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.

A coordinated approach for managing polypharmacy among children with medical complexity: rationale and design of the Pediatric Medication Therapy Management (pMTM) randomized controlled trial.

BACKGROUND: Children with medical complexity (CMC) often rely upon the use of multiple medications to sustain quality of life and control substantial symptom burden. Pediatric polypharmacy (≥ 5 concurrent medications) is prevalent and increases the risk of medication-related problems (MRPs). Although MRPs are associated with pediatric morbidity and healthcare utilization, polypharmacy is infrequently assessed during routine clinical care for CMC. The aim of this randomized controlled trial is to determine if a structured pharmacist-led Pediatric Medication Therapy Management (pMTM) intervention reduces MRP counts, as well as the secondary outcomes of symptom burden and acute healthcare utilization. METHODS: This is a hybrid type 2 randomized controlled trial assessing the effectiveness of pMTM compared to usual care in a large, patient-centered medical home for CMC. Eligible patients include all children ages 2-18 years old, with ≥ 1 complex chronic condition, and with ≥ 5 active medications, as well as their English-speaking primary caregivers. Child participants and their primary parental caregivers will be randomized to pMTM or usual care before a non-acute primary care visit and followed for 90 days. Using generalized linear models, the overall effectiveness of the intervention will be evaluated using total MRP counts at 90 days following pMTM intervention or usual care visit. Following attrition, a total of 296 CMC will contribute measurements at 90 days, which provides > 90% power to detect a clinically significant 1.0 reduction in total MRPs with an alpha level of 0.05. Secondary outcomes include Parent-Reported Outcomes of Symptoms (PRO-Sx) symptom burden scores and acute healthcare visit counts. Program replication costs will be assessed using time-driven activity-based scoring. DISCUSSION: This pMTM trial aims to test hypotheses that a patient-centered medication optimization intervention delivered by pediatric pharmacists will result in lower MRP counts, stable or improved symptom burdens, and fewer cumulative acute healthcare encounters at 90 days following pMTM compared to usual care. The results of this trial will be used to quantify medication-related outcomes, safety, and value for a high-utilization group of CMC, and outcomes may elucidate the role of integrated pharmacist services as a key component of outpatient complex care programs for this priority pediatric population. TRIAL REGISTRATION: This trial was prospectively registered at clinicaltrials.gov (NCT05761847) on Feb 25, 2023.

Characterization of wound microbes in epidermolysis bullosa: A focus on Pseudomonas aeruginosa.

The most common bacteria isolated from wound cultures in patients recorded in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) are Staphylococcus aureus and Pseudomonas aeruginosa. Given the prevalence of P. aeruginosa in this patient population and prior research implicating P. aeruginosa's potential role in carcinogenesis, we sought to further analyze patients with recorded wound cultures positive for Pseudomonas aeruginosa in the EBCCOD. We provide a descriptive analysis of this subset of patients and highlight potential avenues for future longitudinal studies that may have significant implications in our wound care management for patients with epidermolysis bullosa.

Identifying opportunities for pediatric medication therapy management in children with medical complexity.

