Time Trends in Deaths Before Age 50 Years in People with Type 1 Diabetes:a nationwide analysis from Scotland 2004–2017

Acknowledgements We thank the SDRN Epidemiology Group: J. Chalmers (Diabetes Centre, Victoria Hospital, Kirkcaldy, UK), C. Fischbacher (Information Services Division, NHS National Services Scotland, Edinburgh, UK), B. Kennon (Queen Elizabeth University Hospital, Glasgow, UK), G. Leese (Ninewells Hospital, Dundee, UK), R. Lindsay (British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK), J. McKnight (Western General Hospital, NHS, UK), J. Petrie (Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK), R. McCrimmon (Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK), S. Philip (Grampian Diabetes Research Unit, Diabetes Centre, Aberdeen Royal Infirmary, Aberdeen, UK), D. McAllister (Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK), E. Pearson (Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK) and S. Wild (Usher Institute, University of Edinburgh, Edinburgh, UK). The SDRN Epidemiology Group resource was originally set up under Ethics ref. 11/AL/0225, PAC 33/11 now running under PBPP ref. 1617-0147. Funding This study was supported by funding from Diabetes UK (17/0005627).Peer reviewedPublisher PD

Patients treated for hyperthyroidism are at increased risk of becoming obese: findings from a large prospective secondary care cohort

YesBackground: The most commonly reported symptom of hyperthyroidism is weight loss; successful treatment increases weight. Weight gain faced by patients with hyperthyroidism is widely considered a simple reaccumulation of premorbid weight, whereas many patients feel there is a significant weight “overshoot” attributable to the treatment. We aimed to establish if weight gain seen following treatment for hyperthyroidism represents replenishment of premorbid weight or “overshoot” beyond expected regain and, if there is excessive weight gain, whether this is associated with the applied treatment modality. Methods: We calculated the risk of becoming obese (body mass index [BMI] >30 kg/m2) following treatment for hyperthyroidism by comparing BMI of 1373 patients with overt hyperthyroidism seen in a secondary care setting with the age- and sex-matched background population (Health Survey for England, 2007–2009). Next, we investigated the effect of treatment with an antithyroid drug (ATD) alone in regard to ATD with radioactive iodine (131I) therapy. We modeled the longitudinal weight data in relation to the treatment pathway to thyroid function and the need for long-term thyroxine replacement. Results: During treatment of hyperthyroidism, men gained 8.0 kg (standard deviation ±7.5) and women 5.5 kg (±6.8). At discharge, there was a significantly increased risk of obesity in male (odds ratio = 1.7 [95% confidence interval 1.3–2.2], p 10 mIU/L; 0.5 kg, 0.3–0.7, p < 0.001) or free thyroxine (fT4) was reduced (fT4 ≤ 10 pmol/L (0.8 ng/dL); 0.3 kg, 0.1–0.4, p < 0.001) during follow-up. Initiation of levothyroxine was associated with further weight gain (0.4 kg, 0.2–0.6, p < 0.001) and the predicted excess weight gain in 131I-induced hypothyroidism was 1.8 kg. Conclusions: Treatment for hyperthyroidism is associated with significant risks of becoming obese. 131I treatment and subsequent development of hypothyroidism were associated with small but significant amounts of excess weight gain compared with ATD alone. We advocate that the discussion over the weight “overshoot” risk forms part of the individualized treatment decision-making process

Mobile DNA elements in T4 and related phages

Mobile genetic elements are common inhabitants of virtually every genome where they can exert profound influences on genome structure and function in addition to promoting their own spread within and between genomes. Phage T4 and related phage have long served as a model system for understanding the molecular mechanisms by which a certain class of mobile DNA, homing endonucleases, promote their spread. Homing endonucleases are site-specific DNA endonucleases that initiate mobility by introducing double-strand breaks at defined positions in genomes lacking the endonuclease gene, stimulating repair and recombination pathways that mobilize the endonuclease coding region. In phage T4, homing endonucleases were first discovered as encoded within the self-splicing td, nrdB and nrdD introns of T4. Genomic data has revealed that homing endonucleases are extremely widespread in T-even-like phage, as evidenced by the astounding fact that ~11% of the T4 genome encodes homing endonuclease genes, with most of them located outside of self-splicing introns. Detailed studies of the mobile td intron and its encoded endonuclease, I-TevI, have laid the foundation for genetic, biochemical and structural aspects that regulate the mobility process, and more recently have provided insights into regulation of homing endonuclease function. Here, we summarize the current state of knowledge regarding T4-encoded homing endonucleases, with particular emphasis on the td/I-TevI model system. We also discuss recent progress in the biology of free-standing endonucleases, and present areas of future research for this fascinating class of mobile genetic elements

Distant delivery of a mindfulness-based intervention for people with Parkinson's disease: the study protocol of a randomised pilot trial

BACKGROUND: Psychological difficulties, especially depression and anxiety, are the most prevalent non-motor symptoms in Parkinson's disease. Pharmacological treatments for these conditions appear relatively ineffective in Parkinson's disease. Mindfulness courses are increasingly popular and recognised as effective for managing emotional states, and there is growing evidence for the effectiveness of mindfulness courses for people with long-term medical conditions. With this exploratory pilot trial, we want to assess the feasibility of the procedures and processes, including recruitment, most appropriate outcome measure(s), acceptability of type and number of measures, potential nocebo effects, and potential effectiveness and cost-effectiveness of a specially adapted distance-delivered mindfulness-based intervention in people affected by Parkinson's disease. METHODS/DESIGN: This is a pilot two-arm randomised parallel group controlled trial. Sixty participants who meet eligibility criteria will be randomly assigned either to an 8-week mindfulness-based intervention group or a wait-list control group. The mindfulness intervention will include 1-h weekly sessions delivered by a health psychologist trained to facilitate mindfulness courses. Participants in both groups will complete standardised questionnaires assessing anxiety, depression, pain, insomnia, fatigue, and daily activities at four time points (baseline, 4, 8, and 20 weeks). The analysis will also consider potential mechanisms of change, such as acceptance, self-compassion, and tolerance of uncertainty, as well as health economic outcomes. Participants' experiences of the mindfulness interventions will be explored via in-depth interviews. DISCUSSION: A mindfulness-based intervention for people with Parkinson's delivered remotely, through Skype group videoconferences, may represent a viable, more accessible, intervention for people with mobility limitations and people who live in rural areas. The trial will provide important information about the feasibility, potential efficacy and cost-effectiveness, and acceptability of the intervention as well as mechanisms of psychosocial adjustment. The results of this pilot trial will help us design a phase III trial to assess efficacy of an online mindfulness-based intervention in Parkinson's disease and evaluate significance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02683330

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

Weight gain following treatment of hyperthyroidism - A forgotten tale

Hyperthyroidism causes weight loss in the majority, but its effect is variable and 10% of patients gain weight. Its treatment usually leads to weight gain and some studies have reported an excess weight regain. However, there is considerable inter‐individual variability and a differential effect on body weight by different treatments, with some studies reporting more weight increase with radioiodine, and perhaps surgery, compared with anti‐thyroid drugs. The excess weight regain may relate to treatment‐induced hypothyroidism. Furthermore, the transition from hyperthyroidism to euthyroidism may unmask, or exacerbate, the predisposition that some patients have towards obesity. Other risk factors commonly implicated for such weight increase include the severity of thyrotoxicosis at presentation and underlying Graves' disease. Conflicting data exist whether lean body mass or fat mass or both are increased post‐therapy and whether such increments occur concurrently or in a sequential manner; this merits clarification. In any case, clinicians need to counsel their patients regarding this issue at presentation. Limited data on the effect of dietary interventions on weight changes with treatment of hyperthyroidism are encouraging in that they cause significantly lesser weight gain compared to standard care. More research is indicated on the impact of the treatment of hyperthyroidism on various anthropometric indices and the predisposing factors for any excessive weight gain. Regarding the impact of dietary management or other weight loss interventions, there is a need for well‐designed and, ideally, controlled intervention studies