Publications by authors named "Angie Wade"

82 Publications

Minimal change in structural, functional and inflammatory markers of lung disease in newborn screened infants with cystic fibrosis at one year.

J Cyst Fibros 2020 11 7;19(6):896-901. Epub 2020 Feb 7.

Department of Paediatric Respiratory Medicine, Imperial College & Royal Brompton & Harefield Hospital NHS Foundation Trust, London, United Kingdom.

Background: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age.

Methods: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs.

Results: 65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0-1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4-1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT.

Conclusions: In this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes.
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http://dx.doi.org/10.1016/j.jcf.2020.01.006DOI Listing
November 2020

Childhood medulloblastoma-a single institution's historical perspective on survival and functional morbidity.

Childs Nerv Syst 2019 12 4;35(12):2327-2338. Epub 2019 Nov 4.

Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC2N 3JH, UK.

Purpose: To compare results from a third (1995-2010) cohort of children with medulloblastoma with two previous series (J Neurosurg 86:13-21, 1997; Arch Dis Child 54:200-203, 1979) to analyse the effects of management changes aimed at improving both overall and event-free survivals (OS and EFS) and functional outcomes.

Methods: Review of neuro-oncology and imaging databases and previously published results.

Results: There was no statistically significant improvement in the 5-year OS for 104 children diagnosed 1995-2010, 61.5% (95% CI, 52.9, 71.6), compared with 50% of the 80 children presenting 1980-1990 (J Neurosurg 86:13-21, 1997) (difference 11.5%; 95% CI, 2.8, 25.4). Five-year OS for 96 children suitable for risk-stratification was overall 66% (95% CI, 57.9, 75.8); standard risk 77.8% (95% CI, 67.4, 89.7); high risk < 3 years 50.0% (95% CI, 32.3, 77.5); high risk ≥ 3 years 54.5% (95% CI, 37.2, 79.9); 5-year EFS were standard risk 68.5% (95% CI, 57.2, 82.1); high risk < 3 years 40.0% (95% CI, 23.4, 68.4); and high risk ≥ 3 years 36.4% (95% CI, 20.9, 63.2); overall 55.2% (95% CI, 46.1, 66.1). Of 62/63 ≥ 5-year survivor, 9 died later from tumour relapse and 4 from second malignancy. Functional outcomes of 62 of the 63 ≥ 5-year survivors: 67.7% had educational issues requiring remedial input; 18% restricted mobility indoors and outdoors; 59.7% hearing impairment (42% prescribed aids).

Conclusions: 1. Comparison of this single-institution series with its predecessor found that revised chemotherapy and RT protocols and greater accuracy of risk stratification did not result in statistically significant improvements in either survival or treatment-related functional disability. 2. Extended (> 5-year) follow-up is essential if 20% of late deaths from relapse and second malignancies are not to be overlooked.
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http://dx.doi.org/10.1007/s00381-019-04402-xDOI Listing
December 2019

Minimally invasive autopsy for fetuses and children based on a combination of post-mortem MRI and endoscopic examination: a feasibility study.

Health Technol Assess 2019 08;23(46):1-104

Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust and Institute of Child Health/University College London, London, UK.

Background: Less invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known.

Objectives: The aims of this study were to provide empirical data on the acceptability and likely uptake for different types of autopsy among key stakeholders (study 1); and to analyse existing autopsy data sources to provide estimates of the potential efficacy of less invasive autopsy (LIA) and its projected utility in clinical practice (study 2).

Review Methods: Study 1: this was a mixed-methods study. Parents were involved in research design and interpretation of findings. Substudy 1: a cross-sectional survey of 859 parents who had experienced miscarriage, termination of pregnancy for fetal anomaly, stillbirth, infant or child death, and interviews with 20 responders. Substudy 2: interviews with 25 health professionals and four coroners. Substudy 3: interviews with 16 religious leaders and eight focus groups, with 76 members of the Muslim and Jewish community. Study 2: a retrospective analysis of national data in addition to detailed information from an existing in-house autopsy database of > 5000 clinical cases that had undergone standard autopsy to determine the proportion of cases by clinical indication group for which tissue sampling of specific internal organs significantly contributed to the diagnosis.

Results: Substudy 1: 91% of participants indicated that they would consent to some form of LIA, 54% would consent to standard autopsy, 74% to minimally invasive autopsy (MIA) and 77% to non-invasive autopsy (NIA). Substudy 2: participants viewed LIA as a positive development, but had concerns around the limitations of the technology and de-skilling the workforce. Cost implications, skills and training requirements were identified as implementation challenges. Substudy 3: religious leaders agreed that NIA was religiously permissible, but MIA was considered less acceptable. Community members indicated that they might consent to NIA if the body could be returned for burial within 24 hours. Study 2: in 5-10% of cases of sudden unexplained death in childhood and sudden unexplained death in infants, the final cause of death is determined by routine histological sampling of macroscopically normal organs, predominantly the heart and lungs, and in this group routine histological sampling therefore remains an important aspect of investigation. In contrast, routine histological examination of macroscopically normal organs rarely (< 0.5%) provides the cause of death in fetal cases, making LIA and NIA approaches potentially highly applicable.

Limitations: A key limitation of the empirical research is that it is hypothetical. Further research is required to determine actual uptake. Furthermore, because of the retrospective nature of the autopsy data set, findings regarding the likely contribution of organ sampling to final diagnosis are based on extrapolation of findings from historical autopsies, and prospective data collection is required to validate the conclusions.

Conclusions: LIA is viable and acceptable (except for unexplained deaths), and likely to increase uptake. Further health economic, performance and implementation studies are required to determine the optimal service configuration required to offer this as routine clinical care.

Funding: The National Institute for Health Research Health Technology Assessment programme.
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http://dx.doi.org/10.3310/hta23460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732714PMC
August 2019

Analysis of paediatric visual acuity using Bayesian copula models with sinh-arcsinh marginal densities.

Stat Med 2019 08 29;38(18):3421-3443. Epub 2019 May 29.

Great Ormond Street Institute of Child Health, University College London, London, UK.

We analyse paediatric ophthalmic data from a large sample of children aged between 3 and 8 years. We use a Bayesian additive conditional bivariate copula regression model with sinh-arcsinh marginal densities with location, scale, and shape parameters that depend smoothly on a covariate. We perform Bayesian inference about the unknown quantities of our model using a specially tailored Markov chain Monte Carlo algorithm. We gain new insights about the processes, which determine transformations in visual acuity with respect to age, including the nature of joint changes in both eyes as modelled with the age-related copula dependence parameter. We analyse posterior predictive distributions to identify children with unusual sight characteristics, distinguishing those who are bivariate, but not univariate outliers. In this way, we provide an innovative tool that enables clinicians to identify children with unusual sight who may otherwise be missed. We compare our simultaneous Bayesian method with a two-step frequentist generalised additive modelling approach.
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http://dx.doi.org/10.1002/sim.8176DOI Listing
August 2019

Long-term impact of community-based participatory women's groups on child and maternal mortality and child disability: follow-up of a cluster randomised trial in rural Nepal.

BMJ Glob Health 2018 1;3(6):e001024. Epub 2018 Dec 1.

UCL Institute for Global Health, University College London, London, UK.

Background: Community-based women's groups practising participatory learning and action (PLA) can reduce maternal and neonatal mortality in low-income countries. However, it is not clear whether these reductions are associated with subsequent increased or decreased rates of childhood death and disability. We assessed the impact on child deaths and disability beyond the perinatal period among participants in the earliest trial in Nepal 2001-2003.

Methods: Household interviews were conducted with mothers or household heads. At cluster and individual levels, we analysed disability using pairwise log relative risks and survival using multilevel logistic models.

Findings: From 6075 children and 6117 mothers alive at 4 weeks post partum, 44 419 children (73%) were available for interview a mean 11.5 years later. Rates of child deaths beyond the perinatal period were 36.6 and 52.0 per 1000 children in the intervention and control arms respectively. Rates of disability were 62.7 and 85.5 per 1000 children in the intervention and control arms respectively. Individual-level analysis, including random effects for cluster pairing and adjusted for baseline maternal literacy, socioeconomic status and maternal age, showed lower, statistically non-significant, odds of child deaths (OR 0.70 (95% CI 0.43 to 1.18) and disability (0.64 (0.39 to 1.06)) in the intervention arm.

Conclusion: Community-level exposure to women's groups practising PLA did not significantly impact childhood death or disability or death beyond the perinatal period. Follow-up of other trials with larger sample sizes is warranted in order to explore the possibility of potential long-term survival and disability benefits with greater precision.
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http://dx.doi.org/10.1136/bmjgh-2018-001024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278922PMC
December 2018

Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient.

Eur Respir J 2017 11 9;50(5). Epub 2017 Nov 9.

Clinical Epidemiology, Nutrition and Biostatistics, Population, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, London, UK.

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45-1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV on all test occasions, precluding the ability to identify "high-risk" infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up.
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http://dx.doi.org/10.1183/13993003.00326-2017DOI Listing
November 2017

Power and precision in research.

Authors:
Angie Wade

Arch Dis Child 2018 03 31;103(3):280-284. Epub 2017 Oct 31.

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http://dx.doi.org/10.1136/archdischild-2016-311290DOI Listing
March 2018

Effects of dietary nitrate supplementation on symptoms of acute mountain sickness and basic physiological responses in a group of male adolescents during ascent to Mount Everest Base Camp.

Nitric Oxide 2016 11 2;60:24-31. Epub 2016 Sep 2.

University College London, Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport, Exercise and Health, London, UK.

The purpose of this study was to investigate the effects of dietary nitrate supplementation, in the form of beetroot juice, on acute mountain sickness (AMS) symptoms and physiological responses, in a group of young males trekking to Mount Everest Base Camp (EBC). Forty healthy male students (mean age (SD): 16 (1) yrs) trekked to EBC over 11 days. Following an overnight fast, each morning participants completed the Lake Louise AMS questionnaire and underwent a series of physiological tests: resting blood pressure as well as resting and exercising heart rate, respiratory rate, and peripheral oxygen saturation. The exercise test consisted of a standardised 2-min stepping protocol and measurements were taken in the last 10 s. Participants in the intervention arm of the study consumed 140 ml of concentrated beetroot juice daily, containing approximately 10 mmol of nitrate, while those in the control arm consumed 140 ml of concentrated blackcurrant cordial with negligible nitrate content. Drinks were taken for the first seven days at high altitude (days 2-8), in two equal doses; one with breakfast, and one with the evening meal. Mixed modelling revealed no significant between-groups difference in the incidence of AMS (Odds Ratio - nitrate vs.

Control: 1.16 (95% CI: 0.59; 2.29)). Physiological changes occurring during ascent to high altitude generally were not significantly different between the two groups (Model Coef (95% CI) - average difference nitrate vs.

Control: systolic blood pressure, 0.16 (-4.47; 4.79); peripheral oxygen saturation, 0.28 (-0.85; 1.41); heart rate, -0.48 (-8.47; 7.50) (Model Coef (95% CI) - relative difference nitrate vs.

Control: ventilatory rate, 0.95 (0.82; 1.08)). Modelling revealed that diastolic blood pressure was 3.37 mmHg (0.24; 6.49) higher for participants in the beetroot juice, however this difference was no larger than that found at baseline and no interaction effect was observed. Supplementation with dietary nitrate did not significantly change symptoms of AMS or alter key physiological variables, in a group of adolescent males during a high altitude trekking expedition. There was no evidence of harm from dietary nitrate supplementation in this context. Given the wide confidence intervals in all models, a larger sample size would be required to exclude a false negative result. Our data suggest that prolonged oral nitrate supplementation is safe and feasible at altitude but has little physiological or clinical effect.
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http://dx.doi.org/10.1016/j.niox.2016.08.007DOI Listing
November 2016

Natural variability of lung function in young healthy school children.

Eur Respir J 2016 08 13;48(2):411-9. Epub 2016 Apr 13.

Respiratory, Critical Care and Anaesthesia section in Portex Unit, University College London, Institute of Child Health, London, UK.

Knowledge about long-term variability of lung function in healthy children is essential when monitoring and treating those with respiratory disease over time. The aim of this study was to define the natural variability in spirometry in young children after an interval of 12 months.The Size and Lung function In Children study was a prospective study designed to assess spirometry and body size, shape and composition in a multi-ethnic population of London school children. 14 schools with a wide range of socioeconomic circumstances were recruited. Spirometric and anthropometric assessments and parental questionnaires pertaining to respiratory symptoms, previous medical history, pubertal status and socioeconomic circumstances were completed at baseline and ∼1 year later.Technically acceptable spirometry data on two occasions ∼1 year apart (range 9-16 months) were available in 758 children (39% boys, mean±sd age 8.1±1.6 years), 593 of whom were classified as "healthy". Mean±sd within-subject between-test variability was 0.05±0.6 z-scores, with 95% of all the children achieving a between-test variability within ±1.2 z-scores (equating to ∼13% predicted).Natural variations of up to 1.2 z-scores occur in healthy children over ∼1 year. These must be considered when interpreting results from annual reviews in those with lung disease who are otherwise stable, if unnecessary further investigations or changes in treatment are to be avoided.
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http://dx.doi.org/10.1183/13993003.01795-2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950968PMC
August 2016

Lung function in children in relation to ethnicity, physique and socioeconomic factors.

Eur Respir J 2015 Dec 22;46(6):1662-71. Epub 2015 Oct 22.

Respiratory, Critical Care & Anaesthesia Section in IIIP Programme, UCL Institute of Child Health, London, UK.

Can ethnic differences in spirometry be attributed to differences in physique and socioeconomic factors?Assessments were undertaken in 2171 London primary schoolchildren on two occasions 1 year apart, whenever possible, as part of the Size and Lung function In Children (SLIC) study. Measurements included spirometry, detailed anthropometry, three-dimensional photonic scanning for regional body shape, body composition, information on ethnic ancestry, birth and respiratory history, socioeconomic circumstances, and tobacco smoke exposure.Technically acceptable spirometry was obtained from 1901 children (mean (range) age 8.3 (5.2-11.8) years, 46% boys, 35% White, 29% Black-African origin, 24% South-Asian, 12% Other/mixed) on 2767 test occasions. After adjusting for sex, age and height, forced expiratory volume in 1 s was 1.32, 0.89 and 0.51 z-score units lower in Black-African origin, South-Asian and Other/mixed ethnicity children, respectively, when compared with White children, with similar decrements for forced vital capacity (p<0.001 for all). Although further adjustment for sitting height and chest width reduced differences attributable to ethnicity by up to 16%, significant differences persisted after adjusting for all potential determinants, including socioeconomic circumstances.Ethnic differences in spirometric lung function persist despite adjusting for a wide range of potential determinants, including body physique and socioeconomic circumstances, emphasising the need to use ethnic-specific equations when interpreting results.
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http://dx.doi.org/10.1183/13993003.00415-2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668600PMC
December 2015

Comparison of diagnostic performance for perinatal and paediatric post-mortem imaging: CT versus MRI.

Eur Radiol 2016 Jul 21;26(7):2327-36. Epub 2015 Oct 21.

Great Ormond Street Hospital NHS Foundation Trust, London, UK.

Objectives: To compare the diagnostic yield of whole-body post-mortem computed tomography (PMCT) imaging to post-mortem magnetic resonance (PMMR) imaging in a prospective study of fetuses and children.

Methods: We compared PMCT and PMMR to conventional autopsy as the gold standard for the detection of (a) major pathological abnormalities related to the cause of death and (b) all diagnostic findings in five different body organ systems.

Results: Eighty two cases (53 fetuses and 29 children) underwent PMCT and PMMR prior to autopsy, at which 55 major abnormalities were identified. Significantly more PMCT than PMMR examinations were non-diagnostic (18/82 vs. 4/82; 21.9 % vs. 4.9 %, diff 17.1 % (95 % CI 6.7, 27.6; p < 0.05)). PMMR gave an accurate diagnosis in 24/55 (43.64 %; 95 % CI 31.37, 56.73 %) compared to 18/55 PMCT (32.73 %; 95 % CI 21.81, 45.90). PMCT was particularly poor in fetuses <24 weeks, with 28.6 % (8.1, 46.4 %) more non-diagnostic scans. Where both PMCT and PMMR were diagnostic, PMMR gave slightly higher diagnostic accuracy than PMCT (62.8 % vs. 59.4 %).

Conclusion: Unenhanced PMCT has limited value in detection of major pathology primarily because of poor-quality, non-diagnostic fetal images. On this basis, PMMR should be the modality of choice for non-invasive PM imaging in fetuses and children.

Key Points: • Overall 17.1 % more PMCT examinations than PMMR were non-diagnostic • 28.6 % more PMCT were non-diagnostic than PMMR in fetuses <24 weeks • PMMR detected almost a third more pathological abnormalities than PMCT • PMMR gave slightly higher diagnostic accuracy when both were diagnostic.
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http://dx.doi.org/10.1007/s00330-015-4057-9DOI Listing
July 2016

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

Crit Care Med 2015 May;43(5):1070-8

1Population, Policy and Practice, Institute of Child Health, University College London, London, United Kingdom. 2Division of Epidemiology, University of Leeds, Leeds, United Kingdom. 3Paediatric Intensive Care Unit, Great Ormond Street Hospital, London, United Kingdom. 4Paediatric Intensive Care Unit, Evelina London Children's Hospital, London, United Kingdom. 5Department of Healthcare-Associated Infection and Antimicrobial Resistance, Public Health England, London, United Kingdom.

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.
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http://dx.doi.org/10.1097/CCM.0000000000000941DOI Listing
May 2015

Diagnostic accuracy of post mortem MRI for abdominal abnormalities in foetuses and children.

Eur J Radiol 2015 Mar 3;84(3):474-481. Epub 2014 Dec 3.

Department of Histopathology, UCL Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Electronic address:

Background: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for abdominal pathology in foetuses and children, compared to conventional autopsy.

Methods: Institutional ethics approval and parental consent was obtained. 400 unselected foetuses and children underwent PMMR using a 1.5T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data respectively.

Results: Abdominal abnormalities were found in 70/400 (12%) autopsies. Overall sensitivity and specificity (95% confidence interval) of PMMR for abdominal pathology was 72.5% (61.0, 81.6) and 90.8% (87.0, 93.6), with positive (PPV) and negative predictive values (NPV) of 64.1% (53.0, 73.9) and 93.6% (90.2, 95.8) respectively. PMMR was good at detecting renal abnormalities (sensitivity 80%), particularly in foetuses, and relatively poor at detecting intestinal abnormalities (sensitivity 50%). Overall accuracy was 87.4% (83.6, 90.4).

Conclusions: PMMR has high overall accuracy for abdominal pathology in foetuses, newborns and children. PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities.
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http://dx.doi.org/10.1016/j.ejrad.2014.11.030DOI Listing
March 2015

Assessing pubertal status in multi-ethnic primary schoolchildren.

Acta Paediatr 2015 Jan 17;104(1):e45-8. Epub 2014 Nov 17.

Respiratory, Critical Care & Anaesthesia Section (Portex Unit), UCL Institute of Child Health, London, UK.

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http://dx.doi.org/10.1111/apa.12850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463762PMC
January 2015

Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children.

Eur Radiol 2014 Nov 31;24(11):2876-84. Epub 2014 Aug 31.

Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK,

Objectives: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy.

Methods: Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded to the other dataset.

Results: Of 400 non-cardiac thoracic abnormalities, 113 (28 %) were found at autopsy. Overall sensitivity and specificity (95 % confidence interval) of PMMR for any thoracic pathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7, 89.2) respectively, with positive predictive value (PPV) 53.7 % (42.9, 64.0) and negative predictive value (NPV) 77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1, 76.2). PMMR was most sensitive at detecting anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection.

Conclusions: PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities.

Key Points: • PMMR has relatively poor diagnostic detection rates for common intrathoracic pathology • The moderate NPV suggests that normal PMMR appearances exclude most important abnormalities • Lung sampling at autopsy remains the "gold standard" for pulmonary pathology.
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http://dx.doi.org/10.1007/s00330-014-3313-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182596PMC
November 2014

Diagnostic accuracy of postmortem MRI for musculoskeletal abnormalities in fetuses and children.

Prenat Diagn 2014 Dec 6;34(13):1254-61. Epub 2014 Aug 6.

Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; Institute of Child Health, UCL, London, UK.

Objectives: The aim of this study was to compare the diagnostic accuracy of postmortem magnetic resonance (PMMR) imaging specifically for musculoskeletal pathology in fetuses and children, compared with conventional autopsy, with radiographic and histopathology assessment.

Methods: Institutional ethics approval and parental consent was obtained. A total of 400 cases underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data, respectively.

Results: A total of 400 cases were reported, with 277 (69%) fetuses (185 ≤24 weeks' gestation and 92 >24 weeks' gestation) and 123 children (42 newborns aged <1 month, 53 infants ≤12 months and 28 children ≤16 years). Musculoskeletal (MSK) abnormalities were found at autopsy in 47/400 (11.7%). Overall sensitivity and specificity (with 95% confidence interval) of PMMR for MSK pathology were 51.1% (37.0, 65.0) and 98.2% (96.2, 99.2), with positive and negative predictive values of 79.3% (61.6, 90.2) and 93.8% (90.8, 95.9), respectively. Overall accuracy between PMMR and autopsy for MSK abnormalities was 92.7% (89.7, 94.9). In some cases, PMMR detected MSK abnormalities not routinely examined for or detected at traditional autopsy.

Conclusion: Minimally invasive autopsy has good diagnostic accuracy for the exclusion of MSK abnormalities, but sensitivity is relatively poor. When PMMR is used with clinical examination and skeletal radiographs, all skeletal and soft tissue abnormalities of clinical significance are likely to be detected, even if not directly relevant to the cause of death.
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http://dx.doi.org/10.1002/pd.4460DOI Listing
December 2014

Postmortem cardiovascular magnetic resonance imaging in fetuses and children: a masked comparison study with conventional autopsy.

Circulation 2014 May 19;129(19):1937-44. Epub 2014 Mar 19.

Centre for Cardiovascular Imaging, University College London Institute of Cardiovascular Science, London, United Kingdom (A.M.T., S.S., S.T.); Cardiorespiratory Services, Great Ormond Street Hospital for Children (A.M.T.), Department of Histopathology, University College London Institute of Child Health and Great Ormond Street Hospital for Children (N.J.S., M.T.A.), and Department of Histopathology, University College London Hospitals (R.J.S.), National Health Service Foundation Trust, London, United Kingdom; Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, United Kingdom (A.W.); Clinical Molecular Genetics Unit, University College London Institute of Child Health and University College London Hospitals National Health Service Foundation Trust, London, United Kingdom (L.S.C.); and Academic Neonatology, University College London Institute for Women's Health, London, United Kingdom (N.R., S.T.).

Background: Perinatal and pediatric autopsies have declined worldwide in the past decade. We compared the diagnostic accuracy of postmortem, cardiovascular magnetic resonance (CMR) imaging with conventional autopsy and histopathology assessment in fetuses and children.

Methods And Results: We performed postmortem magnetic resonance imaging in 400 fetuses and children, using a 1.5-T Siemens Avanto magnetic resonance scanner before conventional autopsy. A pediatric CMR imager reported the CMR images, masked to autopsy information. The pathologists were masked to the information from CMR images. The institutional research ethics committee approved the study, and parental consent was obtained. Assuming a diagnostic accuracy of 50%, 400 cases were required for a 5% precision of estimate. Three cases were excluded from analysis, 2 with no conventional autopsy performed and 1 with insufficient CMR sequences performed. Thirty-eight CMR data sets were nondiagnostic (37 in fetuses ≤24 weeks; 1 in a fetus >24 weeks). In the remaining 359 cases, 44 cardiac abnormalities were noted at autopsy. Overall sensitivity and specificity (95% confidence interval) of CMR was 72.7% (58.2-83.7%) and 96.2% (93.5-97.8%) for detecting any cardiac pathology, with positive and negative predictive values of 72.7% (58.2-83.7%) and 96.2% (93.5-97.8%), respectively. Higher sensitivity of 92.6% (76.6-97.9%), specificity of 99.1% (97.4-99.7%), positive predictive value of 89.3% (72.8-96.3%), and negative predictive value of 99.4% (97.8-99.8%) were seen for major structural heart disease.

Conclusions: Postmortem CMR imaging may be a useful alternative to conventional cardiac autopsy in fetuses and children for detecting cardiac abnormalities.

Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01417962.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005641DOI Listing
May 2014

Evaluating bias due to data linkage error in electronic healthcare records.

BMC Med Res Methodol 2014 Mar 5;14:36. Epub 2014 Mar 5.

Institute of Child Health, University College London, 30 Guilford Street, London WC1 N 1EH, UK.

Background: Linkage of electronic healthcare records is becoming increasingly important for research purposes. However, linkage error due to mis-recorded or missing identifiers can lead to biased results. We evaluated the impact of linkage error on estimated infection rates using two different methods for classifying links: highest-weight (HW) classification using probabilistic match weights and prior-informed imputation (PII) using match probabilities.

Methods: A gold-standard dataset was created through deterministic linkage of unique identifiers in admission data from two hospitals and infection data recorded at the hospital laboratories (original data). Unique identifiers were then removed and data were re-linked by date of birth, sex and Soundex using two classification methods: i) HW classification - accepting the candidate record with the highest weight exceeding a threshold and ii) PII-imputing values from a match probability distribution. To evaluate methods for linking data with different error rates, non-random error and different match rates, we generated simulation data. Each set of simulated files was linked using both classification methods. Infection rates in the linked data were compared with those in the gold-standard data.

Results: In the original gold-standard data, 1496/20924 admissions linked to an infection. In the linked original data, PII provided least biased results: 1481 and 1457 infections (upper/lower thresholds) compared with 1316 and 1287 (HW upper/lower thresholds). In the simulated data, substantial bias (up to 112%) was introduced when linkage error varied by hospital. Bias was also greater when the match rate was low or the identifier error rate was high and in these cases, PII performed better than HW classification at reducing bias due to false-matches.

Conclusions: This study highlights the importance of evaluating the potential impact of linkage error on results. PII can help incorporate linkage uncertainty into analysis and reduce bias due to linkage error, without requiring identifiers.
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http://dx.doi.org/10.1186/1471-2288-14-36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015706PMC
March 2014

Neonatal encephalopathic cerebral injury in South India assessed by perinatal magnetic resonance biomarkers and early childhood neurodevelopmental outcome.

PLoS One 2014 5;9(2):e87874. Epub 2014 Feb 5.

Perinatal Neurology and Neonatology, Imperial College London, London, United Kingdom.

Unlabelled: Although brain injury after neonatal encephalopathy has been characterised well in high-income countries, little is known about such injury in low- and middle-income countries. Such injury accounts for an estimated 1 million neonatal deaths per year. We used magnetic resonance (MR) biomarkers to characterise perinatal brain injury, and examined early childhood outcomes in South India.

Methods: We recruited consecutive term or near term infants with evidence of perinatal asphyxia and a Thompson encephalopathy score ≥6 within 6 h of birth, over 6 months. We performed conventional MR imaging, diffusion tensor MR imaging and thalamic proton MR spectroscopy within 3 weeks of birth. We computed group-wise differences in white matter fractional anisotropy (FA) using tract based spatial statistics. We allocated Sarnat encephalopathy stage aged 3 days, and evaluated neurodevelopmental outcomes aged 3½ years using Bayley III.

