Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021.

During June 2021, the highly transmissible† B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States. U.S. pediatric COVID-19-related hospitalizations increased during July-August 2021 following emergence of the Delta variant and peaked in September 2021.§ As of May 12, 2021, CDC recommended COVID-19 vaccinations for persons aged ≥12 years,¶ and on November 2, 2021, COVID-19 vaccinations were recommended for persons aged 5-11 years.** To date, clinical signs and symptoms, illness course, and factors contributing to hospitalizations during the period of Delta predominance have not been well described in pediatric patients. CDC partnered with six children's hospitals to review medical record data for patients aged <18 years with COVID-19-related hospitalizations during July-August 2021.†† Among 915 patients identified, 713 (77.9%) were hospitalized for COVID-19 (acute COVID-19 as the primary or contributing reason for hospitalization), 177 (19.3%) had incidental positive SARS-CoV-2 test results (asymptomatic or mild infection unrelated to the reason for hospitalization), and 25 (2.7%) had multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition associated with COVID-19.§§ Among the 713 patients hospitalized for COVID-19, 24.7% were aged <1 year, 17.1% were aged 1-4 years, 20.1% were aged 5-11 years, and 38.1% were aged 12-17 years. Approximately two thirds of patients (67.5%) had one or more underlying medical conditions, with obesity being the most common (32.4%); among patients aged 12-17 years, 61.4% had obesity. Among patients hospitalized for COVID-19, 15.8% had a viral coinfection¶¶ (66.4% of whom had respiratory syncytial virus [RSV] infection). Approximately one third (33.9%) of patients aged <5 years hospitalized for COVID-19 had a viral coinfection. Among 272 vaccine-eligible (aged 12-17 years) patients hospitalized for COVID-19, one (0.4%) was fully vaccinated.*** Approximately one half (54.0%) of patients hospitalized for COVID-19 received oxygen support, 29.5% were admitted to the intensive care unit (ICU), and 1.5% died; of those requiring respiratory support, 14.5% required invasive mechanical ventilation (IMV). Among pediatric patients with COVID-19-related hospitalizations, many had severe illness and viral coinfections, and few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions.

Recurrent Acute Chest Syndrome in Pediatric Sickle Cell Disease: Clinical Features and Risk Factors.

Acute chest syndrome (ACS) is a common and serious lung complication in sickle cell disease. A retrospective medical chart review was performed over a 6-year period in all pediatric ACS patients to investigate whether factors during the initial hospitalization were associated with recurrent ACS episodes. There were 386 episodes of ACS: 149 had only 1 episode of ACS, and 76 had >1 episode of ACS; 172 (76.4%) had hemoglobin SS, and 39 (17.3%) had hemoglobin SC. The most common presenting features were fever (83%), pain (70%), and cough (61%), which changed with the number of ACS episodes. Children <4 years old were at greatest risk of recurrent ACS (P=0.018). In addition, history of asthma (adjusted incident rate ratio [IRR]=1.52; 95% confidence interval [CI], 1.22-1.98; P<0.0001), shortness of breath (IRR, 1.29; 95% CI, 1.02-1.62; P=0.033), and length of hospital stay (IRR, 1.04; 95% CI, 1.01-1.08; P=0.017) were significantly associated with prospective ACS events. Multiple episodes of ACS are common in sickle cell disease, and certain risk factors during the initial hospitalization are associated with recurrent ACS.

Physician Specialty Differences in Unprofessional Behaviors Observed and Reported by Coworkers.

Importance: Because unprofessional behaviors are associated with patient complications, malpractice claims, and well-being concerns, monitoring concerns requiring investigation and individuals identified in multiple reports may provide important opportunities for health care leaders to support all team members. Objective: To examine the distribution of physicians by specialty who demonstrate unprofessional behaviors measured through safety reports submitted by coworkers. Design, Setting, and Participants: This retrospective cohort study was conducted among physicians who practiced at the 193 hospitals in the Coworker Concern Observation Reporting System (CORS), administered by the Vanderbilt Center for Patient and Professional Advocacy. Data were collected from January 2018 to December 2022. Exposure: Submitted reports concerning communication, professional responsibility, medical care, and professional integrity. Main Outcomes and Measures: Physicians' total number and categories of CORS reports. The proportion of physicians in each specialty (nonsurgeon nonproceduralists, emergency medicine physicians, nonsurgeon proceduralists, and surgeons) who received at least 1 report and who qualified for intervention were calculated; logistic regression was used to calculate the odds of any CORS report. Results: The cohort included 35 120 physicians: 18 288 (52.1%) nonsurgeon nonproceduralists, 1876 (5.3%) emergency medicine physicians, 6743 (19.2%) nonsurgeon proceduralists, and 8213 (23.4%) surgeons. There were 3179 physicians (9.1%) with at least 1 CORS report. Nonsurgeon nonproceduralists had the lowest percentage of physicians with at least 1 report (1032 [5.6%]), followed by emergency medicine (204 [10.9%]), nonsurgeon proceduralists (809 [12.0%]), and surgeons (1134 [13.8%]). Nonsurgeon nonproceduralists were less likely to be named in a CORS report than other specialties (5.6% vs 12.8% for other specialties combined; difference in percentages, -7.1 percentage points; 95% CI, -7.7 to -6.5 percentage points; P < .001). Pediatric-focused nonsurgeon nonproceduralists (2897 physicians) were significantly less likely to be associated with a CORS report than nonpediatric nonsurgeon nonproceduralists (15 391 physicians) (105 [3.6%] vs 927 [6.0%]; difference in percentages, -2.4 percentage points, 95% CI, -3.2 to -1.6 percentage points; P < .001). Pediatric-focused emergency medicine physicians, nonsurgeon proceduralists, and surgeons had no significant differences in reporting compared with nonpediatric-focused physicians. Conclusions and Relevance: In this cohort study, less than 10% of physicians ever received a coworker report with a concern about unprofessional behavior. Monitoring reports of unprofessional behaviors provides important opportunities for health care organizations to identify and intervene as needed to support team members.

Factors Associated With Severe Illness in Patients Aged <21 Years Hospitalized for COVID-19.

OBJECTIVES: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness. METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients aged <21 years hospitalized at 6 United States children's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation. RESULTS: Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with respiratory syncytial virus (RSV) (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1 to 4 years (PR 1.96); and obesity in patients aged 5 to 11 (PR 2.20) and 12 to 17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged <1 (PR 1.82), 5 to 11 (PR 3.72), and 12 to 17 years (PR 3.19). CONCLUSIONS: Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged <5 years, obesity in those aged 5 to 17 years, and other underlying conditions for all age groups <18 years. These findings can inform pediatric practice, risk communication, and prevention strategies, including vaccination against COVID-19.

Diagnosing delirium in critically ill children: Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit.

OBJECTIVE: To validate a diagnostic instrument for pediatric delirium in critically ill children, both ventilated and nonventilated, that uses standardized, developmentally appropriate measurements. DESIGN AND SETTING: A prospective observational cohort study investigating the Pediatric Confusion Assessment Method for Intensive Care Unit (pCAM-ICU) patients in the pediatric medical, surgical, and cardiac intensive care unit of a university-based medical center. PATIENTS: A total of 68 pediatric critically ill patients, at least 5 years of age, were enrolled from July 1, 2008, to March 30, 2009. INTERVENTIONS: None. MEASUREMENTS: Criterion validity including sensitivity and specificity and interrater reliability were determined using daily delirium assessments with the pCAM-ICU by two critical care clinicians compared with delirium diagnosis by pediatric psychiatrists using Diagnostic and Statistical Manual, 4th Edition, Text Revision criteria. RESULTS: A total of 146 paired assessments were completed among 68 enrolled patients with a mean age of 12.2 yrs. Compared with the reference standard for diagnosing delirium, the pCAM-ICU demonstrated a sensitivity of 83% (95% confidence interval, 66-93%), a specificity of 99% (95% confidence interval, 95-100%), and a high interrater reliability (κ = 0.96; 95% confidence interval, 0.74-1.0). CONCLUSIONS: The pCAM-ICU is a highly valid reliable instrument for the diagnosis of pediatric delirium in critically ill children chronologically and developmentally at least 5 yrs of age. Use of the pCAM-ICU may expedite diagnosis and consultation with neuropsychiatry specialists for treatment of pediatric delirium. In addition, the pCAM-ICU may provide a means for delirium monitoring in future epidemiologic and interventional studies in critically ill children.

Validation of a gene expression-based subclassification strategy for pediatric septic shock.

OBJECTIVE: Septic shock heterogeneity has important implications for clinical trial implementation and patient management. We previously addressed this heterogeneity by identifying three putative subclasses of children with septic shock based exclusively on a 100-gene expression signature. Here we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort. DESIGN: Prospective observational study involving microarray-based bioinformatics. SETTING: Multiple pediatric intensive care units in the United States. PATIENTS: Separate derivation (n = 98) and validation (n = 82) cohorts of children with septic shock. INTERVENTIONS: None other than standard care. MEASUREMENTS AND MAIN RESULTS: Gene expression mosaics of the 100 class-defining genes were generated for 82 individual patients in the validation cohort. Using computer-based image analysis, patients were classified into one of three subclasses ("A," "B," or "C") based on color and pattern similarity relative to reference mosaics generated from the original derivation cohort. After subclassification, the clinical database was mined for phenotyping. Subclass A patients had higher illness severity relative to subclasses B and C as measured by maximal organ failure, fewer intensive care unit-free days, and a higher Pediatric Risk of Mortality score. Patients in subclass A were characterized by repression of genes corresponding to adaptive immunity and glucocorticoid receptor signaling. Separate subclass assignments were conducted by 21 individual clinicians using visual inspection. The consensus classification of the clinicians had modest agreement with the computer algorithm. CONCLUSIONS: We have validated the existence of subclasses of children with septic shock based on a biologically relevant, 100-gene expression signature. The subclasses have relevant clinical differences.

An ethnic-specific polymorphism in the catalytic subunit of glutamate-cysteine ligase impairs the production of glutathione intermediates in vitro.

Glutathione plays a crucial role in free radical scavenging, oxidative injury, and cellular homeostasis. Previously, we identified a non-synonymous polymorphism (P462S) in the gene encoding the catalytic subunit of glutamate-cysteine ligase (GCLC), the rate-limiting enzyme in glutathione biosynthesis. This polymorphism is present only in individuals of African descent. Presently, we report that this ethnic-specific polymorphism (462S) encodes an enzyme with significantly decreased in vitro activity when expressed by either a bacterial or mammalian cell expression system. In addition, overexpression of the 462P wild-type GCLC enzyme results in higher intracellular glutathione concentrations than overexpression of the 462S isoform. We also demonstrate that apoptotically stimulated mammalian cells overexpressing the 462S enzyme have increased caspase activation and increased DNA laddering compared to cells overexpressing the wild-type 462P enzyme. Finally, we genotyped several African and African-descent populations and demonstrate that the 462S polymorphism is in Hardy-Weinberg disequilibrium, with no individuals homozygous for the 462S polymorphism identified. These findings describe a glutathione production pathway polymorphism present in individuals of African descent with significantly decreased in vitro activity.

Inhaled nitric oxide and related therapies.

Children with congenital heart defects are at risk for perioperative pulmonary hypertension if they require corrective or palliative surgery in the first week of life or if they have defects associated with significant pulmonary overcirculation. In addition, children undergoing cavopulmonary connections for single ventricle lesions require low pulmonary vascular resistance for surgical success. Treatment of perioperative pulmonary hypertension with inhaled nitric oxide has become standard therapy in many centers. Related drugs that increase nitric oxide synthesis, including arginine and citrulline, have also been studied in the perioperative period. In this article, previous clinical trials of inhaled nitric oxide, intravenous arginine, and intravenous and oral citrulline in children with perioperative pulmonary hypertension or elevated pulmonary vascular resistance after a cavopulmonary connection are reviewed. In addition, recommendations are presented for each agent on the clinical use in the perioperative setting including clinical indications, assessment of clinical effect, and length of therapy.

L-Citrulline ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets.

Newborn piglets develop pulmonary hypertension and have diminished pulmonary vascular nitric oxide (NO) production when exposed to chronic hypoxia. NO is produced by endothelial NO synthase (eNOS) in the pulmonary vascular endothelium using l-arginine as a substrate and producing l-citrulline as a byproduct. l-Citrulline is metabolized to l-arginine by two enzymes that are colocated with eNOS in pulmonary vascular endothelial cells. The purpose of this study was to determine whether oral supplementation with l-citrulline during exposure of newborn piglets to 10 days of chronic hypoxia would prevent the development of pulmonary hypertension and increase pulmonary NO production. A total of 17 hypoxic and 17 normoxic control piglets were studied. Six of the 17 hypoxic piglets were supplemented with oral l-citrulline starting on the first day of hypoxia. l-Citrulline supplementation was provided orally twice a day. After 10 days of hypoxia or normoxia, the animals were anesthetized, hemodynamic measurements were performed, and the lungs were perfused in situ. Pulmonary arterial pressure and pulmonary vascular resistance were significantly lower in hypoxic animals treated with l-citrulline compared with untreated hypoxic animals (P < 0.001). In vivo exhaled NO production (P = 0.03) and nitrite/nitrate accumulation in the perfusate of isolated lungs (P = 0.04) were significantly higher in l-citrulline-treated hypoxic animals compared with untreated hypoxic animals. l-Citrulline supplementation ameliorated the development of pulmonary hypertension and increased NO production in piglets exposed to chronic hypoxia. We speculate that l-citrulline may benefit neonates exposed to prolonged periods of hypoxia from cardiac or pulmonary causes.

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: a validated genetic association study.

Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI). A well-characterized polymorphism in the gene encoding CPSI (T1405N) has previously been implicated in neonatal pulmonary hypertension. A consecutive modeling cohort of children (N=131) with congenital heart defects requiring surgery was prospectively evaluated to determine key factors associated with increased postoperative PAP, defined as a mean PAP>20 mmHg for at least 1h during the 48h following surgery measured by an indwelling pulmonary artery catheter. Multiple dimensionality reduction (MDR) was used to both internally validate observations and develop optimal two-variable through five-variable models that were tested prospectively in a validation cohort (N=41). Unconditional logistic regression analysis of the modeling cohort revealed that age (OR=0.92, p=0.01), CPSI T1405N genotype (AC vs. AA: OR=4.08, p=0.04, CC vs. AA: OR=5.96, p=0.01), and Down syndrome (OR=5.25, p=0.04) were independent predictors of this complex phenotype. MDR predicted that the best two-variable model consisted of age and CPSI T1405N genotype (p<0.001). This two-variable model correctly predicted 73% of the outcomes from the validation cohort. A five-variable model that added race, gender and Down's syndrome was not significantly better than the two-variable model. In conclusion, the CPSI T1405N genotype appears to be an important new factor in predicting susceptibility to increased PAP following surgical repair of congenital cardiac defects in children.

Increasing use of extracorporeal life support in methicillin-resistant Staphylococcus aureus sepsis in children.

BACKGROUND: Pediatric cases of fulminant community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections requiring extracorporeal life support (ECLS) have been reported, but the frequency of ECLS use for severe presentations of staphylococcal disease is unknown. OBJECTIVE: To describe the frequency and characteristics of children with MRSA infections requiring ECLS using local and international databases. METHODS: The reasons for use of ECLS in children 0-18 yrs of age were determined in both the Vanderbilt Children's Hospital medical record system and the Extracorporeal Life Support Organization database during the years 1994-2005. Demographic characteristics, ventilatory management, and measurements of cardiopulmonary status in subjects undergoing ECLS with a pre-ECLS diagnosis of infection with Staphylococcus aureus and MRSA were included. RESULTS: Three subjects with MRSA sepsis requiring ECLS were identified at Vanderbilt since 2000. Before that time, no cases due to MRSA were reported. The three subjects were previously healthy adolescents with severe necrotizing pneumonia associated with skin/soft-tissue infection and two died. A total of 45 patients requiring ECLS for MRSA infection were identified in the International Extracorporeal Life Support Organization database, with nearly half reported in the past 2 yrs (20 of 45 patients). The median age was 2.4 yrs (interquartile range, 0.36-14 yrs), with peaks noted in infancy and adolescence. In Extracorporeal Life Support Organization subjects with MRSA, survival to discharge was highest in infants and young children aged 1-4 yrs (65% and 71%, respectively) and lowest in the age ranges of 5-9 yrs and 13-18 yrs (0% and 31%, respectively). There were no statistically significant differences in pre-ECLS ventilatory settings, cardiopulmonary status, or frequency of complications between survivors and nonsurvivors. CONCLUSIONS: The use of ECLS for MRSA infection seems to be increasing both locally and internationally. High mortality rates, particularly in older patients, are concerning and highlight the increasing problem with this pathogen.

Clinical trial design--effect of prone positioning on clinical outcomes in infants and children with acute respiratory distress syndrome.

PURPOSE: This paper describes the methodology of a clinical trial of prone positioning in pediatric patients with acute lung injury (ALI). Nonrandomized studies suggest that prone positioning improves oxygenation in patients with ALI/acute respiratory distress syndrome without the risk of serious iatrogenic injury. It is not known if these improvements in oxygenation result in improvements in clinical outcomes. A clinical trial was needed to answer this question. MATERIALS AND METHODS: The pediatric prone study is a multicenter, randomized, noncrossover, controlled clinical trial. The trial is designed to test the hypothesis that at the end of 28 days, children with ALI treated with prone positioning will have more ventilator-free days than children treated with supine positioning. Secondary end points include the time to recovery of lung injury, organ failure-free days, functional outcome, adverse events, and mortality from all causes. Pediatric patients, 42 weeks postconceptual age to 18 years of age, are enrolled within 48 hours of meeting ALI criteria. Patients randomized to the prone group are positioned prone within 4 hours of randomization and remain prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days. Both groups are managed according to ventilator protocol, extubation readiness testing, and sedation protocols and hemodynamic, nutrition, and skin care guidelines. CONCLUSIONS: This paper describes the process, multidisciplinary input, and procedures used to support the design of the clinical trial, as well as the challenges faced by the clinical scientists during the conduct of the clinical trial.

Effect of prone positioning on clinical outcomes in children with acute lung injury: a randomized controlled trial.

CONTEXT: In uncontrolled clinical studies, prone positioning appeared to be safe and to improve oxygenation in pediatric patients with acute lung injury. However, the effect of prone positioning on clinical outcomes in children is not known. OBJECTIVE: To test the hypothesis that at the end of 28 days infants and children with acute lung injury treated with prone positioning would have more ventilator-free days than those treated with supine positioning. DESIGN, SETTING, AND PATIENTS: Multicenter, randomized, controlled clinical trial conducted from August 28, 2001, to April 23, 2004, of 102 pediatric patients from 7 US pediatric intensive care units aged 2 weeks to 18 years who were treated with supine vs prone positioning. Randomization was concealed and group assignment was not blinded. INTERVENTION: Patients were randomized to either supine or prone positioning within 48 hours of meeting acute lung injury criteria, with those patients in the prone group being positioned within 4 hours of randomization and remaining prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days, after which they were positioned supine. Both groups were treated using lung protective ventilator and sedation protocols, extubation readiness testing, and hemodynamic, nutrition, and skin care guidelines. MAIN OUTCOME MEASURE: Ventilator-free days to day 28. RESULTS: The trial was stopped at the planned interim analysis on the basis of the prespecified futility stopping rule. There were no differences in the number of ventilator-free days between the 2 groups (mean [SD], 15.8 [8.5] supine vs 15.6 [8.6] prone; mean difference, -0.2 days; 95% CI, -3.6 to 3.2; P = .91). After controlling for age, Pediatric Risk of Mortality III score, direct vs indirect acute lung injury, and mode of mechanical ventilation at enrollment, the adjusted difference in ventilator-free days was 0.3 days (95% CI, -3.0 to 3.5; P = .87). There were no differences in the secondary end points, including proportion alive and ventilator-free on day 28 (P = .45), mortality from all causes (P>.99), the time to recovery of lung injury (P = .78), organ-failure-free days (P = .88), and cognitive impairment (P = .16) or overall functional health (P = .12) at hospital discharge or on day 28. CONCLUSION: Prone positioning does not significantly reduce ventilator-free days or improve other clinical outcomes in pediatric patients with acute lung injury.

Implementation of an inhaled nitric oxide protocol decreases direct cost associated with its use.

BACKGROUND: The objective of this study was to determine whether the implementation of an inhaled nitric oxide protocol (INO) in a pediatric ICU (PICU) would reduce cost associated with its use without negatively affecting patient outcomes. METHODS: This is a retrospective cohort study of 76 subjects who required INO therapy in the PICU during the study period. A nitric oxide setup and weaning protocol was implemented in the PICU. The medical records of subjects who had received INO 18 months after protocol implementation, as well as the medical records of subjects who had received INO in the 18 months before protocol implementation, were reviewed. Length of time on INO, cost of INO per subject, mortality, stay, and ventilator hours were recorded. RESULTS: There were 38 subjects in the pre-protocol group and 38 subjects in the post-protocol group. There was a statistically significant decrease in the median per subject cost of INO between the pre- and post-protocol groups (P < .01). There was no statistically significant difference in the median duration of INO use (P = .06), median PICU (P = .42) or hospital (P = .58) stay, median duration of mechanical ventilation (P = .79) or percent mortality (P = .28) between the 2 groups. CONCLUSIONS: Implementation of an INO setup and weaning protocol in a PICU reduces the cost associated with its use without a statistically significant difference in mortality. In an era of increased awareness regarding healthcare spending, implementation of evidence-based protocols can provide a way to ensure the judicious utilization of medical resources.

Ethnic diversity in a critical gene responsible for glutathione synthesis.

The tripeptide glutathione is an important biomolecule that acts as a scavenger of free radicals and plays a role in a number of other cellular processes. A number of diseases, including Parkinson's disease, cancer, sickle cell anemia, and HIV infection, are thought to involve oxidative stress and depletion of glutathione. The heterodimeric enzyme glutamate cysteine ligase catalyzes the first, rate-limiting step in the de novo synthesis of glutathione. Functional polymorphisms within the gene encoding the subunits of glutamate cysteine ligase have the potential to affect the body's capacity to synthesize glutathione and thus, may affect those diseases in which oxidative stress and glutathione have roles. We undertook systematic screening for polymorphisms within the exons and intronic flanking sequences of the gene encoding the catalytic subunit of glutamate cysteine ligase (GCLC). We identified 11 polymorphisms in GCLC and established allele frequencies for those polymorphisms in a population fitting the demographics of the middle Tennessee area. The nonsynonymous polymorphism C1384T was found only in individuals of African descent. In addition, allele frequencies for three other polymorphisms differ between Caucasians and African-Americans. Understanding these polymorphisms may lead to better understanding of diseases where glutathione is important so that better treatments may be developed.

Template of patient-specific summaries facilitates education and outcomes in paediatric cardiac surgery units.

