Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty.

BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).

Cryotherapy following total knee replacement.

BACKGROUND: Total knee replacement (TKR) is a common intervention for people with end-stage symptomatic knee osteoarthritis, resulting in significant improvements in pain, function and quality of life within three to six months. It is, however, acutely associated with pain, local oedema and blood loss. Post-operative management may include cryotherapy. This is the application of low temperatures to the skin surrounding the surgical site, through ice or cooled water, often delivered using specialised devices. This is an update of a review published in 2012. OBJECTIVES: To evaluate the effect of cryotherapy in the acute phase after TKR (within 48 hours after surgery) on blood loss, pain, transfusion rate, range of motion, knee function, adverse events and withdrawals due to adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers, as well as reference lists, related links and conference proceedings on 27 May 2022. SELECTION CRITERIA: We included randomised controlled trials or controlled clinical trials comparing cryotherapy with or without other treatments (such as compression, regional nerve block or continuous passive motion) to no treatment, or the other treatment alone, following TKR for osteoarthritis. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data and assessed risk of bias and certainty of evidence using GRADE. We discussed any disagreements and consulted another review author to resolve them, if required. Major outcomes were blood loss, pain, transfusion rate, knee range of motion, knee function, total adverse events and withdrawals from adverse events. Minor outcomes were analgesia use, knee swelling, length of stay, quality of life, activity level and participant-reported global assessment of success. MAIN RESULTS: We included 22 trials (20 randomised trials and two controlled clinical trials), with 1839 total participants. The mean ages reflected the TKR population, ranging from 64 to 74 years. Cryotherapy with compression was compared to no treatment in four studies, and to compression alone in nine studies. Cryotherapy without compression was compared to no treatment in eight studies. One study compared cryotherapy without compression to control with compression alone. We combined all control interventions in the primary analysis. Certainty of evidence was low for blood loss (downgraded for bias and inconsistency), pain (downgraded twice for bias) and range of motion (downgraded for bias and indirectness). It was very low for transfusion rate (downgraded for bias, inconsistency and imprecision), function (downgraded twice for bias and once for inconsistency), total adverse events (downgraded for bias, indirectness and imprecision) and withdrawals from adverse events (downgraded for bias, indirectness and imprecision). The nature of cryotherapy made blinding difficult and most studies had a high risk of performance and detection bias. Low-certainty evidence from 12 trials (956 participants) shows that cryotherapy may reduce blood loss at one to 13 days after surgery. Blood loss was 825 mL with no cryotherapy and 561 mL with cryotherapy: mean difference (MD) 264 mL less (95% confidence interval (CI) 7 mL less to 516 mL less). Low-certainty evidence from six trials (530 participants) shows that cryotherapy may slightly improve pain at 48 hours on a 0- to 10-point visual analogue scale (lower scores indicate less pain). Pain was 4.8 points with no cryotherapy and 3.16 points with cryotherapy: MD 1.6 points lower (95% CI 2.3 lower to 1.0 lower). We are uncertain whether cryotherapy improves transfusion rate at zero to 13 days after surgery. The transfusion rate was 37% with no cryotherapy and 79% with cryotherapy (risk ratio (RR) 2.13, 95% CI 0.04 to 109.63; 2 trials, 91 participants; very low-certainty evidence). Low-certainty evidence from three trials (174 participants) indicates cryotherapy may improve range of motion at discharge: it was 62.9 degrees with no cryotherapy and 71.2 degrees with cryotherapy: MD 8.3 degrees greater (95% CI 3.6 degrees more to 13.1 degrees more). We are uncertain whether cryotherapy improves function two weeks after surgery. Function was 75.4 points on the 0- to 100-point Dutch Western Ontario and McMaster Universities Arthritis Index (WOMAC) scale (lower score indicates worse function) in the control group and 88.6 points with cryotherapy (MD 13.2 points better, 95% CI 0.5 worse to 27.1 improved; 4 trials, 296 participants; very low-certainty evidence). We are uncertain whether cryotherapy reduces total adverse events: the risk ratio was 1.30 (95% CI 0.53 to 3.20; 16 trials, 1199 participants; very low-certainty evidence). Adverse events included discomfort, local skin reactions, superficial infections, cold-induced injuries and thrombolytic events. We are uncertain whether cryotherapy reduces withdrawals from adverse events (RR 2.71, 95% CI 0.42 to 17.38; 19 trials, 1347 participants; very low-certainty evidence). No significant benefit was found for secondary outcomes of analgesia use, length of stay, activity level or quality of life. Evidence from seven studies (403 participants) showed improved mid-patella swelling between two and six days after surgery (MD 7.32 mm less, 95% CI 11.79 to 2.84 lower), though not at six weeks and three months after surgery. The included studies did not assess participant-reported global assessment of success. AUTHORS' CONCLUSIONS: The certainty of evidence was low for blood loss, pain and range of motion, and very low for transfusion rate, function, total adverse events and withdrawals from adverse events. We are uncertain whether cryotherapy improves transfusion rate, function, total adverse events or withdrawals from adverse events. We downgraded evidence for bias, indirectness, imprecision and inconsistency. Hence, the potential benefits of cryotherapy on blood loss, pain and range of motion may be too small to justify its use. More well-designed randomised controlled trials focusing especially on clinically meaningful outcomes, such as blood transfusion, and patient-reported outcomes, such as knee function, quality of life, activity level and participant-reported global assessment of success, are required.

Is Enoxaparin Associated With a Higher Risk of Persistent Wound Drainage Than Aspirin? A Secondary Analysis of Data From the CRISTAL Randomized Trial.

BACKGROUND: Owing to its association with prosthetic joint infection, persistent wound drainage has become an important clinical entity after THA or TKA. The association between venous thromboembolism (VTE) prophylaxis and persistent wound drainage has not been extensively reported before but has potentially important clinical implications. QUESTIONS/PURPOSES: (1) Is the type of VTE prophylaxis (enoxaparin or aspirin) used after hip arthroplasty or knee arthroplasty associated with a higher risk of persistent wound drainage? (2) In patients who experience persistent wound drainage, is the type of VTE prophylaxis associated with a longer time taken to achieve a dry wound? (3) Is type of VTE prophylaxis associated with a higher risk of joint-related reoperation within 6 months? METHODS: This was a secondary analysis of data from an earlier cluster-randomized trial conducted through the Australian Orthopaedic Association National Joint Replacement Registry; data were drawn from two participating hospitals from that study. According to the trial's allocation sequence, the two participating hospitals were randomized to administer aspirin (100 mg daily) or enoxaparin (40 mg daily) as VTE prophylaxis to all patients undergoing hip arthroplasty for 35 days after the procedure and for all patients undergoing knee arthroplasty for 14 days afterwards. Crossover to the alternate prophylaxis group occurred after the patient enrollment target had been met for the first arm. Between April 2019 and December 2020, 1339 of 1679 eligible patients were included in this study; 82% (707 of 861) of eligible patients were allocated to the enoxaparin group and 77% (632 of 818) of eligible patients we allocated to the aspirin group. The mean age in both groups was 67 ± 10 years and the mean BMI was 32 ± 7 kg/m 2 . There was a higher proportion of male patients (43% [302 of 707] versus 36% [227 of 632]; p = 0.01), hip arthroplasties (36% [254 of 707] versus 29% [182 of 632]; p = 0.006), and patients receiving subcuticular closure (62% [441 of 707] versus 33% [208 of 631]; p < 0.001) in the enoxaparin group than in the aspirin group. Patients were monitored for wound drainage on each postoperative day until discharge, and this was recorded in the medical record once per day. Assessors were not blinded to the type of prophylaxis each patient received. Persistent wound drainage was defined as any wound drainage beyond Postoperative Day 3. For patients who experienced persistent wound drainage, the time taken to achieve a dry wound was defined as the number of days beyond Postoperative Day 3 for the wound to become dry. Logistic regression was used to determine whether the prophylaxis type was associated with persistent wound drainage. For patients with persistent wound drainage, the median time of drainage was compared between groups using the Kruskal-Wallis test. The number of patients undergoing a joint-related reoperation within 6 months was identified through data linkage to the Australian Orthopaedic Association National Joint Replacement Registry and electronic record review, and was compared using a Fisher exact test. RESULTS: We found no difference between the enoxaparin and aspirin groups in terms of the percentage of patients who had persistent wound drainage (9% [65 of 707] versus 8% [49 of 632], odds ratio 1.2 [95% confidence interval 0.8 to 1.8]; p = 0.40). For patients receiving subcuticular closure, after controlling for other potentially confounding variables, including age, sex, BMI, preoperative anticoagulant use, and type of arthroplasty, enoxaparin was associated with a higher risk of persistent wound drainage than aspirin (OR 3.6 [95% CI 1.5 to 10.6]; p = 0.009). For patients receiving a skin staple closure, after controlling for the same variables above, we found enoxaparin was not associated with a higher risk of persistent wound drainage (OR 1.1 [95% CI 0.7 to 1.9]; p = 0.66). For patients who experienced persistent wound drainage patients (114: 65 in the enoxaparin group and 49 in the aspirin group), there was no difference in the median (interquartile range) time taken to achieve a dry wound (enoxaparin: 1 day [IQR 1 to 2 days], aspirin: 1 day [IQR 1 to 3 days]; p = 0.22). There was no difference in the risk of joint-related reoperation within 6 months between enoxaparin (2.4% [17 of 707]) and aspirin (2.2% [14 of 632], OR 1.1 [95% CI 0.5 to 2.4]; p = 0.86). CONCLUSION: Enoxaparin was not associated with an increased risk of persistent wound drainage compared with aspirin for all patients included in this study. Enoxaparin may be associated with a higher risk of drainage for patients receiving subcuticular closure. However, this finding should be interpreted cautiously, given the small sample size in this analysis. The duration of drainage was short regardless of the prophylaxis used, and enoxaparin was not associated with an increased risk of joint-related reoperation. These findings should not deter clinicians from using enoxaparin for VTE prophylaxis after hip or knee arthroplasty. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparative effectiveness of aspirin for symptomatic venous thromboembolism prophylaxis in patients undergoing total joint arthroplasty, a cohort study.

BACKGROUND: This study compares the symptomatic 90-day venous thromboembolism (VTE) rates in patients receiving aspirin to patients receiving low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), after total hip (THA) and total knee arthroplasty (TKA). METHODS: Data were collected from a multi-centre cohort study, including demographics, confounders and prophylaxis type (aspirin alone, LMWH alone, aspirin and LMWH, and DOACs). The primary outcome was symptomatic 90-day VTE. Secondary outcomes were major bleeding, joint related reoperation and mortality within 90 days. Data were analysed using logistic regression, the Student's t and Fisher's exact tests (unadjusted) and multivariable regression (adjusted). RESULTS: There were 1867 eligible patients; 365 (20%) received aspirin alone, 762 (41%) LMWH alone, 482 (26%) LMWH and aspirin and 170 (9%) DOAC. The 90-day VTE rate was 2.7%; lowest in the aspirin group (1.6%), compared to 3.6% for LMWH, 2.3% for LMWH and aspirin and 2.4% for DOACs. After adjusted analysis, predictors of VTE were prophylaxis duration < 14 days (OR = 6.7, 95% CI 3.5-13.1, p < 0.001) and history of previous VTE (OR = 2.4, 95% CI 1.1-5.8, p = 0.05). There were no significant differences in the primary or secondary outcomes between prophylaxis groups. CONCLUSIONS: Aspirin may be suitable for VTE prophylaxis following THA and TKA. The comparatively low unadjusted 90-day VTE rate in the aspirin group may have been due to selective use in lower-risk patients. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, trial number NCT01899443 (15/07/2013).

Quality indicators in primary elective total hip and knee arthroplasty.

PURPOSE: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) represent a significant portion of healthcare spending and are high-priority for quality improvement initiatives. This study aims to develop quality indicators (QIs) in the care of primary elective THA and TKA patients. These QIs serve a number of purposes including documentation of the quality of care, objective comparisons of institutions/providers, facilitating pay-for-performance initiatives, and supporting accountability, regulation, and accreditation. METHODS: A guideline-based approach, initially described by Kötter et al., was utilized. Eight clinical practice guidelines (CPGs) were evaluated for candidate indicators (CIs). CIs with high-quality evidence and consensus statements were extracted. Eighteen additional CIs were included from previous work that evaluated quality improvement databases. Each CI and supporting evidence was submitted for independent review by an expert panel. The RAND Corporation-University of California, Los Angeles (RAND/UCLA) appropriateness methodology was utilized and items were rated based on validity, reliability, and feasibility of measurement. After two rounds of ratings and ranking, a final ranked list of QIs was obtained. RESULTS: Fifty-six CIs were identified from the literature and CPGs or proposed by the expert panel. Two rounds of voting resulted in 12 total QIs that were deemed appropriate measures of high-quality care. The final 12 QIs were ranked by order of importance: use of peri-operative tranexamic acid, infusion of prophylactic antibiotics prior to inflation of tourniquet, appropriate post-operative venous thromboembolic prophylaxis, complication rate, rate of secondary procedure, readmission rate, early mobilization, average change of pre- to one year post-operative functional status, use of multimodal analgesia, use of neuraxial anesthesia, use of peri-articular injection in TKA, and use of pre-operative PO analgesia. CONCLUSION: This study is an expert opinion based on parameters observed in modern and high-quality academic settings. Twelve QIs are proposed to assess the quality of care in the peri-operative management of primary elective THA and TKA patients.

Adherence by orthopaedic surgeons to AHPRA and Australian Orthopaedic Association advertising guidelines.

OBJECTIVES: To examine adherence to Australian Health Practitioner Regulation Agency (AHPRA) and Australian Orthopaedic Association (AOA) advertising guidelines by AOA members. DESIGN, SETTING: Cross-sectional survey, Australia. PARTICIPANTS: Two samples of AOA member orthopaedic surgeons: 81 randomly selected from a list of AOA members with publicly available contact details (AOA random sample); and a sample obtained by searching with Google for "orthopaedic surgeon" and the name of the major city in each of the eight Australian states and territories in turn; the top eight results for each search were considered for inclusion (AOA Google sample). MAIN OUTCOME MEASURES: Non-compliance of advertising material, by surgeon sample, with the AHPRA and AOA guidelines; associations between non-compliance and sample, state, location (metropolitan, regional), and subspecialty. RESULTS: Of the 81 surgeons in the AOA random sample, 52 (64%) were non-compliant with at least one aspect of the AHPRA guidelines, and 53 (65%) were non-compliant with at least one aspect of the AOA guidelines. Of the 59 surgeons in the AOA Google sample, 48 were non-compliant with the AHPRA guidelines (81%) and 46 with the AOA guidelines (78%). Incidence of non-compliance with the AHPRA guidelines was influenced by sample source (AOA Google v AOA random: incidence rate ratio [IRR], 1.37; 95% CI, 1.01-1.87), but not non-compliance with the AOA guidelines (IRR, 1.09; 95% CI, 0.77-1.55). CONCLUSION: A large proportion of AOA members who advertise online do not comply with AHPRA and AOA advertising guidelines.

