Blood-based genome-wide DNA methylation correlations across body-fat- and adiposity-related biochemical traits.

The recent increase in obesity levels across many countries is likely to be driven by nongenetic factors. The epigenetic modification DNA methylation (DNAm) may help to explore this, as it is sensitive to both genetic and environmental exposures. While the relationship between DNAm and body-fat traits has been extensively studied, there is limited literature on the shared associations of DNAm variation across such traits. Akin to genetic correlation estimates, here, we introduce an approach to evaluate the similarities in DNAm associations between traits: DNAm correlations. As DNAm can be both a cause and consequence of complex traits, DNAm correlations have the potential to provide insights into trait relationships above that currently obtained from genetic and phenotypic correlations. Utilizing 7,519 unrelated individuals from Generation Scotland with DNAm from the EPIC array, we calculated DNAm correlations between body-fat- and adiposity-related traits by using the bivariate OREML framework in the OSCA software. For each trait, we also estimated the shared contribution of DNAm between sexes. We identified strong, positive DNAm correlations between each of the body-fat traits (BMI, body-fat percentage, and waist-to-hip ratio, ranging from 0.96 to 1.00), finding larger associations than those identified by genetic and phenotypic correlations. We identified a significant deviation from 1 in the DNAm correlations for BMI between males and females, with sex-specific DNAm changes associated with BMI identified at eight DNAm probes. Employing genome-wide DNAm correlations to evaluate the similarities in the associations of DNAm with complex traits has provided insight into obesity-related traits beyond that provided by genetic correlations.

Total shoulder replacement stems in osteoarthritis-short, long, or reverse? An analysis of the impact of crosslinked polyethylene.

BACKGROUND: The 2021 Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) report indicated that total shoulder replacement using both midhead (TMH) length humeral components and reverse arthroplasty (RTSA) had a lower revision rate than stemmed humeral components in anatomic total shoulder arthroplasty (aTSA)-for all prosthesis types and diagnoses. However, there are many factors that affect the outcome of total shoulder replacement, including stem length and polarity, polyethylene type, and glenoid fixation (cemented vs. cementless). The aim of this study was to assess the impact of these variables in the various primary total arthroplasty alternatives for osteoarthritis (OA) in the shoulder. METHODS: Data from a large national arthroplasty registry were analyzed for the period April 2004 to December 2020. The study population included all primary aTSA, RTSA, and TMH shoulder arthroplasty procedures undertaken for OA using either crosslinked polyethylene (XLPE) or noncrosslinked polyethylene (non-XLPE). Because of the previously documented and reported higher revision rate compared with other anatomic total shoulder replacement options, those using cementless metal-backed glenoid components were excluded. The rate of revision was determined by Kaplan-Meier estimates, with comparisons by Cox proportional hazard models. Reasons for revision were also assessed. RESULTS: For a primary diagnosis of OA, aTSA with a cemented XLPE glenoid component had the lowest revision rate, with a 12-year cumulative revision rate of 4.7%, compared with aTSA with cemented non-XLPE glenoid component at 8.7% and RTSA at 6.8%. The revision rate for TMH (with XLPE or non-XLPE) was lower than aTSA with cemented non-XLPE but was similar to the other implants at the same length of follow-up. The reason for revision of cemented aTSR was most commonly component loosening, not rotator cuff deficiency. CONCLUSION: Long-stem humeral components matched with XLPE in aTSA achieve a lower revision rate compared with shorter stems, long stems with conventional polyethylene, and RTSA when used to treat shoulder OA. In all these cohorts, loosening, not rotator cuff failure, was the most common diagnosis for revision.

THA for a Fractured Femoral Neck: Comparing the Revision and Dislocation Rates of Standard-head, Large-head, Dual-mobility, and Constrained Liners.

BACKGROUND: THA is a reasonable surgical option for some patients with fragility fractures of the femoral neck, but it has the risk of prosthesis dislocation. The prosthesis combination that reduces the risk of dislocation and the rate of revision surgery is not known. QUESTIONS/PURPOSES: In patients receiving primary THA for a femoral neck fracture, does (1) the rate of all-cause revision or (2) the reason for revision and rate of revision for dislocation differ among THA with a standard head size, large head size, dual mobility (DM), or constrained liner? (3) Is there a difference in the revision risk when patients are stratified by age at the time of surgery? METHODS: Data were analyzed for 16,692 THAs performed to treat fractures of the femoral neck reported in the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from January 2008 to December 2018, as this included the first use of DM prostheses. The AOANJRR includes information on more than 98% of arthroplasty procedures performed in Australia. Most patients were female (72%) and the mean age was 74 years ± 11. There were 8582 standard-head prostheses, 5820 large-head prostheses, 1778 DM prostheses, and 512 constrained prostheses identified. The cumulative percent revision (CPR) was determined for all causes as well as CPR for dislocation. The time to the first revision was described using Kaplan-Meier estimates of survivorship, with right censoring for death or closure of the database at the time of analysis. The unadjusted CPR was estimated each year of the first 10 years for standard heads, 10 years for large heads, 8 years for constrained liners, and 7 years for DM prostheses, with 95% confidence intervals using unadjusted pointwise Greenwood estimates. The results were adjusted for age, sex, femoral fixation, and head size where appropriate and were considered by age groups < 70 and ≥ 70 years. RESULTS: When adjusted for age, sex, femoral fixation and head size, there was no difference in the rate of all-cause revision at 7 years for any of the four groups. There was no difference in the rate of all-cause revision when patients were stratified by < 70 or ≥ 70 years of age. Dislocation was the most common reason for revision (32%). When analyzing revision for dislocation alone, large-head THA had a lower rate of revision for dislocation compared with standard head (HR 0.6 [95% CI 0.4 to 0.8]; p < 0.001) and DM prostheses had a lower rate of revision for dislocation than standard head for the first 3 months (HR 0.3 [95% CI 0.1 to 0.7]; p < 0.004) but not after this time point. CONCLUSION: The Australian registry shows that there is no difference in the rate of all-cause revision for standard-head, large-head, DM prostheses or constrained liner THA after femoral neck fractures for all patients or for patients stratified into younger than 70 years and at least 70 years of age groups. Dislocation is the most common cause of revision. Large-head prostheses are associated with a lower revision risk for dislocation and DM prostheses have a lower rate of revision for dislocation than standard heads for the first 3 months only. Surgeons treating a femoral neck fracture with THA might consider a large head size if the diameter of the acetabulum will allow it and a DM prosthesis if a large head size is not possible. The age, life expectancy and level of function of patients with femoral neck fractures minimizes the potential long-term consequences of these prostheses. The lack of significant differences in survival between most prosthesis combinations means surgeons should continue to look for factors beyond head size and prosthesis to minimize dislocation and revision surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.

A Comparison of Revision Rates for Osteoarthritis of Primary Reverse Total Shoulder Arthroplasty to Primary Anatomic Shoulder Arthroplasty with a Cemented All-polyethylene Glenoid: Analysis from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: There has been decreased use of anatomic total shoulder arthroplasty (aTSA) because reverse TSA (rTSA) is increasingly being used for the same indications. Although short-term studies generally have not found survivorship differences between these implant designs, these studies are often small and their follow-up is limited to the short term. Likewise, the degree to which patient characteristics (such as gender, age, and American Society of Anesthesiologists [ASA] score) may or may not be associated with survivorship differences calls for larger and longer-term studies than is often possible in single-center designs. Large national registry studies may be able to help answer these questions. QUESTIONS/PURPOSES: By analyzing a large Australian registry series of primary aTSAs with cemented all-polyethylene glenoids and rTSA for osteoarthritis (OA), we asked: (1) Is the revision risk for OA higher for aTSA with all-polyethylene glenoids or for rTSA, adjusting for patient characteristics such as age, gender, ASA score, and BMI? (2) Is the patient's gender associated with differences in the revision risk after controlling for the potentially confounding factors of age, ASA score, and BMI? METHODS: In this comparative, observational registry study performed between January 1, 2015, and December 31, 2019, all primary aTSAs with all-polyethylene glenoids and rTSA for OA as determined by the treating surgeon and reported to our national registry formed two groups for analysis. The study period was set to time-match for the collection of ASA score and BMI in 2012 and 2015, respectively. Our registry enrolls more than 97% of all shoulder arthroplasties undertaken in Australia. There were 29,294 primary shoulder arthroplasties; 1592 hemiarthroplasties, 1876 resurfacing and stemless shoulders, 269 stemmed, and 11,674 reverse shoulder arthroplasties were excluded for other diagnoses. A total of 1210 metal-backed glenoids in stemmed aTSA for OA were excluded. A total of 3795 primary aTSAs with all-polyethylene glenoids and 8878 primary rTSAs for OA were compared. An aTSA with an all-polyethylene glenoid and rTSA were more likely to be performed in women (56% and 61% of patients, respectively). The mean age was 69 ± 8 years for aTSA with all-polyethylene glenoids and 74 ± 8 years for rTSA. One aTSA for OA was performed in a patient with an unknown glenoid type. The ASA score (n = 12,438) and BMI (n = 11,233) were also recorded. The maximum follow-up was 5 years for both groups, and the mean follow-up was 2.6 ± 1.4 years for aTSA with all-polyethylene glenoids and 2.1 ± 1.4 years for rTSA. The endpoint was time to revision (all causes), and the cumulative percent revision was determined using Kaplan-Meier estimates of survivorship (time to revision) and HRs from Cox proportional hazard models that were adjusted for age, gender, ASA score, and BMI category. RESULTS: Overall, there were no differences in the 4-year cumulative percent revision between the groups; the 4-year cumulative percent revision was 3.5% for aTSA with all-polyethylene glenoids (95% CI 2.9%-4.2%) and 3.0% for rTSA (95% CI 2.6%-3.5%). There was an increased risk of revision of rTSA compared with aTSA using all-polyethylene glenoids in the first 3 months (HR 2.17 [95% CI 1.25-3.70]; p = 0.006, adjusted for age, gender, ASA score, and BMI). After that time, there was no difference in the rate of revision, with the same adjustments. In the first 3 months, men undergoing rTSA had a higher rate of revision than men with aTSA using all-polyethylene glenoids (HR 4.0 [95% CI 1.72-9.09]; p = 0.001, adjusted for age, BMI, and ASA). There was no difference between men in the two groups after that time. Women with aTSA using all-polyethylene glenoids were at a greater risk of revision than women with rTSA from 3 months onward (HR 2.77 [95% CI 1.55-4.92]; p < 0.001, adjusted for age, BMI, and ASA), with no difference before that time. CONCLUSION: Given the absence of survivorship differences at 4 years between rTSA and aTSA, but in light of the differences in the revision risk between men and women, surgeons might select an aTSA with an all-polyethylene glenoid to treat OA, despite the current popularity of rTSA. However, there are survivorship differences between genders. Future studies should evaluate whether our comparative findings are replicated in men and women undergoing aTSA with all-polyethylene glenoids and rTSA for primary diagnoses such as rheumatoid arthritis or post-traumatic arthritis, and whether there are functional differences between the two implant designs when used for OA. LEVEL OF EVIDENCE: Level III, therapeutic study.

The rate of 2nd revision for shoulder arthroplasty as analyzed by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR).

Background and purpose - The increase in shoulder arthroplasty may lead to a burden of revision surgery. This study compared the rate of (2nd) revision following aseptic 1st revision shoulder arthroplasty, considering the type of primary, and the class and type of the revision.Patients and methods - All aseptic 1st revisions of primary total reverse shoulder arthroplasty (rTSA group) and of primary total stemmed and stemless total shoulder arthroplasty (non-rTSA group) procedures reported to our national registry between April 2004 to December 2018 were included. The rate of 2nd revision was determined using Kaplan-Meier estimates and comparisons were made using Cox proportional hazards models.Results - There was an increased risk of 2nd revision in the 1st month only for the rTSA group (n = 700) compared with the non-rTSA group (n = 991); hazard ratio (HR) = 4.8 (95% CI 2.2-9). The cumulative percentage of 2nd revisions (CPR) was 24% in the rTSA group and 20% in the non-rTSA group at 8 years. There was an increased risk of 2nd revision for the type (cup vs. head) HR = 2.2 (CI 1.2-4.2), but not class of revision for the rTSA group. Minor (> 3 months) vs. major class revision, and humeral revision vs. all other revision types were second revision risk factors for the non-rTSA group.Interpretation - The CPR of revision shoulder arthroplasty was > 20% at 8 years and was influenced by the type of primary, the class, and the type of revision. The most common reasons for 2nd revision were instability/dislocation, loosening, and infection.

What Is the Risk of THA Revision for ARMD in Patients with Non-metal-on-metal Bearings? A Study from the Australian National Joint Replacement Registry.

BACKGROUND: There are increasing reports of corrosion between the femoral head and trunnion in primary conventional THA, resulting in metal particulate release often termed trunnionosis. There may be heightened awareness of this condition because of severe soft-tissue reactions initially thought to be solely attributable to prostheses with a metal-on-metal (MoM) bearing surface. It is unclear what percentage of revisions for THA with non-MoM bearing surfaces can be attributed to trunnionosis and to what extent adverse reaction to metal debris (ARMD) seen with MoM bearings may also be seen with other bearing surfaces in THA. QUESTIONS/PURPOSES: We analyzed data from a large national registry to ask: (1) What is the revision risk for the indication of ARMD in patients with conventional THA and modern non-MoM bearing surfaces such as metal or ceramic-on-cross-linked polyethylene (XLPE) or ceramic-on-ceramic? (2) What prosthesis factors are associated with an increased risk of such revision? (3) What is the relative revision risk for ARMD in THAs with large-head MoM bearings, small-head MoM bearings, and non-MoM modern bearing surfaces? METHODS: The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) longitudinally maintains data on all primary and revision joint arthroplasties, with nearly 100% capture. The study population included all THAs using modern bearing surfaces (defined as metal or ceramic heads-on-XLPE and ceramic-on-ceramic bearing couples) revised because of ARMD between September 1999 and December 2018. Prostheses with modular necks were excluded. The cumulative percent revision (CPR) because of ARMD was determined. The study group consisted of 350,027 THAs with a modern bearing surface, 15,184 THAs with a large-head MoM bearing (≥ 36 mm), and 5474 THAs with a small head MoM bearing (≤ 32 mm). The patients in the group who received the modern bearing surfaces were slightly older than the patients in the groups who received the large- and small-head bearing surfaces, with a mean age 68 years (SD 12) versus a mean age 63 years (SD 12), and a mean age 62 years (SD 11), respectively. There was a higher proportion of women in the modern bearing surface group; 55% (193,312 of 350,027), compared with 43% (6497 of 15,184) in the large-head MoM group and 50% (2716 of 5474) in the small-head MoM group. The outcome measure was the CPR, which was defined using Kaplan-Meier estimates of survivorship to describe the time to the first revision for ARMD at 17 years. Hazard ratios (HR) from Cox proportional hazards models, adjusting for age and sex, were performed to compare the revision rates among groups. The registry defines a revision as a reoperation of a previous hip arthroplasty in which one or more of the prosthetic components is replaced or removed, or one or more components is added. RESULTS: The CPR for ARMD for patients with a modern bearing surface at 17 years was 0.1% (95% confidence interval 0.0 to 0.1). After controlling for age and sex, we found that cobalt chrome heads, two specific prostheses (Accolade® I and M/L Taper), and head sizes ≥ 36 mm were associated with an increased risk of revision for ARMD. Metal-on-XLPE had a higher risk of revision for ARMD than ceramic-on-ceramic or ceramic-on-XLPE (HR 3.4 [95% CI 1.9 to 6.0]; p < 0.001). The Accolade 1 and the M/L Taper stems had a higher risk of revision than all other stems (HR, 8.3 [95% CI 4.7 to 14.7]; p < 0.001 and HR 14.4 [95% CI 6.0 to 34.6]; p < 0.001, respectively). Femoral stems with head sizes ≥ 36 mm had a higher rate of revision for ARMD than stems with head sizes ≤ 32 mm (HR 3.2 [95% CI 1.9 to 5.3]; p < 0.001).Large-head MoM bearings had a greater increase in revision for ARMD compared with modern bearing surfaces. The CPR for patients with a large-head MoM bearing at 17 years for ARMD was 15.5% (95% CI 14.5 to 16.6) and it was 0.1% for modern bearing surfaces (HR 340 [95% CI 264.2 to 438.0]; p < 0.001). Modern bearing surfaces likewise had a lower HR for revision for ARMD than did THAs with small-head MoM bearings, which had a 0.9% (95% CI 0.7 to 1.4) CPR compared with modern bearings from 0 to 9 years (HR 10.5 [95% CI 6.2 to 17.7]; p < 0.001). CONCLUSIONS: The revision risk for ARMD with modern bearing surfaces in THA is low. The Accolade 1 and the M/L Taper stem have a higher risk of revision for ARMD and cobalt-chrome heads, and head sizes ≥ 36 mm have a higher rate of revision than ≤ 32 mm head sizes. ARMD is a rare failure mode for THA with non-MoM bearings, but in patients presenting with unexplained pain with no other obvious cause, this diagnosis should be considered and investigated further. LEVEL OF EVIDENCE: Level III, therapeutic study.

Is the Survivorship of Birmingham Hip Resurfacing Better Than Selected Conventional Hip Arthroplasties in Men Younger Than 65 Years of Age? A Study from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: The Birmingham Hip Resurfacing (BHR) prosthesis is the most commonly used metal-on-metal hip resurfacing arthroplasty device. The current manufacturer-recommended target demographic for the BHR is male patients, younger than 65 years requiring a femoral head size of ≥ 50 mm. Female patients, older patients, and individuals with smaller femoral-head diameter (≤ 50 mm) are known to have higher revision rates. Prior studies suggest that the survivorship of the BHR when used in the target demographic is comparable with that of primary conventional THA, but comparing survivorship of the most durable hip resurfacing arthroplasty device to the survivorship of all conventional THA prostheses is not ideal because the THA group comprises a large number of different types of prostheses that have considerable variation in prosthesis survival. A more informative comparison would be with the THA implants with the best survivorship, as this might help address the question of whether survivorship in the BHR target population can be improved by using a well-performing conventional THA. QUESTIONS/PURPOSES: We compared the difference in cumulative percent revision, reasons for revision and types of revision for procedures reported to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) using the BHR prosthesis (femoral-head size > 50 mm) and three conventional THA prostheses identified as having the lowest 10-year cumulative percent revision in the currently recommended BHR target population to ask: (1) Does the BHR have a lower cumulative revision rate than the group of three conventional THA prostheses? (2) Is there a difference in the revision diagnosis between the BHR and the three best conventional THA prostheses? (3) What is the difference in the components used for a revision of a BHR compared with the three best conventional THA prostheses? METHODS: Data reported to the AOANJRR between September 1, 1999 and December 31, 2018 was used for this analysis. This study period includes almost the entire use of the BHR in Australia. The AOANJRR is a large national joint registry with almost 100% completeness, high accuracy, rigorous validation, and little to no loss to follow-up. The study population included males younger than 65 years that had received one hip replacement procedure for osteoarthritis. All patients with bilateral procedures, no matter the time interval between hips, were excluded. Only BHR prostheses with a femoral-head size ≥ 50 mm and conventional THA prostheses with femoral head sizes ≥ 32 mm and either ceramic-on-ceramic or metal, ceramic, ceramicized metal-on-crosslinked polyethylene (XLPE) bearings were included. These femoral head sizes and bearings were selected because they reflect modern conventional THA practice. There is no difference in the revision rate of these bearings in the AOANJRR. There were 4790 BHR procedures and 2696 conventional THA procedures in the study group. The mean (± SD) age for BHR procedures was 52 ± 7.8 years and 56 ± 7.1 years for conventional THA procedures. All comparative analyses were adjusted for age. Other demographics data including American Society Anesthesiologists (ASA) score and BMI were only included in AOANJRR data collection since 2012 and 2015, respectively, and have not been included in this analysis because of the low use of BHR in Australia since that time. The maximum follow-up was 18.7 years for both groups and mean follow-up of 11.9 years for the BHR and 9.3 years for the conventional THA group. Revision rates were determined using Kaplan-Meier estimates of survivorship to describe the time to the first revision, with censoring at the time of death or closure of the database at the time of analysis. A revision was defined as removal, replacement or addition of any component of a joint replacement. Revisions can be further classified as major revisions (removal of a component articulating with bone-usually the stem and/or the shell) or minor revisions (removal of other components-usually the head and/or the liner). The unadjusted cumulative percent revision after the primary arthroplasty (with 95% confidence intervals) was calculated and compared using Cox proportional hazard models adjusted for age. RESULTS: The BHR prosthesis had a statistically higher rate of all-cause revision at 17 years than the selected conventional THA prostheses (HR 2.77 [95% CI 1.78 to 4.32]; p < 0.001). The revision diagnoses differed between the groups, with the BHR demonstrating a higher revision rate for loosening after 2 years than the conventional THA protheses (HR 4.64 [95% CI 1.66 to 12.97]; p = 0.003), as well as a higher fracture rate during the entire period (HR 2.57 [95% CI 1.24 to 5.33]; p = 0.01). There was a lower revision rate for infection for the BHR compared with the THA group in the first 5 years, with no difference between the two groups after this time. All revisions of the BHR were major revisions (such as, removal or exchange of the femoral and/or acetabular components) and this occurred in 4.5% of the primary BHR procedures. Major revision was the most common type of revision for primary THA accounting for 1.7% of all primary THA procedures. Minor revisions (head, inset or both) were undertaken in a further 0.6% of primary THA procedures. CONCLUSIONS: Given the increasing revision risk of the BHR compared with better-performing conventional THA prostheses in the target population, we recommend that patients be counseled about this risk. We suggest that a THA with proven low revision rates might be the better choice, particularly for patients who are concerned about implant durability. Well-controlled prospective studies that show appreciable clinically important differences in patient-reported outcomes and functional results favoring the BHR over conventional THA prostheses using modern bearings are needed to justify the use of the BHR in view of this revision risk. LEVEL OF EVIDENCE: Level III, therapeutic study.

