Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death

Aims This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation.Methods and results We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality.Conclusion Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.Cardiolog

Developing and testing a Talking Mats symbol set to support conversations about social care related quality of life with care home residents

When agents are acting together, they may need a simple mechanism to decide on joint actions. One possibility is to have the agents express their preferences in the form of a ballot and use a voting rule to decide the winning action(s). Unfortunately, agents may try to manipulate such an election by misreporting their preferences. Fortunately, it has been shown that it is NP-hard to compute how to manipulate a number of different voting rules. However, NP-hardness only bounds the worst-case complexity. Recent theoretical results suggest that manipulation may often be easy in practice. To address this issue, I suggest studying empirically if computational complexity is in practice a barrier to manipulation. The basic tool used in my investigations is the identification of computational "phase transitions". Such an approach has been fruitful in identifying hard instances of propositional satisfiability and other NP-hard problems. I show that phase transition behaviour gives insight into the hardness of manipulating voting rules, increasing concern that computational complexity is indeed any sort of barrier. Finally, I look at the problem of computing manipulation of other, related problems like stable marriage and tournament problems.Comment: To appear in Proceedings of 11th International Workshop on Computational Logic in Multi-Agent Systems (CLIMA XI 2010

Stable roommates and constraint programming

In the stable roommates (SR) problem we have n agents, where each agent ranks all n − 1 other agents. The problem is then to match agents into pairs such that no two agents prefer each other to their matched partners. A remarkably simple constraint encoding is presented that uses O(n 2) binary constraints, and in which arc-consistency (the phase-1 table) is established in O(n 3) time. This leads us to a specialized n-ary constraint that uses O(n) additional space and establishes arc-consistency in O(n 2) time. This can model stable roommates with incomplete lists (SRI), consequently it can also model stable marriage (SM) problems with complete and incomplete lists (SMI). That is, one model suffices. An empirical study is performed and it is observed that the n-ary constraint model can read in, model and output all matchings for instances with n = 1,000 in about 2 seconds on current hardware platforms. Enumerating all matchings is a crude solution to the egalitarian SR problem, and the empirical results suggest that although NP-hard, egalitarian SR is practically easy

Subclinical synovitis detected by macrophage PET, but not MRI, is related to short-term flare of clinical disease activity in early RA patients: an exploratory study

INTRODUCTION: Residual subclinical synovitis can still be present in joints of rheumatoid arthritis (RA) patients despite clinical remission and has been linked to ongoing radiological damage. The aim of the present study was to assess subclinical synovitis by positron emission tomography (PET; macrophage tracer (11)C-(R)-PK11195) in early RA patients with minimal disease activity without clinically apparent synovitis (MDA); and its relationship with clinical outcome and magnetic resonance imaging (MRI), respectively. METHODS: Baseline PET and MRI of hands/wrists were performed in 25 early MDA RA patients (DAS 44 < 1.6; no tender/swollen joints) on combined DMARD therapy. PET tracer uptake (semi-quantitative score: 0-3) and MRI synovitis and bone marrow edema (OMERACT RAMRIS) were assessed in MCP, PIP and wrist joints (22 joints/patient; cumulative score). RESULTS: Eleven of 25 patients (44 %) showed enhanced tracer uptake in ≥ 1 joint. Fourteen of these 25 (56 %) patients developed a flare within 1 year: 8/11 (73 %) with a positive, and 6/14 (43 %) with a negative PET. In the latter, in 5/6 patients flare was located outside the scan region. Median cumulative PET scores of patients with a subsequent flare in the hands or wrists were significantly higher than those of patients without a flare (1.5 [IQR 0.8-5.3] vs 0.0 [IQR 0.0-1.0], p = 0.04); significance was lost when all flares were considered (1.0 [IQR 0.0-4.0] vs 0.0 [IQR 0.0-1.0], p = 0.10). No difference in cumulative MRI scores was observed between both groups. CONCLUSIONS: Positive PET scans were found in almost half of early RA patients with MDA. Patients with a subsequent flare in hand or wrist had higher cumulative PET scores but not MRI scores, suggesting that subclinical arthritis on PET may predict clinical flare in follow-up

Conical indentation of incompressible rubber-like materials

In the last decade, the indentation test has become a useful tool for probing mechanical properties of small material volumes. In this context, little has been done for rubber-like materials (elastomers), although there is pressing need to use instrumented indentation in biomechanics and tissue examination. The present work investigates the quasi-static normal instrumented indentation of incompressible rubber-like substrates by sharp rigid cones. A second-order elasticity analysis was performed in addition to finite element analysis and showed that the elastic modulus at infinitesimal strains correlates well with the indentation response that is the relation between the applied force and the resulting vertical displacement of the indentor's tip. Three hyperelastic models were analyzed: the classic Mooney-Rivlin model, the simple Gent model and the one-term Ogden model. The effect of the angle of the cone was investigated, as well as the influence of surface friction. For blunt cones, the indentation response agrees remarkably well with the prediction of linear elasticity and confirms available experimental results of instrumented Vickers indentation. (C) 2008 Elsevier Ltd. All rights reserved