Ignite Creation Date:
2025-12-24 @ 3:21 PM
Ignite Modification Date:
2026-02-04 @ 1:13 AM
Study NCT ID:
NCT04695392
Status:
COMPLETED
Last Update Posted:
2024-04-30
First Post:
2020-12-22
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Restore Resilience in Critically Ill Children
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012128', 'term': 'Respiratory Distress Syndrome'}], 'ancestors': [{'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D012120', 'term': 'Respiration Disorders'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'curley@nursing.upenn.edu', 'phone': '2155739449', 'title': 'Martha A.Q. Curley, RN, PhD', 'organization': 'UPENN'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'From date of enrollment until the date of PICU discharge, assessed for up to 28 days', 'eventGroups': [{'id': 'EG000', 'title': 'Baseline', 'description': 'Usual care', 'otherNumAtRisk': 20, 'deathsNumAtRisk': 20, 'otherNumAffected': 1, 'seriousNumAtRisk': 20, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle', 'otherNumAtRisk': 34, 'deathsNumAtRisk': 34, 'otherNumAffected': 1, 'seriousNumAtRisk': 34, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Extubation failure (reintubation within 24 hours)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 20, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 34, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Unplanned endotracheal tube extubation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 20, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 34, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'DARE (Daytime Activity Ratio Estimate), Post Extubation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '56.7', 'groupId': 'OG000', 'lowerLimit': '47.6', 'upperLimit': '65.5'}, {'value': '61.7', 'groupId': 'OG001', 'lowerLimit': '52.7', 'upperLimit': '64.8'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From immediately after endotracheal extubation to PICU discharge, assessed for up to 28 days', 'description': 'DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.', 'unitOfMeasure': 'Percentage of total activity', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Primary outcome not available for 4 subjects.'}, {'type': 'SECONDARY', 'title': 'Delta Between Average Nighttime and Average Daytime Salivary Melatonin Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '-16.4', 'groupId': 'OG000', 'lowerLimit': '-28.0', 'upperLimit': '-0.1'}, {'value': '0.1', 'groupId': 'OG001', 'lowerLimit': '-5.9', 'upperLimit': '7.5'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Day 5 of PICU hospitalization', 'description': 'Delta between average nighttime (19:00 to 06:59) and average daytime (07:00 to 18:59) salivary melatonin levels', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Data not available for all subjects.'}, {'type': 'SECONDARY', 'title': 'Percentage of Study Days Where Light and Sound Were Modulated', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000', 'lowerLimit': '0', 'upperLimit': '0'}, {'value': '100', 'groupId': 'OG001', 'lowerLimit': '75', 'upperLimit': '100'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of enrollment until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of study days where light and sound were modulated to reflect day-night variation in light and sound levels; 0 = no study days where light and sound were modulated; 100% = light and sound modulated on all study days', 'unitOfMeasure': 'Percentage of study days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Study Days Where the Patient Not Fed Enterally After Bedtime', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '30', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '43', 'groupId': 'OG000', 'lowerLimit': '27', 'upperLimit': '67'}, {'value': '57', 'groupId': 'OG001', 'lowerLimit': '38', 'upperLimit': '100'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of enrollment until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of study days where the patient was not fed enterally after bedtime', 'unitOfMeasure': 'Percentage of study days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Data unavailable for all study subjects.'}, {'type': 'SECONDARY', 'title': 'Continuity in Nursing Care', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '67', 'groupId': 'OG000', 'lowerLimit': '52', 'upperLimit': '77'}, {'value': '67', 'groupId': 'OG001', 'lowerLimit': '57', 'upperLimit': '80'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of enrollment until the date of PICU discharge, assessed for up to 28 days', 'description': 'Continuity in Nursing Care Index (CINC) defined as (N nurses/N shifts)\\*100. Score range 0-100, lower scores are better.', 'unitOfMeasure': 'units on a 0-100 scale', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Pain Free Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '33', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '80', 'groupId': 'OG000', 'lowerLimit': '67', 'upperLimit': '95'}, {'value': '74', 'groupId': 'OG001', 'lowerLimit': '45', 'upperLimit': '86'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of PICU days where pain was assessed (0-10 pain scale) without pain (Pain score \\<4)', 'unitOfMeasure': 'Percentage of study days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Data not available for all subjects.'}, {'type': 'SECONDARY', 'title': 'Agitation Free Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '55', 'groupId': 'OG000', 'lowerLimit': '43', 'upperLimit': '100'}, {'value': '50', 'groupId': 'OG001', 'lowerLimit': '25', 'upperLimit': '75'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of PICU days without agitation (Agitation = State Behavioral Scale \\[SBS; range -3 to +2\\] \\>/= 1)', 'unitOfMeasure': 'Percentage of study days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Delirium Free Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '33', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '74', 'groupId': 'OG000', 'lowerLimit': '50', 'upperLimit': '100'}, {'value': '100', 'groupId': 'OG001', 'lowerLimit': '60', 'upperLimit': '100'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of PICU days, where delirium was assessed, without delirium (using the CAPD, pCAM-ICU or psCAM-ICU; cut score determined by instrument)', 'unitOfMeasure': 'Percentage of study days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Data not available for all subjects.'}, {'type': 'SECONDARY', 'title': 'Iatrogenic Withdrawal Syndrome (IWS) Free Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000', 'lowerLimit': '100', 'upperLimit': '100'}, {'value': '100', 'groupId': 'OG001', 'lowerLimit': '75', 'upperLimit': '100'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of PICU days without IWS (Withdrawal Assessment Tool - version 1 \\[WAT-1\\]; range of scores 0-12 where no IWS = WAT-1 \\< 3)', 'unitOfMeasure': 'Percentage of study days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Subjects still in the PICU on day 5 or later.'}, {'type': 'SECONDARY', 'title': 'Peak Daily Dose of All Opioid Sedative Agents', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '3.5', 'groupId': 'OG000', 'lowerLimit': '1.7', 'upperLimit': '6.1'}, {'value': '2.9', 'groupId': 'OG001', 'lowerLimit': '1.0', 'upperLimit': '4.2'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Highest daily mg/kg dose of all opioid sedative agents', 'unitOfMeasure': 'mg/kg/day', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Cumulative Dose of All Opioid Sedative Agents', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '12.2', 'groupId': 'OG000', 'lowerLimit': '4.6', 'upperLimit': '23.5'}, {'value': '7.6', 'groupId': 'OG001', 'lowerLimit': '2.2', 'upperLimit': '18.8'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Total PICU mg/kg dose of all opioid sedative agents received', 'unitOfMeasure': 'mg/kg', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Total PICU Days of Opioid Sedation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000', 'lowerLimit': '5', 'upperLimit': '11'}, {'value': '7', 'groupId': 'OG001', 'lowerLimit': '4', 'upperLimit': '11'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Total number of PICU days exposed to opioid sedation', 'unitOfMeasure': 'days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'PICU Length of Stay', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '7.0', 'groupId': 'OG000', 'lowerLimit': '4.1', 'upperLimit': '15.3'}, {'value': '7.1', 'groupId': 'OG001', 'lowerLimit': '4.6', 'upperLimit': '11.6'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From date and time of PICU admission until the date and time of PICU discharge', 'description': 'Time between the start and stop of PICU care', 'unitOfMeasure': 'days', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Parent Perception of Being well-cared-for', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}, {'value': '31', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000', 'lowerLimit': '100', 'upperLimit': '100'}, {'value': '100', 'groupId': 'OG001', 'lowerLimit': '86', 'upperLimit': '100'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'On the date of PICU discharge, assessed once within an average of 2 weeks post PICU admission', 'description': 'Percent match on the 7-item family-centered care scale (FCCS); range from 0-100% match; where higher scores indicate a better match', 'unitOfMeasure': 'Percent Match', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Data not available for all subjects.'}, {'type': 'SECONDARY', 'title': 'DARE (Daytime Activity Ratio Estimate), Acute Phase', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '33', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'OG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'classes': [{'categories': [{'measurements': [{'value': '53.3', 'groupId': 'OG000', 'lowerLimit': '46.6', 'upperLimit': '63.4'}, {'value': '62.0', 'groupId': 'OG001', 'lowerLimit': '55.3', 'upperLimit': '65.1'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From study enrollment to endotracheal extubation', 'description': 'DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.', 'unitOfMeasure': 'Percentage of total activity', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Data not available for all subjects.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'FG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '20'}, {'groupId': 'FG001', 'numSubjects': '36'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '20'}, {'groupId': 'FG001', 'numSubjects': '34'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Withdrawn by parent/guardian', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Withdrawn by physician', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'BG000'}, {'value': '34', 'groupId': 'BG001'}, {'value': '54', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Baseline', 'description': 'Usual care'}, {'id': 'BG001', 'title': 'Intervention', 'description': 'RESTORE Resilience (R2), a 7-item individualized care bundle'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '20', 'groupId': 'BG000'}, {'value': '34', 'groupId': 'BG001'}, {'value': '54', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '1.2', 'groupId': 'BG000', 'lowerLimit': '1.0', 'upperLimit': '12.0'}, {'value': '5.3', 'groupId': 'BG001', 'lowerLimit': '1.2', 'upperLimit': '10.4'}, {'value': '3.6', 'groupId': 'BG002', 'lowerLimit': '1.1', 'upperLimit': '10.5'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '20', 'groupId': 'BG001'}, {'value': '34', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '18', 'groupId': 'BG000'}, {'value': '33', 'groupId': 'BG001'}, {'value': '51', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '25', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '20', 'groupId': 'BG000'}, {'value': '34', 'groupId': 'BG001'}, {'value': '54', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-09-18', 'size': 392734, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2020-12-16T11:54', 'hasProtocol': True}, {'date': '2020-05-29', 'size': 325012, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2020-12-16T12:17', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'SUPPORTIVE_CARE', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Pre-post study'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 56}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-09-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2021-12-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-04-26', 'studyFirstSubmitDate': '2020-12-22', 'resultsFirstSubmitDate': '2022-11-18', 'studyFirstSubmitQcDate': '2020-12-31', 'lastUpdatePostDateStruct': {'date': '2024-04-30', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2024-04-26', 'studyFirstPostDateStruct': {'date': '2021-01-05', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2024-04-30', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-12-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'DARE (Daytime Activity Ratio Estimate), Post Extubation', 'timeFrame': 'From immediately after endotracheal extubation to PICU discharge, assessed for up to 28 days', 'description': 'DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.'}], 'secondaryOutcomes': [{'measure': 'Delta Between Average Nighttime and Average Daytime Salivary Melatonin Levels', 'timeFrame': 'Day 5 of PICU hospitalization', 'description': 'Delta between average nighttime (19:00 to 06:59) and average daytime (07:00 to 18:59) salivary melatonin levels'}, {'measure': 'Percentage of Study Days Where Light and Sound Were Modulated', 'timeFrame': 'From date of enrollment until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of study days where light and sound were modulated to reflect day-night variation in light and sound levels; 0 = no study days where light and sound were modulated; 100% = light and sound modulated on all study days'}, {'measure': 'Percentage of Study Days Where the Patient Not Fed Enterally After Bedtime', 'timeFrame': 'From date of enrollment until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of study days where the patient was not fed enterally after bedtime'}, {'measure': 'Continuity in Nursing Care', 'timeFrame': 'From date of enrollment until the date of PICU discharge, assessed for up to 28 days', 'description': 'Continuity in Nursing Care Index (CINC) defined as (N nurses/N shifts)\\*100. Score range 0-100, lower scores are better.'}, {'measure': 'Pain Free Days', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of PICU days where pain was assessed (0-10 pain scale) without pain (Pain score \\<4)'}, {'measure': 'Agitation Free Days', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of PICU days without agitation (Agitation = State Behavioral Scale \\[SBS; range -3 to +2\\] \\>/= 1)'}, {'measure': 'Delirium Free Days', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of PICU days, where delirium was assessed, without delirium (using the CAPD, pCAM-ICU or psCAM-ICU; cut score determined by instrument)'}, {'measure': 'Iatrogenic Withdrawal Syndrome (IWS) Free Days', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Percentage of PICU days without IWS (Withdrawal Assessment Tool - version 1 \\[WAT-1\\]; range of scores 0-12 where no IWS = WAT-1 \\< 3)'}, {'measure': 'Peak Daily Dose of All Opioid Sedative Agents', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Highest daily mg/kg dose of all opioid sedative agents'}, {'measure': 'Cumulative Dose of All Opioid Sedative Agents', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Total PICU mg/kg dose of all opioid sedative agents received'}, {'measure': 'Total PICU Days of Opioid Sedation', 'timeFrame': 'From date of PICU admission until the date of PICU discharge, assessed for up to 28 days', 'description': 'Total number of PICU days exposed to opioid sedation'}, {'measure': 'PICU Length of Stay', 'timeFrame': 'From date and time of PICU admission until the date and time of PICU discharge', 'description': 'Time between the start and stop of PICU care'}, {'measure': 'Parent Perception of Being well-cared-for', 'timeFrame': 'On the date of PICU discharge, assessed once within an average of 2 weeks post PICU admission', 'description': 'Percent match on the 7-item family-centered care scale (FCCS); range from 0-100% match; where higher scores indicate a better match'}, {'measure': 'DARE (Daytime Activity Ratio Estimate), Acute Phase', 'timeFrame': 'From study enrollment to endotracheal extubation', 'description': 'DARE = Daytime Activity Ratio Estimate after endotracheal extubation; DARE was calculated by dividing daytime (07:00-18:59) activity count by 24-hour activity count. A DARE of 50% indicates equal amount of activity between daytime and nighttime periods (loss of circadian rhythm), while a higher DARE indicates increased daytime activity and nighttime sleep consolidation.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Acute Respiratory Distress Syndrome']}, 'referencesModule': {'references': [{'pmid': '26380147', 'type': 'BACKGROUND', 'citation': 'Wieczorek B, Burke C, Al-Harbi A, Kudchadkar SR. Early mobilization in the pediatric intensive care unit: a systematic review. J Pediatr Intensive Care. 2015;2015(4):129-170. doi: 10.1055/s-0035-1563386. Epub 2015 Sep 3.'}, {'pmid': '25985385', 'type': 'BACKGROUND', 'citation': 'Pollack MM, Holubkov R, Funai T, Berger JT, Clark AE, Meert K, Berg RA, Carcillo J, Wessel DL, Moler F, Dalton H, Newth CJ, Shanley T, Harrison RE, Doctor A, Jenkins TL, Tamburro R, Dean JM; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment. Crit Care Med. 2015 Aug;43(8):1699-709. doi: 10.1097/CCM.0000000000001081.'}, {'pmid': '25226501', 'type': 'BACKGROUND', 'citation': 'Pollack MM, Holubkov R, Funai T, Clark A, Berger JT, Meert K, Newth CJ, Shanley T, Moler F, Carcillo J, Berg RA, Dalton H, Wessel DL, Harrison RE, Doctor A, Dean JM, Jenkins TL; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Pediatric intensive care outcomes: development of new morbidities during pediatric critical care. Pediatr Crit Care Med. 2014 Nov;15(9):821-7. doi: 10.1097/PCC.0000000000000250.'}, {'pmid': '27134761', 'type': 'BACKGROUND', 'citation': 'Hopkins RO, Choong K, Zebuhr CA, Kudchadkar SR. Transforming PICU Culture to Facilitate Early Rehabilitation. J Pediatr Intensive Care. 2015 Dec;4(4):204-211. doi: 10.1055/s-0035-1563547.'}, {'pmid': '25230376', 'type': 'BACKGROUND', 'citation': 'Kamdar BB, Niessen T, Colantuoni E, King LM, Neufeld KJ, Bienvenu OJ, Rowden AM, Collop NA, Needham DM. Delirium transitions in the medical ICU: exploring the role of sleep quality and other factors. Crit Care Med. 2015 Jan;43(1):135-141. doi: 10.1097/CCM.0000000000000610.'}, {'pmid': '22851806', 'type': 'BACKGROUND', 'citation': 'Gehlbach BK, Chapotot F, Leproult R, Whitmore H, Poston J, Pohlman M, Miller A, Pohlman AS, Nedeltcheva A, Jacobsen JH, Hall JB, Van Cauter E. Temporal disorganization of circadian rhythmicity and sleep-wake regulation in mechanically ventilated patients receiving continuous intravenous sedation. Sleep. 2012 Aug 1;35(8):1105-14. doi: 10.5665/sleep.1998.'}, {'pmid': '25887528', 'type': 'BACKGROUND', 'citation': 'Huang HW, Zheng BL, Jiang L, Lin ZT, Zhang GB, Shen L, Xi XM. Effect of oral melatonin and wearing earplugs and eye masks on nocturnal sleep in healthy subjects in a simulated intensive care unit environment: which might be a more promising strategy for ICU sleep deprivation? Crit Care. 2015 Mar 19;19(1):124. doi: 10.1186/s13054-015-0842-8.'}, {'pmid': '25881268', 'type': 'BACKGROUND', 'citation': 'Hu RF, Jiang XY, Hegadoren KM, Zhang YH. Effects of earplugs and eye masks combined with relaxing music on sleep, melatonin and cortisol levels in ICU patients: a randomized controlled trial. Crit Care. 2015 Mar 27;19(1):115. doi: 10.1186/s13054-015-0855-3.'}, {'pmid': '23702219', 'type': 'BACKGROUND', 'citation': 'Kudchadkar SR, Aljohani OA, Punjabi NM. Sleep of critically ill children in the pediatric intensive care unit: a systematic review. Sleep Med Rev. 2014 Apr;18(2):103-10. doi: 10.1016/j.smrv.2013.02.002. Epub 2013 May 21.'}, {'pmid': '26194730', 'type': 'BACKGROUND', 'citation': 'Kudchadkar SR, Yaster M, Punjabi AN, Quan SF, Goodwin JL, Easley RB, Punjabi NM. Temporal Characteristics of the Sleep EEG Power Spectrum in Critically Ill Children. J Clin Sleep Med. 2015 Dec 15;11(12):1449-54. doi: 10.5664/jcsm.5286.'}, {'pmid': '4061156', 'type': 'BACKGROUND', 'citation': "Oyarzun F. [Perception of a person's face and the process of personalization-depersonalization]. Actas Luso Esp Neurol Psiquiatr Cienc Afines. 1985 Mar-Apr;13(2):74-6. No abstract available. Spanish."}, {'pmid': '24351578', 'type': 'BACKGROUND', 'citation': 'Aitken LM, Rattray J, Hull A, Kenardy JA, Le Brocque R, Ullman AJ. The use of diaries in psychological recovery from intensive care. Crit Care. 2013 Dec 18;17(6):253. doi: 10.1186/cc13164.'}, {'pmid': '20843344', 'type': 'BACKGROUND', 'citation': 'Jones C, Backman C, Capuzzo M, Egerod I, Flaatten H, Granja C, Rylander C, Griffiths RD; RACHEL group. Intensive care diaries reduce new onset post traumatic stress disorder following critical illness: a randomised, controlled trial. Crit Care. 2010;14(5):R168. doi: 10.1186/cc9260. Epub 2010 Sep 15.'}, {'pmid': '24270169', 'type': 'BACKGROUND', 'citation': 'Kamdar BB, Yang J, King LM, Neufeld KJ, Bienvenu OJ, Rowden AM, Brower RG, Collop NA, Needham DM. Developing, implementing, and evaluating a multifaceted quality improvement intervention to promote sleep in an ICU. Am J Med Qual. 2014 Nov-Dec;29(6):546-54. doi: 10.1177/1062860613509684. Epub 2013 Nov 22.'}, {'pmid': '27104770', 'type': 'BACKGROUND', 'citation': 'Kamdar BB, Knauert MP, Jones SF, Parsons EC, Parthasarathy S, Pisani MA; Sleep in the ICU (SLEEPii) Task Force. Perceptions and Practices Regarding Sleep in the Intensive Care Unit. A Survey of 1,223 Critical Care Providers. Ann Am Thorac Soc. 2016 Aug;13(8):1370-7. doi: 10.1513/AnnalsATS.201601-087OC.'}, {'pmid': '18350967', 'type': 'BACKGROUND', 'citation': 'Benloucif S, Burgess HJ, Klerman EB, Lewy AJ, Middleton B, Murphy PJ, Parry BL, Revell VL. Measuring melatonin in humans. J Clin Sleep Med. 2008 Feb 15;4(1):66-9.'}, {'pmid': '16446601', 'type': 'BACKGROUND', 'citation': 'Curley MA, Harris SK, Fraser KA, Johnson RA, Arnold JH. State Behavioral Scale: a sedation assessment instrument for infants and young children supported on mechanical ventilation. Pediatr Crit Care Med. 2006 Mar;7(2):107-14. doi: 10.1097/01.PCC.0000200955.40962.38.'}, {'pmid': '18838937', 'type': 'BACKGROUND', 'citation': 'Franck LS, Harris SK, Soetenga DJ, Amling JK, Curley MA. The Withdrawal Assessment Tool-1 (WAT-1): an assessment instrument for monitoring opioid and benzodiazepine withdrawal symptoms in pediatric patients. Pediatr Crit Care Med. 2008 Nov;9(6):573-80. doi: 10.1097/PCC.0b013e31818c8328.'}, {'pmid': '34466711', 'type': 'DERIVED', 'citation': 'Perry MA, Dawkins-Henry OS, Awojoodu RE, Blumenthal J, Asaro LA, Wypij D, Kudchadkar SR, Zuppa AF, Curley MAQ. Study protocol for a two-center test of a nurse-implemented chronotherapeutic restoring bundle in critically ill children: RESTORE Resilience (R2). Contemp Clin Trials Commun. 2021 Aug 19;23:100840. doi: 10.1016/j.conctc.2021.100840. eCollection 2021 Sep.'}]}, 'descriptionModule': {'briefSummary': "The study design will allow investigators to describe usual care in each PICU and identify the facilitating and restraining factors impacting the implementation of R2 at each PICU. The purpose of this pilot study is to improve the care, environment, daily routine and sleep patterns of children in the PICU. The goal of this study is to learn what can be improved to support a critically ill child's healing and circadian rhythms.", 'detailedDescription': "Hospitals should do the sick no harm. That noted, modern day pediatric intensive care units (PICUs) are not healing milieus. Immediately upon admission to the PICU, the child's daily routine and sleep patterns are replaced by a well-intended but not patient-centered PICU routine. The interprofessional investigative team believes that PICU care and environments can be modulated to sustain a young child's circadian rhythm (CR) and support their physiological resilience and capacity to heal. The first step in this program of research is to pilot-test RESTORE resilience (R2), a 7-item individualized bundle that we hypothesize will restore CR in critically ill children using a pre-posttest design. Two separate PICUs will each enroll 10 baseline subjects followed by 20 intervention subjects, 6 months to 18 years of age, who are intubated and mechanically ventilated for acute respiratory failure. Specifically, as soon as possible after PICU admission, parents will be interviewed to create an individualized chronotherapeutic bundle to include (1) focused effort to replicate the child's pre-hospitalization daily routine (bedtime/wake time, bedtime/arousal routine, nap time, feeding schedule, active periods), (2) cycled day-night lighting and modulation of sound to match the child's routine, (3) minimal yet effective sedation using a nurse-implemented goal-directed sedation plan (RESTORE), (4) night fasting with bolus enteral daytime feedings, (5) early, developmentally-appropriate, progressive exercise and mobility (PICU Up!), (6) continuity in nursing care, and (7) parent diaries. The overall objective of this study is to pilot-test an intervention that can be implemented in any PICU that will improve sleep-wake patterns with restoration/maintenance of circadian rhythms in critically ill children with acute respiratory failure. Results of this pilot study will be used to inform the design of an adequately powered multicenter randomized trial of R2."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '17 Years', 'minimumAge': '6 Months', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* PICU admission at one of the study sites in which elements of R2 are typically but sporadically implemented\n* Transferred to the PICU from another hospital unit/ward with ≤4 nights in the hospital (≤2 nights in PICU)\n* Between the ages 6 months and 18 years at the time of enrollment (has not had their 18th birthday)\n* Intubated and mechanically ventilated for acute airway or parenchymal disease within last 48 hours\n* Expected to be intubated for more than 12 hours past enrollment\n* Parent/Guardian providing consent, provides primary care for subject\n\nExclusion Criteria:\n\n* A baseline cognitive dysfunction, measured by the Pediatric Cerebral Performance Category (PCPC ≥4)\n* A history of an uncontrolled seizure disorder (seizure within past 3 months), cerebral hypertension, neuromuscular respiratory failure, ventilator dependence (excluding BiPAP or CPAP at night)\n* A history of inability to tolerate bolus enteral feeds (full J-Tube fed patients)\n* The presence of any of the following within 24 hours of admission:\n\n * Modal pain scores greater than 4\n * Persistent hypotension/hypertension unresponsive to standard therapies\n * Use of High Frequency Oscillatory Ventilation or Extracorporeal Membrane Oxygenation\n* Administered melatonin within the past week\n* Has an active do-not-resuscitate plan'}, 'identificationModule': {'nctId': 'NCT04695392', 'acronym': 'R2', 'briefTitle': 'Restore Resilience in Critically Ill Children', 'organization': {'class': 'OTHER', 'fullName': 'University of Pennsylvania'}, 'officialTitle': 'Restore Resilience in Critically Ill Children', 'orgStudyIdInfo': {'id': '828061'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Intervention', 'description': 'R2 Bundle', 'interventionNames': ['Other: R2 Bundle']}, {'type': 'NO_INTERVENTION', 'label': 'Baseline', 'description': 'Usual care'}], 'interventions': [{'name': 'R2 Bundle', 'type': 'OTHER', 'description': "During the intervention phase subjects will receive R2.\n\n1. Focused effort to replicate the child's pre-hospitalization daily routine (bedtime/wake time, bedtime/arousal routine, nap time, feeding schedule, active periods),\n2. Cycled day-night lighting and modulation of sound to match the child's routine,\n3. Minimal yet effective sedation using a nurse-implemented goal-directed sedation plan (RESTORE),\n4. Night fasting with bolus enteral daytime feedings,\n5. Early, developmentally-appropriate, progressive exercise and mobility (PICU Up!),\n6. Continuity in nursing care, and\n7. Parent diaries.", 'armGroupLabels': ['Intervention']}]}, 'contactsLocationsModule': {'locations': [{'zip': '21287', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': "Johns Hopkins University - Charlotte Bloomberg Children's Center", 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': "Children's Hospital of Philadelphia", 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}], 'overallOfficials': [{'name': 'Martha AQ Curley, RN, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Pennsylvania'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Pennsylvania', 'class': 'OTHER'}, 'collaborators': [{'name': 'Johns Hopkins University', 'class': 'OTHER'}, {'name': "Children's Hospital of Philadelphia", 'class': 'OTHER'}, {'name': "Boston Children's Hospital", 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Martha A.Q. Curley, PhD, RN', 'investigatorAffiliation': 'University of Pennsylvania'}}}}