Pre-clinical evaluation of biomarkers for the early detection of nephrotoxicity following alpha-particle radioligand therapy.

PURPOSE: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as an additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLT nephrotoxicity. METHODS: A bifunctional cyclic peptide, melanocortin 1 ligand (MC1L), labeled with [203Pb]Pb-MC1L, was used for [212Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [212Pb]Pb-MC1L in a dose-escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. RESULTS: Biodistribution analysis identified [212Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [212Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [212Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. CONCLUSION: Urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.

Gaps and inconsistencies in the current knowledge and implementation of biosafety and biosecurity practices for rickettsial pathogens.

INTRODUCTION: Rickettsia spp. and Orientia spp. are the causes of neglected infections that can lead to severe febrile and systemic illnesses in humans. Implementing proper biosafety practices when handling these pathogens is crucial to ensure a safe and sustainable work environment. It is essential to assess the current knowledge and identify any potential gaps to develop effective measures that minimise the risk of exposure to these pathogens. By doing so, we can establish a comprehensive framework that promotes safety, mitigates hazards, and safeguards the well-being of personnel and the surrounding community. METHODS AND RESULTS: This review aimed to synthesise and determine the evidence base for biosafety precautions for Rickettsia spp. and Orientia spp. pathogens. Enhancing our understanding of the relative infectious risk associated with different strains of Rickettsia and Orientia spp. requires identifying the infectious dose of these pathogens that can cause human disease. The application of risk groups for Rickettsia and Orientia spp. is inconsistent across jurisdictions. There is also incomplete evidence regarding decontamination methods for these pathogens. With regards to Orientia spp. most of the available information is derived from experiments conducted with Rickettsia spp. CONCLUSIONS: Rickettsia and Orientia spp. are neglected diseases, as demonstrated by the lack of evidence-based and specific biosafety information about these pathogens. In the case of Orientia spp., most of the available information is derived from Rickettsia spp., which may not be appropriate and overstate the risks of working with this pathogen. The advent of effective antibiotic therapy and a better understanding of the true hazards and risks associated with pathogen manipulation should inform decisions, allowing a sustainable and safe work environment.

AAPM Medical Physics Practice Guideline 14.a: Yttrium-90 microsphere radioembolization.

Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.

Clinical and laboratory aspects of condylomata lata lesions of syphilis.

OBJECTIVES: Condylomata lata are a less common but distinctive syphilitic lesion. Variable theories as to their nature and origin exist. The aim of this study was to determine the clinical and laboratory characteristics of condylomata lata by determining (1): the most closely aligned stage of syphilis, based on the rapid plasma reagin (RPR) titre; (2) symptom duration and (3) Treponema pallidum PCR cycle threshold (CT) values, as an indicator of organism load. METHODS: This was a retrospective study of patients with T. pallidum PCR-positive condylomata lata lesions, attending a clinic in Melbourne, Australia, between 2011 and 2021. Syphilis serology was undertaken and RPR titres compared between condylomata lata, primary and secondary syphilis cases. RESULTS: 51 cases with T. pallidum PCR-positive condylomata lata were included. 41 cases were in men, 40 of whom were men who have sex with men (MSM), and 10 in women. Twelve of 51 (24%) cases were in HIV-positive MSM. Thirty-three of 51 (65%) had other mucocutaneous signs of secondary syphilis; 18 (35%) had no other signs of secondary syphilis. The median RPR titre among the 51 condylomata lata cases was 1:128, compared with the median RPR titre of primary syphilis (1:4) and of secondary syphilis (1:128). The median duration of lesions was 24 (IQR 10-60) days, with no significant difference between those with and without other signs of secondary syphilis (p=0.75). Median CT values for condylomata lata (CT=31) and primary syphilis (CT=31) were significantly lower than for other secondary syphilis lesion types (CT=33), indicating higher T. pallidum loads for condylomata lata and primary lesions compared with other secondary syphilis lesion types. DISCUSSION: These findings support condylomata lata as lesions that occur during the secondary stage of syphilis and which are likely to be highly infectious.

Safety and feasibility of same-day discharge following minimally invasive hysterectomy in the morbidly obese patient population.

OBJECTIVES: To determine whether morbid obesity should serve as an independent factor in the decision for same day discharge following minimally invasive hysterectomy. METHODS: Retrospective review was performed of patients with BMI ≥ 40 who underwent minimally invasive hysterectomy within a single comprehensive cancer center between January 2018 - August 2020. Demographics, perioperative factors, post-operative monitoring, complications, and readmissions were compared between patients who underwent same day discharge and overnight observation using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: 374 patients with BMI ≥ 40 were included. Eighty-three (22.2%) patients underwent same day discharge, and 291 (77.8%) patients underwent overnight observation. Factors associated with increased likelihood of same day discharge included younger age (median age 53 vs 58; p = 0.001), lower BMI (median BMI 45 vs 47; p = 0.005), and fewer medical co-morbidities (Charlson Co-Morbidity Index 2 vs 3; p < 0.001). On multivariate regression analysis, frailty (OR 2.16 [1.14-4.11], p = 0.019) and surgical completion time after 12 PM (OR 3.67 [2.16-6.24], p < 0.001) were associated with increased risk of overnight observation. Few patients admitted for routine overnight observation required medical intervention (n = 14, 4.8%); most of these patients were frail (64.3%). The overall hospital readmission rate within 30 days of discharge was 3.2% (n = 12), with no patients discharged on the day of surgery being readmitted. CONCLUSIONS: Morbid obesity alone should not serve as a contraindication to same day discharge following minimally invasive hysterectomy. Admission for observation was associated with low rates of clinically meaningful intervention, and patients who underwent same day discharge were not at increased risk of adverse outcome.

Antibiotic utilisation in primary and revision total hip replacement patients: A registry linkage cohort study of 106 253 patients using the Australian Orthopaedic Association National Joint Replacement Registry.

PURPOSE: Infection is a major complication following joint replacement (JR) surgery. However, little data exist regarding antibiotic utilisation following primary JR and how use changes with subsequent revision surgery. This study aimed to examine variation in antibiotic utilisation rates before and after hip replacement surgery in those revised for infection, revised for other reasons and those without revision. METHODS: This retrospective cohort analysis used linked data from the Australian Orthopaedic Association National Joint Replacement Registry and Australian Government Pharmaceutical Benefits Scheme. Patients were included if undergoing total hip replacement (THR) for osteoarthritis in private hospitals between 2002 and 2017. Three groups were examined: primary THR with no subsequent revision (n = 102 577), primary THR with a subsequent revision for reasons other than periprosthetic joint infection (PJI) (n = 3156) and primary THR with a subsequent revision for PJI (n = 520). Monthly antibiotic utilisation rates and prevalence rate ratios (PRRs) with 95% confidence intervals (CIs) were calculated in the 2 years pre- and post-THR. RESULTS: Prior to primary THR antibiotic utilisation was 9%-10%. After primary THR, antibiotic utilisation rates were higher among patients revised for PJI (PRR 1.69, 95% CI 1.60-1.79) compared to non-revised patients, while the utilisation rate was lower in patients revised for reasons other than infection (PRR 0.96, 95% CI 0.93-0.98). For those revised for infection, antibiotic utilisation post-revision surgery was two times higher than those revised for other reasons (PRR 2.16, 95% CI 2.08-2.23). Utilisation of injectable antibiotics including, vancomycin, flucloxacillin and cephazolin was higher in those revised for PJI patients 0-2 weeks following surgery but not in those revised for other reasons compared to the non-revised group. CONCLUSIONS: Ongoing antibiotic utilisation after primary surgery may be an early signal of problems with the THR and should be a prompt for primary care physicians to refer patients to specialists for further appropriate investigations and management.

Obesity is associated with an increased risk of undergoing shoulder arthroplasty in Australia.

BACKGROUND: The aim of this study was to examine the incidence of overweight and obesity in patients undergoing primary total shoulder arthroplasty (TSA) for osteoarthritis (OA) in Australia compared to the incidence of obesity in the general population. MATERIALS AND METHODS: A 2017/18 cohort consisting of 2997 patients from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) who underwent TSA were compared with matched controls from the Australian Bureau of Statistics (ABS) National Health Survey from the same time period. The 2 groups were analyzed according to body mass index (BMI) category, sex, and age. RESULTS: According to the 2017/18 National Health Survey, 35.6% of Australian adults were overweight and 31.3% were obese. Of the primary TSA cases performed, 34.9% were overweight and 50.1% were obese. The relative risk of requiring TSA for OA increased with increasing BMI category. Class III obese females, aged 55-64, were 8.6 times more likely to receive a TSA compared to their normal weight counterparts. Males in the same age and BMI category were 2.5 times more likely. Class III obese patients underwent TSA 4 years (female) and 6 years (male) younger than their normal weight counterparts. CONCLUSION: Obesity significantly increases the risk of requiring TSA. The association appears to be particularly strong for younger females.

Hip Arthroplasty Outcomes in the Presence of Kidney Failure: A National Data Linkage Study.

BACKGROUND: Patients who have kidney failure are at higher risk of requiring total hip arthroplasty (THA) and are at higher risk of complications. This study compared the rate of revision surgery and mortality following THA between patients who have kidney failure receiving long term dialysis or who had a kidney transplant and those who did not have kidney failure. METHODS: A data linkage study was performed using data from 2 national registries: a registry of dialysis and kidney transplant patients and a registry of THA procedures. Both registries had coverage of almost all procedures or treatments in Australia. Data from September 1999 to December 2016 were used. Mortality and revision surgery were compared between patients receiving dialysis, those who had a functioning kidney transplant, and patients who did not have kidney failure using Cox and Fine-Gray (competing risk) regression models. A total of 383,478 primary THA procedures were identified as people receiving dialysis (n = 490), who had a functioning kidney transplant (n = 459), or who did not have kidney failure (n = 382,529). RESULTS: There was no significant difference in the overall rate of revision surgery between the groups (dialysis versus no kidney failure HR = 1.20; 95% CI 0.76, 1.88, transplant versus no kidney failure (hazard ratio) HR = 1.01; 95% (confidence interval) CI 0.66, 1.53). The risk for death after surgery was significantly higher in the dialysis group compared to both the functioning transplant group (HR = 3.44; 95%CI 1.58, 7.5), and in those without kidney failure (HR = 4.13; 95%CI 3.25, 5.25). CONCLUSION: The rate of mortality after THA in patients on dialysis is higher than in patients who have a functioning transplant or those who do not have kidney failure, but there is no early excess mortality to suggest a difference in this metric due to the surgery.

Anal and oral detection of Treponema pallidum in men who have sex with men with early syphilis infection.

OBJECTIVES: We aimed to characterise patterns of anal and oral detection of Treponema pallidum among men who have sex with men (MSM) with early syphilis. METHODS: 200 MSM with serologically confirmed primary, secondary and early latent syphilis were tested with T. pallidum polA PCR using an anal canal swab, oral rinse, plus swabs from any anal and oral lesions in a prospective, cross-sectional study. Anal and oral T. pallidum cycle threshold values were compared between subsets of men and according to rapid plasma reagin (RPR) titre. RESULTS: Of 200 men with early syphilis, 45 and 48 had anal and oral T. pallidum detected, respectively. Cycle threshold values were lower with anal compared with oral T. pallidum whether lesions were present or not. Among 27 and 42 men with anal and oral T. pallidum detected, respectively, and no anal or oral primary lesion, frequency of detection increased with increasing RPR titre, with 95% (25/27) and 98% (41/42) of shedding from respective sites occurring with RPR titres ≥1:16. 6.5% (13/200) of men with syphilis had concurrent detection of T. pallidum from both anal and oral sites: 9/13 with secondary syphilis, 7/9 of whom had anal lesions with a median duration of 30 days (range 7-180 days). CONCLUSIONS: These data suggest T. pallidum load at the anus is higher than at the oral cavity and that a subset of men with secondary syphilis and prolonged anal lesions may be relatively infectious. Earlier detection and treatment of syphilis, when RPR titres are lower than 1:16, could potentially reduce infectiousness from anal and oral sites.

Timing of primary syphilis treatment and impact on the development of treponemal antibodies: a cross-sectional clinic-based study.

BACKGROUND: Serology is negative in a proportion of primary syphilis cases where Treponema pallidum PCR testing is positive. We aimed to identify discordant, T. pallidum PCR-positive, serology-negative primary syphilis cases and any clinical or laboratory factors associated with failure to subsequently seroconvert. METHODS: Serodiscordant primary syphilis cases that were T. pallidum PCR-positive and serology-negative (including rapid plasma reagin, T. pallidum particle agglutination, T. pallidum enzyme immunoassay or T. pallidum chemiluminescence assay) were identified from the Melbourne Sexual Health Centre electronic records between April 2011 and December 2019. Clinical and laboratory associations were examined. RESULTS: There were 814 primary syphilis cases in the study period and 38 (4.7%) were serodiscordant, 35 in men who have sex with men. Thirty-two had follow-up serology performed a median of 24 days later, of which 16 (50%) seroconverted, mostly (81%) within 6 weeks. Failure to seroconvert was significantly associated with treatment on day 1. Of the 12 cases treated on day 1, 10 (83%) failed to seroconvert compared with 6 of 20 (30%) among those who were treated after day 1. DISCUSSION: Earlier treatment of primary syphilis can prevent the development of serological markers. T. pallidum PCR can identify primary syphilis lesions before the development of serological markers and improve diagnosis of early primary syphilis lesions. Serology alone will miss a proportion of primary syphilis infections and should be repeated if a diagnosis of syphilis is being considered.

Association between socioeconomic status and joint replacement of the hip and knee: a population-based cohort study of older adults in Tasmania.

BACKGROUND: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. AIM: To describe the association between SES and time to THR and TKR. METHODS: One thousand and seventy-two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area-level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group; and (ii) the cohort dichotomised at the quartile 1 cut-point. RESULTS: The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2-13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR; hazard ratio (HR): 0.56; 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90; 95% CI 0.53, 1.54). However, the former became non-significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. CONCLUSIONS: The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES.

