Comparison of the Flexible Parametric Survival Model and Cox Model in Estimating Markov Transition Probabilities using Real-World Data

Background and Objective: Markov micro-simulation models are being increasingly used in health economic evaluations. An important feature of the Markov micro-simulation model is its ability to consider transition probabilities of heterogeneous subgroups with different risk profiles. A survival analysis is generally performed to accurately estimate the transition probabilities associated with the risk profiles. This study aimed to apply a flexible parametric survival model (FPSM) to estimate individual transition probabilities. Materials and Methods: The data were obtained from a cohort study investigating ischemic stroke outcomes in Western China. In total, 585 subjects were included in the analysis. To explore the goodness of fit of the FPSM, we compared the estimated hazard ratios and baseline cumulative hazards, both of which are necessary to the calculate individual transition probabilities, and the Markov micro-simulation models constructed using the FPSM and Cox model to determine the validity of the two Markov micro-simulation models and cost-effectiveness results. Results: The flexible parametric proportional hazards model produced hazard ratio and baseline cumulative hazard estimates that were similar to those obtained using the Cox proportional hazards model. The simulated cumulative incidence of recurrent ischemic stroke and 5-years cost-effectiveness of Incremental cost-effectiveness Ratios (ICERs) were also similar using the two approaches. A discrepancy in the results was evident between the 5-years cost-effectiveness and the 10-years cost-effectiveness of ICERs, which were approximately 0.9 million (China Yuan) and 0.5 million (China Yuan), respectively. Conclusions: The flexible parametric survival model represents a good approach for estimating individual transition probabilities for a Markov micro-simulation model

Biomechanical Evaluation of the Cross-link Usage and Position in the Single and Multiple Segment Posterior Lumbar Interbody Fusion

Objective: Previous studies have neither explored the usage of cross-links nor investigated the optimal position of the cross-links in posterior lumbar interbody fusion (PLIF). This study evaluates biomechanical properties of cross-links in terms of different fixation segments and optimal position in single- and multi-segment posterior lumbar interbody fusion. Methods: Two finite element (FE) models of instrumented lumbosacral spine with single-(L4/5) and multi-segment (L3-S1) PLIF surgery were simulated. On the basis of the two models, the benefits of the usage of cross-links were assessed and compared with the status of no application of cross-links. Moreover, the effects of position of cross-links on multi-segment PLIF surgery were studied in Upper, Middle, and Lower positions. Results: No significant difference was found in the range of motion (ROM), intersegmental rotational angle (IRA) of adjacent segments, and intradiscal pressure (IDP) regardless of the usage of cross-links in the single-segment PLIF surgery, while the cross-link increased the maximum von Mises stress in the fixation (MSF) under the axial rotation (53.65 MPa vs 41.42 MPa). In the multi-segment PLIF surgery, the usage of cross-links showed anti-rotational advantages indicated by ROM (Without Cross-link 2.35o, Upper, 2.24o; Middle, 2.26o; Lower, 2.30o) and IRA (Without Cross-link 1.19o, Upper, 1.08o; Middle, 1.09o; Lower, 1.13o). The greatest values of MSF were found in without cross-link case under the flexion, lateral bending, and axial rotation (37.48, 62.61, and 86.73 MPa). The application of cross-links at the Middle and Lower positions had lower values of MSF (48.79 and 69.62 MPa) under the lateral bending and axial rotation, respectively. Conclusion: The application of cross-links was not beneficial for the single-segment PLIF, while it was found highly advantageous for the multi-segment PLIF. Moreover, the usage of cross-links at the Middle or Lower positions resulted in a better biomechanical stability.</p

Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans

Abstract Ageing exhibits common and distinct features in various tissues, making it critical to decipher the tissue-specific ageing mechanisms. MiRNAs are essential regulators in ageing and are recently highlighted as a class of intercellular messengers. However, little is known about the tissue-specific transcriptomic changes of miRNAs during ageing. C. elegans is a well-established model organism in ageing research. Here, we profile the age-dependent miRNAomic changes in five isolated worm tissues. Besides the diverse ageing-regulated miRNA expression across tissues, we discover numerous miRNAs in the tissues without their transcription. We further profile miRNAs in the extracellular vesicles and find that worm miRNAs undergo inter-tissue trafficking via these vesicles in an age-dependent manner. Using these datasets, we uncover the interaction between body wall muscle-derived mir-1 and DAF-16/FOXO in the intestine, suggesting mir-1 as a messenger in inter-tissue signalling. Taken together, we systematically investigate worm miRNAs in the somatic tissues and extracellular vesicles during ageing, providing a valuable resource to study tissue-autonomous and nonautonomous functions of miRNAs in ageing