Investigating a variance-components approach for linkage analysis in quantitative traits

Model-based linkage methods have had limited success in locating quantitative trait loci (QTLs) in complex traits since the underlying genetic mechanisms are not well known. As a result, robust or model-free approaches for detecting linkage have grown in popularity. We discuss a mixed effects model, which involves the estimation of genetic and non-genetic variance components, as well as recombination fractions. Using the Genometric Analysis Simulation Program (GASP), we first attempt to investigate the properties of this method on simple traits, which differ in terms of their variance components. To further understand its performance in a complex setting, we apply this method to simulated, familial data for an oligogenic disease with quantitative risk factors from the 10th Genetic Analysis Workshop (GAW10). We see that the ability of the variance-components approach to map QTLs depends on the amount of variability it contributes to the quantitative trait. As well, we find that the presence of the recombination fraction in the model results in consistent estimates of the variance components across the chromosome; however, it does not seem to improve the mapping ability of the model.Science, Faculty ofStatistics, Department ofGraduat

The burden of second hip fractures:provincial surgical hospitalizations over 15 years

BACKGROUND: Second hip fractures account for up to 15% of all hip fractures. We sought to determine if the proportion of hip fracture surgeries for second hip fracture changed over time in terms of patient and fracture characteristics. METHODS: We reviewed the records of patients older than 60 years hospitalized for hip fracture surgery between 1990 and 2005 in British Columbia. We studied the proportion of surgeries for second hip fracture among all hip fracture surgeries. Linear regression tested for trends across fiscal years for women and men. RESULTS: We obtained 46 341 patient records. Second hip fracture accounted for 8.3% of hip fracture surgeries. For women the proportion of second hip fracture surgeries increased linearly from 4% to 13% with each age decade (p = 0.001) and across fiscal years (p = 0.002). In men the proportion of second hip fracture surgeries was 5% for each age decade between the ages of 60 and 90 years across fiscal years, increasing to 8% for men older than 90 years across fiscal years (p = 0.20). These sex-specific trends were similar for both pertrochanteric and transcervical fracture types. CONCLUSION: Second hip fracture surgeries account for an increasing proportion of hip fracture surgeries and may require more health care resources to minimize poorer reported outcomes. Future research should determine whether more health care resources are required to manage these patients and optimize their outcomes

On reporting results from randomized controlled trials with recurrent events

Background: Evidence-based medicine has been advanced by the use of standards for reporting the design and methodology of randomized controlled trials (RCT). Indeed, without this information it is difficult to assess the quality of evidence from an RCT. Although a variety of statistical methods are available for the analysis of recurrent events, reporting the effect of an intervention on outcomes that recur is an area that remains poorly understood in clinical research. The purpose of this paper is to outline guidelines for reporting results from RCTs where the outcome of interest is a recurrent event. Methods: We used a simulation study to relate an event process and results from analyses of the gamma-Poisson, independent-increment, conditional, and marginal Cox models. We reviewed the utility of regression models for the rate of a recurrent event by articulating the associated study questions, preenting the risk sets, and interpreting the regression coefficients. Results: Based on a single data set produced by simulation, we reported and contrasted results from statistical methods for evaluating treatment effect from an RCT with a recurrent outcome. We showed that each model has different study questions, assumptions, risk sets, and rate ratio interpretation, and so inferences should consider the appropriateness of the model for the RCT. Conclusion: Our guidelines for reporting results from an RCT involving a recurrent event suggest that the study question and the objectives of the trial, such as assessing comparable groups and estimating effect size, should determine the statistical methods. The guidelines should allow clinical researchers to report appropriate measures from an RCT for understanding the effect of intervention on the occurrence of a recurrent event.Health Care and Epidemiology, Department ofPopulation and Public Health (SPPH), School ofNon UBCMedicine, Faculty ofReviewedFacult

The occurrence of adverse events in relation to time after registration for coronary artery bypass surgery: a population-based observational study

Background: Our objective was to evaluate the effect of delays on adverse events while waiting for coronary artery bypass grafting (CABG). Methods: An observational study that prospectively followed patients from registration on a wait list to removal for planned surgery, death while waiting, or unplanned emergency surgery. The population-based registry provided data on 12,030 patients with a record of registration on a wait list for first-time isolated CABG surgery between 1992 and 2005. Results: In total, 104 patients died and 382 patients underwent an emergency surgery before planned CABG. The death rate was 0.5 per 1000 patient-weeks in the semiurgent group and 0.6 per 1000 patient-weeks the nonurgent group, adjusted OR = 1.07 (95% confidence interval [CI] 0.69—1.65). The emergency surgery rate of 1.2 per 1000 patient-weeks in the nonurgent group was lower compared to 2.1 per 1000 patient-weeks in the semiurgent group (adjusted OR = 0.72, 95% CI 0.54–0.97). However, the nonurgent group had a greater cumulative incidence of preoperative death than the semiurgent group for almost all weeks on the wait list, adjusted OR = 1.92 (95% CI 1.25–2.95). The surgery rate was 1.2 per 1000 patient-weeks in the nonurgent group and 2.1 per 1000 patient-weeks in the semiurgent group, adjusted OR = 0.72 (95% CI 0.54–0.97). The cumulative incidence of emergency surgery before planned CABG was similar in the semiurgent and nonurgent groups, adjusted OR = 0.88, (95% CI 0.64–1.20). Conclusion: Despite similar death rates in the semiurgent and nonurgent groups, the longer waiting times in the nonurgent group result in a greater cumulative incidence of death on the wait list compared to that in the semiurgent group. These longer waiting times also offset the lower rate of emergency surgery before planned admission in the nonurgent group so that the cumulative incidence of the emergency surgery was similar in both groups.Other UBCNon UBCReviewedFacult

Health Care Evaluation Using Computer SimulationConcepts, Methods, and Applications /

XXVI, 406 p.online resource

Cumulative incidence for wait-list death in relation to length of queue for coronary-artery bypass grafting: a cohort study

Background: In deciding where to undergo coronary-artery bypass grafting, the length of surgical wait lists is often the only information available to cardiologists and their patients. Our objective was to compare the cumulative incidence for death on the wait list according to the length of wait lists at the time of registration for the operation. Methods The study cohort included 8966 patients who registered to undergo isolated coronary-artery bypass grafting (82.4% men; 71.9% semi-urgent; 22.4% non-urgent). The patients were categorized according to wait-list clearance time at registration: either "1 month or less" or "more than 1 month". Cumulative incidence for wait-list death was compared between the groups, and the significance of difference was tested by means of regression models. Results Urgent patients never registered on a wait list with a clearance time of more than 1 month. Semi-urgent patients registered on shorter wait lists more often than non-urgent patients (79.1% vs. 44.7%). In semi-urgent and non-urgent patients, the observed proportion of wait-list deaths by 52 weeks was lower in category "1 month or less" than in category "more than 1 month" (0.8% [49 deaths] vs. 1.6% [39 deaths], P < 0.005). After adjustment, the odds of death before surgery were 64% higher in patients on longer lists, odds ratio [OR] = 1.64 (95% confidence interval [CI] 1.02–2.63). The observed death rate was higher in category "more than 1 month" than in category "1 month or less", 0.79 (95%CI 0.54–1.04) vs. 0.58 (95% CI 0.42–0.74) per 1000 patient-weeks, the adjusted OR = 1.60 (95%CI 1.01–2.53). Longer wait times (log-rank test = 266.4, P < 0.001) and higher death rates contributed to a higher cumulative incidence for death on the wait list with a clearance time of more than 1 month. Conclusion Long wait lists for coronary-artery bypass grafting are associated with increased probability that a patient dies before surgery. Physicians who advise patients where to undergo cardiac revascularization should consider the risk of pre-surgical death that is associated with the length of a surgical wait list.Health Care and Epidemiology, Department ofNon UBCMedicine, Faculty ofReviewedFacult