Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.

BACKGROUND: Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children. METHODS: We did a multicentre, pragmatic, parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via antenatal or postnatal services for recruitment of term infants (at least 37 weeks' gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment. FINDINGS: 1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 [95% CI 0·78 to 1·16], p=0·61; adjusted risk difference -1·2% [-5·9 to 3·6]). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09). INTERPRETATION: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn. FUNDING: National Institute for Health Research Health Technology Assessment

Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.

BACKGROUND: Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children. METHODS: We did a multicentre, pragmatic, parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via antenatal or postnatal services for recruitment of term infants (at least 37 weeks' gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment. FINDINGS: 1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 [95% CI 0·78 to 1·16], p=0·61; adjusted risk difference -1·2% [-5·9 to 3·6]). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09). INTERPRETATION: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn. FUNDING: National Institute for Health Research Health Technology Assessment

An Investigation into the Biological Effects of Indirect Potable Reuse Water Using Zebrafish Embryos

© 2021 The Authors. Advanced treatment technologies are being assessed as a proactive measure to assist with the transformation of treated wastewater into a source of water for potable water production. We investigated the biological effects along an advanced water treatment pilot plant, using zebrafish embryos throughout early development. The study compared phenotypic observations with global transcriptome responses, enabling us to keep an open mind about the chemicals that might influence the biological activity. There was no evidence of acute toxicity at any treatment stage, but skeletal, cardiovascular and pigmentation changes occurred in a small proportion of embryos along the treatment process, and in a tap water; not detected in the aquarium water control. Reverse osmosis (RO) reduced the concentration of measured chemical contaminants in the water the most, while eliminating the occurrence of abnormalities detected in fish embryos. Conversely, advanced oxidation reversed the benefits of RO treatment by increasing the frequency of teratogenic and sub-lethal abnormalities seen. Using the molecular responses of zebrafish embryos to different IPR water, we report the bioactivity within the water at different stages of advanced treatment and associate these to perturbed biological functions. Transcriptomic analysis revealed alterations to the retinoid system, which was consistent with the observed teratogenic effects. Changes to tryptophan metabolism (associated with the production of melatonin required for the control of normal circadian rhythms) and somatolactin-beta (associated with normal pigmentation in fish) were also found. We show that underexplored forms of biological activity occur in treated wastewater effluent, and/or may be created depending on the type of advanced treatment process used. By integrating the available analytical chemistry we highlight chemical groups associated to this response. Our study shows that more detailed and in-depth characterisation of chemicals and biological pathways associated with advanced treatment water systems are needed to mitigate possible risks to downstream organisms.Thames Water Utilities Ltd

Does landscape-scale conservation management enhance the provision of ecosystem services?

Biodiversity conservation approaches are increasingly being implemented at the landscape-scale to support the maintenance of metapopulations and metacommunities. However, the impact of such interventions on the provision of ecosystem services is less well defined. Here we examine the potential impacts of landscape-scale conservation initiatives on ecosystem services, through analysis of five case study areas in England and Wales. The provision of multiple ecosystem services was projected according to current management plans and compared with a baseline scenario. Multicriteria analysis indicated that in most cases landscape-scale approaches lead to an overall increase in service provision. Consistent increases were projected in carbon storage, recreation and aesthetic value, as well as biodiversity value. However, most study areas provided evidence of trade-offs, particularly between provisioning services and other types of service. Results differed markedly between study areas, highlighting the importance of local context. These results suggest that landscape-scale conservation approaches are likely to be effective in increasing ecosystem service provision, but also indicate that associated costs can be significant, particularly in lowland areas

What Training, Support, and Resourcing Do Health Professionals Need to Support People Using a Closed-Loop System? A Qualitative Interview Study with Health Professionals Involved in the Closed Loop from Onset in Type 1 Diabetes (CLOuD) Trial.

Background: We explored health professionals' views about the training, support, and resourcing needed to support people using closed-loop technology in routine clinical care to help inform the development of formal guidance. Methods: Interviews were conducted with health professionals (n = 22) delivering the Closed Loop from Onset in Type 1 Diabetes (CLOuD) trial after they had ≥6 months' experience of supporting participants using a closed-loop system. Data were analyzed descriptively. Results: Interviewees described how, compared with other insulin regimens, teaching and supporting individuals to use a closed-loop system could be initially more time-consuming. However, they also noted that after an initial adjustment period, users had less need for initiating contact with the clinical team compared with people using pumps or multiple daily injections. Interviewees highlighted how a lessened need for ad hoc clinical input could result in new challenges; specifically, they had fewer opportunities to reinforce users' diabetes knowledge and skills and detect potential psychosocial problems. They also observed heightened anxiety among some parents due to the constant availability of data and unrealistic expectations about the system's capabilities. Interviewees noted that all local diabetes teams should be empowered to deliver closed-loop system care, but stressed that health professionals supporting closed-loop users in routine care will need comprehensive technology training and standardized clinical guidance. Conclusion: These findings constitute an important starting point for the development of formal guidance to support the rollout of closed-loop technology. Our recommendations, if actioned, will help limit the potential additional burden of introducing closed-loop systems in routine clinical care and help inform appropriate user education and support.NIHR Wellcome Trust Strategic Award (100574/Z/12/Z

Staging quality is related to the survival of women with endometrial cancer: a Scottish population based study.Deficient surgical staging and omission of adjuvant radiotherapy is associated with poorer survival of women diagnosed with endometrial cancer in Scotland during 1996 and 1997

The association between treatment variation and survival of women with endometrial cancer was investigated. A retrospective cohort based upon the complete Scottish population registered on in-patient and day-case hospital discharge data (Scottish Morbidity Record-1) and cancer registration (Scottish Morbidity Record-6) coded C54 and C55 in ICD10, between 1st January 1996 to 31st December 1997 were analysed. Seven hundred and three patients who underwent surgical treatment out of 781 patients that were diagnosed with endometrial cancer in Scotland during 1996 and 1997. The overall quality of surgical staging was poor. The quality of staging was related to both the year that the surgeon passed the Member of the Royal College of Obstetricians and Gynaecologists examination and also to ‘specialist’ status but was not related to surgeon caseload. Two clinically important prognostic factors were found to be associated with survival; whether the International Federation of Obstetrics and Gynaecology stage was documented, RHR=2.0 (95% CI=1.3 to 3.1) and also to the use of adjuvant radiotherapy, RHR=2.2 (95% CI=1.5 to 3.5). The associations with survival were strongest in patients with advanced disease, International Federation of Obstetrics and Gynaecology stages 1C through to stage 3. Deficiencies in staging and variations in the use of adjuvant radiotherapy represent a possible source of avoidable mortality in patients with endometrial cancer. Consequently, there should be a greater emphasis on improving the overall quality of surgical staging in endometrial cancer

Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design

Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability

Duty, desire or indifference? A qualitative study of patient decisions about recruitment to an epilepsy treatment trial

BACKGROUND: Epilepsy is a common neurological condition, in which drugs are the mainstay of treatment and drugs trials are commonplace. Understanding why patients might or might not opt to participate in epilepsy drug trials is therefore of some importance, particularly at a time of rapid drug development and testing; and the findings may also have wider applicability. This study examined the role of patient perceptions in the decision-making process about recruitment to an RCT (the SANAD Trial) that compared different antiepileptic drug treatments for the management of new-onset seizures and epilepsy. METHODS: In-depth interviews with 23 patients recruited from four study centres. All interviews were tape-recorded and transcribed; the transcripts were analysed thematically using a qualitative data analysis package. RESULTS: Of the nineteen informants who agreed to participate in SANAD, none agreed for purely altruistic reasons. The four informants who declined all did so for very specific reasons of self-interest. Informants' perceptions of the nature of the trial, of the drugs subject to trial, and of their own involvement were all highly influential in their decision-making. Informants either perceived the trial as potentially beneficial or unlikely to be harmful, and so agreed to participate; or as potentially harmful or unlikely to be beneficial and so declined to participate. CONCLUSION: Most patients applied 'weak altruism', while maintaining self-interest. An emphasis on the safety and equivalence of treatments allowed some patients to be indifferent to the question of involvement. There was evidence that some participants were subject to 'therapeutic misconceptions'. The findings highlight the individual nature of trials but nonetheless raise some generic issues in relation to their design and conduct

Clinical trial management: a profession in crisis?

Clinical Trial Managers play a vital role in the design and conduct of clinical trials in the UK. There is a current recruitment and retention crisis for this specialist role due to a complex set of factors, most likely to have come to a head due to the Covid-19 pandemic. Academic clinical trials units and departments are struggling to recruit trial managers to vacant positions, and multiple influences are affecting the retention of this highly skilled workforce. Without tackling this issue, we face major challenges in delivery on the Department of Health and Social Care’s Future of UK Clinical Research Delivery implementation plan. This article, led by a leading network of and for UK Trial Managers, presents some of the issues and ways in which national stakeholders may be able to address this

A guide to using the Theoretical Domains Framework of behaviour change to investigate implementation problems

Background: Implementing new practices requires changes in the behaviour of relevant actors, and this is facilitated by understanding of the determinants of current and desired behaviours. The Theoretical Domains Framework (TDF) was developed by a collaboration of behavioural scientists and implementation researchers who identified theories relevant to implementation and grouped constructs from these theories into domains. The collaboration aimed to provide a comprehensive, theory-informed approach to identify determinants of behaviour. The first version was published in 2005, and a subsequent version following a validation exercise was published in 2012. This guide offers practical guidance for those who wish to apply the TDF to assess implementation problems and support intervention design. It presents a brief rationale for using a theoretical approach to investigate and address implementation problems, summarises the TDF and its development, and describes how to apply the TDF to achieve implementation objectives. Examples from the implementation research literature are presented to illustrate relevant methods and practical considerations. Methods: Researchers from Canada, the UK and Australia attended a 3-day meeting in December 2012 to build an international collaboration among researchers and decision-makers interested in the advancing use of the TDF. The participants were experienced in using the TDF to assess implementation problems, design interventions, and/or understand change processes. This guide is an output of the meeting and also draws on the a uthors' collective experience. Examples from the implementation research literature judged by authors to be representative of specific applications of the TDF are included in this guide. Results: We explain and illustrate methods, with a focus on qualitative approaches, for selecting and specifying target behaviours key to implementation, selecting the study design, deciding the sampling strategy, developing study materials, collecting and analysing data, and reporting findings of TDF-based studies. Areas for development include methods for triangulating data, e.g. from interviews, questionnaires and observation and methods for designing interventions based on TDF-based problem analysis. Conclusions: We offer this guide to the implementation community to assist in the application of the TDF to achieve implementation objectives. Benefits of using the TDF include the provision of a theoretical basis for implementation studies, good coverage of potential reasons for slow diffusion of evidence into practice and a method for progressing from theory-based investigation to intervention