (56%) is characterized by individuals with a high early disease activity but an apparently good response to treatment and long-term low disease activity. CONCLUSION: High early disease activity, and treatment resistance in the first few months, predict a more chronic longitudinal course of JDM.

Characterising the effectiveness of social determinants of health-focused hepatitis B interventions: a systematic review.

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.

A Systematic Review of Methods Used by Pediatric Cost-Utility Analyses to Include Family Spillover Effects.

BACKGROUND: A child's health condition affects family members' health and well-being. However, pediatric cost-utility analysis (CUA) commonly ignores these family spillover effects leading to an incomplete understanding of the cost and benefits of a child's health intervention. Methodological challenges exist in assessing, valuing, and incorporating family spillover effects. OBJECTIVE: This study systematically reviews and compare methods used to include family spillover effects in pediatric CUAs. METHODS: A literature search was conducted in MEDLINE, Embase, EconLit, Cochrane collection, CINAHL, INAHTA, and the Pediatric Economic Database Evaluation (PEDE) database from inception to 2020 to identify pediatric CUAs that included family spillover effects. The search was updated to 2021 using PEDE. The data describing in which family members spillover effects were measured, and how family spillover effects were measured, incorporated, and reported, were extracted. Common approaches were grouped conceptually. Further, this review identified theories or theoretical frameworks used to justify approaches for integrating family spillover effects into CUA. RESULTS: Of 878 pediatric CUAs identified, 35 included family spillover effects. Most pediatric CUAs considered family spillover effects on one family member. Pediatric CUAs reported eight different approaches to measure the family spillover effects. The most common method was measuring the quality-adjusted life years (QALY) loss of the caregiver(s) or parent(s) due to a child's illness or disability using an isolated approach whereby family spillover effects were quantified in individual family members separately from other health effects. Studies used four approaches to integrate family spillover effects into CUA. The most common method was to sum children's and parents/caregivers' QALYs. Only two studies used a theoretical framework for incorporation of family spillover effects. CONCLUSIONS: Few pediatric CUAs included family spillover effects and the observed variation indicated no consensus among researchers on how family spillover effects should be measured and incorporated. This heterogeneity is mirrored by a lack of practical guidelines by Health Technology Assessment (HTA) agencies or a theoretical foundation for including family spillover effects in pediatric CUA. The results from this review may encourage researchers to develop a theoretical framework and HTA agencies to develop guidelines for including family spillover effects. Such guidance may lead to more rigorous and standardized methods for including family spillover effects and better-quality evidence to inform decision-makers on the cost-effectiveness of pediatric health interventions.

Canada population norms for the EQ-5D-5L.

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.

Severe Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 Pandemic.

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.

Assessing the Performance of the Clinician-reported Genetic Testing Utility InDEx (C-GUIDE): Further Evidence of Inter-rater Reliability.

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.

Abscess volume as a predictor of surgical intervention in children hospitalized with orbital cellulitis: A multicentre cohort study.

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.

Is Social Participation Associated with Successful Aging among Older Canadians? Findings from the Canadian Longitudinal Study on Aging (CLSA).

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.

Healthcare costs and outcomes associated with laboratory-confirmed Lyme disease in Ontario, Canada: A population-based cohort study.

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.

Comparison of Preferences and Data Quality between Discrete Choice Experiments Conducted in Online and Face-to-Face Respondents.

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 (F2FS) 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% [F2FS] 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 F2FS, modeled preferences differed. Future analyses are needed to clarify whether differences are attributable to preference or data quality variation between modes of data collection.

Bayesian Models with Spatial Correlation Improve the Precision of EQ-5D-5L Value Sets.

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.

Evaluating the Impact of Ex Vivo Lung Perfusion on Organ Transplantation: A Retrospective Cohort Study.

BACKGROUND: Ex vivo lung perfusion (EVLP) sustains and allows advanced assessment of potentially useable donor lungs before transplantation, potentially relieving resource constraints. OBJECTIVE: We sought to characterize the effect of EVLP on organ utilization and patient outcomes. METHODS: We performed a retrospective, before-after cohort study using linked institutional data sources of adults wait-listed for lung transplant and donor organs transplanted in Ontario, Canada between 2005 and 2019. We regressed the annual number of transplants against year, EVLP use, and organ characteristics. Time-to-transplant, waitlist mortality, primary graft dysfunction, tracheostomy insertion, in-hospital mortality, and chronic lung allograft dysfunction were evaluated using propensity score-weighted regression. RESULTS: EVLP availability ( P =0.01 for interaction) and EVLP use ( P <0.001 for interaction) were both associated with steeper increases in transplantation than expected by historical trends. EVLP was associated with more donation after circulatory death and extended-criteria donors transplanted, while the numbers of standard-criteria donors remained relatively stable. Significantly faster time-to-transplant was observed after EVLP was available (hazard ratio=1.64 [1.41-1.92]; P <0.001). Fewer patients died on the waitlist after EVLP was available, but no difference in the hazard of waitlist mortality was observed (HR=1.19 [0.81-1.74]; P =0.176). We observed no difference in the likelihood of chronic lung allograft dysfunction before versus after EVLP was available. CONCLUSIONS: We observed a significant increase in organ transplantation since EVLP was introduced into practice, predominantly from increased acceptance of donation after circulatory death and extended-criteria lungs. Our findings suggest that EVLP-associated increases in organ availability meaningfully alleviated some barriers to transplant.

Causal inference with longitudinal data subject to irregular assessment times.

Data collected in the context of usual care present a rich source of longitudinal data for research, but often require analyses that simultaneously enable causal inferences from observational data while handling irregular and informative assessment times. An inverse-weighting approach to this was recently proposed, and handles the case where the assessment times are at random (ie, conditionally independent of the outcome process given the observed history). In this paper, we extend the inverse-weighting approach to handle a special case of assessment not at random, where assessment and outcome processes are conditionally independent given past observed covariates and random effects. We use multiple outputation to accomplish the same purpose as inverse-weighting, and apply it to the Liang semi-parametric joint model. Moreover, we develop an alternative joint model that does not require covariates for the outcome model to be known at times where there is no assessment of the outcome. We examine the performance of these methods through simulation and illustrate them through a study of the causal effect of wheezing on time spent playing outdoors among children aged 2-9 years and enrolled in the TargetKids! study.

Parent involvement in child anthropometric measurement.

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.

Variation in the Management of Hospitalized Children With Orbital Cellulitis Over 10 Years.

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.

Efficient Designs for Valuation Studies That Use Time Tradeoff (TTO) Tasks to Map Latent Utilities from Discrete Choice Experiments to the Interval Scale: Selection of Health States for TTO Tasks.

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 VJ of the states' latent utilities. We hypothesized that even when these assumptions do not hold, the MSE 1) decreases as VJ increases while holding J fixed and 2) decreases as J increases while holding VJ 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 VJ 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.