Crosswalks between the Oxford hip and knee scores and the HOOS-12 and KOOS-12 instruments.

OBJECTIVE: To develop and validate bi-directional crosswalks between the Oxford Hip Score (OHS) and HOOS-12 summary impact score, and between the Oxford Knee Score (OKS) and KOOS-12 summary impact score. METHODS: Data were sourced from the Australian Orthopaedic Association National Joint Replacement Registry Patient-Reported Outcome Measures Program. Patients undergoing primary joint replacement for osteoarthritis who completed the OHS and HOOS-12 or OKS and KOOS-12 instruments were included in the analysis. An equipercentile method was used to create four crosswalks, with the distribution of scores smoothed using log-linear models prior to equating. Crosswalk validity was assessed through comparison of actual vs derived scores, Pearson correlation coefficients, root mean square errors (RMSE) and Bland-Altman plots. RESULTS: Paired OHS/HOOS-12 data and paired OKS/KOOS-12 data were available for 4,513 patients undergoing total hip replacement and 5,942 patients undergoing total knee replacement, respectively. Minimal differences were observed between actual and crosswalk-derived mean scores (actual OHS 27.55 vs derived OHS 27.56; actual HOOS-12 53.28 vs derived HOOS-12 53.31; actual OKS 27.34 vs derived OKS 27.34; actual KOOS-12 50.51 vs derived KOOS-12 50.58). High correlation was observed between actual and derived scores (Pearson's r for hip-specific instruments: 0.943-0.946; Pearson's r for knee-specific instruments: 0.925-0.931). Plotted actual vs mean derived scores also indicated robust concordance across the breadth of the instrument scales. CONCLUSION: These crosswalks provide close approximations of actual OHS, OKS, HOOS-12 and KOOS-12 scores, as indicated by multiple validation metrics. They offer a resource for clinicians, researchers and arthroplasty registries to support PROMs score conversion and data harmonisation efforts.

The burden of end-stage osteoarthritis in Australia: a population-based study on the incidence of total knee replacement attributable to overweight/obesity.

OBJECTIVES: To determine the risk of total knee replacement (TKR) for primary osteoarthritis (OA) associated with overweight/obesity in the Australian population. METHODS: This population-based study analyzed 191,723 cases of TKR collected by the Australian Orthopaedic Association National Joint Registry and population data from the Australian Bureau of Statistics. The time-trend change in incidence of TKR relating to BMI was assessed between 2015 and 2018. The influence of obesity on the incidence of TKR in different age and gender groups was determined. The population attributable fraction (PAF) was then calculated to estimate the effect of obesity reduction on TKR incidence. RESULTS: The greatest increase in incidence of TKR was seen in patients from obese class III. The incidence rate ratio for having a TKR for obesity class III was 28.683 at those aged 18-54 years but was 2.029 at those aged >75 years. Females in obesity class III were 1.7 times more likely to undergo TKR compared to similarly classified males. The PAFs of TKR associated with overweight or obesity was 35%, estimating 14,287 cases of TKR attributable to obesity in 2018. The proportion of TKRs could be reduced by 20% if overweight and obese population move down one category. CONCLUSIONS: Obesity has resulted in a significant increase in the incidence of TKR in the youngest population in Australia. The impact of obesity is greatest in the young and the female population. Effective strategies to reduce the national obese population could potentially reduce 35% of the TKR, with over 10,000 cases being avoided.

Implications for research and clinical use from a Rasch analysis of the HOOS-12 and KOOS-12 instruments.

OBJECTIVE: To evaluate the structural validity of the 12-item Hip disability and Osteoarthritis Outcome Score (HOOS-12) and 12-item Knee injury and Osteoarthritis Outcome Score (KOOS-12) using Rasch analysis and consider psychometric implications for research and clinical use. METHOD: Individual-level HOOS-12 and KOOS-12 data from the Australian Orthopaedic Association National Joint Replacement Registry, collected before and after primary total hip and knee replacement, were used for this analysis. Using the Rasch analytic approach, overall model fit and item fit were examined, together with potential reasons for misfit including response threshold ordering, differential item functioning, internal consistency, unidimensionality and item targeting. RESULTS: Overall misfit to the Rasch model was evident for both instruments. A degree of item misfit was also observed, although most items demonstrated logical sequencing of response options. Only two items (hip/knee pain frequency and awareness of hip/knee problems) displayed disordered response thresholds. The pain, function, and quality of life domains of the HOOS-12 and KOOS-12 demonstrated excellent internal consistency reliability (person separation index: 0.80-0.93) and unidimensionality. A mismatch between item difficulty and person ability scores at the highest end of the HOOS-12 and KOOS-12 scales contributed to post-operative ceiling effects (mean logit for HOOS-12: 3.57; KOOS-12: 2.58; ≈0 indicates well-targeted scale). CONCLUSION: We found evidence to support the structural validity of the three HOOS-12 and KOOS-12 domains for evaluating joint replacement outcomes. However, there may be missing content in both instruments particularly for high-functioning patients. Minor refinement of some response options may be warranted to improve item performance.

