Feasibility and barriers to rapid establishment of patient-derived primary osteosarcoma cell lines in clinical management.

Osteosarcoma is a highly aggressive primary bone tumor that has seen little improvement in survival rates in the past three decades. Preclinical studies are conducted on a small pool of commercial cell lines which may not fully reflect the genetic heterogeneity of this complex cancer, potentially hindering translatability of in vitro results. Developing a single-site laboratory protocol to rapidly establish patient-derived primary cancer cell lines (PCCL) within a clinically actionable time frame of a few weeks will have significant scientific and clinical ramifications. These PCCL can widen the pool of available cell lines for study while patient-specific data could derive therapeutic correlation. This endeavor is exceedingly challenging considering the proposed time constraints. By proposing key definitions and a clear theoretical framework, this evaluation of osteosarcoma cell line establishment methodology over the past three decades assesses feasibility by identifying barriers and suggesting solutions, thereby facilitating systematic experimentation and optimization.

Discrete-Target Prosthesis Control Using Uncertainty-Aware Classification for Smooth and Efficient Gross Arm Movement.

Current control approaches for gross prosthetic arm movement mainly regulate movement over a continuous range of target poses. However, these methods suffer from output fluctuation caused by input signal variations during gross arm movements. Prosthesis control approaches with a finite number of discrete target poses can address this issue and reduce the complexity of the pose control process. However, it remains under-explored in the literature and suffers from the consequences of misclassifying the target poses. Here, we propose a novel Uncertainty-Aware Discrete-Target Prosthesis Control (UA-DPC) approach. This approach consists of (1) an uncertainty-aware classification scheme to reduce unintended pose switches caused by misclassifications, and (2) real-time trajectory planning that adjusts motion to be rapid or conservative based on low or high quantified uncertainty, respectively. By addressing the impact of misclassification, this approach facilitates more efficient and smooth movements. Human-in-the-loop experiments were conducted in a virtual reality environment with 12 non-disabled participants. The participants controlled a transhumeral prosthesis using three approaches: the proposed UA-DPC, a discrete-target approach based on a traditional off-the-shelf classifier, and a continuous-target approach. The results demonstrate the superior performance of UA-DPC, which provides more efficient task completion with fewer misclassification instances as well as smoother residual limb and prosthesis movement.

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.

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.

Influences on clinical trial participation: Enhancing recruitment through a gender lens - A scoping review.

Background: Suboptimal clinical trial recruitment contributes to research waste. Evidence suggests there may be gender-based differences in willingness to participate in clinical research. Identifying gender-based differences impacting the willingness of trial participation may assist trial recruitment. Objectives: To examine factors that influence the willingness of men and women to participate in clinical trials and to identify modifiable factors that may be targeted to optimise trial participation. Material and methods: Electronic databases were searched with key words relating to 'gender', 'willingness to participate' and 'trial'. Included studies were English language and reported gender-based differences in willingness to participate in clinical trials, or factors that influence a single gender to participate in clinical trials. Studies were excluded if they described the demographic factors of trial participants or if the majority of participants were pregnant. Extracted data were coded, categorized, analysed thematically and interpreted using Arksey and O'Malley's framework. Results: Sixty-three studies were included. Two main themes were identified: trial characteristics and participant characteristics. A number of gender-based differences moderating willingness to participate were observed although only one, 'concern for self' was found to influence actual trial participation rates between genders. Conclusion: The relationship between factors influencing willingness to participate in clinical trials is complex. The influence of gender on willingness to participate, while important, may be moderated by other factors including socioeconomic status, ethnicity and health condition. Exploring factors that influence willingness to participate specific to a study cohort likely offers the most promise to optimise trial recruitment of that cohort.

The impact of infection on length of stay in adult burns: A scoping review.

BACKGROUND: The disruption to the immune system and profound metabolic response to burn injury gives rise to a unique susceptibility to infection. Indeed, infection is one of the most frequently encountered post-burns complications placing significant burden on patients and healthcare system. Advancements in burn care have led to marked improvements in burn-related mortality and morbidity; however, scarce hospital resources hamper adequate burn-related care, and patient length of stay (LOS) in hospital is an important drain on such resources. The aim of this review was to assess and evaluate the existing literature relating to the impact of infections on LOS in hospitalised, adult burn patients. METHODS: Electronic searches were performed in Medline and Embase. Eligible studies were those reporting on LOS and infection in adult burn populations. Articles published before 2000 were excluded to ensure that the analysis was focused on contemporary literature that reflects current, clinical management of burn patients. RESULTS: Nineteen studies (54,397 burn patients) were included in the review. All studies were retrospective, with the majority undertaken in North America (14 studies). The mean age range was 38-67 years and the majority of patients were male. Inhalation injury was recorded in eleven studies. The most common types of infection included pneumonia, blood stream infections (BSI) and burn wound infections. Overall, there was a trend towards a positive association between infection and LOS. CONCLUSION: The results of this scoping review provide an overview of the existing literature on the relationship between infection and LOS in adult burn populations. However, significant gaps remain in knowledge which call for further high-quality research. Standardised definitions for the collection of infection data and the use of burns specific infection control guidelines are also critical to understanding and improving patient outcomes.

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.

Diagnostic Accuracy of Clinical Tests for Assessing Greater Trochanteric Pain Syndrome: A Systematic Review With Meta-analysis.