Results: Of the 54 neonates recruited, Sarnat staging was mild in 30 (56%); moderate in 15 (28%) and severe in 6 (11%), with no encephalopathy in 3 (6%). Six infants died. Of the 48 survivors, 44 had images available for analysis. In these infants, imaging indicated perinatal rather than established antenatal origins to injury. Abnormalities were frequently observed in white matter (n = 40, 91%) and cortex (n = 31, 70%) while only 12 (27%) had abnormal basal ganglia/thalami. Reduced white matter FA was associated with Sarnat stage, deep grey nuclear injury, and MR spectroscopy N-acetylaspartate/choline, but not early Thompson scores. Outcome data were obtained in 44 infants (81%) with 38 (79%) survivors examined aged 3½ years; of these, 16 (42%) had adverse neurodevelopmental outcomes.

Conclusions: No infants had evidence for established brain lesions, suggesting potentially treatable perinatal origins. White matter injury was more common than deep brain nuclei injury. Our results support the need for rigorous evaluation of the efficacy of rescue hypothermic neuroprotection in low- and middle-income countries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087874PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914890PMC
November 2014

Patient-reported quality of life outcomes for children with serious congenital heart defects.

Arch Dis Child 2014 May 9;99(5):413-9. Epub 2014 Jan 9.

MRC Centre of Epidemiology for Child Health, Centre of Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, University College London, , London, UK.

Objective: To compare patient-reported, health-related quality of life (QoL) for children with serious congenital heart defects (CHDs) and unaffected classmates and to investigate the demographic and clinical factors influencing QoL.

Design: Retrospective cohort study.

Setting: UK National Health Service.

Patients: UK-wide cohort of children with serious CHDs aged 10-14 years requiring cardiac intervention in the first year of life in one of 17 UK paediatric cardiac surgical centres operating during 1992-1995. A comparison group of classmates of similar age and sex was recruited.

Main Outcome Measures: Child self-report of health-related QoL scores (Pediatric Quality of Life Inventory, PedsQL) and parental report of schooling and social activities.

Results: Questionnaires were completed by 477 children with CHDs (56% boys; mean age 12.1 (SD 1.0) years) and 464 classmates (55%; 12.0 (SD 1.1) years). Children with CHDs rated QoL significantly lower than classmates (CHDs: median 78.3 (IQR 65.0-88.6); classmates: 88.0 (80.2-94.6)) and scored lower on physical (CHDs: 84.4; classmates: 93.8; difference 9.4 (7.8 to 10.9)) and psychosocial functioning subscales (CHDs: 76.7, classmates: 85.0; difference 8.3 (6.0 to 10.6)). Cardiac interventions, school absence, regular medications and non-cardiac comorbidities were independently associated with reduced QoL. Participation in sport positively influenced QoL and was associated with higher psychosocial functioning scores.

Conclusions: Children with serious CHDs experience lower QoL than unaffected classmates. This appears related to the burden of clinical intervention rather than underlying cardiac diagnosis. Participation in sports activities is positively associated with increased emotional well-being. Child self-report measures of QoL would be a valuable addition to clinical outcome audit in this age group.
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http://dx.doi.org/10.1136/archdischild-2013-305130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995241PMC
May 2014

Linkage, evaluation and analysis of national electronic healthcare data: application to providing enhanced blood-stream infection surveillance in paediatric intensive care.

PLoS One 2013 20;8(12):e85278. Epub 2013 Dec 20.

Institute of Child Health, University College London, London, United Kingdom.

Background: Linkage of risk-factor data for blood-stream infection (BSI) in paediatric intensive care (PICU) with bacteraemia surveillance data to monitor risk-adjusted infection rates in PICU is complicated by a lack of unique identifiers and under-ascertainment in the national surveillance system. We linked, evaluated and performed preliminary analyses on these data to provide a practical guide on the steps required to handle linkage of such complex data sources.

Methods: Data on PICU admissions in England and Wales for 2003-2010 were extracted from the Paediatric Intensive Care Audit Network. Records of all positive isolates from blood cultures taken for children <16 years and captured by the national voluntary laboratory surveillance system for 2003-2010 were extracted from the Public Health England database, LabBase2. "Gold-standard" datasets with unique identifiers were obtained directly from three laboratories, containing microbiology reports that were eligible for submission to LabBase2 (defined as "clinically significant" by laboratory microbiologists). Reports in the gold-standard datasets were compared to those in LabBase2 to estimate ascertainment in LabBase2. Linkage evaluated by comparing results from two classification methods (highest-weight classification of match weights and prior-informed imputation using match probabilities) with linked records in the gold-standard data. BSI rate was estimated as the proportion of admissions associated with at least one BSI.

Results: Reporting gaps were identified in 548/2596 lab-months of LabBase2. Ascertainment of clinically significant BSI in the remaining months was approximately 80-95%. Prior-informed imputation provided the least biased estimate of BSI rate (5.8% of admissions). Adjusting for ascertainment, the estimated BSI rate was 6.1-7.3%.

Conclusion: Linkage of PICU admission data with national BSI surveillance provides the opportunity for enhanced surveillance but analyses based on these data need to take account of biases due to ascertainment and linkage error. This study provides a generalisable guide for linkage, evaluation and analysis of complex electronic healthcare data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085278PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869925PMC
October 2014

Is chest CT useful in newborn screened infants with cystic fibrosis at 1 year of age?

Thorax 2014 Apr 16;69(4):320-7. Epub 2013 Oct 16.

Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, , London, UK.

Rationale: Sensitive outcome measures applicable in different centres to quantify and track early pulmonary abnormalities in infants with cystic fibrosis (CF) are needed both for clinical care and interventional trials. Chest CT has been advocated as such a measure yet there is no validated scoring system in infants.

Objectives: The objectives of this study were to standardise CT data collection across multiple sites; ascertain the incidence of bronchial dilatation and air trapping in newborn screened (NBS) infants with CF at 1 year; and assess the reproducibility of Brody-II, the most widely used scoring system in children with CF, during infancy.

