Beth S Slomine1, Faye S Silverstein2, Kent Page3, Richard Holubkov3, James R Christensen4, J Michael Dean3, Frank W Moler5. 1. Kennedy Krieger Institute, Johns Hopkins University, 707 North Broadway, Baltimore, MD, 21205, USA; Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA. Electronic address: slomine@kennedykrieger.org. 2. Department of Pediatrics, University of Michigan, Room 8301 MSRB3, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-5646, USA. 3. Department of Pediatrics, University of Utah, 295 Chipeta Way, P. O. Box 581289, Salt Lake City, UT, 84158, USA. 4. Kennedy Krieger Institute, Johns Hopkins University, 707 North Broadway, Baltimore, MD, 21205, USA; Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA. 5. Department of Pediatrics, University of Michigan, CS Mott Children's Hospital, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA.
Abstract
AIM: To inform design aspects of future trials by comparing 3 and 12-month neurobehavioural outcomes in children enrolled in Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-Of-Hospital and In-Hospital (THAPCA-OH, THAPCA-IH) trials. METHODS: The THAPCA trials evaluated two targeted temperature management interventions (hypothermia, 32.0-34.0 °C; normothermia, 36.0-37.5 °C). Children, aged 2 days to <18 years, were enrolled from 2009-2015. Three and 12-month post-cardiac arrest (CA) outcomes included the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) (population mean = 100, SD = 15) and the pediatric cerebral performance category (PCPC) scale. Children without significant pre-existing neurodevelopmental deficits were included in primary outcome analyses. Among survivors, favorable 12-month outcome was defined as VABS-II ≥ 70. RESULTS: VABS-II and PCPC were available at 3 and 12 months in 204 of 222 eligible survivors (THAPCA-OH, n = 82; THAPCA-IH, n = 122). Relative to THAPCA-IH, THAPCA-OH had significantly less pre-CA disability and significantly greater 12-month CA impairment, based on both VABS-II and PCPC. Correlations between 3 and 12-month VABS-II scores were strong for THAPCA-OH (r = 0.95) and THAPCA-IH (r = 0.72), and lower (p ≤ 0.001) in THAPCA-IH. Between time-points correlations were lower, but still significant in children <1 year at CA (p < 0.001). In both cohorts, 3-month VABS-II and PCPC categorical outcomes had high sensitivity (≥70%) for predicting favorable 12-month VABS-II outcomes, but specificity was lower for THAPCA-IH (68-89%) relative to THAPCA-OH (≥95%). Overall, 12-month diagnostic accuracy was ≥80% for both VABS-II and PCPC in both cohorts. CONCLUSIONS: In future paediatric cardiac arrest clinical trials that enroll similar cohorts, integration of 3-month neurobehavioral outcome measures should be considered.
AIM: To inform design aspects of future trials by comparing 3 and 12-month neurobehavioural outcomes in children enrolled in Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-Of-Hospital and In-Hospital (THAPCA-OH, THAPCA-IH) trials. METHODS: The THAPCA trials evaluated two targeted temperature management interventions (hypothermia, 32.0-34.0 °C; normothermia, 36.0-37.5 °C). Children, aged 2 days to <18 years, were enrolled from 2009-2015. Three and 12-month post-cardiac arrest (CA) outcomes included the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) (population mean = 100, SD = 15) and the pediatric cerebral performance category (PCPC) scale. Children without significant pre-existing neurodevelopmental deficits were included in primary outcome analyses. Among survivors, favorable 12-month outcome was defined as VABS-II ≥ 70. RESULTS:VABS-II and PCPC were available at 3 and 12 months in 204 of 222 eligible survivors (THAPCA-OH, n = 82; THAPCA-IH, n = 122). Relative to THAPCA-IH, THAPCA-OH had significantly less pre-CA disability and significantly greater 12-month CA impairment, based on both VABS-II and PCPC. Correlations between 3 and 12-month VABS-II scores were strong for THAPCA-OH (r = 0.95) and THAPCA-IH (r = 0.72), and lower (p ≤ 0.001) in THAPCA-IH. Between time-points correlations were lower, but still significant in children <1 year at CA (p < 0.001). In both cohorts, 3-month VABS-II and PCPC categorical outcomes had high sensitivity (≥70%) for predicting favorable 12-month VABS-II outcomes, but specificity was lower for THAPCA-IH (68-89%) relative to THAPCA-OH (≥95%). Overall, 12-month diagnostic accuracy was ≥80% for both VABS-II and PCPC in both cohorts. CONCLUSIONS: In future paediatric cardiac arrest clinical trials that enroll similar cohorts, integration of 3-month neurobehavioral outcome measures should be considered.
Authors: Ericka L Fink; Patrick M Kochanek; Ashok Panigrahy; Sue R Beers; Rachel P Berger; Hülya Bayir; Jose Pineda; Christopher Newth; Alexis A Topjian; Craig A Press; Aline B Maddux; Frederick Willyerd; Elizabeth A Hunt; Ashley Siems; Melissa G Chung; Lincoln Smith; Jesse Wenger; Lesley Doughty; J Wesley Diddle; Jason Patregnani; Juan Piantino; Karen Hallermeier Walson; Binod Balakrishnan; Michael T Meyer; Stuart Friess; David Maloney; Pamela Rubin; Tamara L Haller; Amery Treble-Barna; Chunyan Wang; Robert R S B Clark; Anthony Fabio Journal: JAMA Netw Open Date: 2022-09-01
Authors: Matthew P Kirschen; Daniel J Licht; Jennifer Faerber; Antara Mondal; Kathryn Graham; Madeline Winters; Ramani Balu; Ramon Diaz-Arrastia; Robert A Berg; Alexis Topjian; Arastoo Vossough Journal: Neurology Date: 2020-11-18 Impact factor: 9.910