Royal Devon and Exeter Hospital

About: Royal Devon and Exeter Hospital is a healthcare organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 2282 authors who have published 2526 publications receiving 78866 citations. The organization is also known as: RD&E.

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Abstract: Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

The vitamin K debacle: cut the Gordian knot but first do no harm

Abstract: As clinicians who have contributed to the data and the discussions about vitamin K prophylaxis to prevent vitamin K deficiency bleeding (VKDB) in infancy, we are acutely aware that the debate about the advantages and disadvantages of various forms of prophylaxis may undermine public confidence and so put at risk potential health benefit. Echoing Von Kries1 we suggest in this annotation that a radical solution is urgently required and could be introduced. Sadly, the history of vitamin K prophylaxis is replete with examples of medical practice driven by fashion and controversy. For example, over enthusiastic dosing with synthetic vitamin K2 (Synkavit, Roche, Herts, UK) during the 1960s led to complications of haemolysis, hyperbilirubinaemia, and kernicterus, which brought the practice of vitamin K prophylaxis into some disrepute. The most dramatic controversy, still current, originates from reports by Golding and colleagues that intramuscular prophylaxis with vitamin K1may be associated with an increased incidence of childhood leukaemia and cancer.2 These controversies have been extensively reviewed.1 3 The potential for poorly informed public debate to generate anxiety and undermine confidence in preventive procedures was well illustrated in the 1980s by the reported association of pertussis immunisation with an encephalopathy of infancy. Loss of public confidence in the immunisation led to mortality and morbidity among children whose parents declined it,4 5 while many professionals felt unable to recommend it for all infants. The risk of a similar situation arising from reports of an association between measles, mumps, and rubella immunisation and infantile autism resulted in prompt and unequivocal advice from the Chief Medical Officer, which supported public confidence, although there was an increase in immunisation refusals.6 Another example was the increase in unplanned pregnancies that resulted from the inadequately informed debate about the risks of some oral …

The need for future surgical low rectal cancer studies.

Abstract: Optimal surgery remains the mainstay of best outcome for rectal cancer. The demonstration, during the 3rd Annual Pelican Surgical Workshop Symposium, of an abdomino-perineal excision (APE) performed in the ‘Berlin position’, further added to the debate on optimal surgical technique. Much interest was created at the 1st Pelican symposium with the demonstration, by the Swedish surgeon Dr Torbjorn Holm, of a prone APE and the delivery of a ‘cylindrical’ specimen and the potential to reduce local recurrence using this approach. The high rates of local recurrence following APE and the discussions as to optimal technique have led to the development of a proposed MERCURY Study Group study to assess the benefit of a radical APE, with careful assessment of the impact that this operation may have on morbidity. A German study has also been proposed adopting the UK's multidisciplinary team approach. It aims at targeting preoperative chemoradiotherapy at those patients in whom a radical APE or total mesorectal excision is likely to result in an involved surgical resection margin. In this article we review the evidence for improving the surgical technique for low rectal cancer. We believe improvements may be best achieved through continued European prospective, multi-centre, multidisciplinary studies.

Bilateral microphthalmia, esophageal atresia, and cryptorchidism: The anophthalmia-esophageal-genital syndrome

Abstract: We report on a male infant with bilateral microphthalmia, esophageal atresia, and cryptorchidism. To our knowledge only 4 cases with a similar combination of congenital abnormalities have been previously reported, and it is likely that this represents a distinct entity. We suggest the name “anophthalmia-esophageal-genital-syndrome.” Am. J. Med. Genet. 70:171–173, 1997. © 1997 Wiley-Liss, Inc.

Effectiveness of interventions to reduce ordering of thyroid function tests: a systematic review.

Abstract: Objectives To evaluate the effectiveness of behaviour changing interventions targeting ordering of thyroid function tests. Design Systematic review. Data sources MEDLINE, EMBASE and the Cochrane Database up to May 2015. Eligibility criteria for selecting studies We included studies evaluating the effectiveness of behaviour change interventions aiming to reduce ordering of thyroid function tests. Randomised controlled trials (RCTs), non-randomised controlled studies and before and after studies were included. There were no language restrictions. Study appraisal and synthesis methods 2 reviewers independently screened all records identified by the electronic searches and reviewed the full text of any deemed potentially relevant. Study details were extracted from the included papers and their methodological quality assessed independently using a validated tool. Disagreements were resolved through discussion and arbitration by a third reviewer. Meta-analysis was not used. Results 27 studies (28 papers) were included. They evaluated a range of interventions including guidelines/protocols, changes to funding policy, education, decision aids, reminders and audit/feedback; often intervention types were combined. The most common outcome measured was the rate of test ordering, but the effect on appropriateness, test ordering patterns and cost were also measured. 4 studies were RCTs. The majority of the studies were of poor or moderate methodological quality. The interventions were variable and poorly reported. Only 4 studies reported unsuccessful interventions but there was no clear pattern to link effect and intervention type or other characteristics. Conclusions The results suggest that behaviour change interventions are effective particularly in reducing the volume of thyroid function tests. However, due to the poor methodological quality and reporting of the studies, the likely presence of publication bias and the questionable relevance of some interventions to current day practice, we are unable to draw strong conclusions or recommend the implementation of specific intervention types. Further research is thus justified. Trial registration number CRD42014006192.