Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review

Objective To identify the factors associated with diabetic ketoacidosis at diagnosis of type 1 diabetes in children and young adults

The pathway to diagnosis of type 1 diabetes in children: a questionnaire study.

OBJECTIVE: To explore the pathway to diagnosis of type 1 diabetes (T1D) in children. DESIGN: Questionnaire completed by parents. PARTICIPANTS: Parents of children aged 1 month to 16 years diagnosed with T1D within the previous 3 months. SETTING: Children and parents from 11 hospitals within the East of England. RESULTS: 88/164 (54%) invited families returned the questionnaire. Children had mean±SD age of 9.41±4.5 years. 35 (39.8%) presented with diabetic ketoacidosis at diagnosis. The most common symptoms were polydipsia (97.7%), polyuria (83.9%), tiredness (75.9%), nocturia (73.6%) and weight loss (64.4%) and all children presented with at least one of those symptoms. The time from symptom onset to diagnosis ranged from 2 to 315 days (median 25 days). Most of this was the appraisal interval from symptom onset until perceiving the need to seek medical advice. Access to healthcare was good but one in five children presenting to primary care were not diagnosed at first encounter, most commonly due to waiting for fasting blood tests or alternative diagnoses. Children diagnosed at first consultation had a shorter duration of symptoms (p=0.022) and children whose parents suspected the diagnosis were 1.3 times more likely (relative risk (RR) 1.3, 95% CI 1.02 to 1.67) to be diagnosed at first consultation. CONCLUSIONS: Children present with the known symptoms of T1D but there is considerable scope to improve the diagnostic pathway. Future interventions targeted at parents need to address the tendency of parents to find alternative explanations for symptoms and the perceived barriers to access, in addition to symptom awareness.The study was funded by the Royal College of General Practitioners Scientific Foundation Board (SFB-2011-15). JUS was supported by a National Institute of Health Research (NIHR) Academic Clinical Fellowship and subsequently Clinical Lectureship, and FMW by an NIHR Clinician Scientist award. SJS was supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number MC_UU_12015/1]. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.This is the final version of the article. It was first published by BMJ Group at http://bmjopen.bmj.com/content/5/3/e006470.ful

Repressive and non-repressive chromatin at native telomeres in Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>In <it>Saccharomyces cerevisiae </it>genes that are located close to a telomere can become transcriptionally repressed by an epigenetic process known as telomere position effect. There is large variation in the level of the telomere position effect among telomeres, with many native ends exhibiting little repression.</p> <p>Results</p> <p>Chromatin analysis, using microccocal nuclease and indirect end labelling, reveals distinct patterns for ends with different silencing states. Differences were observed in the promoter accessibility of a subtelomeric reporter gene and a characteristic array of phased nucleosomes was observed on the centromere proximal side of core X at a repressive end. The silent information regulator proteins 2 - 4, the yKu heterodimer and the subtelomeric core X element are all required for the maintenance of the chromatin structure of repressive ends. However, gene deletions of particular histone modification proteins can eliminate the silencing without the disruption of this chromatin structure.</p> <p>Conclusion</p> <p>Our data identifies chromatin features that correlate with the silencing state and indicate that an array of phased nucleosomes is not sufficient for full repression.</p

Improving the Quality of Dentistry (IQuaD):a cluster factorial randomised controlled trial comparing the effectiveness and cost-benefit of oral hygiene advice and/or periodontal instrumentation with routine care for the prevention and management of periodontal disease in dentate adults attending dental primary care

Acknowledgements The authors wish to thank Mark Forrest and the programming team at CHaRT; Cynthia Fraser, our information specialist, for assistance with referencing; Moira Swan, who was the dental research nurse and part of the OA team in Newcastle upon Tyne; Louise Campbell for secretarial support and data management; our original statistician in the group, Andy Elders; senior IT manager Gladys Macpherson; senior trial administrator at the TCOD Marilyn Laird; Luke Vale for his involvement with the design of the health economic analysis at the inception of the trial; Maria Dimitrova, who assisted the health economists in the collection of unit costs; staff of the Scottish Primary Care Research Network, who assisted with screening eligible patients at dental practices; staff of the North East Commissioning Support Unit who assisted with research payments to dental practices in the north-east; members of the TMC and Periodontal Advisory Group for their ongoing advice and support of the trial; the independent members of the TSC and DMC; and the staff at recruitment sites who facilitated recruitment, treatment and follow-up of trial participants. The Health Services Research Unit and the Health Economics Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.Peer reviewedPublisher PD

Hyperfine resolved spectrum of the molecular dication DCl

We have obtained hyperfine-resolved infrared spectra of a PQ23(N) branch line in the v = 2-1 band of the X 3Σ- state of the molecular dication D35Cl2+. Analysis of the hyperfine structure allows us to estimate the magnitude of the Fermi contact interaction for the chlorine nucleus; bF(Cl) = 167 (25) MHz

Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

The non-canonical inflammasome sensor caspase-11 and gasdermin D (GSDMD) drive inflammation and pyroptosis, a type of immunogenic cell death that favors cell-mediated immunity (CMI) in cancer, infection, and autoimmunity. Here we show that caspase-11 and GSDMD are required for CD8+ and Th1 responses induced by nanoparticulate vaccine adjuvants. We demonstrate that nanoparticle-induced reactive oxygen species (ROS) are size dependent and essential for CMI, and we identify 50- to 60-nm nanoparticles as optimal inducers of ROS, GSDMD activation, and Th1 and CD8+ responses. We reveal a division of labor for IL-1 and IL-18, where IL-1 supports Th1 and IL-18 promotes CD8+ responses. Exploiting size as a key attribute, we demonstrate that biodegradable poly-lactic co-glycolic acid nanoparticles are potent CMI-inducing adjuvants. Our work implicates ROS and the non-canonical inflammasome in the mode of action of polymeric nanoparticulate adjuvants and establishes adjuvant size as a key design principle for vaccines against cancer and intracellular pathogens

Factors predicting hospital length-of-stay and readmission after colorectal resection: a population-based study of elective and emergency admissions

<p>Abstract</p> <p>Background</p> <p>The impact of developments in colorectal cancer surgery on length-of-stay (LOS) and re-admission have not been well described. In a population-based analysis, we investigated predictors of LOS and emergency readmission after the initial surgery episode.</p> <p>Methods</p> <p>Incident colorectal cancers (ICD-O2: C18-C20), diagnosed 2002-2008, were identified from the National Cancer Registry Ireland, and linked to hospital in-patient episodes. For those who underwent colorectal resection, the associated hospital episode was identified. Factors predicting longer LOS (upper-quartile, > 24 days) for elective and emergency admissions separately, and whether LOS predicted emergency readmission within 28 days of discharge, were investigated using logistic regression.</p> <p>Results</p> <p>8197 patients underwent resection, 63% (n = 5133) elective and 37% (n = 3063) emergency admissions. Median LOS was 14 days (inter-quartile range (IQR) = 11-20) for elective and 21 (15-33) for emergency admissions. For both emergency and elective admissions, likelihood of longer LOS was significantly higher in patients who were older, had co-morbidities and were unmarried; it was reduced for private patients. For emergency patients only the likelihood of longer LOS was lower for patients admitted to higher-volume hospitals. Longer LOS was associated with increased risk of emergency readmission.</p> <p>Conclusions</p> <p>One quarter of patients stay in hospital for at least 25 days following colorectal resection. Over one third of resected patients are emergency admissions and these have a significantly longer median LOS. Patient- and health service-related factors were associated with prolonged LOS. Longer LOS was associated with increased risk of emergency readmission. The cost implications of these findings are significant.</p

Applying a new concept of embedding qualitative research: An example from a quantitative study of carers of people in later stage dementia

BACKGROUND: Qualitative methods are increasingly included in larger studies to provide a richer understanding of people's experience. This paper explores the potential of using a novel approach to embedded qualitative design as part of an observational study examining the effectiveness of home support for people in later stage dementia in England. The method involved collecting and analysing unsolicited conversational comments made by participants as they completed standardised measures. An evaluation of the method is presented using the voices of participants to illustrate its potential. METHODS: The conversations of 17 carers recruited to an observational study were audio recorded to gather commentary made while completing a structured interview. Data were interrogated using thematic analysis to investigate the feasibility of conducting an embedded qualitative study, the potential richness of the material and participants' reactions to formal questioning and participating in research. RESULTS: The findings revealed that qualitative data were available from this approach. Analysis generated three themes from carers: conflicting carer emotions; the importance of maintaining normality and agency within day-to-day life; and tensions between these desires and making use of formal services. Important issues for carers were revealed establishing the benefit of using the method. The advantages of exploiting unsolicited conversation included enhancing understanding of people's lived experience, reducing participant burden in research and easing the process of data collection. In addition, it provided an opportunity to evaluate individuals' experience of the research process. CONCLUSIONS: The findings demonstrate how unsolicited comments during structured interviews may appear incidental but can reveal important aspects of living with dementia. The method also emphasised methodological challenges for research in dementia, including the influence and impact of the research context. Further research is required to evaluate the method with other groups including people with dementia themselves

Short‐term psychosocial outcomes of adding a non‐contrast abdominal computed tomography (CT) scan to the thoracic CT within lung cancer screening

Objectives To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. Subjects and Methods The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State–Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity. Results A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01–0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. Conclusion Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings