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Summary: This review is part of an annual evidence update on atopic eczema (AE), providing a summary of key findings from 18 systematic reviews published in 2019 on AE risk factors and prevention. Parental atopy, particularly AE, is a risk factor for offspring AE, and this risk is augmented both by the number of parental atopic diseases present and the number of affected parents. Low‐quality evidence suggests that autumn or winter birth increases childhood AE risk compared with birth in spring. There is some evidence to support filaggrin gene–environment interactions; however, this is limited by small underpowered studies. There is no evidence to suggest that polymorphisms in the –1082, –592 and –819 loci of the interleukin‐10 gene increase susceptibility to AE. There is no robust evidence to support a relationship between childhood AE development and either yoghurt consumption in the first year of life, gut microbiota variants, prenatal or infantile paracetamol exposure, maternal antibiotic exposure or air pollution. Three systematic reviews investigated the effect of probiotics given during pregnancy or infancy; although low‐quality evidence suggests benefits of combined probiotics, these studies were limited by significant heterogeneity. No relationship between the age at which complementary food and beverages are introduced and the risk of developing AE in infancy was identified. Consistent evidence showed no relationship between human milk feeding and infant AE development, aside from limited evidence suggesting a protective role in those with atopic heredity. This summary of recent evidence related to AE risk factors and prevention highlights the complex aetiology of AE. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of a series of annual evidence updates on atopic eczema (AE), and provides a summary of key findings from systematic reviews (SRs) published or indexed in 2019 related to AE treatment. Several SRs assessed the efficacy of topical corticosteroids (TCS), topical calcineurin inhibitors, topical phosphodiesterase‐4 inhibitors and topical Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway inhibitors. However, there is a lack of good‐quality trials comparing topical treatment agents with TCS, which remain the standard of care for patients with AE. Most of the included trials lack meaningful comparisons as they used vehicle as a comparator. There is also lack of harmonization of outcome measures for AE across studies. Large, well‐designed RCTs are needed to further determine whether any specific emollients offer superior benefit. There is evidence highlighting limited benefit of oral H1 antihistamines as 'add‐on' therapy to topical treatment of eczema. Mycophenolate mofetil may have a role in patients with refractory AE. Among biologic therapies, most of the efficacy data relate to dupilumab. Furthermore, there is growing evidence for the efficacy and safety of systemic JAK/STAT pathway inhibitors, but the existing data are of low quality. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review is part of a series of annual updates that summarize the evidence base for atopic eczema (AE). The aim is to provide a succinct guide for clinicians on the key findings from 14 systematic reviews on the prevention and topical treatment of AE published or indexed in 2018. Various supplements, including long‐chain polyunsaturated fatty acids, vitamin D and the probiotic Lactobacillus rhamnosus GG, given prenatally and postnatally, have not been shown to prevent AE in infants, although mixed strains of probiotics may decrease the risk of AE if given to the mother during pregnancy and to the infant for the first 6 months of life. In the postnatal period, there is no evidence that hydrolysed formula, compared with cow's milk formula (CMF), reduces the risk of AE in partially breastfed infants. However, weak evidence suggests that a specific partially hydrolysed whey formula decreases the risk of AE compared with CMF. No specific skin practices can be recommended to reduce the eczema risk in healthy term babies. There is weak evidence of a low risk of reversible hypothalamic–pituitary–adrenal axis suppression following 2–4 weeks of treatment with low‐potency topical steroids, and conflicting evidence as to whether bleach bathing affects skin flora or AE severity. A single study demonstrated that the topical Janus kinase inhibitor tofacitinib at 2% significantly reduces the Eczema Area and Severity Index compared with vehicle. Topical naltrexone cream 1% improves pruritus (measured using a visual analogue scale) by 30% more than placebo. There is weak evidence that topical alternative therapies, including antioxidants, micronutrients and some herbal medicines, may improve AE. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent research findings. The focus of this article is systemic therapies used in AE, while a review on prevention and topical therapies is provided in Part 1. In total, 17 SRs on various systemic treatments used in AE were first published or indexed in 2018. There is a lack of evidence to support vitamin D supplementation, montelukast and naltrexone in AE treatment. The adverse effects of systemic corticosteroids are the main barrier to their use, and there is also a lack of data to determine the optimal delivery and duration of treatment with them. Of other immunosuppressants, ciclosporin has the most robust evidence of efficacy. Biologic therapies in AE treatment are being increasingly investigated, and to date, the greatest quantity of data and evidence of efficacy relates to dupilumab. The most commonly reported adverse effects are injection‐site reactions and conjunctivitis. Other biologics showing some evidence of efficacy include nemolizumab, lebrikizumab and tralokinumab, although further data are needed. There are currently insufficient data on oral small molecules, including Janus kinase inhibitors, in the treatment of AE. A Cochrane review on probiotics showed no significant benefit, and SRs and meta‐analyses on complementary and alternative medicines, including probiotics, in paediatric AE demonstrated significant heterogeneity, thereby limiting their interpretation. This summary of recent SRs provides up‐to‐date evidence for clinicians on systemic therapies in AE. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE). It provides a summary of key findings from 25 systematic reviews that were published or indexed during 2017, and focuses on the treatment and prevention of AE. There is high‐quality evidence to demonstrate that dupilumab is better than placebo for the treatment of AE, is not associated with a higher incidence of adverse effects and does not increase the risk of infection compared with placebo; however, comparison studies with other systemic treatments are necessary. Topical tofacitinib is a promising treatment for mild–moderate AE, but currently lacks sufficient evidence from well‐designed randomized controlled trials (RCTs) comparing with other active treatments. Topical doxepin may be effective for pruritus in AE, but available studies have short follow‐up periods and longer‐term outcomes are needed. Bleach baths were no more effective than water baths alone at reducing AE severity. Topical antibiotics cannot be recommended for infected AE, owing to insufficient evidence of benefit. There is little comparison of different emollients in RCTs, but overall evidence indicates that they reduce AE severity, are steroid‐sparing and lead to better outcomes in combination with topical corticosteroids (TCS) than TCS alone. No clear benefit was demonstrated for vitamin D/C/E supplementation in pregnancy for eczema prevention. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This article forms part of a series of annual updates that summarizes the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2017, and focuses on the epidemiology, aetiology and risk factors of AE. AE is the largest single contributor to morbidity associated with skin disease worldwide, once mortality has been excluded. There is a high prevalence of sleep disturbance in individuals with AE and they take more sick leave than controls. While there is a lack of skin bacterial diversity in patients with AE, there is a relative abundance of Staphylococcus aureus and Staphylococcus epidermidis. Compared with controls, affected individuals more often show an IgE response to S. aureus antigens and have higher serum interleukin‐31 levels. Early antibiotic exposure, environmental pollutants, maternal atopy and food allergy are associated with an increased risk of AE, and very preterm birth is associated with decreased risk. Patients with AE have a reduced risk of meningioma, but are more likely to develop attention‐deficit hyperactivity disorder compared with controls. Patients with eosinophilic oesophagitis are significantly more likely than unaffected individuals to have AE. There is no significant overall association between AE and allergic contact dermatitis (ACD), and in children referred for patch testing, ACD was more common in those without AE. Hand eczema is more prevalent in patients with AE. There is no association between AE and Type 2 diabetes, hypertension, stroke or myocardial infarction. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: 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 presents the key findings from 14 systematic reviews published in 2016, focusing on AE epidemiology, aetiology and risk factors. For systematic reviews on the treatment and prevention of AE and for nomenclature and outcome assessments, see Parts 1 and 3 of this update, respectively. The annual self‐reported prevalence of AE is a range of 11.4–24.2%, compared with a general practioner‐diagnosed prevalence of 1.8–9.5%. The mean age of AE diagnosis is 1.6 years. Persistent AE is associated with more severe disease at the time of diagnosis, onset after the age of 2 years and female sex. There is a significant association between having AE and subsequent development of food allergy. Food allergy is also associated with more severe and persistent AE. No consistent association was found between the timing of allergenic food introduction and the risk of developing AE. Evidence from heterogeneous studies indicates that skin absorption is increased in patients with AE, and that there is increased colonization with Staphylococcus aureus in lesional and nonlesional skin and the nasal mucosa of patients with AE compared with controls. There is uncertain evidence indicating an association between AE and smoking exposure, antenatal infection and low maternal vitamin D levels during pregnancy. Weak evidence suggests an increased risk of basal cell carcinoma, but not of melanoma or squamous cell carcinoma, while the risk of glioma is reduced. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE). It presents the key findings from 11 systematic reviews published in 2016 that focus on AE outcome assessment, disease impact and nomenclature. Systematic reviews on the treatment and prevention of AE are summarized in Part 1 of this update, and systematic reviews on the epidemiology of and risk factors for AE are summarized in Part 2. Six reviews summarized what outcome measurement instruments have been used in published AE trials, or summarized validation studies for the available instruments. These reviews were used to inform consensus decisions by the Harmonising Outcome Measures for Eczema initiative. Although validated instruments exist for clinical signs and patient‐reported symptoms, there are currently no validated instruments for capturing quality of life or long‐term control. Four reviews examined the impact of AE on children and their families, but few studies were included. One birth cohort study found no association between AE and educational attainment at 11 years. AE has a moderate impact on health‐related quality of life and a substantial impact on family life. AE is a major risk factor for occupational hand dermatitis, and it is advised that young atopic individuals are informed about high‐risk occupations. Further efforts are required to standardize the nomenclature for AE, which is also commonly known as 'atopic dermatitis' or 'eczema', and preferred terms vary around the world. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review is part of a series of annual updates summarizing the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2016 with a focus on treatment and prevention of AE. There is reasonable evidence of benefit for topical corticosteroids, calcineurin inhibitors, a glycyrrhetinic acid‐containing preparation (Atopiclair®), oral ciclosporin, oral azathioprine, narrowband ultraviolet B radiation and education programmes. Overall, there is evidence that topical corticosteroids and calcineurin inhibitors have similar efficacy and that both can prevent AE flares when used twice weekly as maintenance therapy. However, topical calcineurin inhibitors are costlier and have more adverse reactions, thus topical corticosteroids should remain the standard of care for patients with AE. There is no evidence that multiple applications are better than once‐daily application of topical corticosteroid. There is inconsistent evidence to support omalizumab and specific allergen immunotherapy use in AE. There is some evidence that vitamin D supplementation and synbiotics reduce AE severity, although the margin of improvement may not be clinically meaningful. There is little evidence to support the use of wet wraps or of complementary/alternative medicine (including Chinese herbal medicine). There is some evidence to suggest that a diet high in fish in infancy may be preventative for AE, but other dietary interventions for the prevention of AE show little promise. This review provides a succinct guide for clinicians and patients wishing to remain up to date with the latest evidence for the treatment and prevention of AE. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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 15 systematic reviews that were published during 2015, and focuses on the epidemiology and methodology issues of AE. For systematic reviews on the prevention and treatment of AE, see Part 2 of this update. The worldwide prevalence of AE during childhood has been calculated to be 7.89% (95% CI 7.88–7.89), based on studies of 1 430 329 children from 102 countries. Children with AE are four times more likely than controls to have allergic rhinitis and asthma [relative risk (RR) = 4.24, 95% CI 3.75–4.79]. Twin studies show the heritability of AE to be about 75%. AE is more prevalent in patients with vitiligo and alopecia, and is positively associated with a high body mass index in America and Asia but not in Europe. Possible relationships between AE and exercise, maternal folate supplementation, maternal stress and autism spectrum disorder (ASD) have been assessed, but more high‐quality studies are needed for definitive conclusions. The Harmonising Outcomes Measures for Eczema (HOME) Initiative is developing a core set of outcome measures for AE trials. Suitable instruments for measuring quality of life are yet to be agreed, and use of Investigator Global Assessment in trials requires standardization. Transparent reporting of AE trials remains problematic. [ABSTRACT FROM AUTHOR]

This review summarizes key findings from nine systematic reviews on atopic eczema ( AE) published or first indexed in 2014. It focuses on epidemiology, disease processes and methodological issues. There is reasonable evidence to conclude that high birth weight (> 4000 g) is a risk factor for the development of AE. A lower socioeconomic position is associated with lower prevalence of AE. The effect of exposure to traffic-related air pollution in childhood on the development of AE is uncertain. CD14 polymorphisms do not appear to have an effect in AE. There may be a role for interleukin-18 in AE development. Patients with AE are at decreased risk of brain tumours, but at increased risk of developing attention deficit hyperactivity disorder. Evidence supports the view that normal-appearing skin in AE is in fact structurally abnormal. Lower success rates at inducing remission in AE are associated with increased risk of relapse during long-term follow-up. The Eczema Area Severity Index ( EASI) has been agreed as the preferred core instrument to measure clinical signs in future research. There remains a lack of consensus on the definition of an AE flare. [ABSTRACT FROM AUTHOR]

PurposeLaser 'toys' can be purchased online and imported with relative ease; the variety of such devices is a potential public safety concern. We describe five children with maculopathy following exposure to laser 'toys'.MethodsCase series of maculopathy following exposure to laser 'toys'.ResultsFive children were seen in our Ophthalmic Unit with macular injuries following exposure to laser 'toys'. Clinically, three children had an acute vitelliform-like maculopathy which resolved to leave sub-foveal retinal pigment epithelium changes with reduced vision. One case was complicated by a choroidal neovascular membrane.ConclusionLaser 'toys', which resemble laser pointers, are increasingly available over the internet. Such 'toys' may not meet safety standards. Retinal injury in childhood following exposure to laser 'toys' is a public safety concern. [ABSTRACT FROM AUTHOR]

Six cases of chronic endophthalmitis following extracapsular cataract extraction and lens implantation are reviewed. All were referred for tertiary management by one surgeon over a period of just over 2 years. In two of the cases coagulase negative staphylococci were isolated and in three Propionibacterium spp were retrieved. In the remaining case a mixed growth of coagulase negative staphylococci and Propionibacterium acnes was cultured. The surgical management, microbiological results, and eventual visual outcome are discussed. To our knowledge, this is the first documented outbreak of chronic pseudophakic endophthalmitis with commensal organisms from a single centre. [ABSTRACT FROM PUBLISHER]

Atopic eczema (herein referred to as 'eczema') is a skin disease characterized by remitting and relapsing symptoms. The Harmonising Outcome Measures for Eczema (HOME) initiative was developed to establish a core outcome set (COS) for eczema to be measured for all future eczema trials. The core outcome set for atopic eczema clinical trials includes the domain for patient-reported eczema control, but a review of the validation of available eczema control instruments was lacking. We aimed to review the literature and systematically assess the measurement properties of validated patient-reported outcome instruments that capture eczema control. PubMed and Ovid EMBASE were searched up to 24 January 2020 for any study that reported on PROM instrument development or validation. The COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria were used to assess the quality of eligible studies. We screened 12 036 titles and abstracts and 58 full texts. A total of 12 papers were included, reporting on seven PROMS. These were assessed with respect to development, reliability, construct validity and responsiveness. Two instruments, Recap of Atopic Eczema (RECAP) and the Atopic Dermatitis Control Tool (ADCT), have been developed and validated to a sufficient standard to support their recommendation as patient-reported outcome instruments for measuring control of atopic eczema as part of the HOME Core Outcome Set., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Research impact describes whether and how research results in wider benefits to society beyond academic publication. Little is known about translation of clinical trial research into dermatological practice., Aim: We scoped international impact from four independently funded clinical trials published by our group over the past 10 years., Methods: This was a scoping survey of 35 international colleagues from 22 countries followed by a narrative summary of emergent themes., Results: All recipients kindly responded to the survey. At least 20 emergent themes were identified, which broadly included: (i) interest and enthusiasm in the concept of trying to document clinical trial impact; (ii) direct impacts such as adoption of the drug as tested and recommended from the trial results, including more confidence using the drug in slightly different ways for the same condition; (iii) the finding that trial impact was dependent on factors such as drug availability and country-specific disease patterns; and (iv) the educational value of good trial design for journal club discussions and improving future clinical trial designs in dermatology. Our survey suggests that uptake into clinical practice was surprisingly rapid and widespread., Conclusion: Clinical trial research is of little use unless findings are translated into clinical practice for patient benefit. Our international scoping survey suggests that independent clinical trials that address important questions identified by the dermatology community have substantial, diverse and far-reaching impacts on dermatological practice., (© 2020 British Association of Dermatologists.)

Background: Standardized outcome reporting is crucial for trial evidence synthesis and translation of findings into clinical decision-making. The OMERACT 2.0 Filter and COMET outcome domain taxonomy propose frameworks for consistent reporting of outcomes. There is an absence of a uniform dermatology-specific reporting strategy that uses precise and consistent outcome definitions., Objectives: Our aim was to map efficacy/effectiveness outcomes assessed in dermatological trials to the OMERACT 2.0 Filter as a starting point for developing an outcome taxonomy in dermatology., Methods: We critically appraised 10 Cochrane Skin Reviews randomly selected from all 69 Cochrane Skin Reviews published until 01/2015 and the 220 trials included covering a broad spectrum of dermatological conditions and interventions. Efficacy/effectiveness outcomes were mapped to core areas and domains according to the OMERACT 2.0 Filter. The extracted trial outcomes were used for critical appraisal of outcome reporting in dermatology trials and for the preliminary development of a dermatology-specific outcome taxonomy., Results: The allocation of 1086 extracted efficacy/effectiveness outcomes to the OMERACT 2.0 Filter resulted in a hierarchically structured dermatology-specific outcome classification. In 506 outcomes (47%), the outcome concept to be measured was insufficiently described, hindering meaningful evidence synthesis. Although the core areas assessed in different dermatology trials of the same condition overlap considerably, quantitative evidence synthesis usually failed due to imprecise outcome definitions, non-comparable outcome measurement instruments, metrics and reporting., Conclusions: We present an efficacy/effectiveness outcome classification as a starting point for a dermatology-specific taxonomy to provide trialists and reviewers with the opportunity to better synthesize and compare evidence., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Eczema control has been identified as an important outcome by key stakeholders in eczema research (including patients, carers, healthcare professionals and researchers) but no validated instruments for the domain have been identified., Objectives: To develop a measurement instrument to capture a patient's perspective of eczema control that is suitable for use in eczema clinical trials., Methods: Best practice for the development of a patient-reported outcome was followed. A mixed-methods approach was used to develop and refine a conceptual framework, generate, refine and select items and to test the distribution and construct validity of the final scale. The mixed-methods approach involved expert panel meetings (including patient representatives, healthcare professionals and methodologists), and data collection using a focus group, cognitive interviews and an online survey with people with eczema and caregivers. Multivariable linear regression was used in the item selection process., Results: Fourteen expert panel members co-produced the instrument, with input from people with eczema and caregivers via a focus group (n = 6), cognitive interviews (n = 13) and an online survey (n = 330). The resulting instrument, Recap of atopic eczema (RECAP), is a seven-item questionnaire that captures eczema control via self or caregiver report. The development process aimed to ensure good content validity and feasibility. Initial testing suggested no floor or ceiling effects and good construct validity. Hypothesized correlation with the Patient-Oriented Eczema Measure was confirmed [r(258) = 0·83, P < 0·001]., Conclusions: RECAP has the potential to improve reporting of eczema control in research and clinical practice. Further exploration of measurement properties is required. Linked Comment: Pattinson and Bundy. Br J Dermatol 2020; 183:418-419. What's already known about this topic? Eczema control has been identified as an important outcome by key stakeholders in eczema research (including patients, carers, healthcare professionals and researchers). Qualitative studies suggest eczema control is a multifaceted and individual experience and no instrument has been identified that captures eczema control in this way. What does this study add? We have developed Recap of atopic eczema (RECAP), a seven-item questionnaire to capture the experience of eczema control in all ages and eczema severities; there are two versions: a self-reported version for adults and older children with eczema, and a caregiver-reported version for younger children with eczema. Designed with input from people with eczema, caregivers and healthcare professionals to ensure good content validity. Initial testing of score distributions and construct validity suggests good measurement properties. What are the clinical implications of the work? The RECAP instrument is appropriate and feasible for measuring eczema control in clinical trials and may also be useful in routine practice., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon., (© 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Atopic eczema (AE) is a common chronic inflammatory skin condition. While many AE treatment options are available, the evidence to support their efficacy varies in depth and quality. In 2000, a National Institute for Health Research (NIHR) Health Technology Assessment systematic review identified and evaluated existing randomized controlled trials (RCTs) of AE treatments. To ensure continuing utility, the NIHR commissioned an update to the review. Here, we present an overview of the updated report and its key findings. Systematic reviews and RCTs of AE treatments that included participants with AE (criteria based or diagnosed) were identified using Medline, Embase, CENTRAL, Latin American and Caribbean Health Sciences, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature and Cochrane Skin Group Specialised Register [searched to 31 August 2013 (RCTs) and 31 December 2015 (systematic reviews)]. Outcome measures included symptoms, AE severity, quality of life and adverse effects. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Of the 287 new RCTs identified, only 22 (8%) were judged to have a low risk of bias. When combined with RCTs from the previous review (n = 254), we found 'reasonable evidence of benefit' for corticosteroids, calcineurin inhibitors, Atopiclair ® , ciclosporin, azathioprine, ultraviolet radiation and education programmes. Interventions with reasonable evidence of 'no benefit' included some dietary interventions, ion exchange water softeners, multiple daily applications of topical corticosteroids and antibiotic-containing corticosteroids for noninfected AE. Many common treatments lack evidence of efficacy and warrant further evaluation. The evidence base for AE is still hampered by poor trial design and reporting. The trials included in this review were used to establish the Global Resource of EczemA Trials (GREAT) database., (© 2016 British Association of Dermatologists.)

'Symptoms' is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand-alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms-only data from most published studies. Future trials should report symptom scores to permit meta-analysis of the core outcomes., (© 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Purpose: To elucidate the aetiology of childhood blindness in the Republic of Uzbekistan and to assess the needs for future provision of ophthalmic services for children., Methods: Six hundred and seventy-one children in seven schools for the blind and visually impaired throughout Uzbekistan were examined using the WHO/PBL (World Health Organization Prevention Of Blindness) childhood blindness proforma. The locations were chosen to give a representation of the major areas of population within the country., Results: Of the 671 children examined, 506 (75.4%) were blind or severely visually impaired (corrected visual acuity of less than 6/60 (20/200) in the better eye). Cataract-related blindness (35%), retinal dystrophies (24%) and microphthalmos (23%) formed the three largest diagnostic categories., Conclusions: The commonest avoidable cause of blindness was found to be cataract; the cause of poor vision may be due to unoperated cataract, aphakia, amblyopia or post-operative capsular fibrosis. The high proportion of retinal dystrophies may be related to the common practice of consanguineous marriage. The frequent finding of microphthalmos is discussed and compared with findings from other surveys. Glaucoma accounted for approximately 5% of the avoidable blindness.

A retrospective survey is presented of the case records of 138 patients who had undergone operative treatment for acoustic neuroma. The nature and incidence of ophthalmic features prior to and following surgery is documented. The study covers 12 years in two regional neurosurgical centres, under the care of six different neurosurgeons, one otolaryngologist and nine ophthalmologists. Of the 138 records examined, 61 patients (44%) required lid surgery of one variety or another. 18 (13%) developed minor superficial exposure keratopathy, 13 (9%) developed corneal opacification or clouding, two had recurrent infective abscesses and four developed optic atrophy. The development of corneal complications strongly correlates with the presence of documented preoperative fifth nerve involvement. Postoperative oculomotor cranial nerve palsies were seen in 10 patients (7%). Ophthalmologists should be involved in the perioperative management of these patients and certainly before irreversible corneal damage has occurred.

The presence of fine epithelial deposits in a whorled pattern (cornea verticillata) as a consequence of treatment with amiodarone is well documented. We present a case of amiodarone keratopathy in a grafted cornea which is atypical in that the orientation of the pattern is rotated through nearly 90 degrees to that normally observed. This observation runs counter to the hypothesis that cornea verticillata is a manifestation of the line of lid closure. We speculate on the mechanism directing the migrational pathways of epithelial cells.

The importance of electrostatic interactions between buried charges in determining the properties of membrane proteins is considered. It is demonstrated that in some cases altered properties may result from the extraction of a membrane protein into an aqueous medium even when the protein conformation is unperturbed.

Calculations of the electrostatic interaction energies for four metalloproteins that carry out electron transfer are reported. Each protein has a pH dependent redox potential from which the measured electrostatic interaction energy is obtained. The calculations were made using the X-ray structure coordinates and a semimacroscopic model of the interactions. For cytochrome c-551 and HIPIP the calculated and observed interaction energies were found to be approximately the same, in agreement with the fact that significant conformational changes do not accompany the ionisations. For cytochrome c2 and azurin, however, major differences were found between the calculated and observed values. These are accounted for primarily by the occurrence of significant conformational changes accompanying the ionisations. The reorganisation energies for these conformational changes are approximately 7.0 and approximately 11.1 kJ.mol-1, respectively.

The redox potentials of electron transfer proteins vary over a wide range, even when the type of redox center is the same. Rees [Proc. Natl. Acad. Sci. USA (1985) 82, 3082-3085] proposed that this variation of redox potential partly reflects the different net charges of the proteins, and he presented a linear correlation between these two properties for 36 proteins. A review of the factors that influence protein redox potentials makes it clear that this linear correlation is fortuitous. The key factors influencing redox potentials are the contributions to the Gibbs energy difference between the two redox states, resulting from bonding interactions at the redox center, electrostatic interactions between the redox-center charge and polar groups within the protein and solvent, and redox-state conformational changes. The relative importance of these terms is likely to vary from protein to protein.

The alpha-helix has an electric dipole arising from the alignment of peptide dipoles parallel to the helix axis. The effect of this alpha-helix dipole in the stabilization of the tertiary structure of globular proteins is examined using three of the commonly used dielectric models. These models are; (1) the uniform dielectric model, (2) the distance dependent dielectric model and (3) the cavity dielectric model. Of these the cavity model is the most reasonable since it attempts to describe the markedly different dielectric responses of the solvent and the protein. The protein is set at a low continuous dielectric value and the solvent is set at a high continuous dielectric value. It is found that for the cavity model of the dielectric the calculated interaction energy between two helices is strongly dependent upon how exposed the helix termini are to solvent. For helices with exposed termini the calculations using the cavity model yield electrostatic interaction energies which are lower by an order of magnitude than those obtained using the uniform dielectric model.

An equal mixture of oxidized and reduced cytochrome c551 experiences a change in the potential of the haem iron when one of the propionates attached to the haem is ionized. The change is 65 mV, which corresponds to an effective dielectric between the propionate and the iron of 27. It has been possible to use the algorithm of Warwicker & Watson (1982) to calculate the change in the potential at the haem iron arising from the change in ionization of the propionate. This gives the extra work required to oxidize or reduce the iron. The change in potential that we calculate is 90 mV, which corresponds to an effective dielectric of 19.5, between the propionate and the iron. In comparison with other commonly used dielectric models the agreement is very good.