In Revision THA, Is the Re-revision Risk for Dislocation and Aseptic Causes Greater in Dual-mobility Constructs or Large Femoral Head Bearings? A Study from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Dislocation is one of the most common causes of a re-revision after a revision THA. Dual-mobility constructs and large femoral head bearings (≥ 36 mm) are known options for mitigating this risk. However, it is unknown which of these choices is better for reducing the risk of dislocation and all-cause re-revision surgery. It is also unknown whether there is a difference between dual-mobility constructs and large femoral head bearings according to the size of the acetabular component. QUESTIONS/PURPOSES: We used data from a large national registry to ask: In patients undergoing revision THA for aseptic causes after a primary THA performed for osteoarthritis, (1) Does the proportion of re-revision surgery for prosthesis dislocation differ between revision THAs performed with dual-mobility constructs and those performed with large femoral head bearings? (2) Does the proportion of re-revision surgery for all aseptic causes differ between revision THAs performed with dual-mobility constructs and those performed with large femoral head bearings? (3) Is there a difference when the results are stratified by acetabular component size? METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) were analyzed for 1295 first-revision THAs for aseptic causes after a primary THA performed for osteoarthritis. The study period was from January 2008-when the first dual-mobility prosthesis was recorded-to December 2019. There were 502 dual-mobility constructs and 793 large femoral head bearings. There was a larger percentage of women in the dual-mobility construct group (67% [334 of 502]) compared with the large femoral head bearing group (51% [402 of 793]), but this was adjusted for in the statistical analysis. Patient ages were similar for the dual-mobility construct group (67 ± 11 years) and the large femoral head group (65 ± 12 years). American Society of Anesthesiologists (ASA) class and BMI distributions were similar. The mean follow-up was shorter for dual-mobility constructs at 2 ± 1.8 years compared with 4 ± 2.9 years for large femoral head bearings. The cumulative percent revision (CPR) was determined for a diagnosis of prosthesis dislocation as well as for all aseptic causes (excluding infection). Procedures using metal-on-metal bearings were excluded. The time to the re-revision was described using Kaplan-Meier estimates of survivorship, with right censoring for death or database closure at the time of analysis. The unadjusted CPR was estimated each year of the first 5 years for dual-mobility constructs and for each of the first 9 years for large femoral head bearings, with 95% confidence intervals using unadjusted pointwise Greenwood estimates. The apparent shorter follow-up of the dual-mobility construct group relates to the more recent increase in dual-mobility numbers recorded in the registry. The results were adjusted for age, gender, and femoral fixation. Results were subanalyzed for acetabular component sizes < 58 mm and ≥ 58 mm, set a priori on the basis of biomechanical and other registry data. RESULTS: There was no difference in the proportion of re-revision for prosthesis dislocation between dual-mobility constructs and large femoral head bearings (hazard ratio 1.22 [95% CI 0.70 to 2.12]; p = 0.49). At 5 years, the CPR of the re-revision for prosthesis dislocation was 4.0% for dual mobility constructs (95% CI 2.3% to 6.8%) and 4.1% for large femoral head bearings (95% CI 2.7% to 6.1%). There was no difference in the proportion of all aseptic-cause second revisions between dual-mobility constructs and large femoral head bearings (HR 1.02 [95% CI 0.76 to 1.37]; p = 0.89). At 5 years, the CPR of dual-mobility constructs was 17.6% for all aseptic-cause second revision (95% CI 12.6% to 24.3%) and 17.8% for large femoral head bearings (95% CI 14.9% to 21.2%). When stratified by acetabular component sizes less than 58 mm and at least 58 mm, there was no difference in the re-revision CPR for dislocation or for all aseptic causes between dual-mobility constructs and large femoral head bearings. CONCLUSION: Either dual-mobility constructs or large femoral head bearings can be used in revision THA, regardless of acetabular component size, as they did not differ in terms of re-revision rates for dislocation and all aseptic causes in this registry study. Longer term follow-up is required to assess whether complications develop with either implant or whether a difference in revision rates becomes apparent. Ongoing follow-up and comparison in a registry format would seem the best way to compare long-term complications and revision rates. Future studies should also compare surgeon factors and whether they influence decision-making between prosthesis options and second revision rates. Nested randomized controlled trials in national registries would seem a viable option for future research. LEVEL OF EVIDENCE: Level III, therapeutic study.

What Can We Learn From Surgeons Who Perform THA and TKA and Have the Lowest Revision Rates? A Study from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Long-term implant survivorship in THA and TKA involves a combination of factors related to the patient, the implants used, and the decision-making and technical performance of the surgeon. It is unclear which of these factors is the most important in reducing the proportion of revision surgery. QUESTIONS/PURPOSES: We used data from a large national registry to ask: In patients receiving primary THA and TKA for a diagnosis of osteoarthritis, do (1) the reasons for revision and (2) patient factors, the implants used, and the surgeon or surgical factors differ between surgeons performing THA and TKA who have a lower revision rate compared with all other surgeons? METHODS: Data were analyzed for all THA and TKA procedures performed for a diagnosis of osteoarthritis from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from September 1, 1999, when collection began, to December 31, 2018. The AOANJRR obtains data on more than 98% of joint arthroplasties performed in Australia. The 5-year cumulative percent revision (CPR) was identified for all THAs and TKAs performed for a diagnosis of osteoarthritis with 95% confidence intervals (overall CPR); the 5-year CPR with 95% CIs for each surgeon was calculated for THA and TKA separately. For surgeons to be included in the analysis, they had to have performed at least 50 procedures and have a 5-year CPR. The 5-year CPR with 95% CIs for each THA and TKA surgeon was compared with the overall CPR. Two groups were defined: low revision rate surgeons (the upper confidence level for a given surgeon at 5 years is less than 3.84% for THA and 4.32% for TKA), and all other surgeons (any surgeon whose CPR was higher than those thresholds). The thresholds were determined by setting a cutoff at 20% above the upper confidence level for that class. The approach we used to define a low revision rate surgeon was similar to that used by the AOANJRR for determining the better-performing prostheses and is recommended by the International Prosthesis Benchmarking Working Group. By defining the groups in this way, a significant difference between these two groups is created. Determining a reason for this difference is the purpose of presenting the proportions of different factors within each group. The study group for THA included 116 low revision rate surgeons, who performed 88,392 procedures (1619 revised, 10-year CPR 2.7% [95% CI 2.6% to 2.9%]) and 433 other surgeons, who performed 170,094 procedures (6911 revised, 10-year CPR 5.9% [95% CI 5.7% to 6.0%]). The study group for TKA consisted of 144 low revision rate surgeons, who performed 159,961 procedures (2722 revised, 10-year CPR 2.6% [95% CI 2.5% to 2.8%]) and 534 other surgeons, who performed 287,232 procedures (12,617 revised, 10-year CPR 6.4% [95% CI 6.3% to 6.6%]). These groups were defined a priori by their rate of revision, and the purpose of this study was to explore potential reasons for this observed difference. RESULTS: For THA, the difference in overall revision rate between low revision rate surgeons and other surgeons was driven mainly by fewer revisions for dislocation, followed by component loosening and fracture in patients treated by low revision rate surgeons. For TKA, the difference in overall revision rate between low revision rate surgeons and other surgeons was driven mainly by fewer revisions for aseptic loosening, followed by instability and patellofemoral complications in patients treated by low revision rate surgeons. Patient-related factors were generally similar between low revision rate surgeons and other surgeons for both THA and TKA. Regarding THA, there were differences in implant factors, with low revision rate surgeons using fewer types of implants that have been identified as having a higher-than-anticipated rate of revision within the AOANJRR. Low revision rate surgeons used a higher proportion of hybrid fixation, although cementless fixation remained the most common choice. For surgeon factors, low revision rate surgeons were more likely to perform more than 100 THA procedures per year, while other surgeons were more likely to perform fewer than 50 THA procedures per year. In general, the groups of surgeons (low revision rate surgeons and other surgeons) differed less in terms of years of surgical experience than they did in terms of the number of cases they performed each year, although low revision rate surgeons, on average, had more years of experience and performed more cases per year. Regarding TKA, there were more differences in implant factors than with THA, with low revision rate surgeons more frequently performing patellar resurfacing, using an AOANJRR-identified best-performing prosthesis combination (with the lowest rates of revision), using fewer implants that have been identified as having a higher-than-anticipated rate of revision within the AOANJRR, using highly crosslinked polyethylene, and using a higher proportion of cemented fixation compared with other surgeons. For surgeon factors, low revision rate surgeons were more likely to perform more than 100 TKA procedures per year, whereas all other surgeons were more likely to perform fewer than 50 procedures per year. Again, generally, the groups of surgeons (low revision rate surgeons and other surgeons) differed less in terms of years of surgical experience than they did in terms of the number of cases they performed annually, although low revision rate surgeons, on average, had more years of experience and performed more cases per year. CONCLUSION: THAs and TKAs performed by surgeons with the lowest revision rates in Australia show reductions in all of the leading causes of revision for both THA and TKA, in particular, causes of revision related to the technical performance of these procedures. Patient factors were similar between low revision rate surgeons and all other surgeons for both THA and TKA. Low revision rate THA surgeons were more likely to use cement fixation selectively. Low revision rate TKA surgeons were more likely to use patella resurfacing, crosslinked polyethylene, and cemented fixation. Low revision rate THA and TKA surgeons were more likely to use an AOANJRR-identified best-performing prosthesis combination and to use fewer implants identified by the AOANJRR as having a higher-than-anticipated revision rate. To reduce the rate of revision THA and TKA, surgeons should consider addressing modifiable factors related to implant selection. Future research should identify surgeon factors beyond annual case volume that are important to improving implant survivorship. LEVEL OF EVIDENCE: Level III, therapeutic study.

What Is the Outcome of the First Revision Procedure of Primary THA for Osteoarthritis? A Study From the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Joint arthroplasty registries traditionally report survivorship outcomes mainly on primary joint arthroplasty. The outcome of first revision procedures is less commonly reported, because large numbers of primary procedures are required to analyze a sufficient number of first revision procedures. Additionally, adequate linkage of primary procedures to revisions and mortality is required. When undertaking revision hip surgery, it is important for surgeons to understand the outcomes of these procedures to better inform patients. QUESTIONS/PURPOSES: Using data from a large national joint registry, we asked: (1) What is the overall rate of revision of the first aseptic revision procedure for a primary THA? (2) Does the rate of revision of the first revision vary by the diagnosis for the first revision? (3) What is the mortality after the first revision, and does it vary by the reason for first revision? METHODS: The Australian Orthopaedic Association National Joint Replacement Registry longitudinally maintains data on all primary and revision joint arthroplasties, with nearly 100% capture. The analyses for this study were performed on primary THA procedures in patients with a diagnosis of osteoarthritis up to December 31, 2020, who had undergone subsequent revision. We excluded all primary THAs involving metal-on-metal and ceramic-on-metal bearing surfaces and prostheses with exchangeable necks because these designs may have particular issues associated with revisions, such as extensive soft tissue destruction, that are not seen with conventional bearings, making a comparative analysis of the first revision involving these bearing surfaces more complicated. Metal-on-metal bearing surfaces have not been used in Australia since 2017. We identified 17,046 first revision procedures from the above study population and after exclusions, included 13,713 first revision procedures in the analyses. The mean age at the first revision was 71 ± 11 years, and 55% (7496 of 13,713) of the patients were women. The median (IQR) time from the primary procedure to the first revision was 3 years (0.3 to 7.3), ranging from 0.8 years for the diagnosis of dislocation and instability to 10 years for osteolysis. There was some variation depending on the reason for the first revision. For example, patients undergoing revision for fracture were slightly older (mean age 76 ± 11 years) and patients undergoing revision for dislocation were more likely to be women (61% [2213 of 3620]). The registry has endeavored to standardize the sequence of revisions and uses a numerical approach to describe revision procedures. The first revision is the revision of a primary procedure, the second revision is the revision of the first revision, and so on. We therefore described the outcome of the first revision as the cumulative percent second revision. The outcome measure was the cumulative percent revision, which was defined using Kaplan-Meier estimates of survivorship to describe the time to the second revision. Hazard ratios from Cox proportional hazards models, adjusting for age and gender, were performed to compare the revision rates among groups. When possible, the cumulative percent second revision at the longest follow-up timepoint was determined with the available data, and when there were insufficient numbers, we used appropriate earlier time periods. RESULTS: The cumulative percent second revision at 18 years was 26% (95% confidence interval [CI] 24% to 28%). When comparing the outcome of the first revision by reason, prosthesis dislocation or instability had the highest rate of second revision compared with the other reasons for first revision. Dual-mobility prostheses had a lower rate of second revision for dislocation or instability than head sizes 32 mm or smaller and when compared to constrained prostheses after 3 months. There was no difference between dual-mobility prostheses and head sizes larger than 32 mm. There were no differences in the rate of second revision when first revisions for loosening, periprosthetic fracture, and osteolysis were compared. If cemented femoral fixation was performed at the time of the first revision, there was a higher cumulative percent second revision for loosening than cementless fixation from 6 months to 6 years, and after this time, there was no difference. The overall mortality after a first revision of primary conventional THA was 1% at 30 days, 2% at 90 days, 5% at 1 year, and 40% at 10 years. A first revision for periprosthetic fracture had the highest mortality at all timepoints compared with other reasons for the first revision. CONCLUSION: Larger head sizes and dual-mobility cups may help reduce further revisions for dislocation, and the use of cementless stems for a first revision for loosening seems advantageous. Surgeons may counsel patients about the higher risk of death after first revision procedures, particularly if the first revision is performed for periprosthetic fracture.Level of Evidence Level III, therapeutic study.

Poor Knee-specific and Generic Patient-reported Outcome Measure Scores at 6 Months Are Associated With Early Revision Knee Arthroplasty: A Study From the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: The ability to identify which patients are at a greater risk of early revision knee arthroplasty has important practical and resource implications. Many international arthroplasty registries administer patient-reported outcome measures (PROMs) to provide a holistic assessment of pain, function, and quality of life. However, few PROM scores have been evaluated as potential indicators of early revision knee arthroplasty, and earlier studies have largely focused on knee-specific measures. QUESTIONS/PURPOSES: This national registry-based study asked: (1) Which 6-month postoperative knee-specific and generic PROM scores are associated with early revision knee arthroplasty (defined as revision surgery performed 6 to 24 months after the primary procedure)? (2) Is a clinically important improvement in PROM scores (based on thresholds for the minimal important change) after primary knee arthroplasty associated with a lower risk of early revision? METHODS: Preoperative and 6-month postoperative PROM scores for patients undergoing primary knee arthroplasty were sourced from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and Arthroplasty Clinical Outcomes Registry National. Between January 2013 and December 2020, PROM data were available for 19,402 primary total knee arthroplasties; these data were linked to AOANJRR data on revision knee arthroplasty. Of these, 3448 procedures were excluded because they did not have 6-month PROM data, they had not reached the 6-month postoperative point, they had died before 24 months, or they had received revision knee arthroplasty before the 6-month PROMs assessment. After these exclusions, data were analyzed for 15,954 primary knee arthroplasties. Associations between knee-specific (knee pain, Oxford Knee Score, and 12-item Knee injury and Osteoarthritis Outcome Score [KOOS-12]) or generic PROM scores (5-level EuroQol quality of life instrument [EQ-5D], EQ VAS, perceived change, and satisfaction) and revision surgery were explored using t-tests, chi-square tests, and regression models. Ninety-four revision procedures were performed at 6 to 24 months, most commonly for infection (39% [37 procedures]). The early revision group was younger than the unrevised group (mean age 64 years versus 68 years) and a between-group difference in American Society of Anesthesiologists (ASA) grade was noted. Apart from a small difference in preoperative low back pain for the early revision group (mean low back pain VAS 4.2 points for the early revision group versus 3.3 points for the unrevised group), there were no between-group differences in preoperative knee-specific or generic PROM scores on univariate analysis. As the inclusion of ASA grade or low back pain score did not alter the model results, the final multivariable model included only the most clinically plausible confounders (age and gender) as covariates. Multivariable models (adjusting for age and gender) were also used to examine the association between a clinically important improvement in PROM scores (based on published thresholds for minimal important change) and the likelihood of early revision. RESULTS: After adjusting for age and gender, poor postoperative knee pain, Oxford, KOOS-12, EQ-5D, and EQ VAS scores were all associated with early revision. A one-unit increase (worsening) in knee pain at 6 months was associated with a 31% increase in the likelihood of revision (RR 1.31 [95% confidence interval (CI) 1.19 to 1.43]; p < 0.001). Reflecting the reversed scoring direction, a one-unit increase (improvement) in Oxford or KOOS-12 score was associated with a 9% and 5% reduction in revision risk, respectively (RR for Oxford: 0.91 [95% CI 0.90 to 0.93]; p < 0.001; RR for KOOS-12 summary: 0.95 [95% CI 0.94 to 0.97]; p < 0.001). Patient dissatisfaction (RR 6.8 [95% CI 3.7 to 12.3]) and patient-perceived worsening (RR 11.7 [95% CI 7.4 to 18.5]) at 6 months were also associated with an increased likelihood of early revision. After adjusting for age and gender, patients who did not achieve a clinically important improvement in PROM scores had a higher risk of early revision (RR 2.9 for the knee pain VAS, RR 4.2 for the Oxford Knee Score, RR 6.3 to 8.6 for KOOS-12, and RR 2.3 for EQ-5D) compared with those who did (reference group). CONCLUSION: Knee-specific and generic PROM scores offer an efficient approach to identifying patients at greater risk of early revision surgery, using either the 6-month score or the magnitude of improvement. These data indicate that surgeons can use single- and multi-item measures to detect a patient-perceived unsuccessful surgical outcome at 6 months after primary knee arthroplasty. Surgeons should be alert to poor PROM scores at 6 months or small improvements in scores (for example, less than 2 points for knee pain VAS or less than 10.5 points for Oxford Knee Score), which signal a need for direct patient follow-up or expedited clinical review. LEVEL OF EVIDENCE: Level III, therapeutic study.

Reduced Revision Rates in Total Shoulder Arthroplasty With Crosslinked Polyethylene: Results From the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Loss of glenoid fixation is a key factor affecting the survivorship of primary total shoulder arthroplasty (TSA). It is not known whether the lower revision rates associated with crosslinked polyethylene (XLPE) compared with those of non-XLPE identified in hip and knee arthroplasty apply to shoulder arthroplasty. QUESTIONS/PURPOSES: We used data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to compare the revision rates of primary stemmed anatomic TSA using XLPE to procedures using non-XLPE. In patients receiving a primary stemmed anatomic TSA for osteoarthritis, we asked: (1) Does the rate of revision or reason for revision vary between XLPE and non-XLPE all-polyethylene glenoid components? (2) Is there any difference in the revision rate when XLPE is compared with non-XLPE across varying head sizes? (3) Is there any difference in survival among prosthesis combinations with all-polyethylene glenoid components when they are used with XLPE compared with non-XLPE? METHODS: Data were extracted from the AOANJRR from April 16, 2004, to December 31, 2020. The AOANJRR collects data on more than 97% of joint replacements performed in Australia. The study population included all primary, stemmed, anatomic TSA procedures performed for osteoarthritis using all-polyethylene glenoid components. Procedures were grouped into XLPE and non-XLPE bearing surfaces for comparison. Of the 10,102 primary stemmed anatomic TSAs in the analysis, 39% (3942 of 10,102) used XLPE and 61% (6160 of 10,102) used non-XLPE. There were no differences in age, gender, or follow-up between groups. Revision rates were determined using Kaplan-Meier estimates of survivorship to describe the time to the first revision, with censoring at the time of death or closure of the database at the time of analysis. Revision was defined as removal, replacement, or addition of any component of a joint replacement. The unadjusted cumulative percent revision after the primary arthroplasty (with 95% confidence intervals [CIs]) was calculated and compared using Cox proportional hazard models adjusted for age, gender, fixation, and surgeon volume. Further analyses were performed stratifying according to humeral head size, and a prosthesis-specific analysis adjusted for age and gender was also performed. This analysis was restricted to prosthesis combinations that were used at least 150 times, accounted for at least four revisions, had XLPE and non-XLPE options available, and had a minimum of 3 years of follow-up. RESULTS: Non - XLPE had a higher risk of revision than XLPE after 1.5 years (HR 2.3 [95% CI 1.6 to 3.1]; p < 0.001). The cumulative percent revision at 12 years was 5% (95% CI 4% to 6%) for XLPE and 9% (95% CI 8% to 10%) for non-XLPE. There was no difference in the rate of revision for head sizes smaller than 44 mm. Non-XLPE had a higher rate of revision than XLPE for head sizes 44 to 50 mm after 2 years (HR 2.3 [95% CI 1.5 to 3.6]; p < 0.001) and for heads larger than 50 mm for the entire period (HR 2.2 [95% CI 1.4 to 3.6]; p < 0.001). Two prosthesis combinations fulfilled the inclusion criteria for the prosthesis-specific analysis. One had a higher risk of revision when used with non-XLPE compared with XLPE after 1.5 years (HR 3.7 [95% CI 2.2 to 6.3]; p < 0.001). For the second prosthesis combination, no difference was found in the rate of revision between the two groups. CONCLUSION: These AOANJRR data demonstrate that noncrosslinked, all-polyethylene glenoid components have a higher revision rate compared with crosslinked, all-polyethylene glenoid components when used in stemmed anatomic TSA for osteoarthritis. As polyethylene type is likely an important determinant of revision risk, crosslinked polyethylene should be used when available, particularly for head sizes larger than 44 mm. Further studies will need to be undertaken after larger numbers of shoulder arthroplasties have been performed to determine whether this reduction in revision risk associated with XLPE bears true for all TSA designs. LEVEL OF EVIDENCE: Level III, therapeutic study.

Viscoelastic Testing in an Obstetric Population at High Risk of Hemorrhage.

INTRODUCTION: Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic test used in trauma for goal-directed transfusion. However, there are limited data on baseline ROTEM parameters in the U.S. obstetric population. Obtaining baseline parameters is a first step in implementing a goal-directed massive transfusion protocol in obstetric hemorrhage. OBJECTIVE: Our study aimed to establish pre- and postdelivery baseline parameters in a high-risk obstetric population and determine their association with postpartum hemorrhage (PPH). STUDY DESIGN: Prospective observational study of patients ≥34 weeks' gestation, at high risk of PPH, admitted for delivery. INTEM, EXTEM, FIBTEM, and APTEM assays were performed at the time of admission to labor and delivery and then 2 hours after delivery. Primary outcome was pre- and postdelivery ROTEM parameters among women without PPH. A sample size of 60 women was needed for >90% power to detect at least 50% correlation between pre- and postdelivery assuming a loss of 10% of participants to follow-up. RESULTS: Of 60 women in the study, 10 (17%) had PPH. Baseline characteristics were not different between those with or without PPH. Pre- and postdelivery ROTEM parameters were not significantly different except for APTEM. None of the patients who had PPH, compared with 4 (10%) of those who did not, had shortened clotting time and higher maximum clot firmness in postdelivery APTEM compared with EXTEM, a pattern suggestive of hyperfibrinolysis (p = 0.4). CONCLUSIONS: In this study, we describe baseline ROTEM parameters in women at high risk of PPH. The majority of patients did not have a ROTEM pattern that is suggestive of hyperfibrinolysis, for which tranexamic acid is thought to be beneficial. Based on our findings, previously established obstetric transfusion thresholds for goal-directed massive transfusion protocols are likely valid for the majority of the obstetric population regardless of the presence of comorbidities or pregnancy complications. KEY POINTS: · ROTEM parameters do not vary significantly before and after delivery.. · Most patients did not have a hyperfibrinolysis pattern, for which tranexamic acid is thought to be beneficial.. · Previous goal-directed obstetric transfusion thresholds are likely valid in most populations..

Effect of glenosphere size on reverse shoulder arthroplasty revision rate: an analysis from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR).

BACKGROUND: Modularity is an integral element of reverse total shoulder arthroplasty (RTSA). Glenosphere diameter is a key component, but its effect on revision rate is unknown. The aim of this study was to investigate the relationship between glenosphere size and revision rates in RTSA procedures. METHODS: Data from a large national arthroplasty registry were analyzed for the period April 2004 to 31 December 2019. The study population included all primary RTSA procedures using glenosphere sizes <38 mm, 38-40 mm, and >40 mm. A subanalysis of glenosphere sizes for each of the 3 most commonly implanted prostheses and further analyses by patient age and gender were also performed. The rate of revision was determined by Kaplan-Meier estimates, with comparisons by Cox proportional hazard models. RESULTS: There were 28,817 primary RTSA procedures. Glenosphere sizes <38 mm had a higher revision rate compared to 38-40-mm glenospheres (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.11, 1.48, P < .001) and >40-mm sizes (HR 1.35, 95% CI 1.15, 1.59, P < .001). Males with <38-mm and 38-40-mm glenospheres had significantly higher revision rates compared to >40-mm glenospheres (HR 1.49, 95% CI 1.21, 1.83, P < .001; and HR 1.28, 95% CI 1.03, 1.58, P = .025, respectively). Females with <38-mm and >40-mm glenospheres had higher revision rates compared to females with 38-40-mm glenospheres (HR 1.38, 95% CI 1.14, 1.68, P < .001; and HR 1.41, 95% CI 1.06, 1.88, P = .019, respectively). For patients aged 65-74 years, glenospheres >40 mm had a significantly lower revision rate than both the <38-mm glenospheres (entire period: HR 0.59, 95% CI 0.45, 0.76, P < .001) and 38-40-mm glenospheres (entire period: HR 0.72, 95% CI 0.54, 0.94, P = .017). For patients aged ≥75 years (n = 14,622), <38-mm glenospheres had a significantly higher rate of revision compared with 38-40-mm glenospheres after 3 months (HR  1.43, 95% CI 1.09, 1.86, P = .009). Analysis comparing glenosphere sizes within each of the 3 most commonly implanted prostheses found that the Delta Xtend with 38-40-mm glenospheres had higher revision rates compared with >40-mm glenospheres (HR 1.49, 95% CI 1.14, 1.92, P = .003). The SMR L1 (Lima) 38-40-mm glenospheres had a lower rate of revision compared with the <38-mm (HR 0.50, 95% CI 0.37, 0.67, P < .001) and >40-mm glenospheres (HR 0.60, 95% CI 0.43, 0.85, P = .004). CONCLUSIONS: Glenospheres <38 mm can be expected to increase revision rates in primary RTSAs. The optimum size of glenospheres is gender, age, and prosthesis specific, with revision rates lower for females with 38-40-mm glenospheres and lower for males with >40-mm glenospheres.

Revision for Aseptic Loosening of Highly Porous Acetabular Components in Primary Total Hip Arthroplasty: An Analysis of 20,993 Total Hip Replacements.

BACKGROUND: Highly porous-coated titanium acetabular components have a high coefficient of friction and ultraporous surfaces to enhance bone ingrowth and osseointegration in total hip arthroplasty (THA). There have been concerns with the development of early radiolucent lines and aseptic loosening of highly porous acetabular components. It is unclear whether these concerns relate to a specific implant or the entire class. The aim of this study is to compare the revision rates for aseptic loosening of highly porous acetabular combinations in primary THA using data from a large joint replacement registry. METHODS: Data were retrieved from the Australian Orthopedic Association National Joint Replacement Registry for the study period September 1999 to December 2019. All primary THA procedures recorded and performed for osteoarthritis using the most common combinations for each highly porous acetabular component with highly cross-linked polyethylene and a 32-mm or 36-mm femoral head were included. The primary outcome measure was revision for aseptic loosening of the acetabular component. Results were adjusted for patient age and gender. RESULTS: There were 20,993 primary THA procedures performed for osteoarthritis using a highly porous acetabular component across 6 combinations. Relative to the POLARSTEM/R3 (StikTite), the Exeter V40/Tritanium had a significantly higher risk of revision for aseptic loosening of the acetabular component (hazard ratio 0.21, 95% confidence interval 0.06-0.74, P = .014). There was no difference between any other highly porous acetabular component combination and no late revisions for aseptic loosening. CONCLUSION: Highly porous-coated titanium acetabular components have low rates of aseptic loosening with long-term follow-up. A difference between components may exist. LEVEL OF EVIDENCE: Level III.

Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial.

Importance: There remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Objective: To determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA. Design, Setting, and Participants: Cluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021. Interventions: Hospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation. Main Outcomes and Measures: The primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group. Results: Enrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years; 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin (P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group. Conclusions and Relevance: Among patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis. Trial Registration: ANZCTR Identifier: ACTRN12618001879257.