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Additional file 3. Supplemental Table 3. Patient Characteristics between Patients with and without Return of Spontaneous Circulation.

Additional file 2. Supplemental Table 2. Cardiac Arrest Event Characteristics of Included Versus Excluded Subjects.

Additional file 1. Supplemental Table 1. Patient Characteristics of Included Versus Excluded Subjects.

Additional file 4. Supplemental Table 4. Cardiac Arrest Event Characteristics between Patients with and without Return of Spontaneous Circulation.

To evaluate postdischarge health resource use in pediatric survivors of septic shock and determine patient and hospitalization factors associated with health resource use.Secondary analyses of a multicenter prospective observational cohort study.Twelve academic PICUs.Children greater than or equal to 1 month and less than 18 years old hospitalized for community-acquired septic shock who survived to 1 year.None.For 308/338 patients (91%) with baseline and greater than or equal to one postdischarge survey, we evaluated readmission, emergency department (ED) visits, new medication class, and new device class use during the year after sepsis. Using negative binomial regression with bidirectional stepwise selection, we identified factors associated with each outcome. Median age was 7 years (interquartile range, 2-13), 157 (51%) had a chronic condition, and nearly all patients had insurance (private [n = 135; 44%] or government [n = 157; 51%]). During the year after sepsis, 128 patients (42%) were readmitted, 145 (47%) had an ED visit, 156 (51%) started a new medication class, and 102 (33%) instituted a new device class. Having a complex chronic condition was independently associated with readmission and ED visit. Documented infection and higher sum of Pediatric Logistic Organ Dysfunction--2 hematologic score were associated with readmission, whereas younger age and having a noncomplex chronic condition were associated with ED visit. Factors associated with new medication class use were private insurance, neurologic insult, and longer PICU stays. Factors associated with new device class use were preadmission chemotherapy or radiotherapy, presepsis Functional Status Scale score, and ventilation duration greater than or equal to 10 days. Of patients who had a new medication or device class, most had a readmission (56% and 61%) or ED visit (62% and 67%).Children with septic shock represent a high-risk cohort with high-resource needs after discharge. Interventions and targeted outcomes to mitigate postdischarge resource use may differ based on patients' preexisting conditions.

Supplemental Material, sj-pdf-2-prf-10.1177_02676591211056562 for Anticoagulation practices associated with bleeding and thrombosis in pediatric extracorporeal membrane oxygenation; a multi-center secondary analysis by David K Bailly, Ron W Reeder, Jennifer A Muszynski, Kathleen L Meert, Ashish A Ankola, Peta MA Alexander, Murray M Pollack, Frank W Moler, Robert A Berg, Joseph Carcillo, Christopher Newth, John Berger, Michael J Bell, J M Dean, Carol Nicholson, Pamela Garcia-Filion, David Wessel, Sabrina Heidemann, Allan Doctor, Doctor Harrison, Heidi Dalton and Athena F Zuppa in Perfusion

With the growing use of cloud computing and need for resource effectiveness, the use of container technology has increased compared to virtual machines. This is since containers require fewer resources and are significantly faster to start up. A popular containerplatform is Docker which lets users manage and run containers. The containers are run from images that can be downloaded from different sources, Docker Hub being a popular choice. Because of container technology sharing the OS-kernel with the host, there is a great need to increase and monitor the security of containers and the images they are run from. To find vulnerabilities in images, there are image scanning tools available. In this dissertation, we study 5 different image scanning tools and their performance. Twentyfive random images were selected from popular images on Docker Hub and were then scanned for vulnerabilities with the tools in the study. We aimed to answer the following questions: (1) Are there any clear differences between the number of vulnerabilities found by different image vulnerability scanning tools? (2) Are there any differences between the types of vulnerabilities found by different image vulnerability scanning tools? (3) What is the relative effectiveness of different image vulnerability scanning tools? The results show that there are considerable differences between different container image scanning tools regarding the number of found vulnerabilities. We also found that there were differences regarding the severity-grading of found vulnerabilities between the tested tools. When using our proposed metric for calculation of relative effectiveness, we discovered that the tool with the highest relative effectiveness could still miss approximately 39 percent of the vulnerabilities in images. The tool with the lowest relative effectiveness could miss approximately 77 percent of the vulnerabilities in images.

Supplemental Material, sj-pdf-3-prf-10.1177_02676591211056562 for Anticoagulation practices associated with bleeding and thrombosis in pediatric extracorporeal membrane oxygenation; a multi-center secondary analysis by David K Bailly, Ron W Reeder, Jennifer A Muszynski, Kathleen L Meert, Ashish A Ankola, Peta MA Alexander, Murray M Pollack, Frank W Moler, Robert A Berg, Joseph Carcillo, Christopher Newth, John Berger, Michael J Bell, J M Dean, Carol Nicholson, Pamela Garcia-Filion, David Wessel, Sabrina Heidemann, Allan Doctor, Doctor Harrison, Heidi Dalton and Athena F Zuppa in Perfusion

Supplemental Material, sj-pdf-1-prf-10.1177_02676591211056562 for Anticoagulation practices associated with bleeding and thrombosis in pediatric extracorporeal membrane oxygenation; a multi-center secondary analysis by David K Bailly, Ron W Reeder, Jennifer A Muszynski, Kathleen L Meert, Ashish A Ankola, Peta MA Alexander, Murray M Pollack, Frank W Moler, Robert A Berg, Joseph Carcillo, Christopher Newth, John Berger, Michael J Bell, J M Dean, Carol Nicholson, Pamela Garcia-Filion, David Wessel, Sabrina Heidemann, Allan Doctor, Doctor Harrison, Heidi Dalton and Athena F Zuppa in Perfusion

Supplemental Material, sj-pdf-4-prf-10.1177_02676591211056562 for Anticoagulation practices associated with bleeding and thrombosis in pediatric extracorporeal membrane oxygenation; a multi-center secondary analysis by David K Bailly, Ron W Reeder, Jennifer A Muszynski, Kathleen L Meert, Ashish A Ankola, Peta MA Alexander, Murray M Pollack, Frank W Moler, Robert A Berg, Joseph Carcillo, Christopher Newth, John Berger, Michael J Bell, J M Dean, Carol Nicholson, Pamela Garcia-Filion, David Wessel, Sabrina Heidemann, Allan Doctor, Doctor Harrison, Heidi Dalton and Athena F Zuppa in Perfusion

Additional file 1. Detailed statistical methods overview.

Background Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. Methods We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates. Results Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID-19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1). Conclusions While our findings may overestimate HIV- and tuberculosis-associated COVID-19 mortality risks due to residual confounding, both living with HIV and having current tuberculosis were independently associated with increased COVID-19 mortality. The associations between age, sex, and other comorbidities and COVID-19 mortality were similar to those in other settings.

Additional file 3. Demographics by follow-up survey completion status and experimental arm

Additional file 1. CONSORT Flow Diagram

Additional file 2. Children���s injury information, overall study sample and by experimental arm

Supplemental Material, sj-pdf-1-ajh-10.1177_10499091211015913 for Complicated Grief, Depression and Post-Traumatic Stress Symptoms Among Bereaved Parents following their Child’s Death in the Pediatric Intensive Care Unit: A Follow-Up Study by Markita Suttle, Mark W. Hall, Murray M. Pollack, Robert A. Berg, Patrick S. McQuillen, Peter M. Mourani, Anil Sapru, Joseph A. Carcillo, Emily Startup, Richard Holubkov, J. Michael Dean, Daniel A. Notterman, Kathleen L. Meert and for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) in American Journal of Hospice and Palliative Medicine®

ObjectivesMore children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs.DesignA two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components.SettingMultinational survey.PatientsStakeholder participants from six continents representing clinicians, researchers, and family/advocates.Measurements and main resultsOverall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended.ConclusionsThe PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

Objectives: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs.Design: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% “critical” and less than 15% “not important” advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components.Setting: Multinational survey.Patients: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates.Measurements and Main Results: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% “critical” and less than 15% “not important” and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set—extended.Conclusions: The PICU core outcome set and PICU core outcome set—extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

IMPORTANCE: Approximately 40% of children who experience an in-hospital cardiac arrest survive to hospital discharge. Achieving threshold intra-arrest diastolic blood pressure (BP) targets during cardiopulmonary resuscitation (CPR) and systolic BP targets after the return of circulation may be associated with improved outcomes. OBJECTIVE: To evaluate the effectiveness of a bundled intervention comprising physiologically focused CPR training at the point of care and structured clinical event debriefings. DESIGN, SETTING, AND PARTICIPANTS: A parallel, hybrid stepped-wedge, cluster randomized trial (Improving Outcomes from Pediatric Cardiac Arrest—the ICU-Resuscitation Project [ICU-RESUS]) involving 18 pediatric intensive care units (ICUs) from 10 clinical sites in the US. In this hybrid trial, 2 clinical sites were randomized to remain in the intervention group and 2 in the control group for the duration of the study, and 6 were randomized to transition from the control condition to the intervention in a stepped-wedge fashion. The index (first) CPR events of 1129 pediatric ICU patients were included between October 1, 2016, and March 31, 2021, and were followed up to hospital discharge (final follow-up was April 30, 2021). INTERVENTION: During the intervention period (n = 526 patients), a 2-part ICU resuscitation quality improvement bundle was implemented, consisting of CPR training at the point of care on a manikin (48 trainings/unit per month) and structured physiologically focused debriefings of cardiac arrest events (1 debriefing/unit per month). The control period (n = 548 patients) consisted of usual pediatric ICU management of cardiac arrest. MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1 to 3 or no change from baseline (score range, 1 [normal] to 6 [brain death or death]). The secondary outcome was survival to hospital discharge. RESULTS: Among 1389 cardiac arrests experienced by 1276 patients, 1129 index CPR events (median patient age, 0.6 [IQR, 0.2-3.8] years; 499 girls [44%]) were included and 1074 were analyzed in the primary analysis. There was no significant difference in the primary outcome of survival to hospital discharge with favorable neurologic outcomes in the intervention group (53.8%) vs control (52.4%); risk difference (RD), 3.2% (95% CI, −4.6% to 11.4%); adjusted OR, 1.08 (95% CI, 0.76 to 1.53). There was also no significant difference in survival to hospital discharge in the intervention group (58.0%) vs control group (56.8%); RD, 1.6% (95% CI, −6.2% to 9.7%); adjusted OR, 1.03 (95% CI, 0.73 to 1.47). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial conducted in 18 pediatric intensive care units, a bundled intervention of cardiopulmonary resuscitation training at the point of care and physiologically focused structured debriefing, compared with usual care, did not significantly improve patient survival to hospital discharge with favorable neurologic outcome among pediatric patients who experienced cardiac arrest in the ICU. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02837497

IntroductionPatients who suffer in-hospital cardiac arrest (IHCA) are less likely to survive if the arrest occurs during nighttime versus daytime. Diastolic blood pressure (DBP) as a measure of chest compression quality was associated with survival from pediatric IHCA. We hypothesized that DBP during CPR for IHCA is lower during nighttime versus daytime.MethodsThis is a secondary analysis of data collected from the Pediatric Intensive Care Quality of Cardiopulmonary Resuscitation Study. Pediatric or Pediatric Cardiac Intensive Care Unit patients who received chest compressions for ≥1 min and who had invasive arterial BP monitoring were enrolled. Nighttime was defined as 11:00PM to 6:59AM and daytime as 7:00AM until 10:59PM. Primary outcome was attainment of DBP ≥ 25 mmHg in infants

BackgroundPediatric Intensive Care Unit (PICU) teams provide care for critically ill children with diverse and often complex medical and surgical conditions. Researchers often lack guidance on an approach to select the best outcomes when evaluating this critically ill population. Studies would be enhanced by incorporating multi-stakeholder preferences to better evaluate clinical care. This manuscript outlines the methodology currently being used to develop a PICU Core Outcome Set (COS). This PICU COS utilizes mixed methods, an inclusive stakeholder approach, and a modified Delphi consensus process that will serve as a resource for PICU research programs.MethodsA Scoping Review of the PICU literature evaluating outcomes after pediatric critical illness, a qualitative study interviewing PICU survivors and their parents, and other relevant literature will serve to inform a modified, international Delphi consensus process. The Delphi process will derive a set of minimum domains for evaluation of outcomes of critically ill children and their families. Delphi respondents include researchers, multidisciplinary clinicians, families and former patients, research funding agencies, payors, and advocates. Consensus meetings will refine and finalize the domains of the COS, outline a battery instruments for use in future studies, and prepare for extensive dissemination for broad implementation.DiscussionThe PICU COS will be a guideline resource for investigators to assure that outcomes most important to all stakeholders are considered in PICU clinical research in addition to those deemed most important to individual scientists.Trial registrationCOMET database (http://www.comet-initiative.org/, Record ID 1131, 01/01/18).

AimThe mathematical method used to calculate chest compression (CC) rate during cardiopulmonary resuscitation varies in the literature and across device manufacturers. The objective of this study was to determine the variability in calculated CC rates by applying four published methods to the same dataset.MethodsThis study was a secondary investigation of the first 200 pediatric cardiac arrest events with invasive arterial line waveform data in the ICU-RESUScitation Project (NCT02837497). Instantaneous CC rates were calculated during periods of uninterrupted CCs. The defined minimum interruption length affects rate calculation (e.g., if an interruption is defined as a break in CCs ≥ 2 s, the lowest possible calculated rate is 30 CCs/min). Average rates were calculated by four methods: 1) rate with an interruption defined as ≥ 1 s; 2) interruption ≥ 2 s; 3) interruption ≥ 3 s; 4) method #3 excluding top and bottom quartiles of calculated rates. American Heart Association Guideline-compliant rate was defined as 100-120 CCs/min. A clinically important change was defined as ±5 CCs/min. The percentage of events and epochs (30 s periods) that changed Guideline-compliant status was calculated.ResultsAcross calculation methods, mean CC rates (118.7-119.5/min) were similar. Comparing all methods, 14 events (7%) and 114 epochs (6%) changed Guideline-compliant status.ConclusionUsing four published methods for calculating CC rate, average rates were similar, but 7% of events changed Guideline-compliant status. These data suggest that a uniform calculation method (interruption ≥ 1 s) should be adopted to decrease variability in resuscitation science.

Het syndroom van Susac wordt gevormd door een trias van retinopathie, encefalopathie en gehoorschade, en wordt veroorzaakt door immuungemedieerde zwelling van endotheel, leidend tot micro-infarcering. Het klinisch beeld is divers, waardoor het syndroom gemakkelijk gemist kan worden of vertraging in behandeling optreedt. Snelle en agressieve behandeling met immunosuppressiva is belangrijk voor het verminderen van restverschijnselen. Bij ongeveer de helft van de patiënten is sprake van een enkele ziekteperiode, bij het andere deel treden 1 of meerdere opvlammingen op, soms jaren na het begin van de ziekte. Dit artikel beschrijft 3 patiënten, om de variatie in het klinische spectrum te illustreren. Tevens biedt het een overzicht van de nieuwste inzichten in etiologie, diagnostiek en behandeling van het syndroom van Susac.

Additional file 4.

Additional file 1 Supplementary Material.

Additional file 3.

Additional file 2.

Utstein-style reporting templates provide a structured framework with which to compare systems of care for cardiac arrest. The 2004 Utstein reporting template encompassed both out-of-hospital and in-hospital cardiac arrest. A 2015 update of the Utstein template focused on out-of-hospital cardiac arrest, which makes this update of the in-hospital template timely. Representatives of the International Liaison Committee on Resuscitation developed an updated in-hospital Utstein reporting template iteratively by meeting face-to-face, by teleconference, and by online surveys between 2013 and 2018. Data elements were grouped by hospital factors, patient variables, pre-event factors, cardiac arrest and postresuscitation processes, and outcomes. Elements were classified as core or supplemental by use of a modified Delphi process. Variables were described as core if they were considered essential. Core variables should enable reasonable comparisons between systems and are considered essential for quality improvement programs. Together with core variables, supplementary variables are considered useful for research.

AimDiastolic blood pressure (DBP) during cardiopulmonary resuscitation (CPR) is associated with survival following pediatric in-hospital cardiac arrest. The relationship between intra-arrest haemodynamics and neurological status among survivors of pediatric cardiac arrest is unknown.MethodsThis study represents analysis of data from the prospective multicenter Pediatric Intensive Care Quality of cardiopulmonary resuscitation (PICqCPR) Study. Primary predictor variables were median DBP and median systolic blood pressure (SBP) over the first 10min of CPR. The primary outcome measure was "new substantive morbidity" determined by Functional Status Scale (FSS) and defined as an increase in the FSS of at least 3 points or increase of 2 in a single FSS domain. Univariable analyses were completed to investigate the relationship between new substantive morbidity and BPs during CPR.Results244 index CPR events occurred during the study period, 77 (32%) CPR events met all inclusion criteria as well as having both DBP and FSS data available. Among 77 survivors, 32 (42%) had new substantive morbidity as measured by the FSS score. No significant differences were identified in DBP (median 30.5mmHg vs. 30.9mmHg, p=0.5) or SBP (median 76.3mmHg vs. 63.0mmHg, p=0.2) between patients with and without new substantive morbidity. Children who developed new substantive morbidity were more likely to have lower pre-arrest FSS than those that did not (median [IQR]: 7.5 [6.0-9.0] versus 9.0 [7.0-13.0], p=0.01).ConclusionNew substantive morbidity determined by FSS after a pediatric IHCA was associated with baseline functional status, but not DBP during CPR.

The transport of mitochondria and other cellular components along the axonal microtubule cytoskeleton plays an essential role in neuronal survival. Defects in this system have been linked to a large number of neurological disorders. In multiple sclerosis (MS) and associated models such as experimental autoimmune encephalomyelitis (EAE), alterations in axonal transport have been shown to exist before neurodegeneration occurs. Genome-wide association (GWA) studies have linked several motor proteins to MS susceptibility, while neuropathological studies have shown accumulations of proteins and organelles suggestive for transport deficits. A reduced effectiveness of axonal transport can lead to neurodegeneration through inhibition of mitochondrial motility, disruption of axoglial interaction or prevention of remyelination. In MS, demyelination leads to dysregulation of axonal transport, aggravated by the effects of TNF-alpha, nitric oxide and glutamate on the cytoskeleton. The combined effect of all these pathways is a vicious cycle in which a defective axonal transport system leads to an increase in ATP consumption through loss of membrane organization and a reduction in available ATP through inhibition of mitochondrial transport, resulting in even further inhibition of transport. The persistent activity of this positive feedback loop contributes to neurodegeneration in MS.

AimIn-hospital cardiac arrest occurs in >5000 children each year in the US and almost half will not survive to discharge. Animal data demonstrate that an immediate post-resuscitation burst of hypertension is associated with improved survival. We aimed to determine if systolic and diastolic invasive arterial blood pressures immediately (0-20 min) after return of spontaneous circulation (ROSC) are associated with survival and neurologic outcomes at hospital discharge.MethodsThis is a secondary analysis of the Pediatric Intensive Care Quality of CPR (PICqCPR) study of invasively measured blood pressures during intensive care unit CPR. Patients were eligible if they achieved ROSC and had at least one invasively measured blood pressure within the first 20 min following ROSC. Post-ROSC blood pressures were normalized for age, sex and height. "Immediate hypertension" was defined as at least one systolic or diastolic blood pressure >90th percentile. The primary outcome was survival to hospital discharge.ResultsOf 102 children, 70 (68.6%) had at least one episode of immediate post-CPR diastolic hypertension. After controlling for pre-existing hypotension, duration of CPR, calcium administration, and first documented rhythm, patients with immediate post-CPR diastolic hypertension were more likely to survive to hospital discharge (79.3% vs. 54.5%; adjusted OR = 2.93; 95%CI, 1.16-7.69).ConclusionsIn this post hoc secondary analysis of the PICqCPR study, 68.6% of subjects had diastolic hypertension within 20 min of ROSC. Immediate post-ROSC hypertension was associated with increased odds of survival to discharge, even after adjusting for covariates of interest.

AimApproximately 40% of children who have an in-hospital cardiac arrest (IHCA) in the US survive to discharge. We aimed to evaluate the impact of post-cardiac arrest hypotension during targeted temperature management following IHCA on survival to discharge.MethodsThis is a secondary analysis of the therapeutic hypothermia after pediatric cardiac arrest in-hospital (THAPCA-IH) trial. "Early hypotension" was defined as a systolic blood pressure less than the fifth percentile for age and sex for patients not treated with extracorporeal membrane oxygenation (ECMO) or a mean arterial pressure less than fifth percentile for age and sex for patients treated with ECMO during the first 6 h of temperature intervention. The primary outcome was survival to hospital discharge.ResultsOf 299 children, 142 (47%) patients did not receive ECMO and 157 (53%) received ECMO. Forty-two of 142 (29.6%) non-ECMO patients had systolic hypotension. Twenty-three of 157 (14.7%) ECMO patients had mean arterial hypotension. After controlling for confounders of interest, non-ECMO patients who had early systolic hypotension were less likely to survive to hospital discharge (40.5% vs. 72%; adjusted OR [aOR] 0.34; 95%CI, 0.12-0.93). There was no difference in survival to discharge by blood pressure groups for children treated with ECMO (30.4% vs. 49.3%; aOR = 0.60; 95%CI, 0.22-1.63).ConclusionsIn this secondary analysis of the THAPCA-IH trial, in patients not treated with ECMO, systolic hypotension within 6 h of temperature intervention was associated with lower odds of discharge survival. Blood pressure groups in patients treated with ECMO were not associated with survival to discharge.

ObjectivesLimited data exist on the effects of extracorporeal membrane oxygenation on pharmacokinetics of cefepime in critically ill pediatric patients. The objective was to describe cefepime disposition in children treated with extracorporeal membrane oxygenation using population pharmacokinetic modeling.DesignMulticenter, prospective observational study.SettingThe pediatric and cardiac ICUs of six sites of the Collaborative Pediatric Critical Care Research Network.PatientsSeventeen critically ill children (30 d to < 2 yr old) on extracorporeal membrane oxygenation who received cefepime as standard of care between January 4, 2014, and August 24, 2015, were enrolled.InterventionsNone.Measurements and main resultsA pharmacokinetic model was developed to evaluate cefepime disposition differences due to extracorporeal membrane oxygenation. A two-compartment model with linear elimination, weight effects on clearance, intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (V2) adequately described the data. The typical value of clearance in this study was 7.1 mL/min (1.9 mL/min/kg) for a patient weighing 5.8 kg. This value decreased by approximately 40% with the addition of renal replacement therapy. The typical value for V1 was 1,170 mL. In the setting of blood transfusions, V1 increased by over two-fold but was reduced with increasing age of the extracorporeal membrane oxygenation circuit oxygenator.ConclusionsCefepime clearance was reduced in pediatric patients treated with extracorporeal membrane oxygenation compared with previously reported values in children not receiving extracorporeal membrane oxygenation. The model demonstrated that the age of the extracorporeal membrane oxygenation circuit oxygenator is inversely correlated to V1. For free cefepime, only 14 of the 19 doses (74%) demonstrated a fT_minimum inhibitory concentration of 16 mg/L, an appropriate target for the treatment of pseudomonal infections, for greater than 70% of the dosing interval. Pediatric patients on extracorporeal membrane oxygenation might benefit from the addition of therapeutic drug monitoring of cefepime to assure appropriate dosing.

AimThe primary aim of this study was to evaluate the association between chest compression rates and 1) arterial blood pressure and 2) survival outcomes during pediatric in-hospital cardiopulmonary resuscitation (CPR).MethodsProspective observational study of children ≥37 weeks gestation and 120-140, >140) and outcomes.ResultsCompression rate data were available for 164 patients. More than half (98/164; 60%) were 120-140, p = 0.010; >140, p = 0.077), but not survival. A rate between 80

The purpose of this review is to describe the epidemiology of out-of-hospital cardiac arrest (OHCA), disparities in organisation and outcome, recent advances in treatment and ongoing controversies. We also outline the standard of care that should be provided by the critical care specialist and propose future directions for cardiac arrest research. Narrative review with contributions from international resuscitation experts. Although it is recognised that survival rates from OHCA are increasing there is considerable scope for improvement and many countries have implemented national strategies in an attempt to achieve this goal. More resources are required to enable high-quality randomised trials in resuscitation. Increasing international collaboration should facilitate resuscitation research and knowledge translation. The International Liaison Committee on Resuscitation (ILCOR) has adopted a continuous evidence review process, which facilitate the implementation of resuscitation interventions proven to improve patient outcomes.

Background Quality of cardiopulmonary resuscitation (CPR) is associated with survival, but recommended guidelines are often not met, and less than half the children with an in-hospital arrest will survive to discharge. A single-center before-and-after study demonstrated that outcomes may be improved with a novel training program in which all pediatric intensive care unit staff are encouraged to participate in frequent CPR refresher training and regular, structured resuscitation debriefings focused on patient-centric physiology. Methods/design This ongoing trial will assess whether a program of structured debriefings and point-of-care bedside practice that emphasizes physiologic resuscitation targets improves the rate of survival to hospital discharge with favorable neurologic outcome in children receiving CPR in the intensive care unit. This study is designed as a hybrid stepped-wedge trial in which two of ten participating hospitals are randomly assigned to enroll in the intervention group and two are assigned to enroll in the control group for the duration of the trial. The remaining six hospitals enroll initially in the control group but will transition to enrolling in the intervention group at randomly assigned staggered times during the enrollment period. Discussion To our knowledge, this is the first implementation of a hybrid stepped-wedge design. It was chosen over a traditional stepped-wedge design because the resulting improvement in statistical power reduces the required enrollment by 9 months (14%). However, this design comes with additional challenges, including logistics of implementing an intervention prior to the start of enrollment. Nevertheless, if results from the single-center pilot are confirmed in this trial, it will have a profound effect on CPR training and quality improvement initiatives. Trial registration ClinicalTrials.gov, NCT02837497. Registered on July 19, 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2590-y) contains supplementary material, which is available to authorized users.

ICU length of stay is an important measure of resource use and economic performance. Our primary aims were to characterize the utilization of PICU beds and to develop a new model for PICU length of stay.Prospective cohort. The main outcomes were factors associated with PICU length of stay and the performance of a regression model for length of stay.Eight PICUs.Randomly selected patients (newborn to 18 yr) from eight PICUs were enrolled from December 4, 2011, to April 7, 2013. Data consisted of descriptive, diagnostic, physiologic, and therapeutic information.None.The mean length of stay for was 5.0 days (SD, 11.1), with a median of 2.0 days. The 50.6% of patients with length of stay less than 2 days consumed only 11.1% of the days of care, whereas the 19.6% of patients with length of stay 4.9-19 days and the 4.6% with length of stay greater than or equal to 19 days consumed 35.7% and 37.6% of the days of care, respectively. Longer length of stay was observed in younger children, those with cardiorespiratory disease, postintervention cardiac patients, and those who were sicker assessed by Pediatric Risk of Mortality scores receiving more intensive therapies. Patients in the cardiac ICU stayed longer than those in the medical ICU. The length of stay model using descriptive, diagnostic, severity, and therapeutic factors performed well (patient-level R-squared of 0.42 and institution-level R-squared of 0.76). Standardized (observed divided by expected) length of stay ratios at the individual sites ranged from 0.87 to 1.09.PICU bed utilization was dominated by a minority of patients. The 5% of patients staying the longest used almost 40% of the bed days. The multivariate length of stay model used descriptive, diagnostic, therapeutic, and severity factors and has potential applicability for internal and external benchmarking.

Importance:Out-of-hospital cardiac arrest (OHCA) occurs in more than 6000 children each year in the United States, with survival rates of less than 10% and severe neurologic morbidity in many survivors. Post-cardiac arrest hypotension can occur, but its frequency and association with survival have not been well described during targeted temperature management. Objective:To determine whether hypotension is associated with survival to discharge in children and adolescents after resuscitation from OHCA. Design, Setting, and Participants:This post hoc secondary analysis of the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trial included 292 pediatric patients older than 48 hours and younger than 18 years treated in 36 pediatric intensive care units from September 1, 2009, through December 31, 2012. Participants underwent therapeutic hypothermia (33.0°C) vs therapeutic normothermia (36.8°C) for 48 hours. All participants had hourly systolic blood pressure measurements documented during the initial 6 hours of temperature intervention. Hourly blood pressures beginning at the time of temperature intervention (time 0) were normalized for age, sex, and height. Early hypotension was defined as a systolic blood pressure less than the fifth percentile during the first 6 hours after temperature intervention. With use of forward stepwise logistic regression, covariates of interest (age, sex, initial cardiac rhythm, any preexisting condition, estimated duration of cardiopulmonary resuscitation [CPR], primary cause of cardiac arrest, temperature intervention group, night or weekend cardiac arrest, witnessed status, and bystander CPR) were evaluated in the final model. Data were analyzed from February 5, 2016, through June 13, 2017. Exposures:Hypotension. Main Outcomes and Measure:Survival to hospital discharge. Results:Of 292 children (194 boys [66.4%] and 98 girls [33.6%]; median age, 23.0 months [interquartile range, 5.0-105.0 months]), 78 (26.7%) had at least 1 episode of early hypotension. No difference was observed between the therapeutic hypothermia and therapeutic normothermia groups in the prevalence of hypotension during induction and maintenance (73 of 153 [47.7%] vs 72 of 139 [51.8%]; P = .50) or rewarming (35 of 118 [29.7%] vs 19 of 95 [20.0%]; P = .10) during the first 72 hours. Participants who had early hypotension were less likely to survive to hospital discharge (20 of 78 [25.6%] vs 93 of 214 [43.5%]; adjusted odds ratio, 0.39; 95% CI, 0.20-0.74). Conclusions and Relevance:In this post hoc secondary analysis of the THAPCA trial, 26.7% of participants had hypotension within 6 hours after temperature intervention. Early post-cardiac arrest hypotension was associated with lower odds of discharge survival, even after adjusting for covariates of interest.

Supplemental material, Supplemental_Table_1_and_2 for Acquired infection during neonatal and pediatric extracorporeal membrane oxygenation by Katherine Cashen, Ron Reeder, Heidi J. Dalton, Robert A. Berg, Thomas P. Shanley, Christopher J. L. Newth, Murray M. Pollack, David Wessel, Joseph Carcillo, Rick Harrison, J. Michael Dean, Robert Tamburro and Kathleen L Meert in Perfusion

RationaleExtracorporeal membrane oxygenation (ECMO) is used for respiratory and cardiac failure in children but is complicated by bleeding and thrombosis.Objectives(1) To measure the incidence of bleeding (blood loss requiring transfusion or intracranial hemorrhage) and thrombosis during ECMO support; (2) to identify factors associated with these complications; and (3) to determine the impact of these complications on patient outcome.MethodsThis was a prospective, observational cohort study in pediatric, cardiac, and neonatal intensive care units in eight hospitals, carried out from December 2012 to September 2014.Measurements and main resultsECMO was used on 514 consecutive patients under age 19 years. Demographics, anticoagulation practices, severity of illness, circuitry components, bleeding, thrombotic events, and outcome were recorded. Survival was 54.9%. Bleeding occurred in 70.2%, including intracranial hemorrhage in 16%, and was independently associated with higher daily risk of mortality. Circuit component changes were required in 31.1%, and patient-related clots occurred in 12.8%. Laboratory sampling contributed to transfusion requirement in 56.6%, and was the sole reason for at least one transfusion in 42.2% of patients. Pump type was not associated with bleeding, thrombosis, hemolysis, or mortality. Hemolysis was predictive of subsequent thrombotic events. Neither hemolysis nor thrombotic events increased the risk of mortality.ConclusionsThe incidences of bleeding and thrombosis are high during ECMO support. Laboratory sampling is a major contributor to transfusion during ECMO. Strategies to reduce the daily risk of bleeding and thrombosis, and different thresholds for transfusion, may be appropriate subjects of future trials to improve outcomes of children requiring this supportive therapy.

The LignoJet project aimed to achieve an intermediate lignin-oil product miscible with fossil feedstock and with a significantly reduced oxygen content. A technical concept for production has been studied that involves combined catalysed depolymerisation and hydrodeoxygenation, so called hydrogenolytic depolymerisation, of kraft lignin. Kraft lignin was separated through membrane ultrafiltration from softwood and eucalyptus black liquor followed by precipitation through LignoBoost technology. A difference in lignin properties was observed between ultrafiltration of softwood and eucalyptus black liquor through 15 and 150kDa ceramic membranes. Lignin-oils with similar oxygen content were produced regardless of origin and fractionation technique. A lignin-oil with favourable properties as precursor for refinery integration for jet fuel production as produced in small-scale batch experiments using nickel-based catalyst. Stable pumpable oils with melting point of less than 25-50 deg C and with 20-30% lower oxygen content and aromatic content were obtained that would be suitable as jet fuel precursors. The estimated production cost was found to be competitive with that of other liquid biofuels, while additional revenues could potentially be achieved by also producing chemical and materials from suitable fractions of the lignin-oil.

Background: Experimental autoimmune encephalomyelitis (EAE) is a commonly used experimental model for multiple sclerosis (MS). Experience with this model mainly comes from the field of immunology, while data on its use in studying the neurodegenerative aspects of MS is scarce.New method: The aim of this study is to improve and refine methods to assess neurodegeneration and function in EAE. Using the rotarod, a tool used in neuroscience to monitor motor performance, we evaluated the correlation between motor performance, disease severity as measured using a clinical scale and area covered by inflammatory lesions.Results: The included parameters are highly correlated in a non-linear manner, with motor performance rapidly decreasing in the intermediate values of the clinical scale. The relation between motor performance and histopathological damage is exclusively determined by lesions in the ventral and lateral columns, based on a new method of analysis of the entire spinal cord. Using a set of definitions for distinct disease milestones, we quantified disease duration as well as severity.Comparison with existing methods: The rotarod measures motor performance in a more objective and quantitative manner compared to using a clinical score. The outcome showes a strong correlation to the surface area of inflammatory lesions in the motor systems of the spinal cord.Conclusions: These results provide an improved workflow for interpreting the outcome of EAE from a neurological point of view, with the eventual goal of dissecting neurodegeneration and evaluating neuroprotective drugs in EAE for application in MS. (C) 2016 Elsevier B.V. All rights reserved.

Brief, intermittent cardiopulmonary resuscitation (CPR) training sessions, "Booster Trainings," improve CPR skill acquisition and short-term retention. The objective of this study was to incorporate arterial blood pressure (ABP) tracings into Booster Trainings to improve CPR skill retention. We hypothesized that ABP-directed CPR "Booster Trainings" would improve intensive care unit (ICU) provider 3-month retention of excellent CPR skills without need for interval retraining.A CPR manikin creating a realistic relationship between chest compression depth and ABP was used for training/testing. Thirty-six ICU providers were randomized to brief, bedside ABP-directed CPR manikin skill retrainings: (1) Booster Plus (ABP visible during training and testing) versus (2) Booster Alone (ABP visible only during training, not testing) versus (3) control (testing, no intervention). Subjects completed skill tests pretraining (baseline), immediately after training (acquisition), and then retention was assessed at 12 hours, 3 and 6 months. The primary outcome was retention of excellent CPR skills at 3 months. Excellent CPR was defined as systolic blood pressure of 100 mm Hg or higher and compression rate 100 to 120 per minute.Overall, 14 of 24 (58%) participants acquired excellent CPR skills after their initial training (Booster Plus 75% vs 50% Booster Alone, P = 0.21). Adjusted for age, ABP-trained providers were 5.2× more likely to perform excellent CPR after the initial training (95% confidence interval [95% CI], 1.3-21.2; P = 0.02), and to retain these skills at 12 hours (adjusted odds ratio, 4.4; 95% CI, 1.3-14.9; P = 0.018) and 3 months (adjusted odds ratio, 4.1; 95% CI, 1.2-13.9; P = 0.023) when compared to baseline performance.The ABP-directed CPR booster trainings improved ICU provider 3-month retention of excellent CPR skills without the need for interval retraining.