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PubMed2002

Estimating the effective degrees of freedom in univariate multiple regression analysis.

The general linear model provides the most widely applied statistical framework for analyzing functional MRI (fMRI) data. With the increasing temporal resolution of recent scanning protocols, and more elaborate data preprocessing schemes, data independency is no longer a valid assumption. In this paper, we revise the statistical background of the general linear model in the presence of temporal autocorrelations. First, when detecting the activation signal, we explicitly account for the temporal autocorrelation structure, which yields a generalized F-test and the associated corrected (or effective) degrees of freedom (DOF). The proposed approach is data driven and thus independent of any specific preprocessing method. Then, for event-related protocols, we propose a new model for the temporal autocorrelations ("damped oscillator" model) and compare this model to another, previously used in the field (first-order autoregressive model, or AR(1) model). In the case of long fMRI time series, an efficient approximation for the number of effective DOF is provided for both models. Finally, the validity of our approach is assessed using simulated and real fMRI data and is compared with more conventional methods.

Analysis of Variance↗
PubMed2000

Are beta-blockers effective in patients who develop heart failure soon after myocardial infarction? A meta-regression analysis of randomised trials.

BACKGROUND: The great majority of post-infarction studies of beta-blockers were conducted in an era when these agents were widely held to be contra-indicated for the management of heart failure. We now know that beta-blockers are highly effective for the management of patients with chronic stable heart failure. However, there remains uncertainty about their role in the setting of post-infarction heart failure and ventricular dysfunction. AIM: the primary objective in this paper, was to investigate the extent to which heart failure or evidence of major cardiac dysfunction influenced outcome in previous trials of beta-blockers in heart failure after myocardial infarction. METHODS: We assessed the extent to which the inclusion of patients with heart failure or major cardiac dysfunction influenced outcome in randomised trials of long-term use of beta-blockade after myocardial infarction. The primary analysis was to assess the extent to which the proportion of patients included in each trial with heart failure influenced the relative odds of all-cause mortality in the trials. All randomised trials without crossover with treatment lasting more than one month and with 50 or more patients were considered. All those that provided information on the proportion of patients with heart failure or major cardiac dysfunction in the original or subsequent articles were included in the analysis. RESULTS: Overall treatment with a beta-blocker was associated with a 22.6% reduction in the odds of death (95% C1 11-32.3%). There were very few data on the effects of beta-blockers after myocardial infarction in patients with documented left ventricular systolic dysfunction. In the analysis that included heart failure as a factor, treatment with a beta-blocker was associated with a non-significant interaction with the presence of heart failure. However, because the group including heart failure patients were at higher risk, the absolute benefit of treatment with beta-blockers appeared greater in this group. CONCLUSIONS: This analysis suggests that the relative benefit of beta-blockers on mortality after a myocardial infarction is similar in the presence or absence of heart failure but that the absolute benefit may be greater in the former. However, as current clinical practice has changed radically from the time when the majority of these trials were conducted, further trial evidence would be desirable.

Adrenergic beta-Antagonists↗
PubMed2002

The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure-a meta-regression analysis.

AIMS: To review systematically the use of intravenous (IV) inotropic agents acting through the adrenergic signalling pathway, compared with placebo or an active agent, in patients with heart failure. METHODS: Studies investigating the use of intravenous inotropes in patients with heart failure published between 1966 and 2000 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. In total, 21 trials, that included 632 patients receiving IV inotropic drugs, placebo or non-treatment control, were identified. Drugs of the following classes were included, the beta-agonists; dobutamine, high-dose (>2.5 microg/kg/min) dopamine, dopexamine and the phosphodiesterase (PDE) inhibitors; amrinone, milrinone, enoximone and toborinone. Sixteen trials (474 patients) contributed data from acute invasive haemodynamic studies of symptomatically severe heart failure. Five trials (158 patients) were based on intermittent inotropic therapy in an outpatient context. RESULTS: With few exceptions, trials of intravenous inotropic agents were small and often failed to report clinically important outcomes. Compared to placebo, intravenous inotropic agents acting through the adrenergic system tended to increase mortality (odds ratio 1.50 (95% CI=0.51 to 3.92) but this did not reach significance and insufficient data were available to determine whether symptoms improved. There appeared to be little difference in the effect of beta-agonists compared to PDE inhibitors on patient outcomes but this could be attributed to the paucity of data. CONCLUSIONS: Intravenous inotropic agents acting through the adrenergic pathway are often used in patients with worsening heart failure to achieve arbitrary haemodynamic targets. Our analyses show that there is very little evidence that such treatment improves symptoms or patient outcomes and may not be safe. This highlights the need for further well designed randomised clinical trials.

Adrenergic beta-Agonists↗
PubMed2006

General and disease-specific risk factors for depression after ischemic stroke: a two-step Cox regression analysis.

BACKGROUND: Post-stroke depression (PSD) frequently complicates stroke and is associated with an impaired functional outcome, more severe cognitive deficits, a reduced quality of life, and a higher mortality. The aim of this study was to assess whether general risk factors for major depressive disorder (MDD) in the community are also risk factors for PSD, and to identify additional, stroke-related risk factors. METHODS: In a hospital setting, 190 consecutively admitted patients were assessed for MDD 1 month after stroke, and at follow-up after 3, 6, 9 and 12 months. A Cox model was created with four established risk factors for MDD in the community (female sex, prior personal history of depression, positive family history of depression, and somatic comorbidity other than stroke). Five potential disease-related risk factors (disability, cognitive deterioration, inter- and intrahemispheric lesion location, and generalized vascular damage on computed tomography (CT) scan) were then added individually to this model, to see whether these would improve the significance of the overall model. RESULTS: The Cox model of four general risk factors for depression in the community was shown to be a valid model to predict depression in stroke patients. Of the disease-specific factors, only incorporation of "disability" in this model improved its significance. CONCLUSION: Established risk factors for depression in the community are also predictors of depression in the first year after stroke. Disability is a non-specific disease-related variable that is associated with PSD. The contribution of stroke-specific factors may be less than is generally assumed.

Age Factors↗
PubMed1988

A regression analysis of prognostic factors after resection of Dukes' B and C carcinoma of the rectum and rectosigmoid. Does post-operative radiotherapy change the prognosis?

The prognostic value of several clinical and histopathological characteristics has been evaluated in patients with Dukes' B and C carcinoma of the rectum and the rectosigmoid. Data on 260 Dukes' B and 208 Dukes' C tumours entered into a prospective, randomized clinical trial of post-operative radiotherapy (50 Gy given with 2 Gy/fraction in an overall time of 7 weeks) were analyzed by means of the Cox proportional hazards model. The Dukes' stages B and C were analyzed in two separate multivariate analyses. In patients with Dukes' B tumours, a poor prognosis was associated with age above 60, perineural and venous invasion, tumour located less than 10 cm from the anal verge and elevated pre-operative carcinoembryonic antigen (CEA) (greater than 3.2 ng ml-1). In patients with Dukes' C tumours, perineural and venous invasion, tumour located less than 10 cm from the anal verge, and elevated pre-operative CEA were associated with a poor prognosis. In addition, a large tumour diameter had a strong, negative influence on the prognosis. Males seemed to have a poorer prognosis than females among the Dukes' C patients. Resection of neighbouring organs was also associated with a poor prognosis in this stage. Post-operative radiotherapy as administered in the present series had no significant influence on prognosis. Based on the derived prognostic models patients with a hazard of death above the median in each stage were selected. A separate analysis of the survival in these high risk patients showed no survival benefit from radiotherapy. The proportional hazards model may be a useful tool in selecting patients for more aggressive adjuvant treatment.

Age Factors↗
PubMed1998

Clinical and pharmacokinetic risk factors for high-dose methotrexate-induced toxicity in children with acute lymphoblastic leukemia--a logistic regression analysis.

The clinical and pharmacokinetic risk factors for toxicity after high-dose methotrexate (MTX) in children with acute lymphoblastic leukemia were evaluated using a multivariate statistical analysis. Plasma samples were collected after 44 24-h infusions of MTX (5 or 8 g/m2) in 13 children (age 3.3-12.9 years) and subsequently analyzed by HPLC to determine the MTX and 7-hydroxymethotrexate (7-OHMTX) concentrations. Toxicity was evaluated according to the WHO criteria. Severe toxicity was not observed. Oral mucositis (WHO grade > or = 1) was significantly related to a high plasma MTX concentration at 28 h after starting the infusion (p = 0.013), a low ratio of plasma 7-OHMTX/MTX at 66 h after starting the infusion (p = 0.049), and a slow clearance of MTX (p = 0.048). The risk of leukopenia (WHO grade > or = 2) increased significantly with the number of courses (p = 0.02). Increasing age and a long exposure to a high MTX concentration in plasma (AUC) were significant risk factors (p = 0.047 and p = 0.009, respectively) for developing elevated liver enzymes (ALAT) (WHO grade > or = 2). This study shows how a statistical model can be used to identify clinical and pharmacokinetic factors that may influence MTX-induced toxicity. The therapeutic ratio could thereby potentially be improved.

Bone Marrow↗
PubMed2004

What determines compulsory community treatment? A logistic regression analysis using linked mental health and offender databases.

OBJECTIVE: Western Australia has one of the highest published rates of the use of compulsory treatment orders in the English-speaking world. Differences in patient characteristics, legislation and service setting may explain variations in the reported efficacy of compulsory community treatment. Our objective is to investigate predictors of Community Treatment Orders (CTO) placement in the first year of implementation in Western Australia and see if there were any differences in the type of patients placed on these orders compared to other studies. METHOD: A population-based record linkage study of Mental Health and Offender Databases comparing 265 patients on CTOs with a consecutive control group (CCG) of equal number matched on date of discharge from inpatient care or CTO placement. RESULTS: Previous health service use, after-care placement, mental disorder history including schizophrenic history, a positive forensic history of violence to others as well as patient's marital status were the significant predictors of CTO placement. CONCLUSIONS: Studies of compulsory community treatment appear to be of similar populations. In spite of the comparatively high rate of use, psychiatrists in Western Australia do not appear to be applying community treatment orders to different types of patient compared to elsewhere. We need further research to establish the relative contribution of patient characteristics, legislation and service setting toward the use and outcome of compulsory community treatment.

Adult↗