Survival does not differ by annual center transplant volume-A Pediatric Heart Transplant Society Registry study.

BACKGROUND: There are conflicting data regarding the relationship between center volume and outcomes in pediatric heart transplantation. Previous studies have not fully accounted for differences in case mix, particularly in high-risk congenital heart disease (CHD) groups. We aimed to evaluate the relationship between center volume and outcomes using the Pediatric Heart Transplant Society (PHTS) Registry and explore how case mix may affect outcomes. METHODS: A retrospective cohort study of all pediatric patients in the PHTS Registry who received a heart transplant from 2009 to 2018 was performed. Centers were divided into 5 groups based on average yearly transplant volume. The primary outcome was time to death or graft loss and outcomes were compared using Kaplan-Meier analysis. RESULTS: There were 4583 cases among 55 centers included. There was no difference in time to death or graft loss by center volume in the entire cohort (p = .75), in patients with CHD (p = .79) or in patients with cardiomyopathy (p = .23). There was also no difference in time to death or graft loss by center size in patients undergoing transplant after Norwood, Glenn or Fontan (log rank p = .17, p = .31, and p = .10 respectively). There was a statistically significant difference in outcomes by center size in the positive crossmatch group (p < .0001), though no discernible pattern related to high or low center volume. CONCLUSIONS: Outcomes are similar among transplant centers of all sizes, including for high-risk patient groups with CHD. Future work is needed to understand how patient-specific risk factors may vary among centers of various sizes and whether this influences patient outcomes.

Quantitative and Qualitative Changes in Peripheral Chemoreceptor Activity in Preterm Infants.

Rationale: Preterm infants are at risk for ventilatory control instability that may be due to aberrant peripheral chemoreceptor activity. Although term infants have increasing peripheral chemoreceptor contribution to overall ventilatory drive with increasing postnatal age, how peripheral chemoreceptor contribution changes in preterm infants with increasing postmenstrual age is not known. Objectives: To evaluate peripheral chemoreceptor activity between 32 and 52 weeks postmenstrual age in preterm infants, using both quantitative and qualitative measures. Methods: Fifty-five infants born between 24 weeks, 0 days gestation and 28 weeks, 6 days gestation underwent hyperoxic testing at one to four time points between 32 and 52 weeks postmenstrual age. Quantitative [Formula: see text] decreases were calculated, and qualitative responses were categorized as apnea, continued breathing with a clear reduction in [Formula: see text], sigh breaths, and no response. Measurements and Main Results: A total of 280 hyperoxic tests were analyzed (2.2 ± 0.3 tests per infant at each time point). Mean peripheral chemoreceptor contribution to ventilatory drive was 85.2 ± 20.0% at 32 weeks and 64.1 ± 22.0% at 52 weeks. Apneic responses were more frequent at earlier postmenstrual ages. Conclusions: Among preterm infants, the peripheral chemoreceptor contribution to ventilatory drive was greater at earlier postmenstrual ages. Apnea was a frequent response to hyperoxic testing at earlier postmenstrual ages, suggesting high peripheral chemoreceptor activity. A clearer description of how peripheral chemoreceptor activity changes over time in preterm infants may help explain how ventilatory control instability contributes to apnea and sleep-disordered breathing later in childhood. Clinical trial registered with www.clinicaltrials.gov (NCT03464396).

A pilot randomized controlled trial of a cognitive-behavioral therapy guided self-help mobile app for the post-acute treatment of anorexia nervosa: A registered report.

INTRODUCTION: Relapse following acute treatment for anorexia nervosa (AN) is common. Evidence suggests cognitive-behavioral therapy (CBT) may be useful in the post-acute period, but few patients have access to trained providers. mHealth technologies have potential to increase access to high-quality care for AN, including in the post-acute period. The aim of this study is to estimate the preliminary feasibility and effectiveness of a CBT-based mobile intervention plus treatment as usual (TAU), offered with and without an accompanying social networking feature. METHOD: In the current pilot randomized controlled trial, women with AN who have been discharged from acute treatment in the past 2 months (N = 90) will be randomly assigned to a CBT-based mobile intervention plus treatment as usual (TAU), a CBT-based mobile intervention including social networking plus TAU, or TAU alone. We will examine feasibility, acceptability, and preliminary effectiveness of the three conditions in terms of reducing eating disorder psychopathology, reducing frequency of eating disorder behaviors, achieving weight maintenance, reducing depression and suicidal ideation, and reducing clinical impairment. We will examine rehospitalization and full recovery rates in an exploratory fashion. We will also examine whether the mobile intervention and social networking feature change the proposed targets and whether changes in targets are associated with benefit, as well as conduct exploratory analyses to identify within-mobile intervention predictors and moderators of outcome. DISCUSSION: Ultimately, this research may lead to increased access to evidence-based treatment for individuals with AN and prevention of the extreme negative consequences that can result from this serious disorder. PUBLIC SIGNIFICANCE: Relapse after acute treatment for anorexia nervosa is common, and few patients have access to trained providers to support them following acute care. This study will pilot a coached mobile app, including a social networking component, for this population. If ultimately successful, our approach could greatly increase access to evidence-based treatment for individuals with anorexia nervosa and ultimately prevent the extreme negative consequences that can result from this serious disorder.

Anticoagulation-Free Pediatric Extracorporeal Membrane Oxygenation: Single-Center Retrospective Study.

OBJECTIVES: To analyze hemorrhage and thrombosis data related to anticoagulation-free pediatric extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective cohort study. SETTINGS: High-volume ECMO single institution data. PATIENTS: Children (0-18 yr) supported with ECMO (>24 hr) with initial anticoagulation-free period of greater than or equal to 6 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Utilizing consensus American Thoracic Society definitions for hemorrhage and thrombosis on ECMO, we evaluated thrombosis and associated patient and ECMO characteristics during anticoagulation-free period. Thirty-five patients met inclusion criteria from 2018 to 2021 having a median age (interquartile range [IQR]) of 13.5 months (IQR, 3-91 mo), median ECMO duration of 135 hours (IQR, 64-217 hr), and 964 anticoagulation-free hours. Increased RBC transfusion needs were associated with longer anticoagulation-free periods ( p = 0.03). We identified 20 thrombotic events: only four during the anticoagulation-free period and occurring in three of 35 (8%) patients. Compared with those without thrombotic events, anticoagulation-free clotting events were associated with younger age (i.e., 0.3 mo [IQR, 0.2-0.3 mo] vs 22.9 mo [IQR, 3.6-112.9 mo]; p = 0.02), lower weight (2.7 kg [IQR, 2.7-3.25 kg] vs 13.2 kg [5.9-36.4 kg]; p = 0.006), support with lower median ECMO flow rate (0.5 kg [IQR, 0.45-0.55 kg] vs 1.25 kg [IQR, 0.65-2.5 kg]; p = 0.04), and longer anticoagulation-free ECMO duration (44.5 hr [IQR, 40-85 hr] vs 17.6 hr [IQR, 13-24.1]; p = 0.008). CONCLUSIONS: In selected high-risk-for-bleeding patients, our experience is that we can use ECMO in our center for limited periods without systemic anticoagulation, with lower frequency of patient or circuit thrombosis. Larger multicentered studies are required to assess weight, age, ECMO flow, and anticoagulation-free time limitations that are likely to pose risk for thrombotic events.

Family-Based Behavioral Treatment for Childhood Obesity Implemented in Pediatric Primary Care: A Randomized Clinical Trial.

Importance: Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics. Evidence is lacking on their effectiveness in pediatric primary care settings. Objective: To evaluate the effects of family-based treatment for overweight or obesity implemented in pediatric primary care on children and their parents and siblings. Design, Setting, and Participants: This randomized clinical trial in 4 US settings enrolled 452 children aged 6 to 12 years with overweight or obesity, their parents, and 106 siblings. Participants were assigned to undergo family-based treatment or usual care and were followed up for 24 months. The trial was conducted from November 2017 through August 2021. Interventions: Family-based treatment used a variety of behavioral techniques to develop healthy eating, physical activity, and parenting behaviors within families. The treatment goal was 26 sessions over a 24-month period with a coach trained in behavior change methods; the number of sessions was individualized based on family progress. Main Outcomes and Measures: The primary outcome was the child's change from baseline to 24 months in the percentage above the median body mass index (BMI) in the general US population normalized for age and sex. Secondary outcomes were the changes in this measure for siblings and in BMI for parents. Results: Among 452 enrolled child-parent dyads, 226 were randomized to undergo family-based treatment and 226 to undergo usual care (child mean [SD] age, 9.8 [1.9] years; 53% female; mean percentage above median BMI, 59.4% [n = 27.0]; 153 [27.2%] were Black and 258 [57.1%] were White); 106 siblings were included. At 24 months, children receiving family-based treatment had better weight outcomes than those receiving usual care based on the difference in change in percentage above median BMI (-6.21% [95% CI, -10.14% to -2.29%]). Longitudinal growth models found that children, parents, and siblings undergoing family-based treatment all had outcomes superior to usual care that were evident at 6 months and maintained through 24 months (0- to 24-month changes in percentage above median BMI for family-based treatment and usual care were 0.00% [95% CI, -2.20% to 2.20%] vs 6.48% [95% CI, 4.35%-8.61%] for children; -1.05% [95% CI, -3.79% to 1.69%] vs 2.92% [95% CI, 0.58%-5.26%] for parents; and 0.03% [95% CI, -3.03% to 3.10%] vs 5.35% [95% CI, 2.70%-8.00%] for siblings). Conclusions and Relevance: Family-based treatment for childhood overweight and obesity was successfully implemented in pediatric primary care settings and led to improved weight outcomes over 24 months for children and parents. Siblings who were not directly treated also had improved weight outcomes, suggesting that this treatment may offer a novel approach for families with multiple children. Trial Registration: ClinicalTrials.gov Identifier: NCT02873715.

SARS-CoV-2 mRNA Vaccination Causes Prolonged Increased Cortical Thickening and Vascularity in Ipsilateral Axillary Lymph Nodes.

OBJECTIVES: To describe the serial grey-scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer-BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) messenger RNA (mRNA) vaccine over 24 to 28 weeks. METHODS: The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey-scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. A total of 11 lateral lymph nodes were identified. Cortical thickness was measured and absence or presence of color Doppler flow in the hilum and lymph node cortex was graded (scale: 0-2). RESULTS: Eleven lateral axillary lymph nodes were biopsied over 24 to 28 weeks. Mean thickness varied through time (P < .001) and was greater weeks 2 to 7 compared to weeks 24 to 28 (mean differences of 2.6 to 1.3; P < .006), but weeks 14 to 17 mean thickness was not different from weeks 24 to 28 (0.57; P = .15). Cortical vascularity was increased in all 11 lymph nodes by week 5. Mean vascularity varied through time (P < .001) and was greater weeks 2 to 14 compared to weeks 24 to 28; mean differences ranged from 1.7 to 0.83 (P < .001). CONCLUSIONS: Serial grey-scale and color Doppler appearance of ipsilateral axillary lymph nodes after mRNA vaccination manifest as increased and prolonged cortical thickening and vascularity that diminishes and approaches normal by 24 to 28 weeks.

Changes in Sedation Practices in Association with Delirium Screening in Infants After Cardiopulmonary Bypass.

Sedation in the cardiac intensive care unit (CICU) is necessary to keep critically ill infants safe and comfortable. However, long-term use of sedatives may be associated with adverse neurodevelopmental outcomes. We aimed to examine sedation practices in the CICU after the implementation of the Cornell Assessment of Pediatric Delirium (CAPD). We hypothesize the use of the CAPD would be associated with a decrease in sedative weans at CICU discharge. This is a single institution, retrospective cohort study. The study inclusion criteria were term infants, birthweight > 2.5 kg, cardiopulmonary bypass (CPB), and mechanical ventilation (MV) on postoperative day zero. During the study period, 50 and 35 patients respectively, met criteria pre- and post-implementation of CAPD screening. Our results showed a statistically significant increase in the incidence of sedative habituation wean at CICU discharge after CAPD implementation (24% vs. 45.7%, p = 0.036). There was a statistically significant increase in exposure to opiate (56% vs. 88.6%, p = 0.001) and dexmedetomidine infusions (52% vs 80%, p = 0.008), increased likelihood of clonidine use at CICU discharge (OR 9.25, CI 2.39-35.84), and increase in the duration of intravenous sedative infusions (8.1 days vs. 5.1 days, p = 0.04) No statistical difference was found in exposure to fentanyl (42% vs. 58.8%, p = 0.13) or midazolam infusions (22% vs. 25.7%, p = 0.691); and there was no change in benzodiazepine or opiate use at CICU discharge or dosage. The prevalence of delirium in the CAPD cohort was 92%. CAPD implementation in the CICU was associated with changes in sedation practices, specifically an increase in the use of dexmedetomidine, which possibly explains the increased clonidine weans at CICU discharge. This is the first report of the association between CAPD monitoring and changes in sedative practices. Multi-center prospective studies are recommended to evaluate sedative practices, delirium, and its effects on neurodevelopment.

Caregiver Prediction of Driving Fitness in Older Adults with Dementia.

Objectives: To determine whether caregiver opinion of fitness to drive and the level of assistance needed for functional activities are useful in determining the need for a Comprehensive Driving Evaluation.Methods: This study examined a sample (N = 179) of drivers with dementia. Caregivers completed a questionnaire that included caregiver opinion of driving fitness and the Functional Assessment Questionnaire (FAQ). A univariate simple logistic regression model was used to examine the relationship of road test failure with caregiver opinion of driving fitness and FAQ scores. From the significant predictive variables from the univariate test, multiple logictic regression models were used to examine possible combination of variables as predictors of road test failure.Results: The combination of caregiver opinion of driving fitness and the FAQ sub-item for memory were found to have modest ability in predicting failure on a standardized on-road driving assessment (AUC 0.727).Conclusions: Caregiver opinion of driving fitness and most individual higher order activities of daily living were found to be independent predictors of failure on a standardized road test.Clinical Implications: Caregiver opinion of driving fitness and ratings of functional activities may be useful for families and clinicians in considering whether an adult with dementia should be more carefully assessed for fitness to drive.

Lung transplant outcomes are influenced by severity of neutropenia and granulocyte colony-stimulating factor treatment.

Although neutropenia is a common complication after lung transplant, its relationship with recipient outcomes remains understudied. We evaluated a retrospective cohort of 228 adult lung transplant recipients between 2008 and 2013 to assess the association of neutropenia and granulocyte colony-stimulating factor (GCSF) treatment with outcomes. Neutropenia was categorized as mild (absolute neutrophil count 1000-1499), moderate (500-999), or severe (<500) and as a time-varying continuous variable. Associations with survival, acute rejection, and chronic lung allograft dysfunction (CLAD) were assessed with the use of Cox proportional hazards regression. GCSF therapy impact on survival, CLAD, and acute rejection development was analyzed by propensity score matching. Of 228 patients, 101 (42.1%) developed neutropenia. Recipients with severe neutropenia had higher mortality rates than those of recipients with no (adjusted hazard ratio [aHR] 2.97, 95% confidence interval [CI] 1.05-8.41, P = .040), mild (aHR 14.508, 95% CI 1.58-13.34, P = .018), or moderate (aHR 3.27, 95% CI 0.89-12.01, P = .074) neutropenia. Surprisingly, GCSF treatment was associated with a higher risk for CLAD in mildly neutropenic patients (aHR 3.49, 95% CI 0.93-13.04, P = .063), although it did decrease death risk in severely neutropenic patients (aHR 0.24, 95% CI 0.07-0.88, P = .031). Taken together, our data point to an important relationship between neutropenia severity and GCSF treatment in lung transplant outcomes.

Maternal Milk and Relationships to Early Neurobehavioral Outcome in Preterm Infants.

The purpose of this study was to (1) define medical and sociodemographic factors related to maternal milk feedings and (2) explore relationships between maternal milk feeding and early neurobehavioral outcome. Ninety-two preterm infants born ≤ 32 weeks gestation had maternal milk feeding and breastfeeding tracked in this retrospective analysis. At 34 to 41 weeks postmenstrual age (PMA), neurobehavior was assessed with the NICU Network Neurobehavioral Scale. Maternal milk feeding was often delayed by the use of total parenteral nutrition, administered for a median of 11 (7-26) days, impacting the timing of gastric feeding initiation. Seventy-nine (86%) infants received some maternal milk during neonatal intensive care unit (NICU) hospitalization. Twenty-one (27%) infants continued to receive maternal milk at 34 to 41 weeks PMA, with 10 (48%) of those receiving maternal milk exclusively. Among mothers who initiated maternal milk feeds, 20 (25%) put their infants directly at the breast at least once during hospitalization. Mothers who were younger (P = .02), non-Caucasian (P < .001), or on public insurance (P < .001) were less likely to provide exclusive maternal milk feedings by 34 to 41 weeks PMA. Infants who received maternal milk at 34 to 41 weeks PMA demonstrated better orientation (P = .03), indicating they had better visual and auditory attention to people and objects in the environment. Our findings demonstrate a relationship between maternal milk feedings and better neurobehavior, which is evident before the infant is discharged home from the NICU.

Interrater Reliability and Concurrent Validity of the Neonatal Eating Outcome Assessment.

IMPORTANCE: Few neonatal feeding assessments are currently available, and the Neonatal Eating Outcome Assessment is the only one that identifies feeding impairment while considering the developmental changes that occur from preterm birth to term-equivalent age. OBJECTIVE: To determine the interrater reliability and concurrent validity of the Neonatal Eating Outcome Assessment. DESIGN: Prospective, observational study. SETTING: Level 4 neonatal intensive care unit. PARTICIPANTS: A convenience sample of 7 neonatal therapists participated in reliability testing. For concurrent validity, a prospective cohort of 52 preterm infants born ≤32 wk gestation had feeding assessed at term-equivalent age. OUTCOMES AND MEASURES: Intraclass correlations (ICCs) and Fleiss's κ statistics were used to define reliability across therapists, who independently scored five videos of preterm infants orally feeding using the Neonatal Eating Outcome Assessment. Concurrent validity was determined by evaluating relationships between the Neonatal Oral Motor Assessment Scale (NOMAS) and the Neonatal Eating Outcome Assessment using an independent-samples t test and χ² analysis. RESULTS: The ICC for the Neonatal Eating Outcome Assessment total score was 0.90 (confidence interval [CI] [0.70, 0.99]). Fleiss's κ scores for the 19 scorable items on the Neonatal Eating Outcome Assessment had predominately moderate, fair, and slight agreement, with 3 items having poor agreement. Dysfunctional NOMAS scores were related to lower Neonatal Eating Outcome Assessment scores (t[49.4] = 3.72, mean difference = 12.2, 95% CI [5.60, 18.75], p = .001). CONCLUSIONS AND RELEVANCE: The Neonatal Eating Outcome Assessment has excellent reliability. Concurrent validity was established. WHAT THIS ARTICLE ADDS: This article reports that the final version of the Neonatal Eating Outcome Assessment (Version 5.7) has excellent interrater and concurrent validity and is an important tool to assess the occupation of infant feeding in clinical practice.

Validity and Reliability of the Traffic Sign Naming Test (TSNT) and Written Exam for Driving Decisions (WEDD) as Measures of Fitness to Drive Among Older Adults.

