Delivered relative dose intensity in adolescent and young adult germ cell tumours in England: Assessment of data quality and consistency from clinical trials compared to national cancer registration data.

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.

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

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

ABO blood group in aneurysmal subarachnoid haemorrhage-a pilot study.

PURPOSE: To evaluate the distribution and impact of ABO blood group on the baseline characteristics and clinical outcomes of patients presenting with aneurysmal subarachnoid haemorrhage (aSAH). METHODS: Retrospective, single-centre study of patients admitted to a neurosurgical department in the UK, with a diagnosis of spontaneous subarachnoid haemorrhage between May 2014 and January 2020. Patients were categorised by ABO blood type and by Rhesus status. Clinical outcomes such as initial bleeding, rebleeding, delayed cerebral ischaemia (DIND) and venous thromboembolism were analysed in relation to the size of their association with ABO blood type. Hospital mortality rate, Glasgow Outcome Score (GOS) - at discharge and 3 months post-ictus, requirement for ventriculoperitoneal shunt insertion, discharge destination and inpatient length of stay were also considered. RESULTS: Four-hundred twelve adult patients admitted with aSAH were included in our analysis. The distribution of ABO group or Rhesus status in our cohort did not differ significantly from the general population in the UK. Blood group A patients had a significantly increased risk of developing DIND, compared with non-blood group A patients (OR, 1.88 [95% CI: 1.10-3.21]). CONCLUSIONS: ABO blood type appears to influence aSAH sequelae. Blood group A patients are at highest risk of DIND following aSAH.

Maternal iodine status in a multi-ethnic UK birth cohort: associations with autism spectrum disorder.

BACKGROUND: Maternal iodine requirements increase during pregnancy to supply thyroid hormones essential for fetal brain development. Maternal iodine deficiency can lead to hypothyroxinemia, a reduced fetal supply of thyroid hormones which, in the first trimester, has been linked to an increased risk of autism spectrum disorder (ASD) in the child. No study to date has explored the direct link between maternal iodine deficiency and diagnosis of ASD in offspring. METHODS: Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6955 mothers at 26-28 weeks gestation participating in the Born in Bradford (BiB) cohort. Maternal iodine status was examined in relation to the probability of a Read (CTV3) code for autism being present in a child's primary care records through a series of logistic regression models with restricted cubic splines. RESULTS: Median (inter-quartile range) UIC was 76 µg/L (46, 120) and I:Cr was 83 µg/g (59, 121) indicating a deficient population according to WHO guidelines. Ninety two children (1·3%) in our cohort had received a diagnosis of ASD by the census date. Overall, there was no evidence to support an association between I:Cr or UIC and ASD risk in children aged 8-12 years (p = 0·3). CONCLUSIONS: There was no evidence of an increased clinical ASD risk in children born to mothers with mild-to-moderate iodine deficiency at 26 weeks gestation. Alternative functional biomarkers of exposure and a wider range of conditions may provide further insight.

Early educational attainment in children with major congenital anomaly in the UK.

OBJECTIVE: To describe early educational attainment and special educational needs (SEN) provision in children with major congenital anomaly (CA) compared with peers. DESIGN: Analysis of educational data linked to the ongoing Born in Bradford cohort study. Confounders were identified via causal inference methods and multivariable logistic regression performed. SETTING: Children born in Bradford Royal Infirmary (BRI), West Yorkshire. PATIENTS: All women planning to give birth at BRI and attending antenatal clinic from March 2007 to December 2010 were eligible. 12 453 women with 13 776 pregnancies (>80% of those attending) were recruited. Records of 555 children with major CA and 11 188 without were linked to primary education records. OUTCOMES: Key Stage 1 (KS1) attainment at age 6-7 years in Maths, Reading, Writing and Science. SEN provision from age 4 to 7 years. RESULTS: 41% of children with major CA received SEN provision (compared with 14% without), and 48% performed below expected standards in at least one KS1 domain (compared with 29% without). The adjusted odds of children with CA receiving SEN provision and failing to achieve the expected standard at KS1 were, respectively, 4.30 (95% CI 3.49 to 5.31) and 3.06 (95% CI 2.47 to 3.79) times greater than their peers. Those with genetic, heart, neurological, urinary, gastrointestinal and limb anomalies had significantly poorer academic achievement. CONCLUSIONS: These novel results demonstrate that poor educational attainment extends to children with urinary, limb and gastrointestinal CAs. We demonstrate the need for collaboration between health and education services to assess and support children with major CA, so every CA survivor can maximise their potential.

Neuropathic pain questionnaires for back pain, what do we know?

INTRODUCTION: Low back pain is a global public health concern, with an estimated lifetime prevalence of 84%. Axial low back pain refers to pain confined to an area in the low back and is different to radicular pain which radiates to extremities. Axial low back pain has traditionally been considered as nociceptive. However, research suggests it may have neuropathic components. Neuropathic axial low back pain is an unresolved, hotly contested topic due to controversies surrounding its aetiology, diagnosis, clinical course, prognosis and treatment options. PURPOSE: The reference standard for diagnosing neuropathic pain is by medical history and clinical assessment (i.e., sensory testing), with optional neuropathic screening tools and selective, further diagnostic tests when clinically needed. Neuropathic screening tools are not always specific for neuropathic radiating low back pain, let alone neuropathic axial low back pain. Additionally, not all have been validated for the English language (e.g., PainDETECT). Research also suggests the percentage of patients identified as having neuropathic radiating low back pain may be dependent on the combination of reference standards used. IMPLICATIONS: There is a need for research that works towards improving understanding of neuropathic axial low back pain and developing a standardised, validated and reliable system for assessing and identifying this condition. This body of research will promote earlier stratification and more rapid referral for appropriate treatment, and improve awareness, assessment and visibility of this condition amongst healthcare practitioners and in healthcare settings. This will lead to transformations in Pathways and health guidelines, ultimately improving patient outcomes.

Educational attainment of children with congenital Heart disease in the United Kingdom.

BACKGROUND: Educational attainment in children with congenital heart disease (CHD) within the UK has not been reported, despite the possibility of school absences and disease-specific factors creating educational barriers. METHODS: Children were prospectively recruited to the Born in Bradford birth cohort between March 2007 and December 2010. Diagnoses of CHD were identified through linkage to the congenital anomaly register and independently verified by clinicians. Multivariable regression accounted for relevant confounders. Our primary outcome was the odds of 'below expected' attainment in Maths, Reading and Writing at ages 4-11 years. RESULTS: Educational records of 139 children with non-genetic CHD were compared to 11 188 age-matched children with no major congenital anomaly. Children with CHD had significantly higher odds of 'below expected' attainment in Maths at age 4-5 years (Odds Ratio 1.64, 95% CI 1.07-2.52), age 6-7 (OR 2.03, 95% CI 1.32-3.12), and age 10-11 (OR 2.28, 95% CI 1.01-5.14). Odds worsened with age, with similar results for Reading and Writing. The odds of receiving special educational needs support reduced with age for children with CHD relative to controls (age 4-5: OR 4.84 (2.06-11.40); age 6-7: OR 3.65 (2.41-5.53); age 10-11: OR 2.73 (1.84-4.06)). Attainment was similar for children with and without exposure to cardio-pulmonary bypass. Lower attainment was strongly associated with the number of pre-school hospital admissions. CONCLUSIONS: Children with CHD have lower educational attainment compared to their peers. Deficits are evident from school entry and increase throughout primary school.

Risk stratification of young adult survivors of cancer to estimate hospital morbidity burden: applicability of a pediatric therapy-based approach.

PURPOSE: Children and young adults (CYA) are at risk of late morbidity following cancer treatment, with risk varying by disease type and treatment received. Risk-stratified levels of aftercare which stratify morbidity burden to inform the intensity of long-term follow-up care, are well established for survivors of cancer under the age of 18 years, utilizing the National Cancer Survivor Initiative (NCSI) approach. We investigated the applicability of risk-stratified levels of aftercare in predicting long-term morbidity in young adults (YA), aged 18-29 years. METHODS: Long-term CYA survivors followed-up at a regional center in the North of England were risk-stratified by disease and treatments received into one of three levels. These data were linked with local cancer registry and administrative health data (Hospital Episode Statistics), where hospital activity was used as a marker of late morbidity burden. RESULTS: Poisson modelling with incident rate ratios (IRR) demonstrated similar trends in hospital activity for childhood (CH) and YA cancer survivors across NCSI risk levels. NCSI levels independently predicted long-term hospitalization risk in both CH and YA survivors. Risk of hospitalization was significantly reduced for levels 1 (CH IRR 0.32 (95% CI 0.26-0.41), YA IRR 0.06 (95% CI 0.01-0.43)) and 2; CH IRR 0.46 (95% CI 0.42-0.50), YA IRR 0.49 (95% CI 0.37-0.50)), compared with level 3. CONCLUSIONS: The NCSI pediatric late-effects risk stratification system can be effectively and safely applied to cancer patients aged 18-29, independent of ethnicity or socioeconomic position. IMPLICATIONS FOR CANCER SURVIVORS: To enhance quality of care and resource utilization, long-term aftercare of survivors of YA cancer can and should be risk stratified through adoption of approaches such as the NCSI risk-stratification model.

Prenatal and Postpartum Maternal Iodide Intake from Diet and Supplements, Urinary Iodine and Thyroid Hormone Concentrations in a Region of the United Kingdom with Mild-to-Moderate Iodine Deficiency.

Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Iodine requirements increase in pregnancy, but many women in regions without salt iodization have insufficient intakes. We explored associations between iodide intake and urinary iodine concentration (UIC), urinary iodine/creatinine ratio (I/Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. A total of 246 pregnant women aged 18-40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter at around 12, 26 and 36 weeks' gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24 h recalls. During pregnancy, median (IQR) dietary iodide intake was 101 µg/day (54, 142), with 42% from dairy and 9% from white fish. Including supplements, intake was 143 µg/day (94, 196), with 49% < UK reference nutrient intake (140 µg/day). Women with Pakistani heritage had 129 µg/day (87, 190) median total intake. Total intake during pregnancy was associated with 4% (95% CI: 1%, 7%) higher UIC, 5% (3%, 7%) higher I/Cr, 4% (2%, 6%) lower thyroglobulin and 21% (9%, 32%) lower odds of palpable goiter per 50 µg/day. This cohort consumed less iodide in pregnancy than UK and World Health Organization dietary recommendations. UIC, I/Cr and thyroglobulin were associated with intake. Higher intake was associated with fewer goiters. Because dairy was the dominant source of iodide, women following plant-based or low-dairy diets may be at particular risk of iodine insufficiency.