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 sub-scales 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 two years after surgery, but not at one 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 two 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. CONCLUSION: 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.

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.

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.

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.

Assessing the suitability of general practice electronic health records for clinical prediction model development: a data quality assessment.

BACKGROUND: The use of general practice electronic health records (EHRs) for research purposes is in its infancy in Australia. Given these data were collected for clinical purposes, questions remain around data quality and whether these data are suitable for use in prediction model development. In this study we assess the quality of data recorded in 201,462 patient EHRs from 483 Australian general practices to determine its usefulness in the development of a clinical prediction model for total knee replacement (TKR) surgery in patients with osteoarthritis (OA). METHODS: Variables to be used in model development were assessed for completeness and plausibility. Accuracy for the outcome and competing risk were assessed through record level linkage with two gold standard national registries, Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and National Death Index (NDI). The validity of the EHR data was tested using participant characteristics from the 2014-15 Australian National Health Survey (NHS). RESULTS: There were substantial missing data for body mass index and weight gain between early adulthood and middle age. TKR and death were recorded with good accuracy, however, year of TKR, year of death and side of TKR were poorly recorded. Patient characteristics recorded in the EHR were comparable to participant characteristics from the NHS, except for OA medication and metastatic solid tumour. CONCLUSIONS: In this study, data relating to the outcome, competing risk and two predictors were unfit for prediction model development. This study highlights the need for more accurate and complete recording of patient data within EHRs if these data are to be used to develop clinical prediction models. Data linkage with other gold standard data sets/registries may in the meantime help overcome some of the current data quality challenges in general practice EHRs when developing prediction models.

Opioid Use and Total Joint Replacement.

PURPOSE OF REVIEW: We provide an overview of recent research into the relationship between preoperative opioid use and total joint replacement outcomes. RECENT FINDINGS: Recent findings indicate that total joint replacement patients with a history of preoperative opioid use experience higher rates of infection, revision, short-term complications, and prolonged postoperative opioid use, along with fewer improvements in pain and function following surgery. These risks are particularly pronounced among chronic opioid users. While the baseline risk profiles of these patients may contribute to higher rates of adverse outcomes, it is also plausible that certain outcomes are directly impacted by opioid use through mechanisms such as opioid-induced hyperalgesia and immunosuppression. There is little available data on the efficacy of interventions that aim to mitigate these risks. Well-designed clinical trials are needed to evaluate the efficacy of targeted perioperative interventions that aim to improve outcomes for this high-risk surgical population. Where such trials are not feasible, additional high-quality observational studies are necessary to further our understanding of the mechanisms underlying the relationships between opioid use and specific adverse outcomes.

Patient-reported outcome measures (PROMs): can they be used to guide patient-centered care and optimize outcomes in total knee replacement?

PURPOSE: As patient-reported outcome measures (PROMs) are increasingly integrated into clinical practice, there is a need to translate collected data into valuable information to guide and improve the quality and value of patient care. The purpose of this study was to investigate health-related quality-of-life (QoL) trajectories in the 5 years following total knee replacement (TKR) and the patient characteristics associated with these trajectories. The feasibility of translating QoL trajectories into valuable information for guiding patient-centered care was also explored. METHODS: Data on patients who underwent TKR between 2006 and 2011 from a single-institution registry were extracted including patient-reported QoL (captured using the Short Form Survey (SF-12) instrument) up to 5 years post-surgery. QoL trajectories were modelled using latent class growth analysis. Quality-adjusted life-years (QALYs) were calculated to illustrate longer term health benefit. Multinomial logistic regression analyses were performed to examine the association between trajectory groups and baseline patient characteristics. RESULTS: After exclusions, 1553 patients out of 1892 were included in the analysis. Six unique QoL trajectories were identified; with differing levels at baseline and improvement patterns post-surgery. Only 18.4% of patients were identified to be in the most positive QoL trajectory (low baseline, large sustainable improvement after surgery) associated with the greatest gain in QALY. These patients were likely to be younger, have no co-morbidities and report greater pain at pre-surgery than most in other QoL trajectories. CONCLUSIONS: Our findings demonstrate the importance of underlying heterogeneity in QoL trajectories, resulting in variable QALY gains. There is scope in translating routinely collected PROMs to improve shared decision-making allowing for more patient engagement. However, further research is required to identify suitable approaches of its implementation into practice to guide clinical care and maximize patient outcomes.

What Influences Patient Satisfaction after TKA? A Qualitative Investigation.

BACKGROUND: Patient satisfaction is a common measure of the success of an orthopaedic intervention. However, there is poor understanding of what satisfaction means to patients or what influences it. QUESTIONS/PURPOSES: Using qualitative study methodology in patients undergoing TKA, we asked: (1) What does it mean to be satisfied after TKA? (2) What factors influence satisfaction levels after TKA? METHODS: People in a hospital registry who had completed 12-month follow-up questionnaires and were not more than 18 months post-TKA at the time of sampling were eligible (n = 121). To recruit a sample that provided insight into a range of TKA experiences, we divided eligible candidates on the registry into quadrants based on their responder status and satisfaction level. A responder was an individual who experienced a clinically meaningful change in pain and/or function on the WOMAC according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria. Individuals were considered satisfied unless they indicated somewhat dissatisfied or very dissatisfied for one or more of the four items on the Self-Administered Patient Satisfaction Scale. From the resulting quadrants: responder satisfied, nonresponder satisfied, nonresponder dissatisfied, responder dissatisfied, we identified men and women with a range of ages and invited them to participate (n = 85). The final sample (n = 40), consisted of 10 responder satisfied, nine nonresponder satisfied, eight nonresponder dissatisfied, and 13 responder dissatisfied; 71% were women, with a mean age of 71 ± 7 years and a mean time since TKA surgery of 17 ± 2 months (range 13 to 25 months). Interview transcripts were analyzed by looking for factors in the participants' narrative that appeared to underscore their level of satisfaction and attaching inductive (data-derived, rather than a priori derived) codes to relevant sections of text. Coded data from participants who reported high and low levels of satisfaction were compared/contrasted and emerging patterns were mapped into a conceptual model. Recruitment continued until no new information was uncovered in data analysis of subsequent interviews, signalling to the researchers that further interviews would not change the key themes identified and data collection could cease. RESULTS: In those with high satisfaction levels, satisfaction was conceptualized as an improvement in pain and function. In those with low satisfaction levels, rather than an improvement, satisfaction was conceptualized as completely resolving all symptoms and functional limitations. In addition, we identified three pathways through which participants reached different levels of low and high satisfaction: (1) The full-glass pathway, characterized by no or minimal ongoing symptoms and functional deficits, which consistently led to high levels of satisfaction; (2) the glass-half-full pathway, characterized by ongoing symptoms and functional limitations, which led to high satisfaction; and (3) the glass-half-empty pathway, also characterized by ongoing symptoms and functional limitations, which led to low satisfaction levels. The latter two pathways were mediated by three core mechanisms (recalibration, reframing valued activities, and reconceptualization) influenced either positively or negatively by (1) a persons' thoughts and feelings such as optimism, self-efficacy, pain catastrophizing, external locus of control; and (2) social and contextual factors such as fulfilment of social roles, therapeutic alliance, lack of family/social support. CONCLUSIONS: This qualitative study suggests that for preoperative patients in whom unrealistically high hopes for complete symptom resolution and restoration of functional capacity persists, it may be appropriate to direct them away from TKA due to the risk of low satisfaction. For postoperative patients troubled by ongoing symptoms or functional limitations, clinicians may improve levels of satisfaction by targeting the three core mechanisms (recalibration, reframing valued activities, and reconceptualization) through addressing modifiable negative thoughts and feelings in interventions such as psychology or psychotherapy; and negative social and contextual factors by promoting a strong therapeutic alliance and engagement in community activities. Given that these factors may be identifiable preoperatively, future research is needed to explore if and how addressing them preoperatively may improve satisfaction post-TKA. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Better Knee, Better Me™: effectiveness of two scalable health care interventions supporting self-management for knee osteoarthritis - protocol for a randomized controlled trial.

BACKGROUND: Although education, exercise, and weight loss are recommended for management of knee osteoarthritis, the additional benefits of incorporating weight loss strategies into exercise interventions have not been well investigated. The aim of this study is to compare, in a private health insurance setting, the clinical- and cost-effectiveness of a remotely-delivered, evidence- and theory-informed, behaviour change intervention targeting exercise and self-management (Exercise intervention), with the same intervention plus active weight management (Exercise plus weight management intervention), and with an information-only control group for people with knee osteoarthritis who are overweight or obese. METHODS: Three-arm, pragmatic parallel-design randomised controlled trial involving 415 people aged ≥45 and ≤ 80 years, with body mass index ≥28 kg/m2 and < 41 kg/m2 and painful knee osteoarthritis. Recruitment is Australia-wide amongst Medibank private health insurance members. All three groups receive access to a bespoke website containing information about osteoarthritis and self-management. Participants in the Exercise group also receive six consultations with a physiotherapist via videoconferencing over 6 months, including prescription of a strengthening exercise and physical activity program, advice about management, and additional educational resources. The Exercise plus weight management group receive six consultations with a dietitian via videoconferencing over 6 months, which include a very low calorie ketogenic diet with meal replacements and resources to support behaviour change, in addition to the interventions of the Exercise group. Outcomes are measured at baseline, 6 and 12 months. Primary outcomes are self-reported knee pain and physical function at 6 months. Secondary outcomes include weight, physical activity levels, quality of life, global rating of change, satisfaction with care, knee surgery and/or appointments with an orthopaedic surgeon, and willingness to undergo surgery. Additional measures include adherence, adverse events, self-efficacy, and perceived usefulness of intervention components. Cost-effectiveness of each intervention will also be assessed. DISCUSSION: This pragmatic study will determine whether a scalable remotely-delivered service combining weight management with exercise is more effective than a service with exercise alone, and with both compared to an information-only control group. Findings will inform development and implementation of future remotely-delivered services for people with knee osteoarthritis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12618000930280 (01/06/2018).

A Randomized Controlled Trial Comparing a Medial Stabilized Total Knee Prosthesis to a Cruciate Retaining and Posterior Stabilized Design: A Report of the Clinical and Functional Outcomes Following Total Knee Replacement.

BACKGROUND: The purpose of this randomized controlled trial was to compare the performance of 3 total knee joint replacement (TKJR) designs 6 months after the surgery. METHODS: Patients were recruited between March 2015 and March 2018. Patients with osteoarthritis consented for TKJR were randomly allocated to a medial stabilized (MS), cruciate retaining (CR), or posterior stabilized (PS) design. Primary outcome measures were self-reported improvement in pain and function 6 months after TKJR, using the Oxford Knee Score. Secondary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index, Veterans RAND 12-item Health Survey, Knee Society Score 2011, Timed Up and Go test, and Six-Minute Walk Test. Twelve-month outcomes were also measured. RESULTS: Ninety participants enrolled, 83 were randomized: PS (n = 26), CR (n = 28), and MS (n = 29) designs. One case withdrew before surgery: planned use of non-study implant; 7 did not complete all outcome measures. No 6-month between-group difference was observed for the primary outcome. A 6-month difference was observed in Knee Society Score 2011 Satisfaction: MS favored over CR and PS. Clinically meaningful 12-month differences in Western Ontario and McMaster Universities Osteoarthritis Index Pain, Function, and Global Subscales were observed: MS favored over CR. Twelve-month differences occurred in Veterans RAND 12-item Health Survey mental well-being, favoring MS and PS over CR. CONCLUSION: MS prosthesis can be expected to yield similar clinical and functional outcomes to PS and CR designs 6 months after TKJR, and patients were more satisfied with their outcome. Compared with CR, patients with MS prosthesis also reported superior pain, function, and quality-of-life outcomes at 12 months.