Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up. RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second line immunosuppressive regimen to be superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Post-mortem skeletal survey (PMSS) versus post-mortem computed tomography (PMCT) for the detection of corner metaphyseal lesions (CML) in children.

OBJECTIVES: Corner metaphyseal lesions (CMLs) are specific for child abuse but challenging to detect on radiographs. The accuracy of CT for CML detection is unknown. Our aim was to compare diagnostic accuracy for CML detection on post-mortem skeletal surveys (PMSS, plain radiography) versus post-mortem CT (PMCT). METHODS: A 10-year retrospective review was performed at a children's hospital for patients having PMSS, PMCT and histopathological correlation (reference standard) for suspected CMLs. Twenty-four radiologists independently reported the presence or absence of CMLs in all cases in a blinded randomised cross-over design across two rounds. Logistic regression models were used to compare accuracy between modalities. RESULTS: Twenty CMLs were reviewed for each of the 10 subjects (200 metaphyses in all). Among them, 20 CMLs were confirmed by bone histopathology. Sensitivity for these CMLs was significantly higher for PMSS (69.6%, 95% CI 61.7 to 76.7) than PMCT (60.5%, 95% CI 51.9 to 68.6). Using PMSS for detection of CMLs would yield one extra correct diagnosis for every 11.1 (95% CI 6.6 to 37.0) fractured bones. In contrast, specificity was higher on PMCT (92.7%, 95% CI 90.3 to 94.5) than PMSS (90.5%, 95% CI 87.6 to 92.8) with an absolute difference of 2.2% (95% CI 1.0 to 3.4, p < 0.001). More fractures were reported collectively by readers on PMSS (785) than on PMCT (640). CONCLUSION: PMSS remains preferable to PMCT for CML evaluation. Any investigation of suspected abuse or unexplained deaths should include radiographs of the limbs to exclude CMLs. CLINICAL RELEVANCE STATEMENT: In order to avoid missing evidence that could indicate child abuse as a contributory cause for death in children, radiographs of the limbs should be performed to exclude CMLs, even if a PMCT is being acquired. KEY POINTS: • Corner metaphyseal lesions (CMLs) are indicative for abuse, but challenging to detect. Skeletal surveys (i.e. radiographs) are standard practice; however, accuracy of CT is unknown. • Sensitivity for CML detection on radiographs is significantly higher than CT. • Investigation of unexplained paediatric deaths should include radiographs to exclude CMLs even if CT is also being performed.

Presentation to publication: Changes in paediatric radiology research trends 2010-2016.

BACKGROUND: More than half of paediatric radiology research presented at annual conference meetings between 2010-2012 remains unpublished. It is unclear if there are any improvements in this statistic despite some initiatives to improve awareness of the importance of evidence-based medicine. OBJECTIVES: To determine the abstract to publication rates (APRs) originating from recent paediatric radiology meetings, trends in research topics and factors associated with publication success. MATERIALS AND METHODS: All PubMed cited articles originating from oral presentations at European Society of Paediatric Radiology, Society for Paediatric Radiology or International Paediatric Radiology conferences between 2013-2016 were evaluated, and compared to those from previously published data from the same conferences dated 2010-2012. Publication rates, study design and topic as well as characteristics of the research group (e.g., author affiliations and number) were evaluated and compared between published and unpublished groups. RESULTS: The APR increased to 433/937 (46%) for abstracts presented between 2013-2016, compared to 300/715 (42%) in 2010-2012 (P=0.094). The largest proportion of publications comes from academic and tertiary centres (324/433 [75%]). International collaboration increased to 49/433 (11%) from 18/300 (6%) in 2010-2012 (P=0.018). A greater proportion of work was published within 12 months of conference: 41% in 2013-2016, compared to 29% in 2010-2012 (P=0.02). Paediatric Radiology remained the most popular destination journal, publishing 167/433 (39%) articles. CONCLUSION: There was a slight increase over time in the proportion of abstracts that resulted in publication, yet more than half of abstracts still do not reach publication status. Further work should identify how radiologists (particularly those outside tertiary and academic centres) can be supported to share their research.

Micro-CT yields high image quality in human fetal post-mortem imaging despite maceration.

BACKGROUND: Current clinical post-mortem imaging techniques do not provide sufficiently high-resolution imaging for smaller fetuses after pregnancy loss. Post-mortem micro-CT is a non-invasive technique that can deliver high diagnostic accuracy for these smaller fetuses. The purpose of the study is to identify the main predictors of image quality for human fetal post-mortem micro-CT imaging. METHODS: Human fetuses were imaged using micro-CT following potassium tri-iodide tissue preparation, and axial head and chest views were assessed for image quality on a Likert scale by two blinded radiologists. Simple and multivariable linear regression models were performed with demographic details, iodination, tissue maceration score and imaging parameters as predictor variables. RESULTS: 258 fetuses were assessed, with median weight 41.7 g (2.6-350 g) and mean gestational age 16 weeks (11-24 weeks). A high image quality score (> 6.5) was achieved in 95% of micro-CT studies, higher for the head (median = 9) than chest (median = 8.5) imaging. The strongest negative predictors of image quality were increasing maceration and body weight (p < 0.001), with number of projections being the best positive imaging predictor. CONCLUSIONS: High micro-CT image quality score is achievable following early pregnancy loss despite fetal maceration, particularly in smaller fetuses where conventional autopsy may be particularly challenging. These findings will help establish clinical micro-CT imaging services, addressing the need for less invasive fetal autopsy methods.

Use of ketogenic diet therapy in infants with epilepsy: A systematic review and meta-analysis.

OBJECTIVE: Ketogenic diet therapy (KDT) is a group of high-fat, low-carbohydrate diets used as an effective treatment option for children and adults with drug-resistant epilepsy. There is limited research on the efficacy of KDT in infants, where there is the highest incidence of onset of the epilepsy. We aimed to systematically review studies that have reported on response to KDT in infants with epilepsy. METHODS: An online comprehensive literature search was performed, including studies that provided seizure frequency data for at least one infant younger than 2 years of age who was treated with KDT for ≥1 month. The proportions of infants achieving ≥50% seizure reduction, seizure-freedom rates, retention rates, and reported side effects were extracted from studies. Meta-analyses were performed using a random-effects model, and subgroup analyses were performed to investigate possible between-study heterogeneity. RESULTS: Thirty-three studies met inclusion criteria and were included in the final analysis, with a total of 534 infants with efficacy data. Two studies were randomized-controlled trials, and the remainder were uncontrolled cohort studies. All studies were categorized as low quality. Meta-analyses of uncontrolled studies estimate 59% (95% confidence interval [CI] 53-65) of infants achieved ≥50% seizure reduction and 33% (95% CI 26-43) of infants achieved seizure freedom. Retention rates ranged from 84% at 3 months to 27% at 24 months. The most commonly reported side effects were dyslipidemia (20/171, 12%), vomiting (11/171, 6%), constipation (7/171, 4%), gastroesophageal reflux (6/171, 4%), and diarrhea (6/171, 4%). SIGNIFICANCE: This review indicates that KDT is safe and tolerable and that it can be an effective treatment option for infants with drug-resistant epilepsy. However, there are few studies focusing on infants treated with KDT, and high-quality evidence is lacking. High-quality randomized-controlled trials are needed to confirm the effectiveness, safety, and tolerability of dietary treatment in this vulnerable age group.

Maceration determines diagnostic yield of fetal and neonatal whole body post-mortem ultrasound.

OBJECTIVES: To determine factors in nondiagnostic fetal and neonatal post-mortem ultrasound (PMUS) examinations. METHODS: All fetal and neonatal PMUS examinations were included over a 5-year study period (2014-2019). Nondiagnostic image quality by body parts (brain, spine, thorax, cardiac, and abdomen) was recorded and correlated with patient variables. Descriptive statistics and logistic regression analyses were performed to identify significant factors for nondiagnostic studies. RESULTS: Two hundred sixty-five PMUS examinations were included, with median gestational age of 22 weeks (12-42 wk), post-mortem weight of 363 g (16-4033 g), and post-mortem interval of 8 days (0-39 d). Diagnostic imaging quality was achieved for 178/265 (67.2%) studies. It was high for abdominal (263/265, 99.2%), thoracic (264/265, 99.6%), and spine (265/265, 100%) but lower for brain (210/265, 79.2%) and cardiac imaging (213/265, 80.4%). Maceration was the best overall predictor for nondiagnostic imaging quality (P < .0001). Post-mortem fetal weight was positively associated with cardiac (P = .0133) and negatively associated with brain imaging quality (P = .0002). Post-mortem interval was not a significant predictor. CONCLUSIONS: Fetal maceration was the best predictor for nondiagnostic PMUS, particularly for brain and heart. Fetuses with marked maceration and suspected cardiac or brain anomalies should be prioritised for post-mortem MRI.

The use of whole body diffusion-weighted post-mortem magnetic resonance imaging in timing of perinatal deaths.

OBJECTIVES: Diffusion-weighted MRI provides information regarding body water movement following death, which may be an imaging marker of post-mortem interval (time since death; PMI) or maceration (degree of tissue degradation during intra-uterine retention) in perinatal deaths. Our aim was to evaluate the relationship between maceration, PMI and body organ apparent diffusion coefficient (ADC) values in a cohort of subjects across a wide gestational range. MATERIALS: Whole body post-mortem MRI with diffusion-weighted imaging (DWI) sequences were performed at 1.5 T, with b values of 0, 500 and 1000 mm2/s. Mean ADC values were calculated from regions of interest (ROIs) placed in the lungs, myocardium, spleen, renal cortex, liver and psoas muscle by two independent readers. Multivariable regression analysis was performed against PMI, gestational age, post-mortem weight, maceration score and gender. RESULTS: Eighty perinatal deaths were imaged with mean gestational age of 32 weeks (18-41 weeks), of which 49 (61.3%) were male. The mean PMI was 8 days (1-18 days). Maceration scores were statistically significant predictive factors for ADC values in all included body organs except the lungs, but PMI was not a predictor for ADC values in any body organ. In the absence of maceration (n = 14), PMI was not statistically associated with ADC values in any of the body areas. The ratio of agreement in the majority of body areas was close to 1 (range between 0.95 and 1.10). CONCLUSION: Maceration, not PMI, is significantly associated with ADC values in perinatal deaths. Further research is needed to understand organ-specific changes in the post-mortem period.

Learning effect on perinatal post-mortem magnetic resonance imaging reporting: single reporter diagnostic accuracy of 200 cases.

OBJECTIVE: The objective of the study is to compare diagnostic accuracy of perinatal post-mortem magnetic resonance (PMMR) imaging against conventional autopsy, when reported by a single-blinded observer for all organ systems following a period of initial experience. METHODS: We compared pre-autopsy PMMR with conventional autopsy for the detection of (1) major pathological abnormalities related to the cause of death and (2) all diagnostic findings in five different body organ systems. PMMR was reported blinded to autopsy findings. RESULTS: In 201 cases, 123/146 (84.2%) of major abnormalities were identified by PMMR. Overall diagnostic accuracy of PMMR was 89.6% [95% confidence interval (CI): 84.3, 93.2%] across all cases, with high concordance 91.8% (95% CI: 89.9, 93.4%) across most organ systems. Our study showed higher concordance than single reporter statistics previously reported in neurological [92.2% vs 73.8%; diff 18.4% (95% CI: 11.0, 25.4%) p < 0.01] and thoracic systems [93.7% vs 81.2%; diff 12.5% (95% CI: 6.3, 18.4%) p < 0.01] and slightly better overall [91.8% vs 87.1%; diff 4.7% (95% CI: 2.1, 7.3%) p < 0.01]. CONCLUSION: The PMMR examinations can be reliably reported by a single radiologist, following a period of experience and training with this specific modality, with high-diagnostic accuracy for all organ systems. © 2017 John Wiley & Sons, Ltd.

Presentation to publication: proportion of abstracts published for ESPR, SPR and IPR.

BACKGROUND: Advancement of knowledge requires presentation and publication of high-quality scientific research. Studies submitted for presentation undergo initial peer review before acceptance and the rate of subsequent publication may be taken as an indicator of access to publication for pediatric radiology studies. OBJECTIVES: Evaluate the proportion of abstracts also published in journals for pediatric radiology conferences and identify factors associated with publication success. MATERIALS AND METHODS: All Medline articles that originated from oral presentations at the European Society for Paediatric Radiology (ESPR), the Society for Pediatric Radiology (SPR) or the International Pediatric Radiology (IPR) conferences between 2010 - 2012 were evaluated. Descriptive statistics to evaluate published and unpublished groups were calculated overall and split by characteristics of the abstracts such as number of authors. RESULTS: Overall number of abstracts published was 300/715 (41.9%), with most articles published in radiology specific journals (181/300; 60.3%), with median impact factor 2.31 (interquartile range [IQR]: 1.65-3.14, range: 0-18.03). Those published after the conference (262/300, 87.6%) had a median time to publication of 18 months and for those published before, the median time was -11 months. Median sample size in published articles was 52 (IQR: 33-105, range: 1-6,351). CONCLUSION: Of pediatric radiology oral abstracts, 41.9% achieve publication after a period of at least 3 years from presentation. Studies originating from certain countries and on certain subspecialty topics were more likely to get published.

Assessing Heterogeneity in Random-Effects Meta-analysis.

The random-effects model allows for the possibility that studies in a meta-analysis have heterogeneous effects. That is, observed study estimates vary not only due to random sampling error but also due to inherent differences in the way studies have been designed and conducted. In this chapter, we consider methods to estimate the heterogeneity variance parameter in a random-effects model, consider in more detail what this parameter represents and how the possible explanations for heterogeneity can be explored through statistical methods. Toward the end of this chapter, publication bias is discussed as an alternative explanation for why observed effect estimates might form some distribution other than what we might come to expect.

The effectiveness of psychological interventions for loneliness: A systematic review and meta-analysis.

Chronic loneliness is associated with a range of mental health difficulties. Previous theory and research indicate that psychological interventions show promise for reducing loneliness, however, there have been no systematic reviews or meta-analyses to ascertain the efficacy of these interventions across the lifespan. The aim of this study was to synthesise, meta-analyse and explore the heterogeneity in RCTs of psychological interventions for loneliness in order to establish their efficacy. Five databases (Ovid Embase, Ovid Medline, PsycINFO, Web of Science and CINAHL) were systematically searched in order to identify relevant studies. Included studies were required to be peer-reviewed RCTs examining psychological interventions for loneliness. Two independent coders examined the abstracts of the 3973 studies and 103 full texts, finding 31 studies that met inclusion criteria, 28 of which contained sufficient statistical information to be included in the meta-analysis. The quality of included studies was assessed using the Cochrane Risk of Bias Tool. The 31 studies (N = 3959) that were included in the systematic review were conducted with participants from a diverse range of cultures, age groups and populations. The interventions were of mixed quality and were mostly face to face, group-based and delivered weekly. The most common type of intervention was Cognitive Behavioural Therapy (CBT). 28 studies (N = 3039) were included in a meta-analysis which found that psychological interventions significantly reduced loneliness compared to control groups, yielding a small to medium effect size (g = 0.43). Subgroup analysis and meta-regressions were conducted in order to explore heterogeneity and found that type of psychological intervention was approaching significance as a moderator of the effectiveness of psychological interventions for loneliness. In conclusion, psychological interventions for loneliness across the lifespan are effective. This finding should inform policy makers, researchers and clinicians going forward, especially in the context of increased loneliness due to the COVID-19 pandemic. There was considerable heterogeneity in the effectiveness of the interventions, suggesting that future research should also explore what works for whom and consider personalising psychological treatment.

Impact of the COVID-19 pandemic on radiology appointments in a tertiary children's hospital: a retrospective study.

In this retrospective observational study, we evaluated the impact of the COVID-19 pandemic in London on paediatric radiology activity, as a surrogate of overall hospital activity. We showed a large reduction in overall outpatient imaging activity: 49 250 records occurred in the 371 days post COVID-19 period compared with an expected 67 806 records pre COVID-19 period, representing 18 556 'missed' records. Governmental restrictions were associated with reductions in activity, with the largest reduction in activity during tiers 3 and 4 restrictions. Rescheduling such missed outpatients' appointments represents considerable resource planning and the associated clinical impact on paediatric healthcare remains to be determined.

Incidence and prevalence of hypoglycaemia in type 1 and type 2 diabetes individuals: A systematic review and meta-analysis.

BACKGROUND: Previous meta-analysis investigating the incidence and prevalence of hypoglycaemia in both types of diabetes is limited. The purpose of this review is to conduct a systematic review and meta-analysis of the existing literature which investigates the incidence and prevalence of hypoglycaemia in individuals with diabetes. METHODS: PubMed, Embase and Cochrane library databases were searched up to October 2018. Observational studies including individuals with diabetes of all ages and reporting incidence and/or prevalence of hypoglycaemia were included. Two reviewers independently screened articles, extracted data and assessed the quality of included studies. Meta-analysis was performed using a random effects model with 95% confidence interval (CI) to estimate the pooled incidence and prevalence of hypoglycaemia in individuals with diabetes. RESULTS: Our search strategy generated 35,007 articles, of which 72 studies matched the inclusion criteria and were included in the meta-analysis. The prevalence of hypoglycaemia ranged from 0.074% to 73.0%, comprising a total of 2,462,810 individuals with diabetes. The incidence rate of hypoglycaemia ranged from 0.072 to 42,890 episodes per 1,000 person-years: stratified by type of diabetes, it ranged from 14.5 to 42,890 episodes per 1,000 person-years and from 0.072 to 16,360 episodes per 1,000-person years in type 1 and type 2 diabetes, respectively. CONCLUSION: Hypoglycaemia is very common among individuals with diabetes. Further studies are needed to investigate hypoglycaemia-associated risk factors.

Diagnostic accuracy of perinatal post-mortem ultrasound (PMUS): a systematic review.

OBJECTIVE: Ultrasound is ubiquitous in live paediatric imaging; however, its usage in post-mortem setting is less established. This systematic review aims to evaluate the diagnostic accuracy of paediatric post-mortem ultrasound (PMUS). DESIGN: MEDLINE, Embase and Cochrane Library databases were queried for studies published between 1998 and 2018 assessing PMUS diagnostic accuracy rates in children<18 years old, using autopsy as reference standard. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2. A bivariate random-effects model was used to obtain combined mean estimates of sensitivity and specificity for different body systems. RESULTS: Four studies were included, all relating to ultrasound for perinatal deaths. The mean diagnostic sensitivity and specificity for neurological abnormalities were 84.3% (95% CI: 70.8% to 92.2%) and 96.7% (95% CI: 86.5% to 99.3%); for cardiothoracic abnormalities 52.1% (95% CI: 27.6% to 75.5%,) and 96.6% (95% CI: 86.8% to 99.2%); and for abdominal abnormalities 78.4% (95% CI: 61.0% to 89.4%) and 97.3% (95% CI: 88.9% to 99.4%). Combining all body systems, the mean sensitivity and specificity were 73.3% (95% CI: 59.9% to 83.5%) and 96.6% (95% CI: 92.6% to 98.4%). CONCLUSIONS: PMUS demonstrates a reasonable diagnostic accuracy, particularly for abdominal and neurological abnormalities, although cardiac anomalies were less readily identified. TRIAL REGISTRATION NUMBER: CRD42018106968.

A comparison of heterogeneity variance estimators in simulated random-effects meta-analyses.

Studies combined in a meta-analysis often have differences in their design and conduct that can lead to heterogeneous results. A random-effects model accounts for these differences in the underlying study effects, which includes a heterogeneity variance parameter. The DerSimonian-Laird method is often used to estimate the heterogeneity variance, but simulation studies have found the method can be biased and other methods are available. This paper compares the properties of nine different heterogeneity variance estimators using simulated meta-analysis data. Simulated scenarios include studies of equal size and of moderate and large differences in size. Results confirm that the DerSimonian-Laird estimator is negatively biased in scenarios with small studies and in scenarios with a rare binary outcome. Results also show the Paule-Mandel method has considerable positive bias in meta-analyses with large differences in study size. We recommend the method of restricted maximum likelihood (REML) to estimate the heterogeneity variance over other methods. However, considering that meta-analyses of health studies typically contain few studies, the heterogeneity variance estimate should not be used as a reliable gauge for the extent of heterogeneity in a meta-analysis. The estimated summary effect of the meta-analysis and its confidence interval derived from the Hartung-Knapp-Sidik-Jonkman method are more robust to changes in the heterogeneity variance estimate and show minimal deviation from the nominal coverage of 95% under most of our simulated scenarios.

Methods to calculate uncertainty in the estimated overall effect size from a random-effects meta-analysis.

Meta-analyses are an important tool within systematic reviews to estimate the overall effect size and its confidence interval for an outcome of interest. If heterogeneity between the results of the relevant studies is anticipated, then a random-effects model is often preferred for analysis. In this model, a prediction interval for the true effect in a new study also provides additional useful information. However, the DerSimonian and Laird method-frequently used as the default method for meta-analyses with random effects-has been long challenged due to its unfavorable statistical properties. Several alternative methods have been proposed that may have better statistical properties in specific scenarios. In this paper, we aim to provide a comprehensive overview of available methods for calculating point estimates, confidence intervals, and prediction intervals for the overall effect size under the random-effects model. We indicate whether some methods are preferable than others by considering the results of comparative simulation and real-life data studies.

Chest radiographs versus CT for the detection of rib fractures in children (DRIFT): a diagnostic accuracy observational study.

BACKGROUND: Internationally, chest radiography is the standard investigation for identifying rib fractures in suspected physical abuse in infants. Several small observation studies in children have found that chest CT can provide greater accuracy than radiography for fracture detection, potentially aiding medicolegal proceedings in abuse cases; however, to our knowledge, this greater accuracy has not been comprehensively evaluated. We aimed to determine differences in rib fracture detection rates between post-mortem chest radiographs and chest CT images, using forensic autopsy as the reference standard. METHODS: In this retrospective diagnostic accuracy study, we searched the Great Ormond Street Hospital (London, UK) radiology information system for all children aged 0-16 years who had a post-mortem skeletal survey (ie, full-body radiography), CT, and full autopsy between Jan 1, 2012, and Jan 1, 2017, for a purpose of death investigation. Cases were excluded if the imaging was done for a reason other than a forensic investigation or if image quality was suboptimal. Radiologists were recruited as reporters on a voluntary basis via membership databases from international radiology and post-mortem imaging societies with no specific inclusion or exclusion criteria. Reporters were sent a set of chest radiographs on a password protected and encrypted USB flash drive or via a secure filesharing website and independently reported on the presence of rib fractures, fracture location, and the confidence level of their interpretation. They were masked to the clinical information of the images. 1 month later, the same reporters were sent CTs for the same cases in a random order and asked to report on the same features. The primary objective was to compare the accuracy of detection of rib fractures by use of post-mortem chest radiographs and CTs, with autopsy data as reference standard. Accuracy was assessed by comparison of diagnostic statistics, calculated using random-intercept multilevel logistic models with reporter and patient included as cross-classified random-effects. FINDINGS: 25 cases of children (aged 1 month to 7 years), with 136 rib fractures at autopsy with paired post-mortem chest radiographs and CTs, were selected for analysis. 38 radiologists were recruited as reporters from 23 international centres; 12 (32%) were consultants, median experience of 14·5 years (range 6-27), and 26 (68%) were registrars, median experience of 4 years (range 2-9). Across all radiologists, three times as many rib fractures were correctly detected by use of chest CTs compared with chest radiography (sensitivity 44·9% [95% CI 31·7-58·9] vs 13·5% [8·1-21·5]; difference 31·4% [23·3-37·8; p<0·001]). Sensitivity for detection on the correct rib was higher by use of CT than by use of radiography (62·4% [95% CI 44·9-77·1] vs 23·1% [12·9-37·8]; difference 39·3% [31·9-42·2; p<0·001]), as was diagnosis of a patient with any rib fracture or fractures (81·5% [75·8-86·0] vs 64·7% [57·3-71·4]; difference 16·7% [11·5-22·2; p<0·001]). Radiologist confidence was higher when using CT images than radiographs (highest confidence rating given on 3317 [63·6%] of 5218 fractures for CT vs 1518 [46·6%] of 3303 on radiographs) and was a predictor for accurate fracture detection. INTERPRETATION: Chest CT provides greater accuracy than conventional chest radiography for post-mortem rib fracture detection, irrespective of radiologist experience or fracture location, although both methods detected a substantial number of false positives. The diagnostic accuracy of CT should be studied further in live children ideally in a multicentre trial to assess the applicability of our results. FUNDING: Great Ormond Street Children's Charity, Medical Research Council, Royal College of Radiologists, Research Councils UK, National Institute for Health Research.

Comparative performance of heterogeneity variance estimators in meta-analysis: a review of simulation studies.

Random-effects meta-analysis methods include an estimate of between-study heterogeneity variance. We present a systematic review of simulation studies comparing the performance of different estimation methods for this parameter. We summarise the performance of methods in relation to estimation of heterogeneity and of the overall effect estimate, and of confidence intervals for the latter. Among the twelve included simulation studies, the DerSimonian and Laird method was most commonly evaluated. This estimate is negatively biased when heterogeneity is moderate to high and therefore most studies recommended alternatives. The Paule-Mandel method was recommended by three studies: it is simple to implement, is less biased than DerSimonian and Laird and performs well in meta-analyses with dichotomous and continuous outcomes. In many of the included simulation studies, results were based on data that do not represent meta-analyses observed in practice, and only small selections of methods were compared. Furthermore, potential conflicts of interest were present when authors of novel methods interpreted their results. On the basis of current evidence, we provisionally recommend the Paule-Mandel method for estimating the heterogeneity variance, and using this estimate to calculate the mean effect and its 95% confidence interval. However, further simulation studies are required to draw firm conclusions. Copyright © 2016 John Wiley & Sons, Ltd.

Quality of missing data reporting and handling in palliative care trials demonstrates that further development of the CONSORT statement is required: a systematic review.

OBJECTIVES: Assess (i) the quality of reporting and handling of missing data (MD) in palliative care trials, (ii) whether there are differences in the reporting of criteria specified by the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement compared with those not specified, and (iii) the association of the reporting of MD with journal impact factor and CONSORT endorsement status. STUDY DESIGN AND SETTING: Systematic review of palliative care randomized controlled trials. CENTRAL, MEDLINE, and EMBASE (2009-2014) were searched. RESULTS: One hundred and eight trials (15,560 participants) were included. MD was incompletely reported and not handled in accordance with current guidance. Reporting criteria specified by the CONSORT statement were better reported than those not specified (participant flow, 69%; number of participants not included in the primary outcome analysis, 94%; and the reason for MD, 71%). However, MD in items contributing to scale summaries (10%) and secondary outcomes (9%) were poorly reported, so the proportion of MD stated is likely to be an underestimate. The reason for MD provided was unclear for 54% of participants and only 16% of trials with MD reported a MD sensitivity analysis. The odds of reporting most of the MD and other risk of bias reporting criteria were increased as the journal impact factor increased and in journals that endorsed the CONSORT statement. CONCLUSION: Further development of the CONSORT MD reporting guidance is likely to improve the quality of reporting. Reporting recommendations are provided.

Three-Dimensional Imaging-Based Web Application for Predicting Tracheal Tube Depth in Preterm Neonates.

BACKGROUND: Positioning a tracheal tube (TT) to the correct depth in preterm infants is challenging. Currently, there is no reliable single-predictor model for neonates applicable to the whole range of size or age. OBJECTIVE: In this study, we used post-mortem magnetic resonance imaging (PMMRI) of preterm infants to measure tracheal dimensions and to develop a clinical guide for TT positioning. METHODS: We measured tracheal length (TL) and tracheal diameter (TD) in a cohort of normal neonates and foetuses that underwent PMMRI (cause of death unexplained). The distance between the lips and the mid-tracheal point, i.e., the mid-tracheal length (mid-TL), and the TD measurement were obtained. We produced univariate prediction models of mid-TL and TD, using gestational age (GA), foot length (FL), crown-rump length (CRL) and body weight (BW) as potential predictors, as well as multiple prediction models for mid-TL. RESULTS: Tracheal measurements were performed in 117 cases, with a mean GA of 28.8 weeks (range 14-42 weeks). The best linear association was between mid-TL and FL (mid-TL = FL × 0.914 + 1.859; R2 = 0.94), but was improved by multivariate regression models. We developed a prediction tool using only GA and BW (R2 = 0.92), and all four predictors (GA, BW, FL and CRL; R2 = 0.94) which is now available as a web-based application via the Internet. CONCLUSION: Post-mortem imaging data provide estimates of TT insertion depth. Our prediction tool based on age and BW can be used at the bedside and is ready to be tested in clinical practice.