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OBJECTIVE: Evaluate longitudinal changes in brain microstructure and volumes in very preterm during the first year of life with and without intervention. DESIGN: Descriptive pilot study METHODS: Five preterm infants in a three-arm clinical trial, one SPEEDI Early, two SPEEDI Late, and two usual care. Brain structural and diffusion MRI’s were acquired within 72 hours after neonatal intensive care unit discharge (n=5), three months post-baseline (n=5), and six months post-baseline (n=3). Fractional anisotropy (FA), Mean diffusivity (MD), and volume metrics were computed for five brain regions. RESULTS: More than 60% of eligible participants completed 100% of the scheduled MRIs. FA and volume increased from baseline to six months across all brain regions. Rate of white matter volume change from baseline to six months was highest in SPEEDI Early. CONCLUSIONS: Non-sedated longitudinal MRI is feasible in very preterm infants and appears to demonstrate longitudinal changes in brain structure and connectivity.

Objective The aim of this project is to study the effect of a physical therapist intervention provided in the first months of life on developmental outcomes of infants born very preterm. Secondary aims are to investigate the impact of intervention timing on the efficacy and impact of the intervention on infants with and without cerebral palsy. Methods This study is a multisite longitudinal controlled trial comparing developmental outcomes from infants in the Supporting Play, Exploration, and Early Development Intervention (SPEEDI)_Late or SPEEDI_Early group to a usual care group. Settings are urban Urban and rural areas surrounding 2 academic medical centers. There will be 90 preterm infants enrolled in this study born at Impact More than 270,000 infants are born very preterm in the United States each year, 50% of whom will have neurological dysfunction that limits their ability to keep pace with peers who are typically developing. This study is a step toward understanding the impact that intensive developmental intervention could have in this population in the first months of life.

OBJECTIVES With the Children with Hemiparesis Arm and Hand Movement Project (CHAMP) multisite factorial randomized controlled trial, we compared 2 doses and 2 constraint types of constraint-induced movement therapy (CIMT) to usual customary treatment (UCT). METHODS CHAMP randomly assigned 118 2- to 8-year-olds with hemiparetic cerebral palsy to one of 5 treatments with assessments at baseline, end of treatment, and 6 months posttreatment. Primary blinded outcomes were the assisting hand assessment; Peabody Motor Development Scales, Second Edition, Visual Motor Integration; and Quality of Upper Extremity Skills Test Dissociated Movement. Parents rated functioning on the Pediatric Evaluation of Disabilities Inventory-Computer Adaptive Test Daily Activities and Child Motor Activity Log How Often scale. Analyses were focused on blinded and parent-report outcomes and rank-order gains across all measures. RESULTS Findings varied in statistical significance when analyzing individual blinded outcomes. parent reports, and rank-order gains. Consistently, high-dose CIMT, regardless of constraint type, produced a pattern of greatest short- and long-term gains (1.7% probability of occurring by chance alone) and significant gains on visual motor integration and dissociated movement at 6 months. O’Brien’s rank-order analyses revealed high-dose CIMT produced significantly greater improvement than a moderate dose or UCT. All CIMT groups improved significantly more in parent-reported functioning, compared with that of UCT. Children with UCT also revealed objective gains (eg, 48% exceeded the smallest-detectable assisting hand assessment change, compared with 71% high-dose CIMT at the end of treatment). CONCLUSIONS CHAMP provides novel albeit complex findings: although most individual blinded outcomes fell below statistical significance for group differences, high-dose CIMT consistently produced the largest improvements at both time points. An unexpected finding concerns shifts in UCT toward higher dosages, with improved outcomes compared with previous reports.

AIMS: NADPH oxidase (NOX)-derived reactive oxygen species (ROS) are implicated in the pathophysiology of hypertension in chronic kidney disease patients. Genetic deletion of NOX activator 1 (Noxa1) subunit of NOX1 decreases ROS under pathophysiological conditions. Here, we investigated the role of NOXA1-dependent NOX1 activity in the pathogenesis of angiotensin II (Ang II)-induced hypertension (AIH) and possible involvement of abnormal renal function. RESULTS: NOXA1 is present in epithelial cells of Henle's thick ascending limb and distal nephron. Telemetry showed lower basal systolic blood pressure (BP) in Noxa1(−/−) versus wild-type mice. Ang II infusion for 1 and 14 days increased NOXA1/NOX1 expression and ROS in kidney of male but not female wild-type mice. Mean BP increased 30 mmHg in wild-type males, with smaller increases in Noxa1-deficient males and wild-type or Noxa1(−/−) females. In response to an acute salt load, Na(+) excretion was similar in wild-type and Noxa1(−/−) mice before and 14 days after Ang II infusion. However, Na(+) excretion was delayed after 1–2 days of Ang II in male wild-type versus Noxa1(−/−) mice. Ang II increased epithelial Na(+) channel (ENaC) levels and activation in the collecting duct principal epithelial cells of wild-type but not Noxa1(−/−) mice. Aldosterone induced ROS levels and Noxa1 and Scnn1a expression and ENaC activity in a mouse renal epithelial cell line, responses abolished by Noxa1 small-interfering RNA. INNOVATION AND CONCLUSION: Ang II activation of renal NOXA1/NOX1-dependent ROS enhances tubular ENaC expression and Na(+) reabsorption, leading to increased BP. Attenuation of AIH in females is attributed to weaker NOXA1/NOX1-dependent ROS signaling and efficient natriuresis. Antioxid. Redox Signal. 36, 550–566.

The 2021 Critical Review (CR) on perfluorooctanoate (PFOA), kidney cancer, and testicular cancer (Bartell and Vieira 2021) provides an in-depth examination of evidence regarding sources, distributi...

Objectives To determine rates of influenza immunization among children treated in a pediatric emergency department (ED) and to ascertain parent willingness for children to receive influenza vaccine (IV) in the ED. Methods Interviews were conducted with parents of children 6 months or older evaluated in the ED for minor illness or injury. Demographic data, IV history, and intent and willingness to receive future IV were recorded during the summer of 2013. Participants were contacted in March 2014 to assess IV status, barriers to obtaining IV, and willingness to obtain IV in the ED. Chart review determined number of patients who were at high risk. Results Of 457 families approached, 285 (62%) were enrolled. Two hundred forty-two (85%) intended to vaccinate; 83% reported willingness to receive IV at a future ED visit. Common reasons for not receiving IV were concerns about adverse effects (31%) and lack of time or interest (24%). Of the 224 participants (79%) reached in follow-up, 112 (50%) had received IV in the prior season. Among those who did not receive IV, 65 (66%) had intended to vaccinate, and 54 (55%) indicated they would have accepted IV in the ED. Fifty-three (54%) of unvaccinated patients at follow-up had high risk of influenza complications. Conclusions Our data support an IV program in the pediatric ED as a means of increasing vaccination rates, particularly among high-risk patients. Parents are often concerned about adverse effects of IV, and providers should target education in this area.

