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1.  Peptic ulcer disease and heart disease are associated with periprosthetic fractures after total hip replacement 
Acta Orthopaedica  2012;83(4):353-359.
Background and purpose
There have been no published studies assessing the possible association of medical comorbidities with periprosthetic fracture risk. We therefore assessed whether medical comorbidity is associated with risk of periprosthetic fractures after total hip replacement (THR).
Material and methods
We used prospectively collected data from 1989–2008 in the Mayo Clinic Total Joint Registry for 2 cohorts: primary THR and revision THR. The main variables of interest were Deyo-Charlson comorbidities at the time of surgery. Outcome of interest was p ostoperative periprosthetic fracture at postoperative day 1 onwards. Multivariable
Cox regression models were additionally adjusted for age, sex, body mass index, American Society of Anesthesiology (ASA) class, and operative diagnosis.
We identified 14,065 primary THRs and 6,281 revision THRs with mean follow-up times of 6.3 and 5.6 years, respectively. There were 305 postoperative periprosthetic fractures in the primary THR cohort and 330 in the revision THR cohort. In patients who underwent primary THR, 2 comorbidities were associated with higher risk of periprosthetic fracture: peptic ulcer disease with adjusted hazard ratio of 1.5 (95% CI: 1.1–2.2) and heart disease with adjusted hazard ratio of 1.7 (CI: 1.2–2.4). In patients with revision THR, peptic ulcer disease was associated with a higher adjusted risk of periprosthetic fracture, 1.6 (CI: 1.1–2.3).
Peptic ulcer disease and heart disease in primary THR patients and peptic ulcer disease in revision THR patients were associated with higher postoperative periprosthetic fracture risk. Further studies are needed to understand whether disease severity or specific medications used for treatment, or both, are responsible for this association. This may allow identification of modifiable factors.
PMCID: PMC3427625  PMID: 22900908
2.  Are Gender, Comorbidity and Obesity Risk factors for Postoperative Periprosthetic Fractures Following Primary Total Hip Replacement? 
The Journal of arthroplasty  2012;28(1):126-131.e2.
We studied the frequency and patient risk factors for postoperative periprosthetic fractures after primary total hip replacement (THR). With a mean follow-up of 6.3 years, 305 postoperative periprosthetic fractures occurred in 14,065 primary THRs. In multivariable-adjusted Cox regression analyses, female gender (Hazard ratio [HR], 1.48;95% confidence interval [CI]:1.17–1.88), Deyo-Charlson comorbidity score of 2 (HR, 1.74 for score of 2;95% CI: 1.25–2.43) or 3 or higher (HR, 1.71;95% CI: 1.26–2.32), ASA class of 2 (HR, 1.84;95% CI: 0.90–3.76), 3 (HR, 2.45;95% CI: 1.18–5.1) or 4 or higher (HR, 2.68;95% CI: 0.70–10.28) were significantly associated with higher risk/hazard and cemented implant with lower hazard (HR, 0.68; 95% CI: 0.54–0.87) of postoperative periprosthetic fractures. Interventions targeted at optimizing comorbidity management may decrease postoperative fractures after THR.
PMCID: PMC3414633  PMID: 22552223
3.  Periprosthetic infections after total shoulder arthroplasty: a 33-year perspective 
To examine the rates and predictors of deep periprosthetic infections after primary total shoulder arthroplasty (TSA).
We used prospectively collected data on all primary TSA patients from 1976-2008 at Mayo Clinic Medical Center. We estimated survival free of deep periprosthetic infections after primary TSA using Kaplan-Meier survival. Univariate and multivariable Cox regression was used to assess the association of patient-related factors (age, gender, body mass index), comorbidity (Deyo-Charlson index), American Society of Anesthesiologists class, implant fixation, and underlying diagnosis with risk of infection.
A total of 2,207 patients, with a mean age of 65 years (SD, 12 years), 53% of whom were women, underwent 2,588 primary TSAs. Mean follow-up was 7 years (SD, 6 years), and the mean body mass index was 30 kg/m2 (SD, 6 kg/m2). The American Society of Anesthesiologists class was 1 or 2 in 61% of cases. Thirty-two confirmed deep periprosthetic infections occurred during follow-up. In earlier years, Staphylococcus predominated; in recent years, Propionibacterium acnes was almost as common. The 5-, 10-, and 20-year prosthetic infection–free rates were 99.3% (95% confidence interval [CI], 98.9-99.6), 98.5% (95% CI, 97.8-99.1), and 97.2% (95% CI, 96.0-98.4), respectively. On multivariable analysis, a male patient had a significantly higher risk of deep periprosthetic infection (hazard ratio, 2.67 [95% CI, 1.22-5.87]; P =.01) and older age was associated with lower risk (hazard ratio, 0.97 [95% CI, 0.95-1.00] per year; P =.05).
The periprosthetic infection rate was low at 20-year follow-up. Male gender and younger age were significant risk factors for deep periprosthetic infections after TSA. Future studies should investigate whether differences in bone morphology, medical comorbidity, or other factors are underlying these associations.
PMCID: PMC3586318  PMID: 22516570
Total shoulder arthroplasty; periprosthetic infections
4.  Predictors of use of pain medications for persistent knee pain after primary Total Knee Arthroplasty: a cohort study using an institutional joint registry 
Arthritis Research & Therapy  2012;14(6):R248.
To study the use of pain medications for persistent index knee pain and their predictors after primary Total Knee Arthroplasty (TKA).
The Mayo Total Joint Registry collects patient-reported data including pain medication use on all patients who undergo TKA. We used data from patients who underwent primary TKA from 1993-2005. We examined whether gender, age (reference, ≤60 yrs), body mass index (BMI; reference, <25 kg/m2), comorbidities measured by Deyo-Charlson index (5-point increase), anxiety and depression predicted use of pain medications (non-steroidal anti-inflammatory drugs (NSAIDs) and opioids) 2- and 5-years after primary TKA. Multivariable logistic regression additionally adjusted for operative diagnosis, American Society of Anesthesiologists (ASA) score, implant fixation and distance from the medical center.