Methods: A multicentre observational study of early pulmonary lung disease in NBS infants with CF at age 1 year using volume-controlled chest CT performed under general anaesthetic.

Main Results: 65 infants with NBS-diagnosed CF had chest CT in three centres. Small insignificant variations in lung recruitment manoeuvres but significant centre differences in radiation exposures were found. Despite experienced scorers and prior training, with the exception of air trapping, inter- and intraobserver agreement on Brody-II score was poor to fair (eg, interobserver total score mean (95% CI) κ coefficient: 0.34 (0.20 to 0.49)). Only 7 (11%) infants had a total CT score ≥ 12 (ie, ≥ 5% maximum possible) by either scorer.

Conclusions: In NBS infants with CF, CT changes were very mild at 1 year, and assessment of air trapping was the only reproducible outcome. CT is thus of questionable value in infants of this age, unless an improved scoring system for use in mild CF disease can be developed.
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http://dx.doi.org/10.1136/thoraxjnl-2013-204176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963531PMC
April 2014

Evolution of lung function during the first year of life in newborn screened cystic fibrosis infants.

Thorax 2014 Oct 26;69(10):910-7. Epub 2013 Sep 26.

Portex Unit: Respiratory Physiology and Medicine, UCL Institute of Child Health, London, UK.

Rationale: Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants.

Objective: To assess changes in pulmonary function during the first year of life in CF NBS infants.

Methods: Observational longitudinal study. CF NBS infants and healthy controls were recruited between 2009 and 2011. Lung Clearance Index (LCI), plethysmographic lung volume (plethysmographic functional residual capacity (FRCpleth)) and forced expired volume (FEV₀.₅) were measured at 3 months and 1 year of age.

Main Results: Paired measurements were obtained from 72 CF infants and 44 controls. At 3 months, CF infants had significantly worse lung function for all tests. FEV₀.₅ improved significantly (0.59 (95% CI 0.18 to 0.99) z-scores; p<0.01) in CF infants between 3 months and 1 year, and by 1 year, FEV₀.₅ was only 0.52 (0.89 to 0.15) z-scores less than in controls. LCI and FRCpleth remained stable throughout the first year of life, being on average 0.8 z-scores higher in infants with CF. Pulmonary function at 1 year was predicted by that at 3 months. Among the 45 CF infants with entirely normal LCI and FEV₀.₅ at 3 months, 80% remained so at 1 year, while 74% of those with early abnormalities remained abnormal at 1 year.

Conclusions: This is the first study reporting improvements in FEV₀.₅ over time in stable NBS CF infants treated with standard therapy. Milder changes in lung function occurred by 1 year than previously reported. Lung function at 3 months predicts a high-risk group, who should be considered for intensification of treatment and enrolment into RCTs.
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http://dx.doi.org/10.1136/thoraxjnl-2013-204023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174068PMC
October 2014

Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study.

Lancet 2013 Jul 16;382(9888):223-33. Epub 2013 May 16.

Centre for Cardiovascular Imaging, Institute of Cardiovascular Science, University College London (UCL), London, UK.

Background: Post-mortem MRI is a potential diagnostic alternative to conventional autopsy, but few large prospective studies have compared its accuracy with that of conventional autopsy. We assessed the accuracy of whole-body, post-mortem MRI for detection of major pathological lesions associated with death in a prospective cohort of fetuses and children.

Methods: In this prospective validation study, we did pre-autopsy, post-mortem, whole-body MRI at 1·5 T in an unselected population of fetuses (≤24 weeks' or >24 weeks' gestation) and children (aged <16 years) at two UK centres in London between March 1, 2007 and Sept 30, 2011. With conventional autopsy as the diagnostic gold standard, we assessed MRI findings alone, or in conjunction with other minimally invasive post-mortem investigations (minimally invasive autopsy), for accuracy in detection of cause of death or major pathological abnormalities. A radiologist and pathologist who were masked to the autopsy findings indicated whether the minimally invasive autopsy would have been adequate. The primary outcome was concordance rate between minimally invasive and conventional autopsy.

Findings: We analysed 400 cases, of which 277 (69%) were fetuses and 123 (31%) were children. Cause of death or major pathological lesion detected by minimally invasive autopsy was concordant with conventional autopsy in 357 (89·3%, 95% CI 85·8-91·9) cases: 175 (94·6%, 90·3-97·0) of 185 fetuses at 24 weeks' gestation or less, 88 (95·7%, 89·3-98·3) of 92 fetuses at more than 24 weeks' gestation, 34 (81·0%, 66·7-90·0) [corrected] of 42 newborns aged 1 month or younger, 45 (84·9%, 72·9-92·1) of 53 infants aged older than 1 month to 1 year or younger, and 15 (53·6%, 35·8-70·5) of 28 children aged older than 1 year to 16 years or younger. The dedicated radiologist or pathologist review of the minimally invasive autopsy showed that in 165 (41%) cases a full autopsy might not have been needed; in these cases, concordance between autopsy and minimally invasive autopsy was 99·4% (96·6-99·9).

Interpretation: Minimally invasive autopsy has accuracy similar to that of conventional autopsy for detection of cause of death or major pathological abnormality after death in fetuses, newborns, and infants, but was less accurate in older children. If undertaken jointly by pathologists and radiologists, minimally invasive autopsy could be an acceptable alternative to conventional autopsy in selected cases.

Funding: Policy research Programme, Department of Health, UK.
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http://dx.doi.org/10.1016/S0140-6736(13)60134-8DOI Listing
July 2013

A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein.

Rheumatology (Oxford) 2013 Aug 25;52(8):1467-76. Epub 2013 Apr 25.

Rheumatology Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.

