Hybrid in vitro diffusion cell for simultaneous evaluation of hair and skin decontamination: temporal distribution of chemical contaminants

Most casualty or personnel decontamination studies have focused on removing contaminants from the skin. However, scalp hair and underlying skin are the most likely areas of contamination following airborne exposure to chemicals. The aim of this study was to investigate the interactions of contaminants with scalp hair and underlying skin using a hybrid in vitro diffusion cell model. The in vitro hybrid test system comprised “curtains” of human hair mounted onto sections of excised porcine skin within a modified diffusion cell. The results demonstrated that hair substantially reduced underlying scalp skin contamination and that hair may provide a limited decontamination effect by removing contaminants from the skin surface. This hybrid test system may have application in the development of improved chemical incident response processes through the evaluation of various hair and skin decontamination strategies.Peer reviewedFinal Published versio

The multiple sclerosis risk sharing scheme monitoring study - early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis ( MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist led telephone support for psychological distress in patients undergoing haemodialysis

Introduction: Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Methods: Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. Ethics and dissemination: A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor<br/

SPHR Diabetes Prevention Model: Detailed Description of Model Background, Methods, Assumptions and Parameters

Type-2 diabetes is a complex disease with multiple risk factors and health consequences whose prevention is a major public health priority. We have developed a microsimulation model written in the R programming language that can evaluate the effectiveness and cost-effectiveness of a comprehensive range of different diabetes prevention interventions, either in the general population or in subgroups at high risk of diabetes. Within the model individual patients with different risk factors for diabetes follow metabolic trajectories (for body mass index, cholesterol, systolic blood pressure and glycaemia), develop diabetes, complications of diabetes and related disorders including cardiovascular disease and cancer, and eventually die. Lifetime costs and quality-adjusted life-years are collected for each patient. The model allows assessment of the wider social impact on employment and the equity impact of different interventions. Interventions may be population-based, community-based or individually targeted, and administered singly or layered together. The model is fully enabled for probabilistic sensitivity analysis (PSA) to provide an estimate of decision uncertainty. This discussion paper provides a detailed description of the model background, methods and assumptions, together with details of all parameters used in the model, their sources and distributions for PSA

Impact of Type 2 diabetes prevention programmes based on risk identification and lifestyle intervention intensity strategies: a cost-effectiveness analysis

Aim To develop a cost-effectiveness model to compare Type 2 diabetes prevention programmes that target different at-risk population subgroups through lifestyle interventions of varying intensity. Methods An individual patient simulation model simulated the development of diabetes in a representative sample of adults without diabetes from the UK population. The model incorporates trajectories for HbA1c, 2-h glucose, fasting plasma glucose, BMI, systolic blood pressure, total cholesterol and HDL cholesterol. In the model, patients can be diagnosed with diabetes, cardiovascular disease, microvascular complications of diabetes, cancer, osteoarthritis and depression, or can die. The model collects costs and utilities over a lifetime horizon. The perspective is the UK National Health Service and Personal Social Services. We used the model to evaluate the population-wide impact of targeting a lifestyle intervention of varying intensity to six population subgroups defined as at high risk for diabetes. Results The intervention produces 0.0020 to 0.0026 incremental quality-adjusted life-years and saves £15 to £23 per person in the general population, depending on the subgroup targeted. Cost-effectiveness increases with intervention intensity. The most cost-effective options were to target South-Asian people and those with HbA1c levels > 42 mmol/mol (6%). Conclusion The model indicates that diabetes prevention interventions are likely to be cost-saving. The criteria for selecting at-risk individuals differentially has an impact on diabetes and cardiovascular disease outcomes, and on the timing of costs and benefits. The model is not currently able to account for potential differential uptake or efficacy between subgroups. These findings have implications for deciding who should be targeted for diabetes prevention interventions.NIH

Human volunteer study of the decontamination of chemically contaminated hair and the consequences for systemic exposure

The decontamination of exposed persons is a priority following the release of toxic chemicals. Efficacious decontamination reduces the risk of harm to those directly affected and prevents the uncontrolled spread of contamination. Human studies examining the effectiveness of emergency decontamination procedures have primarily focused on decontaminating skin, with few examining the decontamination of hair and scalp. We report the outcome of two studies designed to evaluate the efficacy of current United Kingdom (UK) improvised, interim and specialist mass casualty decontamination protocols when conducted in sequence. Decontamination efficacy was evaluated using two chemical simulants, methyl salicylate (MeS) and benzyl salicylate (BeS) applied to and recovered from the hair of volunteers. Twenty-four-hour urinary MeS and BeS were measured as a surrogate for systemic bioavailability. Current UK decontamination methods performed in sequence were partially effective at removing MeS and BeS from hair and underlying scalp. BeS and MeS levels in urine indicated that decontamination had no significant effect on systemic exposure raising important considerations with respect to the speed of decontamination. The decontamination of hair may therefore be challenging for first responders, requiring careful management of exposed persons following decontamination. Further work to extend these studies is required with a broader range of chemical simulants, a larger group of volunteers and at different intervention times

Topically Applied therapies for the treatment of skin disease : Past Present and Future

The purpose of this review is to summarize essential biological, pharmaceutical and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin, routes of drug absorption and their limitations is then provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory, microbial infections, skin cancers and genetic skin diseases. The complexity of topical product development through to large scale manufacture along with recommended risk mitigation approaches is then highlighted. As such topical treatments are applied externally patient preferences along with the challenges they invoke are then described and finally the future of this field of drug delivery is discussed with the emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. Significance Statement This review of the key aspects the skin, its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient populations preferences and limitations and the future with regards to new skin diseases and topical medicine approaches.info:eu-repo/semantics/publishedVersio

AAV9-mediated SMN gene therapy rescues cardiac desmin but not lamin A/C and elastin dysregulation in Smn2B/- spinal muscular atrophy mice

This work was supported by Great Ormond Street Hospital Charity (GOSH) and SPARKS Children’s Medical Research Charity (Grant No. V5018 to H.R.F.). M.B. acknowledges general financial support from SMA Angels Charity, SMA UK, Muscular Dystrophy UK, Action Medical Research, Academy of Medical Sciences and Association Française contre les Myopathies for SMA research in her laboratory. H.K.S. and T.H.G. acknowledge support from the Euan MacDonald Centre for Motor Neuron Disease Research and SMA Europe. E.M.C. was partially funded by a scholarship from Royal Holloway University of London. R.J.Y.-M. acknowledges general financial support from SMA UK (formerly The SMA Trust), through the UK SMA Research Consortium, for SMA research in his laboratory.Structural, functional and molecular cardiac defects have been reported in spinal muscular atrophy (SMA) patients and mouse models. Previous quantitative proteomics analyses demonstrated widespread molecular defects in the severe Taiwanese SMA mouse model. Whether such changes are conserved across different mouse models, including less severe forms of the disease, has yet to be established. Here, using the same high-resolution proteomics approach in the less-severe Smn2B/− SMA mouse model, 277 proteins were found to be differentially abundant at a symptomatic timepoint (post-natal day (P) 18), 50 of which were similarly dysregulated in severe Taiwanese SMA mice. Bioinformatics analysis linked many of the differentially abundant proteins to cardiovascular development and function, with intermediate filaments highlighted as an enriched cellular compartment in both datasets. Lamin A/C was increased in the cardiac tissue, whereas another intermediate filament protein, desmin, was reduced. The extracellular matrix (ECM) protein, elastin, was also robustly decreased in the heart of Smn2B/− mice. AAV9-SMN1-mediated gene therapy rectified low levels of survival motor neuron protein and restored desmin levels in heart tissues of Smn2B/− mice. In contrast, AAV9-SMN1 therapy failed to correct lamin A/C or elastin levels. Intermediate filament proteins and the ECM have key roles in cardiac function and their dysregulation may explain cardiac impairment in SMA, especially since mutations in genes encoding these proteins cause other diseases with cardiac aberration. Cardiac pathology may need to be considered in the long-term care of SMA patients, as it is unclear whether currently available treatments can fully rescue peripheral pathology in SMA.Publisher PDFPeer reviewe

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

Background: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation

The effectiveness of interventions aimed at improving access to health and mental health services for looked after children and young people: a systematic review

Background: Compared with children and young people in the general population, looked after children and young people (LACYP) are more likely to experience behavioural, physical and psychological problems. Consequently, LACYP are likely to have greater need of health and mental health services to address any specific problems. This systematic review aimed to identify and synthesise evidence on the effectiveness of interventions to improve access to services accessed by LACYP. Methods: Searches of health, social science and social care databases were conducted and records were screened for relevance. Results: Five studies were included (four prospective cohort studies and one non-comparative study). There was considerable variation in terms of the services, interventions and outcomes reported. Conclusions: Little appropriate evidence was identified by this review, suggesting that the evidence base is at a very early stage