Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation.

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients.

BACKGROUND: Cell-free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell-free DNA (ncfDNA) itself is largely unexplored. OBJECTIVE: Explore the relationship between ncfDNA and clinical events in heart transplant recipients. METHODS: We conducted a multi-center prospective study to investigate the value of cell-free DNA in non-invasive monitoring following heart transplantation. Over 4000 blood samples were collected from 388 heart transplant patients. Total ncfDNA and donor fraction were quantified. Generalized linear models with maximum likelihood estimation for repeated measures with subjects as clusters were used to explore the relationship of ncfDNA and major adverse events. Receiver operating characteristic curves were used to help choose cutpoints. RESULTS: A ncfDNA threshold (50 ng/ml) was identified that was associated with increased risk of major adverse events. NcfDNA was elevated in patients who suffered cardiac arrest, required mechanical circulatory support or died post heart transplantation as well as in patients undergoing treatment for infection. CONCLUSIONS: Elevated ncfDNA correlates with risk for major adverse events in adult and pediatric heart transplant recipients and may indicate a need for enhanced surveillance after transplant.

Relationship between donor fraction cell-free DNA and clinical rejection in heart transplantation.

BACKGROUND: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest. METHODS: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA. RESULTS: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001). CONCLUSION: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.

Detection of changes of functioning over time after asthma exacerbation in children with the use of PROMIS domains.

OBJECTIVES: Patient reported outcome measures, such as the Patient Reported Outcomes Measurement Information System (PROMIS) may be utilized to understand experiences of patients. The purpose of this study was to determine the ability of PROMIS domains to detect changes in pain, physical functioning, and asthma impact over time for children experiencing asthma exacerbation. METHODS: Our prospective cohort study included children presenting to the emergency department (ED) for asthma exacerbation. Children completed PROMIS surveys in the ED, 7-10 days, and 1-3 months post-discharge. We used linear mixed models adjusted for age, gender, acute care utilization, and child global health to determine changes in PROMIS T-scores. We used self-reported child health response (Much better now versus a little better now or worse) at discharge as an anchor to determine if change in PROMIS scores corresponded with changes in health. A change was statistically significant if the 95% CI did not include 0. RESULTS: Our study included 63 children who presented to the ED for acute asthma exacerbation. We identified that children improved significantly in all domains over time. There was improvement over time following discharge from ED for all pain and physical functioning domains, and asthma impact. Using the clinical anchor, those with considerable improvement in asthma symptoms had improved T scores from 4-17. CONCLUSIONS: PROMIS domains of pain, physical functioning, depression, fatigue, peer relationships, and asthma impact are responsive to changes in health states over time. These domains may be used to measure clinically significant change in children experiencing asthma exacerbation.

Measurement properties of Patient Reported Outcomes Measurement Information System domains for children with type 1 diabetes.

OBJECTIVE: Patient Reported Outcomes Measurement Information System (PROMIS) includes numerous domains to assess functioning among the pediatric population. These domains, however, have not been evaluated for use in children with type 1 diabetes (T1D). The objective of this study was to determine the measurement properties of PROMIS domains (pain behavior, pain quality, physical stress experience, physical activity, strength impact, and profile-25) in children with T1D. METHODS: This is a cross-sectional study of children with T1Drecruited from tertiary care facilities. To determine construct validity, we compared PROMIS T-scores between known-groups based on (a) glycemic control, hemoglobin A1c (HbA1c%) and (b) self-reported general health, using t test or analysis of variance. Reliability was determined using Cronbach's alpha and item response theory reliability. We also determined agreement between parent-proxy and child self-report PROMIS scores. RESULTS: Our study included 192 children, mean age 12.7 (SD = 2.9) years, eligible to self-report PROMIS surveys. There were significant differences in physical stress experience and pain intensity between children with HbA1c < 10% and those with HbA1c ≥ 10%. There also were significant differences in T-scores for all domains except physical function mobility and strength impact among children with poor/fair, good, very good/excellent general health. All valid domains had reliability >0.70. More than 40% of child-parent pairs were in agreement, with intraclass correlations coefficients (ICC) ranging between 0.41 and 0.63 for all domains, except pain behavior (%agreement = 23%; ICC = 0.29). CONCLUSIONS: Most of the PROMIS domains tested are valid, reliable, and able to differentiate children with T1D who report different general health states. There is moderate agreement between child-parent pairs for all domains except pain behavior.