Performance of the HOOS-12 and KOOS-12 instruments for evaluating outcomes from joint replacement surgery.

OBJECTIVE: To evaluate the psychometric properties of the 12-item Hip disability and Osteoarthritis Outcome Score (HOOS-12) and Knee injury and Osteoarthritis Outcome Score (KOOS-12) for use in evaluating outcomes after joint replacement for osteoarthritis. DESIGN: Patient-reported outcomes data collected by the Australian Orthopaedic Association National Joint Replacement Registry were used for this analysis. HOOS-12 and KOOS-12 domain (pain, function, quality of life) and summary impact data were available. The Oxford Hip Score (OHS), Oxford Knee Score (OKS) and EQ-5D-5L were used as comparators. Instruments were administered pre-operatively and at 6 months post-operatively. Internal consistency reliability, floor and ceiling effects, convergent validity, known groups validity, and responsiveness were evaluated using standard psychometric techniques. RESULTS: Baseline HOOS-12 and KOOS-12 data were available for 3,023 patients undergoing primary total hip replacement and 4,010 patients undergoing primary total knee replacement. At baseline, high internal consistency was demonstrated for all domains and summary scores (Cronbach's alpha: HOOS-12 = 0.81-0.93; KOOS-12 = 0.82-0.92). Post-operative ceiling effects (>15% of patients scoring the best possible score) were identified for the HOOS-12 pain (46%), function (39%) and quality of life domains (26%) and summary score (17%), and for the KOOS-12 pain (21%) and function domains (18%). The HOOS-12 and KOOS-12 could differentiate between two known groups (lowest/highest OHS or OKS quartiles post-operatively; p < 0.001) and were highly responsive to change (effect sizes for HOOS-12: 2.20-2.83; KOOS-12: 1.82-2.35). CONCLUSION: The HOOS-12 and KOOS-12 have good psychometric properties for capturing joint replacement outcomes including excellent responsiveness, although ceiling effects may limit monitoring of post-operative improvement.

Predictors of total hip replacement in community based older adults: a cohort study.

OBJECTIVE: The purpose of this study is to describe predictors of total hip replacement (THR) in community dwelling older adults. A better understanding of predictors of THR can aid in triaging patients and researching preventative strategies. DESIGN: At baseline, participants had assessment of radiographic OA and cam morphology (from pelvic radiographs), shape mode scores and hip bone mineral density (BMD; from dual energy X-ray absorptiometry (DXA)). After 2.6 and 5 years, participants reported hip pain using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), and had hip structural changes assessed using magnetic resonance imaging (MRI). Risk of THR was analysed using mixed-effect Poisson regression. RESULTS: Incidence of THR for OA over 14 years was 4.6% (37/801). As expected, WOMAC hip pain and hip radiographic OA both predicted risk of THR. Additionally, shape mode 2 score (decreasing acetabular coverage) (RR 1.83/SD; 95% CI 1.1-3.04), shape mode 4 score (non-spherical femoral head) (RR 0.59/SD; 95% CI 0.36-0.96), cam morphology (α > 60°) (RR 2.2/SD; 95% CI 1.33-3.36), neck of femur BMD (RR 2.09/SD, 95% CI 1.48-2.94) and bone marrow lesions (BMLs) increased risk of THR (RR 7.10/unit; 95% CI 1.09-46.29). CONCLUSION: In addition to hip pain and radiographic hip OA, measures of hip shape, cam morphology, BMD and BMLs independently predict risk of THR. This supports the role of hip bone geometry and structure in the pathogenesis of end stage hip OA and has identified factors that can be used to improve prediction models for THR.

Q fever seroprevalence in Australia suggests one in twenty people have been exposed.

Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1-79 years in 2012-2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%-6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%-6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%-8.0%). More males were seropositive (6.9%; 95% CI 5.2%-8.6%) than females (4.2%; 95% CI 2.9%-5.5%) with peak seroprevalence at 50-59 years (9.2%; 95% CI 5.2%-13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.

Patellar tendon enthesis abnormalities and their association with knee pain and structural abnormalities in older adults.

OBJECTIVE: To describe associations between presence of patellar tendon enthesis (PTE) abnormalities and symptoms, structural abnormalities, and total knee replacement (TKR) in older adult cohort. METHODS: PTE abnormalities (presence of abnormal bone signal and/or bone erosion), were measured on T2-weighted magnetic resonance (MR) images at baseline in 961 community-dwelling older adults. Knee pain and function limitation were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Bone marrow lesions (BMLs), cartilage volume and defects score, and infrapatellar fat pad (IPFP) area were measured using validated methods. Incidence of TKR was determined by data linkage. RESULTS: Participants with abnormal PTE bone signal and/or erosion was 20%. Cross-sectionally, presence of PTE abnormalities was associated with greater pain intensity while going up and down stairs (ß = 0.22 (95% confidence interval (CI); 0.03, 0.41)), greater risk of femoral BMLs (RR = 1.46 (1.12, 1.90)) and worse tibial cartilage defects score (RR = 1.70 (1.16, 2.47), and smaller IPFP area (ß = -0.27 (-0.47, -0.06) cm2), after adjustment of confounders. Longitudinally, presence of baseline PTE abnormalities was associated with a deleterious increase in tibial BML size (RR = 1.52 (1.12, 2.05)) over 10.7 years but not symptoms, other structural changes, or TKR. CONCLUSION: PTE abnormalities are common in older adults. Presence of cross-sectional but not longitudinal associations suggests they are commonly co-exist with other knee structural abnormalities but may not play a major role in symptom development or structural change, excepting tibial BMLs.

Relationship of weight and obesity with the risk of knee and hip arthroplasty for osteoarthritis across different levels of physical performance: a prospective cohort study.

OBJECTIVE: To examine the association between obesity and knee and hip arthroplasty for osteoarthritis across a range of physical performance. METHOD: The body mass index and physical performance (on the 36-item Short Form Health Survey) of 9135 Australian Diabetes, Obesity and Lifestyle Study participants were measured in 1999-2000. The incidence of knee and hip arthroplasty during 2002-2011 was determined by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over 9.1 ± 2.3 years (mean ± sd)) of follow-up, 317 participants had knee and 202 had hip arthroplasty for osteoarthritis. Using those with neither obesity nor significantly impaired physical performance as the reference group, participants with both obesity and significantly impaired physical performance had a higher knee arthroplasty risk [hazard ratio (HR) = 5.25, 95% confidence interval (CI) 3.85-7.14] than those with obesity alone (HR = 2.49, 95% CI 1.81-3.44) or impaired physical performance alone (HR = 2.19, 95% CI 1.59-3.02). Similar results were observed for hip arthroplasty (obesity and impaired physical performance: HR = 2.67, 95% CI 1.72-4.15; obesity alone: HR = 1.65, 95% CI 1.08-2.51; impaired physical performance alone: HR = 1.83, 95% CI 1.26-2.66). Among overweight/obese patients, 5 kg greater baseline weight increased the knee arthroplasty risk across all levels of physical performance, and hip arthroplasty risk in those with the highest level of physical performance. CONCLUSION: Although impaired physical performance is an independent risk factor for knee and hip arthroplasty, greater weight increased knee arthroplasty for overweight/obese participants at all levels of physical performance, but hip arthroplasty only in those with good physical performance. Targeting weight loss has the potential to reduce the risk of knee arthroplasty and improve patient outcomes, even in those with poor physical performance.

Prevalence and changes in analgesic medication utilisation 1 year prior to total joint replacement in an older cohort of patients.

