1,909 research outputs found

    Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone trials: secondary analysis of a randomized trial.

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    OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results

    Data Mining for Gene Networks Relevant to Poor Prognosis in Lung Cancer Via Backward-Chaining Rule Induction

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    We use Backward Chaining Rule Induction (BCRI), a novel data mining method for hypothesizing causative mechanisms, to mine lung cancer gene expression array data for mechanisms that could impact survival. Initially, a supervised learning system is used to generate a prediction model in the form of “IF <conditions> THEN <outcome>” style rules. Next, each antecedent (i.e. an IF condition) of a previously discovered rule becomes the outcome class for subsequent application of supervised rule induction. This step is repeated until a termination condition is satisfied. “Chains” of rules are created by working backward from an initial condition (e.g. survival status). Through this iterative process of “backward chaining,” BCRI searches for rules that describe plausible gene interactions for subsequent validation. Thus, BCRI is a semi-supervised approach that constrains the search through the vast space of plausible causal mechanisms by using a top-level outcome to kick-start the process. We demonstrate the general BCRI task sequence, how to implement it, the validation process, and how BCRI-rules discovered from lung cancer microarray data can be combined with prior knowledge to generate hypotheses about functional genomics

    A novel research definition of bladder health in women and girls: Implications for research and public health promotion

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    BACKGROUND:Bladder health in women and girls is poorly understood, in part, due to absence of a definition for clinical or research purposes. This article describes the process used by a National Institutes of Health funded transdisciplinary research team (The Prevention of Lower Urinary Tract Symptoms [PLUS] Consortium) to develop a definition of bladder health. METHODS:The PLUS Consortium identified currently accepted lower urinary tract symptoms (LUTS) and outlined elements of storage and emptying functions of the bladder. Consistent with the World Health Organization's definition of health, PLUS concluded that absence of LUTS was insufficient and emphasizes the bladder's ability to adapt to short-term physical, psychosocial, and environmental challenges for the final definition. Definitions for subjective experiences and objective measures of bladder dysfunction and health were drafted. An additional bioregulatory function to protect against infection, neoplasia, chemical, or biologic threats was proposed. RESULTS:PLUS proposes that bladder health be defined as: "A complete state of physical, mental, and social well-being related to bladder function and not merely the absence of LUTS. Healthy bladder function permits daily activities, adapts to short-term physical or environmental stressors, and allows optimal well-being (e.g., travel, exercise, social, occupational, or other activities)." Definitions for each element of bladder function are reported with suggested subjective and objective measures. CONCLUSIONS:PLUS used a comprehensive transdisciplinary process to develop a bladder health definition. This will inform instrument development for evaluation of bladder health promotion and prevention of LUTS in research and public health initiatives
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