A Bivariate Latent Class Correlated Generalized Ordered Probit Model with an Application to Modeling Observed Obesity Levels

Obesity is a major risk factor for several diseases including diabetes, heart disease and stroke. Increasing rates of obesity internationally are set to cost health systems increasing resources. In the US a conservative estimate puts resources already spent on obesity at $120 billion annually. Given scarce health care resources it is important that categorisation of the overweight and obese is accurate, such that health promotion and public health targeting can be as e§ective as possible. To test the accuracy of current categorisation within the overweight and obese we extend the discrete data latent class literature by explicitly deÖning a latent variable for class membership as a function of both observables and unobservables, thereby allowing the equations deÖning class membership and observed outcomes to be correlated. The procedure is then applied to modeling observed obesity outcomes, based upon an underlying ordered probit equation. We Önd the standard boundaries for converting

A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults

BACKGROUND: Obsessive-compulsive disorder (OCD) is a relatively common and disabling condition. OBJECTIVES: To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults. DATA SOURCES: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014. REVIEW METHODS: We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale-Brown Obsessive-Compulsive Scale or its children's version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net ). RESULTS: We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive-behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias. LIMITATIONS: The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents. CONCLUSIONS: In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions. STUDY REGISTRATION: The study is registered as PROSPERO CRD42012002441. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme

A Bivariate Latent Class Correlated Generalized Ordered Probit Model with an Application to Modeling Observed Obesity Levels

Obesity is a major risk factor for several diseases including diabetes, heart disease and stroke. Increasing rates of obesity internationally are set to cost health systems increasing resources. In the US a conservative estimate puts resources already spent on obesity at $120 billion annually. Given scarce health care resources it is important that categorisation of the overweight and obese is accurate, such that health promotion and public health targeting can be as e§ective as possible. To test the accuracy of current categorisation within the overweight and obese we extend the discrete data latent class literature by explicitly deÖning a latent variable for class membership as a function of both observables and unobservables, thereby allowing the equations deÖning class membership and observed outcomes to be correlated. The procedure is then applied to modeling observed obesity outcomes, based upon an underlying ordered probit equation. We Önd the standard boundaries for converting

Development of an integrated rehabilitation pathway for individuals recovering from COVID-19 in the community

Objective: COVID-19 is a multisystem illness with considerable long-term physical, psychological, cognitive, social and vocational sequelae in survivors. The aim of this study is to describe the development of an integrated rehabilitation pathway using tele-medicine approach to manage these sequelae in a systematic and efficient way. Methods: A multidisciplinary team of professionals used a consensus method to define pathway referral criteria based on the COVID-19 Yorkshire Rehabilitation Screen (C19-YRS) telephone screening tool developed previously by the team. Specialists needed for the pathway to operate were also decided. Results: A rehabilitation pathway, which spans the acute hospital trust, community trust and primary care service within the UK National Health Service (NHS) service model was developed. C19-YRS referral criteria thresholds for informing the decision making process were defined. A dedicated multidisciplinary COVID-19 rehabilitation team is responsible for dealing with the management of complex cases with needs spanning across multiple domains of the health condition. Conclusion: An integrated COVID-19 rehabilitation pathway based on our previously published C19-YRS tool is proposed. Future research is needed for validation of the pathway. We recommend health services dealing with the pandemic to adopt such a pathway to manage the care of the COVID-19 survivors in the community

Pedagogies for the 'dis‐engaged': diverse experiences of the young people’s Arts Award programme

Art education is often praised for its engaging programmes and inclusive pedagogies, with many initiatives created with the intention of widening access for those who are deemed to be lacking. This article investigates one such programme – the young people’s Arts Award, which is a nationally recognised qualification for young people aged 11–25. I call upon a range of pedagogies in order to critique the Arts Award within the context of informal and alternative education settings in the United Kingdom. Drawing on a 12‐month ethnographic study, the research was conducted across five diverse programmes which included youth work projects and alternative provision. I present two cases – ‘learning to be an artist’ and ‘learning to behave’ – which demonstrate a hierarchy of pedagogy in the application of this programme across these particular contexts. Artists’ Signature Pedagogies are used as an analytical framework to explore the affordances of working with artists through the programme. Further, I engage with the Pedagogy of Poverty to demonstrate that young people who were classified as ‘dis‐engaged’ were more likely to receive lower quality programmes, low‐level work and over‐regulated teaching. I argue that despite changes to the ways that young people access art education, there continues to be unequal opportunities. This finding is significant for not only creative practitioners and youth arts workers, but also arts education policy makers and programmers

The ZEPLIN-III dark matter detector: instrument design, manufacture and commissioning

We present details of the technical design and manufacture of the ZEPLIN-III dark matter experiment. ZEPLIN-III is a two-phase xenon detector which measures both the scintillation light and the ionisation charge generated in the liquid by interacting particles and radiation. The instrument design is driven by both the physics requirements and by the technology requirements surrounding the use of liquid xenon. These include considerations of key performance parameters, such as the efficiency of scintillation light collection, restrictions placed on the use of materials to control the inherent radioactivity levels, attainment of high vacuum levels and chemical contamination control. The successful solution has involved a number of novel design and manufacturing features which will be of specific use to future generations of direct dark matter search experiments as they struggle with similar and progressively more demanding requirements.Comment: 25 pages, 19 figures. Submitted to Astropart. Phys. Some figures down sampled to reduce siz

Molecular basis of FIR-mediated c-myc transcriptional control

The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.MRC Grant-in-aid U11757455

Plugging a hole and lightening the burden: A process evaluation of a practice education team

Aim: To investigate the perceptions of clinical and senior managers about the role of Practice Educators employed in one acute hospital in the UK. Background: Producing nurses who are fit for practice, purpose and academic award is a key issue for nurse education partnership providers in the UK. Various new models for practice learning support structures and new roles within health care institutions have been established. To sustain funding and policy support for these models, there is a need for evaluation research. Design: A process evaluation methodology was employed to determine the current value of a practice education team and to provide information to guide future direction. Methods: Data were collected through semi-structured telephone interviews using a previously designed schedule. All senior nurse managers (N=5) and a purposive sample of clinical managers (n=13) who had personal experience of and perceptions about the role of practice educators provided the data. Interview notes were transcribed, coded and a thematic framework devised to present the results. Results: A number of key themes emerged including: qualities needed for being a successful practice educator; visibility and presence of practice educators; providing a link with the university; ‘plugging a hole’ in supporting learning needs; providing relief to practitioners in dealing with ‘the burden of students’; alleviating the ‘plight of students’; and effects on student attrition. Conclusions: Findings provided evidence for the continued funding of the practice educator role with improvements to be made in dealing with stakeholder expectations and outcomes. Relevance to clinical practice: In the UK, there still remain concerns about the fitness for practice of newly registered nurses, prompting a recent national consultation by the professional regulating body. Despite fiscal pressures, recommendations for further strengthening of all systems that will support the quality of practice learning may continue to sustain practice learning support roles

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation:systematic review, network meta-analysis and cost-effectiveness analysis

BACKGROUND: Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements.OBJECTIVE: To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE.DESIGN: Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials.SETTING: Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention).PARTICIPANTS: Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE).INTERVENTIONS: NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network.MAIN OUTCOME MEASURES: Efficacy Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness.DATA SOURCES: MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014.REVIEW METHODS: Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models.RESULTS: Apixaban (Eliquis(rcledR), Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana(rcledR), Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication.CONCLUSIONS: NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE.LIMITATIONS: These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs.FUTURE WORK: Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials.STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005324, CRD42013005331 and CRD42013005330.FUNDING: The National Institute for Health Research Health Technology Assessment programme