Autopsy examination in sudden cardiac death: a current perspective on behalf of the Association for European Cardiovascular Pathology.

In sudden cardiac death, an autopsy is an essential step in establishing a diagnosis of inherited cardiac disease and identifying families that require cardiac screening. To evaluate aspects of post-mortem practice in Europe, a questionnaire was designed and circulated to both clinical and forensic pathologists. There was a 48% response rate and information was obtained from 17 countries. The results showed a wide variety in the management of sudden cardiac death, with a general tendency towards a lack of thorough investigation. In up to 40% of cases, autopsies were not performed in subjects less than 50 years who may have died from cardiac disease. Reasons for this were lack of finance and lack of interest from police, legal authorities, and doctors. Only 50% of pathologists seem to follow a standard protocol for autopsy examination, apparently due to lack of expertise and/or training. When autopsies were performed, histology and toxicology were almost always taken, genetic studies were generally available and retention of the heart for specialist study was usually permitted. Our results suggest that although the standard of practice is appropriate in many centres, many more cases should have autopsies, especially in sudden deaths in subjects less than 50 years

Conservative management of mallet injuries:A national survey of current practice in the UK

Introduction Mallet injuries are common, and usually treated conservatively. Various systematic reviews have found a lack of evidence regarding best management and it is unclear whether this uncertainty is reflected in current UK practice. Methods An online survey was developed to determine current practice for the conservative treatment of mallet injury amongst specialist hand clinicians in the UK, including physiotherapists, occupational therapists and surgeons. Clinician’s views of study outcome selection were also explored to improve future trials. Results 336 professionals completed the survey. Inconsistency in overall practice was observed in splint type choice, time to discharge to GP, and the assessment of adherence. Greater consistency was observed for recommended duration of continuous immobilisation. Bony injuries were most commonly splinted for six weeks (n=228, 78%) and soft tissue injuries for either eight weeks (n=172, 56%) or six weeks (n=119, 39%). Postimmobilisation splinting was frequently recommended, but duration varied between two and 10 weeks. The outcome rated as most important by all clinicians was patient satisfaction. Discussion There is overall variation in the current UK conservative management of mallet injuries, and the development of a standardised, evidence based protocol is required. Clinicians’ opinions may be used to develop a core set of outcome measures, which will improve standardisation and comparability of future trials.</p

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Conservative management of mallet injuries: A national survey of current practice in the UK

Introduction Mallet injuries are common, and usually treated conservatively. Various systematic reviews have found a lack of evidence regarding best management and it is unclear whether this uncertainty is reflected in current UK practice. Methods An online survey was developed to determine current practice for the conservative treatment of mallet injury amongst specialist hand clinicians in the UK, including physiotherapists, occupational therapists and surgeons. Clinician’s views of study outcome selection were also explored to improve future trials. Results 336 professionals completed the survey. Inconsistency in overall practice was observed in splint type choice, time to discharge to GP, and the assessment of adherence. Greater consistency was observed for recommended duration of continuous immobilisation. Bony injuries were most commonly splinted for six weeks (n=228, 78%) and soft tissue injuries for either eight weeks (n=172, 56%) or six weeks (n=119, 39%). Postimmobilisation splinting was frequently recommended, but duration varied between two and 10 weeks. The outcome rated as most important by all clinicians was patient satisfaction. Discussion There is overall variation in the current UK conservative management of mallet injuries, and the development of a standardised, evidence based protocol is required. Clinicians’ opinions may be used to develop a core set of outcome measures, which will improve standardisation and comparability of future trials.</p

Dietary iron does not impact the quality of life of patients with quiescent ulcerative colitis: an observational study

Background: In animal models, excess luminal iron exacerbates colonic inflammation and cancer development. Moreover, in inflammatory bowel disease (IBD) patients with mild to moderate disease activity dietary fortificant iron intake is inversely related to quality of life. Here we sought to determine whether dietary iron intakes were also related to quality of life in IBD patients in remission. Methods. Forty eight patients with ulcerative colitis (UC), 42 of which had quiescent disease during this observational study, and 53 healthy control subjects completed quality of life questionnaires and 7-day food diaries. For comparative analysis, 34/group were matched and the linear relationship between dietary iron intakes (total, haem, non-haem or fortificant) and EuroQol quality of life measures was investigated. For UC patients the linear relationship between dietary iron intakes and the scores from the disease specific inflammatory bowel disease questionnaire (IBDQ) was also considered. Results: The intake of dietary iron, and its various sub-fractions, were not associated with quality of life (EuroQol) in patients with quiescent disease or in healthy control subjects. The picture was similar for the 42 quiescent UC patients when disease-specific IBDQ was used. However, the 6 patients who relapsed during the study again showed an inverse association between IBDQ and dietary iron intake (p = 0.03). Conclusions: Our data suggest that dietary iron does not impact on quality of life in quiescent UC patients but support that, once the disease is triggered, luminal iron may be a permissive factor for exacerbation of disease activity resulting in lower quality of life. © 2013 Tolkien et al.; licensee BioMed Central Ltd

Methods for assessment of patient adherence to removable orthoses used after surgery or trauma to the appendicular skeleton: a systematic review.

Background:&nbsp;Patient adherence to treatment is a key determinant of outcome for healthcare interventions. Whilst non-adherence has been well evidenced in settings such as drug therapy, information regarding patient adherence to orthoses, particularly in the acute setting, is lacking. The aim of this systematic review was to identify, summarise, and critically appraise reported methods for assessing adherence to removable orthoses in adults following acute injury or surgery. Methods:&nbsp;Comprehensive searches of the Ovid versions of MEDLINE, Embase, AMED, CINAHL, Central, the Cochrane Database of Systematic Reviews, and SPORTDiscus identified complete papers published in English between 1990 and September 2018 reporting measurement of adherence to orthoses in adults following surgery or trauma to the appendicular skeleton. Only primary studies with reference to adherence in the title/abstract were included to maintain the focus of the review. Data extraction included study design, sample size, study population, orthosis studied, and instructions for use. Details of methods for assessing adherence were extracted, including instrument/method used, frequency of completion, number of items (if applicable), and score (if any) used to evaluate adherence overall. Validity and reliability of identified methods were assessed together with any conclusions drawn between adherence and outcomes in the study. Results:&nbsp;Seventeen papers (5 randomised trials, 10 cohort studies, and 2 case series) were included covering upper (n&nbsp;=&thinsp;13) and lower (n&nbsp;=&thinsp;4) limb conditions. A variety of methods for assessing adherence were identified, including questionnaires (n&nbsp;=&thinsp;10) with single (n&nbsp;=&thinsp;3) or multiple items (n&nbsp;=&thinsp;7), home diaries (n&nbsp;=&thinsp;4), and discussions with the patient (n&nbsp;=&thinsp;3). There was no consistency in the target behaviour assessed or in the timing or frequency of assessment or the scoring systems used. None of the measures was validated for use in the target population. Conclusions:&nbsp;Measurement and reporting of adherence to orthosis use is currently inconsistent. Further research is required to develop a measurement tool that provides a rigorous and reproducible assessment of adherence in this acute population. Trial registration:&nbsp;PROSPERO:&nbsp;CRD42016048462. Registered on 17/10/2016.</p

Effect of communicating phenotypic and genetic risk of coronary heart disease alongside web-based lifestyle advice

ABSTRACT Objective: To determine whether provision of web-based lifestyle advice and coronary heart disease risk information either based on phenotypic characteristics or phenotypic plus genetic characteristics affects changes in objectively measured health behaviours. Methods: A parallel-group, open randomised trial including 956 male and female blood donors with no previous history of cardiovascular disease (mean [SD] age = 56.7 [8.8] years) randomised to four study groups: control group (no information provided); web-based lifestyle advice only (lifestyle group); lifestyle advice plus information on estimated 10-year coronary heart disease risk based on phenotypic characteristics (phenotypic risk estimate) (phenotypic group); and lifestyle advice plus information on estimated 10-year coronary heart disease risk based on phenotypic (phenotypic risk estimate) and genetic characteristics (genetic risk estimate) (genetic group). The primary outcome was change in physical activity from baseline to 12 weeks assessed by wrist-worn accelerometer. Results: 928 (97.1%) participants completed the trial. There was no evidence of intervention effects on physical activity (difference in adjusted mean change from baseline): lifestyle group vs control group 0.09 milligravity (mg) (95%CI: -1.15 to 1.33); genetic group vs phenotypic group -0.33 mg (-1.55 to 0.90); phenotypic group and genetic group vs control group -0.52 mg (-1.59 to 0.55); and vs lifestyle group -0.61 mg (-1.67 to 0.46). There was no evidence of intervention effects on secondary biological, emotional and health-related behavioural outcomes except self-reported fruit and vegetable intake. Conclusions: Provision of risk information, whether based on phenotypic or genotypic characteristics, alongside web-based lifestyle advice did not importantly affect objectively measured levels of physical activity, other health-related behaviours, biological risk factors or emotional well-being. Clinical Trial Registration: Current Controlled Trials ISRCTN17721237. Prospectively registered 12 January 2015. http://www.isrctn.com/ISRCTN17721237. Key words: cardiovascular disease; genetics; primary prevention; risk assessment; risk reduction behaviourThis work was supported by a European Commission Framework 7 EPIC-CVD Grant agreement no: 279233. NHS Blood and Transplant funded the INTERVAL trial. DNA extraction and genotyping in INTERVAL/INFORM was funded by the National Institute for Health Research. The coordinating team for INTERVAL/INFORM at the Cardiovascular Epidemiology Unit of the University of Cambridge was supported by core funding from: UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), British Heart Foundation Cambridge Cardiovascular Centre of Excellence and UK National Institute for Health Research Cambridge Biomedical Research Centre. BS was supported by the Medical Research Council [MC_UU_12015/4]

The iBRA-2 (immediate breast reconstruction and adjuvant therapy audit) study: protocol for a prospective national multicentre cohort study to evaluate the impact of immediate breast reconstruction on the delivery of adjuvant therapy.

INTRODUCTION: Immediate breast reconstruction (IBR) is routinely offered to improve quality of life for women with breast cancer requiring a mastectomy, but there are concerns that more complex surgery may delay the delivery of adjuvant oncological treatments and compromise long-term oncological outcomes. High-quality evidence, however, is lacking. iBRA-2 is a national prospective multicentre cohort study that aims to investigate the effect of IBR on the delivery of adjuvant therapy. METHODS AND ANALYSIS: Breast and plastic surgery centres in the UK performing mastectomy with or without (±) IBR will be invited to participate in the study through the trainee research collaborative network. All women undergoing mastectomy ± IBR for breast cancer between 1 July and 31 December 2016 will be included. Patient demographics, operative, oncological and complication data will be collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR will be compared to determine the impact that IBR has on the time of delivery of adjuvant therapy. Prospective data on 3000 patients from ∼50 centres are anticipated. ETHICS AND DISSEMINATION: Research ethics approval is not required for this study. This has been confirmed using the online Health Research Authority decision tool. This novel study will explore whether IBR impacts the time to delivery of adjuvant therapy. The study will provide valuable information to help patients and surgeons make more informed decisions about their surgical options. Dissemination of the study protocol will be via the Mammary Fold Academic and Research Collaborative (MFAC) and the Reconstructive Surgery Trials Network (RSTN), the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS). Participating units will have access to their own data and collective results will be presented at relevant surgical conferences and published in appropriate peer-reviewed journals