A magnetic massive star has experienced a stellar merger.

Massive stars (those ≥8 solar masses at formation) have radiative envelopes that cannot sustain a dynamo, the mechanism that produces magnetic fields in lower-mass stars. Despite this, approximately 7% of massive stars have observed magnetic fields, the origin of which is debated. We used multi-epoch interferometric and spectroscopic observations to characterize HD 148937, a binary system of two massive stars. We found that only one star is magnetic and that it appears younger than its companion. The system properties and a surrounding bipolar nebula can be reproduced with a model in which two stars merged (in a previous triple system) to produce the magnetic massive star. Our results provide observational evidence that magnetic fields form in at least some massive stars through stellar mergers.

Spinal epidural abscesses - The role for non-operative management: A systematic review.

BACKGROUND: Spinal Epidural Abscesses (SEAs) are traditionally seen as a surgical emergency. However, SEAs can be discovered in entirely asymptomatic patients. This presents a dilemma for the attending clinician as to whether to subject these patients to significant surgery. This systematic review updates the evidence surrounding the efficacy of non-operative SEA management by means of intravenous antibiotics ± radiologically-guided aspiration. AIMS: 1. To assess failure rates of medical therapy for SEA. The absolute definition of 'failure' used by the study was recorded, and comparisons made. 2. To review of risk factors for success/failure of medical treatment for SEA. METHODS: A database search with the MESH term 'epidural abscess' and keywords ['treatment' OR 'management'] were used. RESULTS: 14 studies were included. The number of SEA patients managed non-operatively ranged from 19 to 142. There was significant heterogeneity across the studies. Pooled Failure of Medical Therapy (FMT) (defined as any poor outcome) was 29.40%. When FMT = mortality the pooled rate was 11.49%. Commonly cited risk factors for FMT included acute neurological compromise, diabetes mellitus, increasing age and Staphylococcus aureus. CONCLUSION: SEA will always be a condition mostly managed surgically. Despite this, there is growing evidence that non-operative management can be possible in the correct patients. The key is in patient selection - patients with any of the above-mentioned risk factors have the potential to deteriorate further on medical treatment and have a worse outcome than if they had undergone emergency surgery straight away. Ongoing research will hopefully further investigate this crucial step.

Current outcomes when optimizing 'standard' sample preparation for single-particle cryo-EM.

Although high-resolution single-particle cryo-electron microscopy (cryo-EM) is now producing a rapid stream of breakthroughs in structural biology, it nevertheless remains the case that the preparation of suitable frozen-hydrated samples on electron microscopy grids is often quite challenging. Purified samples that are intact and structurally homogeneous - while still in the test tube - may not necessarily survive the standard methods of making extremely thin, aqueous films on grids. As a result, it is often necessary to try a variety of experimental conditions before finally finding an approach that is optimal for the specimen at hand. Here, we summarize some of our collective experiences to date in optimizing sample preparation, in the hope that doing so will be useful to others, especially those new to the field. We also hope that an open discussion of these common challenges will encourage the development of more generally applicable methodology. Our collective experiences span a diverse range of biochemical samples and most of the commonly used variations in how grids are currently prepared. Unfortunately, none of the currently used optimization methods can be said, in advance, to be the one that ultimately will work when a project first begins. Nevertheless, there are some preferred first steps to explore when facing specific problems that can be more generally recommended, based on our experience and that of many others in the cryo-EM field.

Extreme lateral interbody fusion (XLIF) as a treatment for acute spondylodiscitis: Leeds spinal unit experience.

Extreme lateral interbody fusion (XLIF) is a minimally invasive lateral trans-psoas approach to the thoraco-lumbar spine that enables surgical debridement of the disc space and facilitates fusion. Previous reports are limited to case series, which have no outcomes measuring improvement. We aim to determine the effectiveness of XLIF in the treatment of patients with spondylodiscitis. We performed a cohort study over four years (2008-2011). Patients were treated with XLIF if they met our selection criteria - symptoms suggestive of discitis with consistent imaging and intractable back pain making patients bedbound. Patients were excluded if medically unfit for surgery. Pre and post-operative VAS and ODI scores were used as formal outcome measures. 14 patients were included and at 12 months, median VAS and ODI scores had improved 4.0 (95% CI, 1.9-6.5) (p = 0.005) and 37.0% (95% CI, 10.7-53.7) (p = 0.015) respectively. All patients with available imaging showed evidence of fusion. Patients typically received 6-8 weeks of antibiotics and all showed normalisation of inflammatory markers. At 5 year follow-up, median VAS and ODI were still improved at 3.0 (95% CI, 1.7-4.4) (p = 0.01) and 40% (95% CI, 10-52) (p = 0.028) respectively. The median length of inpatient stay was 10 days (range 4-40 days). This is the first study to demonstrate that the XLIF technique can significantly improve pain in discitis patients using validated formal outcome measurements. This technique could therefore potentially be used to reduce pain in patients with discitis, help them to mobilise earlier and reduce the duration of their hospital stay.

HIV-1 Transmission Clustering and Phylodynamics Highlight the Important Role of Young Men Who Have Sex with Men.

More persons living with HIV reside in the Southern United States than in any other region, yet little is known about HIV molecular epidemiology in the South. We used cluster and phylodynamic analyses to evaluate HIV transmission patterns in middle Tennessee. We performed cross-sectional analyses of HIV-1 pol sequences and clinical data collected from 2001 to 2015 among persons attending the Vanderbilt Comprehensive Care Clinic. Transmission clusters were identified using maximum likelihood phylogenetics and patristic distance differences. Demographic, risk behavior, and clinical factors were assessed evaluating "active" clusters (clusters including sequences sampled 2011-2015) and associations estimated with logistic regression. Transmission risk ratios for men who have sex with men (MSM) were estimated with phylodynamic models. Among 2915 persons (96% subtype-B sequences), 963 (33%) were members of 292 clusters (distance ≤1.5%, size range 2-39). Most clusters (62%, n = 690 persons) were active, either being newly identified (n = 80) or showing expansion on existing clusters (n = 101). Correlates of active clustering among persons with sequences collected during 2011-2015 included MSM risk and ≤30 years of age. Active clusters were significantly more concentrated in MSM and younger persons than historical clusters. Young MSM (YMSM) (≤26.4 years) had high estimated transmission risk [risk ratio = 4.04 (2.85-5.65) relative to older MSM] and were much more likely to transmit to YMSM. In this Tennessee cohort, transmission clusters over time were more concentrated by MSM and younger age, with high transmission risk among and between YMSM, highlighting the importance of interventions among this group. Detecting active clusters could help direct interventions to disrupt ongoing transmission chains.

Barriers to accessing palliative care for pediatric patients with cancer: A review of the literature.

Although many of the 16,000 children in the United States diagnosed who are with cancer each year could benefit from pediatric palliative care, these services remain underused. Evidence regarding the barriers impeding access to comprehensive palliative care is dispersed in the literature, and evidence specific to pediatric oncology remains particularly sparse. The purpose of the current review was to synthesize the existing literature regarding these barriers and the strategies offered to address them. The authors completed a literature search using the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science databases. In total, 71 articles were reviewed. Barriers to accessing pediatric palliative care were categorized according to the 4 levels of a modified socioecological model (ie, barriers related to policy/payment, health systems, organizations, and individuals). Major themes identified at each level included: 1) the lack of consistent and adequate funding mechanisms at the policy/payment level, 2) the lack of pediatric palliative care programs and workforce at the health systems level, 3) difficulties integrating palliative care into existing pediatric oncology care models at the organizational level, and 4) the lack of knowledge about pediatric palliative care, discomfort with talking about death, and cultural differences between providers and patients and their families at the individual level. Recommendations to address each of the barriers identified in the literature are included. Cancer 2018;124:2278-88. © 2018 American Cancer Society.

D2R2: an evidence-based decision support tool to aid prioritisation of animal health issues for government funding.

An evidence-based decision support tool, 'D2R2', has been developed by Defra. It contains a wide range of standardised information about exotic and endemic diseases held in 'disease profiles'. Each profile includes 40 criteria used for scoring, enabling D2R2 to provide relative priority rankings for every disease profiled. D2R2 also provides a range of reports for each disease and the functionality to explore the impact of changes in any criterion or weighting on a disease's ranking. These outputs aid the prioritisation and management of animal diseases by government. D2R2 was developed with wide stakeholder engagement and its design was guided by clear specifications. It uses the weighted scores of a limited number of criteria to generate impact and risk scores for each disease, and relies on evidence drawn from published material wherever possible and maintained up to date. It allows efficient use of expertise, as maintained disease profiles reduce the need for on call, reactive, expert input for policy development and enables rapid simultaneous access to the same information by multiple parties, for example during exotic disease outbreaks. The experience in developing D2R2 has been shared internationally to assist others with their development of disease prioritisation and categorisation systems.

Factors associated with interest in subspecialty training among neurology residents.

UNLABELLED: PHENOMENON: Previous studies have not explored factors associated with decisions among neurology residents to pursue subspecialty training within neurology. Understanding career choices among neurology residents, particularly decisions regarding subspecialty training, is critical, as neurologists with specialized knowledge can help meet the needs of patients with specific disease conditions. This study addresses the knowledge gap about subspecialty training decisions by examining factors associated with neurology residents' interest in pursuing subspecialty training and the types of subspecialty training neurology residents consider. APPROACH: We surveyed a geographically stratified sample of neurology residents in U.S. training programs using a two-stage survey design. In Stage 1, we randomly sampled half of the accredited neurology residency programs stratified by U.S. census region; Stage 2 involved a survey of neurology residents within these programs. FINDINGS: The majority (approximately 81%) of residents expressed interest in subspecialty training. Resident demographic characteristics and educational debt did not influence interest in pursuing subspecialty training. Residents were more likely to express interest in subspecialty training when they participated in any neurology research (odds ratio [OR] = 2.39), 95% confidence interval (CI) [1.13, 5.07], p = .02, and indicated more interest in careers involving teaching (OR = 8.33), 95% CI [1.64, 42.19], p = .01. Considering the "medical content of subspecialty" as a more important factor approached but did not reach statistical significance (OR = 3.12), 95% CI [0.97, 10.06], p = .06. Insights: Participation in any neurology research and interest in careers involving teaching are associated with interest in subspecialty training among neurology residents. Further research is needed to determine whether exposure to research and teaching stimulates interest in subspecialty training and whether residents believe that subspecialty training is instrumental in pursuing an academic career.

Interest in providing multiple sclerosis care and subspecializing in multiple sclerosis among neurology residents.

BACKGROUND: Although detailed knowledge regarding treatment options for multiple sclerosis (MS) patients is largely limited to neurologists, shortages in the neurologist workforce, including MS subspecialists, are predicted. Thus, MS patients may have difficulties in gaining access to appropriate care. No systematic evaluation has yet been performed of the number of neurology residents planning to pursue MS subspecialization. This study identifies factors affecting interest in providing MS patient care or MS subspecialization among current neurology residents. METHODS: We randomly selected half of all Accreditation Council of Graduate Medical Education-certified neurology residency programs in the continental United States to receive the neurology resident survey. Completed surveys were received from 218 residents. RESULTS: Residents were significantly more likely to have increased interest in MS care when they participated in MS research, were interested in teaching, and indicated that the "ability to improve patient outcomes and quality of life" was a positive factor influencing their desire to provide MS patient care. Residents who were interested in providing MS care, interested in teaching, and indicated that "research opportunities" was a positive factor for providing MS patient care were significantly more likely to express interest in MS subspecialization. CONCLUSIONS: Increasing opportunities to interact with MS patients, learn about MS care, and participate in MS research may increase interest in MS care and subspecialization among neurology residents. Opportunities to educate residents regarding MS patient care may affect residents' attitudes.

The helicase-primase inhibitor BAY 57-1293 reduces the Alzheimer's disease-related molecules induced by herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV1) infection of cultured cells causes the formation of ß-amyloid (Aß) and abnormal tau (P-tau). These molecules comprise the main components of the abnormal protein deposits, amyloid plaques and neurofibrillary tangles, respectively, in Alzheimer's disease (AD) brains, and they have been implicated in disease development. The formation of P-tau, but not of Aß, depends on viral DNA replication, but nonetheless, three antiviral agents that inhibit HSV1 DNA replication, including acyclovir (ACV), were found to reduce greatly the level of Aß as well as P-tau, the former probably through prevention of viral spread. Previous studies showed that HSV1 DNA is present and is active in the brain of many elderly people, including AD patients, and that in combination with the type 4 allele of the apolipoprotein E gene, it is likely to play a role in the disease, perhaps via Aß and P-tau production. With the aim of finding the most suitable antiviral for inhibiting Aß and P-tau formation as well as HSV1 DNA replication, for future use in a clinical trial for treating AD, we compared the efficacy of ACV with that of another antiviral, BAY 57-1293, which acts by a different mechanism from ACV. We found that BAY 57-1293 is more efficient than ACV not only in inhibiting HSV1 replication, confirming previous studies, but also in decreasing Aß and P-tau formation. Also, the cell clusters that are formed during infection are reduced in size much more efficiently by BAY 57-1293 than by ACV. These data suggest that BAY 57-1293 would be a more effective agent than ACV for treating AD.

The presence of a cytopathologist increases the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration cytology for pancreatic adenocarcinoma: a meta-analysis.

OBJECTIVE: A meta-analysis has not been previously performed to evaluate critically the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solely pancreatic ductal adenocarcinoma and address factors that have an impact on variability of accuracy. The aim of this study was to determine whether the presence of a cytopathologist, variability of the reference standard and other sources of heterogeneity significantly impacts diagnostic accuracy. METHODS: We conducted a comprehensive search to identify studies, in which the pooled sensitivity, specificity, likelihood ratios for a positive or negative test (LR+, LR-) and summary receiver-operating curves (SROC) could be determined for EUS-FNA of the pancreas for ductal adenocarcinoma using clinical follow-up, and/or surgical biopsy or excision as the reference standard. RESULTS: We included 34 distinct studies (3644 patients) in which EUS-FNA for a solid pancreatic mass was evaluated. The pooled sensitivity and specificity for EUS-FNA for pancreatic ductal adenocarcinoma was 88.6% [95% confidence interval (CI): 87.2-89.9] and 99.3% (95% CI: 98.7-99.7), respectively. The LR+ and LR- were 33.46 (95% CI: 20.76-53.91) and 0.11 (95% CI: 0.08-0.16), respectively. The meta-regression model showed rapid on-site evaluation (ROSE) (P = 0.001) remained a significant determinant of EUS-FNA accuracy after correcting for study population number and reference standard. CONCLUSION: EUS-FNA is an effective modality for diagnosing pancreatic ductal adencarcinoma in solid pancreatic lesions, with an increased diagnostic accuracy when using on-site cytopathology evaluation.

Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study.

BACKGROUND: In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC). METHODS: Patients received oral regorafenib 60-220 mg daily (160 mg daily in the extension cohort) in cycles of 21 days on, 7 days off treatment. Assessments included toxicity, response, pharmacokinetics and pharmacodynamics. RESULTS: Thirty-eight patients with heavily pretreated CRC (median 4 prior lines of therapy, range 0-7) were enrolled in the dose-escalation and extension phases; 26 patients received regorafenib 160 mg daily. Median treatment duration was 53 days (range 7-280 days). The most common treatment-related toxicities included hand-foot skin reaction, fatigue, voice change and rash. Twenty-seven patients were evaluable for response: 1 achieved partial response and 19 had stable disease. Median progression-free survival was 107 days (95% CI, 66-161). At steady state, regorafenib and its active metabolites had similar systemic exposure. Pharmacodynamic assessment indicated decreased tumour perfusion in most patients. CONCLUSION: Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC. This expanded-cohort phase I study provided the foundation for further clinical trials of regorafenib in this patient population.

Phase i study of the Plk1 inhibitor BI 2536 administered intravenously on three consecutive days in advanced solid tumours.

BACKGROUND: This open-label phase i study with an accelerated titration design was performed to determine the maximum tolerated dose of BI 2536, a potent, highly selective small-molecule polo-like kinase 1 (Plk1) inhibitor. METHODS: Patients with advanced solid tumours received a single 60-minute intravenous infusion of BI 2536 (50-70 mg) on days 1-3 of each 21-day treatment course. Recipients without disease progression or untenable toxicity could receive additional treatment courses. The maximum tolerated dose was determined based on dose-limiting toxicities. Other assessments included safety, pharmacokinetic profile, and antitumour activity according to the Response Evaluation Criteria in Solid Tumors. RESULTS: The study enrolled 21 patients. The maximum tolerated dose for BI 2536 was determined to be 60 mg for the study schedule. Dose-limiting toxicities included hematologic events, hypertension, elevated liver enzymes, and fatigue. The most frequently reported drug-related adverse events were mild-to-moderate fatigue, leukopenia, constipation, nausea, mucosal inflammation, anorexia, and alopecia. The pharmacokinetics of BI 2536 were linear within the dose range tested. Plasma concentration profiles exhibited multi-compartmental pharmacokinetic behaviour, with a terminal elimination half-life of 20-30 hours. CONCLUSIONS: In the present study, BI 2536 showed an acceptable safety profile warranting further investigation of Plk1 inhibitors in this patient population.

Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis.

BACKGROUND: EndoTAG-1 (ET), a novel formulation of cationic liposomes carrying embedded paclitaxel (Taxol), shows antitumoral activity, targeting tumor endothelial cells in solid tumors. Patients with advanced metastatic cancer were evaluated investigating effects on pharmacokinetics and tumor vasculature using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and contrast-enhanced ultrasound (CEUS). PATIENTS AND METHODS: The pharmacokinetic (PK) profile of ET (22 mg/m(2) i.v.) was evaluated after single and repeated doses. DCE-MRI and CEUS explored hepatic metastases before, during and after the 4-week treatment cycle. Angiogenic biomarkers were assessed. Tumor response was evaluated by modified RECIST. RESULTS: The PK profile demonstrated slight accumulation of paclitaxel after repeated doses. DCE-MRI parameters K(trans) and/or iAUC(60) showed a trend to decrease. Changes of blood flow-dependent parameters of DCE-MRI and CEUS were well correlated. Angiogenic biomarkers revealed no clear trend. ET was generally well tolerated; common toxic effects were fatigue and hypersensitivity reactions. Nine (9 of 18) patients had stable disease after the first treatment cycle. Four patients without disease progression continued treatment. CONCLUSIONS: This study including multiple pretreated patients with different metastatic cancer revealed individually distinctive hemodynamic alterations by DCE-MRI. The PK profiles of ET were similar as observed previously.

Targeting ErbB3-mediated stromal-epithelial interactions in pancreatic ductal adenocarcinoma.

BACKGROUND: We sought to investigate the role of ErbB3-mediated signalling on the interaction between pancreatic cancer-associated fibroblasts (CAF) and carcinoma cells in an effort to disrupt tumourigenic pancreatic ductal adenocarcinoma (PDAC) stromal-epithelial cross-communication. METHODS: Primary CAF cultures were established from human PDAC surgical specimens. AsPC-1 pancreatic cancer cell murine subcutaneous xenografts were developed in the presence and absence of CAF and were subsequently treated with epidermal growth factor receptor (EGFR) inhibitors (erlotinib) and ErbB3 inhibitors (MM-121, monoclonal ErbB3 antibody). RESULTS: Cancer-associated fibroblasts were found to secrete neuregulin-1 (NRG-1), which promoted proliferation via phosphorylation of ErbB3 and AKT in AsPC-1 PDAC cells. This signalling cascade was effectively inhibited both in vitro and in vivo by specific ErbB3 blockade with MM-121, with greater degree of tumourigenesis inhibition when combined with erlotinib. The CAF-AsPC-1 pancreatic cancer xenografts reached significantly greater tumour volume than those xenografts lacking CAF and were resistant to the anti-tumour effects of EGFR inhibition with erlotinib. CONCLUSION: Cancer-associated fibroblasts-derived NRG-1 promote PDAC tumourigenesis via ErbB3-AKT signalling and overcomes single-agent EGFR inhibition. Disruption of this stromally mediated tumourigenic mechanism is best obtained through combined EGFR-ErbB3 inhibition with both erlotinib and MM-121. We have identified the NRG-1/ErbB3 axis as an attractive molecular target for the interruption of tumourigenic stromal-epithelial interactions within the PDAC microenvironment.

Is a fracture of the transverse process of L5 a predictor of pelvic fracture instability?

In the management of a pelvic fracture prompt recognition of an unstable fracture pattern is important in reducing mortality and morbidity. It is believed that a fracture of the transverse process of L5 is a predictor of pelvic fracture instability. However, there is little evidence in the literature to support this view. The aim of this study was to determine whether a fracture of the transverse process of L5 is a reliable predictor of pelvic fracture instability. We reviewed our hospital trauma database and identified 80 patients who sustained a pelvic fracture between 2006 and 2010. There were 32 women and 48 men with a mean age of 40 years (10 to 96). Most patients were injured in a road traffic accident or as a result of a fall from a height. A total of 41 patients (51%) had associated injuries. The pelvic fractures were categorised according to the Burgess and Young classification. There were 45 stable and 35 unstable fractures. An associated fracture of the transverse process of L5 was present in 17 patients; 14 (40%) of whom had an unstable fracture pattern. The odds ratio for an unstable fracture of the pelvis in the presence of a fracture of the transverse process of L5 was 9.3 and the relative risk was 2.5. A fracture of the transverse process of L5 in the presence of a pelvic fracture is associated with an increased risk of instability of the pelvic fracture. Its presence should alert the attending staff to this possibility.

A multicentre randomised controlled trial and economic evaluation of ion-exchange water softeners for the treatment of eczema in children: the Softened Water Eczema Trial (SWET).

OBJECTIVES: To determine whether installation of an ion-exchange water softener in the home could improve atopic eczema in children and, if so, to establish its likely cost and cost-effectiveness. DESIGN: An observer-blind, parallel-group randomised controlled trial of 12 weeks duration followed by a 4-week observational period. Eczema was assessed by research nurses blinded to intervention at baseline, 4 weeks, 12 weeks and 16 weeks. The primary outcome was analysed as intent-to-treat, using the randomised allocation rather than actual treatment received. A secondary per-protocol analysis excluded participants who failed to receive their allocated treatment and who were deemed to be protocol violators. SETTING: Secondary and primary care referral centres in England (UK) serving a variety of ethnic and social groups and including children living in both urban and periurban homes. PARTICIPANTS: Three hundred and thirty-six children (aged 6 months to 16 years) with moderate/severe atopic eczema, living in homes in England supplied by hard water (≥ 200 mg/l calcium carbonate). INTERVENTIONS: Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care (group A) for 12 weeks or usual eczema care alone (group B) for 12 weeks. This was followed by a 4-week observational period, during which water softeners were switched off/removed from group A homes and installed in group B homes. Standard procedure was to soften all water in the home, but to provide mains (hard) water at a faucet-style tap in the kitchen for drinking and cooking. Participants were therefore exposed to softened water for bathing and washing of clothes, but continued to drink mains (hard) water. Usual care was defined as any treatment that the child was currently using in order to control his or her eczema. New treatment regimens used during the trial period were documented. MAIN OUTCOME MEASURES: Primary outcome was the difference between group A and group B in mean change in disease severity at 12 weeks compared with baseline, as measured using the Six Area, Six Sign Atopic Dermatitis (SASSAD) score. This is an objective severity scale completed by blinded observers (research nurses) unaware of the allocated intervention. Secondary outcomes included use of topical medications, night-time movement, patient-reported eczema severity and a number of quality of life measures. A planned subgroup analysis was conducted, based on participants with at least one mutation in the gene encoding filaggrin (a protein in the skin thought to be important for normal skin barrier function). RESULTS: Target recruitment was achieved (n = 336). The analysed population included 323 children who had complete data. The mean change in primary outcome (SASSAD) at 12 weeks was -5.0 [standard deviation (SD) 8.8] for the water softener group (group A) and -5.7 (SD 9.8) for the usual care group (group B) [mean difference 0.66, 95% confidence interval (CI) -1.37 to 2.69, p = 0.53]. The per-protocol analysis supported the main analysis, and there was no evidence that the treatment effect varied between children with and without mutations in the filaggrin gene. No between-group differences were found in the three secondary outcomes that were assessed blindly (use of topical medications; night-time movement; proportion showing reasonable, good or excellent improvement). Small, but statistically significant, differences in favour of the water softener were found in three of the secondary outcomes that were assessed by participants [Patient-Oriented Eczema Measure (POEM); well-controlled weeks (WCWs); Dermatitis Family Index (DFI)]. The results of the economic evaluation, and the uncertainty surrounding them, suggest that ion-exchange water softeners are unlikely to be a cost-effective intervention for children with atopic eczema from an NHS perspective. CONCLUSIONS: Water softeners provided no additional benefit to usual care in this study population. Small, but statistically significant, differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias. Whether or not the wider benefits of installing a water softener in the home are sufficient to justify the purchase of a softener is something for individual householders to consider on a case-by-case basis. This trial demonstrated overwhelming demand for non-pharmacological interventions for the treatment of eczema, and this is something that should be considered when prioritising future research in the field. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71423189. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 8. See the HTA programme website for further project information. Results of this trial are also published at www.plosmedicine.org.