Childcare attendance and risk of childhood acute lymphoblastic leukaemia: A register study based on the Danish childcare database

Childhood acute lymphoblastic leukaemia (ALL) is suggested to result from a dysregulated immune response to infections in children with a preleukaemic state. Childcare in early life supposedly may protect against childhood ALL by facilitating sufficient exposure to infections to stimulate and ensure normal maturation of the immune system. We assessed the association between childcare attendance before age 2 years and risk of childhood ALL in a register-based cohort study, including all children aged 2 to 14 years born in Denmark during 1991 to 2014 with available childcare information recorded in the Danish Childcare Database (n = 1 116 185). Cox regression was used to estimate hazard ratios (HRs) comparing children enrolled in childcare and children not enrolled before age 2 years. Further, we assessed the association according to age at enrolment, type of childcare facility and specific ALL subtypes. During 10 460 811 person-years of follow-up, 460 children developed ALL at ages 2 to 14 years. Of these, 57 (12.4%) never attended childcare before age 2 years compared with 10.6% in the total cohort. Compared with homecare, childcare attendance before age 2 years was associated with a statistically non-significantly, marginally decreased risk of childhood ALL with adjusted HR = 0.87 (95% confidence interval [CI]: 0.65-1.16). Risk estimates did neither vary statistically significantly by age at enrolment nor by type of childcare facility and also not between childhood ALL subtypes, including frequently prenatally initiated ALL subtypes. Results from this large, nationwide register-based study provided no evidence that childcare attendance in the first years of life protects against childhood ALL.     

Organ-based tube current modulation in chest CT. A comparison of three vendors

IntroductionOrgan-based tube current modulation (OBTCM) is designed for anterior dose reduction in Computed Tomography (CT). The purpose was to assess dose reduction capability in chest CT using three organ dose modulation systems at different kVp settings. Furthermore, noise, diagnostic image quality and tumour detection was assessed.MethodsA Lungman phantom was scanned with and without OBTCM at 80–135/140 kVp using three CT scanners; Canon Aquillion Prime, GE Revolution CT and Siemens Somatom Flash. Thermo-luminescent dosimeters were attached to the phantom surface and all scans were repeated five times. Image noise was measured in three ROIs at the level of the carina. Three observers visually scored the images using a fivestep scale. A Wilcoxon Signed-Rank test was used for statistical analysis of differences.ResultsUsing the GE revolution CT scanner, dose reductions between 1.10 mSv (12%) and 1.56 mSv (24%) (p < 0.01) were found in the anterior segment and no differences posteriorly and laterally. Total dose reductions between 0.64 (8%) and 0.91 mSv (13%) were found across kVp levels (p < 0.00001). Maximum noise increase with OBTCM was 0.8 HU. With the Canon system, anterior dose reductions of 6–10% and total dose reduction of 0.74–0.76 mSv across kVp levels (p < 0.001) were found with a maximum noise increase of 1.1 HU. For the Siemens system, dose increased by 22–51% anteriorly; except at 100 kVp where no dose difference was found. Noise decreased by 1 to 1.5 HU.ConclusionOrgan based tube current modulation is capable of anterior and total dose reduction with minimal loss of image quality in vendors that do not increase posterior dose.Implications for practiceThis research highlights the importance of being familiar with dose reduction technologies.     

Mental health care professionals' accounts of actions and responsibilities related to managing physical health among people with severe mental illness

Background

Life expectancy of people with severe mental illness (SMI) is greatly shortened compared to the general population, and despite extensive research, this issue is unsolved. Although it is widely recognised that people with SMI need support from health care services to manage health related issues, profound health inequalities exist within provision of health care. The aim of this study was to examine how mental health care professionals accounted for their actions and responsibilities related to managing physical health issues among people with SMI.

Molecular characterisation of TP53 mutated squamous cell carcinomas of the lung to identify putative targets for therapy

Personalised cancer treatment depends on identification of therapeutically relevant biological subgroups of patients for assessing effect of treatment and to discover new therapeutic options. By analyses in heterogeneous patient populations, the effects may be lost in noise. Squamous cell carcinoma of the lung is a major killer worldwide. Despite recent advances, mortality is high and response to therapies varies greatly from patient to patient. Target search in biologically relevant subgroups may identify treatment options not so far discovered. A total of 198 patients undergoing surgery for squamous cell carcinomas of the lung were included in the study. The tumours were analysed for copy number alterations (n = 152) and gene expression from tumour (n = 188) and normal lung (n = 21), with both data levels present in 140 patients. We studied alterations in tumours harbouring mutations in TP53 and in previously published gene expression subtypes. Genes with consistent alterations in both genomic levels were identified as putative biomarkers. Results were validated in TCGA. The most convincing biomarker in TP53 mutated squamous cell carcinomas of the lung was BIRC5 with amplification in 36% of mutated samples, 5% in wild-type samples and a 17%-fold change of expression between TP53 mutated tumours and normal lung tissue. BIRC5 was significantly altered in the classical and primitive subtypes. We suggest BIRC5 as a putative predictive biomarker and putative druggable target in squamous cell lung carcinomas harbouring TP53 mutation or classified as classical and primitive subtypes.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Human papillomavirus and urinary bladder cancer revisited

This review aims to present data on the association between human papillomavirus (HPV) and urinary bladder cancer (BC), especially of the subtype squamous cell carcinoma (SCC). Furthermore, the current data on the relation between p16, HPV, and BC are reviewed. PubMed was searched for ‘Humans’ [MESH] AND ‘Papillomaviridae’ [MESH] AND ‘Urinary Bladder Neoplasms’ [MESH], resulting in 157 potential articles. After profound reviewing, 18 articles were included in this review. Only original articles in English were included. A variable number of HPV genotypes in a small number of cases have been investigated in several studies with various methodology. HPV was present in 0–100% of cases depending on inclusion and exclusion criteria. SCC studies are mostly hampered by low number of cases whereas the few studies with a high number show a slightly higher prevalence of different HPV genotypes compared to pure urothelial carcinoma. Studies on p16 status in HPV positive cases are even more scarcely reported and show conflicting results. Most studies fail to prove clear-cut relevance of HPV in BC irrespectively of histological subtype. Negative p16 staining cannot rule out positive HPV status.