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.

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 .).

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.

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.).

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.

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.

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.

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.

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.

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.

Context and dating of Aurignacian vulvar representations from Abri Castanet, France.

We report here on the 2007 discovery, in perfect archaeological context, of part of the engraved and ocre-stained undersurface of the collapsed rockshelter ceiling from Abri Castanet, Dordogne, France. The decorated surface of the 1.5-t roof-collapse block was in direct contact with the exposed archaeological surface onto which it fell. Because there was no sedimentation between the engraved surface and the archaeological layer upon which it collapsed, it is clear that the Early Aurignacian occupants of the shelter were the authors of the ceiling imagery. This discovery contributes an important dimension to our understanding of the earliest graphic representation in southwestern France, almost all of which was discovered before modern methods of archaeological excavation and analysis. Comparison of the dates for the Castanet ceiling and those directly obtained from the Chauvet paintings reveal that the "vulvar" representations from southwestern France are as old or older than the very different wall images from Chauvet.

Feasibility and perceived benefits of a framework for physician-parent follow-up meetings after a child's death in the PICU.

OBJECTIVE: To evaluate the feasibility and perceived benefits of conducting physician-parent follow-up meetings after a child's death in the PICU according to a framework developed by the Collaborative Pediatric Critical Care Research Network. DESIGN: Prospective observational study. SETTING: Seven Collaborative Pediatric Critical Care Research Network-affiliated children's hospitals. SUBJECTS: Critical care attending physicians, bereaved parents, and meeting guests (i.e., parent support persons, other health professionals). INTERVENTIONS: Physician-parent follow-up meetings using the Collaborative Pediatric Critical Care Research Network framework. MEASUREMENTS AND MAIN RESULTS: Forty-six critical care physicians were trained to conduct follow-up meetings using the framework. All meetings were video recorded. Videos were evaluated for the presence or absence of physician behaviors consistent with the framework. Present behaviors were evaluated for performance quality using a 5-point scale (1 = low, 5 = high). Participants completed meeting evaluation surveys. Parents of 194 deceased children were mailed an invitation to a follow-up meeting. Of these, one or both parents from 39 families (20%) agreed to participate, 80 (41%) refused, and 75 (39%) could not be contacted. Of 39 who initially agreed, three meetings were canceled due to conflicting schedules. Thirty-six meetings were conducted including 54 bereaved parents, 17 parent support persons, 23 critical care physicians, and 47 other health professionals. Physician adherence to the framework was high; 79% of behaviors consistent with the framework were rated as present with a quality score of 4.3 ± 0.2. Of 50 evaluation surveys completed by parents, 46 (92%) agreed or strongly agreed the meeting was helpful to them and 40 (89%) to others they brought with them. Of 36 evaluation surveys completed by critical care physicians (i.e., one per meeting), 33 (92%) agreed or strongly agreed the meeting was beneficial to parents and 31 (89%) to them. CONCLUSIONS: Follow-up meetings using the Collaborative Pediatric Critical Care Research Network framework are feasible and viewed as beneficial by meeting participants. Future research should evaluate the effects of follow-up meetings on bereaved parents' health outcomes.

'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.

Early oxygenation and ventilation measurements after pediatric cardiac arrest: lack of association with outcome.

OBJECTIVES: To explore oxygenation and ventilation status early after cardiac arrest in infants and children. We hypothesize that hyperoxia is common and associated with worse outcome after pediatric cardiac arrest. DESIGN: Retrospective cohort study. SETTING: Fifteen hospitals within the Pediatric Emergency Care Applied Research Network. PATIENTS: Children who suffered a cardiac arrest event and survived for at least 6 hours after return of circulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis of 195 events revealed that abnormalities in oxygenation and ventilation are common during the initial 6 hours after pediatric cardiac arrest. Hyperoxia was frequent, affecting 54% of patients. Normoxia was documented in 34% and hypoxia in 22% of patients. These percentages account for a 10% overlap of patients who had both hyperoxia and hypoxia. Ventilation status was more evenly distributed with hyperventilation observed in 38%, normoventilation in 29%, and hypoventilation in 46%, with a 13% overlap of patients who had both hyperventilation and hypoventilation. Derangements in both oxygenation and ventilation were common early after cardiac arrest such that both normoxia and normocarbia were documented in only 25 patients (13%). Neither oxygenation nor ventilation status was associated with outcome. After controlling for potential confounders, arrest location and rhythm were significantly associated with worse outcome; however, hyperoxia was not (odds ratio for good outcome, 1.02 [0.46, 2.84]; p = 0.96). CONCLUSIONS: Despite recent resuscitation guidelines that advocate maintenance of normoxia and normoventilation after pediatric cardiac arrest, this is uncommonly achieved in practice. Although we did not demonstrate an association between hyperoxia and worse outcome, the small proportion of patients kept within normal ranges limited our power. Preclinical data suggesting potential harm with hyperoxia remain compelling, and further investigation, including prospective, large studies involving robust recording of physiological derangements, is necessary to further advance our understanding of this important topic.

Early lactate elevations following resuscitation from pediatric cardiac arrest are associated with increased mortality*.

OBJECTIVE: To describe the association of lactate levels within the first 12 hours after successful resuscitation from pediatric cardiopulmonary arrest with hospital mortality. DESIGN: Retrospective cohort study. SETTING: Fifteen children's hospital associated with the Pediatric Emergency Care Applied Research Network. PATIENTS: Patients between 1 day and 18 years old who had a cardiopulmonary arrest, received chest compressions more than 1 minute, had a return of spontaneous circulation more than 20 minutes, and had lactate measurements within 6 hours of arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred sixty-four patients had a lactate sampled between 0 and 6 hours (lactate(0-6)) and were evaluable. Of those, 153 patients had a lactate sampled between 7 and 12 hours (lactate(7-12)). One hundred thirty-eight patients (52%) died. After controlling for arrest location, total number of epinephrine doses, initial rhythm, and other potential confounders, the odds of death per 1 mmol/L increase in lactate(0-6) was 1.14 (1.08, 1.19) (p < 0.001) and the odds of death per 1 mmol/L increase in lactate(7-12) was 1.20 (1.11, 1.30) (p < 0.0001). Area under the curve for in-hospital arrest mortality for lactate(0-6) was 0.72 and for lactate(7-12) was 0.76. Area under the curve for out-of-hospital arrest mortality for lactate(0-6) was 0.8 and for lactate(7-12) was 0.75. CONCLUSIONS: Elevated lactate levels in the first 12 hours after successful resuscitation from pediatric cardiac arrest are associated with increased mortality. Lactate levels alone are not able to predict outcomes accurately enough for definitive prognostication but may approximate mortality observed in this large cohort of children's hospitals.

Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study.

OBJECTIVE: To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit. DESIGN: Prospective, observational study with 100% accrual of eligible patients. SETTING: Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network. PATIENTS: Four hundred nineteen children treated with morphine or fentanyl infusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03). CONCLUSIONS: Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of opioid therapy.

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials.

OBJECTIVE: To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. DESIGN: Multicenter randomized controlled trials. SETTING: Pediatric intensive care and cardiac ICUs in the United States and Canada. PATIENTS: Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. INTERVENTIONS: Therapeutic hypothermia or therapeutic normothermia. MEASUREMENTS AND MAIN RESULTS: From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. CONCLUSIONS: Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials.

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.

Fatal and near-fatal asthma in children: the critical care perspective.

OBJECTIVE: To characterize the clinical course, therapies, and outcomes of children with fatal and near-fatal asthma admitted to pediatric intensive care units (PICUs). STUDY DESIGN: This was a retrospective chart abstraction across the 8 tertiary care PICUs of the Collaborative Pediatric Critical Care Research Network (CPCCRN). Inclusion criteria were children (aged 1-18 years) admitted between 2005 and 2009 (inclusive) for asthma who received ventilation (near-fatal) or died (fatal). Data collected included medications, ventilator strategies, concomitant therapies, demographic information, and risk variables. RESULTS: Of the 261 eligible children, 33 (13%) had no previous history of asthma, 218 (84%) survived with no known complications, and 32 (12%) had complications. Eleven (4%) died, 10 of whom had experienced cardiac arrest before admission. Patients intubated outside the PICU had a shorter duration of ventilation (median, 25 hours vs 84 hours; P < .001). African-Americans were disproportionately represented among the intubated children and had a shorter duration of intubation. Barotrauma occurred in 15 children (6%) before admission. Pharmacologic therapy was highly variable, with similar outcomes. CONCLUSION: Of the children ventilated in the CPCCRN PICUs, 96% survived to hospital discharge. Most of the children who died experienced cardiac arrest before admission. Intubation outside the PICU was correlated with shorter duration of ventilation. Complications of barotrauma and neuromyopathy were uncommon. Practice patterns varied widely among the CPCCRN sites.