7,139 of the 10,957 eligible (65%) at 2-years and 4,234 of 7,404 eligible (57%) completed questionnaires. Significant predictors of NSAIDs use were (Odds ratio (95% confidence interval)): male gender at 2- and 5-years, 0.5 (0.4, 0.6) and 0.6 (0.5, 0.8); age >70-80 years, 0.7 (0.5, 0.9), 0.6 (0.4, 0.8); and depression, 1.4 (1.0, 1.8) and 1.7 (1.1, 2.5). BMI ≥40 was associated with NSAIDs use only at 2-years, 1.6 (1.1, 2.5). Significant predictors of opioid pain medication use at 2- and 5-years were: male gender, 0.5 (0.3, 0.9) and 0.4 (0.2, 0.8); age >70-80 years, 0.3 (0.1, 0.6), 0.3 (0.1, 0.8); and anxiety, 3.0 (1.6, 5.7) and 4.0 (1.7, 9.4).
Female gender and younger age were associated with higher risk of use of NSAIDs and opioids after primary TKA. Depression was associated with higher NSAID use and anxiety with higher opioid pain medication use after primary TKA.
PMCID: PMC3674590  PMID: 23157942
5.  Predictors of Moderate-Severe Functional Limitation after Primary Total Knee Arthroplasty (TKA): 4,701 TKAs at 2-years and 2,935 TKAs at 5-years 
Investigate whether body mass index (BMI), comorbidity, gender and age predict patient-reported functional limitation 2- and 5-years after Primary Total Knee Arthroplasty (TKA).
Overall moderate-severe activity limitation was defined as ≥2 activities (walking, stairs, rising chair) with moderate-severe limitation. Complete dependence on walking-aids or inability to walk was assessed (reference, no dependence). Multivariable logistic regressions were adjusted additionally for income, diagnosis, distance from medical center, ASA score and implant type.
Overall moderate-severe activity limitation was reported by 20.7% at 2-years and 27.1% at 5-years. Significantly predictors of overall moderate-severe activity limitation 2-years post-TKA (odds (95% confidence interval)) were: BMI 30–34.9, 1.5 (1.0,2.0), 35–39.9, 1.8 (1.3,2.7) and ≥40, 3.0 (2.0,4.5) versus BMI≤25; higher Deyo-Charlson index, 1.7 (1.4,2.2) per 5-point increase; female gender, 2.0 (1.7,2.5); age 71–80, 2.1 (1.5,2.8) and age>80, 4.1 (2.7,6.1) versus age≤60.
At 5-years post-TKA, significant predictors of overall moderate-severe activity limitation were: BMI 35–39.9, 2.1 (1.4,3.3) and ≥40, 3.9 (2.3,6.5); higher Deyo-Charlson index, 1.4 (1.0,1.8); female gender, 2.2 (1.7,2.7); age 71–80, 2.4 (1.7,3.5) and age>80, 4.7 (2.8,7.9). Complete dependence on walking-aids was significantly higher at 2- and 5-years, respectively, in patients with: higher comorbidity, 2.3 (1.5,3.3) and 2.1 (1.4,3.2); female gender 2.4 (1.5,3.9) and1.7 (1.1,2.6); ;age 71–80, 1.6(1.03,2.5) and 2.1(1.2,3.4); and age >80, 3.2 (1.6,6.7) and 5.1 (2.3,11.0).
Modifiable (BMI, comorbidity) and non-modifiable predictors (age, gender) increased the risk of functional limitation and walking-aid dependence after primary TKA. Interventions targeting comorbidity and BMI pre-operatively may positively impact function post-TKA.
PMCID: PMC3882060  PMID: 20060950
Predictors; Functional Limitation; Total Knee Arthroplasty; Body Mass Index; Comorbidity; Gender; Age
6.  Patient factors Predict Periprosthetic Fractures Following Revision Total Hip Replacement 
The Journal of arthroplasty  2012;27(8):1507-1512.
We assessed important patient risk factors for postoperative periprosthetic fractures after revision total hip replacement (THR) using prospectively collected Institutional Joint Registry data. We used univariate and multivariable-adjusted Cox regression analyses. There were 330 postoperative periprosthetic fractures after 6,281 revision THRs. In multivariable-adjusted analyses, hazard [95% confidence interval] of periprosthetic fracture was higher for: women, 1.66 [1.32, 2.08], p<0.001; higher Deyo-Charlson comorbidity index of 2, 1.46 (1.03, 2.07) and index of 3+, 2.01 (1.48, 2.73), overall p<0.001; and operative diagnosis, especially previous non-union, 5.76 (2.55, 13.02), overall p<0.001. Hazard was lower in 61–70 year old, 0.64 (0.49, 0.84) and 71–80 year old 0.57 (0.43, 0.76), compared to <60 years (overall p<0.0001). Our study identified important modifiable and unmodifiable risk factors for fractures after revision THR.
PMCID: PMC3360118  PMID: 22342128
7.  Outcome and incidence of periprosthetic supracondylar femoral fractures in TKA 
Indian Journal of Orthopaedics  2013;47(6):591-597.
Periprosthetic supracondylar femoral fractures following total knee arthroplasty (TKA) are infrequent, but is a devastating complication. The purpose of this study was to evaluate the incidence and outcomes of periprosthetic supracondylar femoral fractures following TKA using nonoperative as well as open reduction and internal fixation (ORIF) techniques.
Materials and Methods:
Between January 2004 and December 2010, we followed 3,920 operated patients of total knee arthroplasty (TKA) and identified 23 patients with periprosthetic supracondylar fractures. A retrospective analysis of the records of these patients was conducted. Details regarding pre fracture status, treatment offered and the present status were also recorded and analyzed. Time from index arthroplasty to periprosthetic fracture ranged from five days to six years. There were 17 women and 6 men and the average age was 68.26 years (range 52-83 years). Of the 23 patients, 20 patients were treated by operative method, whereas only three patients with relatively undisplaced fractures were treated nonoperatively.
The total incidence of periprosthetic fractures in operated cases of TKA was 0.58%. Three patients had infection after surgery. As per radiological assessment, two of three conservatively treated cases had malunion, whereas among 20 cases treated operatively, 16 had primary union with one malunion. Two patients had union after bone grafting, whereas two had nonunion. The average reduction in the knee score after fracture was 20.53%. Twenty one patients were able to achieve limited but independent activity.