BACKGROUND: Despite potential benefits of medication therapy management (MTM) for complex pediatric patients, implementation of pediatric MTM services is rare. OBJECTIVES: To describe how a standardized pediatric MTM model identifies potential interventions and their impact on medication regimen complexity index (MRCI) scores in children with medical complexity (CMC) and polypharmacy. METHODS: This retrospective proof-of-concept study included pediatric patients receiving primary care in a large outpatient primary care medical home for CMC within a tertiary freestanding children's hospital from August 2020 to July 2021. Medication profiles of established patients aged 0-18 years with at least 5 active medications at the time of the index visit were assessed for medication-related concerns, potential interventions, and potential impact of proposed interventions on MRCI scores. RESULTS: Among 100 patients, an average of 3.4 ± 2.6 medication-related concerns was identified using the pediatric MTM model. Common medication-related concerns (>25% of patients) included inappropriate or unnecessary therapy, suboptimal therapy, undertreated symptom, adverse effect, clinically impactful drug-drug interaction, or duplication of therapy. A total of 97% had opportunities for 5.0 ± 2.9 potential interventions. Most common proposed interventions included drug discontinuation trial (69%), patient or caregiver education (55%), dosage form modification (51%), dose modification (49%), and frequency modification (46%). The mean baseline MRCI score was 32.6 (95% CI 29.3-35.8) among all patients. MRCI scores decreased by a mean of 4.9 (95% CI 3.8-5.9) after application of the theoretical interventions (P < 0.001). Mean potential score reduction was not significantly affected by patient age or number of complex chronic conditions. Potential impact of the proposed interventions on MRCI score was significantly greater in patients with higher baseline medication counts (P < 0.001). CONCLUSION: Most CMC would likely benefit from a pharmacist-guided pediatric MTM service. A standardized review of active medication regimens identified multiple medication-related concerns and potential interventions for nearly all patients. Proposed medication interventions would significantly reduce medication regimen complexity as measured by MRCI. Further prospective evaluation of a pharmacist-guided pediatric MTM service is warranted.

Hospitalization Outcomes for Rural Children with Mental Health Conditions.

OBJECTIVE: To identify where rural children with mental health conditions are hospitalized and to determine differences in outcomes based on location of hospitalization. STUDY DESIGN: This is a retrospective cohort analysis of US rural children aged 0-18 years with a mental health hospitalization between January 1, 2014, and November 30, 2014, using the 2014 Agency for Healthcare Research and Quality's Nationwide Readmissions Database. Hospitalizations for rural children were categorized by children's hospitals, metropolitan non-children's hospitals, or rural hospitals. Associations between hospital location and outcomes were assessed with logistic (readmission) and negative binomial regression (length of stay [LOS]) models. Classification and regression trees (CART) were used to describe the characteristics of most common hospitalizations at a rural hospital. RESULTS: Of 21 666 mental health hospitalizations of rural children, 20.6% were at rural hospitals. After adjustment for clinical and demographic characteristics, LOS was higher at metropolitan non-children's and children's hospitals compared with rural hospitals (LOS: adjusted rate ratio [aRR], 1.35 [95% CI 1.29-1.41] and 1.33 [95% CI, 1.25-1.41]; P < .01 for all). The 30-day readmission was lower at metropolitan non-children's and children's hospitals compared with rural hospitals (aOR, 0.73 [95% CI, 0.63-0.84] and 0.59 [95% CI, 0.48-0.71]; P < .001 for all). Adolescent males living in poverty with externalizing behavior disorder had the highest percentage of hospitalization at rural hospitals (69.4%). CONCLUSIONS: Although hospitalizations at children's and metropolitan non-children's hospitals were longer, patient outcomes were more favorable.

Characterization of wound microbes in epidermolysis bullosa: Results from the epidermolysis bullosa clinical characterization and outcomes database.

BACKGROUND/OBJECTIVES: Patients with epidermolysis bullosa (EB) require care of wounds that are colonized or infected with bacteria. A subset of EB patients are at risk for squamous cell carcinoma, and bacterial-host interactions have been considered in this risk. The EB Clinical Characterization and Outcomes Database serves as a repository of information from EB patients at multiple centers in the United States and Canada. Access to this resource enabled broad-scale analysis of wound cultures. METHODS: A retrospective analysis of 739 wound cultures from 158 patients from 13 centers between 2001 and 2018. RESULTS: Of 152 patients with a positive culture, Staphylococcus aureus (SA) was recovered from 131 patients (86%), Pseudomonas aeruginosa (PA) from 56 (37%), and Streptococcus pyogenes (GAS) from 34 (22%). Sixty-eight percent of patients had cultures positive for methicillin-sensitive SA, and 47%, methicillin-resistant SA (18 patients had cultures that grew both methicillin-susceptible and methicillin-resistant SA at different points in time). Of 15 patients with SA-positive cultures with recorded mupirocin susceptibility testing, 11 had mupirocin-susceptible SA and 6 patients mupirocin-resistant SA (2 patients grew both mupirocin-susceptible and mupirocin-resistant SA). SCC was reported in 23 patients in the entire database, of whom 10 had documented wound cultures positive for SA, PA, and Proteus species in 90%, 50%, and 20% of cases, respectively. CONCLUSIONS: SA and PA were the most commonly isolated bacteria from wounds. Methicillin resistance and mupirocin resistance were reported in 47% and 40% of patients tested, respectively, highlighting the importance of ongoing antimicrobial strategies to limit antibiotic resistance.

Variation of the prevalence of pediatric polypharmacy: A scoping review.

PURPOSE: To examine the range of prevalence of pediatric polypharmacy in literature through a scoping review, focusing on factors that contribute to its heterogeneity in order to improve the design and reporting of quality improvement, pharmacovigilance, and research studies. METHODS: We searched Ovid Medline, PubMed, EMBASE, CINAHL, Ovid PsycINFO, Cochrane CENTRAL, and Web of Science Core Collection databases for studies with concepts of children and polypharmacy, along with a hand search of the bibliographies of six reviews and 30 included studies. We extracted information regarding study design, disease conditions, and prevalence of polypharmacy. RESULTS: Two hundred eighty-four studies reported prevalence of polypharmacy. They were more likely to be conducted in North America (37.7%), published after 2010 (44.4%), cross-sectional (67.3%), in outpatient settings (59.5%). Prevalence ranged from 0.9% to 98.4%, median 39.7% (interquartile range [IQR] 22.0%-54.0%). Studies from Asia reported the highest median prevalence of 45.4% (IQR 27.3%-61.0%) while studies from North America reported the lowest median prevalence of 30.4% (IQR 14.7%-50.2%). Prevalence decreased over time: median 45.6% before 2001, 38.1% during 2001 to 2010, and 34% during 2011 to 2017. Studies involving children under 12 years had a higher median prevalence (46.9%) than adolescent studies (33.7%). Inpatient setting studies had a higher median prevalence (50.3%) than studies in outpatient settings (38.8%). Community level samples, higher number and duration of medications defining polypharmacy, and psychotropic medications were associated with lower prevalence. CONCLUSIONS: The prevalence of pediatric polypharmacy is high and variable. Studies reporting pediatric polypharmacy should account for context, design, polypharmacy definition, and medications evaluated.

Outcome measures in pediatric polypharmacy research: a scoping review.

INTRODUCTION: Various methods have been used to interpret the reports of pediatric polypharmacy across the literature. This is the first scoping review that explores outcome measures in pediatric polypharmacy research. OBJECTIVES: The aim of our study was to describe outcome measures assessed in pediatric polypharmacy research. METHODS: A search of electronic databases was conducted in July 2017, including Ovid Medline, PubMed, Elsevier Embase, Wiley Cochrane Central Register of Controlled Trials (CENTRAL), EBSCO CINAHL, Ovid PsyclNFO, Web of Science Core Collection, ProQuest Dissertations and Thesis A&I. Data were extracted about study characteristics and outcome measures, and also synthesized by harms or benefits mentioned. RESULTS: The search strategy initially identified 8169 titles and screened 4398 using the inclusion criteria after de-duplicating. After the primary screening, a total of 363 studies were extracted for the data analysis. Polypharmacy (prevalence) was identified as an outcome in 31.4% of the studies, prognosis-related outcomes in 25.6%, and adverse drug reactions in 16.5%. A total of 265 articles (73.0%) mentioned harms, including adverse drug reactions (26.4%), side effects (24.2%), and drug-drug interactions (20.9%). A total of 83 studies (22.9%) mentioned any benefit, 48.2% of which identified combination for efficacy, 24.1% combination for treatment of complex diseases, and 19.3% combination for treatment augmentation. Thirty-eight studies reported adverse drug reaction as an outcome, where polypharmacy was a predictor, with various designs. CONCLUSIONS: Most studies of pediatric polypharmacy evaluate prevalence, prognosis, or adverse drug reaction-related out-comes, and underscore harms related to polypharmacy. Clinicians should carefully weigh benefits and harms when introducing medications to treatment regimens.

Approach and Safety of Esophageal Dilation for Treatment of Strictures in Children With Epidermolysis Bullosa.

OBJECTIVE: The aim of the study is to analyze a large series of esophageal balloon dilations in patients with epidermolysis bullosa (EB) to determine procedural approach and frequency of post-endoscopic adverse events (AEs). METHODS: Retrospective chart review for AE occurrence and clinical outcomes in children and adolescents with EB, age 1 to 19, who underwent esophageal dilation for esophageal stricture(s) from January 2003 to April 2016 at an academic, tertiary care, free-standing children's hospital. The primary outcome measure was occurrence of procedural AEs (defined as events occurring within 72 hours after endoscopic dilation procedure). RESULTS: A total of 231 fluoroscopy-guided esophageal balloon dilation procedures (209 anterograde, 20 retrograde, 2 both) were performed in 24 patients. Strictures were more common in the proximal portion of the esophagus with median stricture location 13 cm from the lips. From 2003 to 2012, 4.1% of dilations were retrograde. From 2013 to 2016, 20.2% of dilations were retrograde. AEs attributable to dilation occurred after 10.0% of procedures, and the most common AEs were vomiting, pain, and fever. No esophageal perforations, serious bleeding events, or deaths occurred secondary to dilation. The rate of post-dilation hospitalization was 6.9%. Dilation approach (anterograde vs retrograde) did not impact the likelihood of AEs. CONCLUSIONS: The characteristic esophageal lesion in EB is a single, proximal esophageal stricture. EB patients can safely undergo repeat pneumatic esophageal balloon dilations with minimal risk for severe complication. We observed a trend towards increased use of retrograde esophageal dilation.

Epidemiology of Polypharmacy and Potential Drug-Drug Interactions Among Pediatric Patients in ICUs of U.S. Children's Hospitals.

OBJECTIVES: Polypharmacy is common in hospitalized children in the United States and has been identified as a major risk factor for exposure to potential drug-drug interactions. Little is known about the characteristics and prevalence of exposure of pediatric patients to polypharmacy and potential drug-drug interactions in PICUs. DESIGN: Retrospective cohort study using the Pediatric Health Information System database. SETTING: Forty-two freestanding children's hospitals throughout the United States. PATIENTS: A total of 54,549 patients less than 18 years old cared for in PICUs in 2011. Patients in neonatal ICUs were not included. MEASUREMENTS AND MAIN RESULTS: PICU patients were on average exposed to 10 distinct drugs each hospital day and to 20 drugs cumulatively during their hospitalization. Seventy-five percent of patients were exposed to greater than or equal to one potential drug-drug interaction regardless of severity level, 6% to greater than or equal to one contraindicated potential drug-drug interaction, 69% to greater than or equal to one major potential drug-drug interaction, 57% to greater than or equal to one moderate potential drug-drug interaction, 19% to greater than or equal to one minor potential drug-drug interaction. Potential drug-drug interaction exposures were significantly associated with specific diagnoses (p < 0.001), presence of complex chronic conditions (p < 0.001), increasing number of total distinct drugs used (p < 0.001), increasing length of stay in PICU (p < 0.001), and white race (p < 0.001). CONCLUSIONS: Many PICU patients are exposed to substantial polypharmacy and potential drug-drug interactions. Future research should identify the risk of adverse drug events following specific potential drug-drug interaction exposures, especially the risk of adverse drug events due to multiple potential drug-drug interaction exposures, and determine the probability and magnitude of the actual harm (if any) for each specific potential drug-drug interaction, especially for multiple potential drug-drug interaction exposures.

Outpatient follow-up visits and readmission in medically complex children enrolled in Medicaid.

OBJECTIVE: To examine the association between postdischarge outpatient follow-up and 30-day readmissions in Medicaid enrolled children with complex, chronic conditions. STUDY DESIGN: This was a retrospective cohort analysis of Colorado Medicaid recipients with complex, chronic conditions who were discharged from the hospital between 2006 and 2008. The primary outcome was readmission between 4 and 30 days after index hospital discharge. Using multivariable logistic regression, we examined the association between early postdischarge outpatient visits (≤ 3 days postdischarge) and readmission. We secondarily analyzed the relationship between any outpatient visit from 4 to 29 days of index discharge and readmission. RESULTS: For the 2415 patients with complex, chronic conditions included in the analysis, the 4- to 30-day readmission rate was 6.3%. The odds of readmission was significantly greater for patients with ≥ 1 outpatient visit ≤ 3 days after discharge compared with patients without a visit ≤ 3 days after discharge (aOR 1.7 [1.1-2.4]). The odds of readmission were significantly lower for patients with ≥ 1 outpatient visit from 4 to 29 days after discharge compared with patients without such visits (aOR 0.5 [0.3-0.7]). Other factors associated with readmission included index hospital length of stay and number of complex, chronic conditions. CONCLUSIONS: In medically complex children, there is a positive association between early postdischarge outpatient follow-up and readmission. There is an inverse association between later postdischarge outpatient follow-up and readmission. Outpatient follow-up occurring within 4-29 days after discharge may help to prevent 30-day readmissions. Additional research is needed to inform guidelines regarding longer term postdischarge outpatient follow-up in these children.

The concordance of endoscopic and histologic findings of 1000 pediatric EGDs.

BACKGROUND: Pediatric gastroenterologists frequently perform routine endoscopic biopsies despite normal-appearing mucosa during EGD. Older small studies have supported this practice. OBJECTIVE: To re-evaluate the concordance between endoscopic appearance and histology in the era of high-definition endoscopy. DESIGN: Retrospective cohort study. SETTING: Single tertiary care center. PATIENTS: A total of 1000 pediatric patients undergoing initial EGD. MAIN OUTCOME MEASUREMENTS: Endoscopic and histologic findings. RESULTS: The overall rate of an endoscopic finding was 34.7%, which was 40.4% of a histologic finding. Concordance between the presence of any endoscopic finding and any histologic finding in all locations was 69.9% (Cohen's κ coefficient=0.32). In the esophagus, the concordance between any endoscopic finding and any histologic finding was 82.6% (κ=0.45). The stomach was 73.2% concordant (κ=0.18), and the duodenum was 89.3% concordant (κ=0.42). The κ coefficient decreased when comparing specific findings in each location; it was 0.34 in the esophagus, 0.17 in the stomach, and 0.34 in the duodenum. If biopsy specimens had only been obtained when the endoscopist identified abnormal mucosa, 48.5% of the pathologic findings would have been missed. In patients with histology consistent with eosinophilic esophagitis, 30.2% had normal-appearing mucosa. For celiac disease, 43% had normal-appearing mucosa. In the stomach, an abnormal endoscopic appearance was more likely to have normal histology. LIMITATIONS: The single-center, retrospective nature and more endoscopists than pathologists. CONCLUSIONS: These data support the routine collection of biopsy specimens in the duodenum, stomach, and esophagus during EGD in pediatric patients.

The depth, duration, and degree of outpatient pediatric polypharmacy in Colorado fee-for-service Medicaid patients.

BACKGROUND AND OBJECTIVES: Outpatient pediatric polypharmacy is poorly characterized. Identification of at-risk populations has clinical implications for pharmacy case management programs. We described the degree of exposure to polypharmacy using parameters of depth (concurrent medication count) and duration, reported commonly dispensed medications and exposure to three example potential drug-drug interactions by different depths of polypharmacy, and determined patient characteristics associated with exposure to increased degrees (a function of depth and duration) of polypharmacy. METHODS: Retrospective cohort study of Colorado fee-for-service Medicaid patients aged <18 years with 12 months of continuous enrollment. We calculated depth of polypharmacy using daily concurrent medication counts and duration of polypharmacy using days exposed to a certain depth. Multinomial logistic regression was used to assess patient characteristics associated with different degrees of polypharmacy. RESULTS: Of 242 230 patients, 35% percent were exposed to any depth of polypharmacy, most commonly to anti-infective medications. Patients with higher depth polypharmacy were exposed to less common medications (psychotropic drugs, anticonvulsants, cardiovascular agents, and opioids) and to higher rates of exposure to potential drug-drug interactions. Of 47 972 patients exposed to ≥3 concurrent medications, 50% were exposed for <15 days, 25% for 15-38 days, 15% for 39-111 days, and 10% for 112-327 days. High-degree polypharmacy was associated with increasing age, male gender, and presence of a complex chronic condition. CONCLUSIONS: Outpatient pediatric polypharmacy occurs to a substantial degree for a small but vulnerable population of children, who may be candidates for pharmacy case management. We must determine whether increased exposure to high-degree polypharmacy causes harm.

Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation.

BACKGROUND: The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems. RESULTS: The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset. CONCLUSIONS: The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10.

Pediatric Complex Chronic Condition System Version 3.

Importance: Since implementation of the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) in the US, thousands of new or related codes have been added to represent clinical conditions. The widely used pediatric complex chronic condition (CCC) system required a major update from version 2 (V2) to version 3 (V3) to capture the range of clinical conditions represented in the ICD-10-CM. Objective: To update the CCC V3 system, creating V3, with new, missing, or retired codes; to reconceptualize the system's use of technology codes; and to compare CCC V3 with V2. Design, Setting, and Participants: This repeated cross-sectional study examined US hospitalization data from the Pediatric Health Information System (PHIS) and the Medicaid Merative MarketScan Research Databases from January 1, 2009, to December 31, 2019, for all patients aged 0 to 18 years. Data were analyzed from March 1, 2023, to April 1, 2024. Exposures: The CCCs were identified in both data sources using the CCC V2 and V3 systems. Main Outcomes and Measures: The (1) percentage of pediatric hospitalizations associated with a CCC, (2) numbers of CCC body-system categories per patient, and (3) explanatory power for hospital length of stay and in-hospital mortality were compared over time for V3 vs V2. Results: Among 7 186 019 hospitalizations within PHIS, 54.3% patients were male, the median age was 4 years (IQR, 1-11 years), and 51.2% were aged 0 to 4 years). The CCC V2 identified 2 878 476 (40.1%) patients as having any CCC compared with 2 753 412 (38.3%) identified by V3. In addition, V2 identified 100 065 (1.4%) patients with transplant status compared with 146 683 (2.0%) by V3, and V2 identified 914 835 (12.7%) as having technology codes compared with 805 585 (11.2%) by V3. The 2 systems were similar in accounting for the number of CCC body-system categories per patient and in explaining variation in hospital length of stay and in-hospital mortality. For both V2 and V3, 10.0% of the variance in hospital length of stay and 12.0% of the variance in in-hospital mortality was explained by the presence of a CCC. Similar patterns were observed when analyzing the 2 999 420 Medicaid Merative MarketScan Research Databases' hospitalizations (52.3% of patients were male, the median age was 1 year [IQR, 0-12 years], and 62.0% were 0 to 4 years old), except that the percentages of identified CCCs were all lower: V2 identified 758 110 hospitalizations (25.3%) with any CCC compared with 718 100 (23.9%) identified by V3. Conclusions and Relevance: These results suggest that, moving forward, V3 should be used to identify CCCs, and ongoing, frequent updates to V3, using a transparent, structured process, will enable V3 to accurately reflect the evolving spectrum of clinical conditions represented in the ICD-10-CM.

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

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

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.