Reducing Stress after Trauma (ReSeT): study protocol for a randomized, controlled trial of an online psychoeducational program and video therapy sessions for children hospitalized after trauma.

BACKGROUND: Post-traumatic stress symptoms develop in a quarter to half of injured children affecting their longer-term psychologic and physical health. Evidence-based care exists for post-traumatic stress; however, it is not readily available in some communities. We have developed an eHealth program consisting of online, interactive educational modules and telehealth therapist support based in trauma-focused cognitive behavioral therapy, the Reducing Stress after Trauma (ReSeT) program. We hypothesize that children with post-traumatic stress who participate in ReSeT will have fewer symptoms compared to the usual care control group. METHODS: This is a randomized controlled trial to test the effectiveness of the ReSeT intervention in reducing symptoms of post-traumatic stress compared to a usual care control group. One hundred and six children ages 8-17 years, who were admitted to hospital following an injury, with post-traumatic stress symptoms at 4 weeks post-injury, will be recruited and randomized from the four participating trauma centers. The outcomes compared across groups will be post-traumatic stress symptoms at 10 weeks (primary outcome) controlling for baseline symptoms and at 6 months post-randomization (secondary outcome). DISCUSSION: ReSeT is an evidence-based program designed to reduce post-traumatic stress symptoms among injured children using an eHealth platform. Currently, the American College of Surgeons standards suggest that trauma programs identify and treat patients at high risk for mental health needs in the trauma system. If effectiveness is demonstrated, ReSeT could help increase access to evidence-based care for children with post-traumatic stress within the trauma system. TRIAL REGISTRATION: ClinicalTrials.gov NCT04838977. 8 April 2021.

Tracking the emergence of an organized use of space: A direct comparison of the spatial patterning within Middle and Upper Paleolithic open-air sites.

Although the 'organization of space' is said to be one of the defining characteristics of modern human behavior, the identification and documentation of such organization has proven to be elusive, especially as rendered in artifact patterning. Without directly comparing artifact patterns within multiple sites, there is no benchmark with which to conclude one site to be more or less 'organized' than another. We can objectively identify patterns within the distribution of archaeological materials, but the decision of whether that patterning constitutes as 'organized' is entirely subjective without a comparative model. In this paper, I present the results of a study in which the spatial distribution of artifacts within nine Middle and Upper Paleolithic sites in France are directly compared to one another, and discernible changes in patterning can be identified. The differences in spatial patterning between the Middle and Upper Paleolithic sites suggest that the organization of space likely became increasingly formalized into and throughout the Upper Paleolithic alongside other cultural norms of behavior. Though more sites are needed to thoroughly document this phenomenon, this study suggests that direct comparisons of spatial patterning have the potential to yield more objective results on the question of spatial organization.

Domestic spaces as crucibles of Paleolithic culture: An archaeological perspective.

The places in which people live, sleep, prepare food, and undertake other activities-known variably as homes, residential sites, living sites, and domestic spaces-play a key role in the emergence and evolution of modern human culture. The dynamic influence of domestic spaces began early in human evolutionary history, during the Paleolithic/Stone Age. Drawing on examples from Africa and western Eurasia, this article explores aspects of the changing social and cultural significance of domestic spaces throughout this time using several lines of evidence: repeated site visitation, behavioral structuring of living spaces, and information gained by dissecting palimpsest records. With the development of pyrotechnology, living sites become hearth-centered domestic spaces that provided a common hub for activities. Through time the activities around hearths increased in their complexity and diversity. The parsing of palimpsest records by archaeologists also reveals changes in the nature, variety, and intensity of on-site activities through time, indicating shifts in site function and the spatial expression of cultural norms. Archaeological evidence shows that the entwined development of domestic spaces and human cultural activities was gradual, albeit nonlinear from the Lower Paleolithic through the Upper Paleolithic/later Middle Stone Age. In this process, domestic spaces emerged as common arenas of opportunity for social interaction and knowledge transmission, qualities that may have contributed to and enhanced the development of cumulative culture in Paleolithic society.

As Time Goes by: Understanding Child and Family Factors Shaping Behavioral Outcomes After Traumatic Brain Injury.

Objective: To model pre-injury child and family factors associated with the trajectory of internalizing and externalizing behavior problems across the first 3 years in children with pediatric traumatic brain injury (TBI) relative to children with orthopedic injuries (OI). Parent-reported emotional symptoms and conduct problems were expected to have unique and shared predictors. We hypothesized that TBI, female sex, greater pre-injury executive dysfunction, adjustment problems, lower income, and family dysfunction would be associated with less favorable outcomes. Methods: In a prospective longitudinal cohort study, we examined the level of behavior problems at 12 months after injury and rate of change from pre-injury to 12 months and from 12 to 36 months in children ages 4-15 years with mild to severe TBI relative to children with OI. A structural equation model framework incorporated injury characteristics, child demographic variables, as well as pre-injury child reserve and family attributes. Internalizing and externalizing behavior problems were indexed using the parent-rated Emotional Symptoms and Conduct Problems scales from the Strengths and Difficulties questionnaire. Results: The analysis cohort of 534 children [64% boys, M (SD) 8.8 (4.3) years of age] included 395 with mild to severe TBI and 139 with OI. Behavior ratings were higher after TBI than OI but did not differ by TBI severity. TBI, higher pre-injury executive dysfunction, and lower income predicted the level and trajectory of both Emotional Symptoms and Conduct Problems at 12 months. Female sex and poorer family functioning were vulnerability factors associated with greater increase and change in Emotional Symptoms by 12 months after injury; unique predictors of Conduct Problems included younger age and prior emotional/behavioral problems. Across the long-term follow-up from 12 to 36 months, Emotional Symptoms increased significantly and Conduct Problems stabilized. TBI was not a significant predictor of change during the chronic stage of recovery. Conclusions: After TBI, Emotional Symptoms and Conduct Problem scores were elevated, had different trajectories of change, increased or stayed elevated from 12 to 36 months after TBI, and did not return to pre-injury levels across the 3 year follow-up. These findings highlight the importance of addressing behavioral problems after TBI across an extended time frame.

Trajectories of Children's Executive Function After Traumatic Brain Injury.

Importance: Executive functions are critical for school and social success. Although these functions are adversely affected by pediatric traumatic brain injury (TBI), recovery patterns are not well established. Objective: To examine 3-year trajectories of selected children's executive functions after TBI. Design, Setting, and Participants: This prospective cohort study was conducted from January 22, 2013, to September 30, 2015, with 3-year follow-up at the level I pediatric trauma centers Primary Children's Hospital in Salt Lake City, Utah and Children's Memorial Hermann Hospital in Houston, Texas. Study participants included children aged 2 to 15 years with TBI or orthopedic injury (OI) who were treated at the participating hospitals. Children were consecutively recruited and stratified by injury severity and age group. A total of 625 children consented and completed a baseline survey; 559 (89%) children completed at least 1 follow-up and composed the analysis cohort. It was hypothesized that recovery would differ by injury severity, age at injury, and sex. Data analyses were performed from June to October 2019. Main Outcomes and Measures: Growth curve models examined the pattern of change in the Emotional Control, Inhibit, Working Memory, and Plan-Organize subscales of the Behavior Rating Inventory of Executive Function (BRIEF) or BRIEF-Preschool. For all BRIEF subscales, higher scores indicate worse symptoms, and a score of 65 or greater represents clinical impairment. Results: A total of 559 children (mean [SD] age, 8.6 [4.4] years; 356 boys [64%], 328 non-Hispanic White children [59%]) were included in the study: 155 (28%) children had mild TBI, 162 (29%) had complicated mild or moderate TBI, 90 (16%) had severe TBI, and 152 (27%) had OI. Growth curve trajectories varied by BRIEF subscale and injury severity. Overall, children with TBI did not return to their preinjury baseline, with a stepwise worsening of each outcome at 36 months by TBI severity compared with OI. Among children with severe TBI, trajectories accelerated fastest, indicating increased problems, from injury to 12 months for the Emotional Control (9.0 points; 95% CI, 6.0-11.9 points), Inhibit (3.6 points; 95% CI, 1.6-5.6 points), and Working Memory (7.0 points; 95% CI, 4.1-9.9 points) subscales. Their trajectories plateaued, with a secondary acceleration before 36 months for the Emotional Control and Working Memory subscales. Children with mild TBI had worse 36-month scores on all subscales except Inhibit compared with OI. Recovery patterns were similar for boys and girls. Conclusions and Relevance: In this longitudinal cohort study of children with TBI, trajectory analysis revealed that some children worsen after a recovery plateau, suggesting a need for longitudinal reassessment beyond 1 year postinjury.

Latent Class Analysis to Classify Injury Severity in Pediatric Traumatic Brain Injury.

Heterogeneity of injury severity among children with traumatic brain injury (TBI) classified by the Glasgow Coma Scale (GCS) makes comparisons across research cohorts, enrollment in clinical trials, and clinical predictions of outcomes difficult. The present study uses latent class analysis (LCA) to distinguish severity subgroups from a prospective cohort of 433 children 2.5-15 years of age with TBI who were recruited from two level 1 pediatric trauma centers. Indicator variables available within 48 h post-injury including emergency department (ED) GCS, hospital motor GCS, Abbreviated Injury Score (AIS), Rotterdam Score, hypotension in the ED, and pre-hospital loss of consciousness, intubation, seizures, and sedation were evaluated to define subgroups. To understand whether latent class subgroups were predictive of clinically meaningful outcomes, the Pediatric Injury Functional Outcome Scale (PIFOS) at 6 and 12 months, and the Behavior Rating Inventory of Executive Function at 12 months, were compared across subgroups. Then, outcomes were examined by GCS (primary) and AIS (secondary) classification alone to assess whether LCA provided improved outcome prediction. LCA identified four distinct increasing severity subgroups (1-4). Unlike GCS classification, mean outcome differences on PIFOS at 6 months showed decreasing function across classes. PIFOS differences relative to the lowest latent class (LC1) were: LC2 2.27 (0.83, 3.72), LC3 3.99 (1.88, 6.10), and LC4 11.2 (7.04, 15.4). Differences in 12 month outcomes were seen between the most and least severely injured groups. Differences in outcomes in relation to AIS were restricted to the most and less severely injured at both time points. This study distinguished four latent classes that are clinically meaningful, distinguished a more homogenous severe injury group, and separated children by 6-month functional outcomes better than GCS alone. Systematic reporting of these variables would allow comparisons across research cohorts, potentially improve clinical predictions, and increase sensitivity to treatment effects in clinical trials.

Changing Healthcare and School Needs in the First Year After Traumatic Brain Injury.

OBJECTIVE: To examine children's unmet and unrecognized healthcare and school needs following traumatic brain injury (TBI). SETTING: Two pediatric trauma centers. PARTICIPANTS: Children with all severity of TBI aged 4 to 15 years. DESIGN: Prospective cohort. MAIN MEASURES: Caregivers provided child health and school service use 3 and 12 months postinjury. Unmet and unrecognized needs were categorized compared with norms on standardized physical, cognitive, socioemotional health, or academic competence measures in conjunction with caregiver report of needs and services. Modified Poisson models examined child and family predictors of unmet and unrecognized needs. RESULTS: Of 322 children, 28% had unmet or unrecognized healthcare or school needs at 3 months, decreasing to 24% at 12 months. Unmet healthcare needs changed from primarily physical (79%) at 3 months to cognitive (47%) and/or socioemotional needs (68%) at 12 months. At 3 months, low social capital, preexisting psychological diagnoses, and 6 to 11 years of age predicted higher healthcare needs and severe TBI predicted higher school needs. Twelve months postinjury, prior inpatient rehabilitation, low income, and preexisting psychological diagnoses were associated with higher healthcare needs; family function was important for school and healthcare needs. CONCLUSIONS: Targeted interventions to provide family supports may increase children's access to services.

Longitudinal Developmental Outcomes after Traumatic Brain Injury in Young Children: Are Infants More Vulnerable Than Toddlers?

Children under 4 years of age have the highest incidence of traumatic brain injury (TBI) among the non-elderly and may be at high risk of poor developmental outcomes. We prospectively enrolled a cohort of children injured before 31 months old with TBI or orthopedic injury (OI), from 2013 to 2015 at two pediatric level 1 trauma centers to study very young children's developmental outcomes after injury. We used Ages & Stages-3 and Ages & Stages: Social-Emotional screening tools to measure children's development at pre-injury and 3 and 12 months post-injury. The cohort included 123 children with TBI categorized as mild (n = 48), complicated-mild or moderate (n = 54), and severe (n = 21) and 45 children with OI. Generalized linear models examined effects of injury severity and age at injury controlling for pre-injury ratings. Children with mild or complicated-mild/moderate TBI generally remained on developmental track. Compared to OI, children with severe TBI tended to have a negative developmental trajectory with decrements in communication (-7.07; 95% confidence interval [CI], -13.7, -0.48), gross motor (-15.2; 95% CI, -21.1, -9.19), problem solving (-11.6; 95% CI, -17.9, -5.29), personal-social (-16.8; 95% CI, -22.8, -10.8), and social-emotional (21.0; 95% CI, 7.32, 34.7) domains 12 months post-injury. Developmental effects from TBI differed by age at injury: Infants had more difficulties than older children in communication and problem-solving domains. Despite low developmental scores in 28% of the cohort, only 5% were receiving Early Childhood Intervention (ECI) services 12 months after injury. Early age at injury is a vulnerability factor after TBI. Young age and severe injury should prompt evaluation for ECI.

Persistent Postconcussion Symptoms After Injury.

: media-1vid110.1542/5828371885001PEDS-VA_2018-0939Video Abstract OBJECTIVES: We examined whether preinjury, demographic, and family factors influenced vulnerability to postconcussion symptoms (PCSs) persisting the year after mild traumatic brain injury (mTBI). METHODS: Children with mTBI (n = 119), complicated mild traumatic brain injury (cmTBI) (n = 110), or orthopedic injury (OI) (n = 118), recruited from emergency departments, were enrolled in a prospective, longitudinal cohort study. Caregivers completed retrospective surveys to characterize preinjury demographic, child, and family characteristics. PCSs were assessed using a validated rating scale. With multivariable general linear models adjusted for preinjury symptoms, we examined predictors of PCSs 3, 6, and 12 months after injury in children ages 4 to 8, 9 to 12, and 13 to 15 years at injury. With logistic regression, we examined predictors of chronic PCSs 1 year after traumatic brain injury. RESULTS: Postinjury somatic, emotional, cognitive, and fatigue PCSs were similar in the mTBI and cmTBI groups and significantly elevated compared with the OI group. PCS trajectories varied with age and sex. Adolescents had elevated PCSs that improved; young children had lower initial symptoms and less change. Despite similar preinjury PCSs, girls had elevated symptoms across all time points compared with boys. PCS vulnerability factors included female sex, adolescence, preinjury mood problems, lower income, and family discord. Social capital was a protective factor. PCSs persisted in 25% to 31% of the traumatic brain injury group and 18% of the OI group at 1 year postinjury. The odds of chronic PCSs were almost twice as high in girls as in boys and were >4 times higher in young children with cmTBI than in those with mTBI. CONCLUSIONS: A significant minority of children with mTBI and OI have PCSs that persisted 1 year after injury.

Psychosocial and Executive Function Recovery Trajectories One Year after Pediatric Traumatic Brain Injury: The Influence of Age and Injury Severity.

Time since traumatic brain injury (TBI) and developmental stage at injury may affect the trajectory of outcomes associated with adjustment and school success. We prospectively enrolled a cohort of 519 children with either TBI or orthopedic injury (OI) age 2.5-15 years to examine children's psychosocial and executive function outcomes at 3- and 12-months post-injury. Outcome measures included the Child Behavior Checklist (CBCL), Strengths and Difficulties Questionnaire (SDQ), and Behavior Rating Inventory of Executive Function (BRIEF) ratings. Controlling for pre-injury ratings and using the OI group as the reference, children with TBI, regardless of age or injury severity, had affective, anxiety, and attention-deficit/hyperactivity disorder (ADHD) problems on the CBCL. Symptom trajectories differed both by injury severity and age at injury. Children with mild and complicated mild TBI had a decreasing anxiety trajectory, whereas children with severe TBI had increasing symptoms. Children 6-11 years of age had high ADHD and affective scores; however, the youngest children had increasing symptoms over time. On the SDQ, peer relationships and prosocial behaviors were not significantly affected by TBI but were associated with family environment. Children with severe TBI had the worst executive function scores; however, mild and complicated mild/moderate TBI groups had clinically important working memory deficits. Hispanic ethnicity and strong social capital were positively associated with multiple outcomes. Children's recovery trajectories differed by injury severity, time since injury, and developmental stage when injured. Schools need to reassess children's skills over time as new problems in behavior and learning may emerge.

Cognitive Development One Year After Infantile Critical Pertussis.

OBJECTIVES: Pertussis can cause life-threatening illness in infants. Data regarding neurodevelopment after pertussis remain scant. The aim of this study was to assess cognitive development of infants with critical pertussis 1 year after PICU discharge. DESIGN: Prospective cohort study. SETTING: Eight hospitals comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 18 additional sites across the United States. PATIENTS: Eligible patients had laboratory confirmation of pertussis infection, were less than 1 year old, and were admitted to the PICU for at least 24 hours. INTERVENTIONS: The Mullen Scales of Early Learning was administered at a 1-year follow-up visit. Functional status was determined by examination and parental interview. MEASUREMENTS AND MAIN RESULTS: Of 196 eligible patients, 111 (57%) completed the Mullen Scales of Early Learning. The mean scores for visual reception, receptive language, and expressive language domains were significantly lower than the norms (p < 0.001), but not fine and gross motor domains. Forty-one patients (37%) had abnormal scores in at least one domain and 10 (9%) had an Early Learning Composite score 2 or more SDs below the population norms. Older age (p < 0.003) and Hispanic ethnicity (p < 0.008) were associated with lower mean Early Learning Composite score, but presenting symptoms and PICU course were not. CONCLUSIONS: Infants who survive critical pertussis often have neurodevelopmental deficits. These infants may benefit from routine neurodevelopmental screening.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

What moves us? How mobility and movement are at the center of human evolution.

Movement is central to the survival of all free-living organisms. Consequently, movement and what anthropologists often refer to as mobility, which is the sum of small-scale movements tracked across larger geographic and temporal scales, are key targets of selection. Movement and mobility also underpin many of the key features that make us human and that allowed our lineage to adapt to changing environments across the globe. The most obvious example is the evolution of humans' singular mode of locomotion. Bipedalism is arguably the most important derived anatomical trait of the hominin lineage. The mechanisms and circumstances that gave rise to this novel mode of movement remain subjects of intense research.

Time and space in the middle paleolithic: Spatial structure and occupation dynamics of seven open-air sites.

The spatial structure of archeological sites can help reconstruct the settlement dynamics of hunter-gatherers by providing information on the number and length of occupations. This study seeks to access this information through a comparison of seven sites. These sites are open-air and were all excavated over large spatial areas, up to 2,000 m(2) , and are therefore ideal for spatial analysis, which was done using two complementary methods, lithic refitting and density zones. Both methods were assessed statistically using confidence intervals. The statistically significant results from each site were then compiled to evaluate trends that occur across the seven sites. These results were used to assess the "spatial consistency" of each assemblage and, through that, the number and duration of occupations. This study demonstrates that spatial analysis can be a powerful tool in research on occupation dynamics and can help disentangle the many occupations that often make up an archeological assemblage.

Incidence and Outcomes of Cardiopulmonary Resuscitation in PICUs.

OBJECTIVES: To determine the incidence of cardiopulmonary resuscitation in PICUs and subsequent outcomes. DESIGN, SETTING, AND PATIENTS: Multicenter prospective observational study of children younger than 18 years old randomly selected and intensively followed from PICU admission to hospital discharge in the Collaborative Pediatric Critical Care Research Network December 2011 to April 2013. RESULTS: Among 10,078 children enrolled, 139 (1.4%) received cardiopulmonary resuscitation for more than or equal to 1 minute and/or defibrillation. Of these children, 78% attained return of circulation, 45% survived to hospital discharge, and 89% of survivors had favorable neurologic outcomes. The relative incidence of cardiopulmonary resuscitation events was higher for cardiac patients compared with non-cardiac patients (3.4% vs 0.8%, p <0.001), but survival rate to hospital discharge with favorable neurologic outcome was not statistically different (41% vs 39%, respectively). Shorter duration of cardiopulmonary resuscitation was associated with higher survival rates: 66% (29/44) survived to hospital discharge after 1-3 minutes of cardiopulmonary resuscitation versus 28% (9/32) after more than 30 minutes (p < 0.001). Among survivors, 90% (26/29) had a favorable neurologic outcome after 1-3 minutes versus 89% (8/9) after more than 30 minutes of cardiopulmonary resuscitation. CONCLUSIONS: These data establish that contemporary PICU cardiopulmonary resuscitation, including long durations of cardiopulmonary resuscitation, results in high rates of survival-to-hospital discharge (45%) and favorable neurologic outcomes among survivors (89%). Rates of survival with favorable neurologic outcomes were similar among cardiac and noncardiac patients. The rigorous prospective, observational study design avoided the limitations of missing data and potential selection biases inherent in registry and administrative data.

Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment.

OBJECTIVES: Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality. DESIGN: Prospective cohort study from December 4, 2011, to April 7, 2013. SETTING: General and cardiac/cardiovascular PICUs at seven sites. PATIENTS: Randomly selected PICU patients from their first PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of ≥ 3 from preillness to hospital discharge) were 4.6% (site range, 2.6-7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3-5.0%). Morbidity and mortality were significantly (p < 0.001) associated with physiological instability (measured with the Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality III score. The three-level goodness-of-fit test indicated satisfactory performance for the derivation and validation sets (p > 0.20). Predictive ability assessed with the volume under the surface was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios. CONCLUSIONS: New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality.

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

BACKGROUND: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS: A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials.

OBJECTIVES: The Therapeutic Hypothermia After Pediatric Cardiac Arrest trials will determine whether therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition, in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during Therapeutic Hypothermia After Pediatric Cardiac Arrest protocol development. DESIGN/SETTING: Consensus assessment of potential outcomes and evaluation timepoints. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. Twelve months after arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in Vineland Adaptive Behavior Scales Second Edition from prearrest level, measured as quasicontinuous with death and vegetative status being worst-possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes because of easier interpretability and favored outcomes based solely on postarrest status because of concerns about accurate parental assessment of prearrest status and differing clinical impact of a given Vineland Adaptive Behavior Scales Second Edition change depending on prearrest status. Simulations found only modest power loss from categorizing or dichotomizing quasicontinuous outcomes because of high expected mortality. The primary outcome selected was survival with 12-month Vineland Adaptive Behavior Scales Second Edition no less than two SD below a reference population mean (70 points), necessarily evaluated only among children with prearrest Vineland Adaptive Behavior Scales Second Edition greater than or equal to 70. Two secondary efficacy outcomes, 12-month survival and quasicontinuous Vineland Adaptive Behavior Scales Second Edition change from prearrest level, will be evaluated among all randomized children, including those with compromised function prearrest. CONCLUSIONS: Extensive discussion of optimal efficacy assessment timing, and of the advantages versus drawbacks of incorporating prearrest status and using quasicontinuous versus simpler outcomes, was highly beneficial to the final Therapeutic Hypothermia After Pediatric Cardiac Arrest design. A relatively simple, binary primary outcome evaluated at 12 months was selected, with two secondary outcomes that address the potential disadvantages of primary outcome.

'Fire at will': the emergence of habitual fire use 350,000 years ago.

The use of fire is central to human survival and to the processes of becoming human. The earliest evidence for hominin use of fire dates to more than a million years ago. However, only when fire use became a regular part of human behavioral adaptations could its benefits be fully realized and its evolutionary consequences fully expressed. It remains an open question when the use of fire shifted from occasional and opportunistic to habitual and planned. Understanding the time frame of this 'technological mutation' will help explain aspects of our anatomical evolution and encephalization over the last million years. It will also provide an important perspective on hominin dispersals out of Africa and the colonization of temperate environments, as well as the origins of social developments such as the formation of provisioned base camps. Frequencies of burnt flints from a 16-m-deep sequence of archaeological deposits at Tabun Cave, Israel, together with data from the broader Levantine archaeological record, demonstrate that regular or habitual fire use developed in the region between 350,000-320,000 years ago. While hominins may have used fire occasionally, perhaps opportunistically, for some million years, we argue here that it only became a consistent element in behavioral adaptations during the second part of the Middle Pleistocene.

Recurrent and high-frequency use of the emergency department by pediatric patients.

OBJECTIVES: The authors sought to describe the epidemiology of and risk factors for recurrent and high-frequency use of the emergency department (ED) by children. METHODS: This was a retrospective cohort study using a database of children aged 0 to 17 years, inclusive, presenting to 22 EDs of the Pediatric Emergency Care Applied Research Network (PECARN) during 2007, with 12-month follow-up after each index visit. ED diagnoses for each visit were categorized as trauma, acute medical, or chronic medical conditions. Recurrent visits were defined as any repeat visit; high-frequency use was defined as four or more recurrent visits. Generalized estimating equations (GEEs) were used to measure the strength of associations between patient and visit characteristics and recurrent ED use. RESULTS: A total of 695,188 unique children had at least one ED visit each in 2007, with 455,588 recurrent ED visits in the 12 months following the index visits. Sixty-four percent of patients had no recurrent visits, 20% had one, 8% had two, 4% had three, and 4% had four or more recurrent visits. Acute medical diagnoses accounted for most visits regardless of the number of recurrent visits. As the number of recurrent visits per patient rose, chronic diseases were increasingly represented, with asthma being the most common ED diagnosis. Trauma-related diagnoses were more common among patients without recurrent visits than among those with high-frequency recurrent visits (28% vs. 9%; p<0.001). High-frequency recurrent visits were more often within the highest severity score classifications. In multivariable analysis, recurrent visits were associated with younger age, black or Hispanic race or ethnicity, and public health insurance. CONCLUSIONS: Risk factors for recurrent ED use by children include age, race and ethnicity, and insurance status. Although asthma plays an important role in recurrent ED use, acute illnesses account for the majority of recurrent ED visits.