A Transdisciplinary Complex Adaptive Systems (T-CAS) Approach to Developing a National School-Based Culture of Prevention for Health Improvement: the School Health Research Network (SHRN) in Wales.

The paper reflects on a transdisciplinary complex adaptive systems (T-CAS) approach to the development of a school health research network (SHRN) in Wales for a national culture of prevention for health improvement in schools. A T-CAS approach focuses on key stages and activities within a continuous network cycle to facilitate systems level change. The theory highlights the importance of establishing transdisciplinary strategic partnerships to identify and develop opportunities for system reorientation. Investment in and the linking of resources develops the capacity for key social agents to take advantage of disruption points in the re-orientated system, and engagement activities develop the network to facilitate new social interactions and opportunities for transdisciplinary activities. A focus on transdisciplinary action research to co-produce interventions, generate research evidence and inform policy and practice is shown to play an important part in developing new normative processes that act to self-regulate the emerging system. Finally, the provision of reciprocal network benefits provides critical feedback loops that stabilise the emerging adaptive system and promote the network cycle. SHRN is shown to have embedded itself in the system by securing sustainability funding from health and education, a key role in national and regional planning and recruiting every eligible school to the network. It has begun to reorient the system to one of evidence generation (56 research studies co-produced) and opportunities for data-led practice at multiple levels. Further capacity development will be required to capitalise on these. The advantages of a complex systems approach to address barriers to change and the transferability of a T-CAS network approach across settings and cultures are highlighted.

Code Team Structure and Training in the Pediatric Resuscitation Quality International Collaborative.

OBJECTIVES: Code team structure and training for pediatric in-hospital cardiac arrest are variable. There are no data on the optimal structure of a resuscitation team. The objective of this study is to characterize the structure and training of pediatric code teams in sites participating in the Pediatric Resuscitation Quality Collaborative. METHODS: From May to July 2017, an anonymous voluntary survey was distributed to 18 sites in the international Pediatric Resuscitation Quality Collaborative. The survey content was developed by the study investigators and iteratively adapted by consensus. Descriptive statistics were calculated. RESULTS: All sites have a designated code team and hospital-wide code team activation system. Code team composition varies greatly across sites, with teams consisting of 3 to 17 members. Preassigned roles for code team members before the event occur at 78% of sites. A step stool and backboard are used during resuscitations in 89% of surveyed sites. Cardiopulmonary resuscitation (CPR) feedback is used by 72% of the sites. Of those sites that use CPR feedback, all use an audiovisual feedback device incorporated into the defibrillator and 54% use a CPR coach. Multidisciplinary and simulation-based code team training is conducted by 67% of institutions. CONCLUSIONS: Code team structure, equipment, and training vary widely in a survey of international children's hospitals. The variations in team composition, role assignments, equipment, and training described in this article will be used to facilitate future studies regarding the impact of structure and training of code teams on team performance and patient outcomes.

Pandemics and Beyond: Considerations When Personal Risk and Professional Obligations Converge.

With each novel infectious disease outbreak, there is scholarly attention to healthcare providers' obligation to assume personal risk while they care for infected patients. While most agree that healthcare providers have a duty to assume some degree of risk, the extent of this obligation remains uncertain. Furthermore, these analyses rarely examine healthcare institutions' obligations during these outbreaks. As a result, there is little practical guidance for healthcare institutions that are forced to weigh whether or when to exclude healthcare providers from providing care or allow them to opt out from providing care to protect themselves. This article uses the COVID-19 pandemic to examine the concept of risk and the professional duties of both healthcare providers and healthcare institutions, and proposes a framework that can be used to make concrete institutional policy choices. This framework should be a useful tool for any hospital, clinic, or health agency that must make these choices during the current pandemic and beyond.

Age-Based Percentiles of Measured Mean Arterial Pressure in Pediatric Patients in a Hospital Setting.