Does Knee Prosthesis Survivorship Improve When Implant Designs Change? Findings from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: TKA generally has excellent long-term survivorship. When a new knee system supersedes a previous model, increased survivorship, improved functional performance, or both may be expected, because key areas of design modification are often targeted to address wear, stability, and the patellofemoral articulation. However, not all design changes are beneficial, and to our knowledge, knee arthroplasty has not been systematically evaluated in the context of design changes that occur during the development of new knee arthroplasty systems. QUESTIONS/PURPOSES: Using the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) we performed multiple old-to-new comparisons of frequently used contemporary knee implants to ask: (1) does overall prosthesis survivorship free from revision increase when a new knee prosthesis system is introduced to replace a prior prosthesis system? (2) Has survivorship free from revision improved for the revision indications of wear, instability, and patellofemoral articulation issues, where development efforts have been concentrated? METHODS: Data from the AOANJRR from September 1999 to December 2017 were used to compare the survivorship of prostheses free from revision at a maximum of 17 years in procedures where a new design model was introduced to replace a prior knee system from the same manufacturer. Only prosthesis systems used in a minimum of 2000 primary TKA procedures for osteoarthritis that had a minimum of 5 years of follow-up were included. Varus-valgus constrained and hinge TKA designs were excluded. Cruciate-retaining, posterior-stabilized, and medial pivot-design knees were considered separately. The new and old prosthesis systems were paired for analysis. Survivorship was calculated with Kaplan Meier estimates and comparisons were performed using the Cox proportional hazards method. Subanalyses according to the three main revision indications were performed, and where possible, analyses were performed based on polyethylene types (highly cross-linked polyethylene and ultra-high-molecular-weight polyethylene), combined and separated. Revision was defined as a reoperation of a previous knee arthroplasty in which one or more of the components was removed, replaced, or added. There were 323,955 TKA procedures and 11 new prosthesis system designs that were introduced to replace an earlier knee system from the same manufacturer. Of these prosthesis system pairs, six were cruciate-retaining prostheses, four were posterior-stabilized designs, and one was a medial pivot design. RESULTS: Six of the 11 knee system pairs showed improved survivorship with the new design, three were no different, and in two, the newer prosthesis systems had a higher rate of revision than the old one did. When revision for wear was analyzed, five prosthesis systems showed improvement, five were no different, and one had a higher rate of revision than the previous system did. There was no improvement in the rate of revision for instability; seven new prosthesis systems showed no difference from the previous system and four new prosthesis systems had a higher rate of revision than the previous system did. A subanalysis of revision for patellofemoral complications showed improvement in two comparisons, no difference in six, and a higher revision rate in two; one could not be calculated because of an insufficient number of revisions for this reason. CONCLUSIONS: It is difficult to predict whether a new system will demonstrate better survival than a previous one, and widespread uptake of a new design before a benefit is shown in robust clinical studies is unwise. Similarly, adoption of a new system for which there is no difference in survivorship from a previous model may be premature because a new device may have associated unknown and unintended consequences. Healthcare policy makers and therapeutic device regulators should similarly be guided by results and seek out peer-reviewed evidence before accepting change to established practice. Surgeons must be aware that implant changes may not translate into better survivorship and must seek compelling evidence of improvement in survival and/or function before changing systems. LEVEL OF EVIDENCE: Level III, therapeutic study.

Lower operating volume in shoulder arthroplasty is associated with increased revision rates in the early postoperative period: long-term analysis from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Improved short-term outcomes have been demonstrated with higher surgical volume in shoulder arthroplasty. There is however, little data regarding long-term outcomes. METHOD: Revision data from the Australian Orthopaedic Association National Joint Replacement Registry from 2004-2017 was analyzed according to 3 selected surgeon volume thresholds: <10, 10-20, and >20 shoulder arthroplasty cases per surgeon, per year. RESULTS: There was a significantly higher rate of revision for stemmed total shoulder arthroplasty (TSA) for osteoarthritis (OA) for the <10/yr compared with the >20/yr group for the first 1.5 years only (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.08-1.71, P = .009). For reverse total shoulder arthroplasty (rTSA) performed for OA, there was a higher revision rate for the <10/yr compared with the >20/yr group for the first 3 months only (HR 2.58, 95% CI 1.67-3.97, P < .001). In rTSA for cuff arthropathy, there was a significantly higher rate of revision for the <10/yr compared with the >20/yr group throughout the follow-up period (HR 1.66, 95% CI 1.21-2.28, P = .001). There was no significant difference for the primary diagnosis of fracture. CONCLUSION: Lower surgical volume was associated with higher all-cause revision rates in the early postoperative period in TSA and rTSA for OA and throughout the follow-up period in rTSA for cuff arthropathy. Despite increases in the volume of shoulder arthroplasties performed in recent years, more than 78% of surgeons undertake fewer than 10 procedures per year.

Reverse total shoulder arthroplasty compared to stemmed hemiarthroplasty for proximal humeral fractures: a registry analysis of 5946 patients.

