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

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

Cortical Thinning in Patients with Recent Onset Post-Traumatic Stress Disorder after a Single Prolonged Trauma Exposure

Most of magnetic resonance imaging (MRI) studies about post-traumatic stress disorder (PTSD) focused primarily on measuring of small brain structure volume or regional brain volume changes. There were rare reports investigating cortical thickness alterations in recent onset PTSD. Recent advances in computational analysis made it possible to measure cortical thickness in a fully automatic way, along with voxel-based morphometry (VBM) that enables an exploration of global structural changes throughout the brain by applying statistical parametric mapping (SPM) to high-resolution MRI. In this paper, Laplacian method was utilized to estimate cortical thickness after automatic segmentation of gray matter from MR images under SPM. Then thickness maps were analyzed by SPM8. Comparison between 10 survivors from a mining disaster with recent onset PTSD and 10 survivors without PTSD from the same trauma indicates cortical thinning in the left parietal lobe, right inferior frontal gyrus, and right parahippocampal gyrus. The regional cortical thickness of the right inferior frontal gyrus showed a significant negative correlation with the CAPS score in the patients with PTSD. Our study suggests that shape-related cortical thickness analysis may be more sensitive than volumetric analysis to subtle alteration at early stage of PTSD

HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation