The transcription factor GATA6 is essential for early extraembryonic development

The gene coding for the murine transcription factor GATA6 was inactivated by insertion of a beta-galactosidase marker gene. The analysis of heterozygote GATA6/lacZ mice shows two inductions of GATA6 expression early in development. It is first expressed at the blastocyst stage in part of the inner mass and in the trophectoderm. The second wave of expression is in parietal endoderm (Reichert's membrane) and the mesoderm and endoderm that form the heart and gut. Inactivation leads to a lethality shortly after implantation (5.5 days postcoitum). Chimeric experiments show this to be caused by an indirect effect on the epiblast due to a defect in an extraembryonic tissue

Does resuscitation status affect decision making in a deteriorating patient? Results from a randomised vignette study

Aims and objectives: The aim of this paper is to determine the influence of do not attempt cardiopulmonary resuscitation (DNACPR) orders and the Universal Form of Treatment Options (‘UFTO’: an alternative approach that contextualizes the resuscitation decision within an overall treatment plan) on nurses' decision making about a deteriorating patient. Methods: An online survey with a developing case scenario across three timeframes was used on 231 nurses from 10 National Health Service Trusts. Nurses were randomised into three groups: DNACPR, the UFTO and no-form. Statements were pooled into four subcategories: Increasing Monitoring, Escalating Concern, Initiating Treatments and Comfort Measures. Results: Reported decisions were different across the three groups. Nurses in the DNACPR group agreed or strongly agreed to initiate fewer intense nursing interventions than the UFTO and no-form groups (P < 0.001) overall and across subcategories of Increase Monitoring, Escalate Concern and Initiate Treatments (all P < 0.001). There was no difference between the UFTO and no-form groups overall (P = 0.795) or in the subcategories. No difference in Comfort Measures were observed (P = 0.201) between the three groups. Conclusion: The presence of a DNACPR order appears to influence nurse decision making in a deteriorating patient vignette. Differences were not observed in the UFTO and no-form group. The UFTO may improve the way nurses modulate their behaviours towards critically ill patients with DNACPR status. More hospitals should consider adopting an approach where the resuscitation decisions are contextualised within overall goals of care

Likelihood of ‘falling through the net’ relates to contemporary prevalence of gestational diabetes. Reply to Ikomi A, Mannan S, Anthony R, Kiss S

This project was not supported by any specific funding. Claire Meek receives salary funding from the European Union Seventh Framework Programme (FP7/2007-2013; grant agreement n° 266408) and from the Wellcome Trust Translational Medicine and Therapeutics Programme which is funded by the Wellcome Trust in association with Glaxo SmithKline.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00125-015-3737-

Likelihood of 'falling through the net' relates to contemporary prevalence of gestational diabetes. Reply to Ikomi A, Mannan S, Anthony R, Kiss S [letter].

This project was not supported by any specific funding. Claire Meek receives salary funding from the European Union Seventh Framework Programme (FP7/2007-2013; grant agreement n° 266408) and from the Wellcome Trust Translational Medicine and Therapeutics Programme which is funded by the Wellcome Trust in association with Glaxo SmithKline.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00125-015-3737-

Patient level pooled analysis of 68,500 patients from seven major vitamin D fracture trials in the US and Europe

Objectives To identify participants’ characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium. Design Individual patient data analysis using pooled data from randomised trials. Data sources Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men). Study selection Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants. Data synthesis Logistic regression analysis was used to identify significant interaction terms, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use. Results Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 μg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 μg or 20 μg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy. Conclusion This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. AA acknowledges personal funding from the UK Medical Research Council and Chief Scientist Office of the Scottish Government Health Directorates

Lifting the lid: a clinical audit on commode cleaning

Many healthcare-associated infections (HCAIs) are preventable by infection control procedures designed to interrupt the transmission of organisms from a source. Commodes are in use constantly throughout healthcare facilities. Therefore commode surfaces are constantly handled, and any pathogens present have the potential to be transferred to not only other surfaces but also, more importantly, to patients, thus compromising patient safety. In order to examine the effectiveness and thoroughness of cleaning commodes an audit was undertaken to assess compliance with evidence-based practice. This audit demonstrates a cycle which includes defining best practice, implementing best practice, monitoring best practice and taking action to improve practice. The audit results confirmed an issue that the authors had long suspected. That is, that commodes allocated to individual patients are not always cleaned after every use. Using adenosine triphosphate (ATP) bioluminescence as an indicator of organic soiling also demonstrated that commodes that were considered clean were not always cleaned to a high standard. Implementing the audit recommendations improves staff knowledge through education, standardises cleaning procedures and ultimately improves patient safety

Setting a research agenda to inform intensive comprehensive aphasia programs

Research into intensive comprehensive aphasia programs (ICAPs) has yet to show that this service delivery model is efficacious, effective, has cost utility, or can be broadly implemented. This article describes a phased research approach to the study of ICAPs and sets out a research agenda that considers not only the specific issues surrounding ICAPs, but also the phase of the research. Current ICAP research is in the early phases, with dosing and outcome measurement as prime considerations as well as refinement of the best treatment protocol. Later phases of ICAP research are outlined, and the need for larger scale collaborative funded research is recognized. The need for more rapid translation into practice is also acknowledged, and the use of hybrid models of phased research is encouraged within the ICAP research agenda

Using a realist approach to evaluate smoking cessation interventions targeting pregnant women and young people

Background This paper describes a study protocol designed to evaluate a programme of smoking cessation interventions targeting pregnant women and young people living in urban and rural locations in Northeast Scotland. The study design was developed on so-called 'realist' evaluation principles, which are concerned with the implementation of interventions as well as their outcomes. Methods/design A two-phased study was designed based on the Theory of Change (TOC) using mixed methods to assess both process and outcome factors. The study was designed with input from the relevant stakeholders. The mixed-methods approach consists of semi-structured interviews with planners, service providers, service users and non-users. These qualitative interviews will be analysed using a thematic framework approach. The quantitative element of the study will include the analysis of routinely collected data and specific project monitoring data, such as data on service engagement, service use, quit rates and changes in smoking status. Discussion The process of involving key stakeholders was conducted using logic modelling and TOC tools. Engaging stakeholders, including those responsible for funding, developing and delivering, and those intended to benefit from interventions aimed at them, in their evaluation design, are considered by many to increase the validity and rigour of the subsequent evidence generated. This study is intended to determine not only the components and processes, but also the possible effectiveness of this set of health interventions, and contribute to the evidence base about smoking cessation interventions aimed at priority groups in Scotland. It is also anticipated that this study will contribute to the ongoing debate about the role and challenges of 'realist' evaluation approaches in general, and the utility of logic modelling and TOC approaches in particular, for evaluation of complex health interventions

Systems mapping workshops and their role in understanding medication errors in healthcare

In this paper for Applied Ergonomics, one of the two leading journals for ergonomics/human factors, Buckle et al. discuss the role of mapping workshops in understanding medication errors in healthcare. They draw upon research that used mapping workshops as a method that systems designers, including human factors/ergonomics specialists, can use to help generate a knowledge base for better design requirements. Buckle et al. applied systems mapping workshops for the first time to the problem of medication errors in healthcare. The workshops were designed using experiential group work principles. They involved a range of stakeholders from within the health service as well as those who supply the health sector, including designers who may be able to enhance the safety of products and systems used in healthcare. The opportunity for using these methods to study patient safety issues arose as a result of a scoping study undertaken on behalf of the UK Department of Health and The Design Council. As the scope of patient safety issues within the healthcare system and the range of stakeholder groups is large (National Patient Safety Agency 2005), it was believed that mapping workshops might enhance system design in health. The results were rich from a design perspective, giving specific details of actual incidences, contexts and practices, with further depth of information emerging in the group working sessions. A wealth of detail on aspects of medication error, especially in the community, emerged from creative, primary, secondary and patient-support group sessions. As a process, similar stakeholder workshops could help designers understand better the complexity and range of factors to be taken into account. The methods are now being used in many areas of healthcare and social care design, for example by the Technology Strategy Board funded research into Telecare (see http://www.aktive.org.uk/)

Allergic sensitization: screening methods

Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute