A Systematic Review of the Quality of Clinical Practice Guidelines for Chronic Limb-Threatening Ischemia.

BACKGROUND: To assess the quality of clinical practice guidelines (CPGs) for chronic limb-threatening ischemia (CLTI) using the Appraisal of Guidelines for Research and Evaluation II instrument. METHODS: A systematic review of Medline, Embase, and online CPG databases was carried out. Four CPGs on CLTI were identified: Global Vascular Guidelines (GVG), European Society of Cardiology (ESC), American College of Cardiology, and National Institute for Health and Care Excellence guidelines on lower limb peripheral arterial disease. Two independent appraisers analyzed the 4 CPGs using the Appraisal of Guidelines for Research and Evaluation II instrument. CPGs were ranked across 6 domains with 23 items that ranged from 1 (strongly disagree) to 7 (strongly agree). A scaled domain score was calculated as a percentage of the maximum possible score achievable. A domain score of ≥50% and an overall average domain score of ≥80% reflected a CPG of adequate quality recommended for use. RESULTS: GVG had the highest overall score (82.9%), as an average of all domains, and ESC had the lowest score (50.2%). GVG and National Institute for Health and Care Excellence guidelines had all domains scoring >50%, while American College of Cardiology had 5 and ESC had 3. Two domains, rigor of development and applicability, scored the lowest among the CPGs. There was a lack of detail in describing systematic methods used in the literature review, how guidelines were formulated with minimal bias, and the planned procedure for updating the guidelines. Implications of guideline application and monitoring of outcomes after implementations were not explicitly discussed. CONCLUSIONS: The GVG guideline published in 2019 discussing CLTI is assessed to be of high quality and recommended for use. This review helps to improve clinical decision-making and quality of future CPGs for CLTI.

Association Between Pharmacologic Treatment of Depression and Patient-Reported Outcomes Following Total Hip and Knee Arthroplasty.

BACKGROUND: Depression is associated with inferior outcomes following hip or knee arthroplasty, though it remains unclear if this relationship is modifiable. This study examined the association between pharmacologic treatment of depression and patient-reported outcomes. METHODS: This retrospective cohort study of 1,651 total hip arthroplasty (THA) and 1,792 total knee arthroplasty (TKA) procedures between October 2012 and June 2019 used institutional registry data linked to nationwide pharmaceutical claims. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, with pain and function subscales assessed as secondary outcomes. The TKA and THA patients were analyzed separately via mixed-effect linear regression to compare patients who had depression treated with antidepressants (TKA, n = 210; THA, n = 150) to those who had untreated depression (TKA, n = 43; THA; n = 50), and those who did not have depression (TKA, n = 1,539; THA, n = 1,451). RESULTS: Among patients who had depression, not receiving preoperative antidepressant therapy was associated with smaller improvements in WOMAC global scores (TKA, adjusted mean difference [MD]: -13.1 points, 95% CI [confidence interval]: -21.4 to -4.8; THA, MD: -8.5 points, 95% CI: -15.7 to -1.2) at 2 years after surgery, but not at 1 year (TKA, MD: -5.4 points, 95% CI: -12.9 to 2.1; THA, MD: -6.3 points, 95% CI: -12.9 to 0.3). Those who did not have depression had similar improvements in WOMAC global scores to those who had treated depression at both one (TKA, MD: 0.8 points, 95% CI: -2.7 to 4.4; THA, MD: 1.8 points, 95% CI: -1.8 to 5.4) and 2 years (TKA, MD: -1.1 points, 95% CI: -4.9 to 2.7; THA, MD: -1.6 points, 95% CI: -5.6 to 2.3). The findings were consistent with secondary outcomes. CONCLUSIONS: Among patients who have depression, antidepressant therapy before TKA or THA is associated with improved outcomes. Additional studies are needed to establish the impact of interventions to address untreated depression before surgery.

Penetration of Vancomycin into Noninfected Bone in Patients Undergoing Total Joint Arthroplasty Evaluated by a Minimal Physiologically Based Population Pharmacokinetic Modeling Approach.

Arthroplasty is a healthcare priority and represents high volume, high cost surgery. Periprosthetic joint infection (PJI) results in significant mortality, thus it is vital that the risk for PJI is minimized. Vancomycin is recommended for surgical prophylaxis in total joint arthroplasty (TJA) by current clinical practice guidelines endorsed by the Infectious Diseases Society of America. This study aimed to develop a new assay to determine vancomycin concentrations in serum and bone, and a minimal physiologically based population PK (mPBPK) model to evaluate vancomycin bone penetration in noninfected patients. Eleven patients undergoing TJA received 0.5-2.0 g intravenous vancomycin over 12-150 min before surgery. Excised bone specimens and four blood samples were collected per patient. Bone samples were pulverized under liquid nitrogen using a cryogenic mill. Vancomycin concentrations in serum and bone were analyzed by liquid chromatography-tandem mass spectrometry and subjected to mPBPK modeling. Vancomycin serum and bone concentrations ranged from 9.30 to 86.6 mg/L, and 1.94-37.0 mg/L, respectively. Average bone to serum concentration ratio was 0.41 (0.16-1.0) based on the collected samples. The population mean total body clearance was 2.12L/h/kg0.75. Inclusion of total body weight as a covariate substantially decreased interindividual variability in clearance. The bone/blood partition coefficient (Kpbone) was estimated at 0.635, reflecting the average bone/blood concentration ratio at steady-state. The model predicted median ratio of vancomycin area under the curve (AUC) for bone/AUC for serum was 44%. Observed vancomycin concentrations in bone were overall consistent with perfusion-limited distribution from blood to bone. An mPBPK model overall well described vancomycin concentrations in serum and bone.

The long-term impacts of opioid use before and after joint arthroplasty: matched cohort analysis of New Zealand linked register data.

BACKGROUND: Opioids are commonly used both before and after total joint arthroplasty (TJA). OBJECTIVE: The objective of this study was to estimate the long-term effects of pre- and perioperative opioid use in patients undergoing TJA. METHODS: We used linked population datasets to identify all (n =18,666) patients who had a publicly funded TJA in New Zealand between 2011 and 2013. We used propensity score matching to match individuals who used opioids either before surgery, during hospital stay, or immediately post-discharge with individuals who did not based on a comprehensive set of covariates. Regression analysis was used to estimate the effect of opioid use on health and socio-economic outcomes over 5 years. RESULTS: Opioid use in the 3 months prior to surgery was associated with significant increases in healthcare utilization and costs (number of hospitalizations 6%, days spent in hospital 14.4%, opioid scripts dispensed 181%, and total healthcare costs 11%). Also increased were the rate of receiving social benefits (2 percentage points) and the rates of opioid overdose (0.5 percentage points) and mortality (3 percentage points). Opioid use during hospital stay or post-discharge was associated with increased long-term opioid use, but there was little evidence of other adverse effects. CONCLUSIONS: Opioid use before TJA is associated with significant negative health and economic consequences and should be limited. This has implications for opioid prescribing in primary care. There is little evidence that peri- or post-operative opioid use is associated with significant long-term detriments.

Opioids are commonly used both before and after total joint replacement surgery to manage pain in patients with osteoarthritis. This study investigates the long-term consequences of opioid use around total joint replacement surgery in New Zealand during 2011­2013 using administrative data. We compare the outcomes of surgery patients who used opioids (treatment group) to those who did not (control group) but who had very similar pre-surgery characteristics as the treatment cohort. We find that opioid use in the months prior to surgery was associated with significant increases in healthcare utilization and costs, higher likelihood of receiving social benefits, and higher risk of opioid overdose and mortality 5 years post-surgery. Opioid use during hospital stay or post-discharge was associated with increased long-term opioid use, but there was little evidence of other adverse effects. These results highlight the importance of ongoing efforts to reduce opioid use before surgery.

Patients' Views on AI for Risk Prediction in Shared Decision-Making for Knee Replacement Surgery: Qualitative Interview Study.

BACKGROUND: The use of artificial intelligence (AI) in decision-making around knee replacement surgery is increasing, and this technology holds promise to improve the prediction of patient outcomes. Ambiguity surrounds the definition of AI, and there are mixed views on its application in clinical settings. OBJECTIVE: In this study, we aimed to explore the understanding and attitudes of patients who underwent knee replacement surgery regarding AI in the context of risk prediction for shared clinical decision-making. METHODS: This qualitative study involved patients who underwent knee replacement surgery at a tertiary referral center for joint replacement surgery. The participants were selected based on their age and sex. Semistructured interviews explored the participants' understanding of AI and their opinions on its use in shared clinical decision-making. Data collection and reflexive thematic analyses were conducted concurrently. Recruitment continued until thematic saturation was achieved. RESULTS: Thematic saturation was achieved with 19 interviews and confirmed with 1 additional interview, resulting in 20 participants being interviewed (female participants: n=11, 55%; male participants: n=9, 45%; median age: 66 years). A total of 11 (55%) participants had a substantial postoperative complication. Three themes captured the participants' understanding of AI and their perceptions of its use in shared clinical decision-making. The theme Expectations captured the participants' views of themselves as individuals with the right to self-determination as they sought therapeutic solutions tailored to their circumstances, needs, and desires, including whether to use AI at all. The theme Empowerment highlighted the potential of AI to enable patients to develop realistic expectations and equip them with personalized risk information to discuss in shared decision-making conversations with the surgeon. The theme Partnership captured the importance of symbiosis between AI and clinicians because AI has varied levels of interpretability and understanding of human emotions and empathy. CONCLUSIONS: Patients who underwent knee replacement surgery in this study had varied levels of familiarity with AI and diverse conceptualizations of its definitions and capabilities. Educating patients about AI through nontechnical explanations and illustrative scenarios could help inform their decision to use it for risk prediction in the shared decision-making process with their surgeon. These findings could be used in the process of developing a questionnaire to ascertain the views of patients undergoing knee replacement surgery on the acceptability of AI in shared clinical decision-making. Future work could investigate the accuracy of this patient group's understanding of AI, beyond their familiarity with it, and how this influences their acceptance of its use. Surgeons may play a key role in finding a place for AI in the clinical setting as the uptake of this technology in health care continues to grow.

Assessing the Mortality Rate After Primary Total Knee Arthroplasty: An Observational Study to Inform Future Economic Analysis.

BACKGROUND: Previous research has focused on the perioperative or short-term (<1 year) mortality rate of total knee arthroplasty (TKA), leaving the long-term (>1 year) mortality rate unresolved. In this study, we calculated the mortality rate up to 15 years after primary TKA. METHODS: Data from the New Zealand Joint Registry from April 1998 to December 2021 were analyzed. Patients aged 45 years or older who underwent TKA for osteoarthritis were included. Mortality data were linked with national records from births, deaths, and marriages. To determine the expected mortality rates in the general population, age-sex-specific life tables from statistics New Zealand were used. Mortality rate was presented as standardized mortality ratios (SMRs) - a comparison of relative mortality rate between the TKA and general populations. In total, 98,156 patients with a median follow-up of 7.25 years (range, 0.00 to 23.74) were included. RESULTS: Over the entire follow-up period, 22,938 patients (23.4%) had died. The overall SMR for the TKA cohort was 1.08 (95% confidence interval (CI): 1.06 to 1.09), suggesting that TKA patients have an 8% higher mortality rate compared to the general population. However, a reduction in short-term mortality rate was observed for TKA patients up to 5 years post TKA (SMR 5 years post TKA; 0.59 95% CI: 0.57 to 0.60]). On the contrary, a significantly increased long-term mortality rate was observed in TKA patients with greater than 11 years of follow-up, particularly in men over the age of 75 years (SMR 11 to 15 years post TKA for males ≥ 75 years; 3.13 [95% CI: 2.95 to 3.31]). CONCLUSION: The results suggest a reduction in short-term mortality rate for patients who undergo primary TKA. However, there is an increased long-term mortality rate particularly in men over the age of 75 years. Importantly, the mortality rates observed in this study cannot be causally attributed to TKA alone.

Differences in Outcomes Between Initial Responders and Subsequent Responders to Health Questionnaires for Total Hip and Knee Arthroplasty: An Australian Tertiary Institutional Registry Study.

BACKGROUND: Patient-reported outcome measure (PROM) questionnaires in national arthroplasty registries often have low response rates leading to questions about data reliability. In Australia, the SMART (St. Vincent's Melbourne Arthroplasty Outcomes) registry captures all elective total hip (THA) and total knee (TKA) arthroplasty patients with an approximate 98% response rate for preoperative and 12-month PROM scores. This high response rate is due to dedicated registry staff following up patients who do not initially respond (subsequent responders). This study compared initial responders to subsequent responders to find differences in 12-month PROM outcomes for THA and TKA. METHODS: All elective THA and TKA patients for osteoarthritis from 2012 to 2021 captured by the SMART registry were included. In total, 1,333 THA and 1,340 TKA patients were included. The PROM scores were assessed using the Veterans-RAND 12 (VR12) and Western Ontario and McMasters Universities Arthritis Index (WOMAC) questionnaires. The primary outcome was differences in mean 12-month PROM scores between initial and subsequent responders. RESULTS: Baseline characteristics and PROM scores were similar between initial and subsequent responders. However, 12-month PROM scores varied significantly. The adjusted mean difference showed that for the WOMAC pain score, subsequent responders scored 3.4 points higher in the THA cohort and 7.4 points higher in the TKA cohort compared to initial responders. Significant differences were also found in other WOMAC and VR12 scores for both THA and TKA cohorts at the 12-month timepoint. CONCLUSION: This study found that significant differences in PROM outcomes postsurgery occurred in THA and TKA patients based on response to PROM questionnaires, suggesting that loss to follow-up in PROM outcomes should not be treated as missing completely at random (MCAR).

Reduction in Offset Is Associated With Worse Functional Outcomes Following Total Hip Arthroplasty.

BACKGROUND: Conflicting reports exist about the effect of offset variation on functional outcomes following total hip arthroplasty. Reproducing native hip offset is thought to optimize function by restoring biomechanics and appropriately tensioning the hip abductor muscles. The aim of this study is to assess the effect of failing to restore global hip offset in comparison to the native contralateral hip. METHODS: A retrospective analysis of a prospective patient cohort was performed on patients undergoing an elective primary total hip arthroplasty. A total of 414 patients who had a minimum of 12 months of follow-up were included. Postoperative plain radiographs were analyzed for offset and compared to the contralateral native hip. Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Veterans RAND 12 (VR-12) scores were assessed preoperatively and at 12 months postoperatively. RESULTS: Regression analyses indicated that a reduction in offset of >20 mm resulted in worse WOMAC pain (P = .005) and motion (P = .015) scores compared to those with maintained offset. WOMAC function (P = .063), global (P = .025), and VR-12 scores were not affected (physical P = .656; mental P = .815). Reduction in offset up to 20 mm and increased offset were not significantly associated with patient-reported outcome measures (P-values ranged from .102 to .995). CONCLUSION: This study demonstrated an association between reduction in offset by >20 mm and worse WOMAC pain and motion scores following total hip arthroplasty. Surgeons should avoid decreases in offset >20 mm in order to optimize functional outcomes.

Measuring Quality of Life in Chronic Limb-threatening Ischemia Patients and Informal Carers: A Scoping Review.

OBJECTIVE: To review quality of life (QOL) instruments for chronic limb-threatening ischemia (CLTI) patients and informal carers, and their use in QOL and cost-utility analysis (CUA) studies. BACKGROUND: CLTI is a global health problem with significant morbidity affecting patients and informal carers. QOL is increasingly measured for holistic outcomes assessment and CUA. However, measurement instruments in CLTI are poorly understood. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, COSMIN, PROQOLID, CEA registry, and NHS EED databases were searched for all English language studies up to May 2021. Features of instruments, evidence of measurement property appraisal, and trends in use were assessed. Prospective protocol registration (Open Science Framework: https://doi.org/10.17605/OSF.IO/KNG9U ). RESULTS: A total of 146 studies on QOL instruments (n=43), QOL outcomes (n=97), and CUA (n=9) were included. Four disease-specific QOL instruments are available for lower extremity arterial disease (intermittent claudication or CLTI). VascuQoL-25 and VascuQoL-6 have been used in CLTI. There is no CLTI-specific instrument. Of 14 generic instruments, SF-36, EQ-5D-3L, NHP, and WHOQOL-BREF were most common. Studies reporting partial measurement property appraisal favored VascuQoL-25, VascuQoL-6, and SF-36. Feasibility considerations include mode of administration and responder burden. None of 4 available carer-specific instruments have been used in CLTI. Since 1992, the number of QOL studies has increased considerably, but CUA studies are scarce. Informal carers have not been assessed. CONCLUSIONS: This review provides a comprehensive reference for QOL measurement in CLTI that helps end-users with instrument selection, use, and interpretation. However, a CLTI-specific instrument is needed. There is an opportunity to benefit society through future CUA studies and evaluation of QOL in informal carers.

