A comparison of survival models for prediction of eight-year revision risk following total knee and hip arthroplasty

Background: There is increasing interest in the development and use of clinical prediction models, but a lack of evidence-supported guidance on the merits of diferent modelling approaches. This is especially true for time-to event outcomes, where limited studies have compared the vast number of modelling approaches available. This study compares prediction accuracy and variable importance measures for four modelling approaches in prediction of time-to-revision surgery following total knee arthroplasty (TKA) and total hip arthroplasty (THA). Methods: The study included 321,945 TKA and 151,113 THA procedures performed between 1 January 2003 and 31 December 2017. Accuracy of the Cox model, Weibull parametric model, fexible parametric model, and random survival forest were compared, with patient age, sex, comorbidities, and prosthesis characteristics considered as predictors. Prediction accuracy was assessed using the Index of Prediction Accuracy (IPA), c-index, and smoothed calibration curves. Variable importance rankings from the Cox model and random survival forest were also compared Results: Overall, the Cox and fexible parametric survival models performed best for prediction of both TKA (integrated IPA 0.056 (95% CI [0.054, 0.057]) compared to 0.054 (95% CI [0.053, 0.056]) for the Weibull parametric model), and THA revision. (0.029 95% CI [0.027, 0.030] compared to 0.027 (95% CI [0.025, 0.028]) for the random survival forest). The c-index showed broadly similar discrimination between all modelling approaches. Models were generally well calibrated, but random survival forest underftted the predicted risk of TKA revision compared to regression approaches. The most important predictors of revision were similar in the Cox model and random survival forest for TKA (age, opioid use, and patella resurfacing) and THA (femoral cement, depression, and opioid use). Conclusion: The Cox and fexible parametric models had superior overall performance, although all approaches performed similarly. Notably, this study showed no beneft of a tuned random survival forest over regression models in this setting.Alana R. Cuthbert, Lynne C. Giles, Gary Glonek, Lisa M. Kalisch Ellett, and Nicole L. Prat

Self-similar scaling and evolution in the galaxy cluster X-ray Luminosity-Temperature relation

We investigate the form and evolution of the X-ray luminosity-temperature (LT) relation of a sample of 114 galaxy clusters observed with Chandra at 0.1<z<1.3. The clusters were divided into subsamples based on their X-ray morphology or whether they host strong cool cores. We find that when the core regions are excluded, the most relaxed clusters (or those with the strongest cool cores) follow an LT relation with a slope that agrees well with simple self-similar expectations. This is supported by an analysis of the gas density profiles of the systems, which shows self-similar behaviour of the gas profiles of the relaxed clusters outside the core regions. By comparing our data with clusters in the REXCESS sample, which extends to lower masses, we find evidence that the self-similar behaviour of even the most relaxed clusters breaks at around 3.5keV. By contrast, the LT slopes of the subsamples of unrelaxed systems (or those without strong cool cores) are significantly steeper than the self-similar model, with lower mass systems appearing less luminous and higher mass systems appearing more luminous than the self-similar relation. We argue that these results are consistent with a model of non-gravitational energy input in clusters that combines central heating with entropy enhancements from merger shocks. Such enhancements could extend the impact of central energy input to larger radii in unrelaxed clusters, as suggested by our data. We also examine the evolution of the LT relation, and find that while the data appear inconsistent with simple self-similar evolution, the differences can be plausibly explained by selection bias, and thus we find no reason to rule out self-similar evolution. We show that the fraction of cool core clusters in our (non-representative) sample decreases at z>0.5 and discuss the effect of this on measurements of the evolution in the LT relation.Comment: 21 pages, 15 figures. Submitted to MNRAS. Comments welcom

Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry

\ua9 The Author(s) 2024.Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression

Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry

Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression

MRI in multiple myeloma : a pictorial review of diagnostic and post-treatment findings

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity. This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message aEuro cent Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. aEuro cent Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. aEuro cent Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. aEuro cent Combined morphological and functional MRI provides optimal bone marrow assessment for staging. aEuro cent Combined morphological and functional MRI is of considerable value in treatment follow-up

Listening

In this paper we reflect on the kind of listening that happens in research whilst taking part in a keep fit group and getting sweaty, that pushes us to ask an interviewee 'Are you alright?' and haunts us when the project is over. This is the kind of listening that weaves through, around and beyond what is immediately heard, including the unspoken, the articulateness of objects and the listening that comes through participating. The paper stems from a project concerned with how people live, experience and manage cultural diversity and ethnic difference in their everyday lives in urban England. Divided into two sections, the first part introduces our methods that included participant observation, interviews and repeat in-depth discussion group meetings. The second reflects on our experiences of listening whilst doing, explores feelings that mediate listening and considers the time involved in listening