Abstract. Introduction. Precision health aims to develop personalised and proactive strategies for predicting, preventing, and treating complex diseases such as osteoarthritis (OA), a degenerative joint disease affecting over 300 million people worldwide. Due to OA heterogeneity, which makes developing effective treatments challenging, identifying patients at risk for accelerated disease progression is essential for efficient clinical trial design and new treatment target discovery and development. Objectives. This study aims to create a trustworthy and interpretable precision health tool that predicts rapid knee OA progression based on baseline patient characteristics using an advanced automated machine learning (autoML) framework, “Autoprognosis 2.0”. Methods. All available 2-year follow-up periods of 600 patients from the FNIH OA Biomarker Consortium were analysed using “Autoprognosis 2.0” in two separate approaches, with distinct definitions of clinical outcomes: multi-class predictions (categorising patients into non-progressors, pain-only progressors, radiographic-only progressors, and both pain and radiographic progressors) and binary predictions (categorising patients into non-progressors and progressors). Models were developed using a training set of 1352 instances and all available variables (including clinical, X-ray, MRI, and biochemical features), and validated through both stratified 10-fold cross-validation and hold-out validation on a testing set of 339 instances. Model performance was assessed using multiple evaluation metrics, such as AUC-ROC, AUC-PRC, F1-score, precision, and recall. Additionally, interpretability analyses were carried out to identify important predictors of rapid disease progression. Results. Our final models yielded high accuracy scores for both multi-class predictions (AUC-ROC: 0.858, 95% CI: 0.856–0.860; AUC-PRC: 0.675, 95% CI: 0.671–0.679; F1-score: 0.560, 95% CI: 0.554–0.566) and binary predictions (AUC-ROC: 0.717, 95% CI: 0.712–0.722; AUC-PRC: 0.620, 95% CI: 0.616–0.624; F1-score: 0.676, 95% CI: 0.673–0679). Important predictors of rapid disease progression included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and MRI features. Our models were further successfully validated using a hold-out dataset, which was previously omitted from model development and training (AUC-ROC: 0.877 for multi-class predictions; AUC-ROC: 0.746 for binary predictions). Additionally, accurate ML models were developed for predicting OA progression in a subgroup of patients aged 65 or younger (AUC-ROC: 0.862, 95% CI: 0.861–0.863 for multi-class predictions; AUC-ROC: 0.736, 95% CI: 0.734–0.738 for binary predictions). Conclusions. This study presents a reliable and interpretable precision health tool for predicting rapid knee OA progression using “Autoprognosis 2.0”. Our models provide accurate predictions and offer insights into important predictors of rapid disease progression. Furthermore, the transparency and interpretability of our methods may facilitate their acceptance by clinicians and patients, enabling effective utilisation in clinical practice. Future work should focus on refining these models by increasing the sample size, integrating additional features, and using independent datasets for external validation. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Precision health aims to develop personalised and proactive strategies for predicting, preventing, and treating complex diseases such as osteoarthritis (OA). Due to OA heterogeneity, which makes developing effective treatments challenging, identifying patients at risk for accelerated disease progression is essential for efficient clinical trial design and new treatment target discovery and development. To create a reliable and interpretable precision health tool that predicts rapid knee OA progression over a 2-year period from baseline patient characteristics using an advanced automated machine learning (autoML) framework, “Autoprognosis 2.0”. All available 2-year follow-up periods of 600 patients from the FNIH OA Biomarker Consortium were analysed using “Autoprognosis 2.0” in two separate approaches, with distinct definitions of clinical outcomes: multi-class predictions (categorising disease progression into pain and/or radiographic progression) and binary predictions. Models were developed using a training set of 1352 instances and all available variables (including clinical, X-ray, MRI, and biochemical features), and validated through both stratified 10-fold cross-validation and hold-out validation on a testing set of 339 instances. Model performance was assessed using multiple evaluation metrics. Interpretability analyses were carried out to identify important predictors of progression. Our final models yielded higher accuracy scores for multi-class predictions (AUC-ROC: 0.858, 95% CI: 0.856-0.860) compared to binary predictions (AUC-ROC: 0.717, 95% CI: 0.712-0.722). Important predictors of rapid disease progression included WOMAC scores and MRI features. Additionally, accurate ML models were developed for predicting OA progression in a subgroup of patients aged 65 or younger. This study presents a reliable and interpretable precision health tool for predicting rapid knee OA progression. Our models provide accurate predictions and, importantly, allow specific predictors of rapid disease progression to be identified. Furthermore, the transparency and explainability of our methods may facilitate their acceptance by clinicians and patients, enabling effective translation to clinical practice

