Behaviour change interventions for the management of Raynaud's phenomenon : a systematic review protocol

Introduction Raynaud's phenomenon (RP) describes excessive peripheral vasospasm to cold exposure and/or emotional stress. RP episodes are associated with digital colour changes, pain and reduced quality of life. Pharmacological interventions are of low to moderate efficacy and often result in adverse effects such as facial flushing and headaches. Recommended lifestyle and behavioural interventions have not been evaluated. The objectives of the proposed systematic review are to assess the comparative safety and efficacy of behaviour change interventions for RP and identify what we can learn to inform future interventions. Methods and analysis Studies eligible for inclusion include randomised controlled trials testing behaviour change interventions with a control comparator. A comprehensive search strategy will include peer review and grey literature up until 30 April 2017. Search databases will include Medline, Embase, PsychINFO and Cochrane. Initial sifting, eligibility, data extraction, risk of bias and quality assessment will be subject to review by two independent reviewers with a third reviewer resolving discrepancies. Risk of bias assessment will be performed using Cochrane risk of a bias assessment tool with quality of evidence assessed using Grading of Recommendations Assessment, Development and Evaluation(GRADE). A meta-analysis will be performed if there are sufficient data. Two subgroup analyses are planned: primary versus secondary RP outcomes; comparison of theoretically informed interventions with pragmatic interventions. Ethics and dissemination This review does not require ethical approval as it will summarise published studies with non-identifiable data. This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Findings will be disseminated in peer-reviewed articles and reported according to PRISMA. This review will make a significant contribution to the management of RP where no review of behaviour-change interventions currently exist. The synopsis and protocol for the proposed systematic review is registered in the International Prospective Register of Systematic Reviews (registration number CRD42017049643)

Robust designs for Poisson regression models

We consider the problem of how to construct robust designs for Poisson regression models. An analytical expression is derived for robust designs for first-order Poisson regression models where uncertainty exists in the prior parameter estimates. Given certain constraints in the methodology, it may be necessary to extend the robust designs for implementation in practical experiments. With these extensions, our methodology constructs designs which perform similarly, in terms of estimation, to current techniques, and offers the solution in a more timely manner. We further apply this analytic result to cases where uncertainty exists in the linear predictor. The application of this methodology to practical design problems such as screening experiments is explored. Given the minimal prior knowledge that is usually available when conducting such experiments, it is recommended to derive designs robust across a variety of systems. However, incorporating such uncertainty into the design process can be a computationally intense exercise. Hence, our analytic approach is explored as an alternative

B-type natriuretic peptide trumps other prognostic markers in patients assessed for coronary disease

Background: Risk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous markers have the potential to predict prognosis and guide management, but we currently lack robust 'real-world' evidence for their use. Methods: Prospective, multicentre observational study of consecutive patients referred for elective coronary angiography. Clinicians were blinded to all risk assessments, consisting of conventional factors, radial artery pulse wave analysis, 5-minute heart rate variability, high-sensitivity C-reactive protein and B-type natriuretic peptide (BNP). Blinded, independent adjudication was performed for all-cause mortality and the composite of death, myocardial infarction or stroke, analysed with Cox proportional hazards regression. Results: Five hundred twenty-two patients were assessed with median age 66 years and 21% prior revascularization. Median baseline left ventricular ejection fraction was 64%, and 62% had ≥ 50% stenosis on angiography. During 5.0 years median follow-up, 30% underwent percutaneous and 16% surgical revascularization. In multivariate analysis, only age and BNP were independently associated with outcomes. The adjusted hazard ratio per log unit increase in BNP was 2.15 for mortality (95% CI 1.45-3.19; p = 0.0001) and 1.27 for composite events (1.04-1.54; p = 0.018). Patients with baseline BNP > 100 pg/mL had substantially higher mortality and composite events (20.9% and 32.2%) than those with BNP ≤ 100 pg/mL (5.6% and 15.5%). BNP improved both classification and discrimination of outcomes (p ≤ 0.003), regardless of left ventricular systolic function. Conversely, high-sensitivity C-reactive protein, pulse wave analysis and heart rate variability were unrelated to prognosis at 5 years after risk modification and treatment of coronary disease. Conclusions: Conventional risk factors and other markers of arterial compliance, inflammation and autonomic function have limited value for prediction of outcomes in risk-modified patients assessed for coronary disease. BNP can independently identify patients with subtle impairment of cardiac function that might benefit from more intensive management. Trial registration: Clinicaltrials.gov, NCT00403351 Registered on 22 November 200

Pathogens and Equity in the Pandemic Treaty - Key Takeaways for Negotiators

Pathogens are essential ingredients to monitor the spread of disease, and for developing and producing the vaccines we use to fight infectious disease. Under international law, pathogens are not a resource freely available for use for the greater good. Instead, countries have sovereign rights over the pathogens isolated within their territories, and access can only be provided with the prior informed consent of the country of origin, subject to mutually agreed terms. Under this international system, access to pathogens should be accompanied by the sharing of benefits such as access to medical countermeasures. Such a system has been presented as a tool to counter global inequality in a pandemic. In response to the widespread inequity witnessed during the COVID-19 pandemic, Member States of the World Health Organisation (WHO) are currently negotiating a new international legal instrument, intended to prevent pandemics and mitigate associated inequalities – the Pandemic Accord or the Pandemic Treaty. Negotiations on this Treaty launched in March 2022 and are set to conclude by May 2024; a remarkably short time frame in international law terms. The new instrument is intended to be grounded in equity, with equity positioned as both an objective and as an operational output. The Pandemic Treaty is intended to prevent future pandemics, improve pandemic response, mitigate associated inequalities (such as inequitable vaccine access), and improve compliance with international law during infectious disease emergencies. One option currently being explored in the negotiations for a Pandemic Treaty to operationalise equity is the establishment of a complex system of ABS for pathogens of pandemic potential, under the auspices of the WHO. On 19th July 2023, and with the assistance of funding received from the Royal Society of Edinburgh, project leads Dr Stephanie Switzer (University of Strathclyde) and Dr Mark Eccleston-Turner (King’s College, London), organised an event with the British Institute of International and Comparative Law on pathogen sharing and equity under the Pandemic Treaty, with a particular focus on vaccine inequity during the COVID-19 public health emergency. This event was convened by Anthony Wenton, Research Fellow in Public International Law, British Institute of International and Comparative Law (BIICL), moderated by Dr Stephanie Switzer, with contributions from Professor Gian Luca Burci of the Graduate Institute Geneva, Prof Elisa Morgera, One Ocean Hub, University of Strathclyde, Dr Mark Eccleston-Turner, King’s College London, Dr Michelle Rourke, Griffith University, Australia and Professor John Harrington, University of Cardiff. Harry Upton of King’s College London acted as rapporteur for the event. In the below briefing document, we provide an overview of discussions at the event, accompanied by key reflections, tools, and takeaways for negotiators to the Pandemic Treaty

Examining affective-motivational dynamics and behavioral implications within the interpersonal context of pain

Emotional, motivational, and interpersonal dimensions are considered integral to pain experience but have largely been examined separately. In this focus article, we argue that an integrative theoretical account that acknowledges each of these elements is a critical next step to capture the complexity and nuance of interpersonal pain dynamics and to shape future research. The aim of this focus article is to provide a foundation for such an account by drawing upon established insights from appraisal theory of emotion, influential behavioral models, empathy/interpersonal pain research, and social psychology literature to highlight conceptual relationships, potential mechanisms of action, and avenues of inquiry that have not previously been examined in the context of pain. Specifically, we highlight the interpersonal nature of pain and the conceptual relationship between emotion and motivation in pain experience. We discuss an affective-motivational tension between self- and other-oriented goals that can arise within the interpersonal pain context, and how such dynamics may affect the nature and effectiveness of care giving behavior. We then describe the role of emotion regulation and strategies that may facilitate optimal interpersonal pain dynamics and caregiving within a multiple goal context. Finally, we outline a foundation for an integrative theoretical model and directions for future research. Perspective: Drawing upon insights from appraisal theory of emotion, empathy/interpersonal pain research, influential behavioral models, and social psychology literature, this focus article provides a foundation for an integrative affective-motivational account of interpersonal pain dynamics as a basis for theoretical and clinical advancement. (C) 2017 by the American Pain Societ

Risk factors associated with poor pain outcomes following primary knee replacement surgery: analysis of data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Patient Reported Outcomes as part of the STAR research programme

OBJECTIVE: Identify risk factors for poor pain outcomes six months after primary knee replacement surgery. METHODS: Observational cohort study on patients receiving primary knee replacement from the UK Clinical Practice Research Datalink, Hospital Episode Statistics and Patient Reported Outcomes. A wide range of variables routinely collected in primary and secondary care were identified as potential predictors of worsening or only minor improvement in pain, based on the Oxford Knee Score pain subscale. Results are presented as relative risk ratios and adjusted risk differences (ARD) by fitting a generalized linear model with a binomial error structure and log link function. RESULTS: Information was available for 4,750 patients from 2009 to 2016, with a mean age of 69, of whom 56.1% were female. 10.4% of patients had poor pain outcomes. The strongest effects were seen for pre-operative factors: mild knee pain symptoms at the time of surgery (ARD 18.2% (95% Confidence Interval 13.6, 22.8), smoking 12.0% (95% CI:7.3, 16.6), living in the most deprived areas 5.6% (95% CI:2.3, 9.0) and obesity class II 6.3% (95% CI:3.0, 9.7). Important risk factors with more moderate effects included a history of previous knee arthroscopy surgery 4.6% (95% CI:2.5, 6.6), and use of opioids 3.4% (95% CI:1.4, 5.3) within three months after surgery. Those patients with worsening pain state change had more complications by 3 months (11.8% among those in a worse pain state vs. 2.7% with the same pain state). CONCLUSIONS: We quantified the relative importance of individual risk factors including mild pre-operative pain, smoking, deprivation, obesity and opioid use in terms of the absolute proportions of patients achieving poor pain outcomes. These findings will support development of interventions to reduce the numbers of patients who have poor pain outcomes

Estimation in a multiplicative mixed model involving a genetic relationship matrix

Genetic models partitioning additive and non-additive genetic effects for populations tested in replicated multi-environment trials (METs) in a plant breeding program have recently been presented in the literature. For these data, the variance model involves the direct product of a large numerator relationship matrix A, and a complex structure for the genotype by environment interaction effects, generally of a factor analytic (FA) form. With MET data, we expect a high correlation in genotype rankings between environments, leading to non-positive definite covariance matrices. Estimation methods for reduced rank models have been derived for the FA formulation with independent genotypes, and we employ these estimation methods for the more complex case involving the numerator relationship matrix. We examine the performance of differing genetic models for MET data with an embedded pedigree structure, and consider the magnitude of the non-additive variance. The capacity of existing software packages to fit these complex models is largely due to the use of the sparse matrix methodology and the average information algorithm. Here, we present an extension to the standard formulation necessary for estimation with a factor analytic structure across multiple environments