OBJECTIVE: We aimed to evaluate the accuracy of clinical tests that are used to diagnose greater trochanteric pain syndrome (GTPS) in clinical practice. DESIGN: Diagnostic test accuracy systematic review with meta-analysis. LITERATURE SEARCH: MEDLINE, Embase, CINAHL, AMED, and SPORTDiscus were searched using key words mapped to diagnostic test accuracy for GTPS. STUDY SELECTION CRITERIA: Studies with published or derivable diagnostic accuracy data were included. DATA SYNTHESIS: Risk of bias was assessed using the QUADAS-2 tool, and certainty of evidence, via the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. MetaDTA "R" random-effects models were used to summarize individual and pooled data including sensitivity, specificity, likelihood ratios, and pretest/posttest probabilities. RESULTS: From a database yield of 858 studies, 23 full texts were assessed. We included 6 studies for review, involving 15 tests and 272 participants (314 hips). Overall certainty of evidence ranged from very low to moderate. Meta-analysis of 6 tests revealed sequenced test clusters able to significantly shift pretest-posttest probability for or against a GTPS diagnosis. In people reporting lateral hip pain, a negative gluteal tendon (GT) palpation test followed by a negative resisted hip abduction test significantly reduced the posttest probability of GTPS from 59% to 14%. In those with a positive GT palpation test followed by a positive resisted hip abduction test, the posttest probability of GTPS significantly shifted from 59% to 96%. CONCLUSION: The value of magnetic resonance imaging for diagnosing GTPS is debated. We have identified a straightforward, clinically useful diagnostic test cluster to help confirm or refute the presence of GTPS in people reporting lateral hip pain. J Orthop Sports Phys Ther 2024;54(1):1-24. Epub 10 August 2023. doi:10.2519/jospt.2023.11890.

Feasibility Evaluation of Online Classification-based Control for Gross Movement in a 2-DoF Prosthetic Arm.

Regression and classification models have been extensively studied to exploit the myoelectric and kinematic input information from the residual limb for the control of multiple degree-of-freedom (DoF) powered prostheses. The gross movement control of above-elbow prostheses is mainly based on regression models which map the available inputs to continuous prosthetic poses. However, the regression output is sensitive to the variation in the input signal. The myoelectric signal variation is usually large due to unintentional muscle contractions, which can deteriorate the user-in-the-loop performance with respect to the offline analysis. Alternatively, the classification models offer the advantage of being more robust to the input signal variation, but they were predominantly used for fine motor functions such as grasping. For gross motor functions, the discrete output may cause issues. Therefore, this work attempts to investigate the feasibility of utilising the classification model to control a 2-DoF transhumeral prosthesis for gross movement. The performance of 6 able-bodied subjects was evaluated in performing reaching and orientation matching tasks with a prosthetic arm in a virtual reality environment. The results were compared with the case of using their intact arms and existing results using the regression model. Our findings indicate that the classification-based method provides comparable performance to the regression model, making it a potential alternative for gross arm movement in multi-DoF prosthetic arms.

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.

The regulatory challenge of 3D bioprinting.

New developments in additive manufacturing and regenerative medicine have the potential to radically disrupt the traditional pipelines of therapy development and medical device manufacture. These technologies present a challenge for regulators because traditional regulatory frameworks are designed for mass manufactured therapies, rather than bespoke solutions. 3D bioprinting technologies present another dimension of complexity through the inclusion of living cells in the fabrication process. Herein we overview the challenge of regulating 3D bioprinting in comparison to existing cell therapy products as well as custom-made 3D printed medical devices. We consider a range of specific challenges pertaining to 3D bioprinting in regenerative medicine, including classification, risk, standardization and quality control, as well as technical issues related to the manufacturing process and the incorporated materials and cells.

What are the core recommendations for gout management in first line and specialist care? Systematic review of clinical practice guidelines.

BACKGROUND: Gout is the most common inflammatory arthritis, increasing in prevalence and burden. Of the rheumatic diseases, gout is the best-understood and potentially most manageable condition. However, it frequently remains untreated or poorly managed. The purpose of this systematic review is to identify Clinical Practice Guidelines (CPG) regarding gout management, evaluate their quality, and to provide a synthesis of consistent recommendations in the high-quality CPGs. METHODS: Gout management CPGs were eligible for inclusion if they were (1) written in English and published between January 2015-February 2022; focused on adults aged ≥ 18 years of age; and met the criteria of a CPG as defined by the Institute of Medicine; and (2) were rated as high quality on the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Gout CPGs were excluded if they required additional payment to access; only addressed recommendations for the system/organisation of care and did not include interventional management recommendations; and/or included other arthritic conditions. OvidSP MEDLINE, Cochrane, CINAHL, Embase and Physiotherapy Evidence Database (PEDro) and four online guideline repositories were searched. RESULTS: Six CPGs were appraised as high quality and included in the synthesis. Clinical practice guidelines consistently recommended education, commencement of non-steroidal anti-inflammatories, colchicine or corticosteroids (unless contraindicated), and assessment of cardiovascular risk factors, renal function, and co-morbid conditions for acute gout management. Consistent recommendations for chronic gout management were urate lowering therapy (ULT) and continued prophylaxis recommended based on individual patient characteristics. Clinical practice guideline recommendations were inconsistent on when to initiate ULT and length of ULT, vitamin C intake, and use of pegloticase, fenofibrate and losartan. CONCLUSION: Management of acute gout was consistent across CPGs. Management of chronic gout was mostly consistent although there were inconsistent recommendations regarding ULT and other pharmacological therapies. This synthesis provides clear guidance that can assist health professionals to provide standardised, evidence-based gout care. TRIAL REGISTRATION: The protocol for this review was registered with Open Science Framework (DOI https://doi.org/10.17605/OSF.IO/UB3Y7 ).