PURPOSE: By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). METHODS: We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. RESULTS: We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. CONCLUSION: The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. ispartof: GENETICS IN MEDICINE vol:23 issue:8 pages:1506-1513 ispartof: location:United States status: published

BACKGROUND: Little is known about the relationship of longitudinal growth trajectory in early life with asthma development, particularly in infants with bronchiolitis (a high-risk population). OBJECTIVE: Among infants with bronchiolitis, we aimed to identify growth trajectory profiles and to determine their longitudinal relationship with the risk for developing childhood asthma. METHODS: A multicenter prospective study enrolled infants (aged

* Abbreviations: COVID-19 — : coronavirus disease 2019 PD — : program director Pediatric residency programs must ensure residents achieve competence, despite disruptions from the coronavirus disease 2019 (COVID-19) pandemic.1,2 We conducted a national survey of pediatric program directors (PDs) to determine the extent of disruptions in pediatric resident training and frequency of resident redeployment and COVID-19 illness. We performed a national cross-sectional, electronic survey of pediatric PDs from May to July 2020. We received Institutional Review Board approval from the University of Oklahoma Health Sciences Center. We developed our survey after literature review, cognitive interviews, and pilot testing. In our survey, we included questions about program characteristics, pandemic emergency stage, impact on patient care, and resident illness and exposure. The Accreditation Council for Graduate Medical Education established 3 pandemic emergency stages, in which some … Address correspondence to Monique M. Naifeh, Department of Pediatrics, University of Oklahoma Health Sciences Center, 1200 N Children’s Ave, Suite 12300, Oklahoma City, OK 73104. E-mail: Monique-naifeh{at}ouhsc.edu

Objective:To describe risk factors associated with inappropriate antibiotic prescribing to children.Design:Cross-sectional, retrospective analysis of antibiotic prescribing to children, using Kentucky Medicaid medical and pharmacy claims data, 2017.Participants:Population-based sample of pediatric Medicaid patients and providers.Methods:Antibiotic prescriptions were identified from pharmacy claims and used to describe patient and provider characteristics. Associated medical claims were identified and linked to assign diagnoses. An existing classification scheme was applied to determine appropriateness of antibiotic prescriptions.Results:Overall, 10,787 providers wrote 779,813 antibiotic prescriptions for 328,515 children insured by Kentucky Medicaid in 2017. Moreover, 154,546 (19.8%) of these antibiotic prescriptions were appropriate, 358,026 (45.9%) were potentially appropriate, 163,654 (21.0%) were inappropriate, and 103,587 (13.3%) were not associated with a diagnosis. Half of all providers wrote 12 prescriptions or less to Medicaid children. The following child characteristics were associated with inappropriate antibiotic prescribing: residence in a rural area (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.07–1.1), having a visit with an inappropriate prescriber (OR, 4.15; 95% CI, 4.1–4.2), age 0–2 years (OR, 1.39; 95% CI, 1.37–1.41), and presence of a chronic condition (OR, 1.31; 95% CI, 1.28–1.33).Conclusions:Inappropriate antibiotic prescribing to Kentucky Medicaid children is common. Provider and patient characteristics associated with inappropriate prescribing differ from those associated with higher volume. Claims data are useful to describe inappropriate use and could be a valuable metric for provider feedback reports. Policies are needed to support analysis and dissemination of antibiotic prescribing reports and should include all provider types and geographic areas.

Background Over the last two decades, patient review websites have emerged as an essential online platform for doctor ratings and reviews. Recent studies suggested the significance of such websites as a data source for patients to choose doctors for healthcare providers to learn and improve from patient feedback and to foster a culture of trust and transparency between patients and healthcare providers. However, as compared to other medical specialties, studies of online patient reviews that focus on dentists in the United States remain absent. Objective This study sought to understand to what extent online patient reviews can provide performance feedbacks that reflect dental care quality and patient experience. Methods Using mixed informatics methods incorporating statistics, natural language processing, and domain expert evaluation, we analyzed the online patient reviews of 204,751 dentists extracted from HealthGrades with two specific aims. First, we examined the associations between patient ratings and a variety of dentist characteristics. Second, we identified topics from patient reviews that can be mapped to the national assessment of dental patient experience measured by the Patient Experience Measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Dental Plan Survey. Results Higher ratings were associated with female dentists (t71881=2.45, P Conclusions These findings suggest that online patient reviews could be used as a data source for understanding the patient experience and healthcare quality in dentistry.

Aspirin-Exacerbated Respiratory Disease About 7% of patients with asthma have mucosal swelling, nasal polyps, and worsening of asthma in response to aspirin and other COX-1 inhibitors. Symptoms may...

The rates of mental health diagnoses in children have increased. Children in poverty have the highest rates. The use of psychotropic medication for children has been increasing, which is concerning because of the unknown long-term effects and the increased burden on the health care system. The state of Kentucky ranks among the highest in the United States for children with mental health problems, children living in poverty, and children receiving psychotropic medication.To examine recent trends and determinants of interclass psychotropic polypharmacy (PP) use for children and youth receiving Medicaid to inform intervention development.A retrospective cohort study was conducted using 2012-2015 Kentucky Medicaid claims for children aged 0-17 years, with continuous enrollment for ≥ 90 days with at least 1 behavioral health diagnosis (N = 237,393). Interclass PP was defined as the presence of at least 2 psychotropic medication prescription fills for at least 2 different classes of medication that, if taken as directed, would be used concurrently for at least 90 consecutive days (allowing for a single 15-day lag). The outcome variables were the presence of any interclass PP and the number of months a child received interclass PP. We conducted a descriptive analysis and developed 2 separate generalized linear regression models to test for associations between individual characteristics of children treated with psychotropic medication for ≥ 90 days (n = 75,639) and each outcome of interest.For the sample of children with at least 90 days of psychotropic medication treatment, 38% had at least 3 covered months of PP over the 4 years studied. Children in foster care received alpha agonists (116 vs. 69 per 1,000 children) or antidepressants (225 vs. 176 per 1,000) at a higher rate than other children receiving Medicaid but received stimulants at a lower rate (403 vs. 638 per 1,000). The primary 2-drug class combinations were stimulants with either alpha agonists or antidepressants. Children in foster care (OR = 1.7, 95% CI = 1.58, 1.84, P0.001), with a bipolar disorder (OR = 2.24, 95% CI = 2.10, 2.38, P0.001), mood disorder not otherwise specified (OR = 1.11, 95% CI = 1.04, 1.17, P0.001), or autism spectrum disorders (OR = 1.17, 95% CI = 1.08, 1.26, P0.001) had increased the odds of ever receiving PP. Black children had lower odds (OR = 0.72, 95% CI = 0.67, 0.77, P0.001) of ever receiving PP. Children aged 6-11 years (beta = 3.08, 95% CI = 2.87, 3.29) and 12-17 years (beta = 1.61, 95% CI = 1.38, 1.83) had more covered months with PP compared with those aged 0-5 years. Black children had fewer covered months of PP compared with white children (beta = -1.36, 95% CI = -1.61, -1.11]. Children in foster care (beta = 1.83, 95% CI = 1.53, 2.13) had more covered months with PP. Children residing in nonurban areas had fewer months with PP (beta = -0.4, 95% CI = -0.54, -0.26) compared with those residing in urban areas, as did those children with depression (beta = -3.32, 95% CI = -3.55, -3.1), impulse control disorder (beta = -2.07, 95% CI = -2.28, -1.85), and conduct disorder (beta = -1.34, 95% CI = -1.64, -1.05). Children with bipolar disorder (beta = 3.62, 95% CI = 3.38, 3.86) and autism (beta = 2.04, 95% CI = 1.75, 2.33) had more covered months with PP. As comorbidity increased, the duration of PP treatment increased (beta = 2.49, 95% CI = 2.36, 2.62).The rates of PP are concerning, especially for children in foster care and children aged 6-11 years. Efforts to safeguard medication use are needed, as well as future exploration of racial differences in PP.This project was supported by the Kentucky Cabinet for Health and Family Services, Department for Medicaid; Norton Healthcare; and the School of Medicine, Department of Pediatrics; School of Public Health and Information Sciences; and Kent School of Social Work at the University of Louisville. Kentucky Medicaid approved the use of the data and granted permission to publish but played no role in the interpretation of data. Lui is employed by Kentucky Medicaid. The other authors report no potential conflicts of interest. An earlier version of this study was presented at the Pediatric Academic Societies' Annual Meeting in Baltimore, MD, on April 30-May 3, 2016. A poster presentation was given at the Society for Developmental and Behavioral Pediatrics in Cleveland, OH, on October 14-16, 2017.

