Yoga for older adults with multimorbidity (the Gentle Years Yoga Trial): study protocol for a randomised controlled trial

Background: Multimorbidity is common in older adults and associated with high levels of illness burden and healthcare expenditure. The evidence base for how to manage older adults with multimorbidity is weak. Yoga might be a useful intervention because it has the potential to improve health-related quality of life, physical functioning, and several medical conditions. The British Wheel of Yoga’s Gentle Years Yoga© (GYY) programme was developed specifically for older adults, including those with chronic medical conditions. Data from a pilot trial suggested feasibility of using GYY in this population, but its effectiveness and cost-effectiveness remain uncertain. Methods: This is a multi-site, individually randomised, superiority trial with an embedded process evaluation and an economic analysis of cost-effectiveness. The trial will compare an experimental strategy of offering a 12-week GYY programme against a control strategy of no offer in community-dwelling adults aged 65 or over who have multimorbidity, defined as having two or more chronic conditions from a predefined list. The primary outcome is health-related quality of life measured using the EQ-5D-5L, the primary endpoint being the overall difference over 12 months. Both groups will continue to be able to access their usual care from primary, secondary, community, and social services. Participants, care providers, and yoga teachers will not be blinded to the allocated intervention. Outcome measures are primarily self-reported. The analysis will follow intention-to-treat principles. Discussion: This pragmatic randomised controlled trial will demonstrate if the GYY programme is an effective, costeffective, and viable addition to the management of older adults with multimorbidity. Trial registration: ISRCTN ISRCTN13567538. Registered on 18 March 2019 Keywords: Aged, Multimorbidity, Mind-body therapies, Health-related quality of life, Randomised controlled tria

Carotid artery volumetric measures associate with clinical ten-year cardiovascular (CV) risk scores and individual traditional CV risk factors in rheumatoid arthritis; a carotid-MRI feasibility study

Background: Common carotid artery intima-media thickness (CIMT), as measured by ultrasound, has utility in stratification of the accelerated cardiovascular risk seen in rheumatoid arthritis (RA); however, the technique has limitations. Carotid magnetic resonance imaging (MRI) is emerging as a useful research tool in the general population, but has yet to be applied in RA populations. Our objectives were to describe the utility of carotid artery MRI (carotid-MRI) in patients with RA in comparison to healthy controls and to describe the association with RA disease phenotype. Methods: Sixty-four patients with RA and no history of cardiovascular (CV) disease/diabetes mellitus were assessed for RA and CV profile, including homeostasis model assessment-estimated insulin resistance (HOMA-IR) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All underwent carotid-MRI (3 T), and were compared to 24 healthy controls. Univariable analysis (UVA) and multivariable linear regression models (MVA) were used to determine associations between disease phenotype and carotid-MRI measures. Results: There were no significant differences in carotid arterial wall measurements between patients with RA and controls. Wall and luminal volume correlated with 10-year CV risk scores (adjusted as per 2017 European League Against Rheumatism (EULAR) guidance); rho = 0.33 (p = 0.012) and rho = 0.35 (p = 0.008), respectively, for Joint British Societies-2 risk score. In UVA, carotid-MRI volumetric measures predominantly were associated with traditional CV risk factors including age, ever-smoking and HOMA-IR (p < 0.05). Lower body mass index was associated with wall maximum thickness (r = − 0.25 p = 0.026). In MVA, age was independently associated with wall volume (B 1.13 (95% CI 0.32, 1.93), p = 0.007) and luminal volume (B 3.69 (95% CI 0.55, 6.83, p = 0.022), and RA disease duration was associated with luminal volume (B 3.88 (95% CI 0.80, 6.97), p = 0.015). Conclusions: This study demonstrates the utility of carotid-MRI in RA, reporting an association between three-dimensional measures in particular and CV risk scores, individual traditional CV risk factors and RA disease duration. Carotid-MRI in RA is a promising research tool in the investigation of CVD