Total knee and hip arthroplasty (TKA and THA) are the most commonly performed surgical procedures, the costs of which constitute a significant healthcare burden. Improving access to care for THA/TKA requires better efficiency. It is hypothesized that this may be possible through a two-stage approach that utilizes prediction of surgical time to enable optimization of operating room (OR) schedules. Data from 499,432 elective unilateral arthroplasty procedures, including 302,490 TKAs, and 196,942 THAs, performed from 2014-2019 was extracted from the American College of Surgeons (ACS) National Surgical and Quality Improvement (NSQIP) database. A deep multilayer perceptron model was trained to predict duration of surgery (DOS) based on pre-operative clinical and biochemical patient factors. A two-stage approach, utilizing predicted DOS from a held out “test” dataset, was utilized to inform the daily OR schedule. The objective function of the optimization was the total OR utilization, with a penalty for overtime. The scheduling problem and constraints were simulated based on a high-volume elective arthroplasty centre in Canada. This approach was compared to current patient scheduling based on mean procedure DOS. Approaches were compared by performing 1000 simulated OR schedules. The predict then optimize approach achieved an 18% increase in OR utilization over the mean regressor. The two-stage approach reduced overtime by 25-minutes per OR day, however it created a 7-minute increase in underutilization. Better objective value was seen in 85.1% of the simulations. With deep learning prediction and mathematical optimization of patient scheduling it is possible to improve overall OR utilization compared to typical scheduling practices. Maximizing utilization of existing healthcare resources can, in limited resource environments, improve patient's access to arthritis care by increasing patient throughput, reducing surgical wait times and in the immediate future, help clear the backlog associated with the COVID-19 pandemic

Numerous prediction tools are available for estimating postoperative risk following spine surgery. External validation studies have shown mixed results. We present the development, validation, and comparative evaluation of novel tool (NZSpine) for modelling risk of complications within 30 days of spine surgery. Data was gathered retrospectively from medical records of patients who underwent spine surgery at Waikato Hospital between January 2019 and December 2020 (n = 488). Variables were selected a priori based on previous evidence and clinical judgement. Postoperative adverse events were classified objectively using the Comprehensive Complication Index. Models were constructed for the occurrence of any complication and significant complications (based on CCI >26). Performance and clinical utility of the novel model was compared against SpineSage (. https://depts.washington.edu/spinersk/. ), an extant online tool which we have shown in unpublished work to be valid in our local population. Overall complication rate was 34%. In the multivariate model, higher age, increased surgical invasiveness and the presence of preoperative anemia were most strongly predictive of any postoperative complication (OR = 1.03, 1.09, 2.1 respectively, p <0.001), whereas the occurrence of a major postoperative complication (CCI >26) was most strongly associated with the presence of respiratory disease (OR = 2.82, p <0.001). Internal validation using the bootstrapped models showed the model was robust, with an AUC of 0.73. Using sensitivity analysis, 80% of the model's predictions were correct. By comparison SpineSage had an AUC of 0.71, and in decision curve analysis the novel model showed greater expected benefit at all thresholds of risk. NZSpine is a novel risk assessment tool for patients undergoing acute and elective spine surgery and may help inform clinicians and patients of their prognosis. Use of an objective tool may help to provide uniformity between DHBs when completing the “clinician assessment of risk” section of the national prioritization tool

Introduction. Achieving an appropriate primary stability after implantation is a prerequisite for the long-term viability of a dental implant. Virtual testing of the bone-implant construct can be performed with finite element (FE) simulation to predict primary stability prior to implantation. In order to be translated to clinical practice, such FE modeling must be based on clinically available imaging methods. The aim of this study was to validate an FE model of dental implant primary stability using cone beam computed tomography (CBCT) with ex vivo mechanical testing. Method. Three cadaveric mandibles (male donors, 87-97 years old) were scanned by CBCT. Twenty-three bone samples were extracted from the bones and conventional dental implants (Ø4.0mm, 9.5mm length) were inserted in each. The implanted specimens were tested under quasi-static bending-compression load (cf. ISO 14801). Sample-specific homogenized FE (hFE) models were created from the CBCT images and meshed with hexahedral elements. A non-linear constitutive model with element-wise density-based material properties was used to simulate bone and the implant was considered rigid. The experimental loading conditions were replicated in the FE model and the ultimate force was evaluated. Result. The experimental ultimate force ranged between 67 N and 789 N. The simulated ultimate force correlated better with the experimental ultimate force (R. 2. =0.71) than the peri-implant bone density (R. 2. =0.30). Conclusion. The developed hFE model was demonstrated to provide stronger prediction of primary stability than peri-implant bone density. Therefore, hFE Simulations based on this clinically available low-radiation imaging modality, is a promising technology that could be used in future as a surgery planning tool to assist the clinician in evaluating the load-bearing capacity of an implantation site. Acknowledgements. Funding: EU's Horizon 2020 grant No: 953128 (I-SMarD). Dental implants: THOMMEN Medical AG

Over 300,000 total hip arthroplasties (THA) are performed annually in the USA. Surgical Site Infections (SSI) are one of the most common complications and are associated with increased morbidity, mortality and cost. Risk factors for SSI include obesity, diabetes and smoking, but few studies have reported on the predictive value of pre-operative blood markers for SSI. The purpose of this study was to create a clinical prediction model for acute SSI (classified as either superficial, deep and overall) within 30 days of THA based on commonly ordered pre-operative lab markers and using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. All adult patients undergoing an elective unilateral THA for osteoarthritis from 2011–2016 were identified from the NSQIP database using Current Procedural Terminology (CPT) codes. Patients with active or chronic, local or systemic infection/sepsis or disseminated cancer were excluded. Multivariate logistic regression was used to determine coefficients, with manual stepwise reduction. Receiver Operating Characteristic (ROC) curves were also graphed. The SSI prediction model included the following covariates: body mass index (BMI) and sex, comorbidities such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), smoking, current/previous steroid use, as well as pre-operative blood markers, albumin, alkaline phosphate, blood urea nitrogen (BUN), creatinine, hematocrit, international normalized ratio (INR), platelets, prothrombin time (PT), sodium and white blood cell (WBC) levels. Since the data met logistic assumption requirements, bootstrap estimation was used to measure internal validity. The area under the ROC curve for final derivations along with McFadden's R-squared were utilized to compare prediction models. A total of 130,619 patients were included with the median age of patients at time of THA was 67 years (mean=66.6+11.6 years) with 44.8% (n=58,757) being male. A total of 1,561 (1.20%) patients had a superficial or deep SSI (overall SSI). Of all SSI, 45.1% (n=704) had a deep SSI and 55.4% (n=865) had a superficial SSI. The incidence of SSI occurring annually decreased from 1.44% in 2011 to 1.16% in 2016. Area under the ROC curve for the SSI prediction model was 0.79 and 0.78 for deep and superficial SSI, respectively and 0.71 for overall SSI. CHF had the largest effect size (Odds Ratio(OR)=2.88, 95% Confidence Interval (95%CI): 1.56 – 5.32) for overall SSI risk. Albumin (OR=0.44, 95% CI: 0.37 – 0.52, OR=0.31, 95% CI: 0.25 – 0.39, OR=0.48, 95% CI: 0.41 – 0.58) and sodium (OR=0.95, 95% CI: 0.93 – 0.97, OR=0.94, 95% CI: 0.91 – 0.97, OR=0.95, 95% CI: 0.93 – 0.98) levels were consistently significant in all clinical prediction models for superficial, deep and overall SSI, respectively. In terms of pre-operative blood markers, hypoalbuminemia and hyponatremia are both significant risk factors for superficial, deep and overall SSI. In this large NSQIP database study, we were able to create an SSI prediction model and identify risk factors for predicting acute superficial, deep and overall SSI after THA. To our knowledge, this is the first clinical model whereby pre-operative hyponatremia (in addition to hypoalbuminemia) levels have been predictive of SSI after THA. Although the model remains without external validation, it is a vital starting point for developing a risk prediction model for SSI and can help physicians mitigate risk factors for acute SSI post THA

Abstract. Introduction. Minimising postoperative complications and mortality in COVID-19 patients who were undergoing trauma and orthopaedic surgeries is an international priority. Aim was to develop a predictive nomogram for 30-day morbidity/mortality of COVID-19 infection in patients who underwent orthopaedic and trauma surgery during the coronavirus pandemic in the UK in 2020 compared to a similar period in 2019. Secondary objective was to compare between patients with positive PCR test and those with negative test. Methods. Retrospective multi-center study including 50 hospitals. Patients with suspicion of SARS-CoV-2 infection who had underwent orthopaedic or trauma surgery for any indication during the 2020 pandemic were enrolled in the study (2525 patients). We analysed cases performed on orthopaedic and trauma operative lists in 2019 for comparison (4417). Multivariable Logistic Regression analysis was performed to assess the possible predictors of a fatal outcome. A nomogram was developed with the possible predictors and total point were calculated. Results. Of the 2525 patients admitted for suspicion of COVID-19, 658 patients had negative preoperative test, 151 with positive test and 1716 with unknown preoperative COVID-19 status. Preoperative COVID-19 status, sex, ASA grade, urgency and indication of surgery, use of torniquet, grade of operating surgeon and some comorbidities were independent risk factors associated with 30-day complications/mortality. The 2020 nomogram model exhibited moderate prediction ability. In contrast, the prediction ability of total points of 2019 nomogram model was excellent. Conclusions. Nomograms can be used by orthopaedic and trauma surgeons as a practical and effective tool in postoperative complications and mortality risk estimation

Background. Although there are predictive equations that estimate the total fat mass obtained from multiple-site ultrasound (US) measurements, the predictive equation of total fat mass has not been investigated solely from abdominal subcutaneous fat thickness. Therefore, the aims of this study were; (1) to develop regression-based prediction equations based on abdominal subcutaneous fat thickness for predicting fat mass in young- and middle-aged adults, and (2) to investigate the validity of these equations to be developed. Methods. The study was approved by the Local Research Ethics Committee (Decision number: GO 19/788). Twenty-seven males (30.3 ± 8.7 years) and eighteen females (32.4 ± 9.5 years) were randomly divided into two groups as the model prediction group (19 males and 12 females) and the validation group (8 males and 6 females). Total body fat mass was determined by dual-energy X-ray absorptiometry (DXA). Abdominal subcutaneous fat thickness was measured by US. The predictive equations for total fat mass from US were determined as fat thickness (in mm) × standing height (in m). Statistical analyses were performed using R version 4.0.0. The association between the total fat mass and the abdominal subcutaneous fat thickness was interpreted using the Pearson test. The linear regression analysis was used to predict equations for total body fat mass from the abdominal subcutaneous fat thickness acquired by US. Then these predictive equations were applied to the validation group. The paired t-test was used to examine the difference between the measured and the predicted fat masses, and Lin's concordance correlation coefficient (CCC) was used as a further measure of agreement. Results. There was a significant positive moderate correlation between the total fat mass and the abdominal subcutaneous fat thickness × height in the model prediction group of males (r = 0.588, p = 0.008), whereas significant positive very strong correlation was observed in the model prediction group of females (r = 0.896, p < 0.001). Predictive equations for DXA-measured total body fat mass from abdominal subcutaneous fat thickness using US were as follows: for males “Fat mass-DXA = 0.276 × (Fat thickness-US × Height) + 17.221” (R. 2. = 0.35, SEE = 3.6, p = 0.008); for females “Fat mass-DXA = 0.694 x (Fat thickness-US × Height) + 7.085” (R. 2. = 0.80, SEE = 2.8, p < 0.001). When fat mass prediction equations were applied to the validation groups, measured- and estimated-total fat masses in males and females were found similar (p = 0.9, p = 0.5, respectively). A good level of agreement between measurements in males and females was attained (CCC = 0.84, CCC = 0.76, respectively). Conclusion. We developed and validated prediction equations that are convenient for determining total fat masses in young- and middle-aged adults using abdominal subcutaneous fat thickness obtained from the US. The abdominal subcutaneous fat thickness obtained from a single region by US might provide a noninvasive quick and easy evaluation not only in clinical settings but also on the field

Total knee arthroplasty (TKA) is the most commonly performed elective orthopaedic procedure. With an increasingly aging population, the number of TKAs performed is expected to be ∼2,900 per 100,000 by 2050. Surgical Site Infections (SSI) after TKA can have significant morbidity and mortality. The purpose of this study was to construct a risk prediction model for acute SSI (classified as either superficial, deep and overall) within 30 days of a TKA based on commonly ordered pre-operative blood markers and using audited administrative data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. All adult patients undergoing an elective unilateral TKA for osteoarthritis from 2011–2016 were identified from the NSQIP database using Current Procedural Terminology (CPT) codes. Patients with active or chronic, local or systemic infection/sepsis or disseminated cancer were excluded. Multivariate logistic regression was conducted to estimate coefficients, with manual stepwise reduction to construct models. Bootstrap estimation was administered to measure internal validity. The SSI prediction model included the following co-variates: body mass index (BMI) and sex, comorbidities such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), smoking, current/previous steroid use, as well as pre-operative blood markers, albumin, alkaline phosphatase, blood urea nitrogen (BUN), creatinine, hematocrit, international normalized ratio (INR), platelets, prothrombin time (PT), sodium and white blood cell (WBC) levels. To compare clinical models, areas under the receiver operating characteristic (ROC) curves and McFadden's R-squared values were reported. The total number of patients undergoing TKA were 210,524 with a median age of 67 years (mean age of 66.6 + 9.6 years) and the majority being females (61.9%, N=130,314). A total of 1,674 patients (0.8%) had a SSI within 30 days of the index TKA, of which N=546 patients (33.2%) had a deep SSI and N=1,128 patients (67.4%) had a superficial SSI. The annual incidence rate of overall SSI decreased from 1.60% in 2011 to 0.68% in 2016. The final risk prediction model for SSI contained, smoking (OR=1.69, 95% CI: 1.31 – 2.18), previous/current steroid use (OR=1.66, 95% CI: 1.23 – 2.23), as well as the pre-operative lab markers, albumin (OR=0.46, 95% CI: 0.37 – 0.56), blood urea nitrogen (BUN, OR=1.01, 95% CI: 1 – 1.02), international normalized ratio (INR, OR=1.22, 95% CI:1.05 – 1.41), and sodium levels (OR=0.94, 95% CI: 0.91 – 0.98;). Area under the ROC curve for the final model of overall SSI was 0.64. Models for deep and superficial SSI had ROC areas of 0.68 and 0.63, respectively. Albumin (OR=0.46, 95% CI: 0.37 – 0.56, OR=0.33, 95% CI: 0.27 – 0.40, OR=0.75, 95% CI: 0.59 – 0.95) and sodium levels (OR=0.94, 95% CI: 0.91 – 0.98, OR=0.96, 95% CI: 0.93 – 0.99, OR=0.97, 95% CI: 0.96 – 0.99) levels were consistently significant in all prediction models for superficial, deep and overall SSI, respectively. Overall, hypoalbuminemia and hyponatremia are both significant risk factors for superficial, deep and overall SSI. To our knowledge, this is the first prediction model for acute SSI post TKA whereby hyponatremia (and hypoalbuminemia) are predictive of SSI. This prediction model can help fill an important gap for predicting risk factors for SSI after TKA and can help physicians better optimize patients prior to TKA

Introduction. Diaphyseal tibial fractures account for approximately 1.9% of adult fractures. Several studies demonstrate a high proportion of diaphyseal tibial fractures have ipsilateral occult posterior malleolus fractures, this ranges from 22–92.3%. Materials and Methods. A retrospective review of a prospectively collected database was performed at Liverpool University Hospitals NHS Foundation Trust between 1/1/2013 and 9/11/2020. The inclusion criteria were patients over 16, with a diaphyseal tibial fracture and who underwent a CT. The articular fracture extension was categorised into either posterior malleolar (PM) or other fracture. Results. 764 fractures were analysed, 300 had a CT. There were 127 intra-articular fractures. 83 (65.4%) cases were PM and 44 were other fractures. On univariate analysis for PM fractures, fibular spiral (p=.016) fractures, no fibular fracture(p=.003), lateral direction of the tibial fracture (p=.04), female gender (p=.002), AO 42B1 (p=.033) and an increasing angle of tibial fracture. On multivariate regression analysis a high angle of tibia fracture was significant. Other fracture extensions were associated with no fibular fracture (p=.002), medial direction of tibia fracture (p=.004), female gender (p=.000), and AO 42A1 (p=.004), 42A2 (p=.029), 42B3 (p=.035) and 42C2 (p=.032). On multivariate analysis, the lateral direction of tibia fracture, and AO classification 42A1 and 42A2 were significant. Conclusions. Articular extension happened in 42.3%. A number of factors were associated with the extension, however multivariate analysis did not create a suitable prediction model. Nevertheless, rotational tibia fractures with a high angle of fracture should have further investigation with a CT

Background. Dislocation is a common complication following total hip arthroplasty (THA), and accounts for a high percentage of subsequent revisions. The purpose of this study was to develop a convolutional neural network (CNN) model to identify patients at high risk for dislocation based on postoperative anteroposterior (AP) pelvis radiographs. Methods. We retrospectively evaluated radiographs for a cohort of 13,970 primary THAs with 374 dislocations over 5 years of follow-up. Overall, 1,490 radiographs from dislocated and 91,094 from non-dislocated THAs were included in the analysis. A CNN object detection model (YOLO-V3) was trained to crop the images by centering on the femoral head. A ResNet18 classifier was trained to predict subsequent hip dislocation from the cropped imaging. The ResNet18 classifier was initialized with ImageNet weights and trained using FastAI (V1.0) running on PyTorch. The training was run for 15 epochs using ten-fold cross validation, data oversampling and augmentation. Results. The hip dislocation prediction classifier achieved the following mean performance: accuracy= 49.5(±4.1)%, sensitivity= 89.0(±2.2)%, specificity= 48.8(±4.2)%, positive predictive value= 3.3(±0.3)%, negative predictive value= 99.5(±0.1)%, and area under the receiver operating characteristic curve= 76.7(±3.6)%. Saliency maps demonstrated that the model placed the greatest emphasis on the femoral head and acetabular component. Conclusions. Existing prediction methods fail to identify patients at high risk of dislocation following THA. Our prediction model has high sensitivity and negative predictive value. Therefore, it can be helpful in rapid assessment of risk for dislocation following THA. The model further suggests radiographic locations which may be important in understanding the etiology of prosthesis dislocation

Although 3D-printed porous dental implants may possess improved osseointegration potential, they must exhibit appropriate fatigue strength. Finite element analysis (FEA) has the potential to predict the fatigue life of implants and accelerate their development. This work aimed at developing and validating an FEA-based tool to predict the fatigue behavior of porous dental implants. Test samples mimicking dental implants were designed as 4.5 mm-diameter cylinders with a fully porous section around bone level. Three porosity levels (50%, 60% and 70%) and two unit cell types (Schwarz Primitive (SP) and Schwarz W (SW)) were combined to generate six designs that were split between calibration (60SP, 70SP, 60SW, 70SW) and validation (50SP, 50SW) sets. Twenty-eight samples per design were additively manufactured from titanium powder (Ti6Al4V). The samples were tested under bending compression loading (ISO 14801) monotonically (N=4/design) to determine ultimate load (F. ult. ) (Instron 5866) and cyclically at six load levels between 50% and 10% of F. ult. (N=4/design/load level) (DYNA5dent). Failure force results were fitted to F/F. ult. = a(N. f. ). b. (Eq1) with N. f. being the number of cycles to failure, to identify parameters a and b. The endurance limit (F. e. ) was evaluated at N. f. = 5M cycles. Finite element models were built to predict the yield load (F. yield. ) of each design. Combining a linear correlation between FEA-based F. yield. and experimental F. ult. with equation Eq1 enabled FEA-based prediction of F. e. . For all designs, F. e. was comprised between 10% (all four samples surviving) and 15% (at least one failure) of F. ult. The FEA-based tool predicted F. e. values of 11.7% and 12.0% of F. ult. for the validation sets of 50SP and 50SW, respectively. Thus, the developed FEA-based workflow could accurately predict endurance limit for different implant designs and therefore could be used in future to aid the development of novel porous implants. Acknowledgements: This study was funded by EU's Horizon 2020 grant No. 953128 (I-SMarD). We gratefully acknowledge the expert advice of Prof. Philippe Zysset

