Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for ...the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK.
Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital.
Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%.
Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.
Childhood cancer is increasing in prevalence whilst survival rates are improving. The prevalence of adult survivors of childhood cancer is consequently increasing. Many survivors suffer long‐term ...consequences of their cancer treatment. Whilst many of these are well documented, relatively little is known about the mental health of survivors of childhood cancer. This article aimed to describe the prevalence and spectrum of mental health problems found in adult survivors of childhood cancer using a systematic review methodology. Our review included 67 articles, describing a number of problems, including depression, anxiety, behavioural problems and drug misuse. Factors increasing the likelihood of mental health problems included treatment with high‐dose anthracyclines, cranial irradiation, diagnoses of sarcoma or central nervous system tumours and ongoing physical ill health. There were numerous limitations to the studies we found, including use of siblings of survivors as a control group, self‐report methodology and lack of indications for prescriptions when prescribing data were used. This review has identified many mental health problems experienced by survivors of childhood cancer; however, the exact incidence, prevalence and risk‐factors for their development remain unclear. Further work to identify childhood cancer patients who are at risk of developing late mental health morbidity is essential.
The presence of autoantibodies to multiple-islet autoantigens confers high risk for the development of type 1 diabetes. Four major autoantigens are established (insulin, glutamate decarboxylase, IA2, ...and zinc transporter-8), but the molecular identity of a fifth, a 38-kDa membrane glycoprotein (Glima), is unknown. Glima antibodies have been detectable only by immunoprecipitation from extracts of radiolabeled islet or neuronal cells. We sought to identify Glima to enable efficient assay of these autoantibodies. Mouse brain and lung were shown to express Glima. Membrane glycoproteins from extracts of these organs were enriched by detergent phase separation, lectin affinity chromatography, and SDS-PAGE. Proteins were also immunoaffinity purified from brain extracts using autoantibodies from the sera of patients with diabetes before SDS-PAGE. Eluates from gel regions equivalent to 38 kDa were analyzed by liquid chromatography-tandem mass spectrometry for protein identification. Three proteins were detected in samples from the brain and lung extracts, and in the immunoaffinity-purified sample, but not in the negative control. Only tetraspanin-7, a multipass transmembrane glycoprotein with neuroendocrine expression, had physical characteristics expected of Glima. Tetraspanin-7 was confirmed as an autoantigen by demonstrating binding to autoantibodies in type 1 diabetes. We identify tetraspanin-7 as a target of autoimmunity in diabetes, allowing its exploitation for diabetes prediction and immunotherapy.
Whilst the movement demands of players completing a whole soccer match have been well-documented, comparable information relating to substitutes is sparse. Therefore, this study profiled the ...match-day physical activities performed by soccer substitutes, focusing separately on the pre and post pitch-entry periods. Seventeen English Championship soccer players were monitored using 10 Hz Micromechanical Electrical Systems (MEMS) devices during 13 matches in which they participated as substitutes (35 observations). Twenty physical variables were examined and data were organised by bouts of warm-up activity (pre pitch-entry), and five min epochs of match-play (post pitch-entry). Linear mixed modelling assessed the influence of time (i.e., 'bout' and 'epoch'), playing position, and match scoreline. Substitutes performed 3±1 rewarm-up bouts∙player-1∙match-1. Compared to the initial warm-up, each rewarm-up was shorter (-19.7 to -22.9 min) and elicited less distance (-606 to -741 m), whilst relative total distances were higher (+26 to +69 m∙min-1). Relative total (+13.4 m∙min-1) and high-speed (+0.4 m∙min-1) distances covered during rewarm-ups increased (p <0.001) with proximity to pitch-entry. Players covered more (+3.2 m; p = 0.047) high-speed distance per rewarm-up when the assessed team was losing compared with when winning at the time of pitch-entry. For 10 out of 20 variables measured after pitch-entry, values reduced from 0-5 min thereafter, and substitutes covered greater (p ˂0.05) total (+67 to +93 m) and high-speed (+14 to +33 m) distances during the first five min of match-play versus all subsequent epochs. Midfielders covered more distance (+41 m) per five min epoch than both attackers (p ˂0.001) and defenders (p = 0.016). Acknowledging the limitations of a solely movement data approach and the potential influence of other match-specific factors, such findings provide novel insights into the match-day demands faced by substitute soccer players. Future research opportunities exist to better understand the match-day practices of this population.
Adolescent and young adults (AYA) with germ cell tumours (GCT) have poorer survival rates than children and many older adults with the same cancers. There are several likely contributing factors to ...this, including the treatment received. The prognostic benefit of intended dose intensity is well documented in GCT from trials comparing regimens. However, evidence specific to AYA is limited by poor recruitment of AYA to trials and dose delivery outside trials not being well examined. We examined the utility of cancer registration data and a clinical trials dataset to investigate the delivery of relative dose intensity (RDI) in routine National Health Service practice in England, compared to within international clinical trials. Linked data from the Cancer Outcomes and Services Dataset (COSD) and the Systemic Anti-Cancer Therapy (SACT) dataset, and data from four international clinical trials were analysed. Survival over time was described using Kaplan-Meier estimation; overall, by age category, International Germ-Cell Cancer Collaborative Group (IGCCCG) classification, stage, tumour subtype, primary site, ethnicity and deprivation. Cox regression models were used to determine the fully adjusted effect of RDI on mortality risk. The quality of both datasets was critically evaluated and clinically enhanced. RDI was found to be well maintained in all datasets with higher RDIs associated with improved survival outcomes. Real-world data demonstrated several strengths, including population coverage and inclusion of sociodemographic variables and comorbidity. It is limited in GCT however, by the poor completion of data items enabling risk classification of patients and a higher proportion of missing data.
Peripheral neuropathy affects 1 in 10 adults over the age of 40 years. Given the absence of a reliable diagnostic test for peripheral neuropathy, there has been a surge of research into diffusion ...tensor imaging (DTI) because it characterises nerve microstructure and provides reproducible proxy measures of myelination, axon diameter, fibre density and organisation. Before researchers and clinicians can reliably use diffusion tensor imaging to assess the 'health' of the major nerves of the upper limb, we must understand the "normal" range of values and how they vary with experimental conditions. We searched PubMed, Embase, medRxiv and bioRxiv for studies which reported the findings of DTI of the upper limb in healthy adults. Four review authors independently triple extracted data. Using the meta suite of Stata 17, we estimated the normal fractional anisotropy (FA) and diffusivity (mean, MD; radial, RD; axial AD) values of the median, radial and ulnar nerve in the arm, elbow and forearm. Using meta-regression, we explored how DTI metrics varied with age and experimental conditions. We included 20 studies reporting data from 391 limbs, belonging to 346 adults (189 males and 154 females, ~ 1.2 M:1F) of mean age 34 years (median 31, range 20-80). In the arm, there was no difference in the FA (pooled mean 0.59 mm
/s 95% CI 0.57, 0.62; I
98%) or MD (pooled mean 1.13 × 10
mm
/s 95% CI 1.08, 1.18; I
99%) of the median, radial and ulnar nerves. Around the elbow, the ulnar nerve had a 12% lower FA than the median and radial nerves (95% CI - 0.25, 0.00) and significantly higher MD, RD and AD. In the forearm, the FA (pooled mean 0.55 95% CI 0.59, 0.64; I
96%) and MD (pooled mean 1.03 × 10
mm
/s 95% CI 0.94, 1.12; I
99%) of the three nerves were similar. Multivariable meta regression showed that the b-value, TE, TR, spatial resolution and age of the subject were clinically important moderators of DTI parameters in peripheral nerves. We show that subject age, as well as the b-value, TE, TR and spatial resolution are important moderators of DTI metrics from healthy nerves in the adult upper limb. The normal ranges shown here may inform future clinical and research studies.
Abstract
Background
The coronavirus disease-19 (COVID-19) pandemic had a relatively minimal direct impact on critical illness in children compared to adults. However, children and paediatric ...intensive care units (PICUs) were affected indirectly. We analysed the impact of the pandemic on PICU admission patterns and patient characteristics in the UK and Ireland.
