The Relationship Between Polyethylene Wear and Periprosthetic Osteolysis in Total Hip Arthroplasty at 12 Years in a Randomized Controlled Trial Cohort.

BACKGROUND: Polyethylene acetabular components are common in hip arthroplasty. Highly cross-linked polyethylene (HXLPE) has lower wear than ultra-high molecular weight polyethylene (UHMWPE). Evidence suggests that wear particles induce inflammation causing periprosthetic osteolysis contributing to implant loosening with wear rates of 0.05 mm/y were considered safe. We aimed to compare incidence and volume of periacetabular osteolysis between HXLPE and UHMWPE using computed tomography. METHODS: Initially, 54 hips in 53 patients were randomized to HXLPE or UHMWPE acetabular liner. At 10 years, 39 hips in 38 patients remained for the radiostereometric analysis' demonstrating significantly lower wear in the HXLPE group. At 12 years, 14 hips in 13 patients were lost to follow-up leaving 25 hips for computed tomography assessment. Images were reconstructed to detect osteolysis and where identified, areas were segmented and volumized. RESULTS: Osteolysis was observed in 8 patients, 7 from the UHMWPE group and only 1 from the HXLPE group (Fisher exact, P = .042). There was no correlation between the amount of polyethylene wear and osteolysis volume; however, the radiostereometric analysis-measured wear rate in patients with osteolysis from both groups was significantly higher than overall average wear rate. CONCLUSION: This data demonstrates lower incidence of periacetabular osteolysis in the HXLPE group of a small cohort. Although numbers are too low to estimate causation, in the context of lower wear in the HXLPE group, this finding supports the hypothesis that HXLPE may not elevate osteolysis risk, and hence does not suggest that HXLPE wear particles are more biologically active than those generated by earlier generations of polyethylene.

Controlling Inputter Variability in Vignette Studies Assessing Web-Based Symptom Checkers: Evaluation of Current Practice and Recommendations for Isolated Accuracy Metrics.

BACKGROUND: The rapid growth of web-based symptom checkers (SCs) is not matched by advances in quality assurance. Currently, there are no widely accepted criteria assessing SCs' performance. Vignette studies are widely used to evaluate SCs, measuring the accuracy of outcome. Accuracy behaves as a composite metric as it is affected by a number of individual SC- and tester-dependent factors. In contrast to clinical studies, vignette studies have a small number of testers. Hence, measuring accuracy alone in vignette studies may not provide a reliable assessment of performance due to tester variability. OBJECTIVE: This study aims to investigate the impact of tester variability on the accuracy of outcome of SCs, using clinical vignettes. It further aims to investigate the feasibility of measuring isolated aspects of performance. METHODS: Healthily's SC was assessed using 114 vignettes by 3 groups of 3 testers who processed vignettes with different instructions: free interpretation of vignettes (free testers), specified chief complaints (partially free testers), and specified chief complaints with strict instruction for answering additional symptoms (restricted testers). κ statistics were calculated to assess agreement of top outcome condition and recommended triage. Crude and adjusted accuracy was measured against a gold standard. Adjusted accuracy was calculated using only results of consultations identical to the vignette, following a review and selection process. A feasibility study for assessing symptom comprehension of SCs was performed using different variations of 51 chief complaints across 3 SCs. RESULTS: Intertester agreement of most likely condition and triage was, respectively, 0.49 and 0.51 for the free tester group, 0.66 and 0.66 for the partially free group, and 0.72 and 0.71 for the restricted group. For the restricted group, accuracy ranged from 43.9% to 57% for individual testers, averaging 50.6% (SD 5.35%). Adjusted accuracy was 56.1%. Assessing symptom comprehension was feasible for all 3 SCs. Comprehension scores ranged from 52.9% and 68%. CONCLUSIONS: We demonstrated that by improving standardization of the vignette testing process, there is a significant improvement in the agreement of outcome between testers. However, significant variability remained due to uncontrollable tester-dependent factors, reflected by varying outcome accuracy. Tester-dependent factors, combined with a small number of testers, limit the reliability and generalizability of outcome accuracy when used as a composite measure in vignette studies. Measuring and reporting different aspects of SC performance in isolation provides a more reliable assessment of SC performance. We developed an adjusted accuracy measure using a review and selection process to assess data algorithm quality. In addition, we demonstrated that symptom comprehension with different input methods can be feasibly compared. Future studies reporting accuracy need to apply vignette testing standardization and isolated metrics.

Risk factors associated with poor pain outcomes following primary knee replacement surgery: Analysis of data from the clinical practice research datalink, hospital episode statistics and patient reported outcomes as part of the STAR research programme.

OBJECTIVE: Identify risk factors for poor pain outcomes six months after primary knee replacement surgery. METHODS: Observational cohort study on patients receiving primary knee replacement from the UK Clinical Practice Research Datalink, Hospital Episode Statistics and Patient Reported Outcomes. A wide range of variables routinely collected in primary and secondary care were identified as potential predictors of worsening or only minor improvement in pain, based on the Oxford Knee Score pain subscale. Results are presented as relative risk ratios and adjusted risk differences (ARD) by fitting a generalized linear model with a binomial error structure and log link function. RESULTS: Information was available for 4,750 patients from 2009 to 2016, with a mean age of 69, of whom 56.1% were female. 10.4% of patients had poor pain outcomes. The strongest effects were seen for pre-operative factors: mild knee pain symptoms at the time of surgery (ARD 18.2% (95% Confidence Interval 13.6, 22.8), smoking 12.0% (95% CI:7.3, 16.6), living in the most deprived areas 5.6% (95% CI:2.3, 9.0) and obesity class II 6.3% (95% CI:3.0, 9.7). Important risk factors with more moderate effects included a history of previous knee arthroscopy surgery 4.6% (95% CI:2.5, 6.6), and use of opioids 3.4% (95% CI:1.4, 5.3) within three months after surgery. Those patients with worsening pain state change had more complications by 3 months (11.8% among those in a worse pain state vs. 2.7% with the same pain state). CONCLUSIONS: We quantified the relative importance of individual risk factors including mild pre-operative pain, smoking, deprivation, obesity and opioid use in terms of the absolute proportions of patients achieving poor pain outcomes. These findings will support development of interventions to reduce the numbers of patients who have poor pain outcomes.

The Avon Patellofemoral Joint Replacement: Mid-Term Prospective Results from an Independent Centre.

BACKGROUND: Approximately 10% of patients with osteoarthritis (OA) of the knee have unicompartmental OA confined to the patellofemoral joint (PFJ). The main surgical options are total knee replacement (TKR) and PFJ replacement (PFJR). PFJR has a number of advantages over TKR, including being less invasive, preserving the unaffected parts of the knee, allowing faster recovery and better range of motion and function. We report our prospective mid-term results of the Avon PFJR for established isolated PFJ arthritis in 61 consecutive procedures. METHODS: Sixty-one Avon PFJRs were performed in 57 patients. The outcome measures were the new Oxford knee score (OKS), Hungerford and Kenna score (HKS), and Crosby Insall knee scores. Only patients with severe isolated PFJ OA were included. The diagnosis was based on a combination of clinical, radiological and, where available, arthroscopic findings. RESULTS: Mean follow-up was 5.09 years (range, 12 to 124 years). There were 2 revisions in the first 5 years. The median HKS score was 80 (interquartile range, 70 to 95) and the mean OKS was 31.8 (± standard deviation, 8.7) at 5 years. These were significantly better (p < 0.001) than the preoperative scores. CONCLUSIONS: The Avon prosthesis gives good functional outcomes in the medium term and survives well. Our data support other studies in the literature and is the largest independent prospective study to date.

Expression, localisation and functional activation of NFAT-2 in normal human skin, psoriasis, and cultured keratocytes.

Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis. The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). As calcineurin and NFAT 1 have been shown to be functionally active in cultured human keratocytes, expression of other NFAT family members such as NFAT-2 and possible functional activation was investigated in human keratocytes. RT-PCR and Western Analysis were used to investigate the presence of NFAT-2 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-2 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-2 localisation in these biopsies using a well characterized anti-NFAT-2 antibody. The NFAT-2 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. Moreover, the expression of NFAT-2 in normal skin, non-lesional and lesional psoriasis showed a striking basal staining suggesting a role for NFAT-2 in keratocytes proliferation. A range of cell types in the skin express NFAT-2. The expression of NFAT-2 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. In these experiments the author assessed the expression, localization of NFAT-2 in cultured human keratocytes and measured the degree of nuclear localisaion of NFAT-2 using immunofluorescence and confocal microscopy and whether CsA and tacrolimus inhibit NFAT-2 nuclear translocation. As with NFAT 1, differentiation-promoting agents that increase intracellular calcium concentration induced nuclear translocation of NFAT-2 in cultured keratocytes but with different kinetics. These data provide the first evidence of that NFAT-2 is expressed in normal skin, psoriasis and that NFAT-2 functionally active in human keratocytes and that nuclear translocation of NFAT-2 in human skin cells has different kinetics than NFAT 1 suggesting that NFAT-2 may play an important role in regulation of keratocytes proliferation and differentiation at a different stage. Inhibition of this pathway in human epidermal keratocytes many account, in part for the therapeutic effects of CsA and tacrolimus in skin disorders such as psoriasis. Thus, supporting our previous work data that calcineurin/NFAT is functionally active not only in T cells, but in skin cells.