Multi-state models and arthroplasty histories after unilateral total hip arthroplasties: Introducing the Summary Notation for Arthroplasty Histories

Background and purpose: An increasing number of patients have several joint replacement procedures during their lifetime. We investigated the use and suitability of multi-state model techniques in providing a more comprehensive analysis and description of complex arthroplasty histories held in arthroplasty registries than are allowed for with traditional survival methods. Patients and methods: We obtained data from the Australian Orthopaedic Association National Joint Replacement Registry on patients (n = 84,759) who had undergone a total hip arthroplasty for osteoarthritis in the period 2002–2008. We set up a multi-state model where patients were followed from their first recorded arthroplasty to several possible states: revision of first arthroplasty, either a hip or knee as second arthroplasty, revision of the second arthroplasty, and death. The Summary Notation for Arthroplasty Histories (SNAH) was developed in order to help to manage and analyze this type of data. Results: At the end of the study period, 12% of the 84,759 patients had received a second hip, 3 times as many as had received a knee. The estimated probabilities of having received a second arthroplasty decreased with age. Males had a lower transition rate for receiving a second arthroplasty, but a higher mortality rate. Interpretation: Multi-state models in combination with SNAH codes are well suited to the management and analysis of arthroplasty registry data on patients who experience multiple joint procedures over time. We found differences in the progression of joint replacement procedures after the initial total hip arthroplasty regarding type of joint, age, and sex.Marianne H Gillam, Philip Ryan, Amy Salter, Stephen E Grave

Competing risks survival analysis applied to data from the Australian Orthopaedic Association National Joint Replacement Registry

BACKGROUND AND PURPOSE: The Kaplan-Meier (KM) method is often used in the analysis of arthroplasty registry data to estimate the probability of revision after a primary procedure. In the presence of a competing risk such as death, KM is known to overestimate the probability of revision. We investigated the degree to which the risk of revision is overestimated in registry data. PATIENTS AND METHODS: We compared KM estimates of risk of revision with the cumulative incidence function (CIF), which takes account of death as a competing risk. We considered revision by (1) prosthesis type in subjects aged 75–84 years with fractured neck of femur (FNOF), (2) cement use in monoblock prostheses for FNOF, and (3) age group in patients undergoing total hip arthroplasty (THA) for osteoarthritis (OA). RESULTS: In 5,802 subjects aged 75–84 years with a monoblock prosthesis for FNOF, the estimated risk of revision at 5 years was 6.3% by KM and 4.3% by CIF, a relative difference (RD) of 46%. In 9,821 subjects of all ages receiving an Austin Moore (non-cemented) prosthesis for FNOF, the RD at 5 years was 52% and for 3,116 subjects with a Thompson (cemented) prosthesis, the RD was 79%. In 44,365 subjects with a THA for OA who were less than 70 years old, the RD was just 1.4%; for 47,430 subjects > 70 years of age, the RD was 4.6% at 5 years. INTERPRETATION: The Kaplan-Meier method substantially overestimated the risk of revision compared to estimates using competing risk methods when the risk of death was high. The bias increased with time as the incidence of the competing risk of death increased. Registries should adopt methods of analysis appropriate to the nature of their data.Marianne H. Gillam, Philip Ryan, Stephen E. Graves, Lisa N. Miller, Richard N. de Steiger and Amy Salte

Different competing risks models applied to data from the Australian Orthopaedic Association National Joint Replacement Registry

Purpose: Here we describe some available statistical models and illustrate their use for analysis of arthroplasty registry data in the presence of the competing risk of death, when the influence of covariates on the revision rate may be different to the influence on the probability (that is, risk) of the occurrence of revision. Patients and methods: Records of 12,525 patients aged 75–84 years who had received hemiarthroplasty for fractured neck of femur were obtained from the Australian Orthopaedic Association National Joint Replacement Registry. The covariates whose effects we investigated were: age, sex, type of prosthesis, and type of fixation (cementless or cemented). Extensions of competing risk regression models were implemented, allowing the effects of some covariates to vary with time. Results: The revision rate was significantly higher for patients with unipolar than bipolar prostheses (HR = 1.38, 95% CI: 1.01–1.89) or with monoblock than bipolar prostheses (HR = 1.45, 95% CI: 1.08–1.94). It was significantly higher for the younger age group (75–79 years) than for the older one (80–84 years) (HR = 1.28, 95% CI: 1.05–1.56) and higher for males than for females (HR = 1.37, 95% CI: 1.09–1.71). The probability of revision, after correction for the competing risk of death, was only significantly higher for unipolar prostheses than for bipolar prostheses, and higher for the younger age group. The effect of fixation type varied with time; initially, there was a higher probability of revision for cementless prostheses than for cemented prostheses, which disappeared after approximately 1.5 years. Interpretation: When accounting for the competing risk of death, the covariates type of prosthesis and sex influenced the rate of revision differently to the probability of revision. We advocate the use of appropriate analysis tools in the presence of competing risks and when covariates have time-dependent effects.Marianne H Gillam, Amy Salter, Philip Ryan, and Stephen E Grave

Diversity in collaborative research communities: a multicultural, multidisciplinary thesis writing group in public health

Writing groups for doctoral students are generally agreed to provide valuable learning spaces for Ph.D. candidates. Here an academic developer and the eight members of a writing group formed in a Discipline of Public Health provide an account of their experiences of collaborating in a multicultural, multidisciplinary thesis writing group. We consider the benefits of belonging to such a group for Ph.D. students who are operating in a research climate in which disciplinary boundaries are blurring and where an increasing number of doctoral projects are interdisciplinary in nature; in which both academic staff and students come from enormously diverse cultural and language backgrounds; and in which teamwork, networking and collaboration are prized but not always proactively facilitated. We argue that doctoral writing groups comprising students from diverse cultural and disciplinary backgrounds can be of significant value for postgraduates who wish to collaborate on their own academic development to improve their research writing and communication skills; at the same time, such collaborative work effectively builds an inclusive, dynamic research community.Cally Guerin, Vicki Xafis, Diana V. Doda, Marianne H. Gillam, Allison J. Larg, Helene Luckner, Nasreen Jahan, Aris Widayati and Chuangzhou X

Heart failure after conventional metal-on-metal hip replacements: A retrospective cohort study

Background and purpose — It is unclear whether metal particles and ions produced by mechanical wear and corrosion of hip prostheses with metal-on-metal (MoM) bearings have systemic adverse effects on health. We compared the risk of heart failure in patients with conventional MoM total hip arthroplasty (THA) and in those with metal-on-polyethylene (MoP) THA. Patients and methods — We conducted a retrospective cohort study using data from the Australian Government Department of Veterans’ Affairs health claims database on patients who received conventional THA for osteoarthritis between 2004 and 2012. The MoM THAs were classified into groups: Articular Surface Replacement (ASR) XL Acetabular System, other large-head (LH) (> 32 mm) MoM, and small-head (SH) (≤ 32 mm) MoM. The primary outcome was hospitalization for heart failure after THA. Results — 4,019 patients with no history of heart failure were included (56% women). Men with an ASR XL THA had a higher rate of hospitalization for heart failure than men with MoP THA (hazard ratio (HR) = 3.2, 95% CI: 1.6–6.5). No statistically significant difference in the rate of heart failure was found with the other LH MoM or SH MoM compared to MoP in men. There was no statistically significant difference in heart failure rate between exposure groups in women. Interpretation — An association between ASR XL and hospitalization for heart failure was found in men. While causality between ASR XL and heart failure could not be established in this study, it highlights an urgent need for further studies to investigate the possibility of systemic effects associated with MoM THA

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

Background: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number: NCT02184195

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

BACKGROUND: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). CONCLUSIONS: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. CLINCALTRIALS.GOV NUMBER: NCT02184195.status: publishe