OBJECTIVES: To develop and validate age-specific percentile curves of measured mean arterial pressure for children in a hospital setting. DESIGN: Retrospective observational study of electronic records. SETTING: Tertiary care, freestanding pediatric hospital in Seattle, WA. PATIENTS: Nonpremature children, birth to 18 years old, evaluated in the emergency room, or admitted to either acute care or critical care units. INTERVENTIONS: Oscillometric blood pressure data collected from February 2012 to June 2016 were examined for documentation of systolic, diastolic, and mean arterial pressure values. Quantile curves were developed using restricted cubic splines and validated with two sets of patient data. The effects of birth sex and behavioral state on the curves were examined. The frequency of values less than 5th percentile for mean arterial pressure within a population was compared with four published criteria for hypotension. MEASUREMENTS AND MAIN RESULTS: Eighty-five-thousand two-hundred ninety-eight patients (47% female) provided 2,385,122 mean arterial pressure readings to develop and validate age-based distributions to create percentile curves and a reference table. The behavior state of patients affected the curves, with disturbed behavior state more prevalent in toddler-aged patients. There was no clinical difference between females and males within age brackets. Mean arterial pressure quantiles identified additional hypotensive episodes as compared with systolic blood pressure thresholds and predicted mean arterial pressure values. Code and data available at: https://osf.io/upqtv/. CONCLUSIONS: This is the first study reporting age-specific quantiles of measured mean arterial pressure in children in a hospital setting. The percentile curves may guide care in illnesses when perfusion pressure is critical and serve as parameter for bedside and electronic record-based response to clinical change. Future work to correlate threshold mean arterial pressure values with outcomes would be feasible based on quantile curves.

Outcomes After In-Hospital Pediatric Recurrent Cardiac Arrests.

OBJECTIVES: The objective of this study is to determine outcomes of recurrent cardiac arrest events in the general pediatric inpatient population. DESIGN: Retrospective cohort study of inpatients in a single institution. SETTING: A tertiary care free-standing children's hospital. PATIENTS: All patients less than 18 years old at Seattle Children's Hospital with recurrent cardiac arrest events occurring from January 1, 2010, to March 1, 2018, were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall survival to hospital discharge was 50% and all survivors had a good neurologic outcome, defined as Pediatric Cerebral Performance Category of 3 or less, or unchanged from baseline. Survival among patients who received extracorporeal life support was 43% and among those who received extracorporeal cardiopulmonary resuscitation, 33%. Initial arrest factors associated with survival included initial rhythm of ventricular tachycardia or ventricular fibrillation, shorter duration of cardiopulmonary resuscitation, and absence of multiple organ dysfunction. Additionally, nonsurvivors had more severe metabolic acidosis in the prearrest and postarrest period. CONCLUSIONS: Survival after pediatric in-hospital recurrent cardiac arrest is higher than previously reported. There is also evidence that initial rhythm other than ventricular tachycardia/ventricular fibrillation and longer duration of cardiopulmonary resuscitation as well as multiple organ dysfunction and more severe lactic acidosis in the peri-arrest period are associated with poor outcomes.

Nasal high flow therapy introduction lowers reintubation risk in a Peruvian paediatric intensive care unit.

AIM: We examined the impact of introducing high-flow nasal oxygen therapy (HFNT) on children under five with post-extubation respiratory failure in a paediatric intensive care unit (PICU) in Peru. METHODS: This quasi-experimental study compared clinical outcomes before and after initial HFNT deployment in the PICU at Instituto Nacional de Salud del Niño in Lima in June 2016. We compared three groups: 29 received post-extubation HFNT and 17 received continuous positive airway pressure (CPAP) from 2016-17 and 12 historical controls received CPAP from 2012-16. The primary outcome was the need for mechanical ventilation. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated via survival analysis. RESULTS: High-flow nasal oxygen therapy and CPAP did not alter the need for mechanical ventilation after extubation (aHR 0.47, 95% CI 0.15-1.48 and 0.96, 95% CI 0.35-2.62, respectively) but did reduce the risk of reintubation (aHR 0.18, 95% CI 0.06-0.57 and 0.14, 95% CI 0.03-0.72, respectively). PICU length of stay was 11, 18 and 37 days for CPAP, HFNT and historical CPAP and mortality was 12%, 7% and 27%, respectively. There was no effect on the duration of sedative infusions. CONCLUSION: High-flow nasal oxygen therapy provided effective support for some children, but larger studies in resource-constrained settings are needed.

Cardiopulmonary Resuscitation in the Pediatric Cardiac Catheterization Laboratory: A Report From the American Heart Association's Get With the Guidelines-Resuscitation Registry.

OBJECTIVES: Hospitalized children with underlying heart disease are at high risk for cardiac arrest, particularly when they undergo invasive catheterization procedures for diagnostic and therapeutic interventions. Outcomes for children experiencing cardiac arrest in the cardiac catheterization laboratory remain under-reported with few studies reporting survival beyond the catheterization laboratory. We aim to describe survival outcomes after cardiac arrest in the cardiac catheterization laboratory while identifying risk factors associated with hospital mortality after these events. DESIGN: Retrospective observational study of data from a multicenter cardiac arrest registry from November 2005 to November 2016. Cardiac arrest in the cardiac catheterization laboratory was defined as the need for chest compressions greater than or equal to 1 minute in the cardiac catheterization laboratory. Primary outcome was survival to discharge. Variables analyzed using generalized estimating equations for association with survival included age, illness category (surgical cardiac, medical cardiac), preexisting conditions, pharmacologic interventions, and event duration. SETTING: American Heart Association's Get With the Guidelines-Resuscitation registry of in-hospital cardiac arrest. PATIENTS: Consecutive patients less than 18 years old experiencing an index (i.e., first) cardiac arrest event reported to the Get With the Guidelines-Resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 203 patients met definition of index cardiac arrest in the cardiac catheterization laboratory composed primarily of surgical and medical cardiac patients (54% and 41%, respectively). Children less than 1 year old comprised the majority of patients, 58% (117/203). Overall survival to hospital discharge was 69% (141/203). No differences in survival were observed between surgical and medical cardiac patients (p = 0.15). The majority of deaths (69%, 43/62) occurred in patients less than 1 year old. Bradycardia (with pulse) followed by pulseless electrical activity/asystole were the most common first documented rhythms observed (50% and 27%, respectively). Preexisting metabolic/electrolyte abnormalities (p = 0.02), need for vasoactive infusions (p = 0.03) prior to arrest, and use of calcium products (p = 0.005) were found to be significantly associated with lower rates of survival to discharge on multivariable regression. CONCLUSIONS: The majority of children experiencing cardiac arrest in the cardiac catheterization laboratory in this large multicenter registry analysis survived to hospital discharge, with no observable difference in outcomes between surgical and medical cardiac patients. Future investigations that focus on stratifying medical complexity in addition to procedural characteristics at the time of catheterization are needed to better identify risks for mortality after cardiac arrest in the cardiac catheterization laboratory.

Emergency department risk factors for serious clinical deterioration in a paediatric hospital in Peru.

AIM: Identification of critically ill children upon presentation to the emergency department (ED) is challenging, especially when resources are limited. The objective of this study was to identify ED risk factors associated with serious clinical deterioration (SCD) during hospitalisation in a resource-limited setting. METHODS: A retrospective case-control study of children less than 18 years of age presenting to the ED in a large, freestanding children's hospital in Peru was performed. Cases had SCD during the first 7 days of hospitalisation whereas controls did not. Information collected during initial ED evaluation was used to identify risk factors for SCD. RESULTS: A total of 120 cases and 974 controls were included. In univariate analysis, young age, residence outside Lima, evaluation at another facility prior to ED presentation, congenital malformations, abnormal neurologic baseline, co-morbidities and a prior paediatric intensive care unit admission were associated with SCD. In multivariate analysis, age < 12 months, residence outside Lima and evaluation at another facility prior to ED presentation remained associated with SCD. In addition, comatose neurological status, hypoxaemia, tachycardia, tachypnoea and temperature were also associated with SCD. CONCLUSIONS: Many risk factors for SCD during hospitalisation can be identified upon presentation to the ED. Using these factors to adjust monitoring during and after the ED stay has the potential to decrease SCD events. Further studies are needed to determine whether this holds true in other resource-limited settings.

Implementation of a Cooking Bus intervention to support cooking in schools in Wales, UK.

PURPOSE: The teaching of cooking is an important aspect of school-based efforts to promote healthy diets among children, and is frequently done by external agencies. Within a limited evidence base relating to cooking interventions in schools, there are important questions about how interventions are integrated within school settings. The purpose of this paper is to examine how a mobile classroom (Cooking Bus) sought to strengthen connections between schools and cooking, and drawing on the concept of the sociotechnical network, theorise the interactions between the Bus and school contexts. DESIGN/METHODOLOGY/APPROACH: Methods comprised a postal questionnaire to 76 schools which had received a Bus visit, and case studies of the Bus' work in five schools, including a range of school sizes and urban/rural locations. Case studies comprised observation of Cooking Bus sessions, and interviews with school staff. FINDINGS: The Cooking Bus forged connections with schools through aligning intervention and schools' goals, focussing on pupils' cooking skills, training teachers and contributing to schools' existing cooking-related activities. The Bus expanded its sociotechnical network through post-visit integration of cooking activities within schools, particularly teachers' use of intervention cooking kits. RESEARCH LIMITATIONS/IMPLICATIONS: The paper highlights the need for research on the long-term impacts of school cooking interventions, and better understanding of the interaction between interventions and school contexts. ORIGINALITY/VALUE: This paper adds to the limited evidence base on school-based cooking interventions by theorising how cooking interventions relate to school settings, and how they may achieve integration.

Identifying High-Risk Children in the Emergency Department.

PURPOSE: Early warning scores (EWS) identify high-risk hospitalized patients prior to clinical deterioration; however, their ability to identify high-risk pediatric patients in the emergency department (ED) has not been adequately evaluated. We sought to determine the association between modified pediatric EWS (MPEWS) in the ED and inpatient ward-to-pediatric intensive care unit (PICU) transfer within 24 hours of admission. METHODS: This is a case-control study of 597 pediatric ED patients admitted to the inpatient ward at Seattle Children's Hospital between July 1, 2010, and December 31, 2011. Cases were children subsequently transferred to the PICU within 24 hours, whereas controls remained hospitalized on the inpatient ward. The association between MPEWS in the ED and ward-to-PICU transfer was determined by chi-square analysis. RESULTS: Fifty children experienced ward-to-PICU transfer within 24 hours of admission. The area under the receiver-operator characteristic curve was 0.691. Children with MPEWS > 7 in the ED were more likely to experience ward-to-PICU transfer (odds ratio 8.36, 95% confidence interval 2.98-22.08); however, the sensitivity was only 18.0% with a specificity of 97.4%. Using MPEWS >7 for direct PICU admission would have led to 167 unnecessary PICU admissions and identified only 9 of 50 patients who required PICU care. CONCLUSIONS: Elevated MPEWS in the ED is associated with increased risk of ward-to-PICU transfer within 24 hours of admission; however, an MPEWS threshold of 7 is not sufficient to identify more than a small proportion of ward-admitted children with subsequent clinical deterioration.

Systematic Review and Meta-Analysis of End-Tidal Carbon Dioxide Values Associated With Return of Spontaneous Circulation During Cardiopulmonary Resuscitation.

OBJECTIVE: End-tidal carbon dioxide (ETCO(2)) measurements during cardiopulmonary resuscitation (CPR) reflect variable cardiac output over time, and low values have been associated with decreased survival. The goals of this review are to confirm and quantify this relationship and to determine the mean ETCO(2) value among patients with return of spontaneous circulation (ROSC) as an initial step toward determining an appropriate target for intervention during resuscitation in the absence of prospective data. DATA SOURCES AND STUDY SELECTION: The PubMed database was searched for the key words "end-tidal carbon dioxide" or "capnometry" or "capnography" and "resuscitation" or "return of spontaneous circulation." Randomized controlled trials, cohort studies, or case-control studies that reported ETCO(2) values for participants with and without ROSC were included. DATA EXTRACTION AND SYNTHESIS: Twenty-seven studies met the inclusion criteria for qualitative synthesis. Twenty studies were included in determination of average ETCO(2) values. The mean ETCO(2) in participants with ROSC was 25.8 ± 9.8 mm Hg versus 13.1 ± 8.2 mm Hg (P = .001) in those without ROSC. Nineteen studies were included in a meta-analysis. The mean difference in ETCO(2) was 12.7 mm Hg (95% confidence interval: 10.3-15.1) between participants with and without ROSC (P < .001). The mean difference in ETCO(2) was not modified by the receipt of sodium bicarbonate, uncontrolled minute ventilation, or era of resuscitation guidelines. The overall quality of data by Grades of Recommendations, Assessment, Development and Evaluation criteria is very low, but no prospective data are currently available. CONCLUSIONS: Participants with ROSC after CPR have statistically higher levels of ETCO(2). The average ETCO(2) level of 25 mm Hg in participants with ROSC is notably higher than the threshold of 10 to 20 mm Hg to improve delivery of chest compressions. The ETCO(2) goals during resuscitation may be higher than previously suggested and further investigation into appropriate targets during resuscitation is needed to diminish morbidity and mortality after cardiorespiratory arrest.

Change in fractional anisotropy during treatment of diabetic ketoacidosis in children.

BACKGROUND: The pathophysiology resulting in cerebral edema in pediatric diabetic ketoacidosis (DKA) is unknown. To investigate the changes in white matter microstructure in this disease, we measured diffusion tensor imaging (DTI) parameters, including apparent diffusion coefficient (ADC), fractional anisotropy (FA), and radial and axial diffusivity in children with DKA at two time points during treatment. METHODS: A prospective observational study was conducted at Seattle Children's Hospital, Seattle, WA. Thirty-two children admitted with DKA (pH < 7.3, bicarbonate < 15 mEq/l, glucose > 300 mg/dl, and ketosis; 11.9 ± 3.2 y; and 47% male) were enrolled and underwent two serial paired diffusion magnetic resonance imaging (MRI) scans following hospital admission. Seventeen of the 32 participants had diffusion tensor images of adequate quality for tract-based spatial statistics (TBSS) analysis. RESULTS: TBSS mapping demonstrated main white matter tract areas with a significant increase in FA and areas with a significant decrease in ADC, from the first to the second MRI. Both radial and axial diffusivity terms showed change, with a diffuse pattern of involvement. CONCLUSION: Consistent DTI changes occurred during DKA treatment over a short time frame. These findings describe widespread water diffusion abnormalities in DKA, supporting an association between clinical illness and DTI markers of microstructural change in white matter.

Outcome of pediatric hematopoietic stem cell transplant recipients requiring mechanical ventilation.

PURPOSE: To assess the risk factors for intensive care unit admission among children receiving hematopoietic stem cell transplantation (HSCT) and to test the hypothesis that multiple organ failure (MOF) increases the odds of death among HSCT patients who receive mechanical ventilation (MV). METHODS: The chart of all consecutive HSCTs at Seattle Children's Hospital and pediatric HSCT patients admitted to the pediatric critical care unit of a tertiary care pediatric hospital from January 2000 to September 2006 were reviewed retrospectively. RESULTS: Charts of 266 HSCT patients were reviewed. Nonmalignant disease compared to hematologic malignancy, acute graft versus host disease grades III and IV, and second transplant increased the odds of pediatric intensive care unit admission. Among patients receiving MV for >24 hours, 9 (25%) survived for 6 months, while 8 patients (22%) were long-term survivors with a median follow-up time of 3.6 years, a significant improvement compared to a long-term survival of 7% (odds ratio 0.25, 95% confidence intervals: 0.09-0.72, P = .01) reported in a previously published cohort of pediatric HSCT patients at the same institution from 1983 to 1996. Cardiovascular failure, duration of MV for greater than 1 week, and prolonged receipt of continuous renal replacement therapy (CRRT) increased the risk of mortality. CONCLUSIONS: Six-month survival of pediatric HSCT patients was 25% and the odds of death were increased by cardiovascular failure but not by MOF. Receipt of mechanical support (ventilation, CRRT) or cardiovascular support (inotropic agents) decreased the likelihood of long-term survival.

Transcranial Doppler-based assessment of cerebral autoregulation in critically ill children during diabetic ketoacidosis treatment.

OBJECTIVES: Impaired cerebral autoregulation may be associated with poor outcome in diabetic ketoacidosis. We examined change in cerebral autoregulation during diabetic ketoacidosis treatment. DESIGN: Prospective observational cohort study. SETTING: Tertiary care children's hospital. PATIENTS/SUBJECTS: Children admitted to the ICU with diabetic ketoacidosis (venous pH < 7.3, glucose > 300 mg/dL, HCO3 < 15 mEq/L, and ketonuria) constituted cases, and children with type I diabetes without diabetic ketoacidosis constituted controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between 2005 and 2009, 32 cases and 50 controls were enrolled. Transcranial Doppler ultrasonography was used to measure middle cerebral artery flow velocities, and cerebral autoregulation testing was achieved via tilt-table testing. Cases underwent two and controls underwent one cerebral autoregulation test. Cerebral autoregulation was quantified by the autoregulatory index (autoregulatory index < 0.4 = impaired and autoregulatory index 0.4-1.0 = intact autoregulation). The first autoregulation test was obtained early (time 1, 12-24 hr; median [interquartile range], 8 hr [5-18 hr]) during diabetic ketoacidosis treatment, and a second autoregulation test was obtained during recovery (time 2, 36-72 hr; median [ interquartile range], 46 hr [40-59 hr]) from time 0 (defined as time of insulin start). Cases had lower autoregulatory index at time 1 than time 2 (p < 0.001) as well lower autoregulatory index than control subjects (p < 0.001). Cerebral autoregulation was impaired in 40% (n = 13) of cases at time 1 and in 6% (n = 2) of cases at time 2. Five cases (17%) showed persistent impairment of cerebral autoregulation between times 1 and 2 of treatment. All control subjects had intact cerebral autoregulation. CONCLUSIONS: Impaired cerebral autoregulation was common early during diabetic ketoacidosis treatment. Although the majority improved during diabetic ketoacidosis treatment, 17% of subjects had impairment between 36 and 72 hours after start of insulin therapy. The observed impaired cerebral autoregulation appears specific to the diabetic ketoacidosis process in patients with type I diabetes.

Postcardiac Arrest Care Delivery in Pediatric Intensive Care Units: A Plan and Call to Action.

Background: Despite national pediatric postcardiac arrest care (PCAC) guidelines to improve neurological outcomes and survival, there are limited studies describing PCAC delivery in pediatric institutions. This study aimed to describe PCAC delivery in centers belonging to a resuscitation quality collaborative. Methods: An institutional review board-approved REDCap survey was distributed electronically to the lead resuscitation investigator at each institution in the international Pediatric Resuscitation Quality Improvement Collaborative. Data were summarized using descriptive statistics. A chi-square test was used to compare categorical data. Results: Twenty-four of 47 centers (51%) completed the survey. Most respondents (58%) belonged to large centers (>1,000 annual pediatric intensive care unit admissions). Sixty-seven percent of centers reported no specific process to initiate PCAC with the other third employing order sets, paper forms, or institutional guidelines. Common PCAC targets included temperature (96%), age-based blood pressure (88%), and glucose (75%). Most PCAC included electroencephalogram (75%), but neuroimaging was only included at 46% of centers. Duration of PCAC was either tailored to clinical improvement and neurological examination (54%) or time-based (45%). Only 25% of centers reported having a mechanism for evaluating PCAC adherence. Common barriers to effective PCAC implementation included lack of time and limited training opportunities. Conclusions: There is wide variation in PCAC delivery among surveyed pediatric institutions despite national guidelines to standardize and implement PCAC.

A randomized trial of increasing patching for amblyopia.

OBJECTIVE: After treatment with refractive correction and patching, some patients have residual amblyopia resulting from strabismus or anisometropia. We conducted a clinical trial to evaluate the effectiveness of increasing prescribed daily patching from 2 to 6 hours in children with stable residual amblyopia. DESIGN: Prospective, randomized, multicenter clinical trial. PARTICIPANTS: A total of 169 children aged 3 to <8 years (mean, 5.9 years) with stable residual amblyopia (20/32-20/160) after 2 hours of daily patching for at least 12 weeks. INTERVENTION: Random assignment to continue 2 hours of daily patching or increase patching time to an average of 6 hours/day. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA) in the amblyopic eye after 10 weeks. RESULTS: Baseline VA was 0.44 logarithm of the minimum angle of resolution (logMAR) (20/50(-2)). Ten weeks after randomization, amblyopic eye VA had improved an average of 1.2 lines in the 6-hour group and 0.5 line in the 2-hour group (difference in mean VA adjusted for acuity at randomization = 0.6 line; 95% confidence interval, 0.3-1.0; P = 0.002). Improvement of 2 or more lines occurred in 40% of participants patched for 6 hours versus 18% of those who continued to patch for 2 hours (P = 0.003). CONCLUSIONS: When amblyopic eye VA stops improving with 2 hours of daily patching, increasing the daily patching dosage to 6 hours results in more improvement in VA after 10 weeks compared with continuing 2 hours daily.

CPR quality and outcomes after extracorporeal life support for pediatric In-Hospital cardiac arrest.

AIM OF STUDY: To determine outcomes in pediatric patients who had an in-hospital cardiac arrest and subsequently received extracorporeal cardiopulmonary resuscitation (ECPR). Our secondary objective was to identify cardiopulmonary resuscitation (CPR) event characteristics and CPR quality metrics associated with survival after ECPR. METHODS: Multicenter retrospective cohort study of pediatric patients in the pediRES-Q database who received ECPR after in-hospital cardiac arrest between July 1, 2015 and June 2, 2021. Primary outcome was survival to ICU discharge. Secondary outcomes were survival to hospital discharge and favorable neurologic outcome at ICU and hospital discharge. RESULTS: Among 124 patients included in this study, median age was 0.9 years (IQR 0.2-5) and the majority of patients had primarily cardiac disease (92 patients, 75%). Survival to ICU discharge occurred in 61/120 (51%) patients, 36/61 (59%) of whom had favorable neurologic outcome. No demographic or clinical variables were associated with survival after ECPR. CONCLUSION: In this multicenter retrospective cohort study of pediatric patients who received ECPR for IHCA we found a high rate of survival to ICU discharge with good neurologic outcome.

Effects of melatonin and its receptor antagonist on retinal pigment epithelial cells against hydrogen peroxide damage.

PURPOSE: Recently, we reported finding that circulating melatonin levels in age-related macular degeneration patients were significantly lower than those in age-matched controls. The purpose of this study was to investigate the hypothesis that melatonin deficiency may play a role in the oxidative damage of the retinal pigment epithelium (RPE) by testing the protective effect of melatonin and its receptor antagonist on RPE cells exposed to H(2)O(2) damage. METHODS: Cultured human RPE cells were subjected to oxidative stress induced by 0.5 mM H(2)O(2). Cell viability was measured using the microculture tetrazoline test (MTT) assay. Cells were pretreated with or without melatonin for 24 h. Luzindole (50 µM), a melatonin membrane-receptor antagonist, was added to the culture 1 h before melatonin to distinguish direct antioxidant effects from indirect receptor-dependent effects. All tests were performed in triplicate. RESULTS: H(2)O(2) at 0.5 mM decreased cell viability to 20% of control levels. Melatonin showed dose-dependent protective effects on RPE cells against H(2)O(2). Cell viability of RPE cells pretreated with 10(-10), 10(-8), 10(-6), and 10(-4) M melatonin for 24 h was 130%, 160%, 187%, and 230% of cells treated with H(2)O(2) alone (all p<0.05). Using cells cultured without H(2)O(2) as the control, cell viability of cells treated with H(2)O(2) after pretreatment with 10(-10)-10(-4) M melatonin was still significantly lower than that of the controls, suggesting that melatonin significantly decreased but did not completely abolish the in vitro cytotoxic effects of H(2)O(2). Luzindole completely blocked melatonin's protective effects at low concentrations of melatonin (10(-10)-10(-8) M) but not at high concentrations (10(-6)-10(-4) M). CONCLUSIONS: Melatonin has a partial protective effect on RPE cells against H(2)O(2) damage across a wide range of concentrations (10(-10)-10(-4) M). This protective effect occurs through the activation of melatonin membrane receptors at low concentrations (10(-10)-10(-8) M) and through both the direct antioxidant and indirect receptor activation effects at high concentrations (10(-6)-10(-4) M).

In vitro phototoxicity and hazard identification of nano-scale titanium dioxide.

Titanium dioxide nanoparticles (nano-TiO(2)) catalyze reactions under UV radiation and are hypothesized to cause phototoxicity. A human-derived line of retinal pigment epithelial cells (ARPE-19) was treated with six samples of nano-TiO(2) and exposed to UVA radiation. The TiO(2) nanoparticles were independently characterized to have mean primary particle sizes and crystal structures of 22nm anatase/rutile, 25nm anatase, 31nm anatase/rutile, 59nm anatase/rutile, 142nm anatase, and 214nm rutile. Particles were suspended in cell culture media, sonicated, and assessed for stability and aggregation by dynamic light scattering. Cells were treated with 0, 0.3, 1, 3, 10, 30, or 100µg/ml nano-TiO(2) in media for 24hrs and then exposed to UVA (2hrs, 7.53J/cm(2)) or kept in the dark. Viability was assessed 24hrs after the end of UVA exposure by microscopy with a live/dead assay (calcein-AM/propidium iodide). Exposure to higher concentrations of nano-TiO(2) with UVA lowered cell viability. The 25nm anatase and 31nm anatase/rutile were the most phototoxic (LC(50) with UVA<5µg/ml), while the 142nm anatase and 214nm rutile were the least phototoxic. An acellular assay ranked TiO(2) nanoparticles for their UVA photocatalytic reactivities. The particles were found to be capable of generating thiobarbituric acid reactive substances (TBARS) under UVA. Flow cytometry showed that nano-TiO(2) combined with UVA decreased cell viability and increased the generation of reactive oxygen species (ROS, measured by Mitosox). LC(50) values under UVA were correlated with TBARS reactivity, particle size, and surface area.

Phototoxicity of nano titanium dioxides in HaCaT keratinocytes--generation of reactive oxygen species and cell damage.

Nano-sized titanium dioxide (TiO(2)) is among the top five widely used nanomaterials for various applications. In this study, we determine the phototoxicity of TiO(2) nanoparticles (nano-TiO(2)) with different molecular sizes and crystal forms (anatase and rutile) in human skin keratinocytes under UVA irradiation. Our results show that all nano-TiO(2) particles caused phototoxicity, as determined by the MTS assay and by cell membrane damage measured by the lactate dehydrogenase (LDH) assay, both of which were UVA dose- and nano-TiO(2) dose-dependent. The smaller the particle size of the nano-TiO(2) the higher the cell damage. The rutile form of nano-TiO(2) showed less phototoxicity than anatase nano-TiO(2). The level of photocytotoxicity and cell membrane damage is mainly dependent on the level of reactive oxygen species (ROS) production. Using polyunsaturated lipids in plasma membranes and human serum albumin as model targets, and employing electron spin resonance (ESR) oximetry and immuno-spin trapping as unique probing methods, we demonstrated that UVA irradiation of nano-TiO(2) can induce significant cell damage, mediated by lipid and protein peroxidation. These overall results suggest that nano-TiO(2) is phototoxic to human skin keratinocytes, and that this phototoxicity is mediated by ROS generated during UVA irradiation.