Methods
We performed a retrospective cohort study of all admissions to PICUs in children < 18 years during Jan–Dec 2020, using data collected from 32 PICUs via a central database (PICANet). Admission patterns, case-mix, resource use, and outcomes were compared with the four preceding years (2016–2019) based on the date of admission.
Results
There were 16,941 admissions in 2020 compared to an annual average of 20,643 (range 20,340–20,868) from 2016 to 2019. During 2020, there was a reduction in all PICU admissions (18%), unplanned admissions (20%), planned admissions (15%), and bed days (25%). There was a 41% reduction in respiratory admissions, and a 60% reduction in children admitted with bronchiolitis but an 84% increase in admissions for diabetic ketoacidosis during 2020 compared to the previous years. There were 420 admissions (2.4%) with either PIMS-TS or COVID-19 during 2020. Age and sex adjusted prevalence of unplanned PICU admission reduced from 79.7 (2016–2019) to 63.1 per 100,000 in 2020. Median probability of death 1.2 (0.5–3.4) vs. 1.2 (0.5–3.4) %, length of stay 2.3 (1.0–5.5) vs. 2.4 (1.0–5.7) days and mortality rates 3.4 vs. 3.6%, (risk-adjusted OR 1.00 0.91–1.11,
p
= 0.93) were similar between 2016–2019 and 2020. There were 106 fewer in-PICU deaths in 2020 (
n
= 605) compared with 2016–2019 (
n
= 711).
Conclusions
The use of a high-quality international database allowed robust comparisons between admission data prior to and during the COVID-19 pandemic. A significant reduction in prevalence of unplanned admissions, respiratory diseases, and fewer child deaths in PICU observed may be related to the targeted COVID-19 public health interventions during the pandemic. However, analysis of wider and longer-term societal impact of the pandemic and public health interventions on physical and mental health of children is required.
IntroductionOptimising the health of childhood cancer survivors is important given the high long-term survival rate coupled with a significant late effects burden. Included within the WHO’s ...definition of ‘Health’ are social outcomes. These are of interest given their impact on adult functioning within society, complex interactions with physical and mental health outcomes and potential for cross generational effects. Categories included within the definition of social outcomes are ill defined leading to potential gaps in research and service provision which could affect the ability of survivors to achieve their maximal potential. An e-Delphi study will be used to achieve expert consensus on the most important social outcomes for childhood cancer survivors to inform future research and ultimately, service provision.Methods and analysisA heterogeneous sample of at least 48 panel members will be recruited across four groups chosen to provide different perspectives on the childhood cancer journey: childhood cancer survivors, health professionals, social workers and teachers. Purposive sampling from a UK, regional long-term follow-up clinic will be used to recruit a representative sample of survivors. Other panel members will be recruited through local channels and national professional working groups. Opinions regarding breakdown and relevance of categories of social outcome will be collected through 3–5 rounds of questionnaires using an e-Delphi technique. Open ended, 7-point Likert scale and ranking questions will be used. Each round will be analysed collectively and per group to assess inter-rater agreement. Agreement and strength of agreement will be indicated by a median score of 6 or 7 and mean absolute deviation from the median, respectively.Ethics and disseminationEthical approval for this study has been granted by Regional Ethics Committee 4, West of Scotland (ID 297344). Study findings will be disseminated to involved stakeholders, published in a peer-reviewed journal and presented at conferences.
This study examined the relationship between self-esteem, restrained eating, body image and body mass index during pregnancy. A total of 110 pregnant Israeli and UK women completed the Rosenberg ...Self-Esteem Questionnaire, the Dutch Eating Behaviour Questionnaire, scales to assess body image and demographics. Body mass index was calculated from antenatal records. Regression modelling determined the relationship between variables, countries and body mass index categories. High correlations were found between body image and body mass index with significantly higher body dissatisfaction for Israeli women. Self-esteem scores for pregnant women were similar to those reported for non-pregnant women. Poorer body image and higher prevalence of restrained eating were found in healthy weight Israeli women.
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