Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). DATA SOURCES: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. STUDY SELECTION: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. DATA EXTRACTION: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. DATA SYNTHESIS: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 µg/kg (range, 30-232.7 µg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. CONCLUSIONS: On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

The role of an abbreviated ultrasound in the evaluation of necrotizing enterocolitis.

BACKGROUND: Bowel ultrasound is a useful diagnostic tool in the diagnosis and management of necrotizing enterocolitis (NEC) but can be time-consuming and requires technical expertise, particularly for assessing pneumatosis. Previous literature on sonographic evaluation of NEC has focused on a full bowel ultrasound protocol, but the utility of an abbreviated protocol primarily aimed at identifying high-risk sonographic findings without focused bowel assessment has not been well studied. OBJECTIVE: This study aims to describe the diagnostic accuracy of an abbreviated ultrasound protocol for identifying high-risk NEC findings. MATERIALS AND METHODS: This is a retrospective, institutional review board-approved study. We identified all abbreviated NEC ultrasounds performed between January 2014 and August 2022 at our institution. Exams were reviewed for the presence of high-risk findings including pneumoperitoneum, fluid collections, and complex free fluid. Clinical outcome was categorized as poor or good depending on if emergent surgical intervention or death related to NEC occurred. The frequency of follow-up NEC ultrasounds was reviewed to determine if new findings affected outcome. Sensitivity, specificity, and positive and negative predictive values were generated to assess the performance of the abbreviated ultrasounds to identify high-risk findings. RESULTS: A total of 84 abbreviated abdominal ultrasounds were performed on 73 children. Median age at the time of ultrasound was 41 days (interquartile range (IQR) 53 days) and median gestational age was 35 weeks and 3 days (IQR 80 days), and 44/73 (60%) were male. Thirteen ultrasounds had at least one high-risk finding with nine (69%) resulting in a poor outcome, including seven surgical interventions and four deaths. Two patients had surgical intervention and died as a result of necrotizing enterocolitis. Ultrasounds without high-risk findings were not associated with poor clinical outcomes. Sensitivity, specificity, positive predictive value, and negative predictive value of the abbreviated NEC ultrasound were 100% (95% CI 60-100%), 95% (95% CI 86-98%), 69% (95% CI 39-90%), and 100% (95% CI 94-100%), respectively. Twelve abbreviated ultrasounds were followed by a second NEC ultrasound within 5 days. Five follow-up ultrasounds demonstrated new high- or low-risk findings, but the new findings did not correlate with a change in outcome as predicted by the initial ultrasound. CONCLUSION: An abbreviated NEC ultrasound can be of clinical utility in predicting poor outcomes, particularly during non-business hours when resources are limited.

Factors Impacting Maltreatment Evaluation and Reports to Child Protective Services in Pediatric Substance Exposures.

OBJECTIVES: The objective of this study was to assess demographic, clinical, and psychosocial factors associated with pediatric substance exposures, describe the medical evaluation, and identify factors associated with social work (SW) and hospital-based child protection team (CPT) safety assessments and reports to child protective services (CPS). METHODS: We retrospectively reviewed charts of electronic medical records for children ages 0 to 72 months presenting for accidental ingestion evaluated May 1, 2015 to May 1, 2021 at a level 1 pediatric trauma center. Cases of environmental exposures, iatrogenic medication errors, dosing errors, and allergies/adverse reactions were excluded. Data were analyzed using descriptive statistics; χ 2 and multivariable logistic regression analysis assessed factors associated with two primary outcomes of interest, SW/CPT assessment and CPS report. RESULTS: Among 773 total cases of substance exposures during the studied time frame, 27% were referred to SW/CPT for further safety assessments and 15.4% were reported to CPS. Being admitted to the hospital, prescription medication or recreational/illegal/illicit substance exposures, and increasing psychosocial risk factors were found to be significantly associated with referrals. Age, race, and insurance status were not found to be associated. Toxicology screening was performed in only 24.7% of cases. Of those eligible for further imaging per hospital protocol, skeletal surveys were obtained in 5.5% of cases and head imaging was obtained in 9% of cases. CONCLUSIONS: There is significant variability in pediatric substance exposure assessment practices. Disparities based on demographic characteristics are uncommon. Perceived severity of condition, exposures involving recreational/illegal/illicit substances, and greater prevalence of family psychosocial adversities are associated with higher rates of SW/CPT assessment and CPS reports.

Preliminary evidence of glycine as a biomarker of cardiovascular disease risk in children with obesity.

Glycine (GLY) is a substrate for a wide range of metabolic processes. Several preclinical and adult studies demonstrated inverse associations of GLY with obesity, cardiovascular disease (CVD) and diabetes. However, little evidence is available on relationships between GLY and CVD risk in children. We assessed links between circulating GLY and biomarkers of CVD in children with obesity. Participants included both male and females with normal weight (NW, n = 6) and obesity (OB, n = 15), with age 14-18 years and Tanner stage >IV. Concentrations of GLY, branched chain amino acids (BCAA), and 25-hydroxy vitamin-D [25(OH)D], glucose, insulin, adiponectin, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured using established techniques, and body composition by DXA. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Our study identified major relationships of GLY (p-value < 0.01 for all) of GLY with visceral fat (r2 = 0.40), BCAA (r2 = 0.44), HOMA-IR (r2 = 0.33), 25(OH)D (r2 = 0.48), IL-6 (r2 = 0.46) and adiponectin (r2 = 0.39). Given that CVD progression is a continuum and the disease itself is not present in children and biomarkers are typically used to monitor CVD in children, the links between GLY and biomarkers of CVD provide evidence for the first time of a potential role for GLY in CVD in children with obesity.

Variation of asthma characteristics with atopic march, gastroesophageal reflux, and ENT pathologies.

BACKGROUND: Asthma is a significant cause of morbidity and mortality in the pediatric population. Atopic dermatitis (AD) is often the first step in the atopic march leading to the development of asthma, allergic rhinitis, and food allergies in the future. OBJECTIVE: This study aimed to evaluate the severity differences between asthmatic children with and without atopic march in addition to characteristics of asthmatic patients with GER and ear-nose-and-throat (ENT) pathologies. METHODS: A total of 616 pediatric asthmatic patients were enrolled. The study subjects were divided into two groups. Group A included asthmatic children with a history of AD. Group B had asthmatic children without a history of AD. Multiple factors were studied, including sex, race/ethnicity, family history of atopy, asthma severity, allergic rhinitis, food allergies, smoke exposure, ear-nose-and-throat (ENT) pathologies, gastroesophageal reflux (GER), frequency of systemic steroid use, and hospital admission rates. RESULTS: Our results revealed that patients with atopic march are at risk of developing a higher severity of asthma, resulting in increased morbidity. In contrast, asthmatic patients without atopic march had a milder asthma severity, less need for steroids, and fewer hospital admissions. A higher prevalence of ENT pathologies and/or GER existed among asthmatic children without atopic march. CONCLUSION: Our findings suggest that patients with atopic march should be expected to exhibit a more severe phenotype of asthma with increased asthma morbidity. Asthmatic patients without atopic march had a milder asthma phenotype, less need for steroids, and fewer hospital admissions. A higher prevalence of ENT pathologies and/or GER existed among asthmatic children without atopic march.

Cardiopulmonary Exercise Testing Characterizes Silent Cardiovascular Abnormalities in Asymptomatic Pediatric Cancer Survivors.

Late-onset cardiovascular complications are serious concerns for pediatric cancer survivors (PCS) including those who are asymptomatic. We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS. We examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed. Fifty-three PCS and 60 controls were studied. Peak oxygen consumption (VO2), peak work rate (WR), and ventilatory anaerobic threshold (VAT) were significantly lower in PCS than controls (1.86 ± 0.53 vs. 2.23 ± 0.61 L/min, 125 ± 45 vs. 154 ± 46 W, and 1.20 ± 0.35 vs. 1.42 ± 0.43 L/min, respectively; all p < 0.01), whereas peak heart rate (HR) and ventilatory efficiency (a slope of minute ventilation over CO2 production or ∆VE/∆VCO2) were comparable. Peak respiratory exchange ratio (RER) was significantly higher in PCS (p = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher ∆HR/∆WR) and lower peak oxygen pulse (OP). Twelve PCS with high peak RER (≥ 1.3) revealed lower pVO2 and VAT than the rest of PCS despite higher ventilatory efficiency (lower ∆VE/∆VCO2), suggesting fundamental deficiency in oxygen utilization in some PCS. Poor exercise performance in PCS may be mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multifactorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS.