IMPORTANCE: Occupational therapists need valid and reliable tools to help determine fitness to drive of older drivers with medical conditions such as dementia. OBJECTIVE: To establish the validity and reliability of the Traffic Sign Naming Test (TSNT) and Written Exam for Driving Decisions (WEDD) as measures of fitness to drive of adults with and without dementia. DESIGN: Cross-sectional. SETTING: Washington University Medical School in St. Louis in collaboration with the Rehabilitation Institute of St. Louis. PARTICIPANTS: Older drivers diagnosed with dementia (n = 130) and without dementia (n = 34). Drivers with dementia required a physician referral indicating a medical need for a driving evaluation, a diagnosis of dementia, and an Alzheimer Detection 8 score of 2. Drivers without dementia were required to be age 55 yr or older and not meet criteria for dementia. OUTCOMES AND MEASURES: Participants completed a comprehensive driving evaluation (CDE) that included clinical measures of vision, motor, and cognition; TSNT; and WEDD. The outcome measure was performance on a standardized on-road assessment. RESULTS: The TSNT's interrater reliability was determined to be strong (κ = .80). The TSNT and WEDD demonstrated convergent validity with cognitive measures (p < .001) and discriminant validity with visual and motor measures in the CDE. The TSNT (area under the curve [AUC] = .74) and WEDD (AUC = .71) had fair ability to predict failure on a standardized on-road assessment. CONCLUSION AND RELEVANCE: TSNT and WEDD are recommended for use by occupational therapists in combination with other performance measures when determining fitness to drive or need for a CDE. WHAT THIS ARTICLE ADDS: The TSNT and WEDD can be included as screening tools (in addition to other performance measures) to assist clinicians in determining which clients need to be referred for a CDE. The TSNT and WEDD can also be included as part of a CDE to assist driving rehabilitation specialists in making final recommendations regarding fitness to drive. The scores generated from the TSNT and WEDD address driving knowledge in a way that may be more understandable to clients and more relatable to skills needed to actually drive.

Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

OBJECTIVE: Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. APPROACH AND RESULTS: In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 in a lipid emulsion and dietary cholesterol with cholesterol-d5 and sitostanol-d4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P<0.0001) and low-density lipoprotein cholesterol 19.8±1.9% (P=0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% (P<0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% (P<0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% (P=0.0096). Fecal bile acids were unchanged. CONCLUSIONS: Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. CLINICAL TRIALS REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758.

Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans.

OBJECTIVE: Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. APPROACH AND RESULTS: Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d5 and the nonabsorbable stool marker sitostanol-d4. Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol (r=-0.426; P<0.0001), total cholesterol (r=-0.472; P≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool (r=-0.343; P=0.0012) and was positively correlated with percent cholesterol absorption (r=+0.279; P=0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant (P=0.0008). CONCLUSIONS: Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate measures of reverse cholesterol transport to atherosclerotic disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758.

Impact of routine surveillance biopsy intensity on the diagnosis of moderate to severe cellular rejection and survival after pediatric heart transplantation.

Data are lacking on RSB intensity and outcomes after pediatric heart transplantation. PHTS centers received a survey on RSB practices from 2005 to present. PHTS data were obtained for 2010-2013 and integrated with center-matched survey responses for analysis. Survey response rate was 82.6% (38/46). Centers were classified as low-, moderate-, and high-intensity programs based on RSB frequency (0-more than 8 RSB/y). RSB intensity decreased with increasing time from HT. Age at HT impacted RSB intensity mostly in year 1, with little to no impact in later years. Most centers have not replaced RSB with non-invasive methods, but many added ECHO and biomarker monitoring. Higher RSB intensity was not associated with decreased 4-year mortality (P=.63) or earlier detection of moderate to severe (ISHLT grade 2R/3R) cellular rejection (RSBMSR) in the first year (P=.87). First-year RSBMSR incidence did not differ with intensity or age at HT. Significant variability exists in RSB intensity, but with no impact on timing and incidence of RSBMSR or 4-year mortality. Reduction in RSB frequency may be safe in certain patients after pediatric HT.

A Cross-Sectional Study Assessing Treatment Preference of People With Chronic Low Back Pain.