BACKGROUND: There is an increasing trend toward the use of reverse total shoulder arthroplasty (RTSA) over stemmed hemiarthroplasty (HA) for the management of proximal humeral fractures. There are limited data available comparing the revision rates for RTSA and HA in the setting of a fracture. The aim of this study was to compare the revision rates for RTSA and HA when used for the treatment of a fracture and to analyze the effect of demographics and prosthesis fixation on these revision rates. METHODS: Data obtained from the Australian Orthopaedic Association National Joint Replacement Registry from April 16, 2004, to December 31, 2017, included all procedures for primary diagnosis proximal humeral fracture. The analyses were performed using Kaplan-Meier estimates of survivorship and hazard ratios from Cox proportional hazards models. RESULTS: Over the study period, there were 3049 (51%) RTSA and 2897 (49%) HA procedures. The cumulative percent revision rate at 9 years was lower for the RTSA than for the HA: 7.0% (95% confidence interval [CI], 4.8-10.1) compared with 11.7% (95% CI, 10.3-13.2). Between 0 and 6 months, the HA had a significantly lower revision rate than the RTSA (hazard ratio, 0.50; 95% CI, 0.34-0.72; P < .001). Between 6 month and 3 years, the HA had a significantly higher revision rate. For the RTSA, males have a significantly higher rate of revision compared with females. There is a higher rate of early revision due to instability in younger persons (55-64) and males. For both RTSA and HA, cemented prostheses have lower revision rates compared with cementless prostheses. CONCLUSIONS: RTSA has a significantly lower revision rate compared with HA for the treatment of proximal humeral fractures in females. Younger patients (<65) and males are at risk of early revision secondary to instability. In these patient groups, either alternatives to RTSA or further attention to fixation of tuberosities and shoulder rehabilitation may be indicated.

One-Surgeon vs Two-Surgeon Single-Anesthetic Bilateral Total Knee Arthroplasty: Revision and Mortality Rates From the Australian Orthopedic Association National Joint Replacement Registry.

BACKGROUND: Outcomes following 1-surgeon single-anesthetic sequential bilateral total knee arthroplasty (seq-BTKA) compared to 2-surgeon single-anesthetic simultaneous bilateral total knee arthroplasty (sim-BTKA) are largely unknown. The current study compared revision rates and all-cause mortality following seq-BTKA vs sim-BTKA using data from the Australian Orthopedic Association National Joint Replacement Registry. METHODS: Seq-BTKA and sim-BTKA procedures recorded within the registry between September 1, 1999 and December 31, 2018 were analyzed for subsequent revision and patient mortality. Cumulative percent revision and cumulative percent survival were determined using the Kaplan-Meier method. Revision and mortality rates for sim-BTKA and seq-BTKA were compared using Cox proportional hazards models, adjusting for age and gender. RESULTS: Included in the analysis were 27,480 seq-BTKAs and 471 sim-BTKAs. There was no difference in the cumulative percent revision between the 2 groups (hazard ratio 1.23, 95% confidence interval 0.82-1.85). Cumulative percent patient survival was not significantly different between the 2 groups (hazard ratio 1.20, 95% confidence interval 0.93-1.54). CONCLUSION: Revision rates and mortality were similar for seq-BTKA and sim-BTKA. Investigation of additional outcomes such as complications not requiring revision, pain, function, and cost is required to comprehensively understand the relative merits of each procedure.

Mortality and Implant Survival With Simultaneous and Staged Bilateral Total Hip Arthroplasty: Experience From the Australian Orthopedic Association National Joint Replacement Registry.

BACKGROUND: Total hip arthroplasty (THA) is an effective procedure for relieving pain and restoring function in osteoarthritis. A significant proportion of patients have severe disease bilaterally. Consensus regarding safety and selection of patients for simultaneous bilateral THA or the optimal timing for staged THA has not been reached. The aim of this study is to compare rates, causes of revision, and 30-day mortality between simultaneous and staged bilateral THA using data from the Australian Orthopedic National Joint Replacement Registry. METHODS: Data for 12,359 bilateral THA procedures were collected from September, 1999 to December, 2017. Rates and causes of revision and 30-day mortality were obtained for simultaneous bilateral and staged procedures with intervals of 1 day-6 weeks, 6 weeks-3 months, and 3 months-6 months. Yearly cumulative percent revision or cumulative percent survival with 95% confidence intervals calculated by the Kaplan-Meier method, and adjusted hazard ratios were used for comparisons. RESULTS: Thirty-day mortality is lower in patients who have bilateral procedures within 6 months, regardless of timing, than those who have unilateral procedures (0.06% vs 0.18%). Staged bilateral THA had a significantly lower mortality than simultaneous bilateral THA (odds ratio 0.175, 95% confidence interval = 0.04-0.78, P = .022). When separate time intervals were compared, no significant differences were seen. Bilateral 6 week-3 months has a higher rate of revision from 1.5 years-2years compared with same day bilaterals (hazard ratio = 2.39, 95% confidence interval = 1.12, 5.09, P = .024). There were no other significant differences in the rate of revision between groups. The most common reasons for revision were fracture, loosening, and infection. Simultaneous bilateral procedures have a significantly higher rate of revision for fracture compared with staging 3-6 months (hazard ratio = 1.96 [1.27, 3.03], P = .002). CONCLUSION: This study demonstrates that bilateral THA has a low mortality rate regardless of time interval between procedures. Simultaneous and staged bilateral THA have similar rates of revision.

Similar Risk of Revision After Kinematically Aligned, Patient-Specific Instrumented Total Knee Arthroplasty, and All Other Total Knee Arthroplasty: Combined Results From the Australian and New Zealand Joint Replacement Registries.

BACKGROUND: Kinematic alignment (KA) in total knee arthroplasty (TKA) replicates individual knee joint line orientation and physiological soft tissue balance. There are limited data on the effect of KA on survivorship compared with other methods of implanting a TKA. The aim of this study was to compare the survivorship of the same design of TKA implanted with either patient-specific instrument (PSI) KA or with computer-assisted surgery and conventionally instrumented. METHODS: We performed an observational study of data from 2 national joint registries on all patients who underwent a TKA with a Triathlon cruciate-retaining TKA (Stryker, Mahwah, NJ) from January 2011 to December 31, 2013. The outcomes of knees performed with unrestricted KA using patient-specific instrument were compared with computer-assisted surgery and conventionally instrumented Triathlon cruciate-retaining TKA. The principal outcome measure was time to first revision using Kaplan-Meier estimates of survivorship. Cox proportional hazard ratios, adjusted for age and gender, were used to compare the 2 groups. RESULTS: There were 20,512 TKA procedures recorded, of which 416 were performed using KA-PSI. The KA-PSI group was younger (66.8 ± 8.2 vs 68.3 ± 9.2, P = .001), with an identical gender distribution. The cumulative revision rate at 7 years was 3.1% for the KA-PSI Triathlon cohort and 3.0% for the other Triathlon TKA cohort (P = .89). The most common reasons for revision in the KA-PSI group were maltracking, patella erosion, and arthrofibrosis. CONCLUSION: Kinematically aligned Triathlon TKA using PSI has similar revision rate as all other Triathlon TKA.

Fixation Method for Hip Arthroplasty Stem Following Hip Fracture: A Population-Level Cost-Effectiveness Analysis.

BACKGROUND: Hip arthroplasty is increasing in Australia. The number of procedures for fractured neck of femur was 7500 in 2017. Best practices for fixation method and procedure type require scrutiny. This paper is about the costs and health outcomes of cemented and uncemented hemiarthroplasty and total hip arthroplasty at a national level. METHODS: We created a Markov model for patients <75, aged 75-85, and over 85. Expected costs and health outcomes over 5 years from a decision to change from existing practice to a best practice policy in which all patients with fractured neck of femur received the same fixation method based on age and type of arthroplasty are estimated. The model was populated using prevalence and incidence data from the Australian Orthopedic Association National Joint Replacement Registry, costs from Metro North Hospital and Health Service in Queensland, and probabilities and utilities from the literature. We simulated the uncertainties in outcomes with probabilistic sensitivity analysis. RESULTS: We found that uncemented stem procedures were more costly and provided worse health outcomes compared to cemented stem fixation for hemiarthroplasty and total hip arthroplasty for all age groups. Moving from existing practice to cemented stem arthroplasty could save the Australian health system $2.0 million over 5 years with a gain of 203 quality-adjusted life years. CONCLUSION: We suggest that consideration be given to cemented fixation of the femoral stem for patients receiving both hemiarthroplasty and total hip arthroplasty for fractured neck of femur. Best practice guidelines focused on cost-effectiveness should recommend cemented stem fixation to both save costs and improve patient quality of life.

The Outcome of Total Knee Arthroplasty With and Without Patellar Resurfacing up to 17 Years: A Report From the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Patellar resurfacing in total knee arthroplasty (TKA) remains a controversial issue after more than 4 decades of TKA. Despite a growing body of evidence from registry data, resurfacing is still based largely on a surgeon's preference and training. The purpose of this study is to provide long-term outcomes for patellar resurfaced compared to when the patella is not resurfaced. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry (1999-2017) were used for this study. The analysis included 570,735 primary TKAs undertaken for osteoarthritis. Hazard ratios (HRs) and 17-year cumulative percent revision rates were used to compare revision rates between 4 subgroups: minimally stabilized (MS) patellar resurfacing, posterior stabilized (PS) patellar resurfacing, MS unresurfaced, and PS unresurfaced patella. Additional analyses of the patellar implant type and a comparison of inlay and onlay patellar resurfacing were also performed. RESULTS: For all primary TKA, procedures where the patella was not resurfaced have a higher rate of revision compared to procedures where the patella was resurfaced (HR, 1.31; confidence interval, 1.28-1.35; P < .001). Unresurfaced PS knees have the highest cumulative percent revision at 17 years (11.1%), followed by MS unresurfaced (8.8%), PS resurfaced (7.9%), and MS resurfaced (7.1%). Inlay patellar resurfacing has a higher rate of revision compared to onlay patellar resurfacing (HR, 1.27; confidence interval, 1.17-1.37; P < .001). CONCLUSION: Resurfacing the patella reduces the rate of revision for both MS and PS knees. MS knees with patellar resurfacing have the lowest rate of revision. Onlay patella designs are associated with a lower revision rate compared to inlay patella designs.

How Does Mortality Risk Change Over Time After Hip and Knee Arthroplasty?

BACKGROUND: Mortality after THA and TKA is lower than expected for several years after surgery when compared with age- and sex-adjusted population data. With long-term followup (beyond approximately 10 years), some evidence has suggested that this trend reverses, such that postsurgical mortality is higher than expected as more time passes. However, the degree to which this may be the case has not been clearly established. QUESTIONS/PURPOSES: In this large-registry study, we asked: What is the long-term mortality after THA and TKA compared with the expected mortality, adjusted for age, sex, and calendar year. METHODS: Using data on 243,057 THAs and 363,355 TKAs performed for osteoarthritis from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from 2003 to 2016, and life tables from the Australian Bureau of Statistics the Standardised Mortality Ratio (SMR), relative mortality and excess mortality (relative to the expected mortality for people of the same sex and age in the same country) was calculated separately for hips and knees. The AOANJRR contains near-complete (98%-100%) data from all hospitals in Australia performing arthroplasty but does not include followup data on people who have left the country. Followup was from the date of surgery to 13 years, mean 5.8 years. RESULTS: We found a lower-than-expected mortality for THA and TKA in the early years after surgery. This association diminished over time and the mortality became higher than expected after 12 years for both THA and TKA. For THA, the excess mortality (per thousand people) increased from 11 fewer deaths (95% CI, 10-11 fewer) after 1 year to four more deaths (95% CI, 0-9 more) in the 13th year, and the SMR increased from 0.50 (95% CI, 0.48-0.52) after 1 year to 1.07 (95% CI, 0.99-1.14) in the 13th year. For TKA, the excess mortality (per thousand people) increased from 12 fewer deaths (95% CI, 12-13 fewer) after 1 year to five more deaths (95% CI 2-9 more) in the 13th year, and the SMR increased from 0.39 (95% CI, 0.37-0.40) after 1 year to 1.09 (95% CI, 1.03-1.15) in the 13th year. CONCLUSIONS: Mortality after hip and knee arthroplasty is lower than expected (based on population norms) in the first 8 years to 9 years but gradually increases over time, becoming higher than expected after 12 years. The lower-than-expected mortality in the early years after surgery is likely the result of patient selection with patients undergoing primary arthroplasty having better health at the time of surgery than that of the age- and sex-matched population. The increasing mortality over time cannot be regression to the mean, as late mortality is higher than expected, moving beyond the mean. It is important to understand if there are modifiable factors associated with this increased mortality. The reasons for the change are uncertain. Factors to consider in future research include determining the effect of different patient factors on late mortality. Some of these included higher obesity rates for joint replacement patients and the association or causal impact of osteoarthritis and/or its treatment to increase late mortality in a similar manner to other forms of arthritis. There is also a possibility that the arthroplasty device itself may affect late mortality. LEVEL OF EVIDENCE: Level III, therapeutic study.

Nationwide trends in management of proximal humeral fractures: an analysis of 77,966 cases from 2008 to 2017.

BACKGROUND: There is no consensus as to the treatment of proximal humeral fractures (PHFs), particularly in elderly patients. There is increasing evidence that nonoperative management may have similar functional outcomes to operative management, which is potentially conflicting with increasingly improved surgical techniques and implants. The aim of this study was to investigate the changes in the incidence and management of PHFs across Australia over a 10-year period. MATERIALS AND METHODS: We retrospectively reviewed all hospitalizations of patients with PHFs from 2 Australian national health care databases from 2008 to 2017. We recorded the incidence of PHFs and annual utilization rates of commonly used treatment options including nonoperative management, hemiarthroplasty (HA), reverse total shoulder arthroplasty (RTSA), and open reduction-internal fixation (ORIF). RESULTS: The incidence of PHFs increased from 26.8 per 100,000 person-years in 2008 to 45.7 per 100,000 person-years in 2017. There was a decrease in operative management from 2008 to 2017, with 32.5% and 22.8% of all PHFs treated operatively in 2008 and 2017, respectively (P = .001). ORIF use decreased significantly from 76.6% to 72.6% (P = .004). RTSA use increased significantly from 4.1% to 24.5% (P < .001). HA use decreased significantly from 19.3% to 3% (P < .001). CONCLUSIONS: Whereas the incidence of PHFs increased, the operative management of PHFs decreased significantly from 2008 to 2017, particularly in patients aged 65 years or older. This decrease in operative management was in part due to a significant decrease in ORIF and HA use in patients aged 65 years or older. There was a significant increase in RTSA use.

Use and outcome of 1,220 primary total elbow arthroplasties from the Australian Orthopaedic Association National Joint Arthroplasty Replacement Registry 2008-2018.

Background and purpose - The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was analyzed to determine trends in use of primary total elbow arthroplasty (TEA), the types of prostheses used, primary diagnoses, reasons for and types of revision, and whether the primary diagnosis or prosthesis design influenced the revision rate.Patients and methods - During 2008-2018, 1,220 primary TEA procedures were reported of which 140 TEAs were revised. Kaplan-Meier estimates of survivorship were used to describe the time to first revision and hazard ratios (HR) from Cox proportional hazard models, adjusted for age and sex, were used to compare revision rates.Results - The annual number of TEAs performed remained constant. The 3 most common diagnoses for primary TEA were fracture/dislocation (trauma) (36%), osteoarthritis (OA) (34%), and rheumatoid arthritis (RA) (26%). The cumulative percentage revision for all TEAs undertaken for any reason was 10%, 15%, and 19% at 3, 6, and 9 years. TEAs undertaken for OA had a higher revision rate compared with TEAs for trauma (HR = 1.8, 95% CI 1.1-3.0) and RA (HR = 2.0, CI 1.3-3.1). The Coonrad-Morrey (50%), Latitude (30%), Nexel (10%), and Discovery (9%) were the most used prosthesis designs. There was no difference in revision rates when these 4 designs were compared. The most common reasons for revision were infection (35%) and aseptic loosening (34%).Interpretation - The indications for primary and revision TEA in Australia are similar to those reported for other registries. Revision for trauma is lower than previously reported.

Genetic control of DNA methylation is largely shared across European and East Asian populations.

DNA methylation is an ideal trait to study the extent of the shared genetic control across ancestries, effectively providing hundreds of thousands of model molecular traits with large QTL effect sizes. We investigate cis DNAm QTLs in three European (n = 3701) and two East Asian (n = 2099) cohorts to quantify the similarities and differences in the genetic architecture across populations. We observe 80,394 associated mQTLs (62.2% of DNAm probes with significant mQTL) to be significant in both ancestries, while 28,925 mQTLs (22.4%) are identified in only a single ancestry. mQTL effect sizes are highly conserved across populations, with differences in mQTL discovery likely due to differences in allele frequency of associated variants and differing linkage disequilibrium between causal variants and assayed SNPs. This study highlights the overall similarity of genetic control across ancestries and the value of ancestral diversity in increasing the power to detect associations and enhancing fine mapping resolution.