Preferences in Clinical Care of Individuals With Differences of Sex Development.

OBJECTIVES: To identify the most important attributes related to the process of achieving, and outcomes associated with, successful care for differences of sex development (DSD). METHODS: We developed a best-worst scaling survey administered to 520 DSD stakeholders, including individuals or family members of those with DSD, health care specialists, and patient support and advocacy representatives. Fourteen process-related attributes and 16 outcome-related attributes were identified through qualitative research. We estimated relative importance scores and coefficients from regression analysis to understand the relative importance of attributes and conducted latent class analysis to explore heterogeneity in preferences. RESULTS: The 3 most important process attributes were (1) good communication between care team and patient/family, (2) care team educated patient/family about condition, and (3) care team incorporates the values of patient/family. The 3 most important outcome attributes were (1) patient satisfaction, (2) patient mental health, and (3) treatment maintains physical health. Latent class analyses showed that respondents had heterogeneous preferences. For process-related attributes, we identified 3 respondent groups: "Patient autonomy and support" (46% of respondents), "Education and care transitions" (18%), and "Shared decision-making" (36%). For outcome-related attributes, we identified 2 respondent groups: "Preserving function and appearance" (59% of respondents) and "Patient health and satisfaction" (41%). CONCLUSIONS: Outcomes such as patient satisfaction and health were the most important outcome attributes, and good communication and education from the care team were the most important process attributes. Respondents expressed heterogeneous preferences for selected DSD care attributes that providers should consider to improve satisfaction with and quality of DSD care.

A Cost-Effectiveness Analysis of Population-Level Dental Caries Prevention Strategies in US Children.

OBJECTIVE: To improve oral health disparities and outcomes among US children impacted by dental caries, there is a need to understand the cost-effectiveness of a targeted, risk-based versus universal-based approach for caries prevention. METHODS: Health and economic outcomes were simulated in a cohort of 50,000 US children aged 1-18 years, comparing current practice (CP) to risk-based-prevention (RBP) and prevention-for-all (PFA) strategies using health care sector and limited societal perspectives. Prevention included biannual oral health exams and fluoride varnish application, and one-time dental sealant placement. The primary outcome is the cost-effectiveness ratio (ICER), defined as the additional cost per quality-adjusted life year (QALY) gained when comparing each strategy to the next least costly one. RESULTS: For RBP compared to CP, the ICER was US$83,000/QALY from the health care sector perspective; for PFA compared to RBP the ICER was US$154,000/QALY. Using a limited societal perspective that includes caregiver time spent attending dental or medical setting visits, RBP compared to CP yielded a ratio of $119,000/QALY and PFA compared to RBP was $235,000/QALY. Results were most sensitive to changes in the probability of pain from an episode of dental caries, costs for prevention and restoration, and the loss in health-related quality of life due to dental caries pain. Scenario analyses evaluating a reduced intensity of prevention services yielded lower ICERs. CONCLUSION: Using a risk-based approach that identifies and targets children at increased risk for dental caries to guide the delivery of prevention services represents an economic value similar to other pediatric prevention programs.

Estimating Transition Probabilities for Modeling Major Depression in Adolescents by Sex and Race or Ethnicity Combinations in the USA.

OBJECTIVE: About one-fifth of US adolescents experienced major depressive symptoms, but few studies have examined longitudinal trends of adolescents developing depression or recovering by demographic factors. We estimated new transition probability inputs, and then used them in a simulation model to project the epidemiologic burden and trajectory of depression of diverse adolescents by sex and race or ethnicity combinations. METHODS: Transition probabilities were first derived using parametric survival analysis of data from the National Longitudinal Study of Adolescent to Adult Health and then calibrated to cross-sectional data from the National Survey on Drug Use and Health. We developed a cohort state-transition model to simulate age-specific depression outcomes of US adolescents. A hypothetical adolescent cohort was modeled from 12-22 years with annual transitions. Model outcomes included proportions of youth experiencing depression, recovery, or depression-free cases and were reported for a US adolescent population by sex, race or ethnicity, and sex and race or ethnicity combinations. RESULTS: At 22 years of age, approximately 16% of adolescents had depression, 12% were in recovery, and 72% had never developed depression. Depression prevalence peaked around 16-17 years-old. Adolescents of multiracial or other race or ethnicity, White, American Indian or Alaska Native, and Hispanic, Latino, or Spanish descent were more likely to experience depression than other racial or ethnic groups. Depression trajectories generated by the model matched well with historical observational studies by sex and race or ethnicity, except for individuals from American Indian or Alaska Native and multiracial or other race or ethnicity backgrounds. CONCLUSIONS: This study validated new transition probabilities for future use in decision models evaluating adolescent depression policies or interventions. Different sets of transition parameters by demographic factors (sex and race or ethnicity combinations) were generated to support future health equity research, including distributional cost-effectiveness analysis. Further data disaggregated with respect to race, ethnicity, religion, income, geography, gender identity, sexual orientation, and disability would be helpful to project accurate estimates for historically minoritized communities.

Recommendations for Emerging Good Practice and Future Research in Relation to Family and Caregiver Health Spillovers in Health Economic Evaluations: A Report of the SHEER Task Force.

BACKGROUND: Omission of family and caregiver health spillovers from the economic evaluation of healthcare interventions remains common practice. When reported, a high degree of methodological inconsistency in incorporating spillovers has been observed. AIM: To promote emerging good practice, this paper from the Spillovers in Health Economic Evaluation and Research (SHEER) task force aims to provide guidance on the incorporation of family and caregiver health spillovers in cost-effectiveness and cost-utility analysis. SHEER also seeks to inform the basis for a spillover research agenda and future practice. METHODS: A modified nominal group technique was used to reach consensus on a set of recommendations, representative of the views of participating subject-matter experts. Through the structured discussions of the group, as well as on the basis of evidence identified during a review process, recommendations were proposed and voted upon, with voting being held over two rounds. RESULTS: This report describes 11 consensus recommendations for emerging good practice. SHEER advocates for the incorporation of health spillovers into analyses conducted from a healthcare/health payer perspective, and more generally inclusive perspectives such as a societal perspective. Where possible, spillovers related to displaced/foregone activities should be considered, as should the distributional consequences of inclusion. Time horizons ought to be sufficient to capture all relevant impacts. Currently, the collection of primary spillover data is preferred and clear justification should be provided when using secondary data. Transparency and consistency when reporting on the incorporation of health spillovers are crucial. In addition, given that the evidence base relating to health spillovers remains limited and requires much development, 12 avenues for future research are proposed. CONCLUSIONS: Consideration of health spillovers in economic evaluations has been called for by researchers and policymakers alike. Accordingly, it is hoped that the consensus recommendations of SHEER will motivate more widespread incorporation of health spillovers into analyses. The developing nature of spillover research necessitates that this guidance be viewed as an initial roadmap, rather than a strict checklist. Moreover, there is a need for balance between consistency in approach, where valuable in a decision making context, and variation in application, to reflect differing decision maker perspectives and to support innovation.

Preferences and experiences of pediatricians on implementing national guidelines on universal routine screening of adolescents for major depressive disorder: A qualitative study.

BACKGROUND: To explore the preferences of pediatricians for key factors around the implementation of universal routine screening guidelines for major depressive disorder in adolescent patients in a primary care setting. METHOD: Semi-structured qualitative interviews were conducted with U.S. pediatricians. Participants were recruited by convenience sampling and snowball sampling. Qualitive data were summarized using thematic analysis to identify themes relevant to preferences around implementing screening strategies for adolescent patients. Recruitment ended upon reaching thematic saturation when no new themes were revealed. RESULTS: Of the 14 participants, 11 identified as female, 3 male, 10 white, and 4 Asian. Top themes among pediatrician participants were around the screening modality (14/14 participants), screening validity (14/14), time barriers (14/14), and confidentiality barriers (12/14). Less frequently mentioned themes by pediatricians were workplace coordination and logistics (7/14), alternative starting ages for screening (7/14), more frequent screenings than annual screenings (3/14), and additional clinical training regarding depression diagnosis and treatment (2/14). LIMITATIONS: Pool of interviewed participants was limited by diversity in terms of geography, race/ethnicity, or practice settings. CONCLUSIONS: To promote the uptake of universal routine screening of adolescent major depression, pediatricians expressed it was important to address key implementation factors regarding the screening modality, screening validity, time constraints, and confidential care concerns in a primary care delivery context. Findings could be used to inform the development of implementation strategies to facilitate depression screening in primary care. Future research is needed to quantitively assess decisions and tradeoffs that pediatricians make when implementing universal screening to support adolescent mental health.

Evidence and Recommendation for Guanidinoacetate Methyltransferase Deficiency Newborn Screening.

Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine biosynthesis due to pathogenic variants in the GAMT gene that lead to cerebral creatine deficiency and neurotoxic levels of guanidinoacetate. Untreated, GAMT deficiency is associated with hypotonia, significant intellectual disability, limited speech development, recurrent seizures, behavior problems, and involuntary movements. The birth prevalence of GAMT deficiency is likely between 0.5 and 2 per million live births. On the basis of small case series and sibling data, presymptomatic treatment with oral supplements of creatine, ornithine, and sodium benzoate, and a protein-restricted diet to reduce arginine intake, appear to substantially improve health and developmental outcomes. Without newborn screening, diagnosis typically happens after the development of significant impairment, when treatment has limited utility. GAMT deficiency newborn screening can be incorporated into the tandem-mass spectrometry screening that is already routinely used for newborn screening, with about 1 per 100 000 newborns screening positive. After a positive screen, diagnosis is established by finding an elevated guanidinoacetate concentration and low creatine concentration in the blood. Although GAMT deficiency is significantly more rare than other conditions included in newborn screening, the feasibility of screening, the low number of positive results, the relative ease of diagnosis, and the expected benefit of presymptomatic dietary therapy led to a recommendation from the Advisory Committee on Heritable Disorders in Newborns and Children to the Secretary of Health and Human Services that GAMT deficiency be added to the Recommended Uniform Screening Panel. This recommendation was accepted in January 2023.

Cost-effectiveness of routine annual influenza vaccination by age and risk status.

BACKGROUND: The epidemiology of circulating seasonal influenza strains changed following the 2009 pandemic influenza A(H1N1). A universal influenza vaccination recommendation has been implemented and new vaccine types have become available post-2009. The objective of this study was to evaluate the cost-effectiveness of routine annual influenza vaccination in the context of this new evidence. METHODS: A state transition simulation model was constructed to estimate the health and economic outcomes of influenza vaccination compared to no vaccination for hypothetical US cohorts stratified by age and risk status. Model input parameters were derived from multiple sources, including post-2009 vaccine effectiveness data from the US Flu Vaccine Effectiveness Network. The analysis used societal and healthcare sector perspectives and a one-year time horizon, except permanent outcomes were also included. The primary outcome was the incremental cost-effectiveness ratio (ICER) in dollars per quality-adjusted life years (QALYs) gained. RESULTS: Compared to no vaccination, vaccination yielded ICERs lower than $95,000/QALY for all age and risk groups, except for non-high-risk adults 18-49 years ($194,000/QALY). Vaccination was cost-saving for adults ≥50 years at higher risk for influenza-related complications. Results were most sensitive to changes in the probability of influenza illness. Performing the analysis from the healthcare sector perspective, excluding vaccination time costs, delivering vaccinations in lower-cost settings, and including productivity losses improved the cost-effectiveness of vaccination. Sensitivity analysis revealed that vaccination remains below $100,000/QALY for older persons ≥65 years at vaccine effectiveness estimates as low as 4 %. CONCLUSIONS: Cost-effectiveness of influenza vaccination varied by age and risk status and was less than $95,000/QALY for all subgroups, except for non-high-risk working-age adults. Results were sensitive to the probability of influenza illness and vaccination was more favorable under certain scenarios. Vaccination for higher risk subgroups resulted in ICERs below $100,000/QALY even at low levels of vaccine effectiveness or circulating virus.

Preexisting Financial Hardship Among Caregivers of Hospitalized Children.

This cross-sectional study examines preexisting financial hardship among caregivers of hospitalized children.

Developing Criteria for Health Economic Quality Evaluation Tool.

OBJECTIVES: Because existing publication guidelines and checklists have limitations when used to assess the quality of cost-effectiveness analysis, we developed a novel quality assessment tool for cost-effectiveness analyses, differentiating methods and reporting quality and incorporating the relative importance of different quality attributes. METHODS: We defined 15 quality domains from a scoping review and identified 72 methods and reporting quality attributes (36 each). After designing a best-worst scaling survey, we fielded an online survey to researchers and practitioners to estimate the relative importance of the attributes in February 2021. We analyzed the survey data using a sequential conditional logit model. The final tool included 48 quality attributes deemed most important for assessing methods and reporting quality (24 each), accompanied by a free and web-based scoring system. RESULTS: A total of 524 participants completed the methodology section, and 372 completed both methodology and reporting sections. Quality attributes pertaining to the "modeling" and "data inputs and evidence synthesis" domains were deemed most important for methods quality, including "structure of the model reflects the underlying condition and intervention's impact" and "model validation is conducted." Quality attributes pertaining to "modeling" and "Intervention/comparator(s)" domains were considered most important for reporting quality, including "model descriptions are detailed enough for replication." Despite its growing prominence, "equity considerations" were not deemed as important as other quality attributes. CONCLUSIONS: The Criteria for Health Economic Quality Evaluation tool allows users to differentiate methods and reporting as well as quantifies the relative importance of quality attributes. Alongside other considerations, it could help assess and improve the quality of cost-effectiveness evidence to inform value-based decisions.

Eliciting Trade-Offs Between Equity and Efficiency: A Methodological Scoping Review.

OBJECTIVES: To identify differences in the approaches and results of studies that elicit equity-efficiency trade-offs that can inform equity-informative cost-effectiveness analysis for healthcare resource allocation. METHODS: We searched Ovid (Medline), EconLit, and Scopus prior to June 25, 2021. Inclusion criteria were: (1) peer-reviewed or (2) gray literature; (3) published in English; (4) survey-based; (5) parameterized a social welfare function to quantify inequality aversion or (6) elicited a trade-off in equity and efficiency characteristics of health interventions. Exclusion criteria were: (1) studies that did not conduct a trade-off or (2) theoretical studies. We abstracted details on study methods, results, and limitations. Studies were grouped by following approach: (1) social welfare function or (2) preference ranking and distributional weighting. We described findings separately for each approach category. RESULTS: Seventy-seven papers were included, 28 parameterized social welfare functions and 49 were classified as preference ranking and distributional weighting. Study methods were heterogeneous. Studies were conducted across 29 countries. Sample sizes and composition, survey methods and question framing varied. Preferences for equity were mixed. Across both approach categories: 39 studies were classified as clear evidence of inequality aversion; 33 found mixed evidence; and 4 had no evidence of aversion. Evidence of between and within-study heterogeneity was found. Preferences for equity may differ by gender, profession, political ideology, income, and education. CONCLUSIONS: Substantial variability in study methods limit the direct comparability of findings and their use in equity-informed cost-effectiveness analysis. Future researches using representative samples that explore within and between country heterogeneity is needed.

A Discrete Choice Analysis Comparing COVID-19 Vaccination Decisions for Children and Adults.

Importance: COVID-19 vaccination rates in the US remain below optimal levels. Patient preferences for different attributes of vaccine products and the vaccination experience can be important in determining vaccine uptake decisions. Objective: To assess preferences for attributes of adult and pediatric COVID-19 vaccination among US adults. Design, Setting, and Participants: An online survey of a national panel of 1040 US adults was conducted in May and June 2021. A discrete choice analysis was used to measure the relative value of each attribute in the decision to choose a COVID-19 vaccination option for adults or children. Six attributes were used to described hypothetical vaccination options: vaccine effectiveness, mild side effects, rare adverse events, number of doses, time required for vaccination, and regulatory approval. Respondents chose between hypothetical vaccination profiles or no vaccination. Additional survey questions asked about vaccination beliefs, COVID-19 illness experience, COVID-19 risk factors, vaccination status, and opinions about the risk of COVID-19. Exposures: Respondents chose which vaccine profile they would prefer to receive for themselves (or no vaccination). Respondents then considered an identical set of profiles for a hypothetical child aged 0 to 17 years. Main Outcomes and Measures: Relative value of vaccination-related attributes were estimated using Bayesian logit regression. Preference profiles for subgroups were estimated using latent class analyses. Results: A total of 1040 adults (610 [59%] female; 379 participants [36%] with an age of 55 years and older years) responded to the survey. When asked about vaccination choices for themselves, participants indicated that vaccine effectiveness (95% vs 60%) was a significant attribute (ß, 9.59 [95% CrI, 9.20-10.00] vs ß, 0.41 [95% CrI, 0-0.80]). Respondents also preferred fewer rare adverse events (ß, 6.35 [95% CrI, 5.74-6.86), fewer mild side effects (ß, 5.49; 95% CrI, 5.12-5.87), 1 dose (ß, 5.41; 95% CrI, 5.04-5.78), FDA approval (ß, 6.01; 95% CrI, 5.64-6.41), and shorter waiting times (ß, 5.67; 95% CrI, 4.87-6.48). Results were very similar when framing the question as adult or child vaccination, with slightly stronger preference for fewer rare adverse events for children. Latent class analysis revealed 4 groups of respondents: (1) individuals sensitive to safety and regulatory status, (2) individuals sensitive to convenience, (3) individuals who carefully considered all attributes in making their choices, and (4) individuals who rejected the vaccine. Conclusions and Relevance: In this survey study of US adults, the identification of 4 distinct preference groups provides new information to guide communications to support vaccine decision making. In particular, the group that prioritize convenience (less time required for vaccination and fewer doses) may present an opportunity to create actionable strategies to increase vaccination uptake for both adult and pediatric populations.

Evidence and recommendation for mucopolysaccharidosis type II newborn screening in the United States.

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked condition caused by pathogenic variants in the iduronate-2-sulfatase gene. The resulting reduced activity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans that can progressively affect multiple organ systems and impair neurologic development. In 2006, the US Food and Drug Administration approved idursulfase for intravenous enzyme replacement therapy for MPS II. After the data suggesting that early treatment is beneficial became available, 2 states, Illinois and Missouri, implemented MPS II newborn screening. Following a recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children in February 2022, in August 2022, the US Secretary of Health and Human Services added MPS II to the Recommended Uniform Screening Panel, a list of conditions recommended for newborn screening. MPS II was added to the Recommended Uniform Screening Panel after a systematic evidence review reported the accuracy of screening, the benefit of presymptomatic treatment compared with usual case detection, and the feasibility of implementing MPS II newborn screening. This manuscript summarizes the findings of the evidence review that informed the Advisory Committee's decision.

Cost-Effectiveness Analysis of Vaccination With Recombinant Zoster Vaccine Among Hematopoietic Cell Transplant Recipients and Persons With Other Immunocompromising Conditions Aged 19 to 49 Years.

OBJECTIVES: This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. METHODS: Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. RESULTS: Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions. CONCLUSIONS: Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.

Preferences for Sexually Transmitted Infection and Cancer Vaccines in the United States and in China.

OBJECTIVES: This study assessed preferences for hypothetical vaccines for children in 2 large vaccine markets according to how the vaccine-preventable disease is transmitted via a discrete choice experiment. METHODS: Surveys in China (N = 1350) and the United States (N = 1413) were conducted from April to May 2021. The discrete choice experiment included attributes of cost, age at vaccination, transmission mode of the vaccine-preventable disease, and whether the vaccine prevents cancer. Preference utilities were modeled in a Bayesian, multinomial logistic regression model, and respondents were grouped by vaccine preference classification through a latent class analysis. RESULTS: Individuals favored vaccines against diseases with transmission modes other than sexual transmission (vaccine for sexually transmitted infection [STI] vs airborne disease, in the United States, odds ratio 0.71; 95% credible interval 0.64-0.78; in China, odds ratio 0.76; 95% credible interval 0.69-0.84). The latent class analysis revealed 6 classes: vaccine rejecters (19% in the United States and 8% in China), careful deciders (18% and 17%), preferring cancer vaccination (20% and 19%), preferring vaccinating children at older ages (10% and 11%), preferring vaccinating older ages, but indifferent about cancer vaccines (23% and 25%), and preferring vaccinating children at younger ages (10% and 19%). Vaccine rejection was higher with age in the United States versus more vaccine rejection among those at the age of 18 to 24 and ≥ 64 years in China. CONCLUSION: The public had strong preferences against giving their child an STI vaccine, and the class preferring a cancer vaccine was less accepting of an STI vaccine. Overall, this study points to the need for more education about how some STI vaccines could also prevent cancers.

Economic Evaluation Design within the HEAL Prevention Cooperative.

The rapid rise in opioid misuse, disorder, and opioid-involved deaths among older adolescents and young adults is an urgent public health problem. Prevention is a vital part of the nation's response to the opioid crisis, yet preventive interventions for those at risk for opioid misuse and opioid use disorder are scarce. In 2019, the National Institutes of Health (NIH) launched the Preventing Opioid Use Disorder in Older Adolescents and Young Adults cooperative as part of its broader Helping to End Addiction Long-term (HEAL) Initiative ( https://heal.nih.gov/ ). The HEAL Prevention Cooperative (HPC) includes ten research projects funded with the goal of developing effective prevention interventions across various settings (e.g., community, health care, juvenile justice, school) for older adolescent and young adults at risk for opioid misuse and opioid use disorder (OUD). An important component of the HPC is the inclusion of an economic evaluation by nine of these research projects that will provide information on the costs, cost-effectiveness, and sustainability of these interventions. The HPC economic evaluation is integrated into each research project's overall design with start-up costs and ongoing delivery costs collected prospectively using an activity-based costing approach. The primary objectives of the economic evaluation are to estimate the intervention implementation costs to providers, estimate the cost-effectiveness of each intervention for reducing opioid misuse initiation and escalation among youth, and use simulation modeling to estimate the budget impact of broader implementation of the interventions within the various settings over multiple years. The HPC offers an extraordinary opportunity to generate economic evidence for substance use prevention programming, providing policy makers and providers with critical information on the investments needed to start-up prevention interventions, as well as the cost-effectiveness of these interventions relative to alternatives. These data will help demonstrate the valuable role that prevention can play in combating the opioid crisis.

New and Progressive Medical Conditions After Pediatric Sepsis Hospitalization Requiring Critical Care.

Importance: Children commonly experience physical, cognitive, or emotional sequelae after sepsis. However, little is known about the development or progression of medical conditions after pediatric sepsis. Objective: To quantify the development and progression of 4 common conditions in the 6 months after sepsis and to assess whether they differed after hospitalization for sepsis vs nonsepsis among critically ill children. Design, Setting, and Participants: This cohort study of 101 511 children (<19 years) with sepsis or nonsepsis hospitalization used a national administrative claims database (January 1, 2010, to June 30, 2018). Data management and analysis were conducted from April 1, 2020, to July 7, 2022. Exposures: Intensive care unit hospitalization for sepsis vs all-cause intensive care unit hospitalizations, excluding sepsis. Main Outcomes and Measures: Primary outcomes were the development of 4 target conditions (chronic respiratory failure, seizure disorder, supplemental nutritional dependence, and chronic kidney disease) within 6 months of hospital discharge. Secondary outcomes were the progression of the 4 target conditions among children with the condition before hospitalization. Outcomes were identified via diagnostic and procedural codes, durable medical equipment codes, and prescription medications. Differences in the development and the progression of conditions between pediatric patients with sepsis and pediatric patients with nonsepsis who survived intensive care unit hospitalization were assessed using logistic regression with matching weights. Results: A total of 5150 survivors of pediatric sepsis and 96 361 survivors of nonsepsis intensive care unit hospitalizations were identified; 2593 (50.3%) were female. The median age was 9.5 years (IQR, 3-15 years) in the sepsis cohort and 7 years (IQR, 2-13 years) in the nonsepsis cohort. Of the 5150 sepsis survivors, 670 (13.0%) developed a new target condition, and 385 of 1834 (21.0%) with a preexisting target condition had disease progression. A total of 998 of the 5150 survivors (19.4%) had development and/or progression of at least 1 condition. New conditions were more common among sepsis vs nonsepsis hospitalizations (new chronic respiratory failure: 4.6% vs 1.9%; odds ratio [OR], 2.54 [95% CI, 2.19-2.94]; new supplemental nutritional dependence: 7.9% vs 2.7%; OR, 3.17 [95% CI, 2.80-3.59]; and new chronic kidney disease: 1.1% vs 0.6%; OR, 1.65 [95% CI, 1.25-2.19]). New seizure disorder was less common (4.6% vs 6.0%; OR, 0.77 [95% CI, 0.66-0.89]). Progressive supplemental nutritional dependence was more common (1.5% vs 0.5%; OR, 2.95 [95% CI, 1.60-5.42]), progressive epilepsy was less common (33.7% vs 40.6%; OR, 0.74 [95% CI, 0.65-0.86]), and progressive respiratory failure (4.4% vs 3.3%; OR, 1.35 [95% CI, 0.89-2.04]) and progressive chronic kidney disease (7.9% vs 9.2%; OR, 0.84 [95% CI, 0.18-3.91]) were similar among survivors of sepsis vs nonsepsis admitted to an intensive care unit. Conclusions and Relevance: In this national cohort of critically ill children who survived sepsis, 1 in 5 developed or had progression of a condition of interest after sepsis hospitalization, suggesting survivors of pediatric sepsis may benefit from structured follow-up to identify and treat new or worsening medical comorbid conditions.

Usability of NewSTEPs Data for Assessing the Characteristics of Infants with Newborn Screening Disorders.

Most state newborn screening programs in the U.S. currently contribute case data to the Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs). To assess the usability of these data for research, we examined the completeness of key variables, particularly race and ethnicity. Data included 24,129 cases of 34 newborn screening disorders from 45 states available in NewSTEPs as of 31 August 2020. Birth years of cases ranged between 2006 and 2020. Rates of missing data for sex, gestational age, birth weight, and race/ethnicity were 3.8%, 31.7%, 7.0%, and 39.7%, respectively. After excluding 21 states for which ≥50% of cases had missing data on race and/or ethnicity, 16,010 cases from 24 states remained. The disorders with the highest proportions in which cases were recorded as Hispanic ethnicity/any race were methylmalonic acidemia (48.7%) and maple syrup urine disease (45.7%). Analyses indicated that sex and birth weight data in NewSTEPs are reasonably complete, but missing data are common for gestational age and race/ethnicity. Despite this, our analyses revealed several novel associations between race/ethnicity and newborn screening disorders, such as the high burden of maple syrup urine disease among Hispanic patients. This demonstrates the potential usefulness of NewSTEPs for research if investments in higher-quality data are made.

Projected risks and health benefits of vaccination against herpes zoster and related complications in US adults.

The Advisory Committee on Immunization Practices (ACIP) recommends recombinant zoster vaccine (RZV) to prevent against herpes zoster (HZ) and related complications in immunocompetent adults ≥50 y and immunocompromised adults ≥19 y. In 2019, a statistical safety signal for Guillain-Barré syndrome (GBS) following RZV was identified using data from the Vaccine Safety Datalink (VSD). Subsequently, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and collaborators undertook additional analyses using Centers for Medicare & Medicaid Services (CMS) Medicare data to further investigate the potential risk of GBS following RZV. Concurrently, epidemiologic data suggested a potentially elevated risk of GBS following HZ in U.S. adults. Using data from these sources and a published simulation model, this study evaluated the health benefits and risks associated with vaccinating immunocompetent adults ≥50 y with RZV compared to no vaccination. In the base case analysis, RZV vaccination averted 43,000-63,000 cases of HZ, including GBS complications, per million vaccinated per 10-y age cohort compared to 3-6 additional cases of GBS projected following RZV per million vaccinated in the same population. This analysis highlights the projected health benefits of RZV vaccination compared to the relatively low potential risk of GBS following RZV.

Families' healthcare experiences for children with inherited metabolic diseases: protocol for a mixed methods cohort study.

INTRODUCTION: Children with inherited metabolic diseases (IMDs) often have complex and intensive healthcare needs and their families face challenges in receiving high-quality, family centred health services. Improvement in care requires complex interventions involving multiple components and stakeholders, customised to specific care contexts. This study aims to comprehensively understand the healthcare experiences of children with IMDs and their families across Canada. METHODS AND ANALYSIS: A two-stage explanatory sequential mixed methods design will be used. Stage 1: quantitative data on healthcare networks and encounter experiences will be collected from 100 parent/guardians through a care map, 2 baseline questionnaires and 17 weekly diaries over 5-7 months. Care networks will be analysed using social network analysis. Relationships between demographic or clinical variables and ratings of healthcare experiences across a range of family centred care dimensions will be analysed using generalised linear regression. Other quantitative data related to family experiences and healthcare experiences will be summarised descriptively. Ongoing analysis of quantitative data and purposive, maximum variation sampling will inform sample selection for stage 2: a subset of stage 1 participants will participate in one-on-one videoconference interviews to elaborate on the quantitative data regarding care networks and healthcare experiences. Interview data will be analysed thematically. Qualitative and quantitative data will be merged during analysis to arrive at an enhanced understanding of care experiences. Quantitative and qualitative data will be combined and presented narratively using a weaving approach (jointly on a theme-by-theme basis) and visually in a side-by-side joint display. ETHICS AND DISSEMINATION: The study protocol and procedures were approved by the Children's Hospital of Eastern Ontario's Research Ethics Board, the University of Ottawa Research Ethics Board and the research ethics boards of each participating study centre. Findings will be published in peer-reviewed journals and presented at scientific conferences.