Desirable results for periprosthetic fractures can be obtained if proper and timely intervention is done, taking into account the other comorbid conditions. However, short duration of followup and small number of patients were major limiting factors in this study.
PMCID: PMC3868141  PMID: 24379465
Distal femoral locking plate; periprosthetic fracture; supracondylar femur fracture; total knee arthroplasty
8.  Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study 
BMJ : British Medical Journal  2005;331(7529):1374.
Objectives To evaluate postoperative medical complications and the association between these complications and mortality at 30 days and one year after surgery for hip fracture and to examine the association between preoperative comorbidity and the risk of postoperative complications and mortality.
Design Prospective observational cohort study.
Setting University teaching hospital.
Participants 2448 consecutive patients admitted with an acute hip fracture over a four year period. We excluded 358 patients: all those aged < 60; those with periprosthetic fractures, pathological fractures, and fractures treated without surgery; and patients who died before surgery.
Interventions Routine care for hip fractures.
Main outcome measures Postoperative complications and mortality at 30 days and one year.
Results Mortality was 9.6% at 30 days and 33% at one year. The most common postoperative complications were chest infection (9%) and heart failure (5%). In patients who developed postoperative heart failure mortality was 65% at 30 days (hazard ratio 16.1, 95% confidence interval 12.2 to 21.3). Of these patients, 92% were dead by one year (11.3, 9.1 to 14.0). In patients who developed a postoperative chest infection mortality at 30 days was 43% (8.5, 6.6 to 11.1). Significant preoperative variables for increased mortality at 30 days included the presence of three or more comorbidities (2.5, 1.6 to 3.9), respiratory disease (1.8, 1.3 to 2.5), and malignancy (1.5, 1.01 to 2.3).
Conclusions In elderly people with hip fracture, the presence of three or more comorbidities is the strongest preoperative risk factor. Chest infection and heart failure are the most common postoperative complications and lead to increased mortality. These groups offer a clear target for specialist medical assessment.
PMCID: PMC1309645  PMID: 16299013
9.  Peri-prosthetic Infections after Shoulder Hemiarthroplasty 
To examine the rates and predictors of deep peri-prosthetic infections following shoulder hemi-arthroplasty.
We used prospectively collected Institutional Registry data on all primary shoulder hemi-arthroplasty patients from 1976–2008. We estimated survival-free of deep peri-prosthetic infections using the Kaplan-Meier survival curves. Using univariate Cox regression analyses, we examined the association of patient-related factors (age, gender, body mass index (BMI)), comorbidity (Charlson index), ASA grade, underlying diagnosis and implant fixation with the risk of infection.
1,349 patients, with mean age 63 years (standard deviation, 16) with 63% women, underwent 1,431 primary shoulder hemi-arthroplasties. Mean follow-up was 8 years (standard deviation, 7 years). Fourteen deep peri-prosthetic infections occurred during the follow-up, confirmed by medical record review. Most common organisms were staphylococcus aureus, staphylococcus coagulase negative and Propionobacterium acnes, each accounting for 3 cases (21% each). The 5-, 10- and 20-year prosthetic infection-free rates (95% confidence interval) were 98.9% (98.3%, 99.5%), 98.7% (98.1%, 99.4%) and 98.7% (98.1%, 99.4%) respectively. None of the factors evaluated were significantly associated with risk of prosthetic infection after primary shoulder hemi-arthroplasty, except that an underlying diagnosis of trauma was associated with significantly higher hazard ratio of 3.18 (95% confidence interval, 1.06–9.56) of infection compared to all other diagnoses (p=0.04). A higher body mass index showed a non-statistical trend towards association with higher hazard (p=0.13).
The periprosthetic infection rate after shoulder hemi-arthroplasty was low, estimated at 1.3% at 20-year follow-up. An underlying diagnosis of trauma was associated with a higher risk of periprosthetic infection. These patients should be observed closely for development of infection.
PMCID: PMC3310339  PMID: 22154310
Shoulder hemiarthroplasty; humeral head replacement; infection; age
10.  Ninety day mortality and its predictors after primary shoulder arthroplasty: an analysis of 4,019 patients from 1976-2008 
Examine 90-day postoperative mortality and its predictors following shoulder arthroplasty
We identified vital status of all adults who underwent primary shoulder arthroplasty (Total shoulder arthroplasty (TSA) or humeral head replacement (HHR)) at the Mayo Clinic from 1976-2008, using the prospectively collected information from Total Joint Registry. We used univariate logistic regression models to assess the association of gender, age, body mass index, American Society of Anesthesiologist (ASA) class, Deyo-Charlson comorbidity index, an underlying diagnosis and implant fixation with odds of 90-day mortality after TSA or HHR. Multivariable models additionally adjusted for the type of surgery (TSA versus HHR). Adjusted Odds ratio (OR) with 95% confidence interval (CI) were calculated.
Twenty-eight of the 3, 480 patient operated died within 90-days of shoulder arthroplasty (0.8%). In multivariable-adjusted analyses, the following factors were associated with significantly higher odds of 90-day mortality: higher Deyo-Charlson index (OR, 1.54; 95% CI:1.39, 1.70; p < 0.001); a diagnosis of tumor (OR, 16.2; 95%CI:7.1, 36.7); and ASA class III (OR, 3.57; 95% CI:1.29, 9.91; p = 0.01) or class IV (OR, 13.4; 95% CI:2.44, 73.86; p = 0.003). BMI ≥ 30 was associated with lower risk of 90-day mortality (OR, 0.25; 95% CI:0.08, 0.78). In univariate analyses, patients undergoing TSA had significantly lower 90-day mortality of 0.4% (8/2, 580) compared to 1% in HHR (20/1, 411) (odds ratio, 0.22 (95% CI: 0.10, 0.50); p = 0.0003).
90-day mortality following shoulder arthroplasty was low. An underlying diagnosis of tumor, higher comorbidity and higher ASA class were risk factors for higher 90-day mortality, while higher BMI was protective. Pre-operative comorbidity management may impact 90-day mortality following shoulder arthroplasty. A higher unadjusted mortality in patients undergoing TSA versus HHR may indicate the underlying differences in patients undergoing these procedures.