Background. Postoperative recovery after routine total hip arthroplasty (THA) can lead to the development of prolonged opioid use but there are few tools for predicting this adverse outcome. The purpose of this study was to develop machine learning algorithms for preoperative prediction of prolonged post-operative opioid use after THA. Methods. A retrospective review of electronic health records was conducted at two academic medical centers and three community hospitals to identify adult patients who underwent THA for osteoarthritis between January 1. st. , 2000 and August 1. st. , 2018. Prolonged postoperative opioid prescriptions were defined as continuous opioid prescriptions after surgery to at least 90 days after surgery. Five machine learning algorithms were developed to predict this outcome and were assessed by discrimination, calibration, and decision curve analysis. Results. Overall, 5507 patients underwent THA, of which 345 (6.3%) had prolonged postoperative opioid prescriptions. The factors determined for prediction of prolonged postoperative opioid prescriptions were: age, duration of pre-operative opioid exposure, preoperative hemoglobin, and certain preoperative medications (anti-depressants, benzodiazepines, non-steroidal anti-inflammatory drugs, and beta-2-agonists). The elastic-net penalized logistic regression model achieved the best performance across discrimination (c-statistic = 0.77), calibration, and decision curve analysis. This model was incorporated into a digital application able to provide both predictions and explanations; available here: . https://sorg-apps.shinyapps.io/thaopioid/. Conclusion. If externally validated in independent populations, the algorithms developed in this study could improve preoperative screening and support for THA patients at high-risk for prolonged postoperative opioid use. Early identification and intervention in high-risk cases may mitigate the long-term adverse consequence of opioid dependence. For any tables or figures, please contact the authors directly

Background. There is a 20% dissatisfaction rate with knee replacements. Calls for tools that can pre-operatively identify patients at risk of being dissatisfied postoperatively have been widespread. However, it is unclear what sort of information patients would want from such a tool, how it would affect their decision making process, and at what part of the pathway such a tool should be used. Methods. Using focus groups involving 12 participants and in-depth interviews with 10 participants, we examined the effect outcome prediction has by providing fictitious predictions to patients at different stages of treatment. A qualitative analysis of themes, based on a constant comparative method, is used to analyse the data. This study was approved by the Dyfed Powys Research Ethics Committee (13/WA/0140). Results. Our results demonstrate several interesting findings. Firstly, patients who have received information from friends and family are unwilling to adjust their expectation of outcome down (i.e. to a worse outcome), but highly willing to adjust it up (to a better outcome). This is an example of the optimism bias, and suggests the effect on expectation of any poor outcome prediction would be blunted. Secondly, patients generally wanted a “bottom line” outcome, rather than lots of detail. Thirdly, patients who were earlier in their treatment for osteoarthritis were more likely to find the information useful, and for it to affect their decision, than patients later in their pathway. Conclusion. An outcome prediction tool would have most effect targeted towards people at the start of their treatment pathway, with a “bottom line” prediction of outcome. However, any effect on expectation and decision making of a poor outcome prediction is likely to be blunted by the optimism bias. Level of Evidence. 4

Background. Stability of total knee arthroplasty (TKA) is dependent on correct and precise rotation of the femoral component. Multiple differing surgical techniques are currently utilized to perform total knee arthroplasty. Accurate implant position have been cited as the most important factors of successful TKA. There are two techniques of achieving soft gap balancing in TKA; a measured resection technique and a balanced gap technique. Debate still exists on the choice of surgical technique to achieve the optimal soft tissue balance with opinions divided between the measured resection technique and the gap balance technique. In the measured resection technique, the bone resection depends on size of the prosthesis and is referenced to fixed anatomical landmarks. This technique however may have accompanying problems in imbalanced patients. Prediction of gap balancing technique, tries to overcome these fallacies. Our aim in this study was twofold: 1) To describe our methodology of ROBOTIC TKA using prediction of gap balancing technique. 2) To analyze the clinico-radiological outcome our technique comparison of meseaured resection ROBOTIC TKA after 1year. Methods. Patients that underwent primary TKA using a robotic system were included for this study. Only patients with a diagnosis of primary degenerative osteoarthritis with varus deformity and flexion deformity of were included in this study. Patients with valgus deformity, secondary arthritis, inflammatory arthritis, and severe varus/flexion deformity were excluded. Three hundred ten patients (319 knees) who underwent ROBOTIC TKA using measured resection technique from 2004 – 2009. Two hundred twenty (212 knees) who underwent ROBOTIC TKA using prediction of gap balancing technique from 2010 – 2012. Clinical outcomes including KS and WOMAC scores, and ranges of motion and radiological outcomes including mechanical axis, prosthesis alignments, flexion varus/valgus stabilities were compared after 1year. Results. Leg mechanical axes were significantly different at follow-up 1year versus preoperative values, the mean axes in the Robotic-TKA with measured resection technique and Robotic-TKA with prediction of gap balancing technique improved from 9.6±5.0° of varus to 0.5±1.9° of varus, and from 10.6±5.5° to 0.4±1.3° of varus (p<0.001), respectively. However, no significant intergroup differences were found between mechanical axis or coronal alignments of femoral or tibial prostheses (pï¼ï¿½0.05). Mean varus laxities at 90° of knee flexion in measured resection and gap prediction technique group were 6.4° and 5.3°, respectively, and valgus laxities were 6.2 and 5.2 degrees, respectively, with statistical significance (p=0.045 and 0.032, respectively). KS knee and function scores and WOMAC scores were significantly improved at follow-up 1year (pï¼ï¿½0.05). However, no significant difference was found between the Robotic-TKA with measured resection technique and Robotic-TKA with prediction of gap balancing technique for any clinical outcome parameter at follow-up 1year (pï¼ï¿½0.05). Conclusions. Robotic assisted TKA using measured resection or gap prediction technique provide adequate and practically identical levels of flexion stability at 90° of knee flexion with accurate leg and prosthesis alignment. But, Robotic TKA using measured resection technique have less than flexion stability compared with gap prediction technique with statistical significance after follow-up 1year

Background. Total knee arthroplasty (TKA) is a proven and cost-effective treatment for osteoarthritis. Despite the good to excellent long-term results, some patients remain dissatisfied. Our study aimed at establishing a predictive model to aid patient selection and decision-making in TKA. Methods. Using data from our prospective arthroplasty outcome database, 113 patients were included. Pre- and postoperatively, the patients completed 107 questions in 5 questionnaires: KOOS, OKS, PCS, EQ-5D and KSS. First, outcome parameters were compared between the satisfied and dissatisfied group. Secondly, we developed a new prediction tool using regression analysis. Each outcome score was analysed with simple regression. Subsequently, the predictive weight of individual questions was evaluated applying multiple linear regression. Finally, 10 questions were retained to construct a new prediction tool. Results. Overall satisfaction rate in this study was found to be 88%. We identified a significant difference between the satisfied and dissatisfied group when looking at the preoperative questionnaires. Dissatisfied patients had more preoperative symptoms (such as stiffness), less pain and a lower QOL. They were more likely to ruminate and had a lower preoperative KSS satisfaction score. The developed prediction tool consists of 10 simple, but robust questions. Sensitivity was 97% with a positive predictive value of 93%. Conclusions. Based upon preoperative parameters, we were able to partially predict satisfaction and dissatisfaction after TKA. After further validation this new prediction tool for patient satisfaction following TKA may allow surgeons and patients to evaluate the risks and benefits of surgery on an individual basis and help in patient selection

Introduction. Up to 60% of total hip arthroplasties (THA) in Asian populations arise from avascular necrosis (AVN), a bone disease that can lead to femoral head collapse. Current diagnostic methods to classify AVN have poor reproducibility and are not reliable in assessing the fracture risk. Femoral heads with an immediate fracture risk should be treated with a THA, conservative treatments are only successful in some cases and cause unnecessary patient suffering if used inappropriately. There is potential to improve the assessment of the fracture risk by using a combination of density-calibrated computed tomographic (QCT) imaging and engineering beam theory. The aim of this study was to validate the novel fracture prediction method against in-vitro compression tests on a series of six human femur specimens. Methods. Six femoral heads from six subjects were tested, a subset (n=3) included a hole drilled into the subchondral area of the femoral head via the femoral neck (University of Leeds, ethical approval MEEC13-002). The simulated lesions provided a method to validate the fracture prediction model with respect of AVN. The femoral heads were then modelled by a beam loaded with a single joint contact load. Material properties were assigned to the beam model from QCT-scans by using a density-modulus relationship. The maximum joint loading at which each bone cross-section was likely to fracture was calculated using a strain based failure criterion. Based on the predicted fracture loads, all six femoral heads (validation set) were classified into two groups, high fracture risk and low fracture risk (Figure 1). Beam theory did not allow for an accurate fracture load to be found because of the geometry of the femoral head. Therefore the predicted fracture loads of each of the six femoral heads was compared to the mean fracture load from twelve previously analysed human femoral heads (reference set) without lesions. The six cemented femurs were compression tested until failure. The subjects with a higher fracture risk were identified using both the experimental and beam tool outputs. Results. The computational tool correctly identified all femoral head samples which fractured at a significantly low load in-vitro (Figure 2). Both samples with a low experimental fracture load had an induced lesion in the subchondral area (Figure 3). Discussion. This study confirmed findings of a previous verification study on a disease models made from porcine femoral heads (Preutenborbeck et al. I-CORS2016). It demonstrated that fracture prediction based on beam theory is a viable tool to predict fracture. The tests confirmed that samples with a lesion in the weight bearing area were more likely to fracture at a low load however not all samples with a lesion fractured with a low load experimentally, indicating that a lesion alone is not a sufficient factor to predict fracture. The developed tool takes both structural and material properties into account when predicting the fracture risk. Therefore it might be superior to current diagnostic methods in this respect and it has the added advantage of being largely automated and therefore removing the majority of user bias. For any figures or tables, please contact the authors directly

Introduction and Aims: We propose a new, simple, and universal method to predict adult height: the Height Multiplier Method. Our aim was to calculate height multipliers from various databases and validate their use for height prediction. Method: Standard growth charts, based on a diverse population, were published by the Centres for Disease Control and Prevention (CDC) in 2000. Height multipliers (M) for boys and girls were calculated by dividing the height at skeletal maturity (Htm) by the present height (Ht) (M = Htm/Ht) for each age, gender, and height percentile using CDC data. These multipliers were compared with multipliers derived from various height databases of 28 boys and 24 girls. The accuracy of the multipliers was tested on individual longitudinal data sets from 52 normal children. Results: The average CDC-derived multipliers were significantly different at each age for boys and girls, but within gender, different percentiles at each age were very similar. These multipliers were very similar to multipliers derived from each of the databases. For predictions based on individual data sets from 52 children, the median, 90%, and standard deviation of absolute error prediction (AEP) were calculated. Boys’ median AEP ranged from 1.4–4.3cm; 90% AEP ranged from 1.8–8.3cm. Girls’ median AEP ranged from 0.68–4.38cm; 90% AEP ranged from 1.5–10.6cm. Conclusion: The Height Multiplier Method of stature prediction is as accurate as CDC growth charts when based on single-height measurements and is similar in accuracy to other methods. The Height Multiplier Method has the advantage of percentile, race, nationality, and generation independence. Growth charts have the advantage of showing trends over time

In conventional DXA (Dual-energy X-ray Absorptiometry) analysis, pixel bone mineral density (BMD) is often averaged at the femoral neck. Neck BMD constitutes the basis for osteoporosis diagnosis and fracture risk assessment. This data averaging, however, limits our understanding of localised spatial BMD patterns that could potentially enhance fracture prediction. DXA region free analysis (RFA) is a validated toolkit for pixel-level BMD analysis. We have previously deployed this toolkit to develop a spatio-temporal atlas of BMD ageing in the femur. This study aims first to introduce bone age to reflect the overall bone structural evolution with ageing, and second to quantify fracture-specific patterns in the femur. The study dataset comprised 4933 femoral DXA scans from White British women aged 75 years or older. The total number of fractures was 684, of which 178 were reported at the hip within a follow-up period of five years. BMD maps were computed using the RFA toolkit. For each BMD map, bone age was defined as the age for which the L2-norm between the map and the median atlas at that age is minimised. Next, bone maps were normalised for the estimated bone age. A t-test followed by false discovery rate (FDR) analysis was applied to compare between fracture and non-fracture groups. Excluding the ageing effect revealed subtle localised patterns of loss in BMD oriented in the same direction as principal tensile curves. A new score called f-score was defined by averaging the normalised pixel BMD values over the region with FDR q-value less than 1e–6. The area under the curve (AUC) was 0.731 (95% confidence interval (CI)=0.689–0.761) and 0.736 (95% CI=0.694–0.769) for neck BMD and f-score. Combining bone age and f-score improved the AUC significantly by 3% (AUC=0.761, 95% CI=0.756–0.768) over the neck BMD alone (AUC=0.731, 95% CI=0.726–0.737). This technique shows promise in characterizing spatially-complex BMD changes, for which the conventional region-based technique is insensitive. DXA RFA shows promise to further improve fracture prediction using spatial BMD distribution

During OA the homeostasis of healthy articular chondrocytes is dysregulated, which leads to a phenotypical transition of the cells, further influenced by external stimuli. Chondrocytes sense those stimuli, integrate them at the intracellular level and respond by modifying their secretory and molecular state. This process is controlled by a complex interplay of intracellular factors. Each factor is influenced by a myriad of feedback mechanisms, making the prediction of what will happen in case of external perturbation challenging. Hampering the hypertrophic phenotype has emerged as a potential therapeutic strategy to help OA patients (Ripmeester et al. 2018). Therefore, we developed a computational model of the chondrocyte's underlying regulatory network (RN) to identify key regulators as potential drug targets. A mechanistic mathematical model of articular chondrocyte differentiation was implemented with a semi-quantitative formalism. It is composed of a protein RN and a gene RN(GRN) and developed by combining two strategies. First, we established a mechanistic network based on accumulation of decades of biological knowledge. Second, we combined that mechanistic network with data-driven modelling by inferring an OA-GRN using an ensemble of machine learning methods. This required a large gene expression dataset, provided by distinct public microarrays merged through an in-house pipeline for cross-platform integration. We successfully merged various micro-array experiments into one single dataset where the biological variance was predominant over the batch effect from the different technical platforms. The gain of information provided by this merge enabled us to reconstruct an OA-GRN which subsequently served to complete our mechanistic model. With this model, we studied the system's multi-stability, equating the model's stable states to chondrocyte phenotypes. The network structure explained the occurrence of two biologically relevant phenotypes: a hypertrophic-like and a healthy-like phenotype, recognized based on known cell state markers. Second, we tested several hypotheses that could trigger the onset of OA to validate the model with relevant biological phenomena. For instance, forced inflammation pushed the chondrocyte towards hypertrophy but this was partly rescued by higher levels of TGF-β. However, we could annihilate this rescue by concomitantly mimicking an increase in the ALK1/ALK5 balance. Finally, we performed a screening of in-silico (combinatorial) perturbations (inhibitions and/or over-activations) to identify key molecular factors involved in the stability of the chondrocyte state. More precisely, we looked for the most potent conditions for decreasing hypertrophy. Preliminary validation experiments have confirmed that PKA activation could decrease the hypertrophic phenotype in primary chondrocytes. Importantly the in-silico results highlighted that targeting two factors at the same time would greatly help reducing hypertrophic changes. A priori testing of conditions with in-silico models may cut time and cost of experiments via target prioritization and opens new routes for OA combinatorial therapies