Hand hygiene with hand sanitizer versus handwashing: what are the planetary health consequences?

In order to reduce the transmission of pathogens, and COVID-19, WHO and NHS England recommend hand washing (HW) and/or the use of hand sanitizer (HS). The planetary health consequences of these different methods of hand hygiene have not been quantified. A comparative life cycle assessment (LCA) was carried out to compare the environmental impact of the UK population practising increased levels of hand hygiene during the COVID-19 pandemic for 1 year. Washing hands with soap and water was compared to using hand sanitizer (both ethanol and isopropanol based sanitizers were studied). The isopropanol-based HS had the lowest environmental impact in 14 out of the 16 impact categories used in this study. For climate change, hand hygiene using isopropanol HS produced the equivalent of 1060 million kg CO2, compared to 1460 million for ethanol HS, 2300 million for bar soap HW, and 4240 million for liquid soap HW. For both the ethanol and isopropanol HS, the active ingredient was the greatest overall contributing factor to the environmental impact (83.24% and 68.68% respectively). For HW with liquid soap and bar soap, there were additional contributing factors other than the soap itself: for example tap water use (28.12% and 48.68% respectively) and the laundering of a hand towel to dry the hands (10.17% and 17.92% respectively). All forms of hand hygiene have an environmental cost, and this needs to be weighed up against the health benefits of preventing disease transmission. When comparing hand sanitizers to handwashing with soap and water, this study found that using isopropanol based hand sanitizer is better for planetary health. However, no method of hand hygiene was ideal; isopropanol had a greater fossil fuel resource use than ethanol based hand sanitizer. More research is needed to find hand hygiene sources which do not diminish planetary health, and environmental impact is a consideration for public health campaigns around hand hygiene

Evaluation of a community awareness programme to reduce delays in referrals to early intervention services and enhance early detection of psychosis.

BACKGROUND: Reducing treatment delay and coercive pathways to care are accepted aims for Early Intervention Services (EIS) for people experiencing first episode psychosis but how to achieve this is unclear. A one-year community awareness programme was implemented in a London EIS team, targeting staff in non-health service community organisations. The programme comprised psycho-educational workshops and EIS link workers, and offering direct referral routes to EIS. Its feasibility and its impact on duration of untreated psychosis and pathways to EIS were evaluated. METHODS: Evaluation comprised: pre and post questionnaires with workshop participants assessing knowledge and attitudes to psychosis and mental health services; and a comparison of new service users' "service DUP"(time from first psychotic symptom to first contact with EIS) and pathways to care in the intervention year and preceding year. Focus groups sought stakeholders' views regarding the benefits and limitations of the programme and what else might promote help-seeking. RESULTS: 41 workshops at 36 community organisations were attended by 367 staff. 19 follow up workshops were conducted and 16 services were allocated an EIS link worker. Participants' knowledge and attitudes to psychosis and attitudes to mental health services improved significantly following workshops. In the year of the intervention, only 6 of 110 new service users reached EIS directly via community organisations. For all new referrals accepted by EIS, in the intervention year compared to the previous year, there was no difference in mean or median service DUP. A clear impact on pathways to care could not be discerned. Stakeholders suggested that barriers to referral remained. These included: uncertainty about the signs of early psychosis, disengagement by young people when becoming unwell, and worries about stigma or coercive treatment from mental health services. More general, youth focused, mental health services were proposed. CONCLUSIONS: The community awareness programme did not reduce treatment delays for people experiencing first episode psychosis. Further research is needed regarding effective means to reduce duration of untreated psychosis. Although EIS services are guided to promote access through community engagement, this may not be an effective use of their limited resources. TRIAL REGISTRATION: Current Controlled Trial ISRCTN98260910 Registered 19th May 2010

Turning evidence into recommendations: Protocol of a study guideline development groups

<p>Abstract</p> <p>Background</p> <p>Health care practice based on research evidence requires that evidence is synthesised, and that recommendations based on this evidence are implemented. It also requires an intermediate step: translating synthesised evidence into practice recommendations. There is considerable literature on evidence synthesis and implementation, but little on how guideline development groups (GDGs) produce recommendations. This is a complex process, with many influences on communication and decision-making, <it>e.g</it>., the quality of evidence, methods of presentation, practical/resource constraints, individual values, professional and scientific interests, social and psychological processes. To make this process more transparent and potentially effective, we need to understand these influences. Psychological theories of decision-making and social influence provide a framework for this understanding.</p> <p>Objectives</p> <p>This study aims to investigate the processes by which GDGs formulate recommendations, drawing on psychological theories of decision-making and social influence. The findings will potentially inform the further evolution of GDG methods, such as choice of members and procedures for presenting evidence, conducting discussion and formulating recommendations.</p> <p>Methods</p> <p>Longitudinal observation of the meetings of three National Institute of Health and Clinical Excellence (NICE) GDGs, one from each of acute, mental health and public health, will be tape recorded and transcribed. Interviews with a sample of GDG members at the beginning, middle, and end of the GDG's work will be recorded and transcribed. Site documents including relevant e-mail interchanges, GDG meeting minutes, and stakeholders' responses to the drafts of the recommendations will be collected. Data will be selected for analysis if they refer to either evidence or recommendations; the focus is on "hot spots", <it>e.g</it>., dilemmas, conflicts, and uncertainty. Data will be analysed thematically and by content analysis, drawing on psychological theories of decision-making and social influence.</p

Costs and staffing resource requirements for adaptive clinical trials: quantitative and qualitative results from the Costing Adaptive Trials project.

BACKGROUND: Adaptive designs offer great promise in improving the efficiency and patient-benefit of clinical trials. An important barrier to further increased use is a lack of understanding about which additional resources are required to conduct a high-quality adaptive clinical trial, compared to a traditional fixed design. The Costing Adaptive Trials (CAT) project investigated which additional resources may be required to support adaptive trials. METHODS: We conducted a mock costing exercise amongst seven Clinical Trials Units (CTUs) in the UK. Five scenarios were developed, derived from funded clinical trials, where a non-adaptive version and an adaptive version were described. Each scenario represented a different type of adaptive design. CTU staff were asked to provide the costs and staff time they estimated would be needed to support the trial, categorised into specified areas (e.g. statistics, data management, trial management). This was calculated separately for the non-adaptive and adaptive version of the trial, allowing paired comparisons. Interviews with 10 CTU staff who had completed the costing exercise were conducted by qualitative researchers to explore reasons for similarities and differences. RESULTS: Estimated resources associated with conducting an adaptive trial were always (moderately) higher than for the non-adaptive equivalent. The median increase was between 2 and 4% for all scenarios, except for sample size re-estimation which was 26.5% (as the adaptive design could lead to a lengthened study period). The highest increase was for statistical staff, with lower increases for data management and trial management staff. The percentage increase in resources varied across different CTUs. The interviews identified possible explanations for differences, including (1) experience in adaptive trials, (2) the complexity of the non-adaptive and adaptive design, and (3) the extent of non-trial specific core infrastructure funding the CTU had. CONCLUSIONS: This work sheds light on additional resources required to adequately support a high-quality adaptive trial. The percentage increase in costs for supporting an adaptive trial was generally modest and should not be a barrier to adaptive designs being cost-effective to use in practice. Informed by the results of this research, guidance for investigators and funders will be developed on appropriately resourcing adaptive trials

Mentalization for Offending Adult Males (MOAM): study protocol for a randomized controlled trial to evaluate mentalization-based treatment for antisocial personality disorder in male offenders on community probation.

BACKGROUND: Antisocial personality disorder (ASPD), although associated with very significant health and social burden, is an under-researched mental disorder for which clinically effective and cost-effective treatment methods are urgently needed. No intervention has been established for prevention or as the treatment of choice for this disorder. Mentalization-based treatment (MBT) is a psychotherapeutic treatment that has shown some promising preliminary results for reducing personality disorder symptomatology by specifically targeting the ability to recognize and understand the mental states of oneself and others, an ability that is compromised in people with ASPD. This paper describes the protocol of a multi-site RCT designed to test the effectiveness and cost-effectiveness of MBT for reducing aggression and alleviating the wider symptoms of ASPD in male offenders subject to probation supervision who fulfil diagnostic criteria for ASPD. METHODS: Three hundred and two participants recruited from a pool of offenders subject to statutory supervision by the National Probation Service at 13 sites across the UK will be randomized on a 1:1 basis to 12 months of probation plus MBT or standard probation as usual, with follow-up to 24 months post-randomization. The primary outcome is frequency of aggressive antisocial behaviour as assessed by the Overt Aggression Scale - Modified. Secondary outcomes include violence, offending rates, alcohol use, drug use, mental health status, quality of life, and total service use costs. Data will be gathered from police and criminal justice databases, NHS record linkage, and interviews and self-report measures administered to participants. Primary analysis will be on an intent-to-treat basis; per-protocol analysis will be undertaken as secondary analysis. The primary outcome will be analysed using hierarchical mixed-effects linear regression. Secondary outcomes will be analysed using mixed-effects linear regression, mixed-effects logistic regression, and mixed-effects Poisson models for secondary outcomes depending on whether the outcome is continuous, binary, or count data. A cost-effectiveness and cost-utility analysis will be undertaken. DISCUSSION: This definitive, national, multi-site trial is of sufficient size to evaluate MBT to inform policymakers, service commissioners, clinicians, and service users about its potential to treat offenders with ASPD and the likely impact on the population at risk. TRIAL REGISTRATION: ISRCTN 32309003 . Registered on 8 April 2016

Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants

This is the final version of the article. Available from the publisher via the DOI in this record.Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data, excluding early deaths). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. In GWAS, a nicotine receptor locus(CHRNA3, previously associated with increased smoking and lung cancer) was associated with fathers' survival. Less common variants requiring further confirmation were also identified. Offspring of longer lived parents had more protective alleles for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer's disease. In candidate analyses, variants in the TOMM40/APOE locus were associated with longevity, but FOXO variants were not. Associations between extreme longevity (mother >=98 years, fathers >=95 years, n=1,339) and disease alleles were similar, with an additional association with HDL cholesterol (p=5.7x10-3). These results support a multiple protective factors model influencing lifespan and longevity (top 1% survival) in humans, with prominent roles for cardiovascular-related pathways. Several of these genetically influenced risks, including blood pressure and tobacco exposure, are potentially modifiable.This work was generously funded by an award to DM, TF, AM, LH and CB by the Medical Research Council MR/M023095/1. This research has been conducted using the UK Biobank Resource, under application 1417. The authors wish to thank the UK Biobank participants and coordinators for this unique dataset. S.E.J. is funded by the Medical Research Council (grant: MR/M005070/1). J.T. is funded by a Diabetes Research and Wellness Foundation Fellowship. R.B. is funded by the Wellcome Trust and Royal Society grant: 104150/Z/14/Z. M.A.T., M.N.W. and A.M. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF). R.M.F. is a Sir Henry Dale Fellow (Wellcome Trust and Royal Society grant: 104150/Z/14/Z). A.R.W. H.Y., and T.M.F. are supported by the European Research Council grant: 323195:GLUCOSEGENES-FP7-IDEAS-ERC. The funders had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Framingham Heart Study is supported by Contract No. N01-HC-25195 and HHSN268201500001I and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). The phenotypegenotype association analyses were supported by National Institute of Aging R01AG29451. This work has made use of the resources provided by the University of Exeter Science Strategy and resulting Systems Biology initiative. Primarily these include high-performance computing facilities managed by Konrad Paszkiewicz of the College of Environmental and Life Sciences and Pete Leggett of the University of Exeter Academics services unit

Kailo: a systemic approach to addressing the social determinants of young people’s mental health and wellbeing at the local level [version 1; peer review: awaiting peer review]

The mental health and wellbeing of children and young people is deteriorating. It is increasingly recognised that mental health is a systemic issue, with a wide range of contributing and interacting factors. However, the vast majority of attention and resources are focused on the identification and treatment of mental health disorders, with relatively scant attention on the social determinants of mental health and wellbeing and investment in preventative approaches. Furthermore, there is little attention on how the social determinants manifest or may be influenced at the local level, impeding the design of contextually nuanced preventative approaches. This paper describes a major research and design initiative called Kailo that aims to support the design and implementation of local and contextually nuanced preventative strategies to improve children's and young people’s mental health and wellbeing. The Kailo Framework involves structured engagement with a wide range of local partners and stakeholders - including young people, community partners, practitioners and local system leaders - to better understand local systemic influences and support programmes of youth-centred and evidence-informed co-design, prototyping and testing. It is hypothesised that integrating different sources of knowledge, experience, insight and evidence will result in better embedded, more sustainable and more impactful strategies that address the social determinants of young people’s mental health and wellbeing at the local level

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo