Phage vs. Phage: Direct Selections of Sandwich Binding Pairs.

The sandwich format immunoassay is generally more sensitive and specific than more common assay formats, including direct, indirect, or competitive. A sandwich assay, however, requires two receptors to bind non-competitively to the target analyte. Typically, pairs of antibodies (Abs) or antibody fragments (Fabs) that are capable of forming a sandwiching with the target are identified through a slow, guess-and-check method with panels of candidate binding partners. Additionally, sandwich assays that are reliant on commercial antibodies can suffer from changes to reagent quality outside the researchers' control. This report presents a reimagined and simplified phage display selection protocol that directly identifies sandwich binding peptides and Fabs. The approach yielded two sandwich pairs, one peptide-peptide and one Fab-peptide sandwich for the cancer and Parkinson's disease biomarker DJ-1. Requiring just a few weeks to identify, the sandwich pairs delivered apparent affinity that is comparable to other commercial peptide and antibody sandwiches. The results reported here could expand the availability of sandwich binding partners for a wide range of clinical biomarker assays.

Electrolyte abnormalities and stress dosing predict illness-related hospitalizations among infants and toddlers with congenital adrenal hyperplasia.

OBJECTIVE: Infants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for morbidity/mortality arising from life-threatening adrenal crisis. Management of acute illnesses in CAH requires an understanding of factors leading to emergency department (ED) visits and hospitalizations in the first few years of life. We, therefore, examined adrenal crisis at prehospital and ED stages of illness in young children with CAH as they related to medical outcomes. PATIENTS AND DESIGN: Retrospective cohort study of 39 children with CAH due to 21-hydroxylase deficiency (0-4 years of age) and 27 age-matched controls. MEASUREMENTS: ED visit, acute illness symptoms (fever, vomiting, diarrhoea) and other characteristics (hospitalizations, administration of stress-dose hydrocortisone, electrolyte abnormalities). RESULTS: CAH infants and toddlers had significantly higher rates of ED visits (0.50 [0.25-0.88] per person-year) than controls (0 [0-0] per person-year; p < .001). Moreover, CAH children under 6 months old had significantly higher rates of ED visits compared with older ages. Only 50% (51/102) of illness-related ED visits in CAH children were preceded by the administration of either oral (46/51) or intramuscular (11/51) stress dosing by parents. A total of 10.8% of ED visits resulted in hospital admission. Controlling for age and 17-hydroxyprogesterone at diagnosis, electrolyte abnormalities and administration of parenteral hydrocortisone in the ED significantly predicted hospital admission. Receiving a hydrocortisone injection before the ED was a significant predictor of having electrolyte abnormalities. CONCLUSIONS: Infants and toddlers with classical CAH are at high risk for acute illness and hospitalizations and often do not receive adequate stress dosing before the ED.

Preoperative Educational Intervention Decreases Unplanned Gastrostomy-Related Health Care Utilization.

Apprehension in taking independent care of children with medical devices may lead to unnecessary visits to the ED and/or acute clinic (AC). To address these concerns, our institution implemented a gastrostomy tube (GT) class in 2011 for caretakers. We hypothesized that inappropriate GT-related ED/AC visits would be lower in preoperatively educated caregivers. We performed a retrospective cohort study of all patients aged 0 to 18 who received GT (surgical or percutaneous) at our institution between 2006 and 2015 (n = 1340). Class attendance (trained vs untrained) and unscheduled GT-related ED/AC visits one year after GT placement were reviewed. Gastrostomy-related ED/AC visits were classified as appropriate (hospital-based intervention) or inappropriate (site care and education/reassurance). Occurrence of ED/AC visits was compared between trained and untrained cohorts. We found that 59 per cent of patients had an unscheduled GT-related ED/AC visit within one year of placement. The trained cohort had 27 per cent less unplanned ED/AC visits within one year (mean 1.21 (SD 1.82) vs untrained 1.65 (2.24), P < 0.001). On multivariate analysis, GT education independently decreased one-year GT-related health care utilization (Odds Ratio 0.75, 95% Confidence Interval 0.59-0.95). Formal education seems to decrease GT-related health care utilization within one year of placement and should be integrated into a comprehensive care plan to improve caregiver self-efficacy.

Association between pediatric home management plan of care compliance and asthma readmission.

OBJECTIVES: In 2007, The Joint Commission implemented three children's asthma care (CAC) measures to help improve the quality of care for patients admitted with asthma. Due to lack of consistent evidence showing a relationship between home management plan of care (HMPC) compliance and readmission rates, CAC-3 was retired in 2016. We aimed to understand the relationship between HMPC compliance and revisits to the hospital, and investigate which components of the HMPC, if any, were driving the effect. METHODS: This was a retrospective cohort study at a quaternary care freestanding children's hospital, including patients between 2 and 17 years of age admitted with a primary diagnosis of asthma between January 1, 2006, and July 1, 2013. Bivariate and multiple logistic regression analyses examined effects of HMPC provider compliance on hospital readmission and emergency department utilization for asthma within 180 days of initial discharge, controlling for admission to the intensive care unit, age, gender, ethnicity, insurance type, and whether inhaled corticosteroids were prescribed. RESULTS: A total of 1,176 patients were included. Those discharged with an HMPC (n = 756, of which 84% were fully compliant) were found to have significantly lower readmission rates (7 vs. 11.9%; aOR = 0.63; 95% CI, 0.41-0.95) and ED revisit rates (aOR = 0.73; 95% CI, 0.56-0.96) within 180 days of discharge. CONCLUSIONS: Providing an HMPC upon discharge was found to be associated with decreased asthma readmission and ED utilization rates. This suggests that although HMPC is no longer a required measure, there may still be utility in continuing this practice.

Factors Associated With the Prophylactic Prescription of a Bowel Regimen to Prevent Opioid-Induced Constipation.

OBJECTIVE: Identify factors associated with the prophylactic prescription of a bowel regimen with an inpatient opioid prescription. METHODS: This was a retrospective cohort study from June 1, 2013, to October 31, 2014 of pediatric inpatients prescribed an oral or intravenous opioid on the general medical/surgical floors. We identified patients with or without a prophylactic prescription of a bowel regimen. We obtained patient demographics, prescriber training level and service and used multivariate logistic regression to analyze the factors associated with prophylactic bowel regimen and opioid prescription. RESULTS: Of the 6682 encounters that met study criteria, only 966 (14.5%) encounters had prophylactic prescriptions. Patient factors associated with prophylactic prescription include increasing age (per year; odds ratio [OR] = 1.06, 95% confidence interval [CI] 1.05-1.07) and sickle cell diagnosis (OR = 3.19, 95% CI 2.08-4.91). Medication factors associated with prophylactic prescription include a scheduled opioid prescription (OR = 1.75, 95% CI 1.46-2.1) and a prescription for oxycodone (OR = 3.59, 95% CI 2.57-5.00) or morphine (OR = 1.84, 95% CI 1.39-2.44), compared with acetaminophen-hydrocodone. Compared with medical providers, surgeons were less likely (OR = 0.43, 95% CI 0.35-0.53) and pain service providers were more likely to prescribe a prophylactic bowel regimen (OR = 4.12, 95% CI 3.13-5.43). CONCLUSIONS: More than 85% of inpatient opioid prescriptions did not receive a prophylactic bowel regimen. Future research should examine factors (eg, clinical decision support tools) to increase prophylactic prescription of bowel regimens with opioids for populations found to have lower rates.

Current Roles and Perceived Needs of Pediatric Hospital Medicine Fellowship Graduates.

OBJECTIVES: Pediatric hospitalists report the need for additional training in clinical and nonclinical domains. Pediatric hospital medicine (PHM) fellowships seek to provide this training and produce leaders in the field. Our objective is to describe current roles and perceived training needs of PHM fellowship graduates. METHODS: In 2014, all PHM fellowship graduates were asked to complete a Web-based survey. Survey questions addressed demographics, past training, current roles, and training needs in clinical care, research, education, and administration. Associations between fellowship experiences and outcomes were examined. RESULTS: Fifty-one of 61 eligible individuals completed the survey. Average duration as a pediatric hospitalist was 5 years. Ninety percent completed pediatric categorical residency, whereas 10% completed an Internal Medicine-Pediatrics Residency. Most respondents completed a 1- (38%) or 2-year (46%) fellowship program. Ninety-six percent of respondents currently work in academic environments. The perceived need for additional clinical training was low, except procedures (44%). Nearly all teach medical students and pediatric residents, reporting adequate training in variety of teaching strategies. The majority of respondents conduct research, most commonly quality improvement (QI; 67%) and education (52%). Two-thirds are first authors on at least 1 peer-reviewed article. Research training needs include QI methodology (44%), biostatistics (43%), and obtaining funding (54%). A considerable number of respondents have academic leadership positions. CONCLUSIONS: PHM fellowship graduates are academic hospitalists with diverse responsibilities. Despite a short average career span, many have achieved leadership roles and been academically productive. Future curriculum development should focus on procedures, QI, and research training.

Carotid Intima-Media Thickness Is Associated with Increased Androgens in Adolescents and Young Adults with Classical Congenital Adrenal Hyperplasia.

BACKGROUND/AIMS: Youth with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency develop cardiovascular disease (CVD) risk factors of obesity and hypertension. Carotid intima-media thickness (CIMT), a marker of CVD risk, is increased in CAH young adults. We examined CIMT and its relationship with androgens and obesity in adolescents/young adults with CAH. METHODS: Twenty CAH subjects (age 16 ± 3.3 years, 50% female) and 20 matched controls were studied cross-sectionally. Eight additional obese patients with CAH were included in within-group comparisons. CIMT by high-resolution ultrasound, androgens, anthropometry, bone age (BA), and metabolic/inflammatory markers were assessed. RESULTS: Within the CAH group, CIMT correlated with 17-hydroxyprogesterone (r = 0.48, p < 0.05) and androstenedione (r = 0.46, p < 0.05), and was greater in obese subjects. CIMT was greater in CAH males than females, but similar among CAH females with advanced BA, CAH males with normal BA, and control males. There was no difference in CIMT between CAH and controls, although high-density lipoprotein was inversely correlated with CIMT in both groups. CONCLUSION: CIMT is associated with increased androgens in CAH adolescents and young adults, with loss of sex differences in CAH females with excess androgen exposure. Our findings highlight the importance of hormonal control for CVD prevention in CAH.

Active Videogaming for Individuals with Severe Movement Disorders: Results from a Community Study.

OBJECTIVE: Active videogaming (AVG) has potential to provide positive health outcomes for individuals with cerebral palsy (CP), but their use for individuals with severe motor impairments is limited. Our objective was to evaluate the accessibility and enjoyment of videogames using the Kinect™ (Microsoft, Redmond, WA) with the Flexible Action and Articulated Skeleton Toolkit (FAAST) system (University of Southern California Institute for Creative Technologies, Los Angeles, CA) for individuals with severely limiting CP. MATERIALS AND METHODS: A videogaming system was installed in a community center serving adults with CP, and a staff member was instructed in its use. Participants completed a baseline survey assessing demographics, mobility, and prior videogame experience; they then used the FAAST system with Kinect and completed a 5-point Likert survey to assess their experience. Descriptive statistics assessed overall enjoyment of the system, and Mann-Whitney U tests were conducted to determine whether responses differed by demographic factors, mobility, or prior videogame experience. RESULTS: Twenty-two subjects were recruited. The enjoyment scale demonstrated high internal consistency (Cronbach's alpha=0.88). The mean total enjoyment score was 4.24 out of 5. Median scores did not significantly differ by ethnicity, gender, CP severity, or previous videogame exposure. CONCLUSIONS: The FAAST with Kinect is a low-cost system that engages individuals with severe movement disorders across a wide range of physical ability and videogame experience. Further research should be conducted on in-home use, therapeutic applications, and potential benefits for socialization.