Objectives: In JIA there is an unmet need for biomarkers with which to identify patients who will respond well to MTX. The aim of this study was to define the prognostic value of baseline serum proteins and clinical variables in response to MTX to help inform the clinician at time of diagnosis whether the patient is likely to respond well to MTX.

Methods: JIA patients were recruited into the Childhood Arthritis Response to Medication Study (CHARMS). Clinical data and venous blood were collected before administration of MTX and at follow-up. MRP8/14 and inflammatory cytokines were measured by ELISA and multiplex immunoassay, respectively. CRP and ESR were measured as part of routine clinical assessment. To explore which baseline factors might predict successful treatment, binary logistic regression models were fitted for outcome.

Results: High disease activity (high serum MRP8/14, active joint count or physician's score) pre-MTX was observed in a subgroup of patients with a better response to therapy. In a multivariable analysis, after accounting for MRP8/14 at baseline, no other factors were independently significantly associated with outcome. Patients with baseline MRP8/14 >3000 ng/ml were more likely to respond to MTX at ACR50 or better: odds ratio 16.07 (95% CI 2.00, 129.3).

Conclusion: We have demonstrated that high levels of baseline serum MRP8/14 have prognostic value in predicting a subgroup of patients whose arthritis will improve on MTX. Routine collection of serum prior to the start of medication would be a valuable step in collaborative validation of such biomarkers.
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http://dx.doi.org/10.1093/rheumatology/ket152DOI Listing
August 2013

Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis.

PLoS One 2013 19;8(3):e58834. Epub 2013 Mar 19.

Academic Neonatology, Institute for Women's Health, University College London, London, United Kingdom.

Unlabelled: Although selective or whole body cooling combined with optimal intensive care improves outcomes following neonatal encephalopathy in high-income countries, the safety and efficacy of cooling in low-and middle-income countries is not known.

Objective: We performed a systematic review and meta-analysis of all published randomised or quasi-randomised controlled trials of cooling therapy for neonatal encephalopathy in low-and middle-income countries.

Results: Seven trials, comprising a total of 567 infants were included in the meta-analysis. Most study infants had mild (15%) or moderate encephalopathy (48%) and did not receive invasive ventilation (88%). Cooling devices included water-circulating cooling caps, frozen gel packs, ice, water bottles, and phase-changing material. No statistically significant reduction in neonatal mortality was seen with cooling (risk ratio: 0.74, 95% confidence intervals: 0.44 to 1.25). Data on other neonatal morbidities and long-term neurological outcomes were insufficient.

Conclusion: Cooling therapy was not associated with a statistically significant reduction in neonatal mortality in low-and middle-income countries although the confidence intervals were wide and not incompatible with results seen in high-income countries. The apparent lack of treatment effect may be due to the heterogeneity and poor quality of the included studies, inefficiency of the low technology cooling devices, lack of optimal neonatal intensive care, sedation and ventilatory support, overuse of oxygen, or may be due to the intrinsic difference in the population, for example higher rates of perinatal infection, obstructed labor, intrauterine growth retardation and maternal malnutrition. Evaluation of the safety and efficacy of cooling in adequately powered randomised controlled trials is required before cooling is offered in routine clinical practice in low-and middle-income countries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058834PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602578PMC
September 2013

Whole-body cooling in neonatal encephalopathy using phase changing material.

Arch Dis Child Fetal Neonatal Ed 2013 May 7;98(3):F280-1. Epub 2013 Mar 7.

Academic Neonatology, Institute for Women's Health, University College London, 74 Huntley Street, London WC1E 6AU, UK.

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http://dx.doi.org/10.1136/archdischild-2013-303840DOI Listing
May 2013

Risk-adjusted monitoring of blood-stream infection in paediatric intensive care: a data linkage study.

Intensive Care Med 2013 Jun 12;39(6):1080-7. Epub 2013 Feb 12.

MRC Centre for Epidemiology of Child Health, Institute of Child Health, University College London, 30 Guilford Street, London WC1 N 1EH, UK.

Purpose: National monitoring of variation in the quality of infection control in paediatric intensive care units (PICUs) requires comparisons of risk-adjusted rates. To inform the development of a national monitoring system, we evaluated the effects of risk-adjustment and outcome definition on comparisons of blood-stream infection (BSI) rates in PICU, using linkage of risk-factor data captured by national audit (PICANet) with laboratory records of BSI.

Methods: Admission data for two children's hospitals 2003-2010 were extracted from PICANet and linked using multiple identifiers with laboratory BSI records. We calculated trends of PICU-acquired BSI, defined as BSI occurring between at least 2 days after admission until up to 2 days following discharge. In one PICU, we compared rates of all PICU-acquired BSI with clinically significant PICU-acquired BSI submitted to the national surveillance system.

Results: Of 20,924 admissions, 1,428 (6.8 %) were linked to 1,761 PICU-acquired BSI episodes. The crude incidence rate-ratio for PICU-acquired BSI between PICUs was 1.15 [95 % confidence interval (CI) 1.05-1.26] but increased to 1.26 (1.14-1.39) after risk-adjustment. Rates of PICU-acquired BSI were 13.44 (95 % CI 12.60-14.28) per 1,000 bed-days at PICU 1 and 18.05 (95 % CI 16.80-19.32) at PICU 2. Of PICU-acquired BSI at PICU 2, 41 % was classified as clinically significant. Rates of PICU-acquired BSI decreased by 10 % per year between 2003 and 2010 for skin organisms and 8 % for non-skin organisms.

Conclusions: Risk-adjustment and standardisation of outcome measures are essential for fair comparisons of BSI rates between PICUs. Linkage of risk-factor data and BSI surveillance is feasible and could allow national risk-adjusted monitoring.
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http://dx.doi.org/10.1007/s00134-013-2841-zDOI Listing
June 2013