Total Hip Arthroplasty When Utilised in Young Adults Is a Cost-Effective Procedure:A 10-Year and Lifetime Cost-Utility Analysis

Purpose The primary aim of this study was to determine the cost-effectiveness of total hip arthroplasty (THA) in patients aged 25 years and under by calculating the cost per quality-adjusted life year (QALY) gained at 10 years post-operatively, and over the course of a lifetime. Secondary aims were to describe the change in health-related quality of life (HRQoL), Oxford hip score (OHS), and satisfaction in these patients. Methods From 2000 to 2016, 33 patients undergoing THA aged 25 and under had pre-operative and one-year post-operative EuroQol five-dimensions (EQ-5D) scores and OHS recorded prospectively. Post-operative change in EQ-5D allowed calculation of a health-utility score, which, when combined with life expectancy, gave total QALYs gained. Results The mean age was 20 years (range 13.3-24.9), with 23 females (72.7%). Mean number of QALYs gained was 21.1 (95% CI 14.1-28.2). Total lifetime cost per patient was £14641, giving a mean cost per QALY of £4183 at 10 years post-operatively, and £694 over the total remaining lifetime. Discounting total QALYs gained at a rate of 3.5% and 5% per remaining year of life expectancy increased the mean cost per QALY to £1652 and £2187, respectively. Mean pre- and post-operative EQ-5D index were 0.27 (SD 0.27) and 0.63 (SD 0.29), respectively (p=0.0001). Mean pre-operative and post-operative OHS was 37.5 (SD 7.9) and 19.7 (SD 6.94), respectively (p<0.00001). Conclusion THA remains a cost-effective intervention for patients aged 25 years and under. It is also associated with significant improvement in HRQoL, OHS, and high levels of patient satisfaction in this unique patient group

Optimizing Posterior Condylar Offset and Joint Line Restoration in Revision Total Knee Arthroplasty Using a Contemporary Implant System

We present a variation of the standard operative technique for the Triathlon total stabilized revision knee system that aims to facilitate recreation of an anatomic joint line, and increase the posterior condylar offset through flexion and posterior translation of the femoral component using short cemented intramedullary stems. We illustrate the technique with a sequential single-surgeon series of 29 patients undergoing total stabilized revision total knee arthroplasty. Joint line ratio is maintained and posterior condylar offset ratio increased from preoperative to postoperatively. Patient reported outcome scores (Oxford Knee Score) significantly improved by 15.6 points at 12 months (P < 0.001) with an overall positive satisfaction outcome of 88%

Fifteen-year prospective longitudinal cohort study of outcomes following single radius total knee arthroplasty: patient reported outcome measures, response attrition and survival

AimsThis prospective study reports longitudinal, within-patient, patient-reported outcome measures (PROMs) over a 15-year period following cemented single radius total knee arthroplasty (TKA). Secondary aims included reporting PROMs trajectory, 15-year implant survival, and patient attrition from follow-up.MethodsFrom 2006 to 2007, 462 consecutive cemented cruciate-retaining Triathlon TKAs were implanted in 426 patients (mean age 69 years (21 to 89); 290 (62.7%) female). PROMs (12-item Short Form Survey (SF-12), Oxford Knee Score (OKS), and satisfaction) were assessed preoperatively and at one, five, ten, and 15 years. Kaplan-Meier survival and univariate analysis were performed.ResultsAt 15 years, 28 patients were lost to follow-up (6.1%) and 221 patients (51.9%) had died, with the mean age of the remaining cohort reducing by four years. PROMs response rates among surviving patients were: one-year 63%; five-year 72%; ten-year 94%; and 15-year 59%. OKS and SF-12 scores changed significantly over 15 years (p &lt; 0.001). The mean improvement in OKS was 18.8 (95% confidence (CI) 16.7 to 19.0) at one year. OKS peaked at five years (median 43 years) declining thereafter (p &lt; 0.001), though at 15 years it remained 17.5 better than preoperatively. Age and sex did not alter this trajectory. A quarter of patients experienced a clinically significant decline (≥ 7) in OKS from five to ten years and from ten to 15 years. The SF-12 physical component score displayed a similar trajectory, peaking at one year (p &lt; 0.001). Patient satisfaction was 88% at one, five, and ten years, and 94% at 15 years. In all, 15-year Kaplan-Meier survival was 97.6% (95% CI 96.0% to 99.2%) for any revision, and 98.9% (95% CI 97.9% to 99.9%) for aseptic revision.ConclusionImprovements in PROMs were significant and maintained following single radius TKA, with OKS peaking at five years, and generic physical health peaking at one year. Patient satisfaction remained high at 15 years, at which point 2.4% had been revise

Programmatic Evaluation of a Combined Antigen and Antibody Test for Rapid HIV Diagnosis in a Community and Sexual Health Clinic Screening Programme

Background A substantial proportion of HIV-infected individuals in the UK are unaware of their status and late presentations continue, especially in low prevalence areas. Fourth generation antigen/antibody rapid test kits could facilitate earlier diagnosis of HIV in non-clinical settings but lack data on performance under programmatic conditions. Methods and Findings We evaluated the performance of Determine HIV-1/2 Ag/Ab Combo Test (Determine Combo), a rapid test with indicators for both HIV antibodies and p24 antigen, in participants recruited from community outreach and hospital-based sexual health clinics. HIV infection was confirmed using laboratory enzyme-linked immunosorbent assay (EIA), Line Immuno Assay (LIA) and quantitative polymerase chain reaction (PCR). In total, 953 people underwent HIV testing. HIV antibody (Ab) prevalence was 1.8% (17/953). Four false positive rapid tests were identified: two antibody and two p24 antigen (Ag) reactions. Of participants diagnosed as HIV Ab positive, 2/17 (12%) were recent seroconverters based on clinical history and HIV antibody avidity test results. However, none of these were detected by the p24 antigen component of the rapid test kit. There were no other true positive p24 Ag tests. Conclusion These data lend support to an increasing body of evidence suggesting that 4th generation rapid HIV tests have little additional benefit over 3rd generation HIV kits for routine screening in low prevalence settings and have high rates of false positives. In order to optimally combine community-based case-finding among hard-to-reach groups with reliable and early diagnosis 3rd generation kits should be primarily used with laboratory testing of individuals thought to be at risk of acute HIV infection. A more reliable point of care diagnostic is required for the accurate detection of acute HIV infection under programmatic conditions

Reduction in patient outcomes but implant-derived preservation of function following total knee arthroplasty: longitudinal follow-up of a randomized controlled trial

AimsThere are comparatively few randomized studies evaluating knee arthroplasty prostheses, and fewer still that report longer-term functional outcomes. The aim of this study was to evaluate mid-term outcomes of an existing implant trial cohort to document changing patient function over time following total knee arthroplasty using longitudinal analytical techniques and to determine whether implant design chosen at time of surgery influenced these outcomes.MethodsA mid-term follow-up of the remaining 125 patients from a randomized cohort of total knee arthroplasty patients (initially comprising 212 recruited patients), comparing modern (Triathlon) and traditional (Kinemax) prostheses was undertaken. Functional outcomes were assessed with the Oxford Knee Score (OKS), knee range of movement, pain numerical rating scales, lower limb power output, timed functional assessment battery, and satisfaction survey. Data were linked to earlier assessment timepoints, and analyzed by repeated measures analysis of variance (ANOVA) mixed models, incorporating longitudinal change over all assessment timepoints.ResultsThe mean follow-up of the 125 patients was 8.12 years (7.3 to 9.4). There was a reduction in all assessment parameters relative to earlier assessments. Longitudinal models highlight changes over time in all parameters and demonstrate large effect sizes. Significant between-group differences were seen in measures of knee flexion (medium-effect size), lower limb power output (large-effect size), and report of worst daily pain experienced (large-effect size) favouring the Triathlon group. No longitudinal between-group differences were observed in mean OKS, average daily pain report, or timed performance test. Satisfaction with outcome in surviving patients at eight years was 90.5% (57/63) in the Triathlon group and 82.8% (48/58) in the Kinemax group, with no statistical difference between groups (p = 0.321).ConclusionAt a mean 8.12 years, this mid-term follow-up of a randomized controlled trial cohort highlights a general reduction in measures of patient function with patient age and follow-up duration, and a comparative preservation of function based on implant received at time of surgery

Induction of IgG3 to LPS via Toll-Like Receptor 4 Co-Stimulation

B-cells integrate antigen-specific signals transduced via the B-cell receptor (BCR) and antigen non-specific co-stimulatory signals provided by cytokines and CD40 ligation in order to produce IgG antibodies. Toll-like receptors (TLRs) also provide co-stimulation, but the requirement for TLRs to generate T-cell independent and T-cell dependent antigen specific antibody responses is debated. Little is known about the role of B-cell expressed TLRs in inducing antigen-specific antibodies to antigens that also activate TLR signaling. We found that mice lacking functional TLR4 or its adaptor molecule MyD88 harbored significantly less IgG3 natural antibodies to LPS, and required higher amounts of LPS to induce anti-LPS IgG3. In vitro, BCR and TLR4 signaling synergized, lowering the threshold for production of T-cell independent IgG3 and IL-10. Moreover, BCR and TLR4 directly associate through the transmembrane domain of TLR4. Thus, in vivo, BCR/TLR synergism could facilitate the induction of IgG3 antibodies against microbial antigens that engage both innate and adaptive B-cell receptors. Vaccines might exploit BCR/TLR synergism to rapidly induce antigen-specific antibodies before significant T-cell responses arise

Mechanisms of T cell organotropism

F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation