Association of Digoxin With Interstage Mortality: Results From the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use Dataset

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139107/1/jah31279.pd

Microvascular cerebral hemodynamics in pediatric sickle cell disease with Diffuse Correlation Spectroscopy

Sickle cell disease is a genetic blood disorder that has profound effects on the brain. Chronic anemia combined with both macro- and micro-vascular perfusion abnormalities that arise from stenosis or occlusion of blood vessels, increased blood viscosity, adherence of red blood cells to the vascular endothelium, and impaired autoregulatory mechanisms in sickle cell disease patients all culminate in susceptibility to cerebral infarction. Indeed, the risk of stroke is 250 times higher in children with sickle cell disease than in the general population. Unfortunately, while transcranial Doppler ultrasound (TCD) has been widely clinically adopted to longitudinally monitor macrovascular perfusion in these patients, routine clinical screening of microvascular perfusion abnormalities is challenging with current modalities (e.g., positron emission tomography, magnetic resonance imaging) given their high-cost, requirement for sedation in children \u3c 6y, and need for trained personnel. In this pilot study, we first assess the feasibility of a low-cost, noninvasive optical technique known as Diffuse Correlation Spectroscopy (DCS) to quantify an index of resting-state cortical cerebral blood flow in 11 children with SCD along with 11 sex- and age-matched healthy controls. As expected, blood flow index was significantly higher in sickle subjects compared to healthy controls (p \u3c 0.001). Within sickle subjects, blood flow index was inversely proportional to resting-state arterial hemoglobin levels (p = 0.012), consistent with expected anemia-induced compensatory vasodilation that aims to maintain adequate oxygen delivery to the tissue. Further, in a subset of patients measured with transcranial Doppler ultrasound, DCS-measured blood flow was correlated with TCD-measured blood flow velocity in middle cerebral artery (Rs = 0.68), although the trend was not statistically significant (p=0.11). These results are consistent with those of several previous studies using traditional neuroimaging techniques to quantify cerebral blood flow, suggesting that DCS may be a promising low-cost tool for assessment of tissue-level cerebral blood flow in pediatric sickle cell disease. Finally, given that sickle cell disease is often associated with severe anemia, we next assessed the potentially confounding effects of hematocrit on the DCS-measured blood flow index using a microfluidic tissue-simulating phantom. For a fixed flow rate in the microfluidic channels, we show that blood flow index is inversely correlated with hematocrit, and we present a means to correct the measured blood flow index for hematocrit in anemic conditions

An exploration of concomitant psychiatric disorders in children with autism spectrum disorder

Objective We explored patterns of concomitant psychiatric disorders in a large sample of treatment-seeking children and adolescents with autism spectrum disorder (ASD). Methods Participants were 658 children with ASD (age 3–17 years; mean = 7.2 years) in one of six federally-funded multisite randomized clinical trials (RCT) between 1999 and 2014. All children were referred for hyperactivity or irritability. Study designs varied, but all used the Child and Adolescent Symptom Inventory or Early Childhood Inventory to assess Attention Deficit Hyperactivity Disorder (ADHD), Oppositional-Defiant Disorder (ODD), Conduct Disorder (CD), Anxiety Disorders, and Mood Disorders. In addition, several measures in common were used to assess demographic and clinical characteristics. Results Of the 658 children, 73% were Caucasian and 59% had an IQ >70. The rates of concomitant disorders across studies were: ADHD 81%, ODD 46%, CD 12%, any anxiety disorder 42%, and any mood disorder 8%. Two or more psychiatric disorders were identified in 66% of the sample. Of those who met criteria for ADHD, 50% also met criteria for ODD and 46% for any anxiety disorder. Associations between types of concomitant disorders and a number of demographic and clinical characteristics are presented. Conclusion In this well-characterized sample of treatment-seeking children with ASD, rates of concomitant psychiatric disorders were high and the presence of two or more co-occurring disorders was common. Findings highlight the importance of improving diagnostic practice in ASD and understanding possible mechanisms of comorbidity

Normalized measures and patient characteristics to identify undernutrition in infants and young children treated for cancer

Background: Various measures and definitions for undernutrition are used in pediatrics. Younger children treated for cancer are at high risk, but lack well-defined risk-based screening and intervention. Methods: A retrospective study collected weight longitudinally for patients less than three years-old over two years after initiating cancer treatment. We included those diagnosed 2007-2015 at a large pediatric cancer center. Exclusion criteria included treatment starting outside our system, secondary or relapsed malignancy, or incomplete information. A decrease ≥1 in weight-for-age or weight-for-height z-score signified clinically significant weight loss. Univariate and multivariate models assessed hazards for developing first episode of clinically significant weight loss. Results: Of 372 patients, only 24.6% of patients lost 10% of weight, but 58.6% lost weight-for-age z-score ≥1 and 64.8% lost ≥1 weight-for-height z-score within two years of treatment initiation. Patients who lost weight were younger (median age 15 vs. 24 months, p < 0.001). Compared to patients diagnosed in the first year of life, those diagnosed 24-35 months were less likely to lose weight (HR 0.62, p < 0.001) and lost weight later (median time to weight loss 144 vs. 35 days). Higher treatment intensity increased weight loss risk (HR 2.30, p < 0.001) and decreased time to weight loss (35 vs. 154 days). No differences were found based on sex, diagnosis, enteral or parenteral nutrition, gastroenterology consults, or intensive care admissions. Conclusions: Using normalized z-scores is more sensitive for identifying weight loss. Younger children are more likely to lose weight with higher intensity cancer therapy. Patient and treatment specific information should be used in risk stratifying weight loss screening and nutritional interventions

Comprehensive comparative outcomes in children with congenital heart disease: The rationale for the Congenital Catheterization Research Collaborative

Clinical research in the treatment of patients with congenital heart disease (CHD) is limited by the wide variety of CHD manifestations and therapeutic options as well as the generally low incidence of CHD. The availability of comprehensive, contemporary outcomes studies is therefore limited. This inadequacy may result in a lack of data‐driven medical decision making. In 2013, clinician scientists at two centers began a research collaboration, the Congenital Catheterization Research Collaborative (CCRC). Over time, the CCRC has grown to include nine cardiac centers from across the United States, with a common data coordinating center. The CCRC seeks to generate high‐quality, contemporary, statistically robust, and generalizable outcomes research which can help address important clinical questions in the treatment of CHD. To date, the CCRC has reported on multicenter outcomes in: neonates with congenital aortic stenosis, infants undergoing right ventricular decompression for pulmonary atresia and intact ventricular septum, and infants with ductal‐dependent pulmonary blood flow. The CCRC has been successful at leveraging large multicenter cohorts of patients in a contemporary period to perform comparative studies. In the future, the CCRC plans to continue to perform hypothesis‐driven retrospective and prospective observational studies of CHD populations where controversy exists or where novel interventions or therapies have emerged. Quality improvement efforts including lesion‐specific registry development may be an additional potential future target.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149494/1/chd12737.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149494/2/chd12737_am.pd

Self-Reported Cognitive Function and Mental Health Diagnoses among Former Professional American-Style Football Players

Clinical practice strongly relies on patients' self-report. Former professional American-style football players are hesitant to seek help for mental health problems, but may be more willing to report cognitive symptoms. We sought to assess the association between cognitive symptoms and diagnosed mental health problems and quality of life among a cohort of former professional players. In a cross-sectional design, we assessed self-reported cognitive function using items from the Quality of Life in Neurological Disorders (Neuro-QOL) Item Bank. We then compared mental health diagnoses and quality of life, assessed by items from the Patient-Reported Outcome Measurement Information System (PROMIS ®), between former professional players reporting daily problems in cognitive function and former players not reporting daily cognitive problems. Of the 3758 former professional players included in the analysis, 40.0% reported daily problems due to cognitive dysfunction. Former players who reported daily cognitive problems were more likely to also report depression (18.0% vs. 3.3%, odds ratio [OR] = 6.42, 95% confidence interval [CI] [4.90-8.40]) and anxiety (19.1% vs. 4.3%, OR = 5.29, 95% CI [4.14-6.75]) than those without daily cognitive problems. Further, former players reporting daily cognitive problems were more likely to report memory loss and attention deficit(/hyperactivity) disorder and poorer general mental health, lower quality of life, less satisfaction with social activities and relationships, and more emotional problems. These findings highlight the potential of an assessment of cognitive symptoms for identifying former players with mental health, social, and emotional problems

Response to rhinovirus infection by human airway epithelial cells and peripheral blood mononuclear cells in an in vitro two-chamber tissue culture system.

Human rhinovirus (HRV) infections are associated with the common cold, occasionally with more serious lower respiratory tract illnesses, and frequently with asthma exacerbations. The clinical features of HRV infection and its association with asthma exacerbation suggest that some HRV disease results from virus-induced host immune responses to infection. To study the HRV-infection-induced host responses and the contribution of these responses to disease, we have developed an in vitro model of HRV infection of human airway epithelial cells (Calu-3 cells) and subsequent exposure of human peripheral blood mononuclear cells (PBMCs) to these infected cells in a two-chamber trans-well tissue culture system. Using this model, we studied HRV 14 (species B) and HRV 16 (species A) induced cytokine and chemokine responses with PBMCs from four healthy adults. Infection of Calu-3 cells with either virus induced HRV-associated increases in FGF-Basic, IL-15, IL-6, IL-28A, ENA-78 and IP-10. The addition of PBMCs to HRV 14-infected cells gave significant increases in MIP-1β, IL-28A, MCP-2, and IFN-α as compared with mock-infected cells. Interestingly, ENA-78 levels were reduced in HRV 14 infected cells that were exposed to PBMCs. Addition of PBMCs to HRV 16-infected cells did not induce MIP-1β, IL-28A and IFN-α efficiently nor did it decrease ENA-78 levels. Our results demonstrate a clear difference between HRV 14 and HRV 16 and the source of PBMCs, in up or down regulation of several cytokines including those that are linked to airway inflammation. Such differences might be one of the reasons for variation in disease associated with different HRV species including variation in their link to asthma exacerbations as suggested by other studies. Further study of immune responses associated with different HRVs and PBMCs from different patient groups, and the mechanisms leading to these differences, should help characterize pathogenesis of HRV disease and generate novel approaches to its treatment