Impact of Plans of Safe Care on Prenatally Substance Exposed Infants.

OBJECTIVE: To assess the impact of recent federal statute changes mandating child welfare-based Plan of Safe Care (POSC) supportive programming and community-based linkages to treatment providers, resources, and services for families of infants affected by prenatal substance exposure (IPSE). STUDY DESIGN: Retrospective review of Delaware's statewide child welfare case registry data for IPSE birth notifications and subsequent hotline reports for serious physical injury/fatality concerns from November 1, 2018-October 31, 2020. Abstracted variables included IPSE sex, substance exposure type, family characteristics (maternal personal child welfare history or mental health diagnosis, treatment engagement), and POSC referrals. RESULTS: Of 1436 IPSE, 1347 (93.8%) had POSC support. Most IPSE (67.2%) had exposure to single substance types prenatally. Nearly 90% avoided out-of-home placement. Nearly one-fourth of mothers delivered a prior IPSE; 40% of mothers had personal histories of childhood protective services involvement. Also, 43.5% of mothers and 9.1% of fathers were referred to community-based resources, including substance use, mental health treatment, parenting classes, and home visiting nursing. Nearly 58% of IPSE were referred for pediatric/developmental assessment. Notably, 0.82% (11 out of 1347) of IPSE with POSC sustained serious physical or fatal injury. CONCLUSIONS: POSC promote supportive, potentially protective linkages to community-based programming for IPSE and their families.

Impact of dysglycemia and obesity on the brain in adolescents with and without type 2 diabetes: A pilot study.

OBJECTIVE: Both diabetes and obesity can affect the brain, yet their impact is not well characterized in children with type 2 (T2) diabetes and obesity. This pilot study aims to explore differences in brain function and cognition in adolescents with T2 diabetes and obesity and nondiabetic controls with obesity and lean controls. RESEARCH DESIGN AND METHODS: Participants were 12-17 years old (5 T2 diabetes with obesity [mean HgbA1C 10.9%], 6 nondiabetic controls with obesity and 10 lean controls). Functional MRI (FMRI) during hyperglycemic/euglycemic clamps was performed in the T2 diabetes group. RESULTS: When children with obesity, with and without diabetes, were grouped (mean BMI 98.8%), cognitive scores were lower than lean controls (BMI 58.4%) on verbal, full scale, and performance IQ, visual-spatial and executive function tests. Lower scores correlated with adiposity and insulin resistance but not HgbA1C. No significant brain activation differences during task based and resting state FMRI were noted between children with obesity (with or without diabetes) and lean controls, but a notable effect size for the visual-spatial working memory task and resting state was observed. CONCLUSIONS: In conclusion, our pilot study suggests that obesity, insulin resistance, and dysglycemia may contribute to relatively poorer cognitive function in adolescents with T2 diabetes and obesity. Further studies with larger sample size are needed to assess if cognitive decline in children with obesity, with and without T2 diabetes, can be prevented or reversed.

Utilising pneuRIP device in determining the adequacy of respiratory support when weaning high-flow nasal cannula in paediatric patients with acute respiratory distress: A pilot study.

AIM: Recognition of paediatric respiratory distress and timely intervention is critical, especially during the weaning phase of support in paediatric acute respiratory failure, as weaning too aggressively can lead to further setbacks in a patient's recovery. We aimed to determine if pulmonary function measurements obtained with the pneuRIP device, a noninvasive pulmonary function testing device that provides measurements of labored breathing index (LBI), phase angle and %rib cage (%RC) contribution to breathing, will provide predictive values to assess the adequacy of respiratory support while weaning from HFNC. METHODS: We reviewed patients ages 0-18 years admitted to the PICU for respiratory distress due to respiratory infections receiving HFNC. Patients with history of chronic lung disease and chronic neuromuscular disease with baseline habnormal breathing patterns were excluded. Phase angle, LBI and %RC were obtained every hour and with every wean of HFNC. Nine patients were enroled. RESULTS: Mean LBI range remained 1.27-1.68 when LBI was plotted as a function of the HFNC flow rate. Mean values of %RC contribution to breathing ranged 43.65-57.12 as a function of the HFNC flow rate. No significant deviations existed in either %RC (P = 0.16) or LBI (P = 0.16) during the weaning of HFNC. Mean phase angle for all subjects was 41.48°-74.12° for the duration of wean and showed significant deviation from baseline during the weaning process (p = 0.001). CONCLUSIONS: Measurements of LBI and %RC on the pneuRIP device effectively demonstrated tolerance of weaning HFNC during the recovery phase of acute respiratory failure from a respiratory infection.

