Kaplan-Meier Survival Analysis Overestimates the Risk of Revision Arthroplasty: A Meta-analysis

Background

Although Kaplan-Meier survival analysis is commonly used to estimate the cumulative incidence of revision after joint arthroplasty, it theoretically overestimates the risk of revision in the presence of competing risks (such as death). Because the magnitude of overestimation is not well documented, the potential associated impact on clinical and policy decision-making remains unknown.

Questions/purposes

We performed a meta-analysis to answer the following questions: (1) To what extent does the Kaplan-Meier method overestimate the cumulative incidence of revision after joint replacement compared with alternative competing-risks methods? (2) Is the extent of overestimation influenced by followup time or rate of competing risks?

Methods

We searched Ovid MEDLINE, EMBASE, BIOSIS Previews, and Web of Science (1946, 1980, 1980, and 1899, respectively, to October 26, 2013) and included article bibliographies for studies comparing estimated cumulative incidence of revision after hip or knee arthroplasty obtained using both Kaplan-Meier and competing-risks methods. We excluded conference abstracts, unpublished studies, or studies using simulated data sets. Two reviewers independently extracted data and evaluated the quality of reporting of the included studies. Among 1160 abstracts identified, six studies were included in our meta-analysis. The principal reason for the steep attrition (1160 to six) was that the initial search was for studies in any clinical area that compared the cumulative incidence estimated using the Kaplan-Meier versus competing-risks methods for any event (not just the cumulative incidence of hip or knee revision); we did this to minimize the likelihood of missing any relevant studies. We calculated risk ratios (RRs) comparing the cumulative incidence estimated using the Kaplan-Meier method with the competing-risks method for each study and used DerSimonian and Laird random effects models to pool these RRs. Heterogeneity was explored using stratified meta-analyses and metaregression.

Results

The pooled cumulative incidence of revision after hip or knee arthroplasty obtained using the Kaplan-Meier method was 1.55 times higher (95% confidence interval, 1.43–1.68; p < 0.001) than that obtained using the competing-risks method. Longer followup times and higher proportions of competing risks were not associated with increases in the amount of overestimation of revision risk by the Kaplan-Meier method (all p > 0.10). This may be due to the small number of studies that met the inclusion criteria and conservative variance approximation.

Conclusions

The Kaplan-Meier method overestimates risk of revision after hip or knee arthroplasty in populations where competing risks (such as death) might preclude the occurrence of the event of interest (revision). Competing-risks methods should be used to more accurately estimate the cumulative incidence of revision when the goal is to plan healthcare services and resource allocation for revisions.     

Regional Intraosseous Administration of Prophylactic Antibiotics is More Effective Than Systemic Administration in a Mouse Model of TKA

Background

In human TKA studies, intraosseous regional administration (IORA) of prophylactic antibiotics achieves local tissue antibiotic concentrations 10 times greater than systemic administration. However, it is unclear if such high concentrations provide more effective prophylaxis.

Questions/purposes

We asked: (1) What prophylaxis dosage and route (intravenous [IV] versus IORA of prophylactic antibiotics) produce less in vivo bacterial burden compared with no-antibiotic controls? (2) Compared with controls, what prophylaxis dosage and route yield fewer colony-forming units (CFUs) in euthanized animals in a model of TKA? (3) Is prophylactic IORA of antibiotics more effective than same-dose IV antibiotic administration in reducing CFUs?

Methods

Mice (six to nine per group) were block randomized to one of six prophylaxis regimens: control, systemic cefazolin (C100_IV), IORA of cefazolin (C100_IORA), systemic vancomycin (V110_IV), low-dose systemic vancomycin (V25_IV), and low-dose IORA of vancomycin (V25_IORA). Surgery involved placement of an intraarticular knee prosthesis, followed by an inoculum of bioluminescent Staphylococcus aureus strain Xen36. Biophotonic imaging assessed in vivo bacterial loads, and after 4 days bacterial load was quantified using culture-based techniques. Comparisons were made for each prophylactic regimen to controls and between same-dose IV and IORA of prophylactic antibiotic regimens.

Results

Mice treated with systemic high-dose vancomycin, IORA of vancomycin, or IORA of cefazolin had lower in vivo Staphylococcus aureus burdens (median area under curve, Control: 5.0 × 10⁶; V110_IV: 1.5 × 10⁶, difference of medians 3.5 × 10⁶, p = 0.003; V25_IV: 1.94 × 10⁶, difference 3.07 × 10⁶, p = 0.49; V25_IORA: 1.51 × 10⁶, difference 3.5 × 10⁶, p = 0.0011; C100_IORA: 1.55 × 10⁶, difference 3.46 × 10⁶, p = 0.0016; C100_IV: 2.35 × 10⁶, difference 2.66 × 10⁶, p = 0.23.) Similar findings were seen with culture-based techniques on recovered implants. IORA of prophylactic antibiotics was more effective than same-dose IV administration in reducing bacterial load on recovered implants (median CFUs < 7.0 × 10⁰ vs 2.83 × 10², p = 0.0183).

Conclusions

IORA of prophylactic cefazolin and vancomycin was more effective than the same dose of antibiotic given systemically. The effectiveness of vancomycin in particular was enhanced by IORA of prophylactic antibiotics despite using a lower dose.

Clinical relevance

Our study supports previous studies of IORA of prophylactic antibiotics in humans and suggests this novel form of administration has the potential to enhance the effectiveness of prophylaxis in TKA. Because of concerns regarding antibiotic stewardship, IORA of prophylactic vancomycin may be more appropriately restricted to patients having TKA who are at greater risk of infection, and clinical trials are in progress.     

How Do Acetabular Version and Femoral Head Coverage Change With Skeletal Maturity?

BackgroundNormal changes in acetabular version over the course of skeletal development have not been well characterized. Knowledge of normal version development is important because acetabular retroversion has been implicated in several pathologic hip processes.Questions/purposesThe purpose of this study was to characterize the orientation of the acetabulum by measuring (1) acetabular version and (2) acetabular sector angles in pediatric patients during development. We also sought to determine whether these parameters vary by sex in the developing child.MethodsWe evaluated CT images of 200 hips in 100 asymptomatic pediatric patients (45 boys, 55 girls; mean age, 13.5 years; range, 9–18 years) stratified by the status of the triradiate physis and sex. We determined the acetabular anteversion angle at various levels in the axial plane as well as acetabular sector angles at five radial planes around the acetabulum.ResultsFor both genders, anteversion angle was greater for the closed physis group throughout all levels (p < 0.001) and both open and closed physis groups were more anteverted as the cut moved caudally away from the acetabular roof (p < 0.001). At the center of the femoral head, the mean anteversion angle (± SD) in girls was 15° ± 3° in the open group and 19° ± 5° in the closed group (p < 0.001). In boys, the mean anteversion angle increased from 14° ± 4° in the open group to 19° ± 4° in the closed group (p = 0.003). In the superior, posterosuperior, and posterior planes, the acetabular sector angles were greater in the closed compared with the open physis group for both boys and girls with the largest increase occurring in the male posterosuperior plane (approximately 20°) (all p < 0.05).ConclusionsThis study demonstrates that acetabular anteversion and acetabular sector angles in both male and female subjects increase with skeletal maturity as a result of growth of the posterior wall. This suggests that radiographic appearance of acetabular retroversion may not be attributable to overgrowth of the anterior wall but rather insufficient growth of the posterior wall, which has clinical treatment implications for pincer-type impingement.

Level of Evidence

Level IV diagnostic study.