OBJECTIVE: To assess treatment preference and attributes of 2 exercise-based treatments for people with chronic low back pain (LBP). DESIGN: Cross-sectional study. SETTING: Academic research setting. PARTICIPANTS: Individuals (N=154) with chronic LBP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed a treatment preference assessment (TPA) measure that described 2 treatments for chronic LBP (strength and flexibility [SF] and motor skill training [MST]). Participants rated each treatment on 4 attributes: effectiveness, acceptability/logicality, suitability/appropriateness, and convenience. An overall score for each treatment was calculated as the mean of the 4 attribute ratings. The participants indicated either (1) no treatment preference or (2) preference for SF or MST. RESULTS: One hundred four participants (67.5%) had a treatment preference; of those, 95 (91.3%) preferred SF and 9 (8.7%) preferred MST. The SF preference group rated SF higher than MST overall and on all attributes (all Ps <.01, ds ranged from .48-1.07). The MST preference group did not rate the treatments differently overall or on any of the attributes (all Ps >.05, ds ranged from .43-.66). Convenience of SF (P=.05, d=.79) and effectiveness (d=1.20), acceptability/logicality (d=1.27), and suitability/appropriateness (d=1.52) of MST (all Ps <.01) were rated differently between the 2 preference groups. CONCLUSIONS: When presented with 2 treatment options, a majority of patients preferred SF over MST. Convenience was a particularly important attribute affecting preference. Assessing treatment preference and attributes prior to treatment initiation allows the clinician to identify factors that may need to be addressed to enhance adherence to, and outcomes of, treatment.

Neonatal Eating Outcome Assessment: tool development and inter-rater reliability.

AIM: To define the process of tool development and revision for the Neonatal Eating Outcome (NEO) Assessment and to report preliminary inter-rater reliability. METHODS: Tool development consisted of a review of the literature and observations of feeding performance among 178 preterm infants born ≤32 weeks gestation. 11 neonatal therapy feeding experts provided structured feedback to establish content validity and define the scoring matrix. The tool was then used to evaluate feeding in 50 preterm infants born ≤32 weeks of gestation and 50 full-term infants. Multiple revisions occurred at each stage of development. Finally, six neonatal occupational therapists participated in reliability testing by independently scoring five videos of oral feeding of preterm infants using version 4 of the tool. RESULTS: The intraclass correlation for the 'prefeeding' score was 0.71 (0.37-0.96), and the intraclass correlation for the 'total' score was 0.83 (0.56-0.98). CONCLUSION: The 'total' score had good to excellent reliability. Fleiss' Kappa scores for all 18 scorable items ranged from slight agreement to moderate agreement. Items with the lowest Kappa scores were revised, and additional feedback from therapists engaged in reliability testing was incorporated, resulting in final version 5.

Diffusion MRI quantifies early axonal loss in the presence of nerve swelling.

BACKGROUND: Magnetic resonance imaging markers have been widely used to detect and quantify white matter pathologies in multiple sclerosis. We have recently developed a diffusion basis spectrum imaging (DBSI) to distinguish and quantify co-existing axonal injury, demyelination, and inflammation in multiple sclerosis patients and animal models. It could serve as a longitudinal marker for axonal loss, a primary cause of permanent neurological impairments and disease progression. METHODS: Eight 10-week-old female C57BL/6 mice underwent optic nerve DBSI, followed by a week-long recuperation prior to active immunization for experimental autoimmune encephalomyelitis (EAE). Visual acuity of all mice was assessed daily. Longitudinal DBSI was performed in mouse optic nerves at baseline (naïve, before immunization), before, during, and after the onset of optic neuritis. Tissues were perfusion fixed after final in vivo scans. The correlation between DBSI detected pathologies and corresponding immunohistochemistry markers was quantitatively assessed. RESULTS: In this cohort of EAE mice, monocular vision impairment occurred in all animals. In vivo DBSI detected, differentiated, and quantified optic nerve inflammation, demyelination, and axonal injury/loss, correlating nerve pathologies with visual acuity at different time points of acute optic neuritis. DBSI quantified, in the presence of optic nerve swelling, ~15% axonal loss at the onset of optic neuritis in EAE mice. CONCLUSIONS: Our findings support the notion that axonal loss could occur early in EAE mice. DBSI detected pathologies in the posterior visual pathway unreachable by optical coherence tomography and without confounding inflammation induced optic nerve swelling. DBSI could thus decipher the interrelationship among various pathological components and the role each plays in disease progression. Quantification of the rate of axonal loss could potentially serve as the biomarker to predict treatment outcome and to determine when progressive disease starts.

Auditory Exposure in the Neonatal Intensive Care Unit: Room Type and Other Predictors.

OBJECTIVE: To quantify early auditory exposures in the neonatal intensive care unit (NICU) and evaluate how these are related to medical and environmental factors. We hypothesized that there would be less auditory exposure in the NICU private room, compared with the open ward. STUDY DESIGN: Preterm infants born at ≤ 28 weeks gestation (33 in the open ward, 25 in private rooms) had auditory exposure quantified at birth, 30 and 34 weeks postmenstrual age (PMA), and term equivalent age using the Language Environmental Acquisition device. RESULTS: Meaningful language (P < .0001), the number of adult words (P < .0001), and electronic noise (P < .0001) increased across PMA. Silence increased (P = .0007) and noise decreased (P < .0001) across PMA. There was more silence in the private room (P = .02) than the open ward, with an average of 1.9 hours more silence in a 16-hour period. There was an interaction between PMA and room type for distant words (P = .01) and average decibels (P = .04), indicating that changes in auditory exposure across PMA were different for infants in private rooms compared with infants in the open ward. Medical interventions were related to more noise in the environment, although parent presence (P = .009) and engagement (P = .002) were related to greater language exposure. Average sound levels in the NICU were 58.9 ± 3.6 decibels, with an average peak level of 86.9 ± 1.4 decibels. CONCLUSIONS: Understanding the NICU auditory environment paves the way for interventions that reduce high levels of adverse sound and enhance positive forms of auditory exposure, such as language.

Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury.

OBJECTIVE: To evaluate the clinical effectiveness of bolus-dose fentanyl and midazolam to treat episodic intracranial hypertension in children with severe traumatic brain injury. DESIGN: Retrospective cohort. SETTING: PICU in a university-affiliated children's hospital level I trauma center. PATIENTS: Thirty-one children 0-18 years of age with severe traumatic brain injury (Glasgow Coma Scale score of ≤ 8) who received bolus doses of fentanyl and/or midazolam for treatment of episodic intracranial hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area under the curve from high-resolution intracranial pressure-time plots was calculated to represent cumulative intracranial hypertension exposure: area under the curve for intracranial pressure above 20 mm Hg (area under the curve-intracranial hypertension) was calculated in 15-minute epochs before and after administration of fentanyl and/or midazolam for the treatment of episodic intracranial hypertension. Our primary outcome measure, the difference between predrug and postdrug administration epochs (Δarea under the curve-intracranial hypertension), was calculated for all occurrences. We examined potential covariates including age, injury severity, mechanism, and time after injury; time after injury correlated with Δarea under the curve-intracranial hypertension. In a mixed-effects model, with patient as a random effect, drug/dose combination as a fixed effect, and time after injury as a covariate, intracranial hypertension increased after administration of fentanyl and/or midazolam (overall aggregate mean Δarea under the curve-intracranial hypertension = +17 mm Hg × min, 95% CI, 0-34 mm Hg × min; p = 0.04). The mean Δarea under the curve-intracranial hypertension increased significantly after administration of high-dose fentanyl (p = 0.02), low-dose midazolam (p = 0.006), and high-dose fentanyl plus low-dose midazolam (0.007). Secondary analysis using age-dependent thresholds showed no significant impact on cerebral perfusion pressure deficit (mean Δarea under the curve-cerebral perfusion pressure). CONCLUSIONS: Bolus dosing of fentanyl and midazolam fails to reduce the intracranial hypertension burden when administered for episodic intracranial hypertension. Paradoxically, we observed an overall increase in intracranial hypertension burden following drug administration, even after accounting for within-subject effects and time after injury. Future work is needed to confirm these findings in a prospective study design.