Maintaining musculoskeletal health using a behavioural therapy approach : a population-based randomised controlled trial (the MAmMOTH Study)

Acknowledgements: The study was funded by Arthritis Research UK (now Versus Arthritis) grant number: 20748. Costs for delivery of the intervention were provided by NHS Grampian, NHS Greater Glasgow and Clyde, and NHS Highland. The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. We acknowledge the contribution of the trial steering committee to the successful conduct of the study. The members were Professor Ernest Choy (Cardiff University), Professor Tamar Pincus (Royal Holloway, University of London) and Gordon Taylor (Bath University). We thank Brian Taylor and Mark Forrest from the Centre for Healthcare Randomised Trials (CHaRT) at the University of Aberdeen for their technical assistance and Professor Graeme MacLennan, Director of CHaRT, for methodological input. Professor John Norrie (originally University of Aberdeen now University of Edinburgh) and Dr. Majid Artus (originally Keele University, now the Osmaston surgery, Derbyshire) were study investigators at the time of grant award but subsequently left the study. We thank Kathy Longley (a representative of Fibromyalgia Action UK) for her input to the grant application and the project as well as from members of the public on the University of Aberdeen College of Life Sciences and Medicine Research Interest Group. The prioritisation of “Prevention of chronic pain” arose from a 2012 meeting of the Arthritis Research UK Clinical Study Group in Pain to which patients contributed.Peer reviewedPostprintsupplementary_datasupplementary_dat

Post-fire comparisons of forest floor and soil carbon, nitrogen, and mercury pools with fire severity indices

Forest fires are important contributors of C, N, and Hg to the atmosphere. In the fall of 2011, a large wildfire occurred in northern Minnesota and we were able to quickly access the area to sample the forest floor and mineral soil for C, N, and Hg pools. When compared with unburned reference soils, the mean loss of C resulting from fire in the forest floor and the upper 20 cm of mineral soil was 19.3 Mg ha−1, for N the mean loss was 0.17 Mg ha−1, and for Hg the mean loss was 9.3 g ha−1. To assess the influence of fire severity on the forest floor and mineral soils, we used an established method that included a soil burn severity index and a tree burn severity index with a gradient of severity classes. It was apparent that the unburned reference class had greater forest floor C, N, and Hg pools and higher C/N ratios than the burned classes. The C/N ratios of the 0- to 10- and 10- to 20-cm mineral soils in the unburned reference class were also greater than in the burned classes, indicating that a small amount of C was lost and/or N was gained, potentially through leaching unburned forest floor material. However, with a couple of exceptions, the severity classes were unable to differentiate the forest floor and mineral soil impacts among soil burn and tree burn severity indices. Developing burn severity indices that are reflective of soil elemental impacts is an important first step in scaling ecosystem impacts both within and across fire events

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

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

015 Maintaining musculoskeletal health: a randomised controlled trial of cognitive behaviour therapy among people at high risk of developing chronic widespread pain

Abstract Background Cognitive behaviour therapy (CBT) is effective in the management of fibromyalgia (and its characteristic feature chronic widespread pain (CWP). CBT is recommended in all recent major fibromyalgia management guidelines. From large-scale epidemiological studies, prediction models are available which identify groups at high-risk of developing CWP. We now test whether it is possible to prevent onset of CWP and/or change factors associated with its onset. Methods A randomised controlled trial of CBT delivered by telephone plus usual care (tCBT) was tested against usual care alone (UC). Eligible adults aged at least 25 years were identified by a survey of persons registered with sixteen general practices across Scotland. Respondents reporting regional pain (not CWP) for which they had recently consulted their GP and at least 2 items from a previously validated ‘high risk’ profile (Somatic Symptom Scale, Sleep Problem Scale, Illness Behaviour Scale) were invited to participate. tCBT was delivered across 6 sessions over 8 weeks with booster sessions 3 and 6 months after treatment start. Primary outcome was CWP at 12 months. Secondary outcomes were risk profile measures: fatigue (Chalder Fatigue Scale), Patient Global Impression of Change (PGIC: 7 categories), psychological distress (General Health Questionnaire) and quality of life (EQ-5D-5L) also at 12 months. Analysis used logistic, ordinal logistic or linear regression depending on outcome variable type; expressed as an effect size with 95% confidence interval. Results 1,002 people were randomised, with equal numbers assigned to each arm of the trial: 59% of participants were female, with a median age of 59 (range 25-91) years. 66% of tCBT participants completed treatment and 83% of all participants provided follow-up data at 12 months. There was no difference in the proportion with CWP at 12 months (tCBT 18.0% v. UC 17.5%). There were improvements (all favouring tCBT) in Illness Behaviour Score (mean difference (md) -0.83; -1.55,-0.11), Sleep Problem Scale (md -0.90; -1.45,-0.36), psychological distress (Odds Ratio (OR) per category 0.65; 0.50, 0.85), EQ-5D-5L (md 0.024; 0.009, 0.039), Chalder Fatigue Scale (md -1.05; -1.66,-0.44) and PGIC (OR per category 0.51;0.39,0.67). Specifically 30.2% of those receiving tCBT reported their health as much or very much better, compared to 17.3% of those receiving UC. Conclusion This first-ever large-scale trial of prevention, aimed at persons at high risk, has shown tCBT does not change the likelihood of CWP onset but does improve the underlying risk profile for developing the condition as well as improving distress , fatigue and quality of life. Those receiving tCBT were, 12 months later, significantly more like to consider their health was better. This trial provides evidence for extending the group of people considered to benefit from CBT. Disclosures G.J. Macfarlane None. M. Beasley None. N. Scott None. P. McNamee None. J. McBeth None. G. Prescott None. G.T. Jones None. P. Hannaford None. N. Basu None. P. Keeley None. K. Lovell None

A NATIONAL STUDY OF THE CONSEQUENCES OF FIRE AND FIRE SURROGATE TREATMENTS

Many U.S. forests, especially those with historically short-interval, low- to moderate-severity fire regimes, are too dense and have excessive quantities of fuels. Widespread treatments are needed to restore ecological integrity and reduce the high risk of destructive, uncharacteristically severe fires in these forests. Among possible treatments, however, the appropriate balance among cuttings, mechanical fuel treatments, and prescribed fire is often unclear. For improved decisionmaking, resource managers need much better information about the consequences of alternative management practices involving fire and mechanicaVmanual fire surrogates. Long-term, interdisciplinary research thus should be initiated to quantify the consequences and tradeoffs of alternative fire and fire surrogate treatments. Ecological, economic and social aspects must all be included as integral components. The research needs to be experimental, rather than retrospective or correlative, to permit stronger inferences about cause-and-effect relationships. Only through such research will it be possible to determine which ecosystem functions of fire can be emulated satisfactorily by other means, which may be irreplaceable, and the implications for management. The human dimensions of the problem are equally important. Treatment costs and utilization economics, as well as social and political acceptability, strongly influence decisions about treatment alternatives. Such research must be a cooperative effort, involving land managers, researchers, and other interested parties. A team of scientists and land managers has designed an integrated national network of long-term research sites to address this need, with support from the USDAIUSDI Joint Fire Science Program (http://www.nifc.gov/joint_fire_sci/index.html). The steering committee and other participants in this national FirelFire Surrogate (FFS) study represent a number of federal and state agencies, universities, and private entities, as well as a wide range of disciplines and geographic regions. The study will use a common experimental design to facilitate broad applicability of results

Cognitive Behavior Therapy, Exercise, or Both for Treating Chronic Widespread Pain

Background The clinical impact of telephone-delivered cognitive behavioral therapy (TCBT), exercise, or a combined intervention in primary care patients with chronic widespread pain (CWP) is unclear. Methods A total of 442 patients with CWP (meeting the American College of Rheumatology criteria) were randomized to receive 6 months of TCBT, graded exercise, combined intervention, or treatment as usual (TAU). The primary outcome, using a 7-point patient global assessment scale of change in health since trial enrollment (range: very much worse to very much better), was assessed at baseline and 6 months (intervention end) and 9 months after randomization. A positive outcome was defined as “much better” or “very much better.” Data were analyzed using logistic regression according to the intention-to-treat principle. Results The percentages reporting a positive outcome at 6 and 9 months, respectively, were TAU group, 8% and 8%; TCBT group, 30% and 33%; exercise group, 35% and 24%; and combined intervention group, 37% and 37% (P < .001). After adjustment for age, sex, center, and baseline predictors of outcome, active interventions improved outcome compared with TAU: TCBT (6 months: odds ratio [OR], 5.0 [95% CI, 2.0-12.5]; 9 months: OR, 5.4 [95% CI, 2.3-12.8]), exercise (6 months: OR, 6.1 [95% CI, 2.5-15.1]; 9 months: OR, 3.6 [95% CI, 1.5-8.5]), and combined intervention (6 months: OR, 7.1 [95% CI, 2.9-17.2]; 9 months: OR, 6.2 [95% CI, 2.7-14.4]). At 6 and 9 months, combined intervention was associated with improvements in the 36-Item Short Form Health Questionnaire physical component score and a reduction in passive coping strategies. Conclusions on cost-effectiveness were sensitive to missing data. Conclusion TCBT was associated with substantial, statistically significant, and sustained improvements in patient global assessment