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar

Cardiovascular abnormalities in immune-mediated inflammatory disease

Immune-mediated inflammatory disease (IMID) represents a group of diseases characterised by dysregulation of immune processes with a shared common inflammatory pathway, leading to end-organ damage, of which Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc) are two important examples. An accelerated risk of cardiovascular disease (CVD) with associated increased mortality is observed in those with IMID; the risk in RA being similar to those with diabetes mellitus. In addition, IMID can directly affect the myocardium independently of atherosclerosis, termed primary myocardial disease, causing further excess mortality; best described in SSc. Determining the disease phenotype most at risk of either macrovascular or primary myocardial disease and having a greater understanding of the underlying pathophysiology is vital to develop effective screening strategies to prevent and manage its complications. Surrogate markers of CVD, including soluble cardiovascular (CV) biomarkers and cardiovascular magnetic resonance (CMR) imaging, can inform of subclinical CVD or risk of progression to clinical CVD; with currently limited data in IMID. Using soluble CV biomarkers and CMR, this thesis demonstrates the presence of subclinical CVD in patients with RA and SSc free of clinical CVD. In RA, these abnormalities associate with traditional CV risk factors; emphasising the importance of their aggressive management. Using CMR, this thesis describes a reduction in left ventricular mass in RA; suggesting pathology other than atherosclerosis. This work investigates specific treatment strategies in the reduction of CV risk, reporting improvement in insulin resistance with TNF inhibition in a randomised controlled trial of early RA. In SSc, the utility of CMR in the assessment of primary myocardial disease is demonstrated, describing cardiac fibrosis in those free of known cardiac disease, associating with a poor prognostic phenotype. Finally, this thesis reports the novel use of an implantable loop recorder in SSc, detecting arrhythmias in patients free of known cardiac disease

Cardiovascular outcomes of patients with rheumatoid arthritis prescribed disease modifying anti-rheumatic drugs:a review

Introduction: Rheumatoid arthritis (RA) is associated with a heightened risk of cardiovascular disease (CVD), with both traditional CV risk factors and inflammation contributing to this risk. Areas covered: This review highlights the burden of CVD in RA and associated traditional CV risk factors, including the complexity of dyslipidemia in RA and the so-called ‘lipid paradox.’ Furthermore, the recognized RA-disease-specific factors associated with higher risk of CVD and the role of systemic inflammation in the pathogenesis of CVD in RA will be addressed. With the advent of biologic and targeted synthetic therapies in the treatment of RA, the effect of conventional and newer generation disease modifying anti-rheumatic therapies (DMARDs) on CV risk and associated risk factors will also be discussed. Expert opinion: Identifying the RA phenotype at greatest risk of CVD, understanding the interplay of increased traditional risk factors, common inflammatory processes and RA-specific factors, and personalized use of DMARDs according to disease phenotype and comorbidity to reduce this risk are key areas for future research

Subclinical Systemic Sclerosis Primary Heart Involvement by Cardiovascular Magnetic Resonance Shows No Significant Interval Change

Objective Subclinical systemic sclerosis (SSc) primary heart involvement is commonly described. Whether these findings progress over time is not clear. The study aimed to investigate cardiovascular magnetic resonance (CMR) interval change of subclinical SSc primary heart involvement. Methods Patients with SSc with no cardiovascular disease underwent two CMR scans that included T1 mapping and quantitative stress perfusion. The CMR change (mean difference) and association between CMR measures and clinical phenotype were assessed. The study had a prospective design. Results Thirty-one patients with SSc participated, with a median (interquartile range) follow-up of 33 (17-37) months (10 [32%] in the diffuse subset, 16 [52%] with interstitial lung disease [ILD], and 11 [29%] who were Scl-70+). Four of thirty-one patients had focal late gadolinium enhancement (LGE) at visit 1; one of four had an increase in LGE scar mass between visits. Two patients showed new focal LGE at visit 2. No change in other CMR indices was noted. The three patients with SSc with increased or new LGE at visit 2 had diffuse cutaneous SSc with ILD, and two were Scl-70+. A reduction in forced vital capacity and total lung capacity was associated with a reduction in left ventricular ejection fraction (ρ = 0.413, P = 0.021; ρ = 0.335, P = 0.07) and myocardial perfusion reserve (MPR) (ρ = 0.543, P = 0.007; ρ = 0.627, P = 0.002). An increase in the N-terminal pro–brain natriuretic peptide level was associated with a reduction in MPR (ρ = −0.448, P = 0.042). Patients on disease-modifying antirheumatic drugs (DMARDs) had an increase in native T1 (mean [SD] 1208 [65] vs. 1265 [56] milliseconds, P = 0.008). No other clinically meaningful CMR change in patients receiving DMARDs or vasodilators was noted. Conclusion Serial CMR detects interval subclinical SSc primary heart involvement progression; however, this study suggests abnormalities remain largely stable with follow-up

Information Analysis in the Field of Natural Disaster Science (34)

巨大災害研究センターでは、所員それぞれの研究テーマ以外に、センター全体に関わる活動を継続し、研究成果のアカウンタビリティの向上に貢献している。本年は、1)巨大災害研究センターセミナー、2)第12回地域防災計画実務者セミナー、3)災害対応研究会、4)第7回比較防災ワークショップ、5)データベース「SAIGAI」、について内容を紹介する。The objectives of this paper are to summarize the research activities of Research Center for Disaster Reduction Systems, DPRI. They are systematically organized by not only our staff members but also many researchers and practitioners who do voluntary work in some workshops and symposia. Open symposia were held monthly with large audience. The 12th Seminar for Regional Disaster Prevention Plan was held focusing on the civil protection planning. The 7th Workshop on Comparative Disaster Studies was held to provide an integrated review of the Japanese efforts to reduce vulnerability of the world, and to discuss reconstruction both in United States and Japan. We are also upgrading and expanding the database SAIGAI

A 2x2 randomised factorial SWAT of the use of a pen and small, financial incentive to improve recruitment rates in a randomised controlled trial of yoga for older adults with multimorbidity

Background: Monetary and other incentives may increase recruitment to randomised controlled trials. Methods: 2x2 factorial ‘study within a trial’ of including a pen and/or £5 with a postal recruitment pack to improve randomisation rate (primary outcome) into the host Gentle Years Yoga trial in older adults with multimorbidity. Secondary outcomes: return, and time to return, of screening form, and the cost per additional participant recruited. Binary data were analysed using logistic regression and time to return data using Cox proportional hazards regression. Results: 818 potential host trial participants included. Between those sent a pen (n=409) and not sent a pen (n=409), there was no evidence of a difference in the likelihood of being randomised (15 (3.7%) versus 11 (2.7%); OR 1.38, 95% CI 0.63–3.04), in returning a screening form (66 (16.1%) versus 61 (14.9%); OR 1.10, 95% CI 0.75–1.61) nor in time to return the screening form (HR 1.09, 95% CI 0.77–1.55). There was evidence of improved screening return rates (77 (18.8%) versus 50 (12.2%); OR 1.67, 95% CI 1.13–2.45) and time to return screening form (HR 1.56, 95% CI 1.09–2.22) but not randomisation (14 (3.4%) versus 12 (2.9%); OR 1.18, 95% CI 0.54–2.57) in those sent £5 (n=409) compared with those not sent £5 (n=409). No significant interaction effects between the interventions were observed. The cost per additional participant recruited was £32 for the pen and £1000 for the £5 incentive. Conclusion: Including a small, monetary incentive encouraged increased and faster response to the recruitment invitation but did not result in more participants being randomised into the host trial. Since it is relatively costly, we do not recommend this intervention for use to increase recruitment in this population. Pens are cheaper but did not provide evidence of benefit. Further studies may be required. Registration: Gentle Years Yoga Trial registered on 18 March 2019, ISRCTN13567538; SWAT registered with the Northern Ireland Network for Trials Methodology Research SWAT repository on 1 April 2018, SWAT94. Funding: The GYY trial and SWATs were funded by the United Kingdom National Health Service (NHS) through the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, open call project number 17/94/36. Keywords: study within a trial, pen, financial incentive, recruitment, factorial, randomised controlled trial, older people, multimorbidit