William M. Reichmann

Estimating the Burden of Total Knee Replacement in the United States

BACKGROUND In the last decade, the number of total knee replacements performed annually in the United States has doubled, with disproportionate increases among younger adults. While total knee replacement is a highly effective treatment for end-stage knee osteoarthritis, total knee replacement recipients can experience persistent pain and severe complications. We are aware of no current estimates of the prevalence of total knee replacement among adults in the U.S. METHODS We used the Osteoarthritis Policy Model, a validated computer simulation model of knee osteoarthritis, and data on annual total knee replacement utilization to estimate the prevalence of primary and revision total knee replacement among adults fifty years of age or older in the U.S. We combined these prevalence estimates with U.S. Census data to estimate the number of adults in the U.S. currently living with total knee replacement. The annual incidence of total knee replacement was derived from two longitudinal knee osteoarthritis cohorts and ranged from 1.6% to 11.9% in males and from 2.0% to 10.9% in females. RESULTS We estimated that 4.0 million (95% confidence interval [CI]: 3.6 million to 4.4 million) adults in the U.S. currently live with a total knee replacement, representing 4.2% (95% CI: 3.7% to 4.6%) of the population fifty years of age or older. The prevalence was higher among females (4.8%) than among males (3.4%) and increased with age. The lifetime risk of primary total knee replacement from the age of twenty-five years was 7.0% (95% CI: 6.1% to 7.8%) for males and 9.5% (95% CI: 8.5% to 10.5%) for females. Over half of adults in the U.S. diagnosed with knee osteoarthritis will undergo a total knee replacement. CONCLUSIONS Among older adults in the U.S., total knee replacement is considerably more prevalent than rheumatoid arthritis and nearly as prevalent as congestive heart failure. Nearly 1.5 million of those with a primary total knee replacement are fifty to sixty-nine years old, indicating that a large population is at risk for costly revision surgery as well as possible long-term complications of total knee replacement.

Evaluation of exposure-specific risks from two independent samples: A simulation study

BackgroundPrevious studies have proposed a simple product-based estimator for calculating exposure-specific risks (ESR), but the methodology has not been rigorously evaluated. The goal of our study was to evaluate the existing methodology for calculating the ESR, propose an improved point estimator, and propose variance estimates that will allow the calculation of confidence intervals (CIs).MethodsWe conducted a simulation study to test the performance of two estimators and their associated confidence intervals: 1) current (simple product-based estimator) and 2) proposed revision (revised product-based estimator). The first method for ESR estimation was based on multiplying a relative risk (RR) of disease given a certain exposure by an overall risk of disease. The second method, which is proposed in this paper, was based on estimates of the risk of disease in the unexposed. We then multiply the updated risk by the RR to get the revised product-based estimator. A log-based variance was calculated for both estimators. Also, a binomial-based variance was calculated for the revised product-based estimator. 95% CIs were calculated based on these variance estimates. Accuracy of point estimators was evaluated by comparing observed relative bias (percent deviation from the true estimate). Interval estimators were evaluated by coverage probabilities and expected length of the 95% CI, given coverage. We evaluated these estimators across a wide range of exposure probabilities, disease probabilities, relative risks, and sample sizes.ResultsWe observed more bias and lower coverage probability when using the existing methodology. The revised product-based point estimator exhibited little observed relative bias (max: 4.0%) compared to the simple product-based estimator (max: 93.9%). Because the simple product-based estimator was biased, 95% CIs around this estimate exhibited small coverage probabilities. The 95% CI around the revised product-based estimator from the log-based variance provided better coverage in most situations.ConclusionThe currently accepted simple product-based method was only a reasonable approach when the exposure probability is small (< 0.05) and the RR is ≤ 3.0. The revised product-based estimator provides much improved accuracy.

Impact of Obesity and Knee Osteoarthritis on Morbidity and Mortality in Older Americans

BACKGROUND Obesity and knee osteoarthritis are among the most frequent chronic conditions affecting Americans aged 50 to 84 years. OBJECTIVE To estimate quality-adjusted life-years lost due to obesity and knee osteoarthritis and health benefits of reducing obesity prevalence to levels observed a decade ago. DESIGN The U.S. Census and obesity data from national data sources were combined with estimated prevalence of symptomatic knee osteoarthritis to assign persons aged 50 to 84 years to 4 subpopulations: nonobese without knee osteoarthritis (reference group), nonobese with knee osteoarthritis, obese without knee osteoarthritis, and obese with knee osteoarthritis. The Osteoarthritis Policy Model, a computer simulation model of knee osteoarthritis and obesity, was used to estimate quality-adjusted life-year losses due to knee osteoarthritis and obesity in comparison with the reference group. SETTING United States. PARTICIPANTS U.S. population aged 50 to 84 years. MEASUREMENTS Quality-adjusted life-years lost owing to knee osteoarthritis and obesity. RESULTS Estimated total losses of per-person quality-adjusted life-years ranged from 1.857 in nonobese persons with knee osteoarthritis to 3.501 for persons affected by both conditions, resulting in a total of 86.0 million quality-adjusted life-years lost due to obesity, knee osteoarthritis, or both. Quality-adjusted life-years lost due to knee osteoarthritis and/or obesity represent 10% to 25% of the remaining quality-adjusted survival of persons aged 50 to 84 years. Hispanic and black women had disproportionately high losses. Model findings suggested that reversing obesity prevalence to levels seen 10 years ago would avert 178,071 cases of coronary heart disease, 889,872 cases of diabetes, and 111,206 total knee replacements. Such a reduction in obesity would increase the quantity of life by 6,318,030 years and improve life expectancy by 7,812,120 quality-adjusted years in U.S. adults aged 50 to 84 years. LIMITATIONS Comorbidity incidences were derived from prevalence estimates on the basis of life expectancy of the general population, potentially resulting in conservative underestimates. Calibration analyses were conducted to ensure comparability of model-based projections and data from external sources. CONCLUSION The number of quality-adjusted life-years lost owing to knee osteoarthritis and obesity seems to be substantial, with black and Hispanic women experiencing disproportionate losses. Reducing mean body mass index to the levels observed a decade ago in this population would yield substantial health benefits. PRIMARY FUNDING SOURCE The National Institutes of Health and the Arthritis Foundation.

Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US.

To estimate the incidence and lifetime risk of diagnosed symptomatic knee osteoarthritis (OA) and the age at diagnosis of knee OA based on self‐reports in the US population.

Systematic review of the concurrent and predictive validity of MRI biomarkers in OA

OBJECTIVE To summarize literature on the concurrent and predictive validity of MRI-based measures of osteoarthritis (OA) structural change. METHODS An online literature search was conducted of the OVID, EMBASE, CINAHL, PsychInfo and Cochrane databases of articles published up to the time of the search, April 2009. 1338 abstracts obtained with this search were preliminarily screened for relevance by two reviewers. Of these, 243 were selected for data extraction for this analysis on validity as well as separate reviews on discriminate validity and diagnostic performance. Of these 142 manuscripts included data pertinent to concurrent validity and 61 manuscripts for the predictive validity review. For this analysis we extracted data on criterion (concurrent and predictive) validity from both longitudinal and cross-sectional studies for all synovial joint tissues as it relates to MRI measurement in OA. RESULTS Concurrent validity of MRI in OA has been examined compared to symptoms, radiography, histology/pathology, arthroscopy, CT, and alignment. The relation of bone marrow lesions, synovitis and effusion to pain was moderate to strong. There was a weak or no relation of cartilage morphology or meniscal tears to pain. The relation of cartilage morphology to radiographic OA and radiographic joint space was inconsistent. There was a higher frequency of meniscal tears, synovitis and other features in persons with radiographic OA. The relation of cartilage to other constructs including histology and arthroscopy was stronger. Predictive validity of MRI in OA has been examined for ability to predict total knee replacement (TKR), change in symptoms, radiographic progression as well as MRI progression. Quantitative cartilage volume change and presence of cartilage defects or bone marrow lesions are potential predictors of TKR. CONCLUSION MRI has inherent strengths and unique advantages in its ability to visualize multiple individual tissue pathologies relating to pain and also predict clinical outcome. The complex disease of OA which involves an array of tissue abnormalities is best imaged using this imaging tool.

Summary and recommendations of the OARSI FDA osteoarthritis Assessment of Structural Change Working Group

OBJECTIVE The Osteoarthritis Research Society International initiated a number of working groups to address a call from the US Food and Drug Administration (FDA) on updating draft guidance on conduct of osteoarthritis (OA) clinical trials. The development of disease-modifying osteoarthritis drugs (DMOADs) remains challenging. The Assessment of Structural Change (ASC) Working Group aimed to provide a state-of-the-art critical update on imaging tools for OA clinical trials. METHODS The Group focussed on the performance metrics of conventional radiographs (CR) and magnetic resonance imaging (MRI), performing systematic literature reviews for these modalities. After acquiring these reviews, summary and research recommendations were developed through a consensus process. RESULTS For CR, there is some evidence for construct and predictive validity, with good evidence for reliability and responsiveness of metric measurement of joint space width (JSW). Trials off at least 1 and probably 2 years duration will be required. Although there is much less evidence for hip JSW, it may provide greater responsiveness than knee JSW. For MRI cartilage morphometry in knee OA, there is some evidence for construct and predictive validity, with good evidence for reliability and responsiveness. The responsiveness of semi-quantitative MRI assessment of cartilage morphology, bone marrow lesions and synovitis was also good in knee OA. CONCLUSIONS Radiographic JSW is still a recommended option for trials of structure modification, with the understanding that the construct represents a number of pathologies and trial duration may be long. MRI is now recommended for clinical trials in terms of cartilage morphology assessment. It is important to study all the joint tissues of the OA joint and the literature is growing on MRI quantification (and its responsiveness) of non-cartilage features. The research recommendations provided will focus researchers on important issues such as determining how structural change within the relatively short duration of a trial reflects long-term change in patient-centred outcomes.

Joint space narrowing and Kellgren–Lawrence progression in knee osteoarthritis: an analytic literature synthesis

OBJECTIVE While the interpretation of cartilage findings on magnetic resonance imaging (MRI) evolves, plain radiography remains the standard method for assessing progression of knee osteoarthritis (OA). We sought to describe factors that explain variability in published estimates of radiographic progression in knee OA. DESIGN We searched PubMed between January 1985 and October 2006 to identify studies that assessed radiographic progression using either joint space narrowing (JSN) or the Kellgren-Lawrence (K-L) scale. We extracted cohort characteristics [age, gender, and body mass index (BMI)] and technical and other study factors (radiographic approach, study design, OA-related cohort composition). We performed meta-regression analyses of the effects of these variables on both JSN and K-L progression. RESULTS Of 239 manuscripts identified, 34 met inclusion criteria. The mean estimated annual JSN rate was 0.13 +/- 0.15 mm/year. While we found no significant association between JSN and radiographic approach among observational studies, full extension was associated with greater estimated JSN among randomized control trials (RCTs). Overall, observational studies that used the semi-flexed approach reported greater JSN than RCTs that used the same approach. The overall mean risk of K-L progression by at least one grade was 5.6 +/- 4.9%, with higher risk associated with shorter study duration, OA definition (K-L > or = 2 vs K-L > or = 1) and cohorts composed of subjects with both incident and prevalent OA. CONCLUSION While radiographic approach and study design were associated with JSN, OA definition, cohort composition and study duration were associated with risk of K-L progression. These findings may inform the design of disease modifying osteoarthritis drug (DMOAD) trials and assist clinicians in optimal timing of OA treatments.

Responsiveness to change and reliability of measurement of radiographic joint space width in osteoarthritis of the knee: a systematic review.

OBJECTIVE The goal of this systematic review was to report the responsiveness to change and reliability of conventional radiographic joint space width (JSW) measurement. METHOD We searched the PubMed and Embase databases using the following search criteria: [osteoarthritis (OA) (MeSH)] AND (knee) AND (X-ray OR radiography OR diagnostic imaging OR radiology OR disease progression) AND (joint space OR JSW or disease progression). We assessed responsiveness by calculating the standardized response mean (SRM). We assessed reliability using intra- and inter-reader intra-class correlation (ICC) and coefficient of variation (CV). Random-effects models were used to pool results from multiple studies. Results were stratified by study duration, design, techniques of obtaining radiographs, and measurement method. RESULTS We identified 998 articles using the search terms. Of these, 32 articles (43 estimates) reported data on responsiveness of JSW measurement and 24 (50 estimates) articles reported data on measures of reliability. The overall pooled SRM was 0.33 [95% confidence interval (CI): 0.26, 0.41]. Responsiveness of change in JSW measurement was improved substantially in studies of greater than 2 years duration (0.57). Further stratifying this result in studies of greater than 2 years duration, radiographs obtained with the knee in a flexed position yielded an SRM of 0.71. Pooled intra-reader ICC was estimated at 0.97 (95% CI: 0.92, 1.00) and the intra-reader CV estimated at 3.0 (95% CI: 2.0, 4.0). Pooled inter-reader ICC was estimated at 0.93 (95% CI: 0.86, 0.99) and the inter-reader CV estimated at 3.4% (95% CI: 1.3%, 5.5%). CONCLUSIONS Measurement of JSW obtained from radiographs in persons with knee is reliable. These data will be useful to clinicians who are planning RCTs where the change in minimum JSW is the outcome of interest.

A Retrospective Comparison of the Incidence of Bacterial Infection Following Anterior Cruciate Ligament Reconstruction With Autograft Versus Allograft

PURPOSE To compare the incidence of bacterial infection in anterior cruciate ligament (ACL) reconstruction with autograft versus allograft. METHODS We completed a retrospective medical record review of ACL reconstructions performed at our institutions between 2001 and 2005. These included 170 autograft, 628 allograft, and 3 combined autograft/allograft reconstructions. Data collection included patient demographics, comorbidities, preoperative antibiotics, fixation type, and the occurrence of deep postoperative infection. RESULTS Of the 801 patients who underwent ACL reconstruction, 6 (0.75%) developed a confirmed deep infection. There were 2 confirmed deep infections in 170 autograft reconstructions (1.2%) compared with 4 confirmed deep infections in 628 allograft reconstructions (0.6%). Multivariate analysis revealed that ACL reconstruction using autograft had a nearly twice the risk of infection compared to allograft reconstructions (adjusted odds ratio, 1.83; 95% confidence interval, 0.16 to 12.94). CONCLUSIONS This study failed to find a higher rate of deep bacterial infection in ACL reconstructions when allograft tissue was used. We therefore feel that surgeons should consider allograft tissue as an alternative to autograft when there is a concern about donor-site morbidity, or for revision reconstructions. LEVEL OF EVIDENCE Level III, therapeutic retrospective comparative study.

Type II Odontoid Fractures of the Cervical Spine: Do Treatment Type and Medical Comorbidities Affect Mortality in Elderly Patients?

Study Design. Retrospective cohort study. Objective. To determine the influence of age, comorbidities, and treatment type on mortality in elderly patients with acute Type II odontoid fractures. Summary of Background Data. Prior studies have documented increased morbidity and mortality among geriatric patients sustaining odontoid fractures. However, there is limited data regarding the effect of patient age, medical comorbidities, and treatment selection on mortality after Type II odontoid (C2) fractures in the elderly. Methods. An institutional registry was used to identify all Type II odontoid fractures sustained by patients aged 65 and older from 1991 to 2006. Demographic information, date of injury, associated injuries, treatment type, and comorbidities were abstracted from medical records. Mortality was ascertained using the National Death Index. Risks of mortality and their associated 95% confidence intervals (CIs) were calculated at 3 months, 1 year, 2 years, and 3 years. Multivariable Cox proportional hazard regression was used to evaluate independent factors affecting mortality stratified by age (65–74 years, 75–84 years, ≥85 years) and treatment type (operative or nonoperative treatment, and halo or collar immobilization). Results. Of 156 patients identified with Type II odontoid fracture, the average age was 82 years (SD = 7.8; Range: 65–101). One hundred and twelve patients (72%) were treated nonoperatively. At 3 years postinjury, there was a 39% (95% CI: 32–47) mortality rate for the entire cohort. Mortality for the operative group was 11% (95% CI: 2–21) at 3 months and 21% (95% CI: 9–32) at 1 year compared with 25% (95% CI: 17–33) at 3 months and 36% (95% CI: 27–45) at 1 year in the nonoperative group. The Cox regression model showed that the protective effect of surgery was seen in patients aged 65 to 74 years, in whom the hazard ratio associated with surgery for mortality after odontoid fracture was 0.4 (95% CI: 0.1–1.5). Those aged 75 to 84 years had a hazard ratio of 0.8 (95% CI: 0.3–2.3), and patients 85 years or older had a hazard ratio of 1.9 (95% CI: 0.6–6.1; P value for interaction between age and treatment = 0.09) with operative treatment having a protective effect in patients aged 65 to 74 years. Conclusion. In a cohort of elderly patients, Type II odontoid fractures were associated with a high rate of mortality, regardless of intervention.