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1.
Report on advances for pediatricians in 2018: allergy, cardiology, critical care, endocrinology, hereditary metabolic diseases, gastroenterology, infectious diseases, neonatology, nutrition, respiratory tract disorders and surgery.
Caffarelli, C, Santamaria, F, Mastrorilli, C, Santoro, A, Iovane, B, Petraroli, M, Gaeta, V, Di Pinto, R, Borrelli, M, Bernasconi, S, et al
Italian journal of pediatrics. 2019;(1):126
Abstract
This review reported notable advances in pediatrics that have been published in 2018. We have highlighted progresses in allergy, cardiology, critical care, endocrinology, hereditary metabolic diseases, gastroenterology, infectious diseases, neonatology, nutrition, respiratory tract disorders and surgery. Many studies have informed on epidemiologic observations. Promising outcomes in prevention, diagnosis and treatment have been reported. We think that advances realized in 2018 can now be utilized to ameliorate patient care.
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2.
Assessment of the advantage of the serum S100B protein biomonitoring in the management of paediatric mild traumatic brain injury-PROS100B: protocol of a multicentre unblinded stepped wedge cluster randomised trial.
Bouvier, D, Balayssac, D, Durif, J, Mourgues, C, Sarret, C, Pereira, B, Sapin, V
BMJ open. 2019;(5):e027365
Abstract
INTRODUCTION S100B serum analysis in clinical routine could reduce the number of cranial CT (CCT) scans performed on children with mild traumatic brain injury (mTBI). Sampling should take place within 3 hours of trauma and cut-off levels should be based on paediatric reference ranges. The aim of this study is to evaluate the utility of measuring serum S100B in the management of paediatric mTBI by demonstrating a decrease in the number of CCT scans prescribed in an S100B biomonitoring group compared with a 'conventional management' control group, with the assumption of a 30% relative decrease of the number of CCT scans between the two groups. METHODS AND ANALYSIS The protocol is a randomised, multicentre, unblinded, prospective, interventional study (nine centres) using a stepped wedge cluster design, comparing two groups (S100B biomonitoring and control). Children in the control group will have CCT scans or be hospitalised according to the current recommendations of the French Society of Paediatrics (SFP). In the S100B biomonitoring group, blood sampling to determine serum S100B protein levels will take place within 3 hours after mTBI and subsequent management will depend on the assay. If S100B is in the normal range according to age, the children will be discharged from the emergency department after 6 hours' observation. If the result is abnormal, CCT scans or hospitalisation will be prescribed in accordance with current SFP recommendations. The primary outcome measure will be the proportion of CCT scans performed (absence/presence of CCT scan for each patient) in the 48 hours following mTBI. ETHICS AND DISSEMINATION The protocol presented (Version 5, 03 November 2017) has been approved by the ethics committee Comité de Protection des Personnes sud-est 6 (first approval 08 June 2016, IRB: 00008526). Participation in the study is voluntary and anonymous. The study findings will be disseminated in international peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER NCT02819778.
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3.
The Pediatric Cell Atlas: Defining the Growth Phase of Human Development at Single-Cell Resolution.
Taylor, DM, Aronow, BJ, Tan, K, Bernt, K, Salomonis, N, Greene, CS, Frolova, A, Henrickson, SE, Wells, A, Pei, L, et al
Developmental cell. 2019;(1):10-29
Abstract
Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan.
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4.
Management of vertebral radiotherapy dose in paediatric patients with cancer: consensus recommendations from the SIOPE radiotherapy working group.
Hoeben, BA, Carrie, C, Timmermann, B, Mandeville, HC, Gandola, L, Dieckmann, K, Ramos Albiac, M, Magelssen, H, Lassen-Ramshad, Y, Ondrová, B, et al
The Lancet. Oncology. 2019;(3):e155-e166
Abstract
Inhomogeneities in radiotherapy dose distributions covering the vertebrae in children can produce long-term spinal problems, including kyphosis, lordosis, scoliosis, and hypoplasia. In the published literature, many often interrelated variables have been reported to affect the extent of potential radiotherapy damage to the spine. Articles published in the 2D and 3D radiotherapy era instructed radiation oncologists to avoid dose inhomogeneity over growing vertebrae. However, in the present era of highly conformal radiotherapy, steep dose gradients over at-risk structures can be generated and thus less harm is caused to patients. In this report, paediatric radiation oncologists from leading centres in 11 European countries have produced recommendations on how to approach dose coverage for target volumes that are adjacent to vertebrae to minimise the risk of long-term spinal problems. Based on available information, it is advised that homogeneous vertebral radiotherapy doses should be delivered in children who have not yet finished the pubertal growth spurt. If dose fall-off within vertebrae cannot be avoided, acceptable dose gradients for different age groups are detailed here. Vertebral delineation should include all primary ossification centres and growth plates, and therefore include at least the vertebral body and arch. For partial spinal radiotherapy, the number of irradiated vertebrae should be restricted as much as achievable, particularly at the thoracic level in young children (<6 years old). There is a need for multicentre research on vertebral radiotherapy dose distributions for children, but until more valid data become available, these recommendations can provide a basis for daily practice for radiation oncologists who have patients that require vertebral radiotherapy.
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5.
Pediatric asthma: Principles and treatment.
Devonshire, AL, Kumar, R
Allergy and asthma proceedings. 2019;(6):389-392
Abstract
Approximately one-half of children with asthma present with symptoms before 3 years of age. The typical history describes recurrent episodes of wheezing and/or cough triggered by a viral upper respiratory infection (URI), activity, or changes in weather. When symptoms occur after a viral URI, children with asthma often take longer than the usual week to fully recover from their respiratory symptoms. Wheezing and coughing during exercise or during laughing or crying, and episodes triggered in the absence of infection suggest asthma. A trial of bronchodilator medication should show symptomatic improvement. The goal of asthma therapy is to keep children "symptom free" by preventing chronic symptoms, maintaining lung function, and allowing for normal daily activities. Avoidance of triggers identified by a history, such as second-hand cigarette smoke exposure, and allergens identified by skin-prick testing can significantly reduce symptoms. According to the 2007 National Asthma Education and Prevention Program (NAEPP) report, if impairment symptoms are present for >2 days/week or 2 nights/month, then the disease process is characterized as persistent, and, in all age groups, inhaled corticosteroids (ICS) are recommended as the preferred daily controller therapy. Montelukast is approved for children ages ≥ 12 months and is often used for its ease of daily oral dosing. Long-acting beta-2 adrenergic agonists should only be used in combination with an ICS. For more-severe or difficult-to-control phenotypes, biologic therapy has been developed, which targets the type of inflammation present.
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6.
Antiepileptic Drug Treatment of Epilepsy in Children.
Moosa, ANV
Continuum (Minneapolis, Minn.). 2019;(2):381-407
Abstract
PURPOSE OF REVIEW The treatment of epilepsy in children is highly individualized at each and every major step in the management. This review examines various factors that modify the treatment from the point of initiation of therapy to the decision to stop an antiepileptic drug (AED). RECENT FINDINGS AED therapy leads to seizure freedom in about 70% of all children with epilepsy. AED initiation could be delayed until a second seizure in most children and may be avoided altogether in many children with self-limited childhood focal epilepsies. Three key factors influence the choice of AED: seizure type(s), efficacy of the drug for the seizure type, and the side effect profile of the drug(s). For epileptic spasms, steroids and vigabatrin are the most effective treatment options. For absence seizures, ethosuximide and valproic acid are superior to lamotrigine. For focal seizures, many newer AEDs have favorable side effect profiles with efficacy comparable to older-generation drugs. For generalized epilepsies, valproic acid remains the most effective drug for a broad range of seizure types. Genetic and metabolic etiologies may guide unique treatment choices in some children. After 2 years or more of seizure freedom, if the recurrence risk after AED withdrawal is acceptable, slow weaning of AEDs should be done over the span of 6 weeks or longer. After discontinuation, about 70% of patients remain seizure free, and of those with recurrence, the majority achieve seizure control with restarting an AED. When treatment with two or more AEDs fails, other treatment opportunities for drug-resistant epilepsy, including epilepsy surgery, vagal nerve stimulation, and dietary therapies should be considered. SUMMARY Carefully selected medical therapy guided by seizure type and AED characteristics is effective in more than two-thirds of children with epilepsy.
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7.
Pediatric Musculoskeletal Imaging: The Indications for and Applications of PET/Computed Tomography.
Khalatbari, H, Parisi, MT, Kwatra, N, Harrison, DJ, Shulkin, BL
PET clinics. 2019;(1):145-174
Abstract
The use of PET/computed tomography (CT) for the evaluation and management of children, adolescents, and young adults continues to expand. The principal tracer used is 18F-fluorodeoxyglucose and the principal indication is oncology, particularly musculoskeletal neoplasms. The purpose of this article is to review the common applications of PET/CT for imaging of musculoskeletal issues in pediatrics and to introduce the use of PET/CT for nononcologic issues, such as infectious/inflammatory disorders, and review the use of 18F-sodium fluoride in trauma and sports-related injuries.
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8.
Making the Consult Interaction More Than a Transaction: Helping Fellows Be Better Teachers and Residents Be Better Learners.
Winn, AS, Stafford, DEJ, Miloslavsky, EM, McSparron, JI, Grover, AS, Boyer, D
The Journal of pediatrics. 2019;:3-4.e2
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9.
Effective Implementation of Culturally Appropriate Tools in Addressing Overweight and Obesity in an Urban Underserved Early Childhood Population in Pediatric Primary Care.
Herbst, RB, Khalsa, AS, Schlottmann, H, Kerrey, MK, Glass, K, Burkhardt, MC
Clinical pediatrics. 2019;(5):511-520
Abstract
Overweight and obese children are at an increased risk of remaining obese. The American Academy of Pediatrics recommends addressing healthy habits at well-child checks, but this poses challenges, especially in low-income populations. A clinical innovation project was designed to adapt recommendations in a busy urban clinic and consisted of motivational interviewing, culturally tailored tools, and standardizing documentation. A quasi-experimental design examined innovation outcomes. Of 137 overweight and obese children aged 24 to 66 months, providers' documentation of weight during well-child check visits improved post-innovation ( P < .01), as did development of healthy habits goals ( P < .001). Families were more likely to return for visits post-innovation ( P = .01). A logistic regression analysis showed that adding body mass index to the problem list and establishing a specific follow-up timeframe most predicted follow-up visits to assess progress ( P < .001). Comprehensive innovations consisting of motivational interviewing, implementation of culturally tailored tools, and standardized documentation can enhance engagement in an urban clinic setting.
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10.
Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review with meta-analysis.
Waligora, M, Bala, MM, Koperny, M, Wasylewski, MT, Strzebonska, K, Jaeschke, RR, Wozniak, A, Piasecki, J, Sliwka, A, Mitus, JW, et al
PLoS medicine. 2018;(2):e1002505
Abstract
BACKGROUND Pediatric Phase I cancer trials are critical for establishing the safety and dosing of anti-cancer treatments in children. Their implementation, however, must contend with the rarity of many pediatric cancers and limits on allowable risk in minors. The aim of this study is to describe the risk and benefit for pediatric cancer Phase I trials. METHODS AND FINDINGS Our protocol was prospectively registered in PROSPERO (CRD42015015961). We systematically searched Embase and PubMed for solid and hematological malignancy Phase I pediatric trials published between 1 January 2004 and 1 March 2015. We included pediatric cancer Phase I studies, defined as "small sample size, non‑randomized, dose escalation studies that defined the recommended dose for subsequent study of a new drug in each schedule tested." We measured risk using grade 3, 4, and 5 (fatal) drug-related adverse events (AEs) and benefit using objective response rates. When possible, data were meta-analyzed. We identified 170 studies meeting our eligibility criteria, accounting for 4,604 patients. The pooled overall objective response rate was 10.29% (95% CI 8.33% to 12.25%), and was lower in solid tumors, 3.17% (95% CI 2.62% to 3.72%), compared with hematological malignancies, 27.90% (95% CI 20.53% to 35.27%); p < 0.001. The overall fatal (grade 5) AE rate was 2.09% (95% CI 1.45% to 2.72%). Across the 4,604 evaluated patients, there were 4,675 grade 3 and 4 drug-related AEs, with an average grade 3/4 AE rate per person equal to 1.32. Our study had the following limitations: trials included in our review were heterogeneous (to minimize heterogeneity, we separated types of therapy and cancer types), and we relied on published data only and encountered challenges with the quality of reporting. CONCLUSIONS Our meta-analysis suggests that, on the whole, AE and response rates in pediatric Phase I trials are similar to those in adult Phase I trials. Our findings provide an empirical basis for the refinement and review of pediatric Phase I trials, and for communication about their risk and benefit.