OBJECTIVES: Few educational opportunities exist in paediatric cardiac critical care units (PCCUs). We introduced a new educational activity in the PCCU in the form of of patient-specific summaries (TPSS). Our objective was to study the role of TPSS in the provision of a positive learning experience to the multidisciplinary clinical team of PCCUs and in improving patient-related clinical outcomes in the PCCU. METHODS: Prospective educational intervention with simultaneous clinical assessment was undertaken in PCCU in an academic children's hospital. TPSS was developed utilizing the case presentation format for upcoming week's surgical cases and delivered once every week to each PCCU clinical team member. Role of TPSS to provide clinical education was assessed using five-point Likert-style scale responses in an anonymous survey 1 year after TPSS provision. Paediatric cardiac surgery patients admitted to the PCCU were evaluated for postoperative outcomes for TPSS provision period of 1 year and compared with a preintervention period of 1 year. RESULTS: TPSS was delivered to 259 clinical team members including faculty, fellows, residents, nurse practitioners, nurses, respiratory therapists and others from the Divisions of Anesthesia, Cardiology, Cardio-Thoracic Surgery, Critical Care, and Pediatrics working in the PCCU. Two hundred and twenty-four (86%) members responded to the survey and assessed the role of TPSS in providing clinical education to be excellent based on mean Likert-style scores of 4.32 ± 0.71 in survey responses. Seven hundred patients were studied for the two time periods and there were no differences in patient demographics, complexity of cardiac defect and surgical details. The length of mechanical ventilation for the TPSS period (57.08 ± 141.44 h) was significantly less when compared with preintervention period (117.39 ± 433.81 h) (P < 0.001) with no differences in length of PCICU stay, hospital stay and mortality for the two time periods. CONCLUSIONS: Provision of TPSS in a paediatric cardiac surgery unit is perceived to be beneficial in providing clinical education to multidisciplinary clinical teams and may be associated with improved clinical outcome.

Prospective study of the incidence and predictors of thrombus in children undergoing palliative surgery for single ventricle physiology.

PURPOSE: To determine the incidence and clinical and biomarker predictors of perioperative thrombosis in children with single ventricle physiology undergoing staged palliation. METHODS: Nineteen patients were enrolled and 16 completed the study. Serial ultrasounds of the central venous system were performed to evaluate for thrombus. Plasma antithrombin III, thrombin-antithrombin complex, protein C, protein S, tissue factor pathway inhibitor, plasminogen activator inhibitor-1, tissue plasminogen activator antigen, D-dimer, soluble CD40 ligand, and urinary thromboxane were measured serially before and after surgery. Cardiopulmonary bypass time, aortic cross clamp time, blood product administration, inotrope score, chest tube output, cardiac function by echocardiography, intensive care unit and hospital lengths of stay, and central venous catheter days were recorded. RESULTS: The incidence of perioperative thrombus was 31%. Patients who developed a thrombus had poorer preoperative ventricular function (p = 0.03) and longer cardiopulmonary bypass times (p = 0.03) than those who did not develop a thrombus. Preoperative plasma antithrombin III was lower (p = 0.01) and tissue plasminogen activator antigen concentrations were higher (p = 0.02) in patients with a thrombus compared with patients without a thrombus. When measured over time, antithrombin III remained lower (p = 0.002) and tissue plasminogen activator antigen higher (p = 0.005) in those who developed a thrombus compared with those who did not. There were no other statistically significant differences in biomarkers of coagulation between patients with and without thrombosis. CONCLUSION: One-third of patients undergoing palliative surgery for single ventricle physiology develop thrombosis. Decreased ventricular function, low antithrombin III, and increased tissue plasminogen activator may predict those most suitable for randomized clinical trials of anticoagulation.

Delirium: an emerging frontier in the management of critically ill children.

Delirium is a syndrome of acute brain dysfunction that commonly occurs in critically ill adults and most certainly is prevalent in critically ill children all over the world. The dearth of information about the incidence, prevalence, and severity of pediatric delirium stems from the simple fact that there have not been well-validated instruments for routine delirium diagnosis at the bedside. This article reviewed the emerging solutions to this problem, including description of a new pediatric tool called the pCAM-ICU. In adults, delirium is responsible for significant increases in both morbidity and mortality in critically ill patients. The advent of new tools for use in critically ill children will allow the epidemiology of this form of acute brain dysfunction to be studied adequately, will allow clinical management algorithms to be developed and implemented following testing, and will present the necessary incorporation of delirium as an outcome measure for future clinical trials in pediatric critical care medicine.