University of Iowa Stead Family Children’s Hospital

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

BACKGROUND: Population-based data for pediatric cardiac arrest are scant and largely from urban areas. The Resuscitation Outcomes Consortium (ROC) Epistry-Cardiac Arrest is a population-based emergency medical services registry of out-of-hospital nontraumatic cardiac arrest (OHCA). This study examined age-stratified incidence and outcomes of pediatric OHCA. We hypothesized that survival to hospital discharge is less frequent from pediatric OHCA than adult OHCA. METHODS AND RESULTS: This prospective population-based cohort study in 11 US and Canadian ROC sites included persons <20 years of age who received cardiopulmonary resuscitation or defibrillation by emergency medical service providers and/or received bystander automatic external defibrillator shock or who were pulseless but received no resuscitation by emergency medical services between December 2005 and March 2007. Patients were stratified a priori into 3 age groups: <1 year (infants; n=277), 1 to 11 years (children; n=154), and 12 to 19 years (adolescents; n=193). The incidence of pediatric OHCA was 8.04 per 100 000 person-years (72.71 in infants, 3.73 in children, and 6.37 in adolescents) versus 126.52 per 100,000 person-years for adults. Survival for all pediatric OHCA was 6.4% (3.3% for infants, 9.1% for children, and 8.9% for adolescents) versus 4.5% for adults (P=0.03). Unadjusted odds ratio for pediatric survival to discharge compared with adults was 0.71 (95% confidence interval, 0.37 to 1.39) for infants, 2.11 (95% confidence interval, 1.21 to 3.66) for children, and 2.04 (95% confidence interval, 1.24 to 3.38) for adolescents. CONCLUSIONS: This study demonstrates that the incidence of OHCA in infants approaches that observed in adults but is lower among children and adolescents. Survival to discharge was more common among children and adolescents than infants or adults.

Over the past 15 years, increased attention has been directed at social skills and their relationship to learning disabilities. Using the methods of meta-analysis, this investigation explores the nature of social skill deficits among students with learning disabilities. Across 152 studies, quantitative synthesis shows that, on average, about 75% of students with learning disabilities manifest social skill deficits that distinguish them from comparison samples. Approximately the same level of group differentiation is found across different raters (teachers, peers, self) and across most dimensions of social competence. Although social skill deficits appear to be an integral part of the learning disability experience, a number of questions about the relationship between learning disability and social skill deficits remain unanswered. Until these questions are answered, social skill deficits are best viewed as one among many elements of the learning disability constellation, and no significant definitional changes related to social skill deficits appear warranted.

In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates <1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations.

Importance: Attention-deficit/hyperactivity disorder (ADHD) is common in US children and adolescents. It is important to understand the most recent prevalence of ADHD and its long-term trends over the past decades. Objective: To estimate the prevalence of diagnosed ADHD and 20-year trends from 1997 to 2016 among US children and adolescents using nationally representative data. Design, Setting, and Participants: In this population-based, cross-sectional survey study (National Health Interview Survey), surveys were conducted annually from 1997 to 2016. A total of 186 457 children and adolescents aged 4 to 17 years from 1997 to 2016 were included in this analysis. Data were collected through in-person household interviews with a parent or guardian. The data analysis was performed in January 2018. Main Outcomes and Measures: Attention-deficit/hyperactivity disorder diagnosed by a physician or other health care professional. Results: Among the included 186 457 children and adolescents (96 017 boys [51.5%], 51 350 Hispanic [27.5%], 91 374 non-Hispanic white [49.0%], 28 808 non-Hispanic black [15.5%], 14 925 non-Hispanic other race [8.0%]), 14 704 children and adolescents (7.9%; 10 536 boys [71.7%], 2497 Hispanic [17.0%], 9010 non-Hispanic white [61.3%], 2328 non-Hispanic black [15.8%], and 869 non-Hispanic other race [5.9%]) were reported to have ever been diagnosed with ADHD. The weighted prevalence of diagnosed ADHD was 10.2% (95% CI, 9.6%-10.8%) in 2015-2016. There were significant sex and racial/ethnic disparities in the prevalence of diagnosed ADHD. The prevalence was 14.0% (95% CI, 13.1%-15.0%) in boys and 6.3% (95% CI, 5.6%-7.0%) in girls, 6.1% (95% CI, 5.2%-7.0%) in Hispanic individuals, 12.0% (95% CI, 11.1%-12.9%) in non-Hispanic white individuals, and 12.8% (95% CI, 11.0%-14.5%) in non-Hispanic black individuals. Over the 20-year period, the estimated prevalence of diagnosed ADHD in US children and adolescents increased from 6.1% in 1997-1998 to 10.2% in 2015-2016 (P for trend <.001). All subgroups by age, sex, race/ethnicity, family income, and geographic regions showed a significant increase in the prevalence from 1997-1998 to 2015-2016. Conclusions and Relevance: This study's findings suggest that among US children and adolescents, the estimated prevalence of diagnosed ADHD increased significantly between 1997-1998 and 2015-2016. This study suggests that additional research is needed to better understand the cause of this apparent rise in prevalence.

OBJECTIVE: To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). METHODS: Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. RESULTS: Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. CONCLUSION: Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.

Potential long-lasting adverse effects of child maltreatment have been widely reported, although little is known about the distinctive long-term impact of differing types of maltreatment. Our objective for this special article is to integrate findings from the Mater-University of Queensland Study of Pregnancy, a longitudinal prenatal cohort study spanning 2 decades. We compare and contrast the associations of specific types of maltreatment with long-term cognitive, psychological, addiction, sexual health, and physical health outcomes assessed in up to 5200 offspring at 14 and/or 21 years of age. Overall, psychological maltreatment (emotional abuse and/or neglect) was associated with the greatest number of adverse outcomes in almost all areas of assessment. Sexual abuse was associated with early sexual debut and youth pregnancy, attention problems, posttraumatic stress disorder symptoms, and depression, although associations were not specific for sexual abuse. Physical abuse was associated with externalizing behavior problems, delinquency, and drug abuse. Neglect, but not emotional abuse, was associated with having multiple sexual partners, cannabis abuse and/or dependence, and experiencing visual hallucinations. Emotional abuse, but not neglect, revealed increased odds for psychosis, injecting-drug use, experiencing harassment later in life, pregnancy miscarriage, and reporting asthma symptoms. Significant cognitive delays and educational failure were seen for both abuse and neglect during adolescence and adulthood. In conclusion, child maltreatment, particularly emotional abuse and neglect, is associated with a wide range of long-term adverse health and developmental outcomes. A renewed focus on prevention and early intervention strategies, especially related to psychological maltreatment, will be required to address these challenges in the future.

OBJECTIVE: To determine whether challenging behavior in young children with autism and other developmental disabilities can be treated successfully at lower cost by using telehealth to train parents to implement applied behavior analysis (ABA). METHODS: We compared data on the outcomes and costs for implementing evidence-based ABA procedures to reduce problem behavior by using 3 service delivery models: in-home therapy, clinic-based telehealth, and home-based telehealth. Participants were 107 young children diagnosed with autism or other neurodevelopmental disorders, and data analysis focused on the 94 children who completed treatment. RESULTS: All 3 service delivery models demonstrated successful reduction of problem behavior by training parents to conduct functional analysis and functional communication training. The mean percentage reduction in problem behavior was >90% in all 3 groups after treatment, and treatment acceptability based on parent ratings was high for all groups. Total costs for implementing treatment were lowest for home telehealth, but both telehealth models were significantly less costly than in-home therapy. CONCLUSIONS: This research demonstrated that parents can use ABA procedures to successfully treat behavior problems associated with autism spectrum disorders regardless of whether treatment is directed by behavior consultants in person or via remote video coaching. Because ABA telehealth can achieve similar outcomes at lower cost compared with in-home therapy, geographic barriers to providing access to ABA for treating problem behavior can be minimized. These findings support the potential for using telehealth to provide research-based behavioral treatment to any family that has access to the Internet.

This study estimates the current prevalence of autism spectrum disorder among US children and adolescents from 2014 to 2016 using nationally representative data from the National Health Interview Survey.

Importance: Myocarditis is a leading cause of sudden death in competitive athletes. Myocardial inflammation is known to occur with SARS-CoV-2. Different screening approaches for detection of myocarditis have been reported. The Big Ten Conference requires comprehensive cardiac testing including cardiac magnetic resonance (CMR) imaging for all athletes with COVID-19, allowing comparison of screening approaches. Objective: To determine the prevalence of myocarditis in athletes with COVID-19 and compare screening strategies for safe return to play. Design, Setting, and Participants: Big Ten COVID-19 Cardiac Registry principal investigators were surveyed for aggregate observational data from March 1, 2020, through December 15, 2020, on athletes with COVID-19. For athletes with myocarditis, presence of cardiac symptoms and details of cardiac testing were recorded. Myocarditis was categorized as clinical or subclinical based on the presence of cardiac symptoms and CMR findings. Subclinical myocarditis classified as probable or possible myocarditis based on other testing abnormalities. Myocarditis prevalence across universities was determined. The utility of different screening strategies was evaluated. Exposures: SARS-CoV-2 by polymerase chain reaction testing. Main Outcome and Measure: Myocarditis via cardiovascular diagnostic testing. Results: Representing 13 universities, cardiovascular testing was performed in 1597 athletes (964 men [60.4%]). Thirty-seven (including 27 men) were diagnosed with COVID-19 myocarditis (overall 2.3%; range per program, 0%-7.6%); 9 had clinical myocarditis and 28 had subclinical myocarditis. If cardiac testing was based on cardiac symptoms alone, only 5 athletes would have been detected (detected prevalence, 0.31%). Cardiac magnetic resonance imaging for all athletes yielded a 7.4-fold increase in detection of myocarditis (clinical and subclinical). Follow-up CMR imaging performed in 27 (73.0%) demonstrated resolution of T2 elevation in all (100%) and late gadolinium enhancement in 11 (40.7%). Conclusions and Relevance: In this cohort study of 1597 US competitive athletes with CMR screening after COVID-19 infection, 37 athletes (2.3%) were diagnosed with clinical and subclinical myocarditis. Variability was observed in prevalence across universities, and testing protocols were closely tied to the detection of myocarditis. Variable ascertainment and unknown implications of CMR findings underscore the need for standardized timing and interpretation of cardiac testing. These unique CMR imaging data provide a more complete understanding of the prevalence of clinical and subclinical myocarditis in college athletes after COVID-19 infection. The role of CMR in routine screening for athletes safe return to play should be explored further.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is associated with increased risk of morbidity and mortality in critically ill children and adults. Neonates remain an understudied group, although previous evidence suggests that this association holds true for them as well. RECENT FINDINGS: Attention to the issue of neonatal AKI is increasing. New studies in very low-birthweight infants, infants with congenital heart disease who undergo cardiopulmonary bypass, those who receive extracorporeal membrane oxygenation and infants with perinatal depression continue to demonstrate that AKI is common in neonates and associated with increased risk of morbidity and mortality. Additional advances in the field of neonatal AKI include adaptation of modern, categorical AKI definitions, as well as further evaluation of novel urinary biomarkers (e.g., neutrophil gelatinase-associated lipocalin) in this patient group. SUMMARY: AKI is an independent risk factor for poor outcomes in critically ill neonates. Our ability to improve outcomes for these patients depends on heightened awareness of this issue both at the bedside as well as in research, commitment to using standardized AKI definitions in order to pool and compare data more effectively and improvement in our diagnostic methods with better AKI biomarkers so that we can identify AKI and intervene much earlier in the disease course.

PURPOSE OF REVIEW: Chronic non-bacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder. We summarize the clinical presentation, diagnostic approaches, most recent advances in understanding the pathophysiology, and available treatment options and outcomes in CNO/CRMO. RECENT FINDINGS: Though the exact molecular pathophysiology of CNO/CRMO remains somewhat elusive, it appears likely that variable defects in the TLR4/MAPK/inflammasome signaling cascade result in an imbalance between pro- and anti-inflammatory cytokine expressions in monocytes from CNO/CRMO patients. In this context, we present previously unpublished data on cytokine and chemokine expression in monocytes and tissues. CNO/CRMO is an autoinflammatory bone disorder resulting from imbalanced cytokine expression from innate immune cells. Though the exact molecular pathophysiology remains unclear, variable molecular defects appear to result in inflammasome activation and pro-inflammatory cytokine expression in monocytes from CNO/CRMO patients. Recent advances suggest signaling pathways and single molecules as biomarkers for CNO/CRMO as well as future treatment targets.

