What's new in atopic eczema? An analysis of systematic reviews published in 2015. Part 2: prevention and treatment

This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE), providing a succinct guide for clinicians and patients. It provides a summary of key findings from 26 systematic reviews that were published during 2015, and focuses on the treatment and prevention of AE. For systematic reviews on the epidemiology and methodological issues, see Part 1 of this update. Topical corticosteroid withdrawal syndrome, ‘steroid addiction’, has been evaluated in a high‐quality systematic review, which helps better define this entity and the risk factors for it. A Cochrane Review has not demonstrated any association between topical corticosteroid use in pregnancy and adverse outcomes, although very large quantities of potent/very potent topical corticosteroids may be associated with reduced birth weight. House dust mite avoidance strategies do not appear to prevent AE. Exposure to probiotics prenatally and in early infancy may help prevent AE, but there is no evidence that maternal diet or supplementation has a preventative effect

Advanced Cardiac Resuscitation Evaluation (ACRE): A randomised single-blind controlled trial of peer-led vs. expert-led advanced resuscitation training

<p>Abstract</p> <p>Background</p> <p>Advanced resuscitation skills training is an important and enjoyable part of medical training, but requires small group instruction to ensure active participation of all students. Increases in student numbers have made this increasingly difficult to achieve.</p> <p>Methods</p> <p>A single-blind randomised controlled trial of peer-led vs. expert-led resuscitation training was performed using a group of sixth-year medical students as peer instructors. The expert instructors were a senior and a middle grade doctor, and a nurse who is an Advanced Life Support (ALS) Instructor.</p> <p>A power calculation showed that the trial would have a greater than 90% chance of rejecting the null hypothesis (that expert-led groups performed 20% better than peer-led groups) if that were the true situation. Secondary outcome measures were the proportion of High Pass grades in each groups and safety incidents.</p> <p>The peer instructors designed and delivered their own course material. To ensure safety, the peer-led groups used modified defibrillators that could deliver only low-energy shocks.</p> <p>Blinded assessment was conducted using an Objective Structured Clinical Examination (OSCE). The checklist items were based on International Liaison Committee on Resuscitation (ILCOR) guidelines using Ebel standard-setting methods that emphasised patient and staff safety and clinical effectiveness.</p> <p>The results were analysed using Exact methods, chi-squared and t-test.</p> <p>Results</p> <p>A total of 132 students were randomised: 58 into the expert-led group, 74 into the peer-led group. 57/58 (98%) of students from the expert-led group achieved a Pass compared to 72/74 (97%) from the peer-led group: Exact statistics confirmed that it was very unlikely (p = 0.0001) that the expert-led group was 20% better than the peer-led group.</p> <p>There were no safety incidents, and High Pass grades were achieved by 64 (49%) of students: 33/58 (57%) from the expert-led group, 31/74 (42%) from the peer-led group. Exact statistics showed that the difference of 15% meant that it was possible that the expert-led teaching was 20% better at generating students with High Passes.</p> <p>Conclusions</p> <p>The key elements of advanced cardiac resuscitation can be safely and effectively taught to medical students in small groups by peer-instructors who have undergone basic medical education training.</p

Brain processing of contagious itch in patients with atopic dermatitis

Several studies show that itch and scratching cannot only be induced by pruritogens like histamine or cowhage, but also by the presentation of certain (audio-) visual stimuli like pictures on crawling insects or videos showing other people scratching. This phenomenon is coined Contagious itch (CI). Due to the fact that CI is more profound in patients with the chronic itchy skin disease atopic dermatitis (AD), we believe that it is highly relevant to study brain processing of CI in this group. Knowledge on brain areas involved in CI in AD-patients can provide us with useful hints regarding non-invasive treatments that AD-patients could profit from when they are confronted with itch-inducing situations in daily life. Therefore, this study investigated the brain processing of CI in AD-patients. 11 AD-patients underwent fMRI scans during the presentation of an itch inducing experimental video (EV) and a non-itch inducing control video (CV). Perfusion based brain activity was measured using arterial spin labeling functional MRI. As expected, the EV compared to the CV led to an increase in itch and scratching (p \u3c 0.05). CI led to a significant increase in brain activity in the supplementary motor area, left ventral striatum and right orbitofrontal cortex (threshold: p \u3c 0.001; cluster size k \u3e 50). Moreover, itch induced by watching the EV was by trend correlated with activity in memory-related regions including the temporal cortex and the (pre-) cuneus as well as the posterior operculum, a brain region involved in itch processing (threshold: p \u3c 0.005; cluster size k \u3e 50). These findings suggest that the fronto-striatal circuit, which is associated with the desire to scratch, might be a target region for non-invasive treatments in AD patients. © 2017 Schut, Mochizuki, Grossman, Lin, Conklin, Mohamed, Gieler, Kupfer and Yosipovitch

The XMM Cluster Survey: The Stellar Mass Assembly of Fossil Galaxies

This paper presents both the result of a search for fossil systems (FSs) within the XMM Cluster Survey and the Sloan Digital Sky Survey and the results of a study of the stellar mass assembly and stellar populations of their fossil galaxies. In total, 17 groups and clusters are identified at z < 0.25 with large magnitude gaps between the first and fourth brightest galaxies. All the information necessary to classify these systems as fossils is provided. For both groups and clusters, the total and fractional luminosity of the brightest galaxy is positively correlated with the magnitude gap. The brightest galaxies in FSs (called fossil galaxies) have stellar populations and star formation histories which are similar to normal brightest cluster galaxies (BCGs). However, at fixed group/cluster mass, the stellar masses of the fossil galaxies are larger compared to normal BCGs, a fact that holds true over a wide range of group/cluster masses. Moreover, the fossil galaxies are found to contain a significant fraction of the total optical luminosity of the group/cluster within 0.5R200, as much as 85%, compared to the non-fossils, which can have as little as 10%. Our results suggest that FSs formed early and in the highest density regions of the universe and that fossil galaxies represent the end products of galaxy mergers in groups and clusters. The online FS catalog can be found at http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.html.Comment: 30 pages, 50 figures. ApJ published version, online FS catalog added: http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.htm

Filaggrin inhibits generation of CD1a neolipid antigens by house dust mite-derived phospholipase.

Atopic dermatitis is a common pruritic skin disease in which barrier dysfunction and cutaneous inflammation play a role in pathogenesis. Mechanisms underlying the associated inflammation are not fully understood, and while CD1a-expressing Langerhans cells are known to be enriched within lesions, their role in clinical disease pathogenesis has not been studied. Here we observed that house dust mite (HDM) generates neolipid antigens for presentation by CD1a to T cells in the blood and skin lesions of affected individuals. HDM-responsive CD1a-reactive T cells increased in frequency after birth and showed rapid effector function, consistent with antigen-driven maturation. To define the underlying mechanisms, we analyzed HDM-challenged human skin and observed allergen-derived phospholipase (PLA2) activity in vivo. CD1a-reactive T cell activation was dependent on HDM-derived PLA2 and such cells infiltrated the skin after allergen challenge. Filaggrin insufficiency is associated with atopic dermatitis, and we observed that filaggrin inhibits PLA2 activity and inhibits CD1a-reactive PLA2-generated neolipid-specific T cell activity from skin and blood. The most widely used classification schemes of hypersensitivity, such as Gell and Coombs are predicated on the idea that non-peptide stimulants of T cells act as haptens that modify peptides or proteins. However our results point to a broader model that does not posit haptenation, but instead shows that HDM proteins generate neolipid antigens which directly activate T cells. Specifically, the data identify a pathway of atopic skin inflammation, in which house dust mite-derived phospholipase A2 generates antigenic neolipids for presentation to CD1a-reactive T cells, and define PLA2 inhibition as a function of filaggrin, supporting PLA2 inhibition as a therapeutic approach

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial

Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001). Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term

Thinking outside the gundeck: maritime history, the royal navy, and the outbreak of British civil war, 1625-1642

This is the peer reviewed version of the following article: Thinking outside the gundeck: maritime history, the royal navy and the outbreak of British civil war, 1625–1642, Historical Research, vol. 87 no. 236 (2014), pp. 251-274, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/1468-2281.12049/full. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archiving.Maritime history seems to be suffering an identity crisis, rising in popularity but unsure of its place within historical scholarship and divided in approach. Seafarers, as a consequence, have remained marginal within mainstream history. This article argues that only by integrating the study of maritime topics into wider historical debates can maritime history overcome these doubts, taking as a case study the role of seafarers and the navy in British politics during 1625−42. First examining previous interpretations offered by scholars, largely based on a conception of seafarers as politically and socially isolated from developments ashore, the article then reassesses the available evidence for popular political activity within the maritime community. It argues that seafarers were deeply involved in the political and religious divisions that drove Britain into civil war in 1642; and, more broadly, that scholars should recognize the importance of both local and global approaches to maritime history – that they should think outside the gundeck.Arts and Humanities Research Council (AHRC

Physician-assisted suicide: a review of the literature concerning practical and clinical implications for UK doctors

BACKGROUND: A bill to legalize physician-assisted suicide in the UK recently made significant progress in the British House of Lords and will be reintroduced in the future. Until now there has been little discussion of the clinical implications of physician-assisted suicide for the UK. This paper describes problematical issues that became apparent from a review of the medical and psychiatric literature as to the potential effects of legalized physician-assisted suicide. DISCUSSION: Most deaths by physician-assisted suicide are likely to occur for the illness of cancer and in the elderly. GPs will deal with most requests for assisted suicide. The UK is likely to have proportionately more PAS deaths than Oregon due to the bill's wider application to individuals with more severe physical disabilities. Evidence from other countries has shown that coercion and unconscious motivations on the part of patients and doctors in the form of transference and countertransference contribute to the misapplication of physician-assisted suicide. Depression influences requests for hastened death in terminally ill patients, but is often under-recognized or dismissed by doctors, some of whom proceed with assisted death anyway. Psychiatric evaluations, though helpful, do not solve these problems. Safeguards that are incorporated into physician-assisted suicide criteria probably decrease but do not prevent its misapplication. SUMMARY: The UK is likely to face significant clinical problems arising from physician-assisted suicide if it is legalized. Terminally ill patients with mental illness, especially depression, are particularly vulnerable to the misapplication of physician-assisted suicide despite guidelines and safeguards