Variable selection under multiple imputation using the bootstrap in a prognostic study

Background: Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection. Method: In our prospective cohort study we merged data from three different randomized controlled trials (RCTs) to assess prognostic variables for chronicity of low back pain. Among the outcome and prognostic variables data were missing in the range of 0 and 48.1%. We used four methods to investigate the influence of respectively sampling and imputation variation: MI only, bootstrap only, and two methods that combine MI and bootstrapping. Variables were selected based on the inclusion frequency of each prognostic variable, i.e. the proportion of times that the variable appeared in the model. The discriminative and calibrative abilities of prognostic models developed by the four methods were assessed at different inclusion levels. Results: We found that the effect of imputation variation on the inclusion frequency was larger than the effect of sampling variation. When MI and bootstrapping were combined at the range of 0% (full model) to 90% of variable selection, bootstrap corrected c-index values of 0.70 to 0.71 and slope values of 0.64 to 0.86 were found. Conclusion: We recommend to account for both imputation and sampling variation in sets of missing data. The new procedure of combining MI with bootstrapping for variable selection, results in multivariable prognostic models with good performance and is therefore attractive to apply on data sets with missing values

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

PURPOSE: Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC). METHODS: This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions. RESULTS: In randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture. CONCLUSION: When making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease

The effects of a three-week use of lumbosacral orthoses on trunk muscle activity and on the muscular response to trunk perturbations

<p>Abstract</p> <p>Background</p> <p>The effects of lumbosacral orthoses (LSOs) on neuromuscular control of the trunk are not known. There is a concern that wearing LSOs for a long period may adversely alter muscle control, making individuals more susceptible to injury if they discontinue wearing the LSOs. The purpose of this study was to document neuromuscular changes in healthy subjects during a 3-week period while they regularly wore a LSO.</p> <p>Methods</p> <p>Fourteen subjects wore LSOs 3 hrs a day for 3 weeks. Trunk muscle activity prior to and following a quick force release (trunk perturbation) was measured with EMG in 3 sessions on days 0, 7, and 21. A longitudinal, repeated-measures, factorial design was used. Muscle reflex response to trunk perturbations, spine compression force, as well as effective trunk stiffness and damping were dependent variables. The LSO, direction of perturbation, and testing session were the independent variables.</p> <p>Results</p> <p>The LSO significantly (<it>P </it>< 0.001) increased the effective trunk stiffness by 160 Nm/rad (27%) across all directions and testing sessions. The number of antagonist muscles that responded with an onset activity was significantly reduced after 7 days of wearing the LSO, but this difference disappeared on day 21 and is likely not clinically relevant. The average number of agonist muscles switching off following the quick force release was significantly greater with the LSO, compared to without the LSO (<it>P </it>= 0.003).</p> <p>Conclusions</p> <p>The LSO increased trunk stiffness and resulted in a greater number of agonist muscles shutting-off in response to a quick force release. However, these effects did not result in detrimental changes to the neuromuscular function of trunk muscles after 3 weeks of wearing a LSO 3 hours a day by healthy subjects.</p

Stage T1c prostate cancer: defining the appropriate staging evaluation and the role for pelvic lymphadenectomy

A good staging system should be able to accurately reflect the natural history of a malignant disease, to express the extent of the disease at the time of diagnosis, and stratify patients in prognostically distinctive groups. The staging system for prostate cancer, as it is today, fails to fulfill these requirements. Approximately one third of the patients who undergo surgery for complete excision of prostate cancer in fact do not have a localize disease. The incidence of tumor at the inked margin may reach 30% for T1 stage and up to 60% for clinical T2b prostate cancer according to comparision with pathologic examination of resected specimen. Several concepts have been recently proposed as a means of improving the accuracy of the available staging system. In this paper, we review current aspects of clinical and pathological staging of prostate cancer, and the importance of these new concepts on the early stages of prostate cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47057/1/345_2005_Article_BF01300182.pd