With an average worldwide prevalence of approximately 1.2/1000 live births, orofacial clefts are the most common craniofacial birth defects in humans. Like other complex disorders, these birth defects are thought to result from the complex interplay of multiple genes and environmental factors. Significant progress in the identification of underlying genes and pathways has benefited from large populations available for study, increased international collaboration, rapid advances in genotyping technology, and major improvements in analytic approaches. Here we review recent advances in genetic epidemiological approaches to complex traits and their applications to studies of nonsyndromic orofacial clefts. Our main aim is to bring together a discussion of new and previously identified candidate genes to create a more cohesive picture of interacting pathways that shape the human craniofacial region. In future directions, we highlight the need to search for copy number variants that affect gene dosage and rare variants that are possibly associated with a higher disease penetrance. In addition, sequencing of protein-coding regions in candidate genes and screening for genetic variation in noncoding regulatory elements will help advance this important area of research.

BACKGROUND: Literacy is a national and international problem. Studies have shown the readability of adult and pediatric patient education materials to be too high for average adults. Materials should be written at the 8th-grade level or lower. OBJECTIVE: To determine the general readability of pediatric patient education materials designed for adults on the World Wide Web (WWW). MATERIALS AND METHODS: GeneralPediatrics.com (http://www.generalpediatrics.com) is a digital library serving the medical information needs of pediatric health care providers, patients, and families. Documents from 100 different authoritative Web sites designed for laypersons were evaluated using a built-in computer software readability formula (Flesch Reading Ease and Flesch-Kincaid reading levels) and hand calculation methods (Fry Formula and SMOG methods). Analysis of variance and paired t tests determined significance. RESULTS: Eighty-nine documents constituted the final sample; they covered a wide spectrum of pediatric topics. The overall Flesch Reading Ease score was 57.0. The overall mean Fry Formula was 12.0 (12th grade, 0 months of schooling) and SMOG was 12.2. The overall Flesch-Kincaid grade level was significantly lower (P<.0001), at a mean of 7.1, when compared with the other 2 methods. All author and institution groups had an average reading level above 10.6 by the Fry Formula and SMOG methods. CONCLUSIONS: Pediatric patient education materials on the WWW are not written at an appropriate reading level for the average adult. We propose that a practical reading level and how it was determined be included on all patient education materials on the WWW for general guidance in material selection. We discuss suggestions for improved readability of patient education materials.

Infevers (Internet Fevers; http://fmf.igh.cnrs.fr/ISSAID/infevers), a website dedicated to mutations responsible for hereditary autoinflammatory diseases, was created in 2002 and has continued to evolve. This new version includes eight genes; six were already present: MEFV, MVK, TNFRSF1A, NLRP3, NOD2, PSTPIP1, and two are new, LPIN2 and NLRP7. Currently, Infevers contains over 540 sequence variants. Several new database functions were recently instituted. The website now accepts confidential data and complex alleles. For each gene, a newly created menu offers: 1) a tabular list of the variants that can be sorted by several parameters; 2) a gene graph providing a schematic representation of the variants along the gene; 3) statistical analysis of the data according to the phenotype, alteration type, and location of the mutation in the gene; 4) the cDNA and gDNA sequences of each gene, showing the nucleotide changes along the sequence, with a color-based code highlighting the gene domains, the first ATG, and the termination codon; and 5) a "download" menu making all tables and figures available for the users, which, except for the gene graphs, are all automatically generated and updated upon submission of the variants. Finally, the entire database was curated to comply with the HUGO Gene Nomenclature Committee (HGNC) and HGVS nomenclature guidelines, and wherever necessary, an informative note was provided. Infevers has already proven useful for the scientific community with a mean number of visits per month of 200 in 2002 and 800 in 2007, and its new design will lead to a more comprehensive comparative analysis and interpretation of auto-inflammatory sequence variants.

IMPORTANCE: Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood. OBJECTIVE: To characterize and identify risk factors associated with ARP and CP in childhood. DESIGN, SETTING, AND PARTICIPANTS: A multinational cross-sectional study of children with ARP or CP at the time of enrollment to the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) study at participant institutions of the INSPPIRE Consortium. From August 22, 2012, to February 8, 2015, 155 children with ARP and 146 with CP (aged ≤19 years) were enrolled. Their demographic and clinical information was entered into the REDCap (Research Electronic Data Capture) database at the 15 centers. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables and Pearson χ2 test or Fisher exact test for categorical variables. Disease burden variables (pain variables, hospital/emergency department visits, missed school days) were compared using Wilcoxon rank sum test. MAIN OUTCOMES AND MEASURES: Demographic characteristics, risk factors, abdominal pain, and disease burden. RESULTS: A total of 301 children were enrolled (mean [SD] age, 11.9 [4.5] years; 172 [57%] female); 155 had ARP and 146 had CP. The majority of children with CP (123 of 146 [84%]) reported prior recurrent episodes of acute pancreatitis. Sex distribution was similar between the groups (57% female in both). Hispanic children were less likely to have CP than ARP (17% vs 28%, respectively; odds ratio [OR] = 0.51; 95% CI, 0.29-0.92; P = .02). At least 1 gene mutation in pancreatitis-related genes was found in 48% of patients with ARP vs 73% of patients with CP (P < .001). Children with PRSS1 or SPINK1 mutations were more likely to present with CP compared with ARP (PRSS1: OR = 4.20; 95% CI, 2.14-8.22; P < .001; and SPINK1: OR = 2.30; 95% CI, 1.03-5.13; P = .04). Obstructive risk factors did not differ between children with ARP or CP (33% in both the ARP and CP groups), but toxic/metabolic risk factors were more common in children with ARP (21% overall; 26% in the ARP group and 15% in the CP group; OR = 0.55; 95% CI, 0.31-0.99; P = .046). Pancreatitis-related abdominal pain was a major symptom in 81% of children with ARP or CP within the last year. The disease burden was greater in the CP group compared with the ARP group (more emergency department visits, hospitalizations, and medical, endoscopic, and surgical interventions). CONCLUSIONS AND RELEVANCE: Genetic mutations are common in both ARP and CP. Ethnicity and mutations in PRSS1 or SPINK1 may influence the development of CP. The high disease burden in pediatric CP underscores the importance of identifying predisposing factors for progression of ARP to CP in children.

BACKGROUND: We report a multi-institutional experience with intravascular stenting (IS) for treatment of coarctation of the aorta. METHODS AND RESULTS: Data was collected retrospectively by review of medical records from 17 institutions. The data was broken down to prior to 2002 and after 2002 for further analysis. A total of 565 procedures were performed with a median age of 15 years (mean=18.1 years). Successful reduction in the post stent gradient (<20 mm Hg) or increase in post stent coarctation to descending aorta (DAo) ratio of >0.8 was achieved in 97.9% of procedures. There was significant improvement (P<0.01) in pre versus post stent coarctation dimensions (7.4 mm+/-3.0 mm vs. 14.3+/-3.2 mm), systolic gradient (31.6 mm Hg+/-16.0 mm Hg vs. 2.7 mm Hg+/-4.2 mm Hg) and ratio of the coarctation segment to the DAo (0.43+/-0.17 vs. 0.85+/-0.15). Acute complications were encountered in 81/565 (14.3%) procedures. There were two procedure related deaths. Aortic wall complications included: aneurysm formation (n=6), intimal tears (n=8), and dissections (n=9). The risk of aortic dissection increased significantly in patients over the age of 40 years. Technical complications included stent migration (n=28), and balloon rupture (n=13). Peripheral vascular complications included cerebral vascular accidents (CVA) (n=4), peripheral emboli (n=1), and significant access arterial injury (n=13). Older age was significantly associated with occurrence of CVAs. A significant decrease in the technical complication rate from 16.3% to 6.1% (P<0.001) was observed in procedures performed after January 2002. CONCLUSIONS: Stent placement for coarctation of aorta is an effective treatment option, though it remains a technically challenging procedure. Technical and aortic complications have decreased over the past 3 years due to, in part, improvement in balloon and stent design. Improvement in our ability to assess aortic wall compliance is essential prior to placement of ISs in older patients with coarctation of the aorta.

OBJECTIVE: Hemoglobin A1c (HbA1c) levels among individuals with type 1 diabetes (T1D) influence the longitudinal risk for diabetes-related complications. Few studies have examined HbA1c trends across time in children, adolescents, and young adults with T1D. This study examines changes in glycemic control across the specific transition periods of pre-adolescence-to-adolescence and adolescence-to-young adulthood, and the demographic and clinical factors associated with these changes. RESEARCH DESIGN AND METHODS: Available HbA1c lab results for up to 10 yr were collected from medical records at 67 T1D Exchange clinics. Two retrospective cohorts were evaluated: the pre-adolescent-to-adolescent cohort consisting of 85 016 HbA1c measurements from 6574 participants collected when the participants were 8-18 yr old and the adolescent-to-young adult cohort, 2200 participants who were 16-26 yr old at the time of 17 279 HbA1c measurements. RESULTS: HbA1c in the 8-18 cohort increased over time after age 10 yr until ages 16-17; followed by a plateau. HbA1c levels in the 16-26 cohort remained steady from 16-18, and then gradually declined. For both cohorts, race/ethnicity, income, health insurance, and pump use were all significant in explaining individual variations in age-centered HbA1c (p < 0.001). For the 8-18 cohort, insulin pump use, age of onset, and health insurance were significant in predicting individual HbA1c trajectory. CONCLUSIONS: Glycemic control among patients 8-18 yr old worsens over time, through age 16. Elevated HbA1c levels observed in 18 yr-olds begin a steady improvement into early adulthood. Focused interventions to prevent deterioration in glucose control in pre-adolescence, adolescence, and early adulthood are needed.

Importance: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Previous surveys have reported a steady increase in ASD prevalence in US children over the past decades. Several behavioral therapies and medications have been developed to treat the symptoms of ASD; however, little is known about the current status of treatment usage for children diagnosed as having ASD. Objective: To estimate the prevalence and treatment patterns of ASD among US children using nationally representative data. Design, Setting, and Participants: This study used data from the 2016 National Survey of Children's Health, a nationwide, population-based, cross-sectional survey. We included 43 032 children aged 3 to 17 years. Data were collected through questionnaires completed by a parent or guardian. Data were analyzed from February 2018 to March 2018. Main Outcomes and Measures: Outcome variables included ASD diagnosed by a physician or health professional and the use of behavioral treatment or medication treatment among children with ASD. Results: Of the 43 032 included participants, 22 072 (51.3%) were male, and the mean (SD) age was 10.7 (4.4) years. The weighted prevalence of ever-diagnosed ASD and current ASD were 2.79% (95% CI, 2.46-3.12) and 2.50% (95% CI, 2.21-2.79), respectively. The state-level prevalence of ever-diagnosed ASD varied from 1.54% (95% CI, 0.60-2.48) in Texas to 4.88% (95% CI, 2.72-7.05) in Florida. Nationally, about 70% of children with current ASD (70.5%; 95% CI, 65.1-75.8) were treated; 43.3% (95% CI, 37.4-49.2) received behavioral treatment only, 6.9% (95% CI, 3.7-10.1) received medication treatment only, and 20.3% (95% CI, 16.5-24.1) received both behavioral and medication treatments. The remaining 29.5% (95% CI, 24.2-34.9) of children with current ASD did not receive either behavioral or medication treatment. Conclusions and Relevance: This study showed that the prevalence of ASD in the United States was relatively high, and it varied substantially across US states. Almost 30% of US children with ASD did not receive behavioral or medication treatment, which calls for a critical need to understand and address the barriers for those children to receive appropriate treatments.