Finite element analysis of patient-specific additive-manufactured implants.

Introduction: Bone tumors, characterized by diverse locations and shapes, often necessitate surgical excision followed by custom implant placement to facilitate targeted bone reconstruction. Leveraging additive manufacturing, patient-specific implants can be precisely tailored with complex geometries and desired stiffness, enhancing their suitability for bone ingrowth. Methods: In this work, a finite element model is employed to assess patient-specific lattice implants in femur bones. Our model is validated using experimental data obtained from an animal study (n = 9). Results: The results demonstrate the accuracy of the proposed finite element model in predicting the implant mechanical behavior. The model was used to investigate the influence of reducing the elastic modulus of a solid Ti6Al4V implant by tenfold, revealing that such a reduction had no significant impact on bone behavior under maximum compression and torsion loading. This finding suggests a potential avenue for reducing the endoprosthesis modulus without compromising bone integrity. Discussion: Our research suggests that employing fully lattice implants not only facilitates bone ingrowth but also has the potential to reduce overall implant stiffness. This reduction is crucial in preventing significant bone remodeling associated with stress shielding, a challenge often associated with the high stiffness of fully solid implants. The study highlights the mechanical benefits of utilizing lattice structures in implant design for enhanced patient outcomes.

Predictive Tool Use and Willingness for Surgery in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Despite the increasing number of tools available to predict the outcomes of total knee arthroplasty (TKA), the effect of these predictive tools on patient decision-making remains uncertain. Objective: To assess the effect of an online predictive tool on patient-reported willingness to undergo TKA. Design, Setting, and Participants: This parallel, double-masked, 2-arm randomized clinical trial compared predictive tool use with treatment as usual (TAU). The study was conducted between June 30, 2022, and July 31, 2023. Participants were followed up for 6 months after enrollment. Participants were recruited from a major Australian private health insurance company and from the surgical waiting list for publicly funded TKA at a tertiary hospital. Eligible participants had unilateral knee osteoarthritis, were contemplating TKA, and had previously tried nonsurgical interventions, such as lifestyle modifications, physiotherapy, and pain medications. Intervention: The intervention group was provided access to an online predictive tool at the beginning of the study. This tool offered information regarding the likelihood of improvement in quality of life if patients chose to undergo TKA. The predictions were based on the patient's age, sex, and baseline symptoms. Conversely, the control group received TAU without access to the predictive tool. Main Outcomes and Measures: The primary outcome measure was the reduction in participants' willingness to undergo surgery at 6 months after tool use as measured by binomial logistic regression. Secondary outcome measures included participant treatment preference and the quality of their decision-making process as measured by the Knee Decision Quality Instrument. Results: Of 211 randomized participants (mean [SD] age, 65.8 [8.3] years; 118 female [55.9%]), 105 were allocated to the predictive tool group and 106 to the TAU group. After adjusting for baseline differences in willingness for surgery, the predictive tool did not significantly reduce the primary outcome of willingness for surgery at 6 months (adjusted odds ratio, 0.85; 95% CI, 0.42-1.71; P = .64). Conclusions and Relevance: Despite the absence of treatment effect on willingness for TKA, predictive tools might still enhance health outcomes of patients with knee osteoarthritis. Additional research is needed to optimize the design and implementation of predictive tools, address limitations, and fully understand their effect on the decision-making process in TKA. Trial Registration: ANZCTR.org.au Identifier: ACTRN12622000072718.

Radiotherapy versus limb-sparing surgery alone in low-grade soft-tissue sarcoma of the extremity and trunk wall: a systematic review and meta-analysis.

Current guidelines recommend the use of radiotherapy in the management of intermediate and high-grade soft-tissue sarcoma of the extremity and trunk wall. Its use in low-grade sarcoma is less clear. To date there have been no pooled data analyses regarding its role in this context. Its use is not without complications and therefore must be justified. We aim to assess the oncological impact of radiotherapy versus limb-sparing surgery alone in this subset of sarcoma. Medline, EMBASE and Cochrane's databases were searched from 1982 to present. Studies on or having a subgroup analysis of low-grade soft tissue sarcoma, with a radiotherapy and a surgery only arm were included. Outcomes included local recurrence and overall survival. Patients were at least 16 years of age with primary de-novo sarcoma who had not undergone prior resection or treatment. Those undergoing concomitant therapy were excluded. Data extraction was performed independently by two reviewers. Results were pooled using a random-effects model and presented as a forest plot. Primary outcome measures included local recurrence and overall survival. Eleven unique studies were included, consisting of two RCTs and nine non-randomized studies. Overall, there were 12 799 patients. Four studies were included in meta-analysis and the overall pooled effect showed a limited role of radiotherapy in overall survival outcomes when compared to limb-sparing surgery alone HR 1.00 [0.83-1.20] P = 0.41. Descriptive analysis suggests there is limited role of radiotherapy in improving local recurrence outcomes. This study suggests there is limited role for radiotherapy versus limb-sparing surgery alone in low-grade soft-tissue sarcoma. These findings strongly suggest there is lack of high-quality data and that further research must be undertaken prior to forming any strong conclusions regarding the management of low-grade soft-tissue sarcoma. Demonstrating a role for radiotherapy may help improve the quality of excisional margins and thus potentiate limb-sparing surgery.

Patient perspectives of quality of life in chronic limb-threatening ischemia: a qualitative study.

BACKGROUND: Quality of life (QOL) is an outcome that matters to patients with chronic limb-threatening ischemia (CLTI). However, we identified the lack of and need for a CLTI-specific QOL instrument. Our group is developing this instrument which requires a deep understanding of patient perspectives of QOL in CLTI. METHODS: Qualitative inquiry with patient and public involvement was performed in accordance with the Standards for Reporting Qualitative Research. Reflexive thematic analysis of semi-structured interviews was conducted within a constructivist-interpretivist research paradigm. Data were organized and managed in NVivo. Techniques to enhance trustworthiness included maintaining an audit trail, member checking, mentoring, and peer-debriefing. Patient and the public were consulted for feedback on codes, themes, and thematic maps. RESULTS: Thirteen participants (median age: 74 years, range: 43-90 years) with a variety of patient demographics were interviewed. Four themes were developed on QOL in CLTI: (i) 'independence as key to life satisfaction', (ii) 'change in identity when continuity is needed', (iii) 'coping with intractable disease', and (iv) 'not wanting to be alone'. Member checking with patient and public involvement confirmed the relevance and centrality of these themes to the lived experiences of patients with CLTI. CONCLUSIONS: The thematic outputs contribute important insights into what QOL truly means to patients with CLTI and what matters for their QOL. The content validity of the new CLTI-specific QOL instrument is improved by giving patients voice. This study highlights the value of qualitative inquiry and patient and public involvement in vascular surgical research.

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.

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.

Does a consumer co-designed infographic increase knowledge of physical activity after total knee joint replacement? A randomised controlled trial.

PURPOSE: To determine if a consumer co-designed infographic increased knowledge of physical activity and self-efficacy for exercise after total knee joint replacement surgery. METHODS: Forty-four adults with primary knee joint replacement surgery were recruited from a public and a private hospital in Melbourne, Australia. Participants were randomly allocated to an experimental or control group. The experimental group received a consumer co-designed infographic. All participants received usual care. Primary outcome measures were knowledge of physical activity and self-efficacy for exercise. Outcomes were administered at baseline, week 1 and week 6. Semi-structured interviews with experimental group participants explored the acceptability, implementation and efficacy of the infographic. RESULTS: There were no between-group differences for knowledge of physical activity at week 1 (MD -0.02 units, 95% CI -0.9 to 0.9) or week 6 (MD 0.01 units, 95% CI -0.9 to 0.9). Self-efficacy for exercise increased at week 1 (MD 14.2 units, 95% CI 2.9-25.4) but was not sustained. Qualitative data showed that the infographic was embraced by some participants but not by others. CONCLUSIONS: A consumer co-designed infographic did not improve knowledge of physical activity but may have had a short-term positive effect on self-efficacy for exercise after knee joint replacement. Trial registration ACTRN12621000910808.

Mortality, patient-reported outcome measures, and the health economic burden of prosthetic joint infection.

Prosthetic joint infection (PJI) is one of the most devastating complications for a patient following arthroplasty. This scoping review aims to evaluate the burden of PJI on individual patients and the healthcare system regarding the mortality rate, patient-reported quality of life, and healthcare resource utilisation. Patients with PJI have up to a five-fold higher mortality rate than those who have undergone an uninfected primary arthroplasty. There is an increased use of ambulatory aids and reduced joint function scores in patients with PJI. Global quality of life is poorer, specifically measured by the EQ-5D. Direct hospitalisation costs are two- to five-fold higher, attributed to surgery and prostheses, antibiotics, and a prolonged inpatient stay. There is an immense clinical and health economic burden secondary to PJI worldwide. This is expected to rise exponentially due to the increasing number of primary procedures and an ageing population with comorbidities Improving preventative and treatment strategies is imperative for patients and the healthcare system.

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.

Process of change for people with knee osteoarthritis undergoing cognitive functional therapy: a replicated single-case experimental design study.

PURPOSE: To examine the applicability and process of change of Cognitive Functional Therapy (CFT) in the management of pain and disability in people with knee osteoarthritis who were offered knee replacement surgery and had risk factors for poor response to surgery. METHODS: Single-case experimental design with a mixed-methods, repeated measures approach was used to investigate the process of change through CFT in four participants. Qualitative interviews investigated beliefs, behaviours and coping responses, and self-reported measures assessed pain, disability, psychological factors, and function at 25 timepoints. Study registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619001491156). RESULTS: Qualitative data indicate that CFT promoted helpful changes in all participants, with two responses observed. One reflected a clear shift to a biopsychosocial conceptualisation of osteoarthritis, behavioural re-engagement and the view that a knee replacement was no longer necessary. The other response reflected a mixed conceptualisation with dissonant beliefs about osteoarthritis and its management. Psychological and social factors were identified as potential treatment barriers. Overall, quantitative measures supported the qualitative findings. CONCLUSION: The process of change varies between and within individuals over time. Psychological and social barriers to treatment have implications for future intervention studies for the management of knee osteoarthritis.IMPLICATIONS FOR REHABILITATIONCognitive Functional Therapy is applicable in the management of knee osteoarthritis.Reconceptualisation of osteoarthritis reflected a helpful change.Psychological and social factors emerged as barriers to recovery.

The impact of cost on quality of surgical management in non-metastatic extremity sarcoma: A cross-country narrative literature review with a systematic approach.

BACKGROUND: Extremity sarcoma surgery entails significant costs for patients, governments and insurers. Multiple studies have described individual costs, however, the overall impact of cost on the quality of surgical care remains unclear. OBJECTIVES: A narrative review with a systematic approach was undertaken to compare the impact of cost on the quality of extremity sarcoma care across low-middle-income and high-income countries. DATA SOURCES: MEDLINE, EMBASE, Cochrane, PsycInfo, DARE, NHS-EED, HTA. METHODS: A systematic search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria were: discussion of costs and the surgical management of primary extremity sarcoma. There were no restrictions on study design, publication type, date, geographic location or publication status. A data extraction table was used to identify study location, type and findings. RESULTS: 1012 studies were retrieved and 44 met the inclusion criteria. Four additional studies were identified from the reference lists of included articles. 27 studies were published in high-income countries (HIC) including all four full health economic analyses and 20 studies were published in low-middle income countries (LMC). Within LMC, cost impeded access to diagnosis, resection and options for reconstruction. In HIC, cost varied with choice of management, particularly during the long-term postoperative period. CONCLUSIONS: Within LMC, cost impaired the provision of quality, curative care for patients with extremity sarcoma. Within HIC, while costs varied with chosen management, they were not prohibitive to the provision of quality care. Further research is required, specific to both socioeconomic contexts, to further describe the long-term cost-utility of different methods for the surgical management of extremity sarcoma.

High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production.

Megakaryocytes (MK) generate platelets. Recently, we and others, have reported MK also regulate hematopoietic stem cells (HSC). Here we show high ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of HSC and critical for platelet formation. Using a mouse knockout model (Pf4-Srsf3Δ/Δ) with normal MK numbers, but essentially devoid of LCM, we demonstrate a pronounced increase in BM HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. Severe thrombocytopenia is observed in animals with diminished LCM, although there is no change in MK ploidy distribution, uncoupling endoreduplication and platelet production. When HSC isolated from a microenvironment essentially devoid of LCM reconstitute hematopoiesis in lethally irradiated mice, the absence of LCM increases HSC in BM, blood and spleen, and the recapitulation of thrombocytopenia. In contrast, following a competitive transplant using minimal numbers of WT HSC together with HSC from a microenvironment with diminished LCM, sufficient WT HSC-generated LCM regulates a normal HSC pool and prevents thrombocytopenia. Importantly, LCM are conserved in humans.

Robot-assisted implantation of additively manufactured patient-specific orthopaedic implants: evaluation in a sheep model.

PURPOSE: Bone tumours must be surgically excised in one piece with a margin of healthy tissue. The unique nature of each bone tumour case is well suited to the use of patient-specific implants, with additive manufacturing allowing production of highly complex geometries. This work represents the first assessment of the combination of surgical robotics and patient-specific additively manufactured implants. METHODS: The development and evaluation of a robotic system for bone tumour excision, capable of milling complex osteotomy paths, is described. The developed system was evaluated as part of an animal trial on 24 adult male sheep, in which robotic bone excision of the distal femur was followed by placement of patient-specific implants with operative time evaluated. Assessment of implant placement accuracy was completed based on post-operative CT scans. RESULTS: A mean overall implant position error of 1.05 ± 0.53 mm was achieved, in combination with a mean orientation error of 2.38 ± 0.98°. A mean procedure time (from access to implantation, excluding opening and closing) of 89.3 ± 25.25 min was observed, with recorded surgical time between 58 and 133 min, with this approximately evenly divided between robotic (43.9 ± 15.32) and implant-based (45.4 ± 18.97) tasks. CONCLUSIONS: This work demonstrates the ability for robotics to achieve repeatable and precise removal of complex bone volumes of the type that would allow en bloc removal of a bone tumour. These robotically created volumes can be precisely filled with additively manufactured patient-specific implants, with minimal gap between cut surface and implant interface.

Oncologic outcomes in myxofibrosarcomas: the role of a multidisciplinary approach and surgical resection margins.

BACKGROUNDS: Myxofibrosarcomas (MFS) are malignant soft tissue sarcomas with an infiltrative growth pattern and propensity for local recurrence(LR).We aimed to assess our management of MFS and make recommendations about the role of a multidisciplinary team approach and margin widths. METHODS: Fifty-seven patients were identified with MFS treated at a single sarcoma centre between 1998 and 2020. Patients were stratified based on whether they presented for a planned resection (59.6%) or after an unplanned resection (40.4%) performed at a non-specialized facility. All patients underwent radiotherapy before definitive surgery. RESULTS: 73.7% underwent a combined onco-plastic approach. The 5 year LRFS rate was 78.2% (84.4%, planned, versus 70.1%, unplanned, P = 0.194) and found comparable oncological outcomes between the planned and unplanned groups for the 5 year metastasis free survival (74.5% versus 86.1%, P = 0.257), disease free survival (70.1% versus 72.4%, P = 0.677), and Overall Survival (64.5% versus 75.9%, P = 0.950). Margin width ≥ 2 cm was obtained in 84.2% of cases and improved local control (HR = 0.22; 95% CI 0.06-0.81; P = 0.023), metastasis (HR = 0.24; 95% CI 0.07-0.80; P = 0.019) and mortality rates (HR = 0.23; 95% CI 0.09, 0.61; P = 0.003) compared to <2 cm. Margin width > 3 cm did not further affect oncological outcomes. CONCLUSION: Our study shows that a multidisciplinary team approach allows the achievement of low local recurrence rate and good oncological outcomes of myxofibrosarcomas, regardless of presentation status. We recommend a minimum of 2 cm margin width.

Research Buddy partnership in a MD-PhD program: lessons learned.

BACKGROUND AND AIMS: There is increasing recognition of the importance of patient involvement in research. In recent years, there has also been growing interest in patient partnerships with doctoral studies students. However, it can be difficult to know where to start and how to go about such involvement activities. The purpose of this perspective piece was to share experiential insight of the experience of a patient involvement program such that others can learn from this experience. BODY: This is a co-authored perspective piece centred on the experience of MGH, a patient who has had hip replacement surgery, and DG, a medical student completing a PhD, participating in a Research Buddy partnership over the course of over 3 years. The context in which this partnership took place was also described to facilitate comparison with readers' own circumstances and contexts. DG and MGH met regularly to discuss, and work together on, various aspects of DG's PhD research project. Reflexive thematic analysis was conducted on reflections from DG and MGH regarding their experience in the Research Buddy program to synthesise nine lessons which were then corroborated with reference to published literature on patient involvement in research. These lessons were: learn from experience; tailor the program; get involved early; embrace uniqueness; meet regularly; build rapport; ensure mutual benefit; broad involvement; regularly reflect and review. CONCLUSIONS: In this perspective piece, a patient and a medical student completing a PhD reflected upon their experience co-designing a Research Buddy partnership within a patient involvement program. A series of nine lessons was identified and presented to inform readers seeking to develop or enhance their own patient involvement programs. Researcher-patient rapport is foundational to all other aspects of the patient's involvement.

The importance of patient involvement in research is gaining recognition. Existing research centres, as well as those that are just getting started, need to find their own way to involve patients and community members. However, learning from the experience of others is crucial to ensure every effort is made to do this in a fruitful way. Therefore, we aimed to share our experience and provide a list of lessons learned to help other researchers and patients get started and work together effectively. Our research centre developed a framework for involving patients in joint replacement research. Part of this framework is a 'Research Buddy' program, where a research student partners with a patient so that the research they conduct is more relevant and applicable to the target population. In our case, the research student partnered with someone who had a hip replacement to develop and test a questionnaire for an interview study about artificial intelligence in shared decision-making. The student and patient worked together and wrote this perspective piece outlining nine lessons so readers can learn from their experience of this program. The lessons were: learn from experience, tailor the program, get involved early, embrace uniqueness, meet regularly, build rapport, ensure mutual benefit, broad involvement, regularly reflect and review. People interested in starting, or improving, their own patient involvement activities can learn from our experience. These lessons will need to be adapted to fit the purpose and unique situation of other researchers and patients who have different needs and circumstances.

SMART choice (knee) tool: a patient-focused predictive model to predict improvement in health-related quality of life after total knee arthroplasty.

BACKGROUND: Current predictive tools for TKA focus on clinicians rather than patients as the intended user. The purpose of this study was to develop a patient-focused model to predict health-related quality of life outcomes at 1-year post-TKA. METHODS: Patients who underwent primary TKA for osteoarthritis from a tertiary institutional registry after January 2006 were analysed. The primary outcome was improvement after TKA defined by the minimal clinically important difference in utility score at 1-year post-surgery. Potential predictors included demographic information, comorbidities, lifestyle factors, and patient-reported outcome measures. Four models were developed, including both conventional statistics and machine learning (artificial intelligence) methods: logistic regression, classification tree, extreme gradient boosted trees, and random forest models. Models were evaluated using discrimination and calibration metrics. RESULTS: A total of 3755 patients were included in the study. The logistic regression model performed the best with respect to both discrimination (AUC = 0.712) and calibration (intercept = -0.083, slope = 1.123, Brier score = 0.202). Less than 2% (n = 52) of the data were missing and therefore removed for complete case analysis. The final model used age (categorical), sex, baseline utility score, and baseline Veterans-RAND 12 responses as predictors. CONCLUSION: The logistic regression model performed better than machine learning algorithms with respect to AUC and calibration plot. The logistic regression model was well calibrated enough to stratify patients into risk deciles based on their likelihood of improvement after surgery. Further research is required to evaluate the performance of predictive tools through pragmatic clinical trials. LEVEL OF EVIDENCE: Level II, decision analysis.

Analysis of Rates of Completion, Delays, and Participant Recruitment in Randomized Clinical Trials in Surgery.

Importance: Discontinuation and nonpublication are established sources of avoidable waste among surgical trials, but rates of delayed completion and recruiting shortfalls remain unclear. Objectives: To examine the rate of delayed completion, incomplete enrollment, and discontinuation among randomized clinical trials in surgical populations and the duration of delays and extent of recruiting shortfalls among these trials. Design, Setting, and Participants: This cross-sectional study examined randomized clinical trials in surgical populations registered on ClinicalTrials.gov between January 1, 2010, and December 31, 2014. Analysis was conducted between October 27, 2021, and June 30, 2022. Main Outcomes and Measures: The main outcomes were the percentages of trials completed on time or with full enrollment. Delays and recruiting shortfalls were identified by comparing projected enrollment and study timeframes prespecified at the time of registration with the actual study duration and enrollment reported on completion or discontinuation. Absolute and relative differences between planned and actual trial conduct were presented for discontinued trials and those completed with delays or recruiting shortfalls. Results: In total, 2542 randomized clinical trials in surgical populations were included in the study sample, of which 370 (14.6%; 95% CI, 13.2%-15.9%) were completed both on time and with full enrollment. Approximately 1 in 5 trials (20.4%; 95% CI, 18.9%-22.0%) were completed within their planned timeframe, and 1166 trials (45.9%; 95% CI, 43.9%-47.8%) met their prespecified enrollment target. The median delay among completed trials was 12.2 months (IQR, 5.1-24.3 months) or 66.7% (IQR, 30.1%-135.8%) longer than planned. Among completed trials that did not meet their prespecified enrollment target, the median recruiting shortfall was equivalent to 31.0% (IQR, 12.7%-55.5%) of the planned study sample. A total of 546 trials (21.5%; 95% CI, 19.9%-23.1%) were discontinued. The median time to discontinuation was 26.4 months (IQR, 15.2-45.7 months), and the median recruiting shortfall among discontinued trials was equivalent to 92.7% (IQR, 65.0%-100.0%) of the trial's prespecified enrollment target. Conclusions and Relevance: This cross-sectional study found that delayed completion, recruiting shortfalls, and untimely discontinuation were common among surgical trials. These findings highlight the importance of ensuring that investigators and funders do not overestimate the feasibility of planned trials.

Kinematic function of knee implant designs across a range of daily activities.

The aim of this randomized controlled trial was to measure and compare six-degree-of-freedom (6-DOF) knee joint motion of three total knee arthroplasty (TKA) implant designs across a range of daily activities. Seventy-five TKA patients were recruited to this study and randomly assigned a posterior-stabilized (PS), cruciate-retaining (CR), or medial-stabilized (MS) implant. Six months after surgery, patients performed five activities of daily living: level walking, step-up, step-down, sit-to-stand, and stand-to-sit. Mobile biplane X-ray imaging was used to measure 6-DOF knee kinematics and the center of rotation of the knee in the transverse plane for each activity. Mean 6-DOF knee kinematics were consistently similar for PS and CR, whereas MS was more externally rotated and abducted, and lateral shift was lower across all activities. Peak-to-peak anterior drawer for MS was also significantly lower during walking, step-up, and step-down (p < 0.017). The center of rotation of the knee in the transverse plane was located on the medial side for MS, whereas PS and CR rotated about the lateral compartment or close to the tibial origin. The kinematic function of MS was more similar to that of the healthy knee than PS and CR based on reduced paradoxical anterior translation at low flexion angles and a transverse center of rotation located in the medial compartment. Overall, 6-DOF knee joint motion for PS and CR were similar across all daily activities, whereas that measured for MS was appreciably different. The kinematic patterns observed for MS reflects a highly conforming medial articulation in the MS design.

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.

An Economic Model for Estimating Trial Costs with an Application to Placebo Surgery Trials.

BACKGROUND AND OBJECTIVE: Waste in clinical trials remains rife. We developed an economic model to predict the cost of trials based on input costs, duration, power, number of sites, recruitment eligibility and consenting rates. METHODS: We parameterised the model for three proxy placebo-controlled surgical trials using data from a systematic review, a bespoke cost survey, and from the literature. We used the model to compare target and actual trial performance for (i) a trial that was completed on time but with more sites, (ii) a trial that completed after a time extension, and (iii) an incomplete trial. RESULTS: Successful trials more accurately anticipated the true recruitment rate that they achieved and those that overestimated this were most likely to fail. The costs of overestimating recruitment rates were dramatic: all proxy trials had significantly higher costs than planned, with additional funding of at least AUD$600,000 (50% above budget) required for trials that completed after adding more sites or more time, and over AUD$2 million (260% above budget) for incomplete trials. CONCLUSIONS: This model shows the trade-offs between time and cost, or both, when recruitment is lower than anticipated. Greater consideration is needed to improve trial planning, reviewing, and funding of these trials to avoid costly overruns and incomplete trials.