Pediatric Lyme disease: systematic assessment of post-treatment symptoms and quality of life.

BACKGROUND: Lyme disease is common among children and adolescents. Antibiotic treatment is effective, yet some patients report persistent symptoms following treatment, with or without functional impairment. This study characterized long-term outcome of pediatric patients with Lyme disease and evaluated the case definition of post-treatment Lyme disease (PTLD) syndrome. METHODS: The sample included 102 children with confirmed Lyme disease diagnosed 6 months-10 years prior to enrollment (M = 2.0 years). Lyme diagnosis and treatment information was extracted from the electronic health record; parent report identified presence, duration, and impact of symptoms after treatment. Participants completed validated questionnaires assessing health-related quality of life, physical mobility, fatigue, pain, and cognitive impact. RESULTS: Most parents reported their child's symptoms resolved completely, although time to full resolution varied. Twenty-two parents (22%) indicated their child had at least one persistent symptom >6 months post-treatment, 13 without functional impairment (PTLD symptoms) and 9 with functional impairment (PTLD syndrome). Children with PTLD syndrome had lower parent-reported Physical Summary scores and greater likelihood of elevated fatigue. CONCLUSIONS: In the current study, most children with Lyme disease experienced full resolution of symptoms, including those who initially met PTLD syndrome criteria. Effective communication about recovery rates and common symptoms that may persist post-treatment is needed. IMPACT: The majority of pediatric patients treated for all stages of Lyme disease reported full resolution of symptoms within 6 months. 22% of pediatric patients reported one or more symptom persisting >6 months, 9% with and 13% without accompanying functional impairment. Effective communication with families about recovery rates and common symptoms that may persist post-treatment of Lyme disease is needed.

Pediatric screen exposure and school related headache disability.

BACKGROUND AND OBJECTIVES: Prolonged screen exposure is often cited as a trigger for pediatric headache. We present initial findings evaluating the association between adolescent screen use type, duration, and school disability. METHODS: New patients aged 12-17 years presenting to a headache clinic were screened and surveyed regarding headache characteristics, behavioral habits, school attendance, and screen utilization. RESULTS: 99 adolescents (29 M, 70 F) with average age 14.8 years and average headache frequency of 17 days per month completed the survey. Patients missed an average of five full days and three partial days of school due to headaches over the 90 days prior to survey completion.No statistically significant correlation was found between type or duration of screen exposure and monthly headache frequency, school attendance, or school functioning. A small positive association was seen between increasing duration of computer use, total hours screen use, and school absenteeism. While most adolescents reported prolonged screen use (58.6%) and luminosity (64.6%) worsened headaches, no statistical difference was seen in average number of headache days per month. CONCLUSIONS: Average monthly headache frequency in an adolescent population was not significantly correlated with type or duration of screen exposure. Further studies are needed to elucidate how screen utilization impacts school related headache disability.

Effect of the coronavirus disease 2019 pandemic on morbidity among children hospitalized for an asthma exacerbation.

BACKGROUND: Pediatric asthma exacerbations account for substantial morbidity, including emergency department (ED) visits and hospitalizations. Although the coronavirus disease 2019 (COVID-19) pandemic was associated with a decrease in pediatric asthma ED visits and hospitalizations, there is limited information on the clinical characteristics of children hospitalized with an asthma exacerbation during the pandemic. OBJECTIVE: To investigate the clinical characteristics of children hospitalized with an asthma exacerbation during the pandemic as compared with those hospitalized during the same months in the year prior. METHODS: A retrospective case-control study was conducted at the Children's National Hospital, Washington, DC, comparing demographic and clinical characteristics of all children, 2 to 18 years old, hospitalized for an asthma exacerbation between April to September 2020 (cases) and April to September 2019 (controls). RESULTS: We identified 50 cases and 243 controls. Cases were significantly older than controls (9.8 ± 4.3 years vs 6.7 ± 3.8 years; P < .001), had significantly less eczema (16% vs 32.1%; P = .02) and food allergies (6% vs 18.5%; P = .03), and were more noncompliant with controller medications (46% vs 24.7%; P = .002) than controls. Magnesium sulfate was more frequently administered in the ED to the cases than to the controls (84% vs 63%; P = .004). Its use was associated with older age, African American race, and Hispanic ethnicity, but was independent of comorbid conditions. CONCLUSION: Patients hospitalized for asthma during the COVID-19 pandemic were older and have less atopy than those hospitalized prepandemic. A larger proportion received magnesium sulfate in the ED, suggesting patients had with more severe asthma presentation during the pandemic.

Predicting Failure of Non-Invasive Ventilation With RAM Cannula in Bronchiolitis.

INTRODUCTION: In infants hospitalized for bronchiolitis on non-invasive ventilation (NIV) via the RAM cannula nasal interface, variables predicting subsequent intubation, or NIV non-response, are understudied. We sought to identify predictors of NIV non-response. METHODS: We performed a retrospective cohort study in infants admitted for respiratory failure from bronchiolitis placed on NIV in a quaternary children's hospital. We excluded children with concurrent sepsis, critical congenital heart disease, or with preexisting tracheostomy. The primary outcome was NIV non-response defined as intubation after a trial of NIV. Secondary outcomes were vital sign values before and after NIV initiation, duration of NIV and intubation, and mortality. Primary analyses included Chi-square, Wilcoxon rank-sum, student's t test, paired analyses, and adjusted and unadjusted logistic regression assessing heart rate (HR) and respiratory rate (RR) before and after NIV initiation. RESULTS: Of 138 infants studied, 34% were non-responders. There were no differences in baseline characteristics of responders and non-responders. HR decreased after NIV initiation in responders (156 [143-156] to149 [141-158], p < 0.01) compared to non-responders (158 [149-166] to 158 [145-171], p = 0.73). RR decreased in responders (50 [43-58] vs 47 [41-54]) and non-responders (52 [48-58] vs 51 [40-55], both p < 0.01). Concurrent bacterial pneumonia (OR 6.06, 95% CI: 2.54-14.51) and persistently elevated HR (OR: 1.04, 95% CI: 1.01-1.07) were associated with NIV non-response. CONCLUSION: In children with acute bronchiolitis who fail to respond to NIV and require subsequent intubation, we noted associations with persistently elevated HR after NIV initiation and concurrent bacterial pneumonia.

Alterations in cardiac output in fetuses with congenital heart disease.

OBJECTIVE: Fetuses with severe congenital heart disease (CHD) have altered blood flow patterns. Prior work to assess fetal combined cardiac output (CCO) is limited by sample size and lack of longitudinal gestational data. Our aim was to evaluate CCO in CHD fetuses to determine whether the presence of single ventricle (SV) physiology or aortic obstruction impacts fetal blood flow and cardiovascular hemodynamics. METHOD: Prospective study including singleton fetuses with CHD (n = 141) and controls (n = 118) who underwent a mid- and late-gestation fetal echocardiogram. Ventricular cardiac output was calculated using the standard computation. Combined cardiac output was derived as the sum of the right and left cardiac outputs and indexed to estimated fetal weight. RESULTS: Fetuses with two ventricle (2V) CHD had significantly higher CCO compared to controls and SV CHD fetuses. Fetuses with SV-CHD had similar CCO compared to controls. Fetuses with 2V-CHD and aortic obstruction had significantly higher CCO than fetuses with SV-CHD and aortic obstruction. CONCLUSION: Our findings suggest that the SV can compensate and increase CCO despite the lack of a second functioning ventricle, however, the degree of compensation may be insufficient to support the increased blood flow needed to overcome the hemodynamic and physiologic alternations seen with severe CHD.

Cardiac echocardiogram findings of severe acute respiratory syndrome coronavirus-2-associated multi-system inflammatory syndrome in children.

BACKGROUND: A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic. OBJECTIVES: To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children. METHODS: Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher's exact, and Wilcoxon rank sum. RESULTS: Thirty-nine children with median (interquartile range) age 7.8 (3.6-12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26-61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04). CONCLUSION: Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

An educational intervention to facilitate appropriate subspecialty referrals: a study assessing resident communication skills.

BACKGROUND: Our goal was to improve pediatric residents' advanced communication skills in the setting of referral to address the entrustable professional activity of subspecialty referral identified by the American Board of Pediatrics. To accomplish this aim, we created a referral and consultation curriculum to teach and assess core communication skills in subspecialty referral involving an adolescent with syncope, an anxiety-provoking symptom that is rarely associated with serious pathology. METHODS: We utilized blended multimodal educational interventions to improve resident communication skills in referral of patients. Trainees participated in 1) an interactive online module on syncope focusing on "red-flag" symptoms that would warrant a subspecialty cardiology referral and 2) a 4-h intervention with Standardized Parents (SPs), focusing on the case-based application of communication skills. Communication skills were assessed by two pre- and post- Objective Structured Clinical Examination encounters of patients with syncope, with an SP evaluation using a 20-item checklist. Analysis was performed with Sign test and McNemar's test. Trainees provided feedback on a Critical Incident Questionnaire, which was analyzed qualitatively. RESULTS: Sixty-four residents participated. There was an overall improvement in communication skills based on SP scores (82.7 ± 10.9% to 91.7 ± 5.0%, p < 0.001), and 13/20 items demonstrated significant improvement post-intervention. Residents' improved performance enabled them to address patient/family emotions, explain referral logistics, and clarify concerns to agree on a plan. CONCLUSIONS: By participating in this curriculum, residents' communication skills improved immediately post-intervention. Further research is needed to assess if this intervention improves patient care by providing residents with enduring skills to judiciously manage the referral process.

Early Versus Late Brain Magnetic Resonance Imaging after Neonatal Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia.

OBJECTIVE: To evaluate the agreement in brain injury findings between early and late magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and to compare the ability of early vs late MRI to predict early neurodevelopmental outcomes. STUDY DESIGN: This was a prospective longitudinal study of 49 patients with hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia and had MRI performed at both <7 and ≥7 days of age. MRIs were reviewed by an experienced neuroradiologist and assigned brain injury severity scores according to established systems. Scores for early and late MRIs were assessed for agreement using the kappa statistic. The ability of early and late MRI scores to predict death or developmental delay at 15-30 months of age was assessed by logistic regression analyses. RESULTS: Agreement between the early and late MRI was substantial to near perfect (k > 0.75, P < .001) across MRI scoring systems. In cases of discrepant scoring, early MRI was more likely to identify severe injury when compared with late MRI. Early MRI scores were more consistently predictive of adverse outcomes compared with late MRI. CONCLUSIONS: The results of this study suggest that a single MRI performed in the first week after birth is adequate to assess brain injury and offer prognostic information in this high-risk population.

Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.

Serial plasma biomarkers of brain injury in infants with neonatal encephalopathy treated with therapeutic hypothermia.

BACKGROUND: Neonatal encephalopathy (NE) is a major cause of long-term neurodevelopmental disability in neonates. We evaluated the ability of serially measured biomarkers of brain injury to predict adverse neurological outcomes in this population. METHODS: Circulating brain injury biomarkers including BDNF, IL-6, IL-8, IL-10, VEGF, Tau, GFAP, and NRGN were measured at 0, 12, 24, 48, 72, and 96 h of cooling from 103 infants with NE undergoing TH. The biomarkers' individual and combinative ability to predict death or severe brain injury and adverse neurodevelopmental outcomes beyond 1 year of age was assessed. RESULTS: Early measurements of inflammatory cytokines IL-6, 8, and 10 within 24 HOL (AUC = 0.826) and late measurements of Tau from 72 to 96 HOL (AUC = 0.883, OR 4.37) were accurate in predicting severe brain injury seen on MRI. Late measurements of Tau were predictive of adverse neurodevelopmental outcomes (AUC = 0.81, OR 2.59). CONCLUSIONS: Tau was consistently a predictive marker for brain injury in neonates with NE. However, in the first 24 HOL, IL-6, 8, and 10 in combination were most predictive of death or severe brain injury. The results of this study support the use of a serial biomarker panel to assess brain injury over the time course of disease in NE. IMPACT: While recent studies have evaluated candidate brain injury biomarkers, no biomarker is in current clinical use. This study supports the use of a serial biomarker panel for ongoing assessment of brain injury neonates with NE. In combination, IL6, IL8, and IL10 in the first 24 h of cooling were more predictive of brain injury by MRI than each cytokine alone. Individually, Tau was overall most consistently predictive of adverse neurological outcomes, particularly when measured at or after rewarming.

Early Inflammatory Markers are Associated With Inadequate Post-Induction Infliximab Trough in Pediatric Crohn's Disease.

OBJECTIVES: In pediatric Crohn's disease, infliximab trough concentrations after standard weight-based induction therapy are commonly below 7 µg/mL. Clinical treatment outcomes are associated with post-induction infliximab trough concentration. Markers of inflammation are associated with low infliximab concentrations during maintenance dosing. We sought to determine if early markers of disease activity are associated with inadequate post-induction infliximab trough concentrations in pediatric Crohn's disease. METHODS: We performed a retrospective single-center case-control study of pediatric Crohn's disease patients to assess the association between baseline and week-2 biomarkers (albumin, C-reactive protein, and erythrocyte sedimentation rate) and inadequate post-induction infliximab trough concentration (<7 µg/mL) in patients treated with standard 5 mg/kg dosing. Baseline and week-2 biomarker values were coded as dichotomous variables at clinically useful thresholds. Univariable logistic regression was used to calculate odds ratios of developing an inadequate infliximab trough concentration for each threshold, as well as thresholds in combination. RESULTS: Fifty-five patients were evaluated. Early biomarker thresholds significantly associated with inadequate post-induction infliximab trough concentrations included baseline C-reactive protein >1 mg/dL (odds ratio [OR] 4.58; 95% confidence interval [CI] 1.24--17.01), both baseline C-reactive protein >0.5 mg/dL and albumin <3.5 g/dL (OR 8.31; 95% CI 1.99--34.63), and week-2 C-reactive protein >0.5 mg/dL or albumin <3.5 mg/dL or erythrocyte sedimentation rate >25 mm/hour (OR 11.08; 95% CI 2.14--57.22). CONCLUSIONS: Routine baseline and week-2 markers of disease activity at clinically useful thresholds were associated with inadequate post-induction infliximab trough concentration in pediatric Crohn's disease patients receiving standard weight-based induction dosing.

The Association of Laboratory Test Abnormalities With Mortality Risk in Pediatric Intensive Care.

OBJECTIVES: To determine the bivariable associations between abnormalities of 28 common laboratory tests and hospital mortality and determine how mortality risks changes when the ranges are evaluated in the context of commonly used laboratory test panels. DESIGN: A 2009-2016 cohort from the Health Facts (Cerner Corporation, Kansas City, MO) database. SETTING: Hospitals caring for children in ICUs. PATIENTS: Children cared for in ICUs with laboratory data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 2,987,515 laboratory measurements in 71,563 children. The distribution of laboratory test values in 10 groups defined by population percentiles demonstrated the midrange of tests was within the normal range except for those measured predominantly when significant abnormalities are suspected. Logistic regression analysis at the patient level combined the population-based groups into ranges with nonoverlapping mortality odds ratios. The most deviant test ranges associated with increased mortality risk (mortality odds ratios > 5.0) included variables associated with acidosis, coagulation abnormalities and blood loss, immune function, liver function, nutritional status, and the basic metabolic profile. The test ranges most associated with survival included normal values for chloride, pH, and bicarbonate/total Co2. When the significant test ranges from bivariable analyses were combined in commonly used test panels, they generally remained significant but were reduced as risk was distributed among the tests. CONCLUSIONS: The relative importance of laboratory test ranges vary widely, with some ranges strongly associated with mortality and others strongly associated with survival. When evaluated in the context of test panels rather than isolated tests, the mortality odds ratios for the test ranges decreased but generally remained significant as risk was distributed among the components of the test panels. These data are useful to develop critical values for children in ICUs, to identify risk factors previously underappreciated, for education and training, and for future risk score development.

Severity Trajectories of Pediatric Inpatients Using the Criticality Index.

OBJECTIVES: To assess severity of illness trajectories described by the Criticality Index for survivors and deaths in five patient groups defined by the sequence of patient care in ICU and routine patient care locations. DESIGN: The Criticality Index developed using a calibrated, deep neural network, measures severity of illness using physiology, therapies, and therapeutic intensity. Criticality Index values in sequential 6-hour time periods described severity trajectories. SETTING: Hospitals with pediatric inpatient and ICU care. PATIENTS: Pediatric patients never cared for in an ICU (n = 20,091), patients only cared for in the ICU (n = 2,096) and patients cared for in both ICU and non-ICU care locations (n = 17,023) from 2009 to 2016 Health Facts database (Cerner Corporation, Kansas City, MO). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Criticality Index values were consistent with clinical experience. The median (25-75th percentile) ICU Criticality Index values (0.878 [0.696-0.966]) were more than 80-fold higher than the non-ICU values (0.010 [0.002-0.099]). Non-ICU Criticality Index values for patients transferred to the ICU were 40-fold higher than those never transferred to the ICU (0.164 vs 0.004). The median for ICU deaths was higher than ICU survivors (0.983 vs 0.875) (p < 0.001). The severity trajectories for the five groups met expectations based on clinical experience. Survivors had increasing Criticality Index values in non-ICU locations prior to ICU admission, decreasing Criticality Index values in the ICU, and decreasing Criticality Index values until hospital discharge. Deaths had higher Criticality Index values than survivors, steeper increases prior to the ICU, and worsening values in the ICU. Deaths had a variable course, especially those who died in non-ICU care locations, consistent with deaths associated with both active therapies and withdrawals/limitations of care. CONCLUSIONS: Severity trajectories measured by the Criticality Index showed strong validity, reflecting the expected clinical course for five diverse patient groups.

Criticality: A New Concept of Severity of Illness for Hospitalized Children.

OBJECTIVES: To validate the conceptual framework of "criticality," a new pediatric inpatient severity measure based on physiology, therapy, and therapeutic intensity calibrated to care intensity, operationalized as ICU care. DESIGN: Deep neural network analysis of a pediatric cohort from the Health Facts (Cerner Corporation, Kansas City, MO) national database. SETTING: Hospitals with pediatric routine inpatient and ICU care. PATIENTS: Children cared for in the ICU (n = 20,014) and in routine care units without an ICU admission (n = 20,130) from 2009 to 2016. All patients had laboratory, vital sign, and medication data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A calibrated, deep neural network used physiology (laboratory tests and vital signs), therapy (medications), and therapeutic intensity (number of physiology tests and medications) to model care intensity, operationalized as ICU (versus routine) care every 6 hours of a patient's hospital course. The probability of ICU care is termed the Criticality Index. First, the model demonstrated excellent separation of criticality distributions from a severity hierarchy of five patient groups: routine care, routine care for those who also received ICU care, transition from routine to ICU care, ICU care, and high-intensity ICU care. Second, model performance assessed with statistical metrics was excellent with an area under the curve for the receiver operating characteristic of 0.95 for 327,189 6-hour time periods, excellent calibration, sensitivity of 0.817, specificity of 0.892, accuracy of 0.866, and precision of 0.799. Third, the performance in individual patients with greater than one care designation indicated as 88.03% (95% CI, 87.72-88.34) of the Criticality Indices in the more intensive locations was higher than the less intense locations. CONCLUSIONS: The Criticality Index is a quantification of severity of illness for hospitalized children using physiology, therapy, and care intensity. This new conceptual model is applicable to clinical investigations and predicting future care needs.

High Acuity Therapy Variation Across Pediatric Acute Care Cardiology Units: Results from the Pediatric Acute Care Cardiology Collaborative Hospital Surveys.

We utilized the multicenter Pediatric Acute Care Cardiology Collaborative (PAC3) 2017 and 2019 surveys to describe practice variation in therapy availability and changes over a 2-year period. A high acuity therapies (ATs) score was derived (1 point per positive response) from 44 survey questions and scores were compared to center surgical volume. Of 31 centers that completed the 2017 survey, 26 also completed the 2019 survey. Scores ranged from 11 to 34 in 2017 and 11 to 35 in 2019. AT scores in 2019 were not statistically different from 2017 scores (29/44, IQR 27-32.5 vs. 29.5/44, IQR 27-31, p = 0.9). In 2019, more centers reported initiation of continuous positive airway pressure (CPAP) and Bi-level positive airway pressure (BiPAP) in Acute Care Cardiology Unit (ACCU) (19/26 vs. 4/26, p < 0.001) and permitting continuous CPAP/BiPAP (22/26 vs. 14/26, p = 0.034) compared to 2017. Scores in both survey years were significantly higher in the highest surgical volume group compared to the lowest, 33 ± 1.5 versus 25 ± 8.5, p = 0.046 and 32 ± 1.7 versus 23 ± 5.5, p = 0.009, respectively. Variation in therapy within the ACCUs participating in PAC3 presents an opportunity for shared learning across the collaborative. Experience with PAC3 was associated with increasing available respiratory therapies from 2017 to 2019. Whether AT scores impact the quality and outcomes of pediatric acute cardiac care will be the subject of further investigation using a comprehensive registry launched in early 2019.

Treadmill exercise testing improves diagnostic accuracy in children with concealed congenital long QT syndrome.

BACKGROUND: Resting electrocardiogram (ECG) identification of long QT syndrome (LQTS) has limitations. Uncertainty exists on how to classify patients with borderline prolonged QT intervals. We tested if exercise testing could help serve to guide which children with borderline prolonged QT intervals may be gene positive for LQTS. METHODS: Pediatric patients (n = 139) were divided into three groups: Controls (n = 76), gene positive LQTS with borderline QTc (n = 21), and gene negative patients with borderline QTc (n = 42). Borderline QTc was defined between 440-470 (male) and 440-480 (female) ms. ECGs were recorded supine, sitting, and standing. Patients then underwent treadmill stress testing with Bruce protocol followed by a 9-minute recovery phase. RESULTS: Supine resting QTc, age, and Schwartz score for the three groups were: (a) gene positive: 446 ± 23 ms, 12.4 ± 3.4 years old, 3.2 ± 1.8; (b) gene negative: 445 ± 20 ms, 12.1 ± 2 years old, 2.0 ± 1.2; and (c) control: 400 ± 24 ms, 15.0 ± 3 years old. The three groups could be differentiated by their QTc response at two time points: standing and recovery phase at 6 minutes. Standing QTc ≥460 ms differentiated borderline prolonged QTc patients (gene positive and gene negative) from controls. Late recovery QTc ≥480 ms distinguished gene positive from gene negative patients. CONCLUSION: Exercise stress testing can be useful to identify children who are gene positive borderline LQTS from a normal population and gene negative borderline QTc children, allowing for selective gene testing in a higher risk group of patients with borderline QTc intervals and intermediate Schwartz scores.

Parvovirus B19 infection in sickle cell disease: An analysis from the Centers for Disease Control haemoglobinopathy blood surveillance project.

OBJECTIVE: In the multicentre Haemoglobinopathy Blood Surveillance Project, to evaluate the seroprevalence of parvovirus B19 and DNA viral load in sickle cell disease (SCD). BACKGROUND: Although the epidemiology of parvovirus B19 seropositivity in SCD has been well documented, there are few studies that have assessed possible persistent parvovirus DNAemia and associated risk factors including blood transfusion. METHODS: A qualitative analysis of parvovirus B19 serology using ELISA and quantitative parvovirus B19 DNA by RT-PCR was performed in patients with SCD. RESULTS: Of 322 patients, 113 (35%) were parvovirus IgG positive and 119 (37%) were IgM positive at enrolment. The prevalence of IgG positivity increased with age. 71/322 (22%) were parvovirus DNA positive at enrolment with a mean viral load of 15 227 ± 55 227 SD. (range 72-329 238 IU/mL). Patients who were positive for parvovirus B19 DNA received a significantly higher red blood cell transfusion volume in the prior year compared to patients who were negative (mean RBC volume = 8310 mL vs 5435 mL, respectively; P = .0073). Seventy-seven patients had follow-up testing approximately 1 year after enrolment and 11/28 (39%) patients had persistently positive IgM. CONCLUSION: Further studies are needed to better understand the natural history of parvovirus B19 infection in SCD especially in relation to RBC transfusion as a risk factor, as well as disease outcome and severity.

Medications for Children Receiving Intensive Care: A National Sample.

OBJECTIVE: To examine medication administration records through electronic health record data to provide a broad description of the pharmaceutical exposure of critically ill children. DESIGN: Retrospective cohort study using the Cerner Health Facts database. SETTING: United States. PATIENTS: A total of 43,374 children 7 days old to less than 22 years old receiving intensive care with available pharmacy data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 907,440 courses of 1,080 unique medications were prescribed with a median of nine medications (range, 1-99; 25-75th percentile, 5-16) per patient. The most common medications were acetaminophen, ondansetron, and morphine. Only 45 medications (4.2%) were prescribed to more than 5% of patients, and these accounted for 442,067 (48.7%) of the total courses of medications. Each additional medication was associated with increased univariate risk of mortality (odds ratio, 1.05; 95% CI, 1.05-1.06; p < 0.001). CONCLUSIONS: Children receiving intensive care receive a median of nine medications per patient and one quarter are prescribed at least than 16 medications. Only 45 medications were prescribed to more than 5% of patients, but these accounted for almost half of all medication courses.

Sedation, Analgesia, and Neuromuscular Blockade: An Assessment of Practices From 2009 to 2016 in a National Sample of 66,443 Pediatric Patients Cared for in the ICU.

OBJECTIVES: To describe the pharmaceutical management of sedation, analgesia, and neuromuscular blockade medications administered to children in ICUs. DESIGN: A retrospective analysis using data extracted from the national database Health Facts. SETTING: One hundred sixty-one ICUs in the United States with pediatric admissions. PATIENTS: Children in ICUs receiving medications from 2009 to 2016. EXPOSURE/INTERVENTION: Frequency and duration of administration of sedation, analgesia, and neuromuscular blockade medications. MEASUREMENTS AND MAIN RESULTS: Of 66,443 patients with a median age of 1.3 years (interquartile range, 0-14.5), 63.3% (n = 42,070) received nonopioid analgesic, opioid analgesic, sedative, and/or neuromuscular blockade medications consisting of 83 different agents. Opioid and nonopioid analgesics were dispensed to 58.4% (n = 38,776), of which nonopioid analgesics were prescribed to 67.4% (n = 26,149). Median duration of opioid analgesic administration was 32 hours (interquartile range, 7-92). Sedatives were dispensed to 39.8% (n = 26,441) for a median duration of 23 hours (interquartile range, 3-84), of which benzodiazepines were most common (73.4%; n = 19,426). Neuromuscular-blocking agents were dispensed to 17.3% (n = 11,517) for a median duration of 2 hours (interquartile range, 1-15). Younger age was associated with longer durations in all medication classes. A greater proportion of operative patients received these medication classes for a longer duration than nonoperative patients. A greater proportion of patients with musculoskeletal and hematologic/oncologic diseases received these medication classes. CONCLUSIONS: Analgesic, sedative, and neuromuscular-blocking medications were prescribed to 63.3% of children in ICUs. The durations of opioid analgesic and sedative medication administration found in this study can be associated with known complications, including tolerance and withdrawal. Several medications dispensed to pediatric patients in this analysis are in conflict with Food and Drug Administration warnings, suggesting that there is potential risk in current sedation and analgesia practice that could be reduced with practice changes to improve efficacy and minimize risks.