A behavioural change package to prevent hand dermatitis in nurses working in the national health service (the SCIN trial): study protocol for a cluster randomised controlled trial

BACKGROUND: Hand dermatitis can be a serious health problem in healthcare workers. While a range of skin care strategies and policy directives have been developed in recent years to minimise the risk, their effectiveness and cost-effectiveness remain unclear. Evidence now suggests that psychological theory can facilitate behaviour change with respect to improved hand care practices. Therefore, we will test the hypothesis that a behavioural change intervention to improve hand care, based on the Theory of Planned Behaviour and implementation intentions, coupled with provision of hand moisturisers, can produce a clinically useful reduction in the occurrence of hand dermatitis, when compared to standard care, among nurses working in the UK National Health Service (NHS) who are particularly at risk. Secondary aims will be to assess impacts on participants’ beliefs and behaviour regarding hand care. In addition, we will assess the cost-effectiveness of the intervention in comparison with normal care. METHODS/DESIGN: We will conduct a cluster randomised controlled trial at 35 NHS hospital trusts/health boards/universities, focussing on student nurses with a previous history of atopic disease or hand eczema and on nurses in intensive care units. Nurses at ‘intervention-light’ sites will be managed according to what would currently be regarded as best practice, with provision of an advice leaflet about optimal hand care to prevent hand dermatitis and encouragement to contact their occupational health (OH) department early if hand dermatitis occurs. Nurses at ‘intervention-plus’ sites will additionally receive a behavioural change programme (BCP) with on-going active reinforcement of its messages, and enhanced provision of moisturising cream. The impact of the interventions will be compared using information collected by questionnaires and through standardised photographs of the hands and wrists, collected at baseline and after 12 months follow-up. In addition, we will assemble relevant economic data for an analysis of costs and benefits, and collect information from various sources to evaluate processes. Statistical analysis will be by multi-level regression modelling to allow for clustering by site, and will compare the prevalence of outcome measures at follow-up after adjustment for values at baseline. The principal outcome measure will be the prevalence of visible hand dermatitis as assessed by the study dermatologists. In addition, several secondary outcome measures will be assessed. DISCUSSION: This trial will assess the clinical and cost effectiveness of an intervention to prevent hand dermatitis in nurses in the United Kigdom. TRIAL REGISTRATION: ISRCTN53303171: date of registration, 21 June 2013

Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation

Objective To assess the cost effectiveness of screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus (MRSA) in intensive care units

A behaviour change package to prevent hand dermatitis in nurses working in health care: the SCIN cluster RCT

BACKGROUND: Although strategies have been developed to minimise the risk of occupational hand dermatitis in nurses, their clinical effectiveness and cost-effectiveness remain unclear. OBJECTIVES: The Skin Care Intervention in Nurses trial tested the hypothesis that a behaviour change package intervention, coupled with provision of hand moisturisers, could reduce the point prevalence of hand dermatitis when compared with standard care among nurses working in the NHS. The secondary aim was to assess the impact of the intervention on participants' beliefs and behaviour regarding hand care, and the cost-effectiveness of the intervention in comparison with normal care. DESIGN: Cluster randomised controlled trial. SETTING: Thirty-five NHS hospital trusts/health boards/universities. PARTICIPANTS: First-year student nurses with a history of atopic tendency, and full-time intensive care unit nurses. INTERVENTION: Sites were randomly allocated to be 'intervention plus' or 'intervention light'. Participants at 'intervention plus' sites received access to a bespoke online behaviour change package intervention, coupled with personal supplies of moisturising cream (student nurses) and optimal availability of moisturising cream (intensive care unit nurses). Nurses at 'intervention light' sites received usual care, including a dermatitis prevention leaflet. MAIN OUTCOME MEASURE: The difference between intervention plus and intervention light sites in the change of point prevalence of visible hand dermatitis was measured from images taken at baseline and at follow-up. RANDOMISATION: Fourteen sites were randomised to the intervention plus arm, and 21 sites were randomised to the intervention light arm. BLINDING: The participants, trial statistician, methodologist and the dermatologists interpreting the hand photographs were blinded to intervention assignment. NUMBERS ANALYSED: An intention-to-treat analysis was conducted on data from 845 student nurses and 1111 intensive care unit nurses. RESULTS: The intention-to-treat analysis showed no evidence that the risk of developing dermatitis was greater in the intervention light group than in the intervention plus group (student nurses: odds ratio 1.25, 95% confidence interval 0.59 to 2.69; intensive care unit nurses: odds ratio 1.41, 95% confidence interval 0.81 to 2.44). Both groups had high levels of baseline beliefs about the benefits of using hand moisturisers before, during and after work. The frequency of use of hand moisturisers before, during and after shifts was significantly higher in the intensive care unit nurses in the intervention plus arm at follow-up than in the comparator group nurses. For student nurses, the intervention plus group mean costs were £2 lower than those for the comparator and 0.00002 more quality-adjusted life-years were gained. For intensive care unit nurses, costs were £4 higher and 0.0016 fewer quality-adjusted life-years were gained. HARMS: No adverse events were reported. LIMITATIONS: Only 44.5% of participants in the intervention plus arm accessed the behaviour change package. CONCLUSION: The intervention did not result in a statistically significant decrease in the prevalence of hand dermatitis in the intervention plus group. FUTURE WORK: Participants had a high level of baseline beliefs about the importance of using hand moisturisers before, during and after work. Future research should focus on how workplace culture can be changed in order for that knowledge to be actioned. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53303171. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 58. See the NIHR Journals Library website for further project information

Androgen receptor phosphorylation at serine 515 by Cdk1 predicts biochemical relapse in prostate cancer patients

<br>Background:Prostate cancer cell growth is dependent upon androgen receptor (AR) activation, which is regulated by specific kinases. The aim of the current study is to establish if AR phosphorylation by Cdk1 or ERK1/2 is of prognostic significance.</br> <br>Methods: Scansite 2.0 was utilised to predict which AR sites are phosphorylated by Cdk1 and ERK1/2. Immunohistochemistry for these sites was then performed on 90 hormone-naive prostate cancer specimens. The interaction between Cdk1/ERK1/2 and AR phosphorylation was investigated in vitro using LNCaP cells.</br><br>Results:Phosphorylation of AR at serine 515 (pAR(S515)) and PSA at diagnosis were independently associated with decreased time to biochemical relapse. Cdk1 and pCdk1(161), but not ERK1/2, correlated with pAR(S515). High expression of pAR(S515) in patients with a PSA at diagnosis of ≤20 ng ml(-1) was associated with shorter time to biochemical relapse (P=0.019). This translated into a reduction in disease-specific survival (10-year survival, 38.1% vs 100%, P<0.001). In vitro studies demonstrated that treatment with Roscovitine (a Cdk inhibitor) caused a reduction in pCdk1(161) expression, pAR(S515)expression and cellular proliferation.</br> <br>Conclusion: In prostate cancer patients with PSA at diagnosis of ≤20 ng ml(-1), phosphorylation of AR at serine 515 by Cdk1 may be an independent prognostic marker.</br&gt

Predicting DNA methylation level across human tissues

Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles

Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study

BACKGROUND: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. METHODS: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. RESULTS: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. CONCLUSIONS: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018)

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework

Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials.Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials.Results A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies.Conclusion The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity

Disordered microbial communities in asthmatic airways.

A rich microbial environment in infancy protects against asthma [1], [2] and infections precipitate asthma exacerbations [3]. We compared the airway microbiota at three levels in adult patients with asthma, the related condition of COPD, and controls. We also studied bronchial lavage from asthmatic children and controls.We identified 5,054 16S rRNA bacterial sequences from 43 subjects, detecting >70% of species present. The bronchial tree was not sterile, and contained a mean of 2,000 bacterial genomes per cm(2) surface sampled. Pathogenic Proteobacteria, particularly Haemophilus spp., were much more frequent in bronchi of adult asthmatics or patients with COPD than controls. We found similar highly significant increases in Proteobacteria in asthmatic children. Conversely, Bacteroidetes, particularly Prevotella spp., were more frequent in controls than adult or child asthmatics or COPD patients.The results show the bronchial tree to contain a characteristic microbiota, and suggest that this microbiota is disturbed in asthmatic airways

Small-Scale and Global Dynamos and the Area and Flux Distributions of Active Regions, Sunspot Groups, and Sunspots: A Multi-Database Study

In this work we take advantage of eleven different sunspot group, sunspot, and active region databases to characterize the area and flux distributions of photospheric magnetic structures. We find that, when taken separately, different databases are better fitted by different distributions (as has been reported previously in the literature). However, we find that all our databases can be reconciled by the simple application of a proportionality constant, and that, in reality, different databases are sampling different parts of a composite distribution. This composite distribution is made up by linear combination of Weibull and log-normal distributions -- where a pure Weibull (log-normal) characterizes the distribution of structures with fluxes below (above) $10^{21}$Mx ($10^{22}$Mx). We propose that this is evidence of two separate mechanisms giving rise to visible structures on the photosphere: one directly connected to the global component of the dynamo (and the generation of bipolar active regions), and the other with the small-scale component of the dynamo (and the fragmentation of magnetic structures due to their interaction with turbulent convection). Additionally, we demonstrate that the Weibull distribution shows the expected linear behavior of a power-law distribution (when extended into smaller fluxes), making our results compatible with the results of Parnell et al. (2009)

Correction: Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia

[This corrects the article DOI: 10.1371/journal.pbio.3001480.]