The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.

Lactate, Base Excess, and the Pediatric Index of Mortality: Exploratory Study of an International, Multicenter Dataset.

OBJECTIVES: To investigate the relationship between ICU admission blood lactate, base excess, and ICU mortality and to explore the effect of incorporating blood lactate into the Pediatric Index of Mortality. DESIGN: Retrospective cohort study based on data prospectively collected on every PICU admission submitted to the U.K. Pediatric Intensive Care Audit Network and to the Australia and New Zealand Pediatric Intensive Care Registry. SETTING: Thirty-three PICUs in the United Kingdom/Republic of Ireland and nine PICUs and 20 general ICUs in Australia and New Zealand. PATIENTS: All ICU admissions between January 1, 2012, and December 31, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three thousand two hundred fifty-two admissions were recorded in both datasets; 81,576 (66.2%) in the United Kingdom/Republic of Ireland and 41,676 (33.8%) in Australia and New Zealand. Of these 75,070 (61%) had a base excess recorded, 63,316 (51%) had a lactate recorded, and 60,876 (49%) had both base excess and lactate recorded. Median lactate value was 1.5 mmol/L (interquartile range, 1-2.4 mmol/L) (United Kingdom/Republic of Ireland: 1.5 [1-2.5]; Australia and New Zealand: 1.4 [1-2.3]). Children with a lactate recorded had a higher illness severity, were more likely to be invasively ventilated, admitted after cardiac surgery, and had a higher mortality rate, compared with admissions with no lactate recorded (p < 0.001). The relationship between lactate and mortality was stronger (odds ratio, 1.32; 95% CI, 1.31-1.34) than between absolute base excess and mortality (odds ratio, 1.13; 95% CI, 1.12-1.14). Addition of lactate to the Pediatric Index of Mortality score led to a small improvement in performance over addition of absolute base excess, whereas adding both lactate and absolute base excess achieved the best performance. CONCLUSIONS: At PICU admission, blood lactate is more strongly associated with ICU mortality than absolute base excess. Adding lactate into the Pediatric Index of Mortality model may result in a small improvement in performance. Any improvement in Pediatric Index of Mortality performance must be balanced against the added burden of data capture when considering potential incorporation into the Pediatric Index of Mortality model.

Estimating the current and future prevalence of life-limiting conditions in children in England.

BACKGROUND: Previous studies showed increasing number of children with a life-limiting or life-threatening condition who may benefit from input from pediatric palliative care services. AIM: To estimate the current prevalence of children with a life-limiting condition and to model future prevalence of this population. DESIGN: Observational study using national inpatient hospital data. A population-based approach utilizing ethnic specific population projections was used to estimate future prevalence. SETTING/PARTICIPANTS: All children aged 0-19 years with a life-limiting condition diagnostic code recorded in Hospital Episodes Statistics data in England from 2000/01 to 2017/18. RESULTS: Data on 4,543,386 hospital episodes for 359,634 individuals were included. The prevalence of children with a life-limiting condition rose from 26.7 per 10,000 (95%CI 26.5-27.0) in 2001/02 to 66.4 per 10,000 (95% CI: 66.0-66.8) in 2017/18. Using a more restricted definition of a life-limiting condition reduced the prevalence from 66.4 to 61.1 per 10,000 (95%CI 60.7-61.5) in 2017/18. Highest prevalence was in the under 1-year age group at 226.5 per 10,000 and children with a congenital abnormality had the highest prevalence (27.2 per 10,000 (95%CI: 26.9-27.5)).The prevalence was highest among the most deprived group and in children of Pakistani origin.Predicted future prevalence of life-limiting conditions ranged from 67.0 (95%CI 67.7-66.3) to 84.22 (95%CI 78.66-90.17) per 10,000 by 2030. CONCLUSIONS: The prevalence of children with a life-limiting or life-threatening condition in England has risen over the last 17 years and is predicted to increase. Future data collections must include the data required to assess the complex health and social care needs of these children.

Effect of a Sedation and Ventilator Liberation Protocol vs Usual Care on Duration of Invasive Mechanical Ventilation in Pediatric Intensive Care Units: A Randomized Clinical Trial.

Importance: There is limited evidence on the optimal strategy for liberating infants and children from invasive mechanical ventilation in the pediatric intensive care unit. Objective: To determine if a sedation and ventilator liberation protocol intervention reduces the duration of invasive mechanical ventilation in infants and children anticipated to require prolonged mechanical ventilation. Design, Setting, and Participants: A pragmatic multicenter, stepped-wedge, cluster randomized clinical trial was conducted that included 17 hospital sites (18 pediatric intensive care units) in the UK sequentially randomized from usual care to the protocol intervention. From February 2018 to October 2019, 8843 critically ill infants and children anticipated to require prolonged mechanical ventilation were recruited. The last date of follow-up was November 11, 2019. Interventions: Pediatric intensive care units provided usual care (n = 4155 infants and children) or a sedation and ventilator liberation protocol intervention (n = 4688 infants and children) that consisted of assessment of sedation level, daily screening for readiness to undertake a spontaneous breathing trial, a spontaneous breathing trial to test ventilator liberation potential, and daily rounds to review sedation and readiness screening and set patient-relevant targets. Main Outcomes and Measures: The primary outcome was the duration of invasive mechanical ventilation from initiation of ventilation until the first successful extubation. The primary estimate of the treatment effect was a hazard ratio (with a 95% CI) adjusted for calendar time and cluster (hospital site) for infants and children anticipated to require prolonged mechanical ventilation. Results: There were a total of 8843 infants and children (median age, 8 months [interquartile range, 1 to 46 months]; 42% were female) who completed the trial. There was a significantly shorter median time to successful extubation for the protocol intervention compared with usual care (64.8 hours vs 66.2 hours, respectively; adjusted median difference, -6.1 hours [interquartile range, -8.2 to -5.3 hours]; adjusted hazard ratio, 1.11 [95% CI, 1.02 to 1.20], P = .02). The serious adverse event of hypoxia occurred in 9 (0.2%) infants and children for the protocol intervention vs 11 (0.3%) for usual care; nonvascular device dislodgement occurred in 2 (0.04%) vs 7 (0.1%), respectively. Conclusions and Relevance: Among infants and children anticipated to require prolonged mechanical ventilation, a sedation and ventilator liberation protocol intervention compared with usual care resulted in a statistically significant reduction in time to first successful extubation. However, the clinical importance of the effect size is uncertain. Trial Registration: isrctn.org Identifier: ISRCTN16998143.

Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

Patterns of Use of Heated Humidified High-Flow Nasal Cannula Therapy in PICUs in the United Kingdom and Republic of Ireland.

OBJECTIVES: To 1) describe patterns of use of high-flow nasal cannula therapy, 2) examine differences between patients started on high-flow nasal cannula and those started on noninvasive ventilation, and 3) explore whether patients who failed high-flow nasal cannula therapy were different from those who did not. DESIGN: Retrospective analysis of data collected prospectively by the Paediatric Intensive Care Audit Network. SETTING: All PICUs in the United Kingdom and Republic of Ireland (n = 34). PATIENTS: Admissions to study PICUs (2015-2016) receiving any form of respiratory support at any time during PICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eligible admissions were classified into nine groups based on the combination of the first-line and second-line respiratory support modes. Uni- and multivariate analyses were performed to test the association between PICU and patient characteristics and two outcomes: 1) use of high-flow nasal cannula versus noninvasive ventilation as first-line mode and 2) high-flow nasal cannula failure, requiring escalation to noninvasive ventilation and/or invasive ventilation. We analyzed data from 26,423 admissions; high-flow nasal cannula was used in 5,951 (22.5%) at some point during the PICU stay. High-flow nasal cannula was used for first-line support in 2,080 (7.9%) and postextubation support in 978 admissions (4.5% of patients extubated after first-line invasive ventilation). High-flow nasal cannula failure occurred in 559 of 2,080 admissions (26.9%) when used for first-line support. Uni- and multivariate analyses showed that PICU characteristics as well as patient age, primary diagnostic group, and admission type had a significant influence on the choice of first-line mode (high-flow nasal cannula or noninvasive ventilation). Younger age, unplanned admission, and higher admission severity of illness were independent predictors of high-flow nasal cannula failure. CONCLUSIONS: The use of high-flow nasal cannula is common in PICUs in the United Kingdom and Republic of Ireland. Variation in the choice of first-line respiratory support mode (high-flow nasal cannula or noninvasive ventilation) between PICUs reflects the need for clinical trial evidence to guide future practice.

Changing place of death in children who died after discharge from paediatric intensive care units: A national, data linkage study.

BACKGROUND: Although child mortality is decreasing, more than half of all deaths in childhood occur in children with a life-limiting condition whose death may be expected. AIM: To assess trends in place of death and identify characteristics of children who died in the community after discharge from paediatric intensive care unit. DESIGN: National data linkage study. SETTING/PARTICIPANTS: All children resident in England and Wales when admitted to a paediatric intensive care unit in the United Kingdom (1 January 2004 and 31 December 2014) were identified in the Paediatric Intensive Care Audit Network dataset. Linkage to death certificate data was available up to the end of 2014. Place of death was categorised as hospital (hospital or paediatric intensive care unit) or community (hospice, home or other) for multivariable logistic modelling. RESULTS: The cohort consisted of 110,328 individuals. In all, 7709 deaths occurred after first discharge from paediatric intensive care unit. Among children dying, the percentage in-hospital at the time of death decreased from 83.8% in 2004 to 68.1% in 2014; 852 (0.8%) of children were discharged to palliative care. Children discharged to palliative care were eight times more likely to die in the community than children who died and had not been discharged to palliative care (odds ratio = 8.06 (95% confidence interval = 6.50-10.01)). CONCLUSIONS: The proportion of children dying in hospital is decreasing, but a large proportion of children dying after discharge from paediatric intensive care unit continue to die in hospital. The involvement of palliative care at the point of discharge has the potential to offer choice around place of care and death for these children and families.

Renal Replacement Therapy in the Critically Ill Child.

OBJECTIVES: Although renal replacement therapy is widely used in critically ill children, there have been few comprehensive population-based studies of its use. This article describes renal replacement therapy use, and associated outcomes, in critically ill children across the United Kingdom in the largest cohort study of this patient group. DESIGN: A retrospective observational study using prospectively collected data. SETTING: Data from the Pediatric Intensive Care Audit Network database which collects data on all children admitted to U.K. PICUs. PATIENTS: Children (< 16 yr) in PICU who received renal replacement therapy between January 1, 2005, and December 31, 2012, were identified. INTERVENTIONS: Individual-level data including age, underlying diagnosis, modality (peritoneal dialysis and continuous extracorporeal techniques [continuous renal replacement therapy]), duration of renal replacement therapy, PICU length of stay, and survival were extracted. MEASUREMENTS AND MAIN RESULTS: Three-thousand eight-hundred twenty-five of 129,809 PICU admissions (2.9%) received renal replacement therapy in 30 of 33 centers. Volumes of renal replacement therapy varied considerably from 0% to 8.6% of PICU admissions per unit, but volume was not associated with patient survival. Overall survival to PICU discharge (73.8%) was higher than previous reports. Mortality risk was related to age, with lower risk in older children compared with neonates (odds ratio, 0.6; 95% CI, 0.5-0.8) although mortality did not increase over the age of 1 year; mode of renal replacement therapy, with lower risk in peritoneal dialysis than continuous renal replacement therapy methodologies (odds ratio, 0.7; 0.5-0.9); duration of renal replacement therapy (odds ratio, 1.02/d; 95% CI, 1.01-1.04); and primary diagnosis, with the lowest survival in liver disease patients (53.9%). CONCLUSIONS: This study describes current renal replacement therapy use across the United Kingdom and associated outcomes. We describe a number of factors associated with outcome, including age, underlying diagnosis, and renal replacement therapy modality which will need to be factored into future trial design.

Development of two socioeconomic indices for Saudi Arabia.

BACKGROUND: Health and socioeconomic status (SES) are linked in studies worldwide. Measures of SES exist for many countries, however not for Saudi Arabia (SA). We describe two indices of area-based SES for SA. METHODS: Routine census data has been used to construct two indices of SES at the geographically-delimited administrative region of Governorates in SA (n = 118). The data used included indicators of educational status, employment status, car and material ownership. A continuous measure of SES was constructed using exploratory factor analysis (EFA) and a categorical measure of SES using latent class analysis (LCA). Both indices were mapped by Governorates. RESULTS: The EFA identified three factors: The first explained 51.58% of the common variance within the interrelated factors, the second 15.14%, and the third 14.26%. These proportions were used in the formulation of the standard index. The scores were fixed to range from 100 for the affluent Governorate and 0 for the deprived. The LCA found a 4 class model as the best model fit. Class 1 was termed "affluent" and included 11.01% of Governorates, class 2 "upper middle class" (44.91%), class 3 "lower middle class" (33.05%) and class 4 "deprived" (11.01%). The populated urbanised Governorates were found to be the most affluent whereas the smaller rural Governorates were the most deprived. CONCLUSION: This is the first description of measures of SES in SA at a geographical level. Two measures have been successfully constructed and mapped. The maps show similar patterns suggesting validity. Both indices support the common perception of SES in SA.

Learning Through Chain Event Graphs: The Role of Maternal Factors in Childhood Type 1 Diabetes.

Chain event graphs (CEGs) are a graphical representation of a statistical model derived from event trees. They have previously been applied to cohort studies but not to case-control studies. In this paper, we apply the CEG framework to a Yorkshire, United Kingdom, case-control study of childhood type 1 diabetes (1993-1994) in order to examine 4 exposure variables associated with the mother, 3 of which are fully observed (her school-leaving-age, amniocenteses during pregnancy, and delivery type) and 1 with missing values (her rhesus factor), while incorporating previous type 1 diabetes knowledge. We conclude that the unknown rhesus factor values were likely to be missing not at random and were mainly rhesus-positive. The mother's school-leaving-age and rhesus factor were not associated with the diabetes status of the child, whereas having at least 1 amniocentesis procedure and, to a lesser extent, birth by cesarean delivery were associated; the combination of both procedures further increased the probability of diabetes. This application of CEGs to case-control data allows for the inclusion of missing data and prior knowledge, while investigating associations in the data. Communication of the analysis with the clinical expert is more straightforward than with traditional modeling, and this approach can be applied retrospectively or when assumptions for traditional analyses are not held.

A randomized trial of hyperglycemic control in pediatric intensive care.

BACKGROUND: Whether an insulin infusion should be used for tight control of hyperglycemia in critically ill children remains unclear. METHODS: We randomly assigned children (≤16 years of age) who were admitted to the pediatric intensive care unit (ICU) and were expected to require mechanical ventilation and vasoactive drugs for at least 12 hours to either tight glycemic control, with a target blood glucose range of 72 to 126 mg per deciliter (4.0 to 7.0 mmol per liter), or conventional glycemic control, with a target level below 216 mg per deciliter (12.0 mmol per liter). The primary outcome was the number of days alive and free from mechanical ventilation at 30 days after randomization. The main prespecified subgroup analysis compared children who had undergone cardiac surgery with those who had not. We also assessed costs of hospital and community health services. RESULTS: A total of 1369 patients at 13 centers in England underwent randomization: 694 to tight glycemic control and 675 to conventional glycemic control; 60% had undergone cardiac surgery. The mean between-group difference in the number of days alive and free from mechanical ventilation at 30 days was 0.36 days (95% confidence interval [CI], -0.42 to 1.14); the effects did not differ according to subgroup. Severe hypoglycemia (blood glucose, <36 mg per deciliter [2.0 mmol per liter]) occurred in a higher proportion of children in the tight-glycemic-control group than in the conventional-glycemic-control group (7.3% vs. 1.5%, P<0.001). Overall, the mean 12-month costs were lower in the tight-glycemic-control group than in the conventional-glycemic-control group. The mean 12-month costs were similar in the two groups in the cardiac-surgery subgroup, but in the subgroup that had not undergone cardiac surgery, the mean cost was significantly lower in the tight-glycemic-control group than in the conventional-glycemic-control group: -$13,120 (95% CI, -$24,682 to -$1,559). CONCLUSIONS: This multicenter, randomized trial showed that tight glycemic control in critically ill children had no significant effect on major clinical outcomes, although the incidence of hypoglycemia was higher with tight glucose control than with conventional glucose control. (Funded by the National Institute for Health Research, Health Technology Assessment Program, U.K. National Health Service; CHiP Current Controlled Trials number, ISRCTN61735247.).

Outcomes for Children Receiving Noninvasive Ventilation as the First-Line Mode of Mechanical Ventilation at Intensive Care Admission: A Propensity Score-Matched Cohort Study.

OBJECTIVES: To compare outcomes of children receiving noninvasive ventilation with those receiving invasive ventilation as first-line mode of mechanical ventilation following unplanned intensive care admission. DESIGN: Propensity score-matched cohort study analyzing data prospectively collected by the Pediatric Intensive Care Audit Network over 8 years (2007-2014). SETTING: Thirty-one PICUs in the United Kingdom and Ireland; twenty-one of whom submitted Pediatric Critical Care Minimum Dataset data for the entire study period. PATIENTS: Children consecutively admitted to study PICUs. Planned admissions following surgery, unplanned admissions from other hospitals, those on chronic ventilation, and those who did not receive mechanical ventilation on the day of PICU admission were excluded. INTERVENTIONS: Use of noninvasive ventilation, rather than invasive ventilation, as the first-line mode of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: PICU mortality, length of ventilation, length of PICU stay, and ventilator-free days at day 28. During the study period, there were 151,128 PICU admissions. A total of 15,144 admissions (10%) were eligible for analysis once predefined exclusion criteria were applied: 4,804 (31.7%) received "noninvasive ventilation first," whereas 10,221 (67.5%) received "invasive ventilation first"; 119 (0.8%) admissions could not be classified. Admitting PICU site explained 6.5% of the variation in first-line mechanical ventilation group (95% CI, 2.0-19.0%). In propensity score-matched analyses, receiving noninvasive ventilation first was associated with a significant reduction in mortality by 3.1% (95% CI, 1.7-4.6%), length of ventilation by 1.6 days (95% CI, 1.0-2.3), and length of PICU stay by 2.1 days (95% CI, 1.3-3.0), as well as an increase in ventilator-free days at day 28 by 3.7 days (95% CI, 3.1-4.3). CONCLUSIONS: Use of noninvasive ventilation as first-line mode of mechanical ventilation in critically ill children admitted to PICU in an unplanned fashion may be associated with significant clinical benefits. Further high-quality evidence regarding optimal patient selection and timing of initiation of noninvasive ventilation could lead to less variability in clinical care between institutions and improved patient outcomes.

Incidence and Burden of Wheezing Disorders, Eczema, and Rhinitis in Children: findings from the Born in Bradford Cohort.

BACKGROUND: Bradford city has high infant mortality and there is a major health concern in the community due to environmental pollution. The aim of the study was to investigate the incidence and burden of wheezing disorders, eczema, and rhinitis in children aged 3-7 years . METHODS: It is a prospective cohort study; the participants were 13 734 children from the Born in Bradford cohort. RESULTS: There were a total of 22.1% (95% Confidence Interval (CI) 21.4, 22.8%), 52.4% (95% CI 51.5%, 53.2%), and 19.3% (95% CI 18.6, 19.9%) incidence cases of wheezing disorders, eczema, and rhinitis respectively. A total of 37% (95% CI 36.2%, 37.8%), 19.5% (95% CI 18.9%, 20.2%,) and 5.9% (95% CI 5.5%, 6.3%) of the children were affected by only one, two, and three diseases respectively. Boys to girls incidence rate ratios for wheezing disorders, eczema, and rhinitis was 1.41 (95% CI 1.31, 1.51), 1.02 (95% CI 0.97, 1.07), and 1.18 (95% CI 1.09, 1.28) respectively. The respective incidence rate ratios of Pakistani to White British were 0.94 (95% CI 0.87, 1.02), 1.31 (95% CI 1.24, 1.39), and 2.03 (95% CI 1.83, 2.25) respectively. CONCLUSION: This study shows that the burden of wheezing disorders, eczema, and rhinitis in this cohort is higher than previously reported in earlier studies. In addition, it indicates that while boys are more likely to suffer from wheezing disorders, rhinitis, and multiple diseases than girls, Pakistani children are more likely to suffer from eczema, rhinitis, and multiple diseases than White British children.

Monitoring quality of care through linkage of administrative data: national trends in bloodstream infection in U.K. PICUs 2003-2012.

OBJECTIVES: Interventions to reduce hospital-acquired bloodstream infection have succeeded in reducing rates in U.S. PICUs, but there is a lack of evidence for the impact of similar interventions in the United Kingdom. We assessed variation in bloodstream infection rates within and between PICUs over a 10-year period, during which time infection control strategies (care bundles) were implemented. DESIGN: Observational study linking laboratory data to national audit data of pediatric intensive care admissions (Paediatric Intensive Care Audit Network). SETTING: Twenty PICUs in England and Wales, 2003-2012. PATIENTS: One hundred and two thousand nine hundred ninety-nine children less than 16 years. INTERVENTIONS: Implementation of infection control strategies in PICU captured through a survey of clinicians. MEASUREMENTS AND MAIN RESULTS: Rates of bloodstream infection per 1,000 bed-days were estimated from samples taken between 2 days after admission and up to 2 days following discharge from PICU. Two percent of children experienced at least one bloodstream infection, corresponding to 5.11 (95% CI, 4.90-5.31) per 1,000 bed-days. There was a significant difference in trends preimplementation of infection control strategies (annual decrease of 8.0%; 95% CI, 6.3-9.7%) versus postimplementation (annual decrease of 13.4%; 95% CI, 10.3-16.4%). By 24 months postimplementation, the rate of bloodstream infection had fallen 25.5% and was 15.1% lower than would have been expected if preimplementation trends had continued. CONCLUSIONS: Our population-based study of PICUs in England and Wales demonstrates a steady decline in bloodstream infection rates over time. In addition, there was a significant and incremental further decrease in rates associated with timing of implementation of infection control strategies. Assessment of bloodstream infection trends before as well as after implementation of infection control strategies can be facilitated using data linkage and is important to avoid overestimating the impact of unit-level interventions to improve infection control. Advances in collection and linkage of real-time data could further support quality improvement efforts.

Childhood body mass index and wheezing disorders: a systematic review and meta-analysis.

BACKGROUND: It has been claimed that overweight/obesity, childhood asthma and wheezing disorders are associated, although the results of observational studies have remained inconsistent. We conducted a systematic review and meta-analysis to investigate this. METHODS: An online search of published papers linking childhood asthma and wheezing with overweight/obesity up to May 2014 using EMBASE and MEDLINE medical research databases was carried out. Summary odds ratios (OR) were estimated using random-effects models. Subgroup meta-analyses were performed to assess the robustness of risk associations and between-study heterogeneity. RESULTS: A total of 38 studies comprising 1,411,335 participants were included in our meta-analysis. The summary ORs of underweight (<5th percentile), overweight (>85th to <95th percentile) and obesity (≥ 95 th percentile) were 0.85 (95% CI: 0.75 to 0.97; p = 0.02), 1.23 (95% CI: 1.17 to 1.29; p < 0.001) and 1.46 (95% CI: 1.36 to 1.57, p < 0.001), respectively. Heterogeneity was significant and substantial in all three weight categories, and not accounted for by pre-defined study characteristics. CONCLUSION: Our results suggest that underweight is associated with a reduced risk of childhood asthma, and overweight and obesity are associated with an increased risk of childhood asthma. Although our findings assert that overweight/obesity and childhood asthma are associated, the causal pathway and temporal aspects of this relationship remain unanswered and deserve further epidemiological investigation.

Risk factors for congenital anomaly in a multiethnic birth cohort: an analysis of the Born in Bradford study.

BACKGROUND: Congenital anomalies are a leading cause of infant death and disability and their incidence varies between ethnic groups in the UK. Rates of infant death are highest in children of Pakistani origin, and congenital anomalies are the most common cause of death in children younger than 12 in this ethnic group. We investigated the incidence of congenital anomalies in a large multiethnic birth cohort to identify the causes of the excess of congenital anomalies in this community. METHODS: We obtained questionnaire data from the mothers of children with one or more anomalies from the Born in Bradford study, a prospective birth cohort study of 13,776 babies and their families in which recruitment was undertaken between 2007 and 2011. Details of anomalies were prospectively reported to the study and we cross checked these details against medical records. We linked data for anomalies to maternal questionnaire and clinical data gathered as part of the Born in Bradford study. We calculated univariate and multivariate risk ratios (RRs) with 95% CIs for various maternal risk factors. FINDINGS: Of 11,396 babies for whom questionnaire data were available, 386 (3%) had a congenital anomaly. Rates for congenital anomaly were 305·74 per 10,000 livebirths, compared with a national rate of 165·90 per 10,000. The risk was greater for mothers of Pakistani origin than for those of white British origin (univariate RR 1·96, 95% CI 1·56-2·46). Overall, 2013 (18%) babies were the offspring of first-cousin unions. These babies were mainly of Pakistani origin--1922 (37%) of 5127 babies of Pakistani origin had parents in first-cousin unions. Consanguinity was associated with a doubling of risk for congenital anomaly (multivariate RR 2·19, 95% CI 1·67-2·85); we noted no association with increasing deprivation. 31% of all anomalies in children of Pakistani origin could be attributed to consanguinity. We noted a similar increase in risk for mothers of white British origin older than 34 years (multivariate RR 1·83, 95% CI 1·14-3·00). Maternal education to degree level was protective (0·53, 95% CI 0·38-0·75), irrespective of ethnic origin. INTERPRETATION: Consanguinity is a major risk factor for congenital anomaly. The risk remains even after adjustment for deprivation, and accounts for almost a third of anomalies in babies of Pakistani origin. High levels of educational attainment are associated with reduced risk in all ethnic groups. Our findings will be valuable in health promotion and public health, and to those commissioning antenatal, paediatric, and clinical genetic services. Sensitive advice about the risks should be provided to communities at increased risk, and to couples in consanguineous unions, to assist in reproductive decision making. FUNDING: National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care programme.

Population mixing for leukaemia, lymphoma and CNS tumours in teenagers and young adults in England, 1996-2005.

BACKGROUND: Little aetiological epidemiological research has been undertaken for major cancers occurring in teenagers and young adults (TYA). Population mixing, as a possible proxy for infectious exposure, has been well researched for childhood malignancies. We aimed to investigate effects of population mixing in this older age group using an English national cancer dataset. METHODS: Cases of leukaemia, lymphoma and central nervous system (CNS) tumours amongst 15-24 year olds in England (diagnosed 1996-2005) were included in the study. Data were obtained by ward of diagnosis and linked to 1991 census variables including population mixing (Shannon index); data on person-weighted population density and deprivation (Townsend score) were also used and considered as explanatory variables. Associations between TYA cancer incidence and census variables were investigated using negative binomial regression, and results presented as incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: A total of 6251 cases of leukaemia (21%), lymphoma (49%) and CNS tumours (30%) were analysed. Higher levels of population mixing were associated with a significant decrease in the incidence of CNS tumours (IRR=0.83, 95% CI=0.75-0.91), accounted for by astrocytomas and 'other CNS tumours'; however, there was no association with leukaemia or lymphoma. Incidence of CNS tumours and lymphoma was 3% lower in more deprived areas (IRR=0.97, 95% CI=0.96-0.99 and IRR=0.97, 95% CI=.96-0.98 respectively). Population density was not associated with the incidence of leukaemia, lymphoma or CNS tumours. CONCLUSIONS: Our results suggest a possible role for environmental risk factors with population correlates in the aetiology of CNS tumours amongst TYAs. Unlike studies of childhood cancer, associations between population mixing and the incidence of leukaemia and lymphoma were not observed.

Patterns of diagnoses among children and young adults with life-limiting conditions: A secondary analysis of a national dataset.

BACKGROUND: Numbers of children and young people with life-limiting conditions are rising, and increasing lifespans require young adults with life-limiting condition to transit to appropriate adult services. AIM: To describe the prevalence of life-limiting condition in children and young adults by age, sex, diagnostic group, ethnicity and deprivation. DESIGN: A secondary analysis of the English Hospital Episode Statistics dataset was undertaken to calculate prevalence per 10,000 population. SETTING/PARTICIPANTS: Individuals (0-40 years) with life-limiting conditions were identified within an English Hospital Episode Statistics dataset by applying a customised coding framework of International Classification of Diseases, 10th Edition, disease codes. RESULTS: There were 462,962 inpatient hospital admissions for 92,129 individual patients with a life-limiting condition. Prevalence-by-age group curve is U shaped with the highest overall prevalence in the under 1-year age group (127.3 per 10,000), decreasing until age 21-25 years (21.1 per 10,000) before rising steeply to reach 55.5 per 10,000 in the 36-40 -year age group. The distribution by diagnostic group varies by age: congenital anomalies are most prevalent in children until age 16-20 years with oncology diagnoses then becoming the most prevalent. CONCLUSION: Non-malignant diagnoses are common in children and young adults, and services that have historically focussed on oncological care will need to widen their remit to serve this population of life-limited patients. The diagnosis determining a patient's life-limiting condition will strongly influence their palliative care service needs. Therefore, understanding the diagnostic and demographic breakdown of this population of teenagers and young adults is crucial for planning future service provision.

Effects of out-of-hours and winter admissions and number of patients per unit on mortality in pediatric intensive care.

OBJECTIVE: To investigate the effect of out-of-hours and winter admissions, and unit size on risk adjusted mortality in pediatric intensive care. STUDY DESIGN: A national pediatric intensive care clinical audit provided data on over 86000 admissions to 29 pediatric intensive care units (2006-2011). Multivariate logistic regression modeled risk adjusted mortality prior to discharge with out-of-hours (night, weekend, public holiday) admissions, admissions per unit, winter admission, and potential confounders, overall and separately for emergency and planned admissions. RESULTS: Nearly one-half (47.1%) of admissions were out-of-hours (n = 40948) and 79.2% of those were emergencies. Mortality for all out-of-hours admissions was raised (OR 1.1; 95% CI 1.02-1.2; P = .013), accounted for by planned admissions (OR 1.99; 95% CI 1.67-2.37; P < .001) compared with a reduced risk for emergency admissions (OR 0.93; 95% CI 0.86-1.1; P = .07). Winter admissions were associated with increased risk. Unit size did not affect mortality. CONCLUSIONS: A child admitted to pediatric intensive care as an out-of-hours emergency is not at increased risk of dying compared with a weekday daytime admission, indicating pediatric intensive care units provide consistent quality of care around the clock. Excess mortality in planned out-of-hours admissions may be explained by admissions following complex operations where risk-adjustment models underestimate the true probability of mortality. In winter, a time of seasonally high bed occupancy, there was an increased mortality risk, an effect which requires further investigation. Despite the different characteristics of small units, the absence of any effect of unit size on mortality suggests that number of admissions per unit does not influence standards of care.

Paediatric index of mortality 3: an updated model for predicting mortality in pediatric intensive care*.

OBJECTIVES: To provide an updated version of the Paediatric Index of Mortality 2 for assessing the risk of mortality among children admitted to an ICU. DESIGN: International, multicenter, prospective cohort study. SETTING: Sixty ICUs that accept pediatric admissions in Australia, New Zealand, Ireland, and the United Kingdom. PATIENTS: All children admitted in 2010 and 2011 younger than 18 years old at the time of admission and either died in ICU or were discharged. Patients who were transferred to another ICU were not included. Fifty-three thousand one hundred twelve patient admissions were included in the analysis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: A revised prediction model was built using logistic regression. Variable selection was based on significance at the 95% level and overall improvement of the model's discriminatory performance and goodness of fit. The final model discriminated well (area under the curve, 0.88, 0.88-0.89); however, the model performed better in Australia and New Zealand than in the United Kingdom and Ireland (area under the curve was 0.91, 0.90-0.93 and 0.85, 0.84-0.86, respectively). CONCLUSIONS: Paediatric Index of Mortality 3 provides an international standard based on a large contemporary dataset for the comparison of risk-adjusted mortality among children admitted to intensive care.