A Combined Analysis of Peak and Submaximal Exercise Parameters in Delineating Underlying Mechanisms of Sex Differences in Healthy Adolescents.

Peak exercise parameters are considered the gold standard to quantify cardiac reserve in cardiopulmonary exercise testing (CPET). We studied whether submaximal parameters would add additional values in analyzing sex differences in CPET. We reviewed CPET of age-matched healthy male and female adolescents by cycle ergometer. Besides peak parameters, submaximal CPET parameters, including ventilatory anaerobic threshold (VAT), oxygen uptake efficiency slope (OUES), and submaximal slopes of Δoxygen consumption (ΔVO2)/Δwork rate (ΔWR), Δheart rate (ΔHR)/ΔWR, ΔVO2/ΔHR, and Δminute ventilation (ΔVE)/ΔCO2 production (ΔVCO2), were obtained. We studied 35 male and 40 female healthy adolescents. Peak VO2 (pVO2), peak oxygen pulse (pOP), and VAT were significantly lower in females than males (1.9 ± 0.4 vs. 2.5 ± 0.6 L/min; 10 ± 2.0 vs. 13.2 ± 3.5 ml/beat; 1.23 ± 0.3 vs. 1.52 ± 0.5 L/min, respectively, all p < 0.005). Females showed significantly lower pVO2, VAT, and OUES with the same body weight than males, implying higher skeletal muscle mass in males. When simultaneously examining ΔHR/ΔWR and pOP, females showed higher dependency on increases in HR than in stroke volume. Females demonstrated significantly lower pOP with the same levels of ΔVO2/ΔHR, suggesting more limited exercise persistence than males under an anaerobic condition at peak exercise. Oxygen uptake efficiency in relation to peak VE was significantly higher in males. There was no sex difference in either ΔVO2/ΔWR or ΔVE/ΔVCO2. Combinational assessment of peak and submaximal CPET parameters delineates the multiple mechanisms that contribute to the sex differences in exercise performance.

Factors Associated with Child-Welfare Involvement among Prenatally Substance-Exposed Infants.

OBJECTIVE: To assess factors impacting child-welfare involvement and child abuse and neglect outcomes among prenatally substance-exposed infants. STUDY DESIGN: This was a retrospective review of case registry data regarding substance-exposed infants tracked statewide in Delaware from 2014 to 2018. Differences in maternal, infant, and substance exposure factors by level of child-welfare involvement (screened-in vs screened-out case status) and child abuse and neglect outcomes were examined. Screened-in status was defined as case acceptance for investigation, family assessment, or treatment referral. Using logistic regression, associations between factors and screened-in status and between factors and child abuse and neglect outcomes were assessed. Cases involving child abuse and neglect were analyzed qualitatively. RESULTS: Among 1222 substance-exposed infants, 70% were screened-in by child welfare for ongoing involvement; 28 (2.3%) of substance-exposed infants were identified as child abuse and neglect victims sustaining serious physical or fatal injury before 1 year of age. Most substance-exposed infants remained with caregivers; few entered foster care. Polysubstance exposure and maternal mental health condition were factors associated with screened-in status. Neither substance exposure type nor maternal mental health condition reliably predicted future child abuse and neglect. CONCLUSIONS: Substance-exposed infants had a significant risk for child abuse and neglect. Although maternal and substance exposure factors were associated with screened-in case status, they unreliably predicted future risk of child abuse and neglect.

Surveillance imaging in pediatric ependymoma.

BACKGROUND: Management of pediatric patients with ependymoma includes posttreatment surveillance imaging to identify asymptomatic recurrences. However, it is unclear whether early detection translates into improved survival. The objective was to determine whether detection of ependymoma relapses on surveillance imaging translates into a survival benefit. PROCEDURE: Patients with ependymoma aged <21 years at diagnosis treated in the Nemours' Children's Health System between January 2003 and October 2016 underwent chart review. Relapsed patients' charts were assessed for details of initial therapy, surveillance imaging regimen, details of relapse including detection and therapy, and outcome. Median follow up of the entire cohort was 6.5 years from diagnosis and 3.5 years from relapse. RESULTS: Ninety of 198 (45%) patients experienced relapse with 61 (68%) detected by surveillance imaging and 29 (32%) detected based on symptoms. Five-year OS in the surveillance group was 67% (confidence interval [CI] 55-82%, SE 0.1) versus 51% (CI 35-73%, SE 0.19) in the symptoms group (P = .073). From relapse, the 3-year OS in the surveillance group was 62% (CI 50-78%, SE 0.11) versus 55% (CI 39-76%, SE 0.17) in the symptoms group (P = .063) and the 3-year SPFS was 45% (CI 33-61%, SE 0.16) in the surveillance group versus 32% (CI 19-55%, SE 0.27) in the symptoms group (P = .028). CONCLUSION: Surveillance imaging may identify recurrences in patients when they are more amenable to salvage therapy, resulting in superior 3-year SPFS, but given limited salvage options for children with recurrent ependymoma, the survival advantage of frequent surveillance imaging in asymptomatic patients remains ambiguous.

Validation of the Healthcare Transition Outcomes Inventory for Young Adults With Type 1 Diabetes.

OBJECTIVE: We recently developed and content validated the Healthcare Transition Outcomes Inventory (HCTOI), a stakeholder vetted, multidimensional measure of the outcomes of the transition from pediatric to adult healthcare for young adults (YA) with type 1 diabetes (T1D). In this study, we aimed to evaluate the psychometric properties of the HCTOI. METHODS: We collected and analyzed cross-sectional data from 128 YA (18-25 years old) with T1D to evaluate the psychometric properties of the HCTOI. We conducted confirmatory factor analysis (CFA), item analysis, and examined reliability and validity in relation to measures of quality of life, diabetes distress, regimen adherence, and glycemic control. RESULTS: CFA supported a five-factor solution: integration of T1D into emerging adult roles, balance of parental support with T1D autonomy, establishing and maintaining continuity of care, forming a collaborative patient-provider relationship, and ownership of T1D. We reduced the HCTOI from 54 to 34 items. The HCTOI demonstrated adequate internal consistency (α's = 0.62-0.87) and significant correlations demonstrated construct (quality of life, diabetes distress) and criterion validity (adherence, glycemic control). CONCLUSIONS: The HCTOI demonstrated promising initial psychometric properties. As the first measure of the multiple dimensions of healthcare transition outcomes, the HCTOI provides a means to examine longitudinal relations between transition readiness and outcomes and to assess the efficacy or effectiveness of interventions and programs designed to improve the transition process for YA with T1D.

Impact of route of administration on genotoxic oestrogens concentrations using oral vs transdermal oestradiol in girls with Turner syndrome.

OBJECTIVE: The established link between oestrogen and breast cancer occurs via both oestrogen receptor (ER)-mediated and non ER-mediated mechanisms. The term genotoxic estrogens describes mutagenic metabolites, including oestrogen catechols and quinones, which have been linked to breast carcinogenesis in post-menopausal women. We aimed to assess whether the route of administration of 17ß oestradiol (E2 ) affects the accumulation of genotoxic oestrogen metabolites in a model of ovarian failure in young girls with Turner syndrome. METHODS: Stored plasma samples obtained at 0 and 12 months were used from 40 adolescents with Turner syndrome who participated in a 12 months randomized controlled trial of the metabolic impact of E2 orally (2 mg/d) vs transdermally (100 µg/d); dose escalation allowed matching of unconjugated E2 levels in the parent study. We measured 12 oestrogen metabolites (total concentrations = conjugated and unconjugated) using a highly sensitive LCMSMS assay. Results from 48 normally menstruating adolescents were used for comparison. RESULTS: After treatment, least square mean (SE) total E2 concentrations were higher in the oral vs transdermal group (6784 pmol/L vs 1123 [1614], P < 0.0001), as was oestrone (E1 ) (91 060 pmol/L vs 19 278 [16 534], P < 0.0001). Also, higher after oral treatment were catechol-oestrogens 4-hydroxy-E2 (149 vs 28 [±49] pmol/L), 2-hydroxy-E2 (300 vs 76 [±52]), 4-hydroxy-E1 (450 vs 105 [±113]), 2-hydroxy-E1 (3094 vs 740 [±684]) and 16α-hydroxy-E1 (3,007 vs 157 [±534]) (<0.001 between groups). Levels were much closer to controls in the transdermal group. CONCLUSIONS: Common feminizing doses of oral oestradiol for 12 months result in substantial accumulation of unphysiologic, genotoxic oestrogens compared to transdermal oestradiol, expanding concerns about oral oestrogens' first hepatic passage. Further studies assessing long-term risks of these metabolites in women taking different forms of oestrogen are needed.

Age-related ranges of respiratory inductance plethysmography (RIP) reference values for infants and children.

The current noninvasive method for respiratory monitoring is respiratory inductance plethysmography (RIP); two bands are connected, one each to the chest and the abdomen, to measure the breathing pattern. RIP requires post hoc analysis to calculate indices such as respiratory rate, phase angle, labored breathing index, and percent of rib cage contribution to breathing. Clinical studies have provided patient RIP values and age-matched normal values, but they lack global evaluation of normative data for a wide age range of pediatric subjects. Herein, we compiled normative RIP indices from numerous studies for a large range of pediatric ages. From these data, we derived regression equations useful for computing normal RIP parameters as a function of age. The presented review will provide caregivers the ability to compare RIP data of pediatric patients against the regression analysis. This comparison will help identify patients with pulmonary complications and aid in guiding respiratory therapy.

Poor adherence to early childhood blood pressure measurement guidelines in a large pediatric healthcare system.

BACKGROUND: Children who were born prematurely, those with a very low birthweight, or who have survived the neonatal intensive care unit (NICU) are at risk for the development of hypertension and chronic kidney disease (CKD), and thus require blood pressure screening less than 3 years of age, per American Academy of Pediatrics (AAP) 2004 and 2017 guidelines. METHODS: We reviewed the practice patterns of a large pediatric health care system and assessed adherence to the AAP clinical practice guidelines on blood pressure measurements in children less than 3 years of age for hypertension and CKD with the following risk factors: prematurity, very low birthweight, and a neonatal intensive care setting encounter. This retrospective chart review included a total of 9965 patients with a median gestational age of 34 weeks. RESULTS: Overall, 38% of patients had at least one blood pressure measured less than 3 years of age. Primary care accounted for 41% of all outpatient encounters and 4% of all blood pressure measurements. Surgical specialties (i.e., ophthalmology, otolaryngology, and orthopedics) accounted for many non-primary care visits and were less likely than medical specialties (i.e., cardiology and nephrology) to obtain a blood pressure measurement (p < 0.0001). CONCLUSIONS: This study of a large healthcare system's practice revealed a lack of basic screening for hypertension in a population known to be at risk for hypertension and CKD.

Safety of using real-time sensor glucose values for treatment decisions in adolescents with poorly controlled type 1 diabetes mellitus: a pilot study.

BACKGROUND: This study explored the safety of using real-time sensor glucose (SG) data for treatment decisions in adolescents with poorly controlled type 1 diabetes. METHODS: Ten adolescents with type 1 diabetes, HbA1c ≥9% on insulin pumps were admitted to the clinical research center and a continuous glucose sensor was inserted. Plasma glucose was measured at least hourly using Yellow Springs Instrument's (YSI) glucose analyzer. Starting at dinner, SG rather than YSI was used for treatment decisions unless YSI was <70 mg/dL (<3.9 mmol/L) or specific criteria indicating SG and YSI were very discordant were met. Participants were discharged after lunch the next day. RESULTS: Ten participants (seven males; 15.2-17.8 year old) completed the study. The range of differences between high glucose correction doses using SG vs YSI for calculations was -2 (SG < YSI dose) to +1 (SG > YSI dose); this difference was two units in only 2 of 23 correction doses given (all SG < YSI dose). There were five episodes of mild hypoglycemia in two patients, two of which occurred after using SG for dose calculations. There was no severe hypoglycemia and no YSI glucose >350 mg/dL (19.4 mmol/L). Mean (±SE) pre- and postmeal YSI glucose were 163 ± 11 and 183 ± 12 mg/dL (9.1 ± 0.6 and 10.2 ± 0.7 mmol/L), respectively. CONCLUSION: Use of real-time continuous glucose monitoring for treatment decisions was safe and did not result in significant over- or undertreatment. Use of SG for treatment decisions under supervised inpatient conditions is a suitable alternative to repeated fingerstick glucose monitoring. Outpatient studies using SG in real-time are needed.

Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution?

BACKGROUND: Obese children for unknown reasons report greater asthma symptoms. Asthma and obesity both independently associate with gastro-oesophageal reflux symptoms (GORS). Determining if obesity affects the link between GORS and asthma will help elucidate the obese-asthma phenotype. OBJECTIVE: Extend our previous work to determine the degree of associations between the GORS and asthma phenotype. METHODS: We conducted a cross-sectional study of lean (20%-65% body mass index, BMI) and obese (≥95% BMI) children aged 10-17 years old with persistent, early-onset asthma. Participants contributed demographics, GORS and asthma questionnaires and lung function data. We determined associations between weight status, GORS and asthma outcomes using multivariable linear and logistic regression. Findings were replicated in a second well-characterised cohort of asthmatic children. RESULTS: Obese children had seven times higher odds of reporting multiple GORS (OR=7.7, 95% CI 1.9 to 31.0, interaction p value=.004). Asthma symptoms were closely associated with GORS scores in obese patients (r=0.815, p<0.0001) but not in leans (r=0.291, p=0.200; interaction p value=0.003). Higher GORS scores associated with higher FEV1-per cent predicted (p=0.003), lower airway resistance (R10, p=0.025), improved airway reactance (X10, p=0.005) but significantly worse asthma control (Asthma Control Questionnaire, p=0.007). A significant but weaker association between GORS and asthma symptoms was seen in leans compared with obese in the replicate cohort. CONCLUSION: GORS are more likely to associate with asthma symptoms in obese children. Better lung function among children reporting gastro-oesophageal reflux and asthma symptoms suggests that misattribution of GORS to asthma may be a contributing mechanism to excess asthma symptoms in obese children.

A randomized, double blind, placebo-controlled pilot trial of the safety and efficacy of atorvastatin in children with elevated low-density lipoprotein cholesterol (LDL-C) and type 1 diabetes.

BACKGROUND: Children with type 1 diabetes (T1D) and elevated LDL-C have an increased risk for cardiovascular disease, a process that can begin in childhood. OBJECTIVE: To assess the safety and efficacy of atorvastatin improving lipid profiles in children with T1D and elevated LDL-C. SUBJECTS: Sixty children (31M/29F) with T1D, mean age: 15 ± 0.3 yr, mean diabetes duration: 6.8 ± 0.5 yr, HbA(1c) : 8.8 ± 0.2%, with mean LDL-C 124 ± 4.0mg/dl were recruited. METHODS: After a 3-month run-in period, subjects were randomized double-blindly to atorvastatin or placebo for 6 months. Lipoprotein subfractions were measured by ion mobility and glucose control by HbA1C; continuous glucose monitors were worn quarterly. RESULTS: After a run-in period, 42 subjects were randomized. There were decreases in total cholesterol (-21%), LDL-C (-32%), non-HDL-C (-31%) and apoB (-26%) in the atorvastatin group versus placebo (p < 0.001). Lipoprotein subparticles (LDL-large 1 and 2A, IDL-large and small, VLDL- medium and small) decreased with statins (p < 0.03 all). Insulin sensitivity scores remained constant in both groups and correlated inversely with apoB (r = -0.312 p = 0.039) and small LDL 3A (r = -0.404 p = 0.007). One subject had asymptomatic elevation of creatinine kinase which normalized after atorvastatin discontinuation. CONCLUSIONS: Atorvastatin lowered LDL-C, apoB, and atherogenic lipoprotein subparticles in children with T1D and elevated LDL-C without worsening insulin resistance. The drug was well tolerated and safe. Long-term studies would provide better insight on the impact of these interventions in the development of cardiovascular disease in children with diabetes.