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.

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.

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.

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.

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.

Small-area analyses of bone cancer diagnosed in Great Britain provide clues to aetiology.

BACKGROUND: The aetiology of bone cancers is poorly understood. This study examined geographical patterning in incidence of primary bone cancers diagnosed in 0-49 year olds in Great Britain during 1980-2005 to provide information on factors linked with disease development. We investigated putative associations with deprivation and population density. METHODS: Data on osteosarcoma and Ewing sarcoma were obtained from national population-based registries. Negative binomial regression was used to examine the relationship between incidence rates and the Townsend deprivation score (and its component variables) and small-area population density. RESULTS: The study analyzed 2566 osteosarcoma and 1650 Ewing sarcoma cases. For females with osteosarcoma, statistically significant decreased risk was associated with higher levels of deprivation (relative risk [RR] per unit increase in deprivation score = 0.969; 95% confidence interval [CI] 0.946-0.993). For all Ewing sarcoma combined, statistically significant decreased risk was associated with greater area-level population density and higher levels of non-car ownership (RR per person per hectare increase = 0.984; 95% CI 0.976-0.993, RR per 1% increase in non-car ownership = 0.994; 95% CI 0.991-0.998). CONCLUSIONS: Higher incidence of osteosarcoma was observed for females in areas with lower deprivation levels indicating increased risk is linked to some aspect of affluent living. Higher incidence of Ewing sarcoma occurred in areas of low population density and where more people owned cars, both characteristic of rural environments. The study adds substantially to evidence associating Ewing sarcoma risk with rural environmental exposures. Putative risk factors include agricultural exposures, such as pesticides and zoonotic agents.

Creating a national register of childhood type 1 diabetes using routinely collected hospital data.

INTRODUCTION: There is no national register of childhood type 1 diabetes mellitus for England. Our aim was to assess the feasibility of using routine hospital admissions data as a surrogate for a childhood diabetes register across England, and to create a geographically referenced childhood diabetes dataset for use in epidemiologic studies and health service research. METHODS: Hospital Episodes Statistics data for England from April 1992 to March 2006 referring to a type 1 diabetes diagnosis in 0-14 yr olds were cleaned to approximate an incident dataset. The cleaned data were validated against regional population-based register data, available for Yorkshire and the area of the former Oxford Regional Health Authority. RESULTS: There were 32 665 unique cases of type 1 and type unknown diabetes over the study period. The hospital-derived data improved in quality over time (91% concordance with regional register data over the period 2000-2006 vs. 52% concordance over the period 1992-1999), and data quality was better for younger (0-9 yr) (86.5% concordance with regional register data) than older cases (10-14 yr). Overall incidence was 24.99 (95% confidence interval 24.71-25.26) per 100 000. Basic trends in age distribution, seasonality of onset, and incidence matched well with previously reported findings. CONCLUSION: We were able to create a surrogate register of childhood diabetes based on national hospital admissions data, containing approximately 2300 cases/yr, and geo-coded to a high resolution. For younger cases (0-9 yr) and more recent years (from 2000) these data will be a useful resource for epidemiological studies exploring the determinants of childhood diabetes.

A cohort study of children and young people with progressive neuromuscular disorders: clinical and demographic profiles and changing patterns of referral for palliative care.

BACKGROUND: Progressive neuromuscular disease in children is life limiting and these children and young people would benefit from palliative care services, but data are limited on the number and demography of these children. AIM: To describe the clinical and demographic profile of children referred to a Children's hospice in the UK with progressive neuromuscular disease. SETTING/PARTICIPANTS: All children and young people with progressive neuromuscular disorders referred to Martin House Children's Hospice between 1987 and 2010. DESIGN: Retrospective cohort study. RESULTS: 300 children with progressive neuromuscular disease were referred to the hospice. Seventy percent (210) of these children had Duchenne Muscular Dystrophy, 22% (67) had Spinal Muscular Atrophy (34 with Type I) and 8% had other neuromuscular diseases. Numbers of referrals have not significantly increased over the last 15 years, although an increasing number come from a South Asian background (from 4% to 32%) and a higher number of children have conditions other than Duchenne Muscular Dystrophy. A total of 55.3% (166) of all referrals came from areas of the highest deprivation. Survival patterns varied by diagnostic group, but ethnicity and deprivation were not associated with survival in these children. CONCLUSIONS: The profile of children with progressive neuromuscular conditions who were referred for palliative care has changed over the last 20 years, with a different spectrum of underlying diagnoses and a greater number from a South Asian background. The higher than expected proportion of children living in areas of high deprivation has been consistent over time.

Effect of specialist retrieval teams on outcomes in children admitted to paediatric intensive care units in England and Wales: a retrospective cohort study.

BACKGROUND: Intensive care services for children have undergone substantial centralisation in the UK. Along with the establishment of regional paediatric intensive care units (PICUs), specialist retrieval teams were set up to transport critically ill children from other hospitals. We studied the outcome of children transferred from local hospitals to PICUs. METHODS: We analysed data that were gathered for a cohort of children (

Referral to a specialist paediatric palliative care service in oncology patients.

Cancer is the second most common cause of death in children and young people (0-19 years) accounting for 16.2% of deaths in England and Wales in 2005. Only 37.6% children and young people who died from cancer in Yorkshire were referred to Martin House Children's Hospice (MH) during the period 1990-2005. A significantly higher proportion with central nervous system tumours and a significantly lower than expected proportion with leukaemia or lymphoma were referred for palliative care. There is potential to increase the proportion of children and young people with cancer who are referred to specialist palliative care services.

Severe head injury in children: intensive care unit activity and mortality in England and Wales.

OBJECTIVE: To explore the relationship between volume of paediatric intensive care unit (PICU) head injury (HI) admissions, specialist paediatric neurosurgical PICU practice, and mortality in England and Wales. METHODS: Analysis of HI cases (age  <16 years) from the Paediatric Intensive Care Audit Network national cohort of sequential PICU admissions in 27 units in England and Wales, in the 5 years 2004-2008. Risk-adjusted mortality using the Paediatric Index of Mortality (PIM) model was compared between PICUs aggregated into quartile groups, first to fourth based on descending number of HI admissions/year: highest volume, medium-higher volume, medium-lower volume, and lowest volume. The effect of category of PICU interventions - observation only, mechanical ventilation (MV) only, and intracranial pressure (ICP) monitoring - on outcome was also examined. Observations were reported in relation to specialist paediatric neurosurgical PICU practice. RESULTS: There were 2575 admissions following acute HI (4.4% of non-cardiac surgery PICU admissions in England and Wales). PICU mortality was 9.3%. Units in the fourth-quartile (lowest volume) group did not have significant specialist paediatric neurosurgical activity on the PICU; the other groups did. Overall, there was no effect of HI admissions by individual PICU on risk-adjusted mortality. However, there were significant effects for both intensive care intervention category (p<0.001) and HI admissions by grouping (p<0.005). Funnel plots and control charts using the PIM model showed a hierarchy in increasing performance from lowest volume (group IV), to medium-higher volume (group II), to highest volume (group I), to medium-lower volume (group III) sectors of the health care system. CONCLUSIONS: The health care system in England and Wales for critically ill HI children requiring PICU admission performs as expected in relation to the PIM model. However, the lowest-volume sector, comprising 14 PICUs with little or no paediatric neurosurgical activity on the unit, exhibits worse than expected outcome, particularly in those undergoing ICP monitoring. The best outcomes are seen in units in the mid-volume sector. These data do not support the hypothesis that there is a simple relationship between PICU volume and performance.