Antibiotic Treatment and Health Care Use in Children and Adolescents With Conjunctivitis.

This cohort study examines ambulatory care revisits and same-day topical antibiotic prescription in insured patients with acute infectious conjunctivitis.

Attitudes, Knowledge, and Risk Perceptions of Patients who Received Elective Genomic Testing as a Clinical Service.

BACKGROUND: Elective genomic testing (EGT) is increasingly available clinically. Limited real world evidence exists about attitudes and knowledge of EGT recipients. METHODS: After web-based education, patients who enrolled in an EGT program at a rural nonprofit healthcare system completed a survey that assessed attitudes, knowledge, and risk perceptions. RESULTS: From August 2020 to April 2022, 5,920 patients completed the survey and received testing. Patients most frequently cited interest in learning their personal disease risks as their primary motivation. Patients most often expected results to guide medication management (74.0%), prevent future disease (70.4%), and provide information about risks to offspring (65.4%). Patients were "very concerned" most frequently about the privacy of genetic information (19.8%) and how well testing predicted disease risks (18.0%). On average, patients answered 6.7 of 11 knowledge items correctly (61.3%). They more often rated their risks for colon and breast cancers as lower rather than higher than the average person, but more often rated their risk for a heart attack as higher rather than lower than the average person (all p<0.001). CONCLUSION: Patients pursued EGT because of the utility expectations, but often misunderstood the test's capabilities.

GSDMB/ORMDL3 Rare/Common Variants Are Associated with Inhaled Corticosteroid Response among Children with Asthma.

Inhaled corticosteroids (ICS) are efficacious in the treatment of asthma, which affects more than 300 million people in the world. While genome-wide association studies have identified genes involved in differential treatment responses to ICS in asthma, few studies have evaluated the effects of combined rare and common variants on ICS response among children with asthma. Among children with asthma treated with ICS with whole exome sequencing (WES) data in the PrecisionLink Biobank (91 White and 20 Black children), we examined the effect and contribution of rare and common variants with hospitalizations or emergency department visits. For 12 regions previously associated with asthma and ICS response (DPP10, FBXL7, NDFIP1, TBXT, GLCCI1, HDAC9, TBXAS1, STAT6, GSDMB/ORMDL3, CRHR1, GNGT2, FCER2), we used the combined sum test for the sequence kernel association test (SKAT) adjusting for age, sex, and BMI and stratified by race. Validation was conducted in the Biorepository and Integrative Genomics (BIG) Initiative (83 White and 134 Black children). Using a Bonferroni threshold for the 12 regions tested (i.e., 0.05/12 = 0.004), GSDMB/ORMDL3 was significantly associated with ICS response for the combined effect of rare and common variants (p-value = 0.003) among White children in the PrecisionLink Biobank and replicated in the BIG Initiative (p-value = 0.02). Using WES data, the combined effect of rare and common variants for GSDMB/ORMDL3 was associated with ICS response among asthmatic children in the PrecisionLink Biobank and replicated in the BIG Initiative. This proof-of-concept study demonstrates the power of biobanks of pediatric real-life populations in asthma genomic investigations.

The Association of Race, Ethnicity, and Insurance Status with the Visual Acuity of Retinoblastoma Survivors in the IRIS® Registry.

PURPOSE: To identify sociodemographic factors associated with the visual outcomes of retinoblastoma survivors. METHODS: Retrospective cohort study using a US-based clinical data registry. All individuals < 18 years of age with a history of retinoblastoma in the Intelligent Research in Sight (IRIS®) Registry (1/1/2013-12/31/2020). The primary outcome was visual acuity below the threshold for legal blindness (20/200 or worse) in at least one eye. Multivariable logistic regression was used to evaluate the association between visual outcomes and age, sex, laterality, race, ethnicity, type of insurance, and geographic location. RESULTS: This analysis included 1545 children with a history of retinoblastoma. The median length of follow-up was 4.1 years (IQR, 2.2-5.9 years) and the median age at most recent clinical visit was 12 years (IQR, 8-16 years). Retinoblastoma was unilateral in 54% of cases. Poor vision in at least one eye was identified in 78% of all children and poor vision in both eyes in 17% of those with bilateral disease. Poor visual outcomes were associated with unilateral diagnosis (OR, 1.55; 95% CI,1.13-2.12; p = .007), Black race (OR, 2.03; 95% CI, 1.19-3.47; p = .010), Hispanic ethnicity (OR, 1.65; 95% CI, 1.16-2.37; p = .006), and non-private insurance (OR, 1.47; 95% CI, 1.02-2.10; p = .037). CONCLUSIONS: Poor visual outcomes appear to be more common among Black, Hispanic, and publicly insured children with a history of retinoblastoma, raising concerns regarding healthcare inequities. Primary care physicians should ensure that young children receive red reflex testing during routine visits and consider retinoblastoma in the differential diagnosis of abnormal eye exams.

Smaller Differences in the Comparative Effectiveness of Biologics in Reducing Asthma-Related Hospitalizations Compared With Overall Exacerbations.

BACKGROUND: Evidence on the comparative effectiveness of respiratory biologics remains sparse. OBJECTIVE: We sought to evaluate the comparative effectiveness of omalizumab, mepolizumab, benralizumab, and dupilumab in a matched retrospective cohort of patients with asthma. METHODS: We identified patients with asthma aged ≥18 years who were incident users of these biologics between November 1, 2018, and June 30, 2023, in administrative claims data from the Food and Drug Administration's Sentinel System and Merative MarketScan Commercial Database. We compared asthma-related exacerbations and hospitalizations in the 12 months since biologic prescription in pairwise comparisons of propensity score-matched cohorts. Covariates used in matching included age, sex, allergic comorbidities, baseline asthma medications use, and the Charlson Comorbidity Index. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using negative binomial regression models. RESULTS: A total of 893 patients on mepolizumab, 1300 on benralizumab, 1170 on omalizumab, and 1863 on dupilumab were identified. The average age was 55 years, and two-thirds of the participants were female. At baseline, over 80% of these individuals had an active prescription for an inhaled corticosteroid. Almost half of patients on dupilumab had concomitant nasal polyposis compared with 6% to 13% of patients on the other biologics. Covariates were balanced after matching. In matched analyses, dupilumab was associated with the lowest incidence of exacerbations over the follow-up period (vs dupilumab): mepolizumab (IRR: 1.36; 95% CI: 1.12, 1.64), omalizumab (IRR: 1.33; 95% CI: 1.13, 1.58), benralizumab (IRR: 1.19; 95% CI: 1.00, 1.41). For exacerbations leading to hospitalizations, benralizumab and mepolizumab were associated with the lowest incidence of hospitalizations, and the greatest difference was between mepolizumab versus dupilumab (IRR: 0.76; 95% CI: 0.56, 1.03). CONCLUSIONS: Dupilumab was associated with the lowest incidence of overall exacerbations, and mepolizumab with the lowest incidence of asthma hospitalizations in this administrative claims-based cohort of individuals with asthma. Despite matching propensity scores, residual confounding, such as baseline eosinophil count, may explain some of these findings.

Machine Learning Prediction of Treatment Response to Inhaled Corticosteroids in Asthma.

BACKGROUND: Although inhaled corticosteroids (ICS) are the first-line therapy for patients with persistent asthma, many patients continue to have exacerbations. We developed machine learning models to predict the ICS response in patients with asthma. METHODS: The subjects included asthma patients of European ancestry (n = 1371; 448 children; 916 adults). A genome-wide association study was performed to identify the SNPs associated with ICS response. Using the SNPs identified, two machine learning models were developed to predict ICS response: (1) least absolute shrinkage and selection operator (LASSO) regression and (2) random forest. RESULTS: The LASSO regression model achieved an AUC of 0.71 (95% CI 0.67-0.76; sensitivity: 0.57; specificity: 0.75) in an independent test cohort, and the random forest model achieved an AUC of 0.74 (95% CI 0.70-0.78; sensitivity: 0.70; specificity: 0.68). The genes contributing to the prediction of ICS response included those associated with ICS responses in asthma (TPSAB1, FBXL16), asthma symptoms and severity (ABCA7, CNN2, PTRN3, and BSG/CD147), airway remodeling (ELANE, FSTL3), mucin production (GAL3ST), leukotriene synthesis (GPX4), allergic asthma (ZFPM1, SBNO2), and others. CONCLUSIONS: An accurate risk prediction of ICS response can be obtained using machine learning methods, with the potential to inform personalized treatment decisions. Further studies are needed to examine if the integration of richer phenotype data could improve risk prediction.

Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting.

CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. In patients initiating antiplatelet therapy for ACS or PCI, we compared medical records data from 67 patients who received CYP2C19 genotyping preemptively (results >7 days before need), against medical records data from 67 propensity score-matched patients who received early genotyping (results within 7 days of need). We also examined data from 140 patients who received late genotyping (results >7 days after need). We compared the impact of genotyping approaches on medication selections, specialty visits, MACE and bleeding events over 1 year. Patients with CYP2C19 loss-of-function alleles were less likely to be initiated on clopidogrel if they received preemptive rather than early or late genotyping (18.2%, 66.7%, and 73.2% respectively, p = 0.001). No differences were observed by genotyping approach in the number of specialty visits or likelihood of MACE or bleeding events (all p > 0.21). Preemptive genotyping had a strong impact on initial antiplatelet selection and a comparable impact on patient outcomes and healthcare utilization, compared to genotyping ordered after a need for antiplatelet therapy had been identified.

Gaps in the Vision Screening Pathway for School-Aged US Children.

This cross-sectional study uses a nationally representative survey of the US pediatric population to identify gaps in the vision screening pathway.

Asthma exacerbations and eosinophilia in the UK Biobank: a genome-wide association study.

Background: Asthma exacerbations reflect disease severity, affect morbidity and mortality, and may lead to declining lung function. Inflammatory endotypes (e.g. T2-high (eosinophilic)) may play a key role in asthma exacerbations. We aimed to assess whether genetic susceptibility underlies asthma exacerbation risk and additionally tested for an interaction between genetic variants and eosinophilia on exacerbation risk. Methods: UK Biobank data were used to perform a genome-wide association study of individuals with asthma and at least one exacerbation compared to individuals with asthma and no history of exacerbations. Individuals with asthma were identified using self-reported data, hospitalisation data and general practitioner records. Exacerbations were identified as either asthma-related hospitalisation, general practitioner record of asthma exacerbation or an oral corticosteroid burst prescription. A logistic regression model adjusted for age, sex, smoking status and genetic ancestry via principal components was used to assess the association between genetic variants and asthma exacerbations. We sought replication for suggestive associations (p<5×10-6) in the GERA cohort. Results: In the UK Biobank, we identified 11 604 cases and 37 890 controls. While no variants reached genome-wide significance (p<5×10-8) in the primary analysis, 116 signals were suggestively significant (p<5×10-6). In GERA, two single nucleotide polymorphisms (rs34643691 and rs149721630) replicated (p<0.05), representing signals near the NTRK3 and ABCA13 genes. Conclusions: Our study has identified reproducible associations with asthma exacerbations in the UK Biobank and GERA cohorts. Confirmation of these findings in different asthma subphenotypes in diverse ancestries and functional investigation will be required to understand their mechanisms of action and potentially inform therapeutic development.

Housing Insecurity and Asthma Outcomes.

Asthma is a chronic respiratory disease with widespread prevalence that affects children, adolescents, and adults. Asthma morbidity and mortality can be exacerbated in the setting of housing insecurity. In this Grand Rounds Review article, we present a case and discuss the implications that housing insecurity has on asthma outcomes in the United States. We then highlight ways in which providers can advocate for patients with asthma and housing insecurity.

Enrollment of Pediatric Patients in COVID-19 Interventional Trials.

This cross-sectional study uses information gathered from ClinicalTrials.gov to assess the inclusion of children in COVID-19 interventional trials conducted in the US.

Association between antenatal corticosteroid treatment and severe adverse events in pregnant women.

BACKGROUND: Antenatal corticosteroids are considered the standard of care for pregnant women at risk for preterm birth, but studies examining their potential risks are scarce. We aimed to estimate the associations of antenatal corticosteroids with three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding, in pregnant women. METHODS: Of 2,157,321 pregnant women, 52,119 at 24 weeks 0/7 days to 36 weeks 6/7 days of gestation were included in this self-controlled case series study during the study period of 2009-2018. We estimated incidence rates of three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding. Conditional Poisson regression was used to calculate incidence rate ratios (IRRs) for comparing incidence rates of the adverse events in each post-treatment period compared to those during the baseline period among pregnant women exposed to a single course of antenatal corticosteroid treatment. RESULTS: Among 52,119 eligible participants who received antenatal corticosteroid treatment, the estimated incidence rates per 1000 person-years were 0.76 (95% confidence interval (CI): 0.69-0.83) for sepsis, 0.31 (95% CI: 0.27-0.36) for heart failure, and 11.57 (95% CI: 11.27-11.87) for gastrointestinal bleeding. The IRRs at 5 ~ 60 days after administration of antenatal corticosteroids were 5.91 (95% CI: 3.10-11.30) for sepsis and 4.45 (95% CI: 2.63-7.55) for heart failure, and 1.26 (95% CI: 1.02-1.55) for gastrointestinal bleeding; and the IRRs for days 61 ~ 180 were 2.00 (95% CI: 1.01-3.96) for sepsis, 3.65 (95% CI: 2.14-6.22) for heart failure, and 1.81 (95% CI: 1.56-2.10) for gastrointestinal bleeding. CONCLUSIONS: This nationwide population-based study suggests that a single course of antenatal corticosteroids is significantly associated with a 1.3- to 5.9-fold increased risk of sepsis, heart failure, and gastrointestinal bleeding in pregnant women. Maternal health considerations, including recommendations for adverse event monitoring, should be included in future guidelines for antenatal corticosteroid treatment.

National Patterns of Outpatient Follow-Up Visits After Emergency Care for Acute Bronchiolitis.

This cohort study examines the frequency of postdischarge follow-up visits among US emergency department encounters for bronchiolitis and assesses whether follow-up was associated with decreased hospital reutilization or increased treatment with nonrecommended medications.

Vision Testing for Adolescents in the US.

Importance: Untreated refractive error contributes to the racial, ethnic, and socioeconomic disparities in visual function of adolescent children in the US. Objective: To describe patterns in vision testing as a function of age among US adolescents and identify sociodemographic factors associated with vision testing. Design, Setting, and Participants: This cross-sectional study used data from the National Survey of Children's Health (2018-2019), a nationally representative survey of the noninstitutionalized US pediatric population. A total of 24 752 adolescent children (aged 12 to <18 years) were included. Data were analyzed from March 22 to August 11, 2023. Main Outcomes and Measures: The primary outcome was the caregiver report of vision testing within the last 12 months. Linear regression was used to describe the patterns in reported vision testing as a function of participant age. Logistic regression was used to describe the association of sociodemographic factors with the report of vision testing in each setting. Results: Among 24 752 adolescents, the median (IQR) age was 14 (13-16) years; 12 918 (weighted, 51%) were male. Vision testing in any setting within the previous year was reported by caregivers of 18 621 adolescents (weighted, 74%). Vision testing was reported to have occurred at an eye clinic in 13 323 participants (weighted, 51%), at a primary care clinic in 5230 participants (weighted, 22%), at a school in 2594 participants (weighted, 11%), and at a health center in 635 participants (weighted, 4%). The percentage of adolescents reported to have vision tested decreased with age (-1.3% per year; 95% CI, -2.5% to 0% per year) due to a decrease in testing in primary care and school settings. After adjusting for age and sex, there were lower odds of vision testing reported for adolescents who were uninsured vs insured (adjusted odds ratio [AOR], 0.81; 95% CI, 0.76-0.87), had caregivers with less than vs greater than high school education (AOR, 0.89; 95% CI, 0.84-0.95), and were from a family born outside vs inside the US (AOR, 0.90; 95% CI, 0.82-0.98). Conclusions and Relevance: In this cross-sectional study, vision testing in adolescents decreased as a function of age due to fewer reported tests performed in primary care and school-based settings. Relative to children in socioeconomically advantaged families, those from disadvantaged families were less likely to report receiving vision testing in clinical settings. Efforts to expand the role of school-based vision testing for older adolescents from disadvantaged backgrounds may enable opportunities to address disparities in untreated refractive error.

Prevalence and prescribing patterns of oral corticosteroids in the United States, Taiwan, and Denmark, 2009-2018.

Oral corticosteroids (OCS) are commonly prescribed for acute, self-limited conditions, despite studies demonstrating toxicity. Studies evaluating longitudinal OCS prescribing in the general population are scarce and do not compare use across countries. This study investigated and compared OCS prescription patterns from 2009 to 2018 in the general populations of the United States, Taiwan, and Denmark. This international population-based longitudinal cohort study used nationwide claims databases (United States: Optum Clinformatics Data Mart; de-identified; Taiwan: National Health Insurance Research Database; and Denmark: National Prescription and Patient Registries/Danish National Patient Registry) to evaluate OCS prescribing. We classified annual OCS duration as short-term (1-29 days), medium-term (30-89 days), or long-term (≥90 days). Longitudinal change in annual prevalence of OCS use and physician prescribing patterns were reported. Among 54,630,437 participants, average annual percentage of overall OCS use was 6.8% in the United States, 17.5% in Taiwan, and 2.2% in Denmark during 2009-2018. Prevalence of OCS prescribing increased at an average annual rate of 0.1%-0.17%, mainly driven by short-term prescribing to healthy adults. One-quarter to one-fifth of OCS prescribing was associated with a diagnosis of respiratory infection. Family practice and internal medicine physicians were among the highest OCS prescribers across countries and durations. Age- and sex-stratified trends mirrored unstratified trends. This study provides real-world evidence of an ongoing steady increase in OCS use in the general populations of the United States, Taiwan, and Denmark. This increase is largely driven by short-term OCS prescribing to healthy adults, a practice previously viewed as safe but recently shown to incur substantial population-level risk.

Utilization and Spending With Preventive Drug Lists for Asthma Medications in High-Deductible Health Plans.

Importance: High-deductible health plans with health savings accounts (HDHP-HSAs) incentivize patients to use less health care, including necessary care. Preventive drug lists (PDLs) exempt high-value medications from the deductible, reducing out-of-pocket cost sharing; the associations of PDLs with health outcomes among patients with asthma is unknown. Objective: To evaluate the associations of a PDL for asthma medications on utilization, adverse outcomes, and patient spending for HDHP-HSA enrollees with asthma. Design, Setting, and Participants: This case-control study used matched groups of patients with asthma before and after an insurance design change using a national commercial health insurance claims data set from 2004-2017. Participants included patients aged 4 to 64 years enrolled for 1 year in an HDHP-HSA without a PDL in which asthma medications were subject to the deductible who then transitioned to an HDHP-HSA with a PDL that included asthma medications; these patients were compared with a matched weighted sample of patients with 2 years of continuous enrollment in an HDHP-HSA without a PDL. Models controlled for patient demographics and asthma severity and were stratified by neighborhood income. Analyses were conducted from October 2020 to June 2023. Exposures: Employer-mandated addition of a PDL that included asthma medications to an existing HDHP-HSA. Main Outcomes and Measures: Outcomes of interest were utilization of asthma medications on the PDL (controllers and albuterol), asthma exacerbations (oral steroid bursts and asthma-related emergency department use), and out-of-pocket spending (all and asthma-specific). Results: A total of 12 174 participants (mean [SD] age, 36.9 [16.9] years; 6848 [56.25%] female) were included in analyses. Compared with no PDL, PDLs were associated with increased rates of 30-day fills per enrollee for any controller medication (change, 0.10 [95% CI, 0.03 to 0.17] fills per enrollee; 12.9% increase) and for combination inhaled corticosteroid long-acting ß2-agonist (ICS-LABA) medications (change, 0.06 [95% CI, 0.01 to 0.10] fills per enrollee; 25.4% increase), and increased proportion of days covered with ICS-LABA (6.0% [0.7% to 11.3%] of days; 15.6% increase). Gaining a PDL was associated with decreased out-of-pocket spending on asthma care (change, -$34 [95% CI, -$47 to -$21] per enrollee; 28.4% difference), but there was no significant change in asthma exacerbations and no difference in results by income. Conclusions and Relevance: In this case-control study, reducing cost-sharing for asthma medications through a PDL was associated with increased adherence to controller medications, notably ICS-LABA medications used by patients with more severe asthma, but was not associated with improved clinical outcomes. These findings suggest that PDLs are a potential strategy to improve access and affordability of asthma care for patients in HDHP-HSAs.