Assessment of pediatric asthma exacerbation with the use of new PROMIS measures.

OBJECTIVE: Patient reported outcome measures, such as the Patient Reported Outcomes Measurement Information System (PROMIS) may be used to assess patient functioning for asthma and aid in understanding the impact of asthma exacerbation. These domains may be utilized as endpoints in clinical trials and to guide clinical care. The purpose of this study was to determine psychometric properties of the new PROMIS measures for children with asthma, at baseline and with exacerbation. METHODS: We conducted a cross-sectional analysis of children with acute asthma exacerbation or at baseline health. Psychometric properties of validity (using known groups and correlation) and reliability (using Cronbach's alpha and IRT) for the new PROMIS measures were determined. RESULTS: Our study included 220 subjects, 102 were enrolled during an acute exacerbated state. Cronbach's alpha and IRT reliability was greater or equal to 0.75. Our subjects experiencing an acute exacerbated state reported worse T-scores for pain related domains: pain behavior 45.7 vs 53.5 (p < 0.001), pain quality sensory 44.4 vs 48.5 (p < 0.005), pain quality affective 42.5 vs 51.3 (p < 0.001), and physical stress experience 60.5 vs 65.4 (p < 0.001); and asthma impact 47.9 vs 61.0 (p < 0.001), than subjects at baseline. Child and parent-proxy agreement ranged from 35% to 56%. CONCLUSIONS: The new Pediatric PROMIS domains are valid and reliable for use in children with asthma, for both child-reported and parent-proxy reported outcomes. It was determined that children with acute asthma exacerbation have worse patient reported outcomes (PROs) for the new pain related domains and asthma impact.

Can PROMIS domains of pain and physical functioning detect changes in health over time for children with sickle cell disease?

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) includes multiple domains that measure pain and physical functioning which are valid and reliable for use in children with sickle cell disease. The responsiveness of these measures to detect changes in health status over time among children with sickle cell disease is unknown. PROCEDURE: We conducted a prospective cohort study of children presenting to emergency department (ED) with vaso-occlusive crises. Children completed PROMIS surveys in the ED and at two follow-up time points (7-10 days and 1-3 months) after their acute care visit. Linear mixed models were used to determine if there were significant changes in PROMIS T scores over time. We used a patient's global assessment of change in pain question to anchor the changes in PROMIS scores (mean and 95% confidence interval). A change was considered statistically significant if the 95% CI did not include 0. RESULTS: We found that patients improved significantly in all domains 1 to 3 months after discharge from an acute care visit for pain. In addition, the pain and physical stress experience domains were responsive to change 7 to 10 days after discharge. Using the anchor of change in pain, for children who had considerable improvement in pain, there were significant changes in PROMIS T scores ranging from 6 to 15. CONCLUSIONS: Relevant PROMIS domains detect changes in children experiencing acute vaso-occlusive crises. These domains can be used in research and clinic settings to measure clinically relevant change in children with sickle cell disease.

Efficacy and Safety of Carbon Dioxide Versus Air Insufflation for Colonoscopy in Deeply Sedated Pediatric Patients.

OBJECTIVES: Studies have shown the advantages of carbon dioxide (CO2) over air insufflation in the adult population during colonoscopies. This study was designed to investigate the efficacy and safety of CO2 insufflation in deeply sedated children undergoing colonoscopy. METHODS: This was a prospective, randomized, double-blind clinical trial. We recruited 100 consecutive pediatric patients who had colonoscopy under deep sedation for various indications. Patients were first randomized by history of abdominal pain and then randomly assigned to either CO2 or air insufflation. Postprocedural abdominal pain scores were registered on a 10-point visual analog rating scale and significant pain was defined as a score of 3 or higher. Abdominal circumferences and end tidal CO2 (ETCO2) levels were measured. Complications during and after the procedure were recorded. RESULTS: We did not find statistically significant difference between CO2 and air insufflation on univariate analysis because of low number of children experiencing significant pain after colonoscopy. After adjusting for baseline pain, we found that pain was significantly lower in patients after CO2 versus air insufflation on multivariable analysis (P = 0.03). The significant factors related to pain were duration of the procedure (P = 0.006), history of abdominal pain (P = 0.002) and previous abdominal surgery (P = 0.02). CO2 insufflation was associated with decreased abdominal circumference after colonoscopy (P = 0.002). Girls were more likely to have pain regardless of intervention (P = .04). CONCLUSIONS: Most children tolerate endoscopic procedures without significant pain. Our study was underpowered to show significant difference between air and CO2 on univariate analysis. CO2 insufflation during colonoscopy, however, may reduce postprocedural abdominal pain. Significant factors for increased pain on multivariate analysis included colonoscopy length over 30 minutes, history of abdominal pain, and previous abdominal surgery.

Use of the new pediatric PROMIS measures of pain and physical experiences for children with sickle cell disease.

BACKGROUND: There are new pediatric domains to measure patients' pain and physical experiences in the Patient-Reported Outcomes Measurement Information System (PROMIS). The objective of this study was to establish the psychometric properties of these domains for children with sickle cell disease (SCD). PROCEDURE: We conducted a cross-sectional analysis of PROMIS assessments of children with SCD recruited from a pediatric tertiary care clinic. Validity of the new PROMIS domains was determined by comparing scores between known groups and describing their correlations with previously validated PROMIS measures. Cronbach's alpha and item response theory (IRT) reliability were used to assess internal consistency reliability. Agreement between parent-proxy and child self-report was determined for all domains. RESULTS: Our study included 164 subjects, of whom 117 were eligible to self-report. The mean T-scores for physical stress experience, strength impact, pain behavior, and pain quality sensory scores were significantly different between children who used pain medications in the prior week and those who did not. There were also differences in T-scores across children reporting mild, moderate, and severe pain on the pain intensity scale. All measures had Cronbach's alpha and IRT reliability > 0.80. The percentage of agreement between child and parent-proxy PROMIS domains ranged from 36% to 60% depending on the domain. CONCLUSIONS: The new PROMIS domains of physical stress experience, strength impact, pain behavior, and pain quality sensory domains are valid and reliable for children with SCD. The low-moderate agreement between parent-proxy and child self-report scores support the complementary information provided by the two perspectives.

Enteral Nutrition Initiation in Children Admitted to Pediatric Intensive Care Units After Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and long-term disability among injured children. Early feeding has been shown to improve outcomes in adults, with some similar evidence in children with severe TBI. We aimed to examine the current practice of initiation of enteral nutrition in children with TBI and to evaluate the risk factors associated with delayed initiation of enteral nutrition. METHODS: This retrospective, multicenter study used the Pediatric Trauma Assessment and Management Database including all children with head trauma discharged from five pediatric intensive care units (PICU) at pediatric trauma centers between January 1, 2013 and December 31, 2013. We compared demographics, injury and procedure data, time to initiation of nutrition, and injury and illness severity scores between patients who received enteral nutrition early (≤ 48 h) and late (> 48 h). Fisher's exact and Mann-Whitney U tests compared discrete and continuous variables. Univariate and multivariable analyses evaluated variables associated with delayed initiation of feeding. Outcomes of interest included mortality, complications, ventilator days, hospital and ICU length of stay, and functional status at ICU discharge. RESULTS: In the 416 patients in the study, the overall mortality was 2.6%. The majority of patients (83%; range 69-88% between five sites, p = 0.0008) received enteral nutrition within 48 h of PICU admission. Lower Glasgow Coma Scale scores and higher Injury Severity Score (ISS) were independently associated with delayed initiation of enteral nutrition. Delayed enteral nutrition was independently associated with worse functional status at PICU discharge (p = 0.02) but was not associated with mortality or increased length of stay. CONCLUSIONS: Children with severe TBI and higher ISS were more likely to have delayed initiation of enteral nutrition. Delayed enteral nutrition was an independent risk factor for worse functional status at ICU discharge for the entire cohort, but not for the severe TBI group.

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States.

von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population.

Central Venous Catheter-associated Venous Thromboembolism in Children With Hematologic Malignancy.

In pediatric oncology, the diagnosis of a hematologic malignancy and presence of a central venous catheter (CVC) have been identified as significant risk factors for the development of a venous thromboembolism (VTE). There remain little data regarding CVC factors associated with CVC-related VTE. Using the VTE and oncology database in a quaternary care center, a retrospective cohort study was conducted in children below 18 years old with hematologic cancer from November 5, 2012 to April 4, 2016. Patient, CVC factors, and VTE occurrence were analyzed to identify significant patient and CVC factors associated with the development of clinically identified CVC-related VTE. Utilizing the χ, Mann-Whitney, and the Fisher exact tests, patient factors were compared across VTE yes/no groups. Of the 198 study patients, 22 VTE cases were identified. Eighteen VTE events were CVC-associated, occurring in 9% of study population. Peripherally inserted central catheter lines and older ages were associated with VTE. The use of tissue-plasminogen activator for CVC occlusion was associated with decreased VTE rates, suggesting a protective potential.

Comparison of Complication Rates of Central Venous Catheters Versus Peripherally Inserted Central Venous Catheters in Pediatric Patients.

OBJECTIVES: The purpose of our study is to compare the rate of central line-associated blood stream infections and venous thromboembolism in central venous catheters versus peripherally inserted central catheters in hospitalized children. There is a growing body of literature in adults describing an increased rate of venous thromboembolisms and similar rates of central line-associated blood stream infection associated with peripherally inserted central catheters versus central venous catheters. It is not known if the rate of central line-associated blood stream infection and venous thromboembolism differs between peripherally inserted central catheters and central venous catheters in children. Based on current adult literature, we hypothesize that central line-associated blood stream infection rates for peripherally inserted central catheters and central venous catheters will be similar, and the rate of venous thromboembolism will be higher for peripherally inserted central catheters versus central venous catheters. DESIGN: This is a cohort study using retrospective review of medical records and prospectively collected hospital quality improvement databases. SETTING: Quaternary-care pediatric hospital from October 2012 to March 2016. PATIENTS: All patients age 1 day to 18 years old with central venous catheters and peripherally inserted central catheters placed during hospital admission over the study dates were included. Central venous catheters that were present upon hospital admission were excluded. The primary outcomes were rate of central line-associated blood stream infection and rate of venous thromboembolism. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,709 catheters included in the study, 1,126 were peripherally inserted central catheters and 1,583 were central venous catheters. Peripherally inserted central catheters demonstrated a higher rate of both infection and venous thromboembolism than central venous catheters in all reported measures. In multivariable analysis, peripherally inserted central catheters had increased association with central line-associated blood stream infection (odds ratio of 3.15; 95% CI, 1.74-5.71; p = 0.0002) and increased association with venous thromboembolism (odds ratio of 2.71; 95% CI, 1.65-4.45; p < 0.0001) compared with central venous catheters. CONCLUSIONS: Rates of central line-associated blood stream infection and venous thromboembolism were higher in hospitalized pediatric patients with peripherally inserted central catheters as compared to central venous catheters. Our study confirms the need for further investigation into the safety of central access devices to assist in proper catheter selection.

Correlation of Bedside Pediatric Early Warning System Score to Interventions During Peritransport Period.

BACKGROUND: The Bedside Pediatric Early Warning System score is a validated measure of severity of illness in acute care inpatient settings. Its potential as a remote assessment tool for interfacility transport has not been evaluated. We hypothesized that the Bedside Pediatric Early Warning System score was associated with need for intervention during the peritransport period and patient disposition. METHODS: We retrospectively evaluated children transported by a regional pediatric team during a 6-month period. Bedside Pediatric Early Warning System scores were calculated at the triage phone call, the transport team arrival, and at transfer of care to the hospital team. The primary outcome was the receipt of significant intervention during the peritransport period, with additional outcomes of destination (ICU, ward, emergency department) in the regional hospital. Scores are presented as median values (interquartile range). RESULTS: There were 564 children who underwent transport; 139 (25%) received interventions; and 205 (36%) were transferred to the PICU, 231 (41%) to the ward, and 127 (23%) to the emergency department. Scores were 2 (1-5; median interquartile range) in children receiving no in-transport interventions, 8 (5-11) in children receiving any intervention (p < 0.001), and 10 (7-14) in children receiving more than one intervention. Children transferred to the PICU had higher scores 6 (3-10), than children transferred to a ward 3 (1-6) or the emergency department 2 (1-3) (p < 0.001). CONCLUSIONS: The Bedside Pediatric Early Warning System score at the time of initial referral is a useful measure of severity of illness reflected by the subsequent provision of significant peritransport intervention and the transfer destination.

Multicenter Review of Current Practices Associated With Venous Thromboembolism Prophylaxis in Pediatric Patients After Trauma.

OBJECTIVES: Frequency of venous thromboembolism in pediatric trauma patients admitted to PICUs is not insignificant, ranging up to 6%. Risk factors have been identified in this population. However, there is little consensus of actual venous thromboembolism prophylaxis practice. We examined factors associated with venous thromboembolism prophylaxis in PICUs. DESIGN: A retrospective study evaluating associations with mechanical venous thromboembolism prophylaxis, pharmacologic venous thromboembolism prophylaxis, or dual therapy (DUAL) prophylaxis compared with no venous thromboembolism prophylaxis. Multivariable logistic regression explored the relationship between prophylaxis type and selected covariates with stepwise selection method to identify the independent predictors of venous thromboembolism prophylaxis utilization. SETTING: Five level I/II pediatric trauma centers in the United States. PATIENTS: Children less than 18 years from January 1, 2013, to December 31, 2013, admitted to the PICU after a trauma, identified through combined trauma registry and Virtual Pediatric Systems database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six hundred ninety-two patients were included in the database, with 55 excluded for missing data. Of the remaining 637 patients, 538 (84.5%) had no venous thromboembolism prophylaxis by 48 hours, 77 (12.1%) had only mechanical venous thromboembolism prophylaxis, 11 (1.7%) had DUAL, and 11 (1.7%) had pharmacologic venous thromboembolism prophylaxis alone. Multivariable analysis showed increased age, and orthopedic procedure was associated with all forms of prophylaxis. Orthopedic procedures were associated with higher utilization of dual prophylaxis use (odds ratio, 5.2; 95% CI, 1.2-21.8), pharmacologic venous thromboembolism prophylaxis (odds ratio, 8.5; 95% CI, 2.3-31.7), and mechanical venous thromboembolism prophylaxis (odds ratio, 2.2; 95% CI, 1.1-4.2) alone. Brain/spinal cord procedures (odds ratio, 3.7; 95% CI, 1.9-7.3) and abdominal procedures (odds ratio, 6.6; 95% CI, 2.5-17.1) were associated with mechanical venous thromboembolism prophylaxis. Head injury was associated with a decreased use of any prophylaxis (odds ratio, 0.5; 95% CI, 0.3-0.9). Patient comorbidities were associated with decreased use of mechanical venous thromboembolism prophylaxis (odds ratio, 0.5; 95% CI, 0.3-1.0). CONCLUSIONS: Pharmacologic venous thromboembolism prophylaxis is not common in critically ill children after trauma. Patient age, orthopedic and vascular procedures, and higher injury severity are associated with pharmacologic venous thromboembolism prophylaxis.

Low near infrared spectroscopic somatic oxygen saturation at admission is associated with need for lifesaving interventions among unplanned admissions to the pediatric intensive care unit.

To investigate the association between low near infrared spectroscopy (NIRS) somatic oxygen saturation (<70%) at admission and the need for lifesaving interventions (LSI) in the initial 24 h of a PICU admission. Retrospective chart review of all unplanned admissions to the pediatric intensive care unit (PICU) with NIRS somatic oxygen saturation data available within 4 h of admission, excluding admissions with a cardiac diagnosis. LSI data were collected for the first 24 h after admission. Hemodynamic parameters, laboratory values, illness severity scores and diagnoses were collected. Included PICU admissions were stratified by lowest NIRS value in the first 4 h after admission: low NIRS (<70%) and normal NIRS (≥70%) groups. Rate of LSI from 4 h to 24 h was compared between the two groups. Association of LSI with NIRS saturation and other clinical and laboratory parameters was measured by univariate and multivariate methods. We reviewed 411 consecutive unplanned admissions to the PICU of which 184 (44%) patients underwent NIRS monitoring. A higher proportion of patients who underwent somatic NIRS monitoring required LSIs compared to those without NIRS monitoring (36.4 vs 5.7% respectively, p < 0.0001). The proportion of patients who required LSI was higher in the group with low NIRS (<70%) within the first 4 h compared to those with normal NIRS (≥70%) (77.1 vs 22.1%, p < 0.0001). Fluid resuscitation, blood products and vasoactive medications were the most common LSIs. Multivariable modeling showed NIRS < 70% and heart rate > 2SD for age to be associated with LSIs. ROC curve analysis of the combination of NIRS < 70% and HR >2SD for age had an area under the curve of 0.79 with 78% sensitivity and 76% specificity for association with LSI. Compared to the normal NIRS group, the low NIRS group had higher mortality (10.4 vs 0.7%, p = 0.005) and longer median hospital length of stay (2.9 vs 1.6 days, p < 0.0001). Low somatic NIRS oxygen saturation (<70%) in the first 4 h of an unplanned PICU admission is associated with need for higher number of subsequent lifesaving interventions up to 24 h after admission. Noninvasive, continuous, somatic NIRS monitoring may identify children at high risk of medical instability.

Treatment with ActRIIB-mFc Produces Myofiber Growth and Improves Lifespan in the Acta1 H40Y Murine Model of Nemaline Myopathy.

Nemaline myopathies (NMs) are a group of congenital muscle diseases caused by mutations in at least 10 genes and associated with a range of clinical symptoms. NM is defined on muscle biopsy by the presence of cytoplasmic rod-like structures (nemaline rods) composed of cytoskeletal material. Myofiber smallness is also found in many cases of NM and may represent a cause of weakness that can be counteracted by treatment. We have used i.p. injection of activin type IIB receptor (ActRIIB)-mFc (an inhibitor of myostatin signaling) to promote hypertrophy and increase strength in our prior murine work; we therefore tested whether ActRIIB-mFc could improve weakness in NM mice through myofiber hypertrophy. We report a study of ActRIIB-mFc treatment in the Acta1 H40Y mouse model of NM. Treatment of Acta1 H40Y mice produced significant increases in body mass, muscle mass, quadriceps myofiber size, and survival, but other measurements of strength (forelimb grip strength, ex vivo measurements of contractile function) did not improve. Our studies also identified that the complications of urethral obstruction are associated with mortality in male hemizygote Acta1 H40Y mice. The incidence of urethral obstruction and histologic evidence of chronic obstruction (inflammation) were significantly lower in Acta1 H40Y mice that had been treated with ActRIIB-mFc. ActRIIB-mFc treatment produces a mild benefit to the disease phenotype in Acta1 H40Y mice.

Patient-reported neuropathic pain in adolescent and young adult cancer patients.

BACKGROUND: Neuropathic pain, a known complication of cancer and its treatments, negatively impacts quality of life. There are limited data using screening tools to aid in the diagnosis of neuropathic pain in cancer patients. Our primary objective was to determine the proportion of adolescent and young adult cancer patients reporting neuropathic pain on a patient-completed, neuropathic pain screening tool. PROCEDURES: This prospective, cohort study enrolled patients 14-39 years of age who were receiving therapy for primary cancer diagnosis, cancer relapse, or had recently completed treatment. The painDETECT, a patient-completed, neuropathic pain screening tool used down to age 14, was administered a maximum of three times in on-therapy patients and once in off-therapy patients. Provider documentation of neuropathic pain at the corresponding visit was abstracted from the medical record. RESULTS: Seventy-eight patients participated. Median (interquartile range) age at study enrollment was 18.1 (16-19.4) years and 47% were female. Cancer diagnoses included 41% leukemia, 26% solid tumor, 23% lymphoma, and 10% central nervous system tumor. The proportion of patients reporting neuropathic pain was 26% (95% confidence interval [CI] 16-40%) in on-therapy patients and 11% (95% CI 3-27%) in off-therapy patients. In patients reporting neuropathic pain, only 26% had a clinical diagnosis of neuropathic pain documented in the medical record at the corresponding visit. CONCLUSIONS: Neuropathic pain occurs in one in four adolescents and young adults receiving cancer therapy. Use of screening tools may increase the detection of neuropathic pain in adolescents and young adults receiving cancer therapy and could ultimately improve pain treatment.

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use.

Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: (i) SCD baseline and controls, and (ii) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean ± standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32·4 ± 11·6 vs. 22·9 ± 7·6, P = 0·0009). SP in SCD pain was higher than baseline (78·1 ± 43·4 vs. 32·4 ± 11·6, P = 0·004). Haemolysis correlated with increased SP: Hb (r = -0·7, P = 0·0002), reticulocyte count (r = 0·61, P = 0·0016), bilirubin (r = 0·68, P = 0·0216), lactate dehydrogenase (r = 0·62, P = 0·0332), aspartate aminotransferase (r = 0·68, P = 0·003). Patients taking hydroxycarbamide had increased SP (ß = 29·2, P = 0·007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment.