Preoperative psychosocial risk factors for poor outcomes at 1 and 5 years after total knee replacement:A cohort study of 266 patients

Background and purpose — Psychosocial factors are important risk factors for poor outcomes in the first year after total knee replacement (TKR), however their impact on long-term outcomes is unclear. We aimed to identify preoperative psychosocial risk factors for poor outcomes at 1 year and 5 years after TKR. Patients and methods — 266 patients were recruited prior to TKR surgery. Knee pain and function were assessed preoperatively and at 1 and 5 years postoperative using the WOMAC Pain score, WOMAC Function score and American Knee Society Score (AKSS) Knee score. Preoperative depression, anxiety, catastrophizing, pain self-efficacy and social support were assessed. Statistical analyses involved multiple linear regression and mixed effect linear regression. Results — Higher anxiety was a risk factor for worse pain at 1 year postoperative. No psychosocial factors were associated with any outcomes at 5 years postoperative. Analysis of change over time found that patients with higher pain self-efficacy had lower preoperative pain and experienced less improvement in pain up to 1 year postoperative. Higher pain self-efficacy was associated with less improvement in the AKSS up to 1 year postoperative but more improvement between 1 and 5 years postoperative. Interpretation — Preoperative anxiety was found to influence pain at 1 year after TKR. However, none of the psychosocial variables were risk factors for a poor outcome at 5 years post­operative, suggesting that the negative effects of anxiety on outcome do not persist in the longer-term

The association between cement type and the subsequent risk of revision surgery in primary total hip replacement:199, 205 hips from the National Joint Registry for England, Wales and Northern Ireland

<p><b>Background and purpose</b> — To further improve the success of joint replacement surgery, attention needs to be paid to variations associated with improved or worsened outcomes. We investigated the association between the type of bone cement used and the risk of revision surgery after primary total hip replacement.</p> <p><b>Methods</b> — We conducted a prospective study of data from the National Joint Registry for England and Wales between April 1, 2003 and December 31, 2013. 199,205 primary total hip replacements performed for osteoarthritis where bone cement was used were included. A multilevel over-dispersed piecewise Poisson model was used to estimate differences in the rate of revision by bone cement type adjusted for implant type, head size, age, sex, ASA grade, and surgical approach.</p> <p><b>Results</b> — The rate of revision was higher in DePuy CMW3 medium viscosity with gentamicin (IRR 2.0, 95% CI 1.5–2.7) and DePuy SmartSet high viscosity plain (IRR 2.7, 95% CI 1.1–5.5), and lower in DePuy CMW1 high viscosity plain (IRR 0.44, 95% CI 0.19–0.89) bone cements compared with Heraeus Palacos high viscosity with gentamicin. Revision rates were similar between plain and antibiotic-loaded bone cement.</p> <p><b>Interpretation</b> — The majority of bone cements performed similarly well, excluding DePuy SmartSet high viscosity and CMW3 high viscosity with gentamicin, which both had higher revision rates. We found no clear differences by viscosity or antibiotic content.</p

HAPRAP: a haplotype-based iterative method for statistical fine mapping using GWAS summary statistics

Motivation Fine mapping is a widely used approach for identifying the causal variant(s) at disease-associated loci. Standard methods (e.g. multiple regression) require individual level genotypes. Recent fine mapping methods using summary-level data require the pairwise correlation coefficients (r2 ) of the variants. However, haplotypes rather than pairwise r2 , are the true biological representation of linkage disequilibrium (LD) among multiple loci. In this article, we present an empirical iterative method, HAPlotype Regional Association analysis Program (HAPRAP), that enables fine mapping using summary statistics and haplotype information from an individual-level reference panel. Results Simulations with individual-level genotypes show that the results of HAPRAP and multiple regression are highly consistent. In simulation with summary-level data, we demonstrate that HAPRAP is less sensitive to poor LD estimates. In a parametric simulation using Genetic Investigation of ANthropometric Traits height data, HAPRAP performs well with a small training sample size (N < 2000) while other methods become suboptimal. Moreover, HAPRAP’s performance is not affected substantially by single nucleotide polymorphisms (SNPs) with low minor allele frequencies. We applied the method to existing quantitative trait and binary outcome meta-analyses (human height, QTc interval and gallbladder disease); all previous reported association signals were replicated and two additional variants were independently associated with human height. Due to the growing availability of summary level data, the value of HAPRAP is likely to increase markedly for future analyses (e.g. functional prediction and identification of instruments for Mendelian randomization)

Estimating an individual's probability of revision surgery after knee replacement : a comparison of modeling approaches using a national dataset

Tools that provide personalized risk prediction of the outcomes after surgical procedures help patients to make preference-based decisions amongst the available treatment options. However, it is unclear which modeling approach provides the most accurate risk estimation. We constructed and compared several parametric and non-parametric models for predicting prosthesis survivorship after knee replacement surgery for osteoarthritis. We used 430,455 patient-procedure episodes between April 2003 and September 2015 from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. The flexible parametric survival and random survival forest models most accurately captured the observed probability of remaining event-free. The concordance index for the flexible parametric model was the highest (0.705; 95% confidence interval: 0.702, 0.707) for total knee replacement, 0.639 (95% confidence interval: 0.634, 0.643) for unicondylar knee replacement and 0.589 (95% confidence interval: 0.586, 0.592) for patellofemoral replacement. The observed-to-predicted ratios for both the flexible parametric and the random survival forest approaches indicated that models tended to underestimate the risks for most risk groups. Our results show that the flexible parametric model has a better overall performance compared to other tested parametric methods, and better discrimination compared to the random survival forest approach

Cost-utility and value of information analysis of tisagenlecleucel for relapsed/refractory diffuse large B-cell lymphoma in the Irish healthcare setting

ABSTRACTBackground The evidence base of tisagenlecleucel is uncertain.Objective To evaluate the cost-effectiveness of tisagenlecleucel. To conduct expected value of perfect information (EVPI) and partial EVPI (EVPPI) analyses.Study Design A three-state partitioned survival model. A short-term decision tree partitioned patients in the tisagenlecleucel arm according to infusion status. Survival was extrapolated to 5 years; general population mortality with a standardised mortality ratio was then applied. EVPI and EVPPI were scaled up to population according to the incidence of the decision.Setting Irish healthcare payer.Participants Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).Interventions Tisagenlecleucel versus Salvage Chemotherapy (with or without haematopoietic stem cell transplant).Main Outcome Measure Incremental cost-effectiveness ratio (ICER). Population EVPI and EVPPI.Results At list prices, the ICER was €119,509 per quality-adjusted life year (QALY) (incremental costs €218,092; incremental QALYs 1.82). Probability of cost-effectiveness, at a €45,000 per QALY threshold, was 0%. Population EVPI was €0.00. Population EVPI, at the price of tisagenlecleucel that reduced the ICER to €45,000 per QALY, was €3,989,438. Here, survival analysis had the highest population EVPPI (€1,128,053).Conclusion Tisagenlecleucel is not cost-effective, versus salvage chemotherapy (with or without haematopoietic stem cell transplant), for R/R DLBCL in Ireland. At list prices, further research to decrease decision uncertainty may not be of value