PMCID: PMC3206490  PMID: 21992475
mortality; shoulder arthroplasty; humeral head replacement; shoulder hemiarthroplasty
11.  Prevalence and risk factors for periprosthetic fracture in older recipients of total hip replacement: a cohort study 
The growing utilization of total joint replacement will increase the frequency of its complications, including periprosthetic fracture. The prevalence and risk factors of periprosthetic fracture require further study, particularly over the course of long-term follow-up. The objective of this study was to estimate the prevalence and risk factors for periprosthetic fractures occurring in recipients of total hip replacement.
We identified Medicare beneficiaries who had elective primary total hip replacement (THR) for non-fracture diagnoses between July 1995 and June 1996. We followed them using Medicare Part A claims data through 2008. We used ICD-9 codes to identify periprosthetic femoral fractures occurring from 2006–2008. We used the incidence density method to calculate the annual incidence of these fractures and Cox proportional hazards models to identify risk factors for periprosthetic fracture. We also calculated the risk of hospitalization over the subsequent year.
Of 58,521 Medicare beneficiaries who had elective primary THR between July 1995 and June 1996, 32,463 (55%) survived until January 2006. Of these, 215 (0.7%) developed a periprosthetic femoral fracture between 2006 and 2008. The annual incidence of periprosthetic fracture among these individuals was 26 per 10,000 person-years. In the Cox model, a greater risk of periprosthetic fracture was associated with having had a total knee replacement (HR 1.82, 95% CI 1.30, 2.55) or a revision total hip replacement (HR1.40, 95% CI 0.95, 2.07) between the primary THR and 2006. Compared to those without fractures, THR recipients who sustained periprosthetic femoral fracture had three-fold higher risk of hospitalization in the subsequent year (89% vs. 27%, p < 0.0001).
A decade after primary THR, periprosthetic fractures occur annually in 26 per 10,000 persons and are especially frequent in those with prior total knee or revision total hip replacements.
PMCID: PMC4033675  PMID: 24885707
Hip replacement; Periprosthetic fracture; Fracture; Implant; Risk factor; Epidemiology
12.  Patient-related Risk Factors for Postoperative Mortality and Periprosthetic Joint Infection in Medicare Patients Undergoing TKA 
The impact of specific baseline comorbid conditions on the relative risk of postoperative mortality and periprosthetic joint infection (PJI) in elderly patients undergoing TKA has not been well defined.
We calculated the relative risk of postoperative mortality and PJI associated with 29 comorbid conditions in Medicare patients undergoing TKA.
Patients and Methods
The Medicare 5% sample was used to calculate the relative risk of 90-day postoperative mortality and PJI as a function of 29 preexisting comorbid conditions in 83,011 patients who underwent primary TKA between 1998 and 2007.
The independent risk factors for 90-day postoperative mortality (in decreasing order of significance) were congestive heart failure, metastatic cancer, renal disease, peripheral vascular disease, cerebrovascular disease, lymphoma, cardiac arrhythmia, dementia, pulmonary circulation disorders, and chronic liver disease. The independent risk factors for PJI (in decreasing order of significance) were congestive heart failure, chronic pulmonary disease, preoperative anemia, diabetes, depression, renal disease, pulmonary circulation disorders, obesity, rheumatologic disease, psychoses, metastatic tumor, peripheral vascular disease, and valvular disease.
We believe this information important when counseling elderly patients regarding the risks of mortality and PJI after TKA and risk-adjusting publicly reported TKA patient outcomes.
Level of Evidence
Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3237966  PMID: 21874391
13.  Cardiac and Thromboembolic Complications and Mortality in Patients Undergoing Total Hip and Total Knee Arthroplasty 
Annals of the Rheumatic Diseases  2011;70(12):2082-2088.
Study 90-day cardiac and thromboembolic complications and all-cause mortality following total hip or knee arthroplasty (THA/TKA).
In a population-based cohort of all Olmsted County residents who underwent a THA or TKA between 1994 and 2008, we assessed 90-day occurrence and predictors of cardiac complications (myocardial infarction, cardiac arrhythmia or congestive heart failure), thromboembolic complications (deep venous thrombosis (DVT) or pulmonary embolism (PE)) and mortality.
Among the Olmsted County THA and TKA cohorts, 90-day complication rates were as follows: cardiac, 15.8% and 6.9%; thromboembolic, 4.9% and 4.0%; and mortality, 0.7% and 0.4%, respectively. Unadjusted frequency of cardiac/thromboembolic events differed by history of prior respective event. In multivariable-adjusted logistic regression analyses, ASA class III–IV (OR, 6.1, 95% CI:1.6, 22.8) and higher Deyo-Charlson comorbidity score (OR, 1.2, 95% CI:1.0,1.4) were significantly associated with odds of 90-day cardiac event post-THA in patients with no known prior cardiac event. In those with known prior cardiac disease, ASA class III–IV (OR, 4.4, 95% CI:2.0, 9.9), male gender (OR, 0.5, 95% CI:0.3,0.9) and history of thromboembolic disease (OR, 3.2; 95% CI:1.4,7.0) were significantly associated with odds of cardiac complication 90-day post-THA. No significant predictors of thromboembolism were found in THA patients.
In TKA patients with no prior cardiac history, age >65 years (OR, 4.1, 95% CI:1.2, 14.0), and ASA class III–IV (OR, 2.8, 95% CI:1.1,6.8) and in TKA patients with known cardiac disease, ASA class III–IV (OR, 3.2, 95% CI:1.8,5.7) was significantly associated with odds of 90-day cardiac event. In TKA patients with no prior thromboembolic disease, male gender (OR, 0.5, 95% CI:0.2,0.9) and higher Charlson index (OR, 1.2, 95% CI:1.1,1.3) and in patients with known thromboembolic disease, higher Charlson index score (OR, 1.1, 95% CI:1.1,1.4) was associated with odds of 90-day thromboembolic event.
Older age, higher comorbidity, higher ASA class and prior history of cardiac/thromboembolic disease was associated with an increased risk of 90-day cardiac and thromboembolic complications.
PMCID: PMC3315837  PMID: 22021865
Cardiac; Thromboembolic; Total Hip Arthroplasty; Total Knee Arthroplasty; Mortality
14.  Medical and psychological comorbidity predicts poor pain outcomes after total knee arthroplasty 
Rheumatology (Oxford, England)  2013;52(5):916-923.
Objective. To study comorbidity correlates of moderate to severe pain after total knee arthroplasty (TKA).
Methods. We analysed prospectively collected Total Joint Registry data to examine whether medical (heart disease, peripheral vascular disease, renal disease, chronic obstructive pulmonary disease, diabetes and CTD) and psychological (anxiety and depression) comorbidity is associated with moderate to severe pain after primary or revision TKA. Multivariable-adjusted logistic regression simultaneously adjusted for all comorbidities, age, sex, BMI, underlying diagnosis, American Society of Anesthesiologist (ASA) class, distance from medical centre and implant fixation (only for primary TKA) was used to analyse primary and revision TKA separately.
Results. The primary TKA cohort consisted of 7139 and 4234 TKAs (response rates 65% and 57%) and the revision TKA cohort consisted of 1533 and 881 TKAs at 2 and 5 years (response rates 57% and 48%), respectively. In the primary TKA cohort, anxiety was associated with 1.4 higher odds (95% CI 1.0, 2.0) of moderate to severe index knee pain at 2 years; at 5 years, heart disease (OR 1.7; 95% CI 1.1, 2.6), depression (OR 1.7; 95% CI 1.1, 2.5) and anxiety (OR 1.9; 95% CI 1.2, 3.1) were significantly associated with moderate to severe pain. For revision TKA, CTD (OR 0.5; 95% CI 0.2, 0.9) and depression (OR 1.8; 95% CI 1.1, 3.1) were significantly associated with moderate to severe pain.
Conclusion. This study identified medical and psychological comorbidity risk factors for moderate to severe pain after primary and revision TKA. This information can be used to provide realistic outcome expectations for patients before undergoing primary or revision TKA.
PMCID: PMC3630396  PMID: 23325037
pain; function; functional limitation; total knee replacement; primary; arthroplasty; joint replacement; outcomes; patient-reported outcomes
15.  Depression in primary TKA and higher medical comorbidities in revision TKA are associated with suboptimal subjective improvement in knee function 
To characterize whether medical comorbidities, depression and anxiety predict patient-reported functional improvement after total knee arthroplasty (TKA).
We analyzed the prospectively collected data from the Mayo Clinic Total Joint Registry for patients who underwent primary or revision TKA between 1993–2005. Using multivariable-adjusted logistic regression analyses, we examined whether medical comorbidities, depression and anxiety were associated with patient-reported subjective improvement in knee function 2- or 5-years after primary or revision TKA. Odds ratios (OR), along with 95% confidence intervals (CI) and p-value are presented.
We studied 7,139 primary TKAs at 2- and 4,234 at 5-years; and, 1,533 revision TKAs at 2-years and 881 at 5-years. In multivariable-adjusted analyses, we found that depression was associated with significantly lower odds of 0.5 (95% confidence interval [CI]: 0.3 to 0.9; p = 0.02) of ‘much better’ knee functional status (relative to same or worse status) 2 years after primary TKA. Higher Deyo-Charlson index was significantly associated with lower odds of 0.5 (95% CI: 0.2 to 1.0; p = 0.05) of ‘much better’ knee functional status after revision TKA for every 5-point increase in score.
Depression in primary TKA and higher medical comorbidity in revision TKA cohorts were associated with suboptimal improvement in index knee function. It remains to be seen whether strategies focused at optimization of medical comorbidities and depression pre- and peri-operatively may help to improve TKA outcomes. Study limitations include non-response bias and the use of diagnostic codes, which may be associated with under-diagnosis of conditions.
PMCID: PMC3990241  PMID: 24725511
Total knee arthroplasty; Knee function; Functional limitation; Primary; Arthroplasty; Joint replacement; Outcomes; Patient-reported outcomes
16.  What Are the Rates and Causes of Hospital Readmission After Total Knee Arthroplasty? 
Total knee arthroplasty (TKA) and related interventions such as revision TKA and the treatment of infected TKAs are commonly performed procedures. Hospital readmission rates are used to measure hospital performance, but risk factors (both medical and surgical) for readmission after TKA, revision TKA, and treatment for the infected TKA have not been well characterized.
We measured (1) the unplanned hospital readmission rate in primary TKA and revision TKA, including antibiotic-spacer staged revision TKA to treat infection. We also evaluated (2) the medical and surgical causes of readmission and (3) risk factors associated with unplanned hospital readmission.
This retrospective cohort study included a total of 1408 patients (1032 primary TKAs, 262 revision TKAs, 113 revision of infected TKAs) from one institution. All hospital readmissions within 90 days of discharge were evaluated for timing and cause. Diagnoses at readmission were categorized as surgical or medical. Readmission risk was assessed using a Cox proportional hazards model that incorporated patient demographics and medical comorbidities.
The unplanned readmission rate for the entire cohort was 4% at 30 days and 8% at 90 days. At 90 days postoperatively, revision of an infected TKA had the highest readmission rate, followed by revision TKA, with primary TKA having the lowest rate. Approximately three-fourths of readmissions were the result of surgical causes, mostly infection, arthrofibrosis, and cellulitis, whereas the remainder of readmissions were the result of medical causes. Procedure type (primary TKA versus revision TKA or staged treatment for infected TKA), hospital stay more than 5 days, discharge destination, and a fluid/electrolyte abnormality were each associated with risk of unplanned readmission.
Patients having revision TKA, whether for infection or other causes, are more likely to have an unplanned readmission to the hospital than are patients having primary TKA. When assessing hospital performance for TKA, it is important to distinguish among these surgical procedures.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3889434  PMID: 23645339
17.  Can total knee arthroplasty be safely performed in patients with chronic renal disease? 
Acta Orthopaedica  2014;85(1):71-78.
Background and purpose
The prevalence of chronic renal disease (CRD) is rising worldwide. Patients with CRD are more likely to have associated medical problems and are at greater risk of postoperative morbidity and mortality. We evaluated patient characteristics and risk of early revision, surgical site infection (SSI), thromboembolic events, mortality, and re-admission of patients with CRD undergoing total knee arthroplasty (TKA). We hypothesized that this patient population would have higher rates of complications.
Patients and methods
We conducted a retrospective analysis of data that had been prospectively collected by a Total Joint Replacement Registry. All primary TKAs performed from 2005 through 2010 were included. 41,852 primary TKA cases were evaluated, of which 2,686 (6.4%) TKA procedures had been performed in CRD patients. Patient characteristics, comorbidities, and general health status were evaluated. Cox proportional hazard regressions and logistic regressions were used to evaluate the association of CRD with outcomes while adjusting for confounding variables.
The mean age of the CRD cohort was 67 years and approximately two-thirds of the patients were female. The median follow-up time was 2.1 years. Compared to TKA patients without CRD the CRD patients were older, had poorer general health, and had a higher prevalence of comorbidities. They had a higher incidence of deep SSI (0.9% vs. 0.7%), superficial SSI (0.5% vs. 0.3%), deep vein thrombosis (0.6% vs. 0.4%), any-time mortality (4.7% vs. 2.4%), 90-day mortality (0.4% vs. 0.2%), and 90-day re-admission (10% vs. 6.0%) than patients without CRD. However, after adjustment for confounding variables, CRD patients were at 1.9 times (95% CI: 1.1–3.5) increased risk of superficial SSI, 1.3 times (CI: 1.1–1.6) increased risk of re-admission within 90 days, and 1.5 times (CI: 1.2–1.8) increased risk of mortality at any point after the procedure. The risks of all other complications were not statistically significantly different in patients with CRD compared to patients without CRD.
CRD patients undergoing TKA have more comorbidities and a higher risk for superficial SSI, 90-day re-admission, and any-time mortality.
PMCID: PMC3940995  PMID: 24397745
18.  What Are the Causes of Revision Total Knee Arthroplasty in Japan? 
There is limited information regarding the cause of revision TKA in Asia, especially Japan. Owing to differences in patient backgrounds and lifestyles, the modes of TKA failures in Asia may differ from those in Western countries.
We therefore determined (1) causes of revision TKA in a cohort of Japanese patients with revision TKA and (2) whether patient demographic features and underlying diagnosis of primary TKA are associated with the causes of revision TKA.
We assessed all revision TKA procedures performed at five major centers in Hokkaido from 2006 to 2011 for the causes of failures. Demographic data and underlying diagnosis for index primary TKA of the revision cases were compared to those of randomly selected primary TKAs during the same period.
One hundred forty revision TKAs and 4047 primary TKAs were performed at the five centers, indicating a revision burden of 3.3%. The most common cause of revision TKA was mechanical loosening (40%) followed by infection (24%), wear/osteolysis (9%), instability (9%), implant failure (6%), periprosthetic fracture (4%), and other reasons (8%). The mean age of patients with periprosthetic fracture was older (77 versus 72 years) and the male proportion in patients with infection was higher (33% versus 19%) than those of patients in the primary TKA group. There was no difference in BMI between primary TKAs and any type of revision TKA except other causes.
The revision burden at the five referral centers in Hokkaido was 3.3%, and the most common cause of revision TKA was mechanical loosening followed by infection. Demographic data such as age and sex might be associated with particular causes of revision TKA.
PMCID: PMC3613556  PMID: 23385774
19.  Higher Body Mass Index Is Not Associated with Worse Pain Outcomes After Primary or Revision Total Knee Arthroplasty (TKA) 
The Journal of arthroplasty  2010;26(3):366-374.e1.
We assessed whether higher Body Mass Index (BMI) is associated with higher risk of moderate-severe knee pain 2- and 5-years after primary or revision Total Knee Arthroplasty (TKA). We adjusted for gender, age, comorbidity, operative diagnosis and implant fixation in multivariable logistic regression. BMI (reference, <25 kg/m2) was not associated with moderate-severe knee pain at 2-years post-primary TKA (odds ratio (95% confidence interval): 25-29.9, 1.02 (0.75,1.39), p=0.90; 30-34.9, 0.93 (0.65,1.34), p=0.71; 35-39.9, 1.16 (0.77,1.74), p=0.47; ≥40, 1.09 (0.69,1.73), (all p-values ≥0.47). Similarly, BMI was not associated with moderate-severe pain at 5-year primary TKA and at 2- and 5-yr revision TKA follow-up. Lack of association of higher BMI with poor pain outcomes post-TKA implies that TKA should not be denied to obese patients for fear of suboptimal outcomes.
PMCID: PMC2930933  PMID: 20413245
20.  Mortality After Distal Femur Fractures in Elderly Patients 
Hip fractures in the elderly are associated with high 1-year mortality rates, but whether patients with other lower extremity fractures are exposed to a similar mortality risk is not clear.
We evaluated the mortality of elderly patients after distal femur fractures; determined predictors for mortality; analyzed the effect of surgical delay; and compared survivorship of elderly patients with distal femur fractures with subjects in a matched hip fracture group.
Patients and Methods
We included 92 consecutive patients older than 60 years with low-energy supracondylar femur fractures treated between 1999 and 2009. Patient, fracture, and treatment characteristics were extracted from operative records, charts, and radiographs. Data regarding mortality were obtained from the Social Security Death Index.
Age-adjusted Charlson Comorbidity Index and a previous TKA were independent predictors for decreased survival. Congestive heart failure, dementia, renal disease, and history of malignant tumor led to shorter survival times. Patients who underwent surgery more than 4 days versus 48 hours after admission had greater 6-month and 1-year mortality risks. No differences in mortality were found comparing patients with native distal femur fractures with patients in a hip fracture control group.
Periprosthetic fractures and fractures in patients with dementia, heart failure, advanced renal disease, and metastasis lead to reduced survival. The age-adjusted Charlson Comorbidity Index may serve as a useful tool to predict survival after distal femur fractures. Surgical delay greater than 4 days increases the 6-month and 1-year mortality risks. Mortality after native fractures of the distal femur in the geriatric population is high and similar to mortality after hip fractures.
Level of Evidence
Level II, prognostic study. See the guidelines online for a complete description of evidence.
PMCID: PMC3048257  PMID: 20830542
21.  Risk Factors for Periprosthetic Joint Infection after Total Hip Arthroplasty and Total Knee Arthroplasty in Chinese Patients 
PLoS ONE  2014;9(4):e95300.
The purpose of this hospital-based case–control study was to evaluate the risk factors for periprosthetic joint infection (PJI) of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients.
From January 2000 to December 2012, 45 patients undergoing THA and TKA who developed PJI were recruited for case subjects; controls were 252 without PJI, matched by year of index for surgery and type of surgery. Conditional logistic regressions were run to compute odds ratios (ORs) and 95% confidence intervals (CIs).
Demographic factors and comorbid conditions associated with an increased adjusted risk of PJI (in decreasing order of significance) were diabetes (OR = 5.47, 95% CI: 1.77–16.97; p = 0.003), age (65–75 vs. 45–65 years) (OR = 3.36, 95% CI: 1.30–8.69; p = 0.013), BMI (≥28 vs. 18.5–28 kg/m2) (OR = 2.77, 95% CI: 1.20–6.40; p = 0.017), place of residence (rural) (OR = 2.63, 95% CI: 1.13–6.10; p = 0.025) and alcohol abuse (OR = 2.95, 95% CI: 1.06–8.23; p = 0.039).
Patients with diabetes, older age, BMI of ≥28 kg/m2 and alcohol abuse or living in rural areas, had increased PJI risk. Additional systematic large-scale studies are needed to verify these results.
PMCID: PMC3991645  PMID: 24748009
22.  The Outcome and Complications of the Locked Plating Management for the Periprosthetic Distal Femur Fractures after a Total Knee Arthroplasty 
Clinics in Orthopedic Surgery  2013;5(2):124-128.
The osteosynthesis of the periprosthetic fractures following a total knee arthroplasty (TKA) can be technically difficult with the relatively small satisfactory outcomes and the high complication rates. The purpose of the study is to analyze the mid-term radiological and functional outcomes following the locked plating of the distal femur periprosthetic fractures after a TKA.
Records of 20 patients with a periprosthetic distal femur fracture following TKA treated by the locked plate osteosynthesis were retrospectively evaluated. The union rate, complications and functional outcome measures were analyzed.
Successful union was achieved in 18 of the 19 patients available for the follow-up. The mean follow-up was 39 ± 10 months. Significant reductions (p < 0.05) in the range of motion and Western Ontario and McMaster Universities Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were evident in the follow-up. Secondary procedures were required in 5 patients to address the delay in union and the reduced knee range of motion. The osteosynthesis failed in 1 patient who underwent a revision TKA.
The satisfactory union rates can be achieved with the locked plate osteosynthesis in the periprosthetic distal femur fractures after TKA. Prolonged rehabilitation coupled with the un-modifiable risk factors can decrease the activity and satisfaction levels, which can significantly alter the functional outcome.
PMCID: PMC3664671  PMID: 23730476
Total knee arthroplasty; Periprosthetic fractures; Locked plating; Distal femur fractures; Osteosynthesis
23.  Are outcomes after total knee arthroplasty worsening over time? A time-trends study of activity limitation and pain outcomes 
To examine whether function and pain outcomes of patients undergoing primary total knee arthroplasty (TKA) are changing over time.
The Mayo Clinic Total Joint Registry provided data for time-trends in preoperative and 2-year post-operative activity limitation and pain in primary TKA patients from 1993-2005. We used chi-square test and analysis for variance, as appropriate. Multivariable-adjusted analyses were done using logistic regression.
In a cohort of 7,229 patients who underwent primary TKA during 1993-2005, mean age was 68.4 years (standard deviation (SD), 9.8), mean BMI was 31.1 (SD, 6.0) and 55% were women. Crude estimates showed that preoperative moderate-severe overall limitation were seen in 7.3% fewer patients and preoperative moderate-severe pain in 2.7% more patients in 2002-05, compared to 1992-95 (p < 0.001 for both). At 2-years, crude estimates indicated that compared to 1992-95, moderate-severe post-TKA overall limitation was seen in 4.7% more patients and moderate-severe post-TKA pain in 3.6% more patients in 2002-05, both statistically significant (p ≤ 0.018) and clinically meaningful. In multivariable-adjusted analyses that adjusted for age, sex, anxiety, depression, Deyo-Charlson index, body mass index and preoperative pain/limitation, patients had worse outcomes 2-year post-TKA in 2002-2005 compared to 1993-95 with an odds ratio (95% confidence interval (CI); p-value) of 1.34 (95% CI: 1.02, 1.76, p = 0.037) for moderate-severe activity limitation and 1.79 (95% CI: 1.17, 2.75, p = 0.007) for moderate-severe pain.
Patient-reported function and pain outcomes after primary TKA have worsened over the study period 1993-95 to 2002-05. This time-trend is independent of changes in preoperative pain/limitation and certain patient characteristics.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2474-15-440) contains supplementary material, which is available to authorized users.
PMCID: PMC4301928  PMID: 25519240
Total knee replacement; Time trends; Arthroplasty; Joint replacement; Pain; Function
24.  The Risk of Fractures Associated with Thiazolidinediones: A Self-controlled Case-Series Study 
PLoS Medicine  2009;6(9):e1000154.
Ian Douglas and colleagues analyze records from the UK General Practice Research Database, and find that among individuals prescribed thiazolidinediones who develop a fracture, fractures are more common during periods of thiazolidinedione exposure than unexposed periods.
The results of clinical trials have suggested that the thiazolidinedione antidiabetic agents rosiglitazone and pioglitazone are associated with an increased risk of fractures, but such studies had limited power. The increased risk in these trials appeared to be limited to women and mainly involved fractures of the arm, wrist, hand, or foot: risk patterns that could not be readily explained. Our objective was to further investigate the risk of fracture associated with thiazolidinedione use.
Methods and Findings
The self-controlled case-series design was used to compare rates of fracture during thiazolidinedione exposed and unexposed periods and thus estimate within-person rate ratios. We used anonymised primary care data from the United Kingdom General Practice Research Database (GPRD). All patients aged 40 y or older with a recorded fracture and at least one prescription for a thiazolidinedione were included (n = 1,819). We found a within-person rate ratio of 1.43 (95% confidence interval [CI] 1.25–1.62) for fracture at any site comparing exposed with unexposed periods among patients prescribed any thiazolidinedione. This association was similar in men and women and in patients treated with either rosiglitazone or pioglitazone. The increased risk was also evident at a range of fracture sites, including hip, spine, arm, foot, wrist, or hand. The risk increased with increasing duration of thiazolidinedione exposure: rate ratio 2.00 (95% CI 1.48–2.70) for 4 y or more of exposure.
Within individuals who experience a fracture, fracture risk is increased during periods of exposure to thiazolidinediones (both rosiglitazone and pioglitazone) compared with unexposed periods. The increased risk is observed in both men and women and at a range of fracture sites. The risk also increases with longer duration of use.
Please see later in the article for the Editors' Summary
Editors' Summary
Worldwide, nearly 250 million people have diabetes and this number is increasing rapidly, particularly in developing countries. Diabetes is a chronic disease characterized by dangerous amounts of sugar (glucose) in the blood. Blood-sugar levels are normally controlled by insulin, a hormone that the pancreas releases when blood-sugar levels rise after eating (the digestion of food produces glucose). Blood-sugar control fails in people with diabetes because they make no insulin (type 1 diabetes) or because the fat cells and muscle cells that usually respond to insulin by removing sugar from the blood have become insulin insensitive (type 2 diabetes). Type 1 diabetes is treated with insulin injections; type 2 diabetes—the most common type of diabetes—is controlled with diet, exercise, and antidiabetic pills, drugs that help the pancreas make more insulin (for example, sulfonylureas) or that make cells more sensitive to insulin (for example, thiazolidinediones). Long-term complications of diabetes include kidney failure, blindness, and nerve damage, and an increased risk of developing cardiovascular problems, including heart disease and strokes.
Why Was This Study Done?
Thiazolidinediones are widely used to treat type 2 diabetes but, worryingly, these drugs seem to increase people's risk of developing cardiovascular problems. In addition, they may increase the risk of bone fractures although the evidence for this particular association is limited. Given the large number of people with diabetes, it is important to understand the benefits and risks of thiazolidinedione treatment of diabetes as fully as possible. In this self-controlled case-series study, therefore, the researchers investigate the risk of fracture associated with the use of rosiglitazone and pioglitazone (two thiazolidinedione antidiabetic agents). A “self-controlled case-series study” compares how often an event (in this case, a fracture) occurs (the event's “rate”) in a population of individuals during a period of time when the individuals are not exposed to a medical intervention (in this case, treatment with thiazolidinediones) to its rate during a period when they are exposed to the intervention. Because each person acts as their own control, this study design helps to eliminate the possibility that unrecognized characteristics that vary between people (“confounders”) are responsible for differences in the event rate rather than the intervention itself.
What Did the Researchers Do and Find?
The researchers identified 1,819 people aged 40 years or older with a recorded fracture and at least one prescription for a thiazolidinedione by searching the UK General Practice Research Database, which contains personal and health data for more than 6 million UK residents. They compared these people's fracture rate during periods when they were taking a thiazolidinedione to their fracture rate when they weren't taking one of these drugs. After adjusting for age (age is a potential confounder because the risk of fractures increases with age and all the patients were older during their exposed period than during their unexposed period), the rate ratio for fracture at any site in patients during thiazolidinedione-exposed periods compared with thiazolidinedione-unexposed periods was 1.43. That is, nearly one and half times as many fractures occurred when people were taking thiazolidinediones than when they were not taking these drugs. The association between taking thiazolidinediones and the risk of fracture was similar in men and women and at several fracture sites but increased with the length of thiazolidinedione exposure.
What Do These Findings Mean?
These findings suggest that taking thiazolidinediones is associated with an increased risk of fracture at a wide range of sites in both men and women. They also suggest that the risk of fracture increases with treatment duration. These findings do not prove that thiazolidinediones cause fractures because, despite the self-controlled case-series design of this study, it remains possible that the people who have fractures share some unknown characteristic that affects their chances of breaking a bone. The accuracy of the findings is also dependent on the quality of the data in the General Practice Research Database. Nonetheless, these results are in keeping with the findings of clinical trials and other observational studies, suggesting they represent a real effect of treatment with thiazolidinediones. Although it is not clear yet how thiazolidinediones weaken bones, these findings need to be included in the ongoing debate about the risks and benefits of the treatment of type 2 diabetes with thiazolidinediones.
Additional Information
Please access these Web sites via the online version of this summary at
The International Diabetes Federation provides information about all aspects of diabetes
The US National Diabetes Information ClearingHouse provides detailed information about diabetes (including information on medicines for diabetes) for patients, health-care professionals, and the general public (in English and Spanish)
The UK National Health Service also provides information for patients and carers about type 2 diabetes (in several languages)
MedlinePlus provides links to further resources and advice about diabetes and diabetes medicines (in English and Spanish)
Information about the UK General Practice Research Database and about the self-controlled case-series method is available
More information is available where the research was done at The London School of Hygiene & Tropical Medicine
PMCID: PMC2741577  PMID: 19787025
25.  Obese Diabetic Patients are at Substantial Risk for Deep Infection after Primary TKA 
We conducted a prospective study of 1214 consecutive primary TKAs to compare the deep prosthetic infection rate between obese and nonobese patients during the first 12 months after surgery. We also sought to determine whether patient or surgical variables such as comorbidities, age, gender, blood transfusion, use of surgical drains, and antibiotic-impregnated cement were predictors of subsequent prosthetic infection after primary TKA. The overall prosthetic infection rate was 1.5% (n = 18). The odds for a deep prosthetic infection were greater in patients with morbid obesity (odds ratio [OR], 8.96; 95% confidence interval, 1.59–50.63) and diabetes (OR, 6.87; 95% confidence interval, 2.42–19.56). Men were more likely to have a prosthetic infection develop than women (OR, 5.93; 95% confidence interval, 1.95–18.04) and the prosthetic infection rate was lower (OR, 0.24; 95% confidence interval, 0.06–0.95) in patients when a surgical drain was used. There were no prosthetic infections in patients with diabetes who were not obese. This compares with 11 prosthetic infections in patients who were obese and diabetic and four prosthetic infections in patients who were obese but not diabetic. Morbid obesity and obesity combined with diabetes are risk factors for periprosthetic infection after TKA.
Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2674158  PMID: 18841430

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