Effectiveness of Pharmacological-Based Interventions, Including Education and Prescribing Strategies, to Reduce Subacute Pain After Total Hip or Knee Arthroplasty: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) surgeries are among the most common elective procedures. Moderate to severe postoperative pain during the subacute period (defined here as the period from hospital discharge to 3 months postoperatively) is a predictor of persistent pain 12 months postoperatively. This review aimed to examine the available postdischarge pharmacological interventions, including educational and prescribing strategies, and their effect on reducing pain during the subacute period after TKA or THA. METHODS: We searched seven electronic databases from inception to April 22, 2021. Published randomized controlled trials of adults who underwent TKA or THA and received a pharmacological-based intervention commencing within 1 week after hospital discharge and conducted for up to 3 months postoperatively were compared with any treatment. Two reviewers independently extracted data on the primary outcome, pain intensity. This review was registered prospectively on PROSPERO (ID: CRD42021250384). RESULTS: Four trials involving 660 participants were included. Interventions included changing analgesic prescribing practices upon hospital discharge and education on analgesic use. Providing multimodal non-opioid analgesia in addition to reduced opioid quantity was associated with lower subacute pain (coefficient -0.81; 95% confidence interval -1.33 to -0.29; P = 0.003). Education on analgesic use during multidisciplinary home visits was effective for reducing pain intensity during the subacute period (6.25 ± 10.13 vs 35.67 ± 22.05; P < 0.001) compared with usual care. CONCLUSIONS: Interventions involving the provision of multimodal non-opioid analgesia and education on analgesic use show positive effects on reducing pain intensity during the subacute period after TKA and THA.

Do Dual-mobility Cups Reduce Revision Risk in Femoral Neck Fractures Compared With Conventional THA Designs? An International Meta-analysis of Arthroplasty Registries.

BACKGROUND: Dual-mobility cups in THA were designed to reduce prosthesis instability and the subsequent risk of revision surgery in high-risk patients, such as those with hip fractures. However, there are limited data from clinical studies reporting a revision benefit of dual-mobility over conventional THA. Collaboration between anthroplasty registries provides an opportunity to describe international practice variation and compare between-country, all-cause revision rates for dual-mobility and conventional THA. QUESTIONS/PURPOSES: We summarized observational data from multiple arthroplasty registries for patients receiving either a dual-mobility or conventional THA to ask: (1) Is dual-mobility use associated with a difference in risk of all-cause revision surgery compared with conventional THA? (2) Are there specific patient characteristics associated with dual-mobility use in the hip fracture population? (3) Has the use of dual-mobility constructs changed over time in patients receiving a THA for hip fracture? METHODS: Six member registries of the International Society of Arthroplasty Registries (from Australia, Denmark, Sweden, the Netherlands, the United Kingdom, and the United States) provided custom aggregate data reports stratified by acetabular cup type (dual-mobility or conventional THA) in primary THA for hip fracture between January 1, 2002, and December 31, 2019; surgical approach; and patient demographic data (sex, mean age, American Society of Anesthesiologists class, and BMI). The cumulative percent revision and mortality were calculated for each registry. To determine a global hazard ratio of all-cause revision for dual-mobility compared with conventional THA designs, we used a pseudoindividual patient data approach to pool Kaplan-Meier prosthesis revision data from each registry and perform a meta-analysis. The pseudoindividual patient data approach is a validated technique for meta-analysis of aggregate time-to-event survival data, such as revision surgery, from multiple sources. Data were available for 15,024 dual-mobility THAs and 97,200 conventional THAs performed for hip fractures during the study period. RESULTS: After pooling of complete Kaplan-Meier survival data from all six registries, the cumulative percent revision for conventional THA was 4.3% (95% confidence interval [CI] 4.2% to 4.5%) and 4.7% (95% CI 4.3% to 5.3%) for dual-mobility THA at 5 years. We did not demonstrate a lower risk of all-cause revision for patients receiving dual-mobility over conventional THA designs for hip fracture in the meta-analysis once between-registry differences were adjusted for (HR 0.96 [95% CI 0.86 to 1.06]). A lower proportion of dual-mobility procedures were revised for dislocation than conventional THAs (0.9% versus 1.4%) but a higher proportion were revised for infection (1.2% versus 0.8%). In most registries, a greater proportion of dual-mobility THA patients were older, had more comorbidities, and underwent a posterior approach compared with conventional THA (p < 0.001). The proportion of dual-mobility THA used to treat hip fractures increased in each registry over time and constituted 21% (2438 of 11,874) of all THA procedures in 2019. CONCLUSION: The proportion of dual-mobility THAs in patients with hip fractures increased over time, but there was large variation in use across countries represented here. Dual-mobility cups were not associated with a reduction in the overall risk of revision surgery in patients with hip fractures. A randomized controlled trial powered to detect the incidence of dislocation and subsequent revision surgery is required to clarify the efficacy of dual-mobility cups to treat hip fractures. LEVEL OF EVIDENCE: Level III, therapeutic study.

Preoperative Factors and Patient-Reported Outcomes After Total Hip Arthroplasty: Multivariable Prediction Modeling.

BACKGROUND: Although total hip arthroplasty (THA) has been established as a cost-effective intervention, some patients experience ongoing pain and dissatisfaction. There is interest in predicting postoperative outcomes based on preoperative data, but the relative contribution of different preoperative factors is unclear. The study's aim was to develop multivariable prediction models for the assessment of patient-reported outcomes. METHOD: Registry data on 1412 patients undergoing THA for osteoarthritis at two hospitals between 2013 and 2018 was used. Potential predictors included age, sex, body mass index, spoken language, education level, previous THA, American Society of Anaesthesiologists (ASA) score, lower back pain, depression/anxiety, other lower limb arthritis, number of other comorbidities, the preoperative expectation of pain and function, EuroQol Visual Analogue Scale (EQ-VAS) and preoperative OHS. Radiographic scores were also used: joint space narrowing (JSN), osteophytes, sclerosis, and an overall grade based on the Kellgren-Lawrence (KL) classification. Outcomes assessed were the patient-rated improvement, satisfaction, and OHS at six months. RESULTS: JSN or overall KL scores were the most important predictors (P < .001) for all outcomes, with better radiographic scores associated with worse outcomes. Other predictors associated with poorer outcomes were lower back pain and lower expectation (predicting poor improvement), lower education and higher ASA (predicting lower satisfaction) and younger age, female sex, non-English speakers, lower preoperative EQ-VAS, lower education, back pain, and anxiety/depression (predicting lower OHS). CONCLUSION: Preoperative radiological scores are an important predictor of patient-reported outcomes at six months postoperatively. Understanding the relative strengths and significance of different factors in predicting outcomes will help the clinician and patient decision-making for THA.

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.

Associations between pre-surgical daily opioid use and short-term outcomes following knee or hip arthroplasty: a prospective, exploratory cohort study.

BACKGROUND: Retrospective studies have found that daily opioid use pre-arthroplasty predicts worse longer-term service, clinical and patient-reported outcomes. Prospective studies are needed to confirm these observations. This prospective, exploratory study aimed to determine: the proportion of total knee or hip arthroplasty (TKA, THA) patients who use opioids regularly (daily) pre-surgery; if opioid use pre-surgery is associated with acute and sub-acute outcomes to 12-weeks post-surgery. METHODS: Consecutive patients undergoing primary TKA or THA were prospectively enrolled pre-surgery and followed-up by telephone to 12-weeks post-surgery. Acute-care (oral morphine equivalent dosage (OMED), length of stay, discharge to inpatient rehabilitation, complications) and 12-week outcomes (Oxford Knee or Hip Score, Euroqol 'today' health score, current use of opioids, and complications including readmissions) were monitored. Unadjusted and adjusted Odds Ratios (ORs) (95% Confidence Interval, CI), Rate Ratios and ß coefficients (standard error) were calculated. RESULTS: Five Hundred Twenty-One patients were included (TKA n = 381). 15.7% (95%CI 12.6 to 18.9) used opioids regularly pre-surgery. 86.8% (452/521) were available for follow-up at 12-weeks. In unadjusted analyses, pre-surgical opioid use was significantly associated with higher average acute daily OMED [ß 0.40 (0.07), p <  0.001], presence of an acute complication [OR 1.75 (1.02 to 3.00)], and ongoing use of opioids at 12-weeks [OR 5.06 (2.86 to 8.93)]. After adjusting for covariates, opioid use pre-surgery remained significantly associated with average acute daily OMED [ß 0.40 (0.07), p <  0.001] and ongoing use at 12-weeks [OR 5.38 (2.89 to 9.99)]. CONCLUSION: People who take daily opioids pre-surgery have significantly greater odds for greater opioid consumption acutely and ongoing use post-surgery. Adequately powered prospective studies are required to confirm whether pre-surgical opioid use is or is not associated with poorer joint and quality of life scores or a complication in the short-term.

Implementing early mobilisation after knee or hip arthroplasty to reduce length of stay: a quality improvement study with embedded qualitative component.

BACKGROUND: Models of care for managing total knee or hip arthroplasty (TKA, THA) incorporating early mobilisation are associated with shorter acute length-of-stay (LOS). Few studies have examined the effect of implementing early mobilisation in isolation, however. This study aimed to determine if an accelerated mobilisation protocol implemented in isolation is associated with a reduced LOS without undermining care. METHOD: A Before-After (quasi-experimental) study was used. Standard practice pre-implementation of the new protocol was physiotherapist-led mobilisation once per day commencing on post-operative Day 1 (Before phase). The new protocol (After phase) aimed to mobilise patients four times by end of Day 2 including an attempt to commence on Day 0; physiotherapy weekend coverage was necessarily increased. Poisson regression modelling was used to determine associations between study period and LOS. Additional outcomes to 12 weeks post-surgery were monitored to identify unintended consequences of the new protocol. Time to first mobilisation (hours) and proportion mobilising Day 0 were monitored to assess protocol compliance. An embedded qualitative component captured staff perspectives of the new protocol. RESULTS: Five hundred twenty consecutive patients (n = 278, Before; n = 242, After) were included. The new protocol was associated with no change in unadjusted LOS, a small reduction in adjusted LOS (8.1%, p = 0.046), a reduction in time to first mobilisation (28.5 (10.8) vs 22.6 (8.1) hrs, p < 0.001), and an increase in the proportion mobilising Day 0 (0 vs 7%, p < 0.001). Greater improvements were curtailed by an unexpected decrease in physiotherapy staffing (After phase). There were no significant changes to the rates of complications or readmissions, joint-specific pain and function scores or health-related quality of life to 12 weeks post-surgery. Qualitative findings of 11 multidisciplinary team members highlighted the importance of morning surgery, staffing, and well-defined roles. CONCLUSION: Small reductions in LOS are possible utilising an early mobilisation protocol in isolation after TKA or THA although staff burden is increased likely undermining both sustainability and the magnitude of the change. Simultaneous incorporation of other changes within the pathway would likely secure larger reductions in LOS.

Selecting and optimising patients for total knee arthroplasty.

The minimum requirements for total knee arthroplasty (TKA) are significant, prolonged symptoms with supporting clinical and radiological signs. Despite interest in screening tools, there is limited evidence for a specific symptom threshold that justifies surgery. Non-operative treatments including medications, exercise and weight loss are unlikely to reverse radiographic changes, but they may improve symptoms and delay the need for surgery. Many patient factors such as mental health and obesity affect both the level of symptomatic improvement after surgery and risks of surgery, but none have been identified as contraindications for the procedure as significant health gains can still be achieved. Although age and sex are associated with patient-reported outcomes and risk of revision, these factors cannot be used to restrict access to TKA, and age cut-offs are not recommended. Evidence regarding pre-operative optimisation of patients to improve post-operative TKA outcomes is limited by the few interventional trials available, particularly in the areas of patient expectation, diabetes, obesity and vascular disease. There is good evidence from randomised controlled trials that pre-operative rehabilitation primarily focusing on exercises for the joint or limb has minimal effect on post-operative TKA outcomes, and there is some evidence from randomised controlled trials that an intensive smoking cessation program before surgery may improve post-operative outcomes. Detailed international guidelines exist on the optimisation of the cardiorespiratory status of surgical patients, and these should be followed for TKA surgery.

Predictors of seeking financial compensation following motor vehicle trauma: inception cohort with moderate to severe musculoskeletal injuries.

BACKGROUND: Compensation related factors have been repeatedly associated with poor recovery following orthopaedic trauma. There is limited research into the factors associated with seeking financial compensation. Further understanding of these factors could facilitate injury recovery by purposeful compensation scheme design. The aim of this study was to investigate the predictors of seeking financial compensation, namely making a claim and seeking legal representation, following motor vehicle related orthopaedic trauma. The study was conducted in New South Wales (NSW), Australia, in motor vehicle crash and workers' compensation schemes. METHODS: Participants were patients admitted with upper or lower extremity factures following a motor vehicle crash to two trauma hospitals. Data were collected at baseline within two weeks of injury. Participants were followed up at six months. Analysis involved: descriptive statistics for baseline characteristics; comparison of compensable and non-compensable participants with Analysis of Variance (ANOVA) and chi-squared tests; and logistic regression for predictor models. RESULTS: The cohort consisted of 452 participants with a mean age 40 years; 75% male; 74% working pre-injury; 30% in excellent pre-injury health; 56% sustained serious injuries with an Injury Severity Score (ISS) 9-15; 61% had a low-middle range household income; and 35% self-reported at fault in the crash. There was no significant difference in pre-injury/baseline health between compensable and non-compensable participants. Follow up data was available for 301 (67%) participants. The significant predictor of claiming compensation in the adjusted analysis was higher body mass index (BMI) (overweight Odds Ratio [OR] 3.05, 95% Confidence Interval [CI] 1.63-5.68; obese OR 1.63, 95% CI 0.83-3.20). Participants less likely to claim were: involved in a motorcycle crash (OR 0.47, 95% CI 0.28-0.82); socioeconomically less disadvantaged (OR 0.37, 95% CI 0.17-0.82) or least disadvantaged (OR 0.39, 95% CI 0.17-0.90); at risk for short term harm (injury) due to alcohol consumption (OR 0.56, 95% CI 0.32-0.97); and with fair-poor pre-injury health (OR 0.30, 95% CI 0.09-0.94). The predictors for seeking legal representation were speaking a language other than English at home (OR 2.80, 95% CI 1.2-6.52) and lower household income (OR 3.63, 95% CI 1.22-10.72). Participants less likely to seek legal representation were least socioeconomically disadvantaged (OR 0.15, 95% CI 0.04-0.50). CONCLUSIONS: Seeking financial compensation was associated with a higher pre-injury BMI rather than injury-related factors. Seeking legal representation was solely related to socio-economic factors.

Are outcomes reported in surgical randomized trials patient-important? A systematic review and meta-analysis.

BACKGROUND: The dangers of using surrogate outcomes are well documented. They may have little or no association with their patient-important correlates, leading to the approval and use of interventions that lack efficacy. We sought to assess whether primary outcomes in surgical randomized controlled trials (RCTs) are more likely to be patient-important outcomes than surrogate or laboratory-based outcomes. METHODS: We reviewed RCTs assessing an operative intervention published in 2008 and 2009 and indexed in MEDLINE, EMBASE or the Cochrane Central Register of Controlled Trials. After a pilot of the selection criteria, 1 reviewer selected trials and another reviewer checked the selection. We extracted information on outcome characteristics (patient-important, surrogate, or laboratory-based outcome) and whether they were primary or secondary outcomes. We calculated odds ratios (OR) and pooled in random-effects meta-analysis to obtain an overall estimate of the association between patient importance and primary outcome specification. RESULTS: In 350 included RCTs, a total of 8258 outcomes were reported (median 18 per trial. The mean proportion (per trial) of patient-important outcomes was 60%, and 66% of trials specified a patient-important primary outcome. The most commonly reported patient-important primary outcomes were morbid events (41%), intervention outcomes (11%), function (11%) and pain (9%). Surrogate and laboratory-based primary outcomes were reported in 33% and 8% of trials, respectively. Patient-important outcomes were not associated with primary outcome status (OR 0.82, 95% confidence interval 0.63-1.1, I2 = 21%). CONCLUSION: A substantial proportion of surgical RCTs specify primary outcomes that are not patient-important. Authors, journals and trial funders should insist that patient-important outcomes are the focus of study.

CONTEXTE: Les dangers de l'utilisation de critères de substitution sont bien documentés. Ils peuvent avoir peu de liens, voire aucun, avec leurs corrélats importants pour le patient, menant à l'approbation et à l'utilisation d'interventions inefficaces. Nous avons tenté de déterminer si les résultats primaires d'essais cliniques randomisés en chirurgie sont plus susceptibles d'être des résultats importants pour le patient que des critères de substitution ou des résultats de laboratoire. MÉTHODES: Nous avons examiné des essais cliniques randomisés portant sur l'évaluation d'une intervention chirurgicale, publiés en 2008 et 2009 et répertoriés dans MEDLINE, EMBASE ou le Cochrane Central Register of Controlled Trials. Après l'essai du critère de sélection, un examinateur a choisi les essais et un autre examinateur a vérifié la sélection. Nous avons obtenu les renseignements sur les caractéristiques des résultats (importants pour le patient, de substitution ou de laboratoire) et déterminé s'il s'agissait de résultats primaires ou secondaires. Nous avons calculé le rapport des cotes (RC) et regroupé une méta-analyse à effets aléatoires afin d'obtenir une estimation globale du lien entre l'importance pour le patient et la spécification du résultat primaire. RÉSULTATS: Un total de 8258 résultats ont été signalés dans les 350 essais cliniques randomisés inclus (pour une médiane de 18 par essai). La proportion moyenne (par essai) de résultats importants pour le patient était de 60 %, et 66 % des essais précisaient un résultat primaire important pour le patient. Les résultats primaires importants pour le patient les plus couramment signalés étaient les événements morbides (41 %), les résultats liés à une intervention (11 %), le fonctionnement (11 %) et la douleur (9 %). Des résultats primaires de substitution ou de laboratoire ont été signalés dans 33 % et 8 % des essais, respectivement. Les résultats importants pour le patient n'étaient pas associés à la situation du résultat primaire (RC 0,82, intervalle de confiance de 95 %, 0,63-1,1, I2 = 21 %). CONCLUSION: Un nombre important d'essais cliniques randomisés en chirurgie précisent des résultats primaires qui ne sont pas importants pour le patient. Les auteurs, les revues et les organismes de financement des essais devraient insister pour que les résultats importants pour le patient soient l'objet principal de l'étude.

Quality of conduct and reporting of meta-analyses of surgical interventions.

BACKGROUND: Meta-analyses are useful tools for summarizing surgical evidence as they aim to encompass multiple sources of information on a particular research question, but they may be prone to methodological and reporting biases. We evaluated the conduct and reporting of meta-analyses of surgical interventions. METHODS AND FINDINGS: We performed a systematic review of 150 meta-analyses of randomized trials of surgical interventions published between January 2010 and June 2011. A comprehensive search strategy was executed using MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews. Data were independently extracted by 2 authors using the PRISMA statement (preferred reporting items for systematic reviews and meta-analyses, a standardized quality of reporting guideline) and AMSTAR (a tool for methodological quality). Descriptive statistics were used for individual items, and as a measure of overall compliance, PRISMA and AMSTAR scores were calculated as the sum of adequately reported domains. A median of 8 trials (interquartile range = 8) was included in each meta-analysis. One third of all meta-analyses had an author with a background in epidemiology and/or statistics. Forty-four percent were published in PRISMA-endorsing journals with a median impact factor of 3.5. There was moderate compliance with PRISMA, with an average of 71% of items reported, but poorer compliance with AMSTAR, with 48% of items adequately described, on average. CONCLUSIONS: Substantial gaps in the conduct and reporting of meta-analyses within the surgical literature exist, mainly in the specification of aims and/or objectives, the use of preplanned protocols, and the evaluation of potential bias at the review (rather than trial) level. Editorial insistence on using reporting guidelines would improve this situation.

Tapentadol Versus Oxycodone for Opioid-Related Adverse Drug Events and Clinical Outcomes After Inpatient Surgery.

Oxycodone is a commonly prescribed opioid for postoperative pain. However, there has been a marked increase in the use of tapentadol over the previous decade due to a perceived superior safety profile of tapentadol compared to oxycodone. There is limited real-world evidence on the safety of tapentadol compared to oxycodone after surgery. The primary objective was to examine the impact of tapentadol compared to oxycodone use on the incidence of opioid-related adverse drug events after surgery. Data for adult surgical patients receiving tapentadol or oxycodone during hospitalization between January 1, 2018, and December 31, 2021, were collected from electronic medical records of 3 tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events. Patients receiving tapentadol or oxycodone were matched using nearest-neighbour propensity score matching. In the matched cohorts (n = 1,530 vs n = 2,775; mean [standard deviation] age 62.3 [17.0] years vs 61.9 [standard deviation 17.9] years; 43% vs 45% male for the tapentadol vs oxycodone groups, respectively), patients given tapentadol experienced a similar incidence of adverse events overall (14.4%, 220/1,530 vs 12.6%, 349/2,775; P = .100; 95% CI -.35% to 3.95%). Secondary outcomes included an increased risk of delirium (2.7%, 41/1,530 vs 1.3%, 37/2,775), arrhythmias (3.4%, 52/1,530 vs 2.2%, 62/2,775), and length of hospital stay (5 [range 1-201] vs 4 [range 1-226] days) compared with oxycodone use. Further real-world studies are warranted to determine the impact of tapentadol use on a broad range of patient outcomes. PERSPECTIVE: This study provides an early signal that tapentadol use may be associated with an increased risk of some adverse events and a longer length of stay. Further research is needed to examine the impact of tapentadol use on a broad range of patient outcomes in clinical practice settings.

Remote Delivery of Partial Meal Replacement for Weight Loss in People Awaiting Arthroplasty.

Background: Obesity is linked to higher rates of complications; lower absolute recovery of mobility, pain, and function; and increased costs of care following total knee or hip arthroplasty (TKA, THA). The aim of this prospective cohort study was to evaluate the effectiveness of a 12-week partial meal replacement (PMR) weight loss program for people awaiting TKA or THA and living with obesity (body mass index (BMI) ≥ 30 kg/m2). Methods: The intervention was delivered remotely and included a 12-week PMR plan of 1200 calories/day, incorporating two meal replacement shakes/soups and a third suitable simple meal option. The intervention support was provided through online group education sessions, one-to-one teleconsultation with a dietitian, and access to a structured PMR App with functions for goal setting and providing educational content on diet, physical activity, and behaviour changes. Results: Of the 182 patients approached, 29 provided consent to participate, 26 participants commenced the program, and 22 participants completed the 12-week PMR plan. Completers exhibited statistically significant weight loss from baseline to 12 weeks, with a paired difference of 6.3 kg (95% CI: 4.8, 7.7; p < 0.001), with 15 out of 22 (68.2%) participants achieving at least 5% weight loss. Statistically significant reductions in HbA1c and low density lipoprotein (LDL) were observed at 12 weeks compared to baseline. Moreover, a significant increase in the proportion of participants in the action and maintenance phases of the readiness to change diet, physical activity, and weight were observed at 12 weeks. The majority of program completers (18 out of 22) expressed willingness to pay for the service if offered on a long-term basis following the arthroplasty. Conclusions: This study's findings demonstrated that significant weight loss is achievable for people living with obesity awaiting arthroplasty following a 12-week PMR weight loss program. The remote delivery of the intervention was feasible and well accepted by people awaiting TKA or THA.

Participant recruitment and attrition in surgical randomised trials with placebo controls versus non-operative controls: a meta-epidemiological study and meta-analysis.

OBJECTIVE: To compare differences in recruitment and attrition between placebo control randomised trials of surgery, and trials of the same surgical interventions and conditions that used non-operative (non-placebo) controls. DESIGN: Meta-epidemiological study. DATA SOURCES: Randomised controlled trials were identified from an electronic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from their inception date to 21 November 2018. STUDY SELECTION: Placebo control trials evaluating efficacy of any surgical intervention and non-operative control trials of the same surgical intervention were included in this study. 25 730 records were retrieved from our systemic search, identifying 61 placebo control and 38 non-operative control trials for inclusion in analysis. OUTCOME MEASURES: Primary outcome measures were recruitment and attrition. These were assessed in terms of recruitment rate (number of participants enrolled, as a proportion of those eligible) and overall attrition rate (composite of dropout, loss to follow-up and cross-overs, expressed as proportion of total sample size). Secondary outcome measures included participant cross-over rate, dropout and loss to follow-up. RESULTS: Unadjusted pooled recruitment and attrition rates were similar between placebo and non-operative control trials. Study characteristics were not significantly different apart from time to primary timepoint which was shorter in studies with placebo controls (365 vs 274 days, p=0.006). After adjusting for covariates (follow-up duration and number of timepoints), the attrition rate of placebo control trials was almost twice as high compared with non-operative controlled-trials (incident rate ratio (IRR) (95% CI) 1.8 (1.1 to 3.0), p=0.032). The incorporation of one additional follow-up timepoint (regardless of follow-up duration) was associated with reduced attrition in placebo control surgical trials (IRR (95% CI) 0.64 (0.52 to 0.79), p<0.001). CONCLUSIONS: Placebo control trials of surgery have similar recruitment issues but higher attrition compared with non-operative (non-placebo) control trials. Study design should incorporate strategies such as increased timepoints for given follow-up duration to mitigate losses to follow-up and dropout. PROSPERO REGISTRATION NUMBER: CRD42019117364.