Background Permanent hypoparathyroidism (hypoPT) represents the most common postoperative complication associated with total thyroidectomy. Current treatment relies on high-dose calcium and/or vitamin D supplementation, but often this is insufficient and some patients remain symptomatic. Parathyroid allotransplantation is a new therapeutic option described recently in the literature. This study aims to investigate the patients’ acceptability of parathyroid transplantation as a potential new treatment for hypoPT. Method Online survey of members of HypoParaUK, a support group for individuals affected by hypoPT. Results Responses were received from 252 hypoPT patients. Majority declared to experience severe symptoms despite regular medical treatment. On a severity scale of 0–5, symptoms that were most troublesome were fatigue (3.8), low sense of well-being (3.5), and numbness/tingling (2.9). On a scale of 0–10, on average, their current quality of life (QoL) was 5 ± 3 and they expected this would improve to 7 ± 2 with correction of their hypoPT. Forty-four percent of patients were extremely interested in a potential technique involving intramuscular injection of parathyroid cell suspension compared to just 14% who were interested in the more invasive procedure of implantation of a parathyroid allograft into the forearm. The main concerns expressed were related to the possible need for immunosuppressive therapy. Conclusion Patients with severe symptomatic hypoPT seem interested to consider participation in a clinical trial exploring the feasibility and success rate of parathyroid transplantation. Electronic supplementary material The online version of this article (10.1007/s00423-018-1693-y) contains supplementary material, which is available to authorized users.

Objective Participation in scholarly activity (SA) is an Accreditation Council for Graduate Medical Education requirement. Our previous research with program directors (PDs) suggests that pediatric SA training is variable and suboptimal. To help programs better meet requirements, our objective was to understand the resident perspective regarding SA training, including factors associated with satisfaction and productivity. Methods We conducted cross-sectional surveys of second- and third-year pediatric residents and PDs at 22 diverse programs in 2016. Surveys assessed resident demographics, career intentions, program characteristics, beliefs, barriers, satisfaction, and productivity, defined as SA accepted at a regional or national meeting, for publication, or grant funding. Data were analyzed using descriptive statistics and multivariable logistic regression. Results A total of 464 (60.2%) of 771 residents and 22 PDs (100%) responded. Most residents believed that residents should participate in SA (n = 380, 81.9%). However, only 37.9% (n = 175) were extremely or very satisfied with their training. Residents who reported that training to conduct research (adjusted odds ratio [AOR] = 1.9, 95% confidence interval [CI] 1.1–3.5), availability of a research curriculum (AOR = 1.9, 95% CI 1.2–3.1), and adequate faculty mentorship (AOR = 2.5, 95% CI 1.6–4.1) were not barriers were more satisfied. Protected time was associated with satisfaction (AOR = 1.7, 95% CI 1.1–2.7). A total of 43.8% of residents (n = 203) were productive. Productivity was associated with future plans to conduct research (AOR = 3.3, 95% CI 2.1–5.1). Conclusions Residents believe SA training is important. Dedicated program infrastructure, protected time, and adequate mentorship appear to be crucial to improving quality perceptions.

Non-steroidal anti-inflammatory drug (NSAIDs) are documented as causing the second highest number of medication-related hypersenstivity reactions and as the third highest reason for allergy consulations. The prevalence of hypersentivity to NSAIDs in the general population at large between 0.5 and 2.5%. Estimation of prevalence depends, however, on diagnostic methodology and patient characteristics, such as gender, age and the presence of comorbidity such as asthma, persistent rhinosinusitis, nasal polyps and chronic hives. Being asthmatics carries a 10-20% risk, whilst being asthmatic and having nasal polyposis carries a 30-40% risk of having NSAID-hypersensitivity. Children are less frequently affected than adults; and there is a female predilection. Classification of NSAID-hypersensitivity are based on clinical picture, whether an underlying pathology is present, and extent to which cross-reaction occurs with other members of the COX-1 inhibitor group. NSAID-exacerbated respiratory disease (NERD) refers to the combination of asthma, chronic rhinosinusitis with nasal polyposis, and acute upper and lower respiratory tract reactions to the ingestion of NSAID. Disscussion in this chapter is confined to NERD.

Aging is characterized by increased aortic stiffness, an early, independent predictor and cause of cardiovascular disease. Oxidative stress from excess reactive oxygen species (ROS) production increases with age. Mitochondria and NADPH oxidases (NOXs) are two major sources of ROS in cardiovascular system. We showed previously that increased mitochondrial ROS levels over a lifetime induce aortic stiffening in a mouse oxidative stress model. Also, NADPH oxidase 4 (NOX4) expression and ROS levels increase with age in aortas, aortic vascular smooth muscle cells (VSMCs) and mitochondria, and are correlated with age-associated aortic stiffness in hypercholesterolemic mice. The present study investigated whether young mice (4 months-old) with increased mitochondrial NOX4 levels recapitulate vascular aging and age-associated aortic stiffness. We generated transgenic mice with low (Nox4TG605; 2.1-fold higher) and high (Nox4TG618; 4.9-fold higher) mitochondrial NOX4 expression. Young Nox4TG618 mice showed significant increase in aortic stiffness and decrease in phenylephrine-induced aortic contraction, but not Nox4TG605 mice. Increased mitochondrial oxidative stress increased intrinsic VSMC stiffness, induced aortic extracellular matrix remodeling and fibrosis, a leftward shift in stress-strain curves, decreased volume compliance and focal adhesion turnover in Nox4TG618 mice. Nox4TG618 VSMCs phenocopied other features of vascular aging such as increased DNA damage, increased premature and replicative senescence and apoptosis, increased proinflammatory protein expression and decreased respiration. Aortic stiffening in young Nox4TG618 mice was significantly blunted with mitochondrial-targeted catalase overexpression. This demonstration of the role of mitochondrial oxidative stress in aortic stiffness will galvanize search for new mitochondrial-targeted therapeutics for treatment of age-associated vascular dysfunction., Graphical abstract Image 1, Highlights • Aortic stiffness in aging is associated with increased mitochondrial NOX4 levels. • Young mitochondrial Nox4 overexpressing transgenic mice phenocopy aortic stiffness. • Nox4 transgenic mice show increased VSMC stiffness, aortic remodeling and fibrosis. • Nox4 transgenic mouse VSMC show DNA damage, senescence, apoptosis and inflammation. • High mitochondrial catalase levels blunt aortic stiffness in Nox4 transgenic mice.

Training residents to be scholars is endorsed by leading medical education organizations. Our previous research suggests that the scholarly activity (SA) training experience is highly variable across pediatric residency programs, and residents and program directors (PDs) are generally dissatisfied. Understanding how PD and resident views align can help programs better guide resource allocation and improvement efforts.We conducted cross-sectional surveys of second and third year pediatric residents and PDs at 22 diverse US categorical programs. We compared resident and PD responses to SA training beliefs, barriers, and satisfaction by 2-proportion z tests. We used descriptive statistics to describe resident responses in relation to same-institution PD responses.About 464 of 771 residents (60.2%) and 22 PDs (100%) responded. Across programs, PDs more strongly agreed that all residents should participate in SA (59% of PDs [n = 13] versus 27% of residents [n = 127], P = .002). Residents more strongly believed all residents should have protected SA time (91% of residents [n = 424] versus 68% of PDs [n = 15], P = .001). PDs more strongly perceived gaps in other resources as barriers, including lack of funding to conduct or present SA (P.001, P = .02), lack of statistical support (P = .03), and lack of faculty mentorship (P.001). Within program concordance was low.Discordance exists between PDs and residents with respect to SA participation and necessary resources, particularly, protected time. Programs must help residents identify when SA can be accomplished. Clearer national guidelines around SA training may also be necessary to reduce discordance and improve perceptions.

Fingerprints have been proposed as a promising new matrix for drug testing. In previous work it has been shown that a fingerprint can be used to distinguish between drug users and nonusers. Herein, we look at the possibility of using a fingerprint to distinguish between dermal contact and administration of heroin. Fingerprint samples were collected from (i) 10 patients attending a drug rehabilitation clinic, (ii) 50 nondrug users and (iii) participants who touched 2 mg street heroin, before and after various hand cleaning procedures. Oral fluid was also taken from the patients. All samples were analyzed using a liquid chromatography—high resolution mass spectrometry method validated in previous work for heroin and 6-AM. The HRMS data were analyzed retrospectively for morphine, codeine, 6-acetylcodeine and noscapine. Heroin and 6-AM were detected in all fingerprint samples produced from contact with heroin, even after hand washing. In contrast, morphine, acetylcodeine and noscapine were successfully removed after hand washing. In patient samples, the detection of morphine, noscapine and acetylcodeine (alongside heroin and 6-AM) gave a closer agreement to patient testimony on whether they had recently used heroin than the detection of heroin and 6-AM alone. This research highlights the importance of washing hands prior to donating a fingerprint sample to distinguish recent contact with heroin from heroin use.

Aims: Oxidative stress is implicated in cardiomyocyte cell death and cardiac remodeling in the failing heart. The role of NADPH oxidase 4 (NOX4) in cardiac adaptation to pressure overload is controversial, but its function in myocardial ischemic stress has not been thoroughly elucidated. This study examined the function of NOX4 in the pathogenesis of ischemic heart failure, utilizing mouse models, cell culture, and human heart samples. Results: Nox4(−/−) mice showed a protective phenotype in response to permanent left anterior descending coronary artery ligation with smaller infarction area, lower cardiomyocyte cross-sectional area, higher capillary density, and less cell death versus wild-type (WT) mice. Nox4(−/−) mice had lower activity of soluble epoxide hydrolase (sEH), a potent regulator of inflammation. Nox4(−/−) mice also showed a 50% reduction in the number of infiltrating CD68(+) macrophages in the peri-infarct zone versus WT mice. Adenoviral overexpression of NOX4 in cardiomyoblast cells increased sEH expression and activity and CCL4 and CCL5 levels; inhibition of sEH activity in NOX4 overexpressing cells attenuated the cytokine levels. Human hearts with ischemic cardiomyopathy showed adverse cardiac remodeling, increased NOX4 and sEH protein expression and CCL4 and CCL5 levels compared with control nonfailing hearts. Innovation and Conclusion: These data from the Nox4(−/−) mouse model and human heart tissues show for the first time that oxidative stress from increased NOX4 expression has a functional role in ischemic heart failure. One mechanism by which NOX4 contributes to ischemic heart failure is by increasing inflammatory cytokine production via enhanced sEH activity.

The purpose of this study was to explore the relation of physical activity (PA) and sedentary time (SED) to insulin sensitivity and adipokines. We assessed PA and SED using Actical accelerometers and insulin resistance (HOMA-IR) in 2109 participants (free of type 1 and 2 diabetes mellitus) from Framingham Generation 3 and Omni 2 cohorts (mean age 46 years, 54% women). Systemic inflammation (C-reactive protein [CRP]) and circulating adipokines were measured 6 years earlier. Steps per day, moderate-to-vigorous PA (MVPA) and SED per wear time (%SED) were predictor variables in multivariable regression analyses, with HOMA-IR, CRP and circulating adipokines as outcome measures. We reported that higher MVPA and more steps per day were associated with lower HOMA-IR, adjusting for %SED (β = -0.036, P = 0.002; β = -0.041, P = 0.005). Steps were inversely associated with CRP, but were directly associated with insulin-like growth factor (IGF)-1 levels (β = -0.111, P = 0.002; β = 3.293, P = 0.007). %SED was positively associated with HOMA-IR (β = 0.033, P

Aspirin-exacerbated respiratory disease is a significant endotype of both asthma and chronic rhinosinusitis with nasal polyps. The disease demonstrates what seems to be a unified inflammatory mechanism culminating in highly eosinophilic nasal polyp disease and asthma. The rate of polyp recurrence and morbidity from asthma exacerbations are significant and warrant separating this group diagnostically from aspirin-tolerant peers. Given the unique anti-inflammatory effects of aspirin and the evolving landscape of new, targeted biologic treatments, it is even more incumbent to consider this diagnosis and offer patients treatment specific for the disease.

Among children hospitalized with bronchiolitis, we examined the associations between in utero exposure to maternal cigarette smoking, postnatal tobacco smoke exposure, and risk of admission to the intensive care unit (ICU).We performed a 16-center, prospective cohort study of hospitalized children aged2 years with a physician admitting diagnosis of bronchiolitis. For 3 consecutive years, from November 1, 2007 until March 31, 2010, site teams collected data from participating families, including information about prenatal maternal smoking and postnatal tobacco exposure. Analyses used chi-square, Fisher's exact, and Kruskal-Wallis tests and multivariable logistic regression.Among 2207 enrolled children, 216 (10%) had isolated in utero exposure to maternal smoking, 168 (8%) had isolated postnatal tobacco exposure, and 115 (5%) experienced both. Adjusting for age, sex, race, birth weight, viral etiology, apnea, initial severity of retractions, initial oxygen saturation, oral intake, and postnatal tobacco exposure, children with in utero exposure to maternal smoking had greater odds of being admitted to the ICU (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.14-2.00). Among children with in utero exposure to maternal smoking, those with additional postnatal tobacco exposure had a greater likelihood of ICU admission (aOR 1.95, 95% CI 1.13-3.37) compared to children without postnatal tobacco smoke exposure (aOR 1.47, 95% CI 1.05-2.04).Maternal cigarette smoking during pregnancy puts children hospitalized with bronchiolitis at significantly higher risk of intensive care use. Postnatal tobacco smoke exposure may exacerbate this risk. Health care providers should incorporate this information into counseling messages.

Background Kentucky (KY) consistently has one of the highest rates of outpatient pediatric antibiotic prescribing in the nation. Previous analyses identified significant variation in volume of antibiotic prescribing by geographic location, patient demographics, and provider type, but less is known about the appropriateness of this prescribing. We describe appropriateness of outpatient antibiotic prescribing in children insured by KY Medicaid. Methods We utilized KY Medicaid pharmacy and medical claims from 2017 for children < 20 years. Patient demographic variables were abstracted from Medicaid enrollment data. Antibiotic prescriptions were identified by NDC and matched to medical claims within 3 days prior to fill date to identify corresponding diagnoses via ICD-10 codes. A previously published appropriateness classification scheme (Chua, BMJ 2019) was applied to categorize antibiotic prescriptions as “appropriate”, “potentially appropriate”, “inappropriate” or “not associated with indication”. Results Of the 779,751 antibiotic prescriptions included, 19.5% were appropriate, 45.3% were potentially appropriate, 20.8% were inappropriate, and 14.4% were not associated with an indication (Table 1). Inappropriate prescriptions were more common among children 0-2 years (24.4%) and those living in non-metro areas (22.2%). Antibiotics prescribed by general practitioners were also more likely to be inappropriate (22.2%). The most common diagnoses for each category are summarized in Table 2. Amoxicillin was the most commonly prescribed antibiotic in all categories. Azithromycin was more frequently prescribed for inappropriate indications or those not associated with a diagnosis code. Cefdinir was more common for appropriate and potentially appropriate indications. Table 1: Antibiotic Prescription Characteristics, 2017 Table 2: Top Diagnoses for Antibiotic Prescriptions by Category Conclusion Inappropriate antibiotic prescribing is more common among young children living in non-metro areas seen by general practitioners. Outpatient antibiotic stewardship interventions should target these patient demographics and provider types. This classification scheme to describe inappropriate prescribing is feasible for use in pediatric Medicaid patients and could serve as a valuable metric for provider feedback reports on antibiotic use. Disclosures Bethany A. Wattles, PharmD, Kentucky Medicaid (Grant/Research Support)Merck (Grant/Research Support) Michael J. Smith, MD, MSC.E, Kentucky Medicaid (Grant/Research Support)Merck (Grant/Research Support)

IntroductionThe Children with Hemiparesis Arm and Movement Project (CHAMP) addresses two pressing issues concerning paediatric constraint-induced movement therapy (CIMT): effects of two dosages and two types of constraint on functional outcomes. Systematic reviews conclude that CIMT is one of the most efficacious treatments, but wide variations in treatment protocols, outcome measures and patient characteristics have prevented conclusions about potential effects of dosage levels and constraint methods.Methods and analysisCHAMP is a multisite comparative efficacy randomised controlled trial of 135 children (2–8 years) with hemiparetic cerebral palsy. The 2×2 factorial design tests two dosage levels—60 hours (3.0 hours/day, 5 days/week × 4 weeks) and 30 hours (2.5 hours/day, 3 days/week × 4 weeks) and two constraint conditions—full-arm, full-time cast and part-time splint, plus usual and customary (UCT) controls, yielding five groups: (1) 60 hours CIMT+full-time cast, (2) 60 hours CIMT+part-time splint, (3) 30 hours CIMT+full-time cast, (4) 30 hours CIMT+part-time splint and (5) UCT. Trained therapists deliver the standardised ACQUIREc protocol for CIMT. Blinded assessments at baseline, end of treatment, and 6 and 12 months post treatment include the Assisting Hand Assessment, and subscales from the Peabody Developmental Motor Scales-2 and modified Quality of Upper Extremity Skills Test. Parents complete the Pediatric Motor Activity Log and Pediatric Evaluation of Disability Inventory. A new Fidelity of Implementation Rehabilitation Measure monitors treatment delivery. Data analyses involve repeated-measures multivariate analysis of co-variance controlling for selected baseline variables.Ethics and disseminationEthics boards at site universities approved the study protocol. To promote equipoise, parents of UCT controls are offered ACQUIREc after 6 months. A Data Safety and Monitoring Committee reviews results regularly, including measures of child and family stress. We will disseminate CHAMP results via peer-reviewed publications and presentations to professional and advocacy organisations.Trial registration numberNCT01895660; Pre-results.

Restrictions on federal funding for research pertaining to firearm policy have stymied academic inquiry by social science and public health researchers for over two decades. As a result, most researchers agree that our public discourse about this urgent issue is woefully under-informed, or even ill-informed, on both sides of the debate. Legal academia, which does not operate under the same grant-writing regime as most other disciplines, can and should help fill this gap in researching and theorizing the unresolved questions related to firearm policy. In fact, theoretical development and clarification from the legal academy is often a necessary antecedent for empirical researchers in other fields to frame and develop their own studies properly, especially about the real-world effects of competing policy approaches to firearms. This Essay sets forth a plea to law professors to undertake much-needed research in this area and offers suggestions of understudied topics with low entry barriers for legal commentators. Recommendations for interdisciplinary collaborative efforts round out this discussion. A brief conclusion reaches the endgame issue: ensuring access to the work we produce.

BACKGROUND AND OBJECTIVES: It remains unclear whether hyponatremia independently predicts a higher severity of bronchiolitis in children. The objective of this study was to investigate the association between hyponatremia and bronchiolitis severity in children hospitalized in the ICU for bronchiolitis. METHODS: We conducted a 16-center, prospective cohort study of hospitalized children aged RESULTS: Of 231 children hospitalized in the ICU for bronchiolitis, 193 (84%) were categorized into the normonatremic group and 38 (16%) into the hyponatremic group. Compared with children with normonatremia, those with hyponatremia had higher risks of mechanical ventilation use (40% vs 58%; P = .04) and longer ICU LOS (median, 3 vs 6 days; P = .007). Likewise, in the adjusted analyses, children with hyponatremia had significantly higher risks of mechanical ventilation use (odds ratio, 2.14 [95% confidence interval, 1.03–4.48; P = .04) and longer ICU LOS (β-coefficient, 2.21 days [95% confidence interval, 0.68–3.73; P = .005]). CONCLUSIONS: In this prospective, multicenter study of children hospitalized for bronchiolitis, hyponatremia on the day of hospitalization was associated with a higher severity of disease. Our data support hyponatremia as a prognostic factor that might improve the ability of clinicians to predict the disease course of children with severe bronchiolitis.

Studies have shown an increase in the use of antipsychotics to preschoolers for disruptive behavior and aggression. This study investigated the use of atypical antipsychotics in children ≤6 years of age in Kentucky who were on Medicaid.Kentucky Medicaid prescription claims data between 2001 and 2010 were examined for all children ≤6 years of age who had received an atypical antipsychotic. Drug type, diagnosis codes, and geographic trends were analyzed using descriptive statistics.A total of 70,777 prescriptions were written to 6915 distinct children ≤6 years of age. The use of atypical antipsychotics in this age group increased over the years 2001-2010 with a peak ∼ 1.0% in 2004, and averaged 0.75% in 2010. Older male children were more likely to receive atypical antipsychotics, and risperidone accounted for two thirds of the prescriptions written. Mood disorders, primarily bipolar disorder, accounted for almost 75% of the diagnoses provided. Only 32% of the prescriptions were written by child psychiatrists. Geographic analysis showed significantly higher use in the Western part of the state (more than three times the state mean in some counties).The use of atypical antipsychotics in children ≤6 years of age has declined from its peak, but remains substantial. The prescription rates for atypical antipsychotics by providers other than child psychiatrists, and the marked geographic variation in use across the state of Kentucky suggest that improved systems of mental healthcare for this population are needed.

OBJECTIVE The aim of this study was to determine the predictors of pediatric ambulance transport and evaluate changes in utilization over a 10-year period. METHODS The National Health Ambulatory Medical Care Survey emergency department (ED) data for visits by children aged younger than 19 years from 2000 to 2009 were analyzed using logistic regression. Age, ethnicity, race, sex, triage level, time of arrival, injury/poisoning, insurance, disposition, critical patient status, metropolitan statistical area (MSA), region, and hospital type were used to predict the mode of arrival (ambulance or nonambulance). Significant variables were evaluated for trends over time. RESULTS Representing 209 million ED visits, 60,761 records were analyzed. Ambulance transport was more likely among children who were aged 12 to 18 years (P < 0.05), black (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.06-1.38), evaluated for an injury/poisoning (OR, 3.03; 95% CI, 2.75-3.34), publicly insured (OR, 1.16; 95% CI, 1.03-1.31), living in an MSA (OR, 1.73; 95% CI, 1.34-2.23), living in the northeast (P < 0.05), and overnight arrivals (OR, 1.47; 95% CI, 1.26-1.7). They were more likely to have an urgency of less than 15 minutes (OR, 4.46; 95% CI, 3.56-5.59), require admission (OR, 2.82; 95% CI, 2.33-3.41), and considered critical (OR, 5.15; 95% CI, 3.43-7.73). There was no significant change in ambulance utilization in children; however, about half of critical patients and over 80% of those with a high triage level did not arrive by ambulance. CONCLUSIONS Ambulance transport to the ED is used more often by teens, blacks, publicly insured, overnight arrivals, and those living in an MSA or the northeast. It is concerning that many children triaged with a high urgency or requiring critical care did not arrive by ambulance.

Study objectives The rate of iatrogenic pneumothorax associated with thoracic central venous catheterization in community emergency departments (EDs) is poorly described, although such information is vital to inform the procedure's risk/benefit analysis. We undertook this multicenter study to estimate the incidence of immediate catheter-related pneumothorax in community EDs and to determine associations with site of access, failed access, and positive pressure ventilation. Methods This was a secondary analysis of 2 retrospective cohort studies of adults who underwent attempted thoracic central venous catheterization in 1 of 21 EDs. Pneumothorax was identified by postprocedural anteroposterior chest radiograph or emergent evacuation for presumed tension pneumothorax. Frequencies were compared using Fisher's exact test. Results Among 1249 patient encounters, the initial vein of catheterization was internal jugular in 1054 cases (84.4%) and subclavian in 195 cases (15.6%). Success at the initial internal jugular vein was more common than at the initial subclavian vein (95.4% vs 83.6%, P P P = .05), and among patients receiving positive pressure ventilation (1.6% vs 0.1%, P Conclusion The incidence of pneumothorax from thoracic central venous catheterization in community EDs is low. The risk of pneumothorax is higher with a subclavian vein approach, failed access at the initial vein, and positive pressure ventilation.

Objective To determine which coexisting conditions have the strongest associations with healthcare use and spending among children with cerebral palsy (CP). Study design Retrospective analysis of 16 695 children ages 0-18 years with CP – identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes – using Medicaid from January 1, 2013 to December 31, 2013 from 10 states in the Truven MarketScan Medicaid Database. Using generalized linear models, we assessed which coexisting conditions (including medical technology) identified with Agency for Healthcare Research and Quality's Chronic Condition Indicators had the strongest associations with total healthcare spending across the healthcare continuum. Results Median per-patient annual Medicaid spending for children with CP was $12 299 (IQR $4826-$35 582). Most spending went to specialty (33.1%) and hospital (26.7%) care. The children had a median 6 (IQR 4-10) coexisting conditions; epilepsy was the most common (38.1%). Children with epilepsy accounted for 59.6% ($364 million) of all CP spending. In multivariable analysis, the coexisting conditions most strongly associated with increased spending were tracheostomy (median additional cost per patient = $56 567 [95%CI $51 386-61 748]) and enterostomy (median additional cost per patient = $25 707 [95%CI $23 753-27 660]). Conclusions Highly prevalent in children with CP using Medicaid, coexisting conditions correlate strongly with healthcare spending. Tracheostomy and enterostomy, which indicate significant functional impairments in breathing and digestion, are associated with the highest spending. Families, providers, payers, and legislators may leverage these findings when designing policies positioned to enable the best health and care for children with cerebral palsy.

OBJECTIVE The use of computed tomography (CT) and ultrasound (US) in patients with acute abdominal pain has substantial variation across pediatric emergency departments (EDs). This study compares the cost of diagnosing and treating suspected appendicitis across a multicenter network of children's hospitals. METHODS This study is a secondary analysis using deidentified data of a prospective, observational study of patients with suspected appendicitis at nine pediatric EDs. The study included patients 3 to 18 years old who presented to the ED with acute abdominal pain of

Background Atherosclerosis progression during aging culminates in the development of vulnerable plaques, which may increase the risk of cardiovascular events. Increased generation and/or decreased scavenging of reactive oxygen species in the vascular wall are major contributors to atherogenesis. We previously showed that superoxide dismutase 2 deficiency increased vascular oxidative stress and reduced aortic compliance in aged wild‐type mice and that young Apoe −/− / Sod2 +/− had increased mitochondrial DNA damage and atherosclerosis versus young Apoe −/− mice. Here we investigated the effects of superoxide dismutase 2 deficiency on atherosclerosis progression and plaque morphology in middle‐aged Apoe −/− mice. Methods and Results Compared with Apoe −/− , middle‐aged Apoe −/− / Sod2 +/− mice had increased vascular wall reactive oxygen species ( P P Apoe −/− / Sod2 +/− mice had an increased necrotic core with higher inflammatory cell infiltration, a thinned fibrous cap with depleted smooth muscle content, and intraplaque hemorrhage. In addition, the plaque shoulder area had higher levels of calpain‐2, caspase‐3, and matrix metalloproteinase‐2 in intimal smooth muscle cells and depleted fibrous cap collagen. Targeting mitochondrial reactive oxygen species with Mito TEMPO attenuated features of atherosclerotic plaque vulnerability in middle‐aged Apoe −/− / Sod2 +/− mice by lowering expression of calpain‐2, caspase‐3, and matrix metalloproteinase‐2 and decreasing smooth muscle cell apoptosis and matrix degradation. Conclusions Enhanced mitochondrial oxidative stress under hyperlipidemic conditions in aging induces plaque instability, in part by increasing smooth muscle cell apoptosis, necrotic core expansion, and matrix degradation. Targeting mitochondrial reactive oxygen species or its effectors may be a viable therapeutic strategy to prevent aging‐associated and oxidative stress–related atherosclerosis complications.

BACKGROUND Recent publications have explored the possibility of using fingerprints to confirm drug use, but none has yet dealt with environmental contamination from fingertips. Here we explored the possibility of establishing an environmental cutoff for drug testing from a single fingerprint. METHODS Fingerprint samples (n = 100) were collected from the hands of 50 nondrug users before and after handwashing to establish separate environmental cutoff values and testing protocols for cocaine, benzoylecgonine, heroin, and 6-monoacetylmorphine. The cutoff was challenged by testing the fingerprints of drug-free volunteers after shaking hands with drug users. Fingerprints from patients who testified to taking cocaine (n = 32) and heroin (n = 24) were also collected and analyzed. RESULTS A different cutoff value needed to be applied, depending on whether the fingerprints were collected as presented or after handwashing. Applying these cutoffs gave a 0% false-positive rate from the drug-free volunteers. After application of the cutoff, the detection rate (compared to patient testimony) for washed hands of patients was 87.5% for cocaine use and 100% for heroin use. CONCLUSIONS Fingerprints show enhanced levels of cocaine, heroin, and their respective metabolites in patients who testified to taking the substances, compared with the population of naïve drug users surveyed, and a cutoff (decision level) can be established. The cutoff is robust enough to account for small increases in analyte observed after secondary transfer.

This study assessed distal femur and lumbar spine bone mineral density (BMD) Z-scores in children with cerebral palsy. BMD z-score was lower in non-ambulatory than in ambulatory children. Somewhat surprisingly, among ambulatory children, those with better walking abilities had higher BMD z-score than those with more impaired walking ability. Children with cerebral palsy (CP) have increased risk for low bone mineral density (BMD). The aim was to explore the difference in BMD at the distal femur and lumbar spine between ambulatory and non-ambulatory children with CP and the relationship between vitamin D status and BMD. Fifty-one children (age range 8–18 years; 20 girls) with CP participated. Their BMD Z-scores were measured in the lumbar spine and the distal femur using dual X-ray absorptiometry, and 25-hydroxy-vitamin D (25-OHD) concentrations were measured in serum. Children with GMFCS level I–III were defined as ‘walkers’ while children with level IV–V were defined as ‘non-walkers. Non-walkers had lower mean BMD Z-scores (range −1.7 to −5.4) than walkers at all sites (range −0.8 to −1.5). Among walkers, BMD Z-scores at the distal femur were lower in those with GMFCS level II than with level I (p values

Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1-6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.

Background There is growing concern that residents are not receiving the necessary experience to become proficient with medical procedures. We created a structured curriculum to improve resident comprehension, experience and confidence with pediatric procedures. Methods A two-week procedure curriculum commenced with a three-day training course to review 26 pediatric procedures using lectures, videos, demonstrations and simulations. Residents spent the remainder of the rotation as the hospital's on-call procedure resident. Pre- and post-rotation surveys, knowledge testing and procedure logging were used to evaluate course effectiveness, along with follow up metrics a year after completing the rotation. Results were compared to a control group of residents completing their second year of residency who did not participate in the curriculum. Results Participants (N = 35) averaged 67.2 procedures over the 2 weeks, compared to 41.3 procedures for controls (N = 20) during their first 2 years of residency. Participants had a higher confidence than controls (3.0 vs. 2.5 on a five-point scale) and better knowledge (65% vs. 47% correct on testing), both statistically significant. Compared to their own individual pre-rotation scores, participants showed improved knowledge (49% vs. 65%) and confidence (2.0 vs. 3.0), both statistically significant. Long-term follow up showed that these improvements were mostly sustained a year later. Conclusions Overall, interns completing the rotation demonstrated procedure counts, knowledge levels, and confidence greater than rising third year residents. Participants were inclined to have superior confidence in procedures where higher procedure counts were achieved. Most results were sustained over the course of one year.

OBJECTIVE: To identify risk factors for inpatient apnea among children hospitalized with bronchiolitis. METHODS: We enrolled 2207 children, aged RESULTS: Inpatient apnea was identified in 108 children (5%, 95% confidence interval [CI] 4%–6%). Statistically significant, independent predictors of inpatient apnea included: corrected ages of 70 (OR 2.26), compared with 40 to 49; and having a preadmission room air oxygen saturation CONCLUSIONS: In this prospective, multicenter study of children hospitalized with bronchiolitis, inpatient apnea was associated with younger corrected age, lower birth weight, history of apnea, and preadmission clinical factors including low or high respiratory rates and low room air oxygen saturation. Several bronchiolitis pathogens were associated with apnea, with similar apnea risk across the major viral pathogens.

Andrew Szczeklik was born in 1938 and died on Feb 3rd, 2012. He was the most influential expert in the field of aspirin and NSAID sensitivity reactions and associated diseases in the world. This edition of NACAI is dedicated to Andrew. In the introductory chapter, we elected to highlight his accomplishments as reflected in his publications. Andrew published at least 503 articles including many invited review articles. We present 20 of his most important publications all of which contributed significantly to our understanding of these diseases.

The occurrence of an emergent need for aspirin therapy in an aspirin or nonsteroidal anti-inflammatory drug (NSAID)-"allergic" individual presents one of the more challenging situations the allergist may face. A common request is for the allergist to evaluate an acutely ill patient in a monitored hospitalized setting with a vague and remote history of a "reaction to aspirin." Because of significant diagnostic limitations, introducing aspirin can be very difficult. The concern about the potential for causing anaphylaxis in an acutely ill patient can lead to fear about performing any challenge or desensitization in these patients. The objective of this article was to review the literature regarding aspirin challenges and desensitization in the emergency setting and present a rational approach to administering aspirin to patients that require this drug.

To investigate longitudinal changes of habitual physical activity (HPA) and sedentary time in children with cerebral palsy (CP) aged 1 year 6 months to 5 years across all functional abilities.At study entry, 95 children (62 males, 33 females) were classified using the Gross Motor Function Classification System (GMFCS) at levels I (50), II (9), III (16), IV (6), and V (14). Physical activity was recorded on a total of 159 occasions at four possible time points: 1 year 6 months to 2 years; 2 years 6 months to 3 years; 4 years; and 5 years using ActiGraph for 3 days. Mixed-effects regression models were used for analyses.Participants classified at GMFCS levels I and II had stable HPA as they aged. HPA significantly decreased at 5 years in children classified at GMFCS levels III to V. Sedentary time significantly increased at 4 years and 5 years in all participants. Annual HPA significantly reduced in children classified at GMFCS levels III to V (-123 counts/min, 95% confidence interval [CI] -206 to -40) while annual sedentary time significantly increased in all participants (GMFCS levels I-II: 2.4%, 95% CI 0.7-4.1; GMFCS levels III-V: 6.9%, 95% CI 4.6-9.2).Children with CP at all GMFCS levels should be encouraged to be physically active from early childhood as HPA levels start to decline from 4 years. Breaks in sedentary time are required for all children with CP from the age of 3 years.

Background Aspirin prevents coronary thrombosis and is used extensively in cardiovascular prophylaxis. However, patients with a prior history of an aspirin "reaction" are routinely denied this medication. Objective To characterize the clinical presentation of a cohort of patients with coronary artery disease (CAD) and aspirin reactions. Methods Between 2009 and 2012, using a retrospective computer analysis, information was collected on all patients within a county-wide health care system presenting with CAD and a prior history of aspirin reactions. Results Of 9,565 patients with CAD, a prior history of aspirin reactions was recorded in 142 patients. Of these 142 patients, 30 (21%) had histories compatible with cutaneous and/or respiratory reactions. The other patients described adverse effects to aspirin, mostly gastrointestinal intolerance and bleeding. Aspirin-induced anaphylaxis was recorded in patients but may have been misdiagnosed, describing instead respiratory hypersensitivity reactions. Of the 142 patients, only 34 (24%) were receiving daily cardiovascular prophylaxis with aspirin. Of 108 patients not receiving aspirin, 25 (17.6%) were prescribed clopidogrel. Conclusion Histories of aspirin reactions in patients with CAD are uncommon, occurring in only 1.5% of our study population. The 21% of patients with histories compatible with aspirin hypersensitivities can be challenged and, if the results are positive, successfully desensitized. Moreover, almost all patients with gastric intolerance to aspirin can be treated with aspirin and a proton pump inhibitor. However, both approaches, which result in restoration of cardiovascular prophylaxis, were seriously underused in our study population.

Purpose. Undernutrition is a prevalent and serious problem in children with cerebral palsy (CP) who have severe cognitive and motor impairment. Decision-making concerning the initiation of enteral (gastrostomy) feeding is complex, for many reasons. The Castang and Novartis Foundations convened a meeting to present research pertinent to the management of undernutrition in children with CP. The meeting was held in London on 5 and 6 February 2004. Methods. Twenty-five participants representing the disciplines usually involved in decision-making about the need for enteral feeding came from 11 countries on 4 continents. Conference participants had a mean of 16.5 years of experience treating undernutrition in children with CP. To ascertain the opinion of participants about management issues, a case-based format was used. Cases were briefly presented and questions about them addressed important issues in decision-making about instituting enteral feeding. Opinions were based on clinical experience and knowledge of the pertinent literature. Results. There were five consensus opinions, with 90% of participants agreeing that: (1) Weight and height should be plotted on growth charts at each visit and that a subjective assessment of nutritional state and growth trajectories should be made. (2) Undernutrition severe enough to result in diminished subcutaneous fat with or without muscle wasting results in adverse health consequences. (3) The initiation of enteral feeding in children with CP results in weight gain, reduces adverse consequences of undernutrition, improves the quality of life of children, and improves the quality of life of caregivers. (4) The effect of enteral feeding on longevity (lifespan) is not known. (5) A decision by parents to provide only palliative care for a child with life-threatening undernutrition is unethical and that in such a situation reporting parents to civil authorities for child neglect would be necessary. There was a majority opinion (60-90% of conference participants agreeing) that parents should have the right to defer enteral feeding if the severity of nutrition is not thought to be life-threatening. No participant knew of a legal precedent in his or her country that ordered the initiation of enteral feeding in a child with CP, over parental refusal. Among physicians, there was no agreement about any indication or contraindication for performing an anti-reflux procedure at the time of gastrostomy in undernourished children with CP. Conclusions. For no issue is the relevant literature sufficient to provide a 'standard of care' or a 'guideline for care' for the management of undernutrition in children with CP. Therefore, this survey cannot be used for medical-legal purposes. This survey was intended to provide guidance to clinicians until there is more evidence in the literature. © 2007 Taylor and Francis.

Objective To develop a clinical score to predict appendicitis among older, male children who present to the emergency department with suspected appendicitis. Methods Patients with suspected appendicitis were prospectively enrolled at 9 pediatric emergency departments. A total of 2625 patients enrolled; a subset of 961 male patients, age 8–18 were analyzed in this secondary analysis. Outcomes were determined using pathology, operative reports, and follow-up calls. Clinical and laboratory predictors with 0.4 were entered into a multivariable model. Resultant β-coefficients were used to develop a clinical score. Test performance was assessed by calculating the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios. Results The mean age was 12.2 years; 49.9% (480) had appendicitis, 22.3% (107) had perforation, and the negative appendectomy rate was 3%. In patients with and without appendicitis, overall imaging rates were 68.6% (329) and 84.4% (406), respectively. Variables retained in the model included maximum tenderness in the right lower quadrant, pain with walking/coughing or hopping, and the absolute neutrophil count. A score ≥8.1 had a sensitivity of 25% (95% confidence interval [CI], 20%–29%), specificity of 98% (95% CI, 96%–99%), and positive predictive value of 93% (95% CI, 86%–97%) for ruling in appendicitis. Conclusions We developed an accurate scoring system for predicting appendicitis in older boys. If validated, the score might allow clinicians to manage a proportion of male patients without diagnostic imaging.

Altered body composition in children with cerebral palsy (CP) could be due to differences in energy intake, habitual physical activity (HPA), and sedentary time.We investigated the longitudinal relation between the weight-for-age z score (WZ), fat-free mass (FFM), percentage of body fat (%BF), and modifiable lifestyle factors for all Gross Motor Function Classification System (GMFCS) levels (I-V).The study was a longitudinal population-based cohort study of children with CP who were aged 18-60 mo (364 assessments in 161 children; boys: 61%; mean ± SD recruitment age: 2.8 ± 0.9 y; GMFCS: I, 48%; II, 11%; III, 15%; IV, 11%; and V, 15%). A deuterium dilution technique or bioelectrical impedance analysis was used to estimate FFM, and the %BF was calculated. Energy intake, HPA, and sedentary time were measured with the use of a 3-d weighed food diary and accelerometer wear. Data were analyzed with the use of a mixed-model analysis.Children in GMFCS group I did not differ from age- and sex-specific reference children with typical development for weight. Children in GMFCS group IV were lighter-for-age, and children in GMFCS group V had a lower FFM-for-height than those in GMFCS group I. Children in GMFCS groups II-V had a higher %BF than that of children in GMFCS group I, with the exception of orally fed children in GMFCS group V. The mean %BF of children with CP classified them as overfat or obese. There was a positive association between energy intake and FFM and also between HPA level and FFM for children in GMFCS group I.Altered body composition was evident in preschool-age children with CP across functional capacities. Gross motor function, feeding method, energy intake, and HPA level in GMFCS I individuals are the strongest predictors of body composition in children with CP between the ages of 18 and 60 mo.

OBJECTIVE White blood cell (WBC) count and absolute neutrophil count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted. METHODS This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of WBC count and ANC across three age groups

BACKGROUND: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. METHODS: We conducted a case–control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. RESULTS: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58–15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56–12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. CONCLUSIONS: In this case–control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis.

Although resident participation in scholarly activity is mandated by the Accreditation Council for Graduate Medical Education, programmatic factors associated with success are not defined. This systematic review's objective was to determine which interventions are effective in increasing resident scholarly activity productivity (RSAP), as measured by participation in scholarly activity, presentations, or publications.The PubMed, MEDLINE, Cochrane Library of Systematic Reviews, PsycINFO, CINAHL, and ERIC databases were searched through October 2013. English-language articles evaluating interventions to increase RSAP in U.S. or Canadian residency programs were included, without date limits. Two independent reviewers selected articles for inclusion and extracted data. Discrepancies were resolved by consensus.Of the 6,248 records screened, 80 studies underwent data abstraction. Twenty-six described outcomes without a comparison group, leaving 54 studies representing 13 medical and surgical specialties. Interventions included required scholarly activity participation, protected research time, research curricula, research directors, dedicated research days, and research tracks. Focusing on the 35 studies reporting statistical analysis, RSAP was associated with all interventions. There were some differences in intervention effectiveness between medical and surgical specialties.Interventions, including protected time, research curricula, or specialized research tracks, generally result in increased participation in scholarly activity in residency programs, with mixed effects on resident presentations or publications. In many studies, interventions were bundled, suggesting that programs may need to provide increased structure and rigor through multiple pathways. The findings highlight the need for a clear definition of resident scholarly activity success aligned specifically to individual program and resident aims.