Guideline-Concordant Antiviral Treatment in Children at High Risk for Influenza Complications.

BACKGROUND: National guidelines recommend antiviral treatment for children with influenza at high risk for complications regardless of symptom duration. Little is known about concordance of clinical practice with this recommendation. METHODS: We performed a cross-sectional study of outpatient children (aged 1-18 years) at high risk for complications who were diagnosed with influenza during the 2016-2019 influenza seasons. High-risk status was determined using an existing definition that includes age, comorbidities, and residence in a long-term care facility. The primary outcome was influenza antiviral dispensing within 2 days of influenza diagnosis. We determined patient- and provider-level factors associated with guideline-concordant treatment using multivariable logistic regression. RESULTS: Of the 274 213 children with influenza at high risk for influenza complications, 159 350 (58.1%) received antiviral treatment. Antiviral treatment was associated with the presence of asthma (aOR, 1.13; 95% confidence interval [CI], 1.11-1.16), immunosuppression (aOR, 1.10; 95% CI, 1.05-1.16), complex chronic conditions (aOR, 1.04; 95% CI, 1.01-1.07), and index encounter in the urgent care setting (aOR, 1.3; 95% CI, 1.26-1.34). Factors associated with decreased odds of antiviral treatment include age 2-5 years compared with 6-17 years (aOR, 0.95; 95% CI, .93-.97), residing in a chronic care facility (aOR, .61; 95% CI, .46-.81), and index encounter in an emergency department (aOR, 0.66; 95% CI, .63-.71). CONCLUSIONS: Among children with influenza at high risk for complications, 42% did not receive guideline-concordant antiviral treatment. Further study is needed to elucidate barriers to appropriate use of antivirals in this vulnerable population.

Association of Race/Ethnicity and Social Determinants with Rehospitalization for Mental Health Conditions at Acute Care Children's Hospitals.

OBJECTIVE: To evaluate associations of race/ethnicity and social determinants with 90-day rehospitalization for mental health conditions to acute care nonpsychiatric children's hospitals. STUDY DESIGN: We conducted a retrospective cohort analysis of mental health hospitalizations for children aged 5-18 years from 2016 to 2018 at 32 freestanding US children's hospitals using the Children's Hospital Association's Pediatric Health Information System database to assess the association of race/ethnicity and social determinants (insurance payer, neighborhood median household income, and rurality of patient home location) with 90-day rehospitalization. Risk factors for rehospitalization were modeled using mixed-effects multivariable logistic regression. RESULTS: Among 23 556 index hospitalizations, there were 1382 mental health rehospitalizations (5.9%) within 90 days. Non-Hispanic Black children were 26% more likely to be rehospitalized than non-Hispanic White children (aOR 1.26, 95% CI 1.08-1.48). Those with government insurance were 18% more likely to be rehospitalized than those with private insurance (aOR 1.18, 95% CI 1.04-1.34). In contrast, those living in a suburban location were 22% less likely to be rehospitalized than those living in an urban location (suburban: aOR 0.78, 95% CI 0.63-0.97). CONCLUSIONS: Non-Hispanic Black children and those with public insurance were at greatest risk for 90-day rehospitalization, and risk was lower in those residing in suburban locations. Future work should focus on upstream interventions that will best attenuate social disparities to promote equity in pediatric mental healthcare.

Prevalence, Risk Factors, and Outcomes of Influenza-Associated Neurologic Complications in Children.

OBJECTIVE: To determine the frequency of neurologic complications associated with influenza in hospitalized children. STUD DESIGN: We performed a cross-sectional study of children (2 months through 17 years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression. RESULTS: Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2). CONCLUSIONS: Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations.

Impact of multimorbidity subgroups on the health care use of early pediatric cancer survivors.

BACKGROUND: Although pediatric cancer survivors in the United States are at an increased risk of developing chronic conditions, to the authors' knowledge there is limited information regarding the types and combinations of conditions they experience in the years immediately after the completion of cancer therapy. METHODS: An observational cohort study of early pediatric cancer survivors (children who were ≥2 years from the end of therapy and aged ≤18 years) was conducted using the Truven Health MarketScan (r) Commercial Claims and Encounters database (2009-2014). Latent class analysis was used to identify comorbidity groups among the subset with ≥2 conditions. Group-level health care use was compared with survivors without chronic conditions using multivariate regression. RESULTS: A total of 3687 early survivors were identified, of whom approximately 41.2% had no chronic conditions, 22.5% had 1 chronic condition, and 36.3% had ≥2 chronic conditions. Among those with ≥2 chronic conditions, 5 groups emerged: 1) general pediatric morbidity (35.4%); 2) central nervous system (CNS) (22.4%); 3) mental health conditions (22.2%); 4) endocrine (26.2%); and 5) CNS with endocrine (3.8%). The CNS group experienced the highest expenditures, at $17,964 more per year (95% CI, $1446-$34,482) compared with survivors without chronic conditions. The CNS group also had the highest odds of an emergency department visit (adjusted odds ratio, 1.71; 95% CI, 1.15-2.56). The endocrine group had the highest odds of hospitalization (odds ratio, 2.29; 95% CI, 1.24-4.22). CONCLUSIONS: Multimorbidity is common among pediatric cancer survivors. The current study identified 5 distinct comorbidity subgroups, all of which experienced high, yet differential, rates of health care use. The results of the current study highlight the complex health care needs of early survivors and provide evidence for the design of targeted survivorship services and interventions.

Children with reported penicillin allergy: Public health impact and safety of delabeling.

OBJECTIVE: To review the relevant literature related to children with reported penicillin allergy and highlight the different ways in which children could be delabeled and to evaluate the public health impact that a penicillin allergy has for children. DATA SOURCES: Data for this review were obtained via PubMed searches and then retrieval of articles from their respective journals for further review. STUDY SELECTIONS: Studies regarding the safety of different ways to evaluate penicillin allergy in children were identified via PubMed searches. Any study that reported different ways of testing (3-tier, direct oral challenge, 5-day oral challenges) were included. This same format was used when selecting relevant articg:les related to the costs, prescription patterns, and stewardship trends associated with a penicillin allergy label. RESULTS: This review found that penicillin allergy testing is a safe and effective way to delabel those with reported allergy. In children with low-risk allergy symptoms, a direct oral challenge approach may be optimal. In those children with a history of high-risk allergy symptoms, a 3-tiered approach is ideal. The review also found that there is a significant cost associated with reported penicillin allergy and that there are increased negative health benefits to those children with reported allergy. CONCLUSION: Penicillin allergy is overdiagnosed, often incorrectly, and the label is frequently first applied during childhood. Targeting children for the removal of the incorrect penicillin allergy label provides a mechanism to reduce the use of broader-spectrum and less effective antibiotics.

Multimorbidity and healthcare utilization among early survivors of pediatric cancer.

Early survivors of pediatric cancer are at increased risk of experiencing chronic conditions; however, little is known about the morbidity burden in this population. In this observational cohort study of commercially insured pediatric cancer survivors in the United States (2009-2014), we find that 22.5% of survivors had one chronic condition, and 36.3% had multiple. Compared with survivors without chronic conditions, the presence of multiple conditions significantly increased the odds of an emergency department visit by 70% (odds ratios [OR], 1.7; 95% confidence interval [CI], 1.4-2.1) and of a hospitalization almost four-fold (OR, 3.8; 95% CI], 2.5-5.5). Findings are important for informing pediatric survivorship care plans in the years following completion of therapy.

Impact of Discharge Components on Readmission Rates for Children Hospitalized with Asthma.

OBJECTIVES: To describe hospital-based asthma-specific discharge components at children's hospitals and determine the association of these discharge components with pediatric asthma readmission rates. STUDY DESIGN: This is a multicenter retrospective cohort study of pediatric asthma hospitalizations in 2015 at children's hospitals participating in the Pediatric Health Information System. Children ages 5 to 17 years were included. An electronic survey assessing 13 asthma-specific discharge components was sent to quality leaders at all 49 hospitals. Correlations of combinations of asthma-specific discharge components and adjusted readmission rates were calculated. RESULTS: The survey response rate was 92% (45 of 49 hospitals). Thirty-day and 3-month adjusted readmission rates varied across hospitals, ranging from 1.9% to 3.9% for 30-day readmissions and 5.7% to 9.1% for 3-month readmissions. No individual or combination discharge components were associated with lower 30-day adjusted readmission rates. The only single-component significantly associated with a lower rate of readmission at 3 months was having comprehensive content of education (P < .029). Increasing intensity of discharge components in bundles was associated with reduced adjusted 3-month readmission rates, but this did not reach statistical significance. This was seen in a 2-discharge component bundle including content of education and communication with the primary medical doctor, as well as a 3-discharge component bundle, which included content of education, medications in-hand, and home-based environmental mitigation. CONCLUSIONS: Children's hospitals demonstrate a range of asthma-specific discharge components. Although we found no significant associations for specific hospital-level discharge components and asthma readmission rates at 30 days, certain combinations of discharge components may support hospitals to reduce healthcare utilization at 3 months.

The Relationship Between Oseltamivir and Suicide in Pediatric Patients.

PURPOSE: Studies examining the association between use of oseltamivir and neuropsychiatric events (including suicide) among children have had mixed findings and have been limited by small sample size, reliance on older data, and potential confounding. We undertook an analysis that addresses these limitations. METHODS: Using a national administrative claims database and a case-crossover design that minimized confounding, we analyzed data from 5 contemporary influenza seasons (2009-2013) for individuals aged 1 to 18 years and ascertained oseltamivir exposure from pharmacy dispensing. RESULTS: We identified 21,407 suicide-related events during this study period, 251 of which were in oseltamivir-exposed children. In case-crossover analysis, we did not find any significant association with suicide either for oseltamivir exposure (odds ratio = 0.64; 95% CI, 0.39-1.00; P = .05) or for influenza diagnosis alone (odds ratio = 0.63; 95% CI, 0.34-1.08; P = .10). CONCLUSION: Our findings suggest that oseltamivir does not increase risk of suicide in the pediatric population.

Incidence, outcomes, and resource use in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND/OBJECTIVES: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions, typically to drugs or infection. The incidence and outcomes of these conditions in children are unknown. The objective of this study was to report the overall burden of Stevens-Johnson syndrome and toxic epidermal necrolysis in children in the United States. METHODS: We performed a retrospective cohort analysis of children and adolescents younger than 18 years of age using the 2009 and 2012 Kids' Inpatient Database. RESULTS: We identified 1486 children and adolescents hospitalized with a diagnosis of Stevens-Johnson syndrome or toxic epidermal necrolysis. The national incidence per 100 000 was 6.3 for Stevens-Johnson syndrome, 0.7 for Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome, and 0.5 for toxic epidermal necrolysis. The highest incidence in children was in those aged 11-15 years (38.4 per 100 000). Toxic epidermal necrolysis and Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome were associated with longer stay, greater mortality, and higher hospital charges than those with Stevens-Johnson syndrome. Hospital mortality was highest in children with toxic epidermal necrolysis and in children aged 0-5 years. CONCLUSIONS: The incidence of Stevens-Johnson syndrome and toxic epidermal necrolysis in children is higher than reported in adults, and there are significant age-based variations in incidence and outcomes across the pediatric population. Further study is needed to determine the most effective treatment strategies to reduce costs and improve outcomes in children hospitalized with severe cutaneous reactions.

Evans Syndrome Secondary to Common Variable Immune Deficiency.

Evans syndrome is an underdiagnosed condition consisting of simultaneous or sequential combination of autoimmune hemolytic anemia and immune-mediated thrombocytopenia. We report a case of severe Evans syndrome presenting as altered mental status, a rare presenting sign of the disease. This case highlights the difficulty in diagnosing Evans syndrome and provides a review of the literature and management strategies for treating the disorder.

Preferential star strand biogenesis of pre-miR-24-2 targets PKC-alpha and suppresses cell survival in MCF-7 breast cancer cells.

microRNAs (miRNA) are regulators of cellular pathways and alterations of normal miRNA expression levels have been shown to increase tumorigenesis. miR-24 has been demonstrated as having both tumor suppressive and oncogenic properties depending on cell context. Here, we demonstrate a possible role for pre-miR-24-2 as a tumor suppressor in the MCF-7 breast cancer cell line through the preferential processing of mature miR-24-2* over miR-24. Specifically, we show that the ectopic expression of miR-24-2* in MCF-7 breast cancer cells results in a suppression of cellular survival both in vivo and in vitro. Notably, the overexpression of miR-24-2* results in a dampening of cell survival through the targeted suppression of PKCα. In addition, a similar biological change is observed in vivo where MCF-7 cells overexpressing pre-miR-24-2 have decreased tumorigenicity and tumor incidence. Taken together our data demonstrate that when overexpressed biogenesis of the pre-miR-24-2 favors miR-24-2* in the MCF-7 breast cancer cell line and suggests a tumor suppressive role for miR-24-2* observed through the inhibition of PKCα-mediated cellular survival.

3-Ketone-4,6-diene ceramide analogs exclusively induce apoptosis in chemo-resistant cancer cells.

Multidrug-resistance is a major cause of cancer chemotherapy failure in clinical treatment. Evidence shows that multidrug-resistant cancer cells are as sensitive as corresponding regular cancer cells under the exposure to anticancer ceramide analogs. In this work we designed five new ceramide analogs with different backbones, in order to test the hypothesis that extending the conjugated system in ceramide analogs would lead to an increase of their anticancer activity and selectivity towards resistant cancer cells. The analogs with the 3-ketone-4,6-diene backbone show the highest apoptosis-inducing efficacy. The most potent compound, analog 406, possesses higher pro-apoptotic activity in chemo-resistant cell lines MCF-7TN-R and NCI/ADR-RES than the corresponding chemo-sensitive cell lines MCF-7 and OVCAR-8, respectively. However, this compound shows the same potency in inhibiting the growth of another pair of chemo-sensitive and chemo-resistant cancer cells, MCF-7 and MCF-7/Dox. Mechanism investigations indicate that analog 406 can induce apoptosis in chemo-resistant cancer cells through the mitochondrial pathway. Cellular glucosylceramide synthase assay shows that analog 406 does not interrupt glucosylceramide synthase in chemo-resistant cancer cell NCI/ADR-RES. These findings suggest that due to certain intrinsic properties, ceramide analogs' pro-apoptotic activity is not disrupted by the normal drug-resistance mechanisms, leading to their potential use for overcoming cancer multidrug-resistance.

Major Drug-Drug Interaction Exposure Among Medicaid-Insured Children in the Outpatient Setting.

BACKGROUND AND OBJECTIVES: Drug-drug interactions (DDIs) can cause adverse drug events, but little is known about DDI exposure in children in the outpatient setting. This study aimed to determine the prevalence of major DDI exposure and factors associated with higher DDI exposure rates among children in an outpatient setting. METHODS: We performed a cross-sectional study of children aged 0 to 18 years with ≥1 ambulatory encounter, and ≥2 dispensed outpatient prescriptions study using the 2019 Marketscan Medicaid database. DDIs (exposure to a major DDI for ≥1 day) and the adverse physiologic effects of each DDI were identified using DrugBank's interaction database. Primary outcomes included the prevalence and rate of major DDI exposure. We used logistic regression to assess patient characteristics associated with DDI exposure. We examined the rate of DDI exposures per 100 children by adverse physiologic effects category, and organ-level effects (eg, heart rate-corrected QT interval prolongation). RESULTS: Of 781 019 children with ≥2 medication exposures, 21.4% experienced ≥1 major DDI exposure. The odds of DDI exposure increased with age and with medical and mental health complexity. Frequently implicated drugs included: Clonidine, psychiatric medications, and asthma medications. The highest adverse physiologic effect exposure rate per 100 children included: Increased drug concentrations (14.6), central nervous system depression (13.6), and heart rate-corrected QT interval prolongation (9.9). CONCLUSIONS: One in 5 Medicaid-insured children with ≥2 prescription medications were exposed to major DDIs annually, with higher exposures in those with medical or mental health complexity. DDI exposure places children at risk for negative health outcomes and adverse drug events, especially in the harder-to-monitor outpatient setting.

Incidence of Influenza-associated Neurologic and Psychiatric Complications Requiring Hospitalization in Children Ages 5-17 Years.

BACKGROUND: The spectrum and incidence of influenza-associated neuropsychiatric complications are not well-characterized. The objective of this study was to define the incidence of specific neurologic and psychiatric complications associated with influenza in children and adolescents. METHODS: We assembled a retrospective cohort of children 5-17 years of age with an outpatient or emergency department International Classification of Diseases, 10th revision influenza diagnosis and enrolled in Tennessee Medicaid from 2016 to 2020. Serious neurologic or psychiatric complications requiring hospitalization were identified using a validated algorithm. Incidence rates of complications were expressed per 100,000 person-weeks of influenza and 95% confidence intervals (CIs) were reported. RESULTS: A total of 156,611 influenza encounters (median age of 9.3 years) were included. The overall incidence of neurologic complications was 30.5 (95% CI: 24.0-38.6) per 100,000 person-weeks of influenza and 1880.9 (95% CI: 971.9-3285.5) among children with an underlying neurologic comorbidity. The distribution of antiviral treatment was similar among those with and without neurologic or psychiatric complications. The overall incidence of psychiatric complications was 20.2 (95% CI: 15.1-27.0) per 100,000 person-weeks of influenza and 111.8 (95% CI: 77.9-155.5) among children with an underlying psychiatric comorbidity. Seizures (17.5, 95% CI: 12.8-23.9) were the most common neurologic complications whereas encephalitis (0.5, 95% CI: 0.02-2.5) was rare. Mood disorders (17.5, 95% CI: 12.8-23.9) were the most frequent psychiatric complications and self-harm events (0.9, 95% CI: 0.3-3.3) were the least common. DISCUSSION: Our findings reveal that the incidence of neuropsychiatric complications of influenza is overall low; however, the incidence among children with underlying neurologic or psychiatric condition is significantly higher than among children without these conditions.

Disparities in Pharmacologic Restraint for Children Hospitalized in Mental Health Crisis.

BACKGROUND AND OBJECTIVES: Children hospitalized with a mental health crisis often receive pharmacologic restraint for management of acute agitation. We examined associations between pharmacologic restraint use and race and ethnicity among children admitted for mental health conditions to acute care nonpsychiatric children's hospitals. METHODS: We performed a retrospective cohort study of children (aged 5-≤18 years) admitted for a primary mental health condition from 2018 to 2022 at 41 US children's hospitals. Pharmacologic restraint use was defined as parenteral administration of medications for acute agitation. The association of race and ethnicity and pharmacologic restraint was assessed using generalized linear multivariable mixed models adjusted for clinical and demographic factors. Stratified analyses were performed based on significant interaction analyses between covariates and race and ethnicity. RESULTS: The cohort included 61 503 hospitalizations. Compared with non-Hispanic Black children, children of non-Hispanic White (adjusted odds ratio [aOR], 0.81; 95% confidence interval [CI], 0.72-0.92), Asian (aOR, 0.82; 95% CI, 0.68-0.99), or other race and ethnicity (aOR, 0.68; 95% CI, 0.57-0.82) were less likely to receive pharmacologic restraint. There was no significant difference with Hispanic children. When stratified by sex, racial/ethnic differences were magnified in males (aORs, 0.49-0.68), except for Hispanic males, and not found in females (aORs, 0.83-0.93). Sensitivity analysis revealed amplified disparities for all racial/ethnic groups, including Hispanic youth (aOR, 0.65; 95% CI, 0.47-0.91). CONCLUSIONS: Non-Hispanic Black children were significantly more likely to receive pharmacologic restraint. More research is needed to understand reasons for these disparities, which may be secondary to implicit bias and systemic and interpersonal racism.

Intravenous antibiotics for urinary tract infections in children with neurologic impairment.

BACKGROUND: Children with high-intensity neurologic impairment (HINI) have an increased risk of urinary tract infection (UTI) and prolonged intravenous (IV) antibiotic exposure. OBJECTIVE: To determine the association between short (≤3 days) and long (>3 days) IV antibiotic courses and UTI treatment failure in hospitalized children with HINI. METHODS: We performed a retrospective cohort study examining UTI hospitalizations at 49 hospitals in the Pediatric Health Information System from 2016 to 2021 for children (1-18 years) with HINI. The primary outcome was UTI readmission within 30 days. Our secondary outcome was the association of hospital-level variation in short IV antibiotic course use with readmission. Readmission rates were compared between short and long courses using multivariable regression. RESULTS: Of 5612 hospitalizations, 3840 (68.4%) had short IV antibiotic courses. In our adjusted model, children with short IV courses were less likely than with long courses to have a 30-day UTI readmission (4.0%, 95% CI [3.6%, 4.5%] vs. 6.3%, 95% CI [5.1%, 7.8%]). Despite marked hospital-level variation in short IV course use (50.0%-87.5% of hospitalizations), there was no correlation with readmissions. CONCLUSIONS: Children with HINI hospitalized with UTI had low UTI readmission rates, but those who received long IV antibiotic courses were more likely to experience UTI readmission versus those receiving short courses. While residual confounding may influence our results, we did not find that short IV courses impacted readmission at the hospital level despite variation in use across institutions. Long IV antibiotic courses are associated with risks and may not confer benefit in this population.

Opportunities for Pharmacogenetic Testing to Guide Dosing of Medications in Youths With Medicaid.

Importance: There are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement. Objectives: To investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug. Design, Setting, and Participants: This serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to 17 years in the Marketscan Medicaid database. Data were analyzed from August to December 2022. Main Outcomes and Measures: PGx drugs were defined as any medication with level A evidence as determined by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The number of unique youths dispensed each PGx drug in each year was determined. PGx drugs were grouped by their associated genes for which there was CPIC level A evidence to guide dosing, and a dispensing rate (No. of PGx drugs/100 000 youths) was determined for each group for the year 2019. Demographics were compared between youths dispensed at least 1 PGx drug and those not dispensed any PGx drugs. Results: The number of Medicaid-insured youths queried ranged by year from 2 078 683 youths in 2011 to 4 641 494 youths in 2017, including 4 126 349 youths (median [IQR] age, 9 [5-13] years; 2 129 926 males [51.6%]) in 2019. The proportion of Medicaid-insured youths dispensed PGx drugs increased from 289 709 youths (13.9%; 95% CI, 13.8%-14.0%) in 2011 to 740 072 youths (17.9%; 95% CI, 17.9%-18.0%) in 2019. Genes associated with the most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 8731.5 drugs [95% CI, 8702.5-8759.5 drugs], and 3426.8 drugs [95% CI, 3408.1-3443.9 drugs] per 100 000 youths, respectively). There was a higher percentage of youths with at least 1 chronic medical condition among youths dispensed at least 1 PGx drug (510 445 youths [69.0%; 95% CI, 68.8%-69.1%]) than among 3 386 277 youths dispensed no PGx drug (1 381 544 youths [40.8%; 95% CI, 40.7%-40.9%) (P < .001) in 2019. Conclusions and Relevance: In this study, there was an increasing prevalence of dispensings for PGx drugs. This finding suggests that pharmacogenetic testing of specific drug-gene pairs should be considered for frequently prescribed PGx drugs and their implicated genes.

Prognostic clinical decision support for pneumonia in the emergency department: A randomized trial.

BACKGROUND: Hospitalization rates for childhood pneumonia vary widely. Risk-based clinical decision support (CDS) interventions may reduce unwarranted variation. METHODS: We conducted a pragmatic randomized trial in two US pediatric emergency departments (EDs) comparing electronic health record (EHR)-integrated prognostic CDS versus usual care for promoting appropriate ED disposition in children (<18 years) with pneumonia. Encounters were randomized 1:1 to usual care versus custom CDS featuring a validated pneumonia severity score predicting risk for severe in-hospital outcomes. Clinicians retained full decision-making authority. The primary outcome was inappropriate ED disposition, defined as early transition to lower- or higher-level care. Safety and implementation outcomes were also evaluated. RESULTS: The study enrolled 536 encounters (269 usual care and 267 CDS). Baseline characteristics were similar across arms. Inappropriate disposition occurred in 3% of usual care encounters and 2% of CDS encounters (adjusted odds ratio: 0.99, 95% confidence interval: [0.32, 2.95]) Length of stay was also similar and adverse safety outcomes were uncommon in both arms. The tool's custom user interface and content were viewed as strengths by surveyed clinicians (>70% satisfied). Implementation barriers include intrinsic (e.g., reaching the right person at the right time) and extrinsic factors (i.e., global pandemic). CONCLUSIONS: EHR-based prognostic CDS did not improve ED disposition decisions for children with pneumonia. Although the intervention's content was favorably received, low subject accrual and workflow integration problems likely limited effectiveness. Clinical Trials Registration: NCT06033079.

Accuracy of Influenza ICD-10 Diagnosis Codes in Identifying Influenza Illness in Children.

Importance: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown. Objective: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings. Design, Setting, and Participants: Children younger than 18 years presenting to the ED or inpatient settings with fever and/or respiratory symptoms at 7 US pediatric medical centers affiliated with the Centers for Disease Control and Prevention-sponsored New Vaccine Surveillance Network from December 1, 2016, to March 31, 2020, were included in this cohort study. Nasal and/or throat swabs were collected for research molecular testing for influenza, regardless of clinical testing. Data, including ICD-10 discharge diagnoses and clinical testing for influenza, were obtained through medical record review. Data analysis was performed in August 2023. Main Outcomes and Measures: The accuracy of ICD-10-coded discharge diagnoses was characterized using molecular clinical or research laboratory test results as reference. Measures included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Estimates were stratified by setting (ED vs inpatient) and age (0-1, 2-4, and 5-17 years). Results: A total of 16 867 children in the ED (median [IQR] age, 2.0 [0.0-4.0] years; 9304 boys [55.2%]) and 17 060 inpatients (median [IQR] age, 1.0 [0.0-4.0] years; 9798 boys [57.4%]) were included. In the ED, ICD-10 influenza diagnoses were highly specific (98.0%; 95% CI, 97.8%-98.3%), with high PPV (88.6%; 95% CI, 88.0%-89.2%) and high NPV (85.9%; 95% CI, 85.3%-86.6%), but sensitivity was lower (48.6%; 95% CI, 47.6%-49.5%). Among inpatients, specificity was 98.2% (95% CI, 98.0%-98.5%), PPV was 82.8% (95% CI, 82.1%-83.5%), sensitivity was 70.7% (95% CI, 69.8%-71.5%), and NPV was 96.5% (95% CI, 96.2%-96.9%). Accuracy of ICD-10 diagnoses varied by patient age, influenza season definition, time between disease onset and testing, and clinical setting. Conclusions and Relevance: In this large cohort study, influenza ICD-10 discharge diagnoses were highly specific but moderately sensitive in identifying laboratory-confirmed influenza; the accuracy of influenza diagnoses varied by clinical and epidemiological factors. In the ED and inpatient settings, an ICD-10 diagnosis likely represents a true-positive influenza case.