Quality of Life in Chronic Limb Threatening Ischaemia: Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the comparative effectiveness and temporal changes in quality of life (QoL) outcomes after revascularisation, major lower extremity amputation (MLEA), and conservative management (CM) in chronic limb threatening ischaemia (CLTI). DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. REVIEW METHODS: A systematic review and meta-analysis were performed on QoL measured by any QoL instrument in adult patients with CLTI after open surgery (OS), endovascular intervention (EVI), MLEA, or CM. Randomised controlled trials and prospective observational studies published in any language between 1 January 1990 and 21 May 2021 were included. There was a pre-specified measurement time point of six months. Random effects meta-analysis was conducted on total scores for each QoL instrument. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach (PROSPERO registration: CRD42021253953). RESULTS: Fifty-five studies with 8 909 patients were included. There was significant heterogeneity in the methods used to measure QoL, and the study characteristics. In particular, 14 different QoL instruments were used with various combinations of disease specific and generic instruments within each study. A narrative summary is therefore presented. Comparative effectiveness data showed there was reasonable certainty that QoL was similar between OS and EVI at six months. Temporal outcomes suggested small to moderate improvements in QOL six months after OS and EVI compared with baseline. Limited data indicated that QoL can be maintained or slightly improved after MLEA or CM. Treatment effects were overestimated owing to small study effects, selective non-reporting, attrition, and survivorship bias. CONCLUSION: QoL after OS and EVI appears to be similar. Revascularisation may provide modest QoL benefits, while MLEA or CM can maintain QoL. However, certainty of evidence is generally low or very low, and interpretation is hampered by significant heterogeneity. There is a need for a CLTI specific QoL instrument and methodological standardisation in QoL studies.

A Systematic Review of Cost-Utility Analyses in Chronic Limb-Threatening Ischemia.

BACKGROUND: To review and describe the available literature on cost-utility analysis of revascularization and non-revascularization treatment approaches in chronic limb-threatening ischemia. METHODS: A systematic review was performed on cost-utility analysis studies evaluating revascularization (open surgery or endovascular), major lower extremity amputation, or conservative management in adult chronic limb-threatening ischemia patients. Six bibliographic databases and online registries were searched for English language articles up to August 2021. The outcome for cost-utility analysis was quality-adjusted in life years. Procedures were compared using incremental cost-effectiveness ratios which were converted to 2021 United States dollars. Study reporting quality was assessed using the 2022 Consolidated Health Economic Evaluation Reporting Standards statement. The study was registered in International Prospective Register of Systematic Reviews (CRD42021273602). RESULTS: Three trial-based and five model-based studies were included for review. Studies met between 14/28 and 20/28 criteria of the Consolidated Health Economic Evaluation Reporting Standards CHEERS statement. Only one study was written according to standardized reporting guidelines. Most studies evaluated infrainguinal disease, and adopted a health care provider perspective. There was a large variation in the incremental cost-effectiveness ratios presented across studies. Open surgical revascularization (incremental cost-effectiveness ratios: $3,678, $58,828, and $72,937), endovascular revascularization (incremental cost-effectiveness ratios: $52,036, $125,329, and $149,123), and mixed open or endovascular revascularization (incremental cost-effectiveness ratio: $8,094) maybe more cost-effective than conservative management. CONCLUSIONS: The application of cost-utility analyses in chronic limb-threatening ischemia is in its infancy. Revascularization in infrainguinal disease may be favored over major lower extremity amputation or conservative management. However, data is inadequate to support recommendations for a specific treatment. This review identifies short and long-term considerations to address the current state of evidence. Cost-utility analysis is an important tool in healthcare policy and should be encouraged amongst the vascular surgical community.

A Review of Illness Perceptions in Chronic Limb-Threatening Ischemia: Current Knowledge Gaps and a Framework for Future Studies.

BACKGROUND: The aim of this study is to review illness perceptions (IPs) in chronic limb-threatening ischemia (CLTI) patients undergoing revascularization (open surgical or endovascular), major lower extremity amputation, or conservative management. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, WOS, and Scopus databases were searched from inception to August 20, 2021 for studies evaluating IP in CLTI according to Leventhal's common sense model (CSM). Since only 1 study was identified, a post hoc secondary literature search of MEDLINE was performed for reviews of IP in cardiovascular disease and diabetes to identify potential learning points for future research. All studies underwent narrative synthesis guided by tabulated data. RESULTS: One study and 7 reviews were included from the primary and secondary literature searches, respectively. Timeline and controllability were the main aspects of IP that predict prosthetic use in CLTI patients, more so at 6 months than 1 month. Other reviews in cardiovascular disease and diabetes identified important targets for future research: (1) factors that affect IP and whether IP can be used as an outcome measure, (2) relationship between IP and clinician-reported and patient-reported outcomes, and (3) methods to educate and change maladaptive IP. The importance of using valid and reliable measures of IP that encompass all components of Leventhal's' CSM was stressed. CONCLUSIONS: Knowledge of IP in CLTI patients is severely limited in contrast to other fields in cardiovascular disease and diabetes. This review helps to close this gap by raising awareness of IP and its importance within the vascular surgical community, and by providing a framework for future studies.

Evaluating willingness for surgery using the SMART Choice (Knee) patient prognostic tool for total knee arthroplasty: study protocol for a pragmatic randomised controlled trial.

BACKGROUND: Approximately 1 in 5 patients feel unsatisfied after total knee arthroplasty (TKA). Prognostic tools may aid in the patient selection process and reduce the proportion of patients who experience unsatisfactory surgery. This study uses the prognostic tool SMART Choice (Patient Prognostic Tool for Total Knee Arthroplasty) to predict patient improvement after TKA. The tool aims to be used by the patient without clinician input and does not require clinical data such as X-ray findings or blood results. The objective of this study is to evaluate the SMART Choice tool on patient decision making, particularly willingness for surgery. We hypothesise that the use of the SMART Choice tool will influence willingness to undergo surgery, especially when used earlier in the patient TKA journey. METHODS: This is a multicentred, pragmatic, randomised controlled trial conducted in Melbourne, Australia. Participants will be recruited from the St. Vincent's Hospital, Melbourne (SVHM) Orthopaedic Clinic, and the client base of HCF, Australia (private health insurance company). Patients over 45 years of age who have been diagnosed with knee osteoarthritis and considering TKA are eligible for participation. Participants will be randomised to either use the SMART Choice tool or treatment as usual. The SMART Choice tool provides users with a prediction for improvement or deterioration / no change after surgery based on utility score change calculated from the Veterans-RAND 12 (VR-12) survey. The primary outcome of the study is patient willingness for TKA surgery. The secondary outcomes include evaluating the optimal timing for tool use and using decision quality questionnaires to understand the patient experience when using the tool. Participants will be followed up for 6 months from the time of recruitment. DISCUSSION: The SMART Choice tool has the potential to improve patient decision making for TKA. Although many prognostic tools have been developed for other areas of surgery, most are confined within academic bodies of work. This study will be one of the first to evaluate the impact of a prognostic tool on patient decision making using a prospective clinical trial, an important step in transitioning the tool for use in clinical practice. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12622000072718 . Prospectively registered - 21 January 2022.

Low grade of radiographic osteoarthritis predicts unsatisfactory response of the contralateral knee replacement in two-stage bilateral total knee arthroplasty.

PURPOSE: It is difficult to counsel patients with bilateral osteoarthritis who are unsatisfied with their first knee replacement as to whether they are likely to have a better outcome after the contralateral knee is replaced. The purpose of this study was to determine whether predictive factors can be found to prognosticate outcome of the second-side knee replacement when a patient has an unsatisfactory response to the first, with the hypothesis that predictors, such as prosthetic factors and radiographic level of osteoarthritis, may be able to predict a satisfactory response to the contralateral knee replacement. MATERIALS AND METHODS: An analysis of staged bilateral knee replacements performed at a tertiary arthroplasty centre from 2012 to 2018 was undertaken. A total of 550 knee replacements in 275 patients were included in this study. The primary variable measured was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Satisfactory response to surgery was defined as a WOMAC score improved by 17 points or more, and 56 or greater. Patients who did not achieve a satisfactory response with their first knee replacement were further analysed for predictive factors (age, sex, pre-operative score, mental score, socioeconomic status, type of prosthesis, use of navigation, patella resurfacing and radiographic osteoarthritis) of an unsatisfactory response for their contralateral knee replacement. RESULTS: Overall, 44 (16%) patients failed to achieve a satisfactory response from both their first and contralateral knee replacements. The factor most predictive of an unsatisfactory response to their first knee replacement was pre-operative mental health score. However, in patients who did not achieve a satisfactory response with their first knee replacement, radiographic osteoarthritis, as measured by the Kellgren-Lawrence (KL) score was the main predictor of satisfactory response for their contralateral knee replacement. Only patients with KL grade 4 osteoarthritis were likely to have a satisfactory response with their contralateral knee replacements (KL4 versus KL3, Odds ratio 3.57 (CI 1.26-10.03) p = 0.016*). Patients with KL grade 3 osteoarthritis were unlikely to have a satisfactory response, and in this series, no patient with KL grade 2 osteoarthritis had a satisfactory response. CONCLUSION: In a patient who has an unsatisfactory response to their first knee replacement, the best predictor of achieving a satisfactory response to his/her contralateral knee replacement is the level of radiographic osteoarthritis in that knee. LEVEL OF EVIDENCE: IV: Retrospective Cohort study.

No Difference in Quality-Of-Life Outcomes in the First 7 Years Following Primary Total Knee Arthroplasty Performed Using Computer Navigation Versus Conventional Referencing: A Propensity Score-Matched Analysis.

BACKGROUND: Computer navigation techniques can potentially improve both the accuracy and precision of prosthesis implantation in total knee arthroplasty (TKA) but its impact on quality-of-life outcomes following surgery remains unestablished. METHODS: An institutional arthroplasty registry was queried to identify patients with TKA performed between January 1, 2007 and December 31, 2019. Propensity score matching based on demographical, medical, and surgical variables was used to match computer-navigated to conventionally referenced cases. The primary outcomes were Veterans RAND 12 Item Health Survey scores (VR-12 PCS and MCS), Short Form 6 Dimension utility values (SF-6D), and quality-adjusted life years (QALYs) in the first 7 years following surgery. RESULTS: A total of 629 computer-navigated TKAs were successfully matched to 1,351 conventional TKAs. The VR-12 PCS improved by a mean of 12.75 and 11.94 points in computer-navigated and conventional cases at 12-month follow-up (P = .25) and the VR-12 MCS by 6.91 and 5.93 points (P = .25), respectively. The mean VR-12 PCS improvement at 7-year follow-up (34.4% of the original matched cohort) for navigated and conventional cases was 13.00 and 12.92 points (P = .96) and for the VR-12 MCS was 4.83 and 6.30 points (P = .47), respectively. The mean improvement in the SF-6D utility score was 0.164 and 0.149 points at 12 months (P = .11) and at 7 years was 0.115 and 0.123 points (P = .69), respectively. Computer-navigated cases accumulated 0.809 QALYs in the first 7 years, compared to 0.875 QALYs in conventionally referenced cases (P = .65). There were no differences in these outcomes among a subgroup analysis of obese patients (body mass index ≥ 30 kg/m2). CONCLUSION: The use of computer navigation did not provide an incremental benefit to quality-of-life outcomes at a mean of 2.9 years following primary TKA performed for osteoarthritis when compared to conventional referencing techniques.

Patterns and Predictors of Outpatient Antibiotic Dispensation Following Total Hip and Knee Arthroplasty.

BACKGROUND: This study aimed to evaluate the month-to-month prevalence of antibiotic dispensation in the 12 months before and after total knee arthroplasty (TKA) and total hip arthroplasty (THA) and to identify factors associated with antibiotic dispensation in the month immediately following the surgical procedure. METHODS: In total, 4,115 THAs and TKAs performed between April 2013 and June 2019 from a state-wide arthroplasty referral center were analyzed. A cross-sectional study used data from an institutional arthroplasty registry, which was linked probabilistically to administrative dispensing data from the Australian Pharmaceutical Benefits Scheme. Multivariable logistic regression was carried out to identify patient and surgical risk factors for oral antibiotic dispensation. RESULTS: Oral antibiotics were dispensed in 18.3% of patients following primary TKA and 12.0% of patients following THA in the 30 days following discharge. During the year after discharge, 66.7% of TKA patients and 58.2% of THA patients were dispensed an antibiotic at some point. Patients with poor preoperative health status were more likely to have antibiotics dispensed in the month following THA or TKA. Older age, undergoing TKA rather than THA, obesity, inflammatory arthritis, and experiencing an in-hospital wound-related or other infectious complications were associated with increased antibiotic dispensation in the 30 days following discharge. CONCLUSION: A high rate of antibiotic dispensation in the 30 days following THA and TKA has been observed. Although resource constraints may limit routine wound review for all patients by a surgeon, a select cohort may benefit from timely specialist review postoperatively. Several risk factors identified in this study may aid in identifying appropriate candidates for such changes to follow-up care.

Placebo Surgery Controlled Trials: Do They Achieve What They Set Out To Do? A Systematic Review.

OBJECTIVE: To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual design aspects of trials identified through systematic review methods. SUMMARY BACKGROUND: Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns. METHODS: Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted "projected" design aspects from protocols and "actual" design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size ("completed") and were concluded in a timely fashion. Pairs of authors assessed risk of bias. RESULTS: Of 24 trials with data available to analyse; 3 were completed and concluded within target timeframe; 10 were completed and concluded outside the target timeline; 4 were completed without clear target timeframes; 2 were incomplete and concluded within the target framework; 5 were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%. CONCLUSIONS: Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors. REVIEW REGISTRATION: PROSPERO (CRD42019133296).

Circulating tumor DNA for malignant peripheral nerve sheath tumors in neurofibromatosis type 1.

PURPOSE: The leading cause of early death in patients with neurofibromatosis type 1 (NF1) is malignant peripheral nerve sheath tumor (MPNST). The principles of management include early diagnosis, surgical clearance and close monitoring for tumor recurrence. Current methods for diagnosis, detection of residual disease and monitoring tumor burden are inadequate, as clinical and radiological features are non-specific for malignancy in patients with multiple tumors and lack the sensitivity to identify early evidence of malignant transformation or tumor recurrence. Circulating tumor DNA (ctDNA) is a promising tool in cancer management and has the potential to improve the care of patients with NF1. In the following article we summarise the current understanding of the genomic landscape of MPNST, report on the previous literature of ctDNA in MPNST and outline the potential clinical applications for ctDNA in NF1 associated MPNST. Finally, we describe our prospective cohort study protocol investigating the utility of using ctDNA as an early diagnostic tool for MPNSTs in NF1 patients.

Characterising the immune microenvironment in liposarcoma, its impact on prognosis and the impact of radiotherapy.

BACKGROUND AND OBJECTIVES: Limited literature exists examining the immune microenvironment in liposarcoma, particularly with regard to the impact of radiotherapy. A major problem is the lack of scoring system for the tumour-infiltrating lymphocytes (TILs) in sarcoma. This study aims to describe the immune environment pre- and postradiotherapy and identify the optimal immune infiltrate scoring system for sarcoma. METHODS: Thirty-nine paired tissue samples (pre- and postradiotherapy) from patients with liposarcoma were scored by two pathologists for TILs using pre-existing systems (for breast cancer and melanoma) and compared for interobserver reliability. Immunohistochemical staining was performed for various immune markers. RESULTS: The TIL scoring system for breast cancer yielded perfect agreement (κ = 1.000). 21% of patients had increased TILs after radiotherapy, 87.5% of whom had dedifferentiated liposarcoma. Immune suppressor expression was increased frequently after radiotherapy (CD68 increased in 59.4%, PD-L1 increased in 25%). Immune effector expression (CD8) was unchanged in 84.4%. CONCLUSIONS: Breast cancer TIL scoring is reproducible in liposarcoma and has high interobserver reliability. Radiotherapy was observed to have a limited impact on immune effectors but seemed to have more impact in upregulating immune suppressors, suggesting radiotherapy may contribute to disease control through immunomodulatory effects. Dedifferentiated liposarcoma represents a uniquely responsive subtype.

How Do People Communicate About Knee Osteoarthritis? A Discourse Analysis.

OBJECTIVE: To explore the ways in which people talk about knee osteoarthritis and how this may influence engagement in physical activity and activity-based interventions as recommended by clinical practice guidelines. DESIGN: A qualitative synthesis using discourse analysis methods. METHODS: Systematic review methods were used to identify qualitative studies exploring the perceptions of people with knee osteoarthritis, their carers, and/or clinicians. Methodological quality was evaluated through the use of the Critical Appraisal Skills Programme. Raw quotes extracted from each study were analyzed with inductive discourse analysis. RESULTS: A search of five electronic databases from inception until August 2019 yielded 778 articles. Sixty-two articles from 56 studies were included, reporting data (1,673 direct quotes) from people with knee osteoarthritis, carers, and clinicians in 16 countries. Two overarching discourses were identified-impairment and participation. The overarching impairment discourse prevailed in all participant groups and study settings. In this discourse, knee osteoarthritis was likened to a machine that inevitably wore down over time and required a doctor to repair. The overarching participatory discourse almost always coexisted alongside an impairment discourse. According to this discourse, a "busy body" was perceived as "healthy," and people could remain active despite knee osteoarthritis. CONCLUSION: The prevailing impairment discourse may potentially discourage people from using knees that have passed their "use-by date" and increase reliance on doctors to repair joint damage. Consistent with recommendations in clinical practice guidelines, a participatory discourse may provide an alternative way of communicating that may encourage people with knee osteoarthritis to continue to engage in physical activity by focusing on what they can do, rather than what they cannot do.