Minimizing confounding in comparative observational studies with time-to-event outcomes: An extensive comparison of covariate balancing methods using Monte Carlo simulation.

Observational studies are frequently used in clinical research to estimate the effects of treatments or exposures on outcomes. To reduce the effects of confounding when estimating treatment effects, covariate balancing methods are frequently implemented. This study evaluated, using extensive Monte Carlo simulation, several methods of covariate balancing, and two methods for propensity score estimation, for estimating the average treatment effect on the treated using a hazard ratio from a Cox proportional hazards model. With respect to minimizing bias and maximizing accuracy (as measured by the mean square error) of the treatment effect, the average treatment effect on the treated weighting, fine stratification, and optimal full matching with a conventional logistic regression model for the propensity score performed best across all simulated conditions. Other methods performed well in specific circumstances, such as pair matching when sample sizes were large (n = 5000) and the proportion treated was < 0.25. Statistical power was generally higher for weighting methods than matching methods, and Type I error rates were at or below the nominal level for balancing methods with unbiased treatment effect estimates. There was also a decreasing effective sample size with an increasing number of strata, therefore for stratification-based weighting methods, it may be important to consider fewer strata. Generally, we recommend methods that performed well in our simulations, although the identification of methods that performed well is necessarily limited by the specific features of our simulation. The methods are illustrated using a real-world example comparing beta blockers and angiotensin-converting enzyme inhibitors among hypertensive patients at risk for incident stroke.

Variance estimation of the risk difference when using propensity-score matching and weighting with time-to-event outcomes.

Observational studies are increasingly being used in medicine to estimate the effects of treatments or exposures on outcomes. To minimize the potential for confounding when estimating treatment effects, propensity score methods are frequently implemented. Often outcomes are the time to event. While it is common to report the treatment effect as a relative effect, such as the hazard ratio, reporting the effect using an absolute measure of effect is also important. One commonly used absolute measure of effect is the risk difference or difference in probability of the occurrence of an event within a specified duration of follow-up between a treatment and comparison group. We first describe methods for point and variance estimation of the risk difference when using weighting or matching based on the propensity score when outcomes are time-to-event. Next, we conducted Monte Carlo simulations to compare the relative performance of these methods with respect to bias of the point estimate, accuracy of variance estimates, and coverage of estimated confidence intervals. The results of the simulation generally support the use of weighting methods (untrimmed ATT weights and IPTW) or caliper matching when the prevalence of treatment is low for point estimation. For standard error estimation the simulation results support the use of weighted robust standard errors, bootstrap methods, or matching with a naïve standard error (i.e., Greenwood method). The methods considered in the article are illustrated using a real-world example in which we estimate the effect of discharge prescribing of statins on patients hospitalized for acute myocardial infarction.

Using real-world data from health systems to evaluate the safety and effectiveness of a catheter to treat ischemic ventricular tachycardia.

BACKGROUND: The ThermoCool STSF catheter is used for ablation of ischemic ventricular tachycardia (VT) in routine clinical practice, although outcomes have not been studied and the catheter does not have Food and Drug Administration (FDA) approval for this indication. We used real-world health system data to evaluate its safety and effectiveness for this indication. METHODS: Among patients undergoing ischemic VT ablation with the ThermoCool STSF catheter pooled across two health systems (Mercy Health and Mayo Clinic), the primary safety composite outcome of death, thromboembolic events, and procedural complications within 7 days was compared to a performance goal of 15%, which is twice the expected proportion of the primary composite safety outcome based on prior studies. The exploratory effectiveness outcome of rehospitalization for VT or heart failure or repeat VT ablation at up to 1 year was averaged across health systems among patients treated with the ThermoCool STSF vs. ST catheters. RESULTS: Seventy total patients received ablation for ischemic VT using the ThermoCool STSF catheter. The primary safety composite outcome occurred in 3/70 (4.3%; 90% CI, 1.2-10.7%) patients, meeting the pre-specified performance goal, p = 0.0045. At 1 year, the effectiveness outcome risk difference (STSF-ST) at Mercy was - 0.4% (90% CI: - 25.2%, 24.3%) and at Mayo Clinic was 12.6% (90% CI: - 13.0%, 38.4%); the average risk difference across both institutions was 5.8% (90% CI: - 12.0, 23.7). CONCLUSIONS: The ThermoCool STSF catheter was safe and appeared effective for ischemic VT ablation, supporting continued use of the catheter and informing possible FDA label expansion. Health system data hold promise for real-world safety and effectiveness evaluation of cardiovascular devices.

Comparison of Clinical Outcomes of Gripping Surface Technology Staple Reloads versus Standard Staple Reloads Used with Manual Linear Surgical Staplers.

Purpose: Linear surgical staplers reduce rates of surgical adverse events (bleeding, leaks, infections) compared to manual sutures thereby reducing patient risks, surgeon workflow disruption, and healthcare costs. However, further improvements are needed. Ethicon Gripping Surface Technology (GST) reloads, tested and approved by regulatory authorities in combination with powered staplers, may reduce surgical risks through improved tissue grip. While manual staplers are used in some regions due to affordability, clinical data on GST reloads used with manual staplers are unavailable. This study compared surgical adverse event rates of manual staplers with GST vs standard reloads. These data may be used for label changes in China and Latin America. Patients and Methods: Patients undergoing general or thoracic surgery between October 1, 2015 and August 31, 2021 using ECHELON FLEX™ manual staplers with GST or standard reloads were identified from the Premier Healthcare Database. GST reloads were compared to standard reloads for non-inferiority in bleeding and anastomotic leak for general surgery. Secondary outcomes included sepsis for general surgery, and bleeding and prolonged air leak for thoracic surgery. Covariate balancing was performed using stable balancing weights. Results: The general and thoracic surgery cohorts contained 4571 (GST: 2780; standard: 1791) and 814 (GST: 514; standard: 300) patients, respectively. GST reloads were non-inferior to standard reloads for bleeding and anastomotic leak (adjusted cumulative incidence ratio: 1.02 [90% CI: 0.71, 1.45] and 1.03 [90% CI: 0.72, 1.46], respectively) for general surgery. Compared with standard reloads, GST reloads had a similar incidence of sepsis (2.2% vs 2.1%) for general surgery and lower incidences of bleeding (9.5% vs 16.0%) and prolonged air leak (12.6% vs 14.0%,) for thoracic surgery. Conclusion: GST reloads, compared to standard reloads, used with ECHELON FLEX™ manual staplers had comparable perioperative bleeding and anastomotic leak for general surgery, and lower incidences of safety events for thoracic surgery.

Partition testing for real-world evidence studies.

Traditional approaches to hypothesis testing in comparative post-approval safety and effectiveness studies of medical products are often inadequate because of a limited scope of possible inferences (e.g., superiority or inferiority). Often there is interest in simultaneously testing for superiority, equivalence, inferiority, non-inferiority, and non-superiority, which can be achieved using a partition testing framework. Partition testing only requires selection of an equivalence margin and calculation of a two-sided Wald confidence interval. In addition to permitting a broader range of inferences, the strengths of the approach include: mitigating publication bias, avoiding use of a clinically irrelevant nil hypothesis, and more transparent and impartial appraisal of the clinical importance of a study's findings by pre-specifying an equivalence margin. However, a challenge in implementing the approach can be the process for identifying an equivalence margin. The methodology is illustrated using a published study of the safety of Ondansetron for the off-label treatment of nausea and vomiting during pregnancy. Applying the method to the study results would have led to a conclusion that women exposed to Ondansetron in comparison to those that are not, are equivalent with respect to risk of cardiac malformations and oral clefts. These conclusions are more in line with the magnitude of the observed effects than the conclusions resulting from a traditional inferiority/superiority testing conducted by the study authors.

Safety and Effectiveness of a Catheter With Contact Force and 6-Hole Irrigation for Ablation of Persistent Atrial Fibrillation in Routine Clinical Practice.

Importance: The ThermoCool SmartTouch catheter (ablation catheter with contact force and 6-hole irrigation [CF-I6]) is approved by the US Food and Drug Administration (FDA) for paroxysmal atrial fibrillation (AF) ablation and used in routine clinical practice for persistent AF ablation, although clinical outcomes for this indication are unknown. There is a need to understand whether data from routine clinical practice can be used to conduct regulatory-grade evaluations and support label expansions. Objective: To use health system data to compare the safety and effectiveness of the CF-I6 catheter for persistent AF ablation with the ThermoCool SmartTouch SurroundFlow catheter (ablation catheter with contact force and 56-hole irrigation [CF-I56]), which is approved by the FDA for this indication. Design, Setting, and Participants: This retrospective, comparative-effectiveness cohort study included patients undergoing catheter ablation for persistent AF at Mercy Health or Mayo Clinic from January 1, 2014, to April 30, 2021, with up to a 1-year follow-up using electronic health record data. Exposures: Use of the CF-I6 or CF-I56 catheter. Main Outcomes and Measures: The primary safety outcome was a composite of death, thromboembolic events, and procedural complications within 7 to 90 days. The exploratory effectiveness outcome was a composite of AF-related hospitalization events after a 90-day blanking period. Propensity score weighting was used to balance baseline covariates. Risk differences were estimated between catheter groups and averaged across the 2 health care systems, testing for noninferiority of the CF-I6 vs the CF-I56 catheter with respect to the safety outcome using 2-sided 90% CIs. Results: Overall, 1450 patients (1034 [71.3%] male; 1397 [96.3%] White) underwent catheter ablation for persistent AF, including 949 at Mercy Health (186 CF-I6 and 763 CF-I56; mean [SD] age, 64.9 [9.2] years) and 501 at Mayo Clinic (337 CF-I6 and 164 CF-I56; mean [SD] age, 63.7 [9.5] years). A total of 798 (55.0%) had been treated with class I or III antiarrhythmic drugs before ablation. The safety outcome (CF-I6 - CF-I56) was similar at both Mercy Health (1.3%; 90% CI, -2.1% to 4.6%) and Mayo Clinic (-3.8%; 90% CI, -11.4% to 3.7%); the mean difference was noninferior, with a mean of 0.5% (90% CI, -2.6% to 3.5%; P < .001). The effectiveness was similar at 12 months between the 2 catheter groups (mean risk difference, -1.8%; 90% CI, -7.3% to 3.7%). Conclusions and Relevance: In this cohort study, the CF-I6 catheter met the prespecified noninferiority safety criterion for persistent AF ablation compared with the CF-I56 catheter, and effectiveness was similar. This study demonstrates the ability of electronic health care system data to enable safety and effectiveness evaluations of medical devices.

Comparative Safety of the TFN-ADVANCED Proximal Femoral Nailing System: Findings from a U.S. Health-Care Database.

BACKGROUND: Proximal femoral fractures are often treated with cephalomedullary nails. Although nail breakages following fracture repair are infrequent, a recent implant retrieval study suggested that the TFN-ADVANCED (TFNA) Proximal Femoral Nailing System (DePuy Synthes) was susceptible to post-implant breakage. It is unclear whether the risk of breakage among patients who receive the TFNA implant is higher than patients who receive other comparable cephalomedullary nails. The current study was designed to evaluate the comparative risk of breakage of the TFNA nail. METHODS: Using data from a large U.S. health-care database, the current study was designed to determine whether TFNA nails have equal, lower, or higher risk of breakage relative to all other comparable, single-head-element (with no additional lag screws), cephalomedullary nails, the Stryker Gamma3 and the Zimmer Natural Nail, referred to in this study as the non-TFNA group. Data were from patients who received the TFNA implant or non-TFNA nails in 365 hospitals between February 1, 2014, and September 30, 2019. Analysis of nail breakage post-implantation was prespecified as the difference between the TFNA group and the non-TFNA group in cumulative incidence at 18 months, with a prespecified equivalence margin of 0.5%, using data balanced on measured covariates by propensity score weighting. RESULTS: Within the first 18 months of implantation, in 14,370 patients with TFNA nails, there were 27 nail breakages, and in 8,260 patients with non-TFNA nails, there were 29 nail breakages. The mean time to nail breakage was 4.72 months for the TFNA group and 4.05 months for the non-TFNA group. In the balanced data, the risk of breakage at 18 months was 0.26% (95% confidence interval [CI], 0.17% to 0.36%) for the TFNA group and 0.25% (95% CI, 0.05% to 0.45%) for the non-TFNA group, with a risk difference of 0.01% (95% CI, -0.21% to 0.24%). This result indicates that the cumulative incidence of nail breakage was equivalent (between -0.5% and 0.5%) for both nail groups. The risk differences were also within the equivalence margin in subgroup analyses: pertrochanteric fractures only (-0.08% [95% CI, -0.34% to 0.19%]), pertrochanteric or subtrochanteric fractures (-0.04% [95% CI, -0.29% to 0.21%]), and those with International Classification of Diseases, Tenth Revision (ICD-10) data only (0.03% [95% CI, -0.18% to 0.25%]). CONCLUSIONS: The risk of nail breakage was equivalent for TFNA and comparator cephalomedullary nails. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Propensity score methods for time-dependent cluster confounding.

In observational studies, subjects are often nested within clusters. In medical studies, patients are often treated by doctors and therefore patients are regarded as nested or clustered within doctors. A concern that arises with clustered data is that cluster-level characteristics (e.g., characteristics of the doctor) are associated with both treatment selection and patient outcomes, resulting in cluster-level confounding. Measuring and modeling cluster attributes can be difficult and statistical methods exist to control for all unmeasured cluster characteristics. An assumption of these methods however is that characteristics of the cluster and the effects of those characteristics on the outcome (as well as probability of treatment assignment when using covariate balancing methods) are constant over time. In this paper, we consider methods that relax this assumption and allow for estimation of treatment effects in the presence of unmeasured time-dependent cluster confounding. The methods are based on matching with the propensity score and incorporate unmeasured time-specific cluster effects by performing matching within clusters or using fixed- or random-cluster effects in the propensity score model. The methods are illustrated using data to compare the effectiveness of two total hip devices with respect to survival of the device and a simulation study is performed that compares the proposed methods. One method that was found to perform well is matching within surgeon clusters partitioned by time. Considerations in implementing the proposed methods are discussed.

Variance estimation when using propensity-score matching with replacement with survival or time-to-event outcomes.

Propensity-score matching is a popular analytic method to estimate the effects of treatments when using observational data. Matching on the propensity score typically requires a pool of potential controls that is larger than the number of treated or exposed subjects. The most common approach to matching on the propensity score is matching without replacement, in which each control subject is matched to at most one treated subject. Failure to find a matched control for each treated subject can lead to "bias due to incomplete matching." To avoid this bias, it is important to identify a matched control subject for each treated subject. An alternative to matching without replacement is matching with replacement, in which control subjects are allowed to be matched to multiple treated subjects. A limitation to the use of matching with replacement is that variance estimation must account for both the matched nature of the sample and for some control subjects being included in multiple matched sets. While a variance estimator has been proposed for when outcomes are continuous, no such estimator has been proposed for use with time-to-event outcomes, which are common in medical and epidemiological research. We propose a variance estimator for the hazard ratio when matching with replacement. We conducted a series of Monte Carlo simulations to examine the performance of this estimator. We illustrate the utility of matching with replacement to estimate the effect of smoking cessation counseling on survival in smokers discharged from hospital with a heart attack.

Postmarket surveillance of arthroplasty device components using machine learning methods.

PURPOSE: While joint arthroplasty is generally a safe and effective procedure, there are concerns that some devices are at increased risk of failure. Early identification of total hip arthroplasty devices with increased risk of failure can be challenging because devices consist of multiple components, hundreds of distinct components are currently used in surgery, and any estimated effect needs to address confounding due to device and patient factors. The purpose of this study was to assess the effectiveness of machine learning approaches at identifying recalled components listed by the US Food and Drug Administration using data from a US total joint arthroplasty registry. METHODS: An open cohort study was conducted using data (January 1, 2001, to December 31, 2015) from 74 520 implantations and 348 unique components in the Kaiser Permanente Total Joint Replacement Registry. Exposures of interest were device components used in elective primary total hip arthroplasty. The outcome was time to first revision surgery, defined as exchange, removal, or addition of any component. Machine learning methods included regularized/unregularized Cox models and random survival forest. RESULTS: Among the recalled components detected were ASR acetabular shell/large femoral head, Durom acetabular shell/Metasul large femoral head, and Rejuvenate modular neck stem. The three components not identified were characterized by small numbers of devices recorded in the registry. CONCLUSIONS: The novel approaches to signal detection may improve postmarket surveillance of frequently used arthroplasty devices, which in turn will improve public health.

An international comparison of THA patients, implants, techniques, and survivorship in Sweden, Australia, and the United States.

Background and purpose - International comparisons of total hip arthroplasty (THA) practices and outcomes provide an opportunity to enhance the quality of care worldwide. We compared THA patients, implants, techniques, and survivorship in Sweden, Australia, and the United States. Patients and methods - Primary THAs due to osteoarthritis were identified using Swedish (n = 159,695), Australian (n = 279,693), and US registries (n = 69,641) (2003-2015). We compared patients, practices, and implant usage across the countries using descriptive statistics. We evaluated time to all-cause revision using Kaplan-Meier survival curves. We assessed differences in countries' THA survival using chi-square tests of survival probabilities. Results - Sweden had fewer comorbidities than the United States and Australia. Cement fixation was used predominantly in Sweden and cementless in the United States and Australia. The direct anterior approach was used more frequently in the United States and Australia. Smaller head sizes (≤ 32 mm vs. ≥ 36 mm) were used more often in Sweden than the United States and Australia. Metal-on-highly cross-linked polyethylene was used more frequently in the United States and Australia than in Sweden. Sweden's 5- (97.8%) and 10-year THA survival (95.8%) was higher than the United States' (5-year: 97.0%; 10-year: 95.2%) and Australia (5-year: 96.3%; 10-year: 93.5%). Interpretation - Patient characteristics, surgical techniques, and implants differed across the 3 countries, emphasizing the need to adjust for demographics, surgical techniques, and implants and the need for global standardized definitions to compare THA survivorship internationally.

A review and empirical comparison of causal inference methods for clustered observational data with application to the evaluation of the effectiveness of medical devices.

Observational studies are commonplace in medicine. A frequent concern is confounding bias due to differences in patient characteristics across treatment groups, but other important issues include dependency among observations nested within clusters (e.g. patients clustered within physicians or surgeons) and confounding due to cluster characteristics (e.g. physician or surgeon experience or training). Given the frequency with which these issues arise in medical research, as well as their relative complexity, methods for the analysis of clustered observational data are reviewed. We argue for estimating causal treatment effects using marginal models that either match or weight observations using a suitable distance metric (e.g. the propensity score). Simulation results demonstrated that methods incorporating clustering into calculation of the variance were generally more accurate than those that did not. Moreover, methods that account for cluster confounding when estimating the treatment effect were least biased and most accurate. Throughout the paper we illustrate the proposed methods in a medical device setting that compares the effectiveness of femoral heads used in total hip replacements. Whenever possible the clustered aspect of the data should be considered in the design of the study when constructing the distance measure or in the matching process, as well as in the analysis when estimating the variance of the treatment effect.

Survival and Reintervention Risk by Patient Age and Preoperative Abdominal Aortic Aneurysm Diameter after Endovascular Aneurysm Repair.

BACKGROUND: Endovascular aneurysm repair (EVAR) has become the standard of care for abdominal aortic aneurysm (AAA), but questions remain regarding the benefit in high-risk and elderly patients. The purpose of this study was to examine the effect of age, preoperative AAA diameter, and their interaction on survival and reintervention rates after EVAR. METHODS: Our integrated health system's AAA endograft registry was used to identify patients who underwent elective EVAR between 2010 and 2014. Of interest was the effect of patient age at the time of surgery (≤80 vs. >80 years old), preoperative AAA diameter (≤5.5 cm vs. >5.5 cm), and their interaction. Primary endpoints were all-cause mortality and reintervention. Between-within mixed-effects Cox models with propensity score weights were fit. RESULTS: Of 1,967 patients undergoing EVAR, unadjusted rates for survival at 4 years after EVAR was 76.1%, and reintervention-free rate was 86.0%. For mortality, there was insufficient evidence for an interaction between age and AAA size (P = 0.309). Patient age >80 years was associated with 2.53-fold higher mortality risk (hazard ratios [HR] = 2.53; 95% confidence intervals [CI], 1.73-3.70; P < 0.001), whereas AAA > 5.5 cm was associated with 1.75-fold higher mortality risk (HR = 1.75; 95% CI, 1.26-2.45; P = 0.001). For reintervention risk, there were no significant interactions or main effects for age or AAA diameter. CONCLUSIONS: Age and AAA diameter are independent predictors of reduced survival after EVAR, but the effect is not amplified when both are present. Age >80 years or AAA size >5.5 cm did not increase the risk of reintervention. No specific AAA size, patient age, or combination thereof was identified that would contraindicate AAA repair.

Risk Factors for Mortality and Readmission After Shoulder Hemiarthroplasty for Fracture.

BACKGROUND: Limited information exists regarding mortality and readmission following proximal humerus fracture. This study examines risk factors following hemiarthroplasty for these fractures. METHODS: A retrospective analysis of prospectively collected data on 788 patients treated with hemiarthroplasty for acute proximal humerus fracture from January 2005 to December 2011 was conducted. One-year mortality and 30- and 90-day hospital readmission were evaluated. Patient risk factors included age, race, gender, diabetes, American Society of Anesthesiologists (ASA) score, and body mass index. RESULTS: One-year mortality rate was 5.2%. Patients with ASA ≥3 had 2.37 times (95% confidence interval [CI]: 1.05-5.32) greater mortality risk versus patients with ASA1/2. The 30-day readmission rate was 8.4% and at 90 days was 12.6%. Females had 0.53 risk of readmission versus males (95% CI: 0.29-0.96). Patients with ASA ≥3 had 1.79 (95% CI: 1.04-3.09) risk of 90-day readmission versus patients with ASA1/2; females had 0.52 (95% CI: 0.31-0.85) risk of readmission versus males. Increased age increased all odds ratios. CONCLUSIONS: Readmission rate after hemiarthroplasty for proximal humerus fracture is significant both at 30 and 90 days and is higher in males. Age and ASA ≥3 correlate with this. Diabetes and obesity were not significant risk factors for readmission or mortality.

Meta-analysis of individual registry results enhances international registry collaboration.

Background and purpose - Although common in medical research, meta-analysis has not been widely adopted in registry collaborations. A meta-analytic approach in which each registry conducts a standardized analysis on its own data followed by a meta-analysis to calculate a weighted average of the estimates allows collaboration without sharing patient-level data. The value of meta-analysis as an alternative to individual patient data analysis is illustrated in this study by comparing the risk of revision of porous tantalum cups versus other uncemented cups in primary total hip arthroplasties from Sweden, Australia, and a US registry (2003-2015). Patients and methods - For both individual patient data analysis and meta-analysis approaches a Cox proportional hazard model was fit for time to revision, comparing porous tantalum (n = 23,201) with other uncemented cups (n = 128,321). Covariates included age, sex, diagnosis, head size, and stem fixation. In the meta-analysis approach, treatment effect size (i.e., Cox model hazard ratio) was calculated within each registry and a weighted average for the individual registries' estimates was calculated. Results - Patient-level data analysis and meta-analytic approaches yielded the same results with the porous tantalum cups having a higher risk of revision than other uncemented cups (HR (95% CI) 1.6 (1.4-1.7) and HR (95% CI) 1.5 (1.4-1.7), respectively). Adding the US cohort to the meta-analysis led to greater generalizability, increased precision of the treatment effect, and similar findings (HR (95% CI) 1.6 (1.4-1.7)) with increased risk of porous tantalum cups. Interpretation - The meta-analytic technique is a viable option to address privacy, security, and data ownership concerns allowing more expansive registry collaboration, greater generalizability, and increased precision of treatment effects.

Between-within effects in survival models with cross-classified clustering: Application to the evaluation of the effectiveness of medical devices.

In many medical applications involving observational survival data there will be a cross-classification of doctors and hospitals, as well as an interest in controlling for potentially confounding doctor and hospital effects when evaluating the effectiveness of a medical intervention. In this paper, we propose the use of a between-within model with cross-classified random effects and show through simulation that it performs better than alternative models. A real data example illustrates the application of the proposed model in a study of the survival of hip implants. The proposed model has broad utility in determining the effectiveness of medical interventions.

Midterm-Adjusted Survival Comparing the Best Performing Unicompartmental and Total Knee Arthroplasties in a Registry.

BACKGROUND: Recent literature suggests that the difference in revision risk between unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) can be influenced by surgeon volume and other confounders. We hypothesized that implant selection might decrease the relative risk of revision in an adjusted model. METHODS: We selected the best performing (BP) primary UKAs and TKAs performed for osteoarthritis between January 2001 and December 2012 collected through a joint replacement registry. We compared aseptic and all-cause risk of revision using a surgeon-stratified Cox regression model with propensity score adjustment. RESULTS: One thousand fifty-four UKAs were compared with 74,185 TKAs. The rate for all-cause revision was lower for UKAs (2.1%) than for TKAs (2.4%), whereas the rate for aseptic revision was higher for UKAs (2.0%) than TKAs (1.4%). The adjusted risk of aseptic revision was not significantly higher for UKA than TKA (hazard ratio = 2.02 [0.68, 5.96], P = .203) or all-cause revision (hazard ratio = 1.24 [0.52, 2.98], P = .603). CONCLUSION: When comparing the survivorship of the BP UKAs to the BP TKAs in our registry, the adjusted risk of revision remained higher for UKAs than for TKAs, although the difference did not reach statistical significance.

Comparative Effectiveness and Safety of Drug Prophylaxis for Prevention of Venous Thromboembolism After Total Knee Arthroplasty.

BACKGROUND: Rates of venous thromboembolism in contemporary studies of primary total knee arthroplasty (TKA) have been reported to be as high as 3.5%. Although drug prophylaxis is effective, the best option among these regimens is not well established. The purpose of this study was to evaluate the comparative effectiveness and safety of aspirin, low-molecular-weight heparin, synthetic pentasaccharide factor Xa inhibitors, and vitamin K antagonist. METHODS: Data were from a US total joint replacement registry, with 30,499 patients receiving unilateral TKA from May 16, 2006, to December 31, 2013. Patients received either aspirin (324-325 mg daily), enoxaparin (40-60 mg daily), fondaparinux (2.5 mg daily), or warfarin (all doses) and were followed up 90 days postoperatively on several outcomes: deep vein thrombosis, pulmonary embolism, major bleeding, wound complications, infection, and death. RESULTS: There was no evidence that fondaparinux, enoxaparin, or warfarin were superior to aspirin in the prevention of pulmonary embolism, deep vein thrombosis, or venous thromboembolism or that aspirin was safer than these alternatives. However, enoxaparin was found to be as safe as aspirin with respect to bleeding, and fondaparinux was as safe as aspirin for risk of wound complications. CONCLUSION: Among TKA patients, we did not find evidence for decreased effectiveness or increased safety with use of aspirin, but enoxaparin had comparable safety to aspirin for bleeding and fondaparinux had comparable safety to aspirin for wound complications.

Is There a Difference in Revision Risk Between Metal and Ceramic Heads on Highly Crosslinked Polyethylene Liners?

BACKGROUND: The most common bearing surface used among primary THAs worldwide is a metal or ceramic femoral head that articulates against a highly crosslinked ultrahigh-molecular-weight polyethylene (HXLPE) acetabular liner. Despite their widespread use, relatively little is known about the comparative effectiveness of ceramic versus metal femoral heads with respect to risk of revision and dislocation as well as the role of head size in this relationship. QUESTIONS/PURPOSES: The purpose of this study was to evaluate the risk of (1) all-cause revision in metal versus ceramic femoral heads when used with an HXLPE liner, including an evaluation of the effect of head size; and (2) dislocation in metal versus ceramic femoral heads when used with an HXLPE liner as well as an assessment of the effect of head size. METHODS: Data were collected as part of the Kaiser Permanente Total Joint Replacement Registry between 2001 and 2013. Patients in this study were on average overweight (body mass index = 29 kg/m2), 67 years old, mostly female (57%), and had osteoarthritis (93%) as the primary indication for surgery. The material of the femoral head (metal, ceramic) was crossed with head size (< 32, 32, 36, > 36 mm), yielding eight device groupings. Only uncemented devices were evaluated. The primary outcome was all-cause revision (n = 28,772) and the secondary outcome was dislocation within 1 year (n = 19,623). Propensity scores were used to adjust for potential confounding at the implant/patient level using between-within semiparametric survival models that control for surgeon and hospital confounding and adjust estimates for the within-cluster correlation among observations on the response. RESULTS: For all-cause revision, there was no difference between ceramic versus metal (reference) heads in combination with an HXLPE liner (hazard ratio [HR] = 0.82 [0.65-1.04], p = 0.099). Smaller metal head sizes of < 32 mm were associated with increased risk of revision relative to 36 mm (HR = 1.66 [1.20-2.31], p = 0.002, adjusted p = 0.025). For dislocation, ceramic heads increased risk relative to metal at < 32 mm only (HR = 4.39 [1.72-11.19], p = 0.002, adjusted p = 0.020). Head sizes < 32 mm were associated with increased risk of dislocation relative to 36 mm for metal (HR = 2.99 [1.40-6.39], p = 0.005, adjusted p = 0.047) and ceramic heads (HR = 15.69 [6.07-40.55], p < 0.001, adjusted p < 0.001). CONCLUSIONS: The results did not provide evidence for use of one femoral head material over another when used with HXLPE liners for the outcome of revision, but for dislocation, metal performed better than ceramic with < 32-mm heads. Overall, the findings suggest increased risk of revision/dislocation with head sizes < 32 mm. LEVEL OF EVIDENCE: Level III, therapeutic study.