OBJECTIVES: To evaluate the prevalence and change in analgesic medications use prior to joint replacement in older patients between 2001 and 2012. METHODS: A population based epidemiological study was conducted. Opioids, non-steroidal anti-inflammatories (NSAIDs), paracetamol, corticosteroid injections, medications for neuropathic pain, hypnotics, and muscle relaxants supplied 1 year prior to total knee replacement (TKR, n = 15,517) and hip replacement (THR, n = 10,018) were assessed. Patient characteristics and surgical indication adjusted prevalence ratios (PRs) and 95% confidence intervals (CI) are provided. RESULTS: From 2001 to 2012, in the TKR cohort (median age 78.9) the prevalence of opioid use prior to surgery increased from 37% to 49% (PR = 1.01, 95% CI 1.00-1.01, P = 0.01), while in the THR cohort (median age 81.1) it increased from 44% to 54% (PR = 1.01, 95% CI 1.01-1.02, P < 0.001). Paracetamol use increased from 52% to 61% (PR = 1.0, 95% CI 1.0-1.0, P = 0.913) in the TKR cohort and from 55% to 67% (PR = 1.01, 95% CI 1.00-1.01, P = 0.005) in the THR cohort. Neuropathic pain medication use increased from 5% to 11% in the TKR cohort (PR = 1.04, 95% CI 1.02-1.06, P < 0.0001) and from 6% to 12% in the THR cohort (PR = 1.06, 95% CI 1.04-1.09, P < 0.0001). NSAID use decreased from 76% to 50% in the TKR cohort (PR = 0.96, 95% CI 0.95-0.96, P < 0.0001), and from 81% to 47% in THR cohort (PR = 0.95, 95% CI 0.94-0.95, P < 0.0001). Corticosteroid injections prevalence also decreased (TKR: 21-18%, PR = 0.97, 95% CI 0.96-0.97, P < 0.001, THR: 18-17%, PR = 0.97, 95% CI 0.96-0.98, P < 0.001). CONCLUSION: Pain medication utilization prior to joint replacement surgery changed significantly in this national older cohort of patients during the 2000s.

The association between ambulatory activity, body composition and hip or knee joint replacement due to osteoarthritis: a prospective cohort study.

OBJECTIVE: To examine the association between ambulatory activity (AA), body composition measures and hip or knee joint replacement (JR) due to osteoarthritis. DESIGN: At baseline, 1082 community-dwelling older-adults aged 50-80 years were studied. AA was measured objectively using pedometer and body composition by dual-energy X-ray absorptiometry. The incidence of primary (first-time) JR was determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). Log binomial regression with generalized estimating equations were used to estimate the risk of JR associated with baseline AA and body composition measures, adjusting for age, sex, X-ray disease severity, and pain. RESULTS: Over 13 years of follow-up, 74 (6.8%) participants had a knee replacement (KR) and 50 (4.7%) a hip replacement (HR). AA was associated with a higher risk of KR (RR 1.09/1000 steps/day, 95% CI 1.01, 1.16) and a lower risk of HR (RR 0.90/1000 steps/day, 95% CI 0.81, 0.99). Body mass index (BMI) (RR 1.07/kg/m2, 95% CI 1.03, 1.12), total fat mass (RR 1.03/kg, 95% CI 1.01, 1.06), trunk fat mass (RR 1.05/kg, 95% CI 1.00, 1.09), and waist circumference (RR 1.02/cm, 95% CI 1.00, 1.04) were associated with a higher risk of KR. Body composition measures were not associated with HR. CONCLUSIONS: An objective measure of AA was associated with a small increased risk of KR and a small reduced risk of HR. Worse body composition profiles were associated with KR, but not HR. Altogether this may suggest different causal pathways for each site with regard to habitual activity and obesity.

Polar methane accumulation and rainstorms on Titan from simulations of the methane cycle.

Titan has a methane cycle akin to Earth's water cycle. It has lakes in polar regions, preferentially in the north; dry low latitudes with fluvial features and occasional rainstorms; and tropospheric clouds mainly (so far) in southern middle latitudes and polar regions. Previous models have explained the low-latitude dryness as a result of atmospheric methane transport into middle and high latitudes. Hitherto, no model has explained why lakes are found only in polar regions and preferentially in the north; how low-latitude rainstorms arise; or why clouds cluster in southern middle and high latitudes. Here we report simulations with a three-dimensional atmospheric model coupled to a dynamic surface reservoir of methane. We find that methane is cold-trapped and accumulates in polar regions, preferentially in the north because the northern summer, at aphelion, is longer and has greater net precipitation than the southern summer. The net precipitation in polar regions is balanced in the annual mean by slow along-surface methane transport towards mid-latitudes, and subsequent evaporation. In low latitudes, rare but intense storms occur around the equinoxes, producing enough precipitation to carve surface features. Tropospheric clouds form primarily in middle and high latitudes of the summer hemisphere, which until recently has been the southern hemisphere. We predict that in the northern polar region, prominent clouds will form within about two (Earth) years and lake levels will rise over the next fifteen years.

Projected increase in total knee arthroplasty in the United States - an alternative projection model.

OBJECTIVE: The purpose of our study was to estimate the future incidence rate (IR) and volume of primary total knee arthroplasty (TKA) in the United States from 2015 to 2050 using a conservative projection model that assumes a maximum IR of procedures. Furthermore, our study compared these projections to a model assuming exponential growth, as done in previous studies, for illustrative purposes. METHODS: A population based epidemiological study was conducted using data from US National Inpatient Sample (NIS) and Census Bureau. Primary TKA procedures performed between 1993 and 2012 were identified. The IR, 95% confidence intervals (CI), or prediction intervals (PI) of TKA per 100,000 US citizens over the age of 40 years were calculated. The estimated IR was used as the outcome of a regression modelling with a logistic regression (i.e., conservative model) and Poisson regression equation (i.e., exponential growth model). RESULTS: Logistic regression modelling suggests the IR of TKA is expected to increase 69% by 2050 compared to 2012, from 429 (95%CI 374-453) procedures/100,000 in 2012 to 725 (95%PI 121-1041) in 2050. This translates into a 143% projected increase in TKA volume. Using the Poisson model, the IR in 2050 was projected to increase 565%, to 2854 (95%CI 2278-4004) procedures/100,000 IR, which is an 855% projected increase in volume compared to 2012. CONCLUSIONS: Even after using a conservative projection approach, the number of TKAs in the US, which already has the highest IR of knee arthroplasty in the world, is expected to increase 143% by 2050.

Substantial rise in the lifetime risk of primary total knee replacement surgery for osteoarthritis from 2003 to 2013: an international, population-level analysis.

OBJECTIVE: To estimate and compare the lifetime risk of total knee replacement surgery (TKR) for osteoarthritis (OA) between countries, and over time. METHOD: Data on primary TKR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of TKR was calculated for 2003 and 2013 using registry, life table and population data. RESULTS: Marked international variation in lifetime risk of TKR was evident, with females consistently demonstrating the greatest risk. In 2013, Finland had the highest lifetime risk for females (22.8%, 95%CI 22.5-23.1%) and Australia had the highest risk for males (15.4%, 95%CI 15.1-15.6%). Norway had the lowest lifetime risk for females (9.7%, 95%CI 9.5-9.9%) and males (5.8%, 95%CI 5.6-5.9%) in 2013. All countries showed a significant rise in lifetime risk of TKR for both sexes over the 10-year study period, with the largest increases observed in Australia (females: from 13.6% to 21.1%; males: from 9.8% to 15.4%). CONCLUSIONS: Using population-based data, this study identified significant increases in the lifetime risk of TKR in all five countries from 2003 to 2013. Lifetime risk of TKR was as high as 1 in 5 women in Finland, and 1 in 7 males in Australia. These risk estimates quantify the healthcare resource burden of knee OA at the population level, providing an important resource for public health policy development and healthcare planning.

Evaluation of three co-morbidity measures to predict mortality in patients undergoing total joint arthroplasty.

OBJECTIVE: To evaluate the 90 days and 1 year mortality predictive ability of the RxRisk-V, Charlson, and Elixhauser co-morbidity measures in total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. METHOD: A retrospective study of 11,848 THAs and 18,972 TKAs (2001-2002) was conducted. Death within 90 days and 1 year of the surgery were the main endpoints. Co-morbidity measures were calculated using either medication or hospitalisation history. Logistic regression models were employed and discrimination and calibration were assessed. Specifically, models with unweighted and weighted measure scores, models with the specific conditions, and a model combining conditions identified by all measures were assessed. RESULTS: In THAs, the best performing prediction models included co-morbidities from all three measures (90 days: c = 0.84, P = 0.284, 1 year: c = 0.79, P = 0.158). Individually, the model with Charlson conditions performed best at 90 days mortality (c = 0.80, P = 0.777) and the Charlson and Elixhauser performed similarly at 1 year (both c = 0.77, P > 0.05). In TKAs, the best performing prediction model included co-morbidities from all measures (90 days: c = 0.82, P = 0.349, 1 year: c = 0.78, P = 0.873). Individually, the model with Elixhauser conditions performed best with 90 days mortality (c = 0.79, P = 0.435) and all performed similarly at 1 year (c = 0.74-0.75, all P > 0.05). CONCLUSIONS: A combined model with co-morbidities identified by the Elixhauser, Charlson, and RxRisk-V was the best mortality prediction model. The RxRisk-V did not perform as well as the others. Because of the Elixhauser and Charlson's similar performance we suggest basing the choice of measurement use on factors such as the need of specific conditions and modelling limitations.

Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men.

OBJECTIVE: Few studies have examined the association between circulating sex steroid concentrations and risk of osteoarthritis (OA) in men with inconsistent results. Our aim was to examine whether concentrations of circulating sex steroid hormones were associated with the incidence of primary knee and hip arthroplasty for OA in a prospective cohort study. DESIGN: Two thousand four hundred and ninety four men from the Melbourne Collaborative Cohort Study (MCCS) had circulating sex steroid concentrations measured in blood samples drawn at recruitment (1990-1994) and stored in liquid nitrogen. The plasma concentrations of sex hormones, including dehydroepiandrosterone sulphate, androstenedione, testosterone, estradiol, androstanediol glucuronide, and sex hormone binding globulin, were measured. The incidence of total knee and hip arthroplasty for OA during 2001-2013 was determined by linking MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: One hundred and four men had knee and 80 had hip arthroplasty for OA over 10.7 (SD 3.8) years. Higher concentrations of androstenedione were associated with a decreased risk of total knee (hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.77-0.98) and hip (HR 0.84 95% CI 0.71-1.00) arthroplasty for OA in overweight and obese men. No significant association was observed for the other measured hormones. CONCLUSION: Low plasma androstenedione concentration is associated with an increased risk of both knee and hip arthroplasty for OA for overweight and obese men. While the findings need to be confirmed in other cohort studies, they suggest that circulating sex steroids may play a role in the pathogenesis of OA in men.

Association between serum concentration of 25-hydroxyvitamin D and the risk of hip arthroplasty for osteoarthritis: result from a prospective cohort study.

OBJECTIVES: There is ongoing debate regarding the optimal serum concentrations of 25-hydroxy-vitamin D for musculoskeletal health, including osteoarthritis (OA). The aim of this prospective cohort study was to determine whether serum 25-hydroxy-vitamin D concentrations were associated with the risk of hip arthroplasty for OA. DESIGN: This study examined 9135 participants from the Australian Diabetes, Obesity and Lifestyle Study who had serum 25-hydroxy-vitamin D measured in 1999-2000 and were aged ≥40 years at the commencement of arthroplasty data collection. The incidence of hip arthroplasty for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over an average 9.1 (standard deviation (SD) 2.7) years of follow-up, 201 hip arthroplasties for OA were identified (males n = 90; females n = 111). In males, a one-standard-deviation increase in 25-hydroxy-vitamin D was associated with a 25% increased incidence (HR 1.25, 95% CI 1.02-1.56), with a dose response relationship evident by quartiles of 25-hydroxy-vitamin D concentration (P for trend 0.04). These results were independent of age, body mass index (BMI), ethnicity, smoking status, physical activity, season of blood collection, latitude, hypertension and diabetes, area level disadvantage or after excluding those with extreme low 25-hydroxy-vitamin D concentrations. No significant association was observed in women (HR 1.10, 95% CI 0.87, 1.39). CONCLUSIONS: Increasing serum 25-hydroxy-vitamin D concentrations were associated with an increased risk of hip arthroplasty for OA in males, while no significant association was observed in females. The mechanism for the association warrants further investigation.

Retinal arteriolar narrowing and incidence of knee replacement for osteoarthritis: a prospective cohort study.

OBJECTIVES: The role of the microcirculation in the pathogenesis of osteoarthritis (OA) remains unclear. This prospective cohort study examined the association between retinal vascular calibre and incidence of knee replacement for OA. DESIGN: 1838 participants of the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study had retinal vascular calibre measured using a nonmydriatic digital fundus camera in 1999-2000 and were aged ≥ 40 years at joint replacement data collection commencement. The incidence of knee replacement for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). RESULTS: 77 participants underwent knee replacement for OA. They had narrower retinal arteriolar calibre compared with those without knee replacement (166.1 ± 24.8 µm vs 174.3 ± 24.5 µm, P = 0.004). For every one standard deviation reduction in retinal arteriolar calibre, the incidence of knee replacement increased by 25% (HR 1.25, 95% confidence interval (CI) 1.00-1.56). Participants in the narrower two-thirds of arteriolar calibre had twice the risk of knee replacement compared with those in the widest one-third (HR 2.00, 95% CI 1.07-3.74, P = 0.03) after adjustment for sex, body mass index (BMI), physical activity and HbA1c. There was no association for retinal venular calibre. CONCLUSIONS: Retinal arteriolar narrowing is associated with increased risk of knee replacement for OA suggesting that further work is warranted to determine the role of the microcirculation in the pathogenesis of knee OA.

Canine DLA-79 gene: an improved typing method, identification of new alleles and its role in graft rejection and graft-versus-host disease.

Developing a preclinical canine model that predicts outcomes for hematopoietic cell transplantation in humans requires a model that mimics the degree of matching between human donor and recipient major histocompatibility complex (MHC) genes. The polymorphic class I and class II genes in mammals are typically located in a single chromosome as part of the MHC complex. However, a divergent class I gene in dogs, designated dog leukocyte antigen-79 (DLA-79), is located on chromosome 18 while other MHC genes are on chromosome 12. This gene is not taken into account while DLA matching for transplantation. Though divergent, this gene shares significant similarity in sequence and exon-intron architecture with other class I genes, and is transcribed. Little is known about the polymorphisms of DLA-79 and their potential role in transplantation. This study was aimed at exploring the reason for high rate of rejection seen in DLA-matched dogs given reduced intensity conditioning, in particular, the possibility that DLA-79 allele mismatches may be the cause. We found that about 82% of 407 dogs typed were homozygous for a single, reference allele. Owing to the high prevalence of a single allele, 87 of the 108 dogs (∼80%) transplanted were matched for DLA-79 with their donor. In conclusion, we have developed an efficient method to type alleles of a divergent MHC gene in dogs and identified two new alleles. We did not find any statistical correlation between DLA-79 allele disparity and graft rejection or graft-versus-host disease, among our transplant dogs.

The progression of end-stage osteoarthritis: analysis of data from the Australian and Norwegian joint replacement registries using a multi-state model.

OBJECTIVE: The incidence of joint replacements is considered an indicator of symptomatic end-stage osteoarthritis (OA). We analysed data from two national joint replacement registries in order to investigate whether evidence of a pattern of progression of end-stage hip and knee OA could be found in data from large unselected populations. DESIGN: We obtained data on 78,634 hip and 122,096 knee arthroplasties from the Australian Orthopaedic Association National Joint Replacement Registry and 19,786 hip and 12,082 knee arthroplasties from the Norwegian Arthroplasty Register. A multi-state model was developed where individuals were followed from their first recorded hip or knee arthroplasty for OA to receiving subsequent hip and/or knee arthroplasties. We used this model to estimate relative hazard rates and probabilities for each registry separately. RESULTS: The hazard rates of receiving subsequent arthroplasties in non-cognate joints were higher on the contralateral side than on the ipsilateral side to the index arthroplasty, especially if the index was a hip arthroplasty. After 5 years, the estimated probabilities of having received a knee contralateral to the index hip were more than 1.7 times the probabilities of having received a knee ipsilateral to the index hip. CONCLUSION: The results indicate that there is an association between the side of the first hip arthroplasty and side of subsequent knee arthroplasties. Further studies are needed to investigate whether increased risk of receiving an arthroplasty in the contralateral knee is related to having a hip arthroplasty and/or preoperative factors such as pain and altered gait associated with hip OA.

Queensland tick typhus: three cases with unusual clinical features.

Queensland tick typhus (QTT), caused by Rickettsia australis, is usually a relatively mild illness but can occasionally be severe. We describe three cases of probable QTT with unusual clinical features, namely splenic infarction, fulminant myopericarditis and severe leukocytoclastic vasculitis. QTT may present with uncommon clinical features in addition to the more common manifestations. A high index of suspicion enables specific antibiotic therapy that may hasten recovery.