Adaptation of the robust method to large distributions of reference values: program modifications and comparison of alternative computational methods.

The objective of this research was to compute reference limits using reference values from patients entering pharmaceutical development clinical trials by the nonparametric method and the robust method of Horn and Pesce, with and without outlier exclusion, and compare the methods with respect to influence on the limits. Reference limits were computed for 38 analytes with over 130,000 subjects contributing reference values. Subjects were partitioned into 10 demographic strata for limit computation.

Reference Limits for Outlier Analyses in Randomized Clinical Trials.

Background: Reference limits used in clinical medicine to screen and manage patients are typically developed nonparametrically using reference values from a limited number of healthy subjects using a 95th percentile reference interval. We have evaluated alternative methods of computation and the resulting limits for use in the analyses of treatment-emergent outliers in clinical trials.

Methods: We developed a set of alternative reference limits for 38 laboratory analytes based on alternative statistical methods and assessed their relative performance in clinical trial analysis.

Relationship between drain volume/fill volume ratio and clinical outcomes associated with overfill complaints in peritoneal dialysis patients.

Background: To better understand the spectrum of overfill reports and their corresponding clinical severity and etiology, we conducted a review of overfill reports from the Manufacturer and User Facility Device Experience (MAUDE) database, which is within the Food and Drug Administration (FDA) Web site (www.fda.gov).

Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study.

Background: CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer biomarkers. Except for CA125, their behavior in the prediagnostic period has not been evaluated.

Methods: Immunoassays were used to determine concentrations of CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in prediagnostic serum specimens (1-11 samples per participant) that were contributed 0-18 years before ovarian cancer diagnosis from 34 patients with ovarian cancer (15 with advanced-stage serous carcinoma) and during a comparable time interval before the reference date from 70 matched control subjects who were participating in the Carotene and Retinol Efficacy Trial.

A combined crystalloid and colloid pd solution as a glucose-sparing strategy for volume control in high-transport apd patients: a prospective multicenter study.

Background: Evidence is accumulating that the continuous exposure to high glucose concentrations during peritoneal dialysis (PD) is an important cause of ultrafiltration (UF) failure. The cornerstone of prevention and treatment of UF failure is reduction of glucose exposure, which will also alleviate the systemic impact of significant free glucose absorption. The challenge for the future is to discover new therapeutic strategies to enhance fluid and sodium removal while diminishing glucose load and exposure using combinations of available osmotic agents.

Low-fat, increased fruit, vegetable, and grain dietary pattern, fractures, and bone mineral density: the Women's Health Initiative Dietary Modification Trial.

Background: The effects of dietary changes on osteoporosis, low bone density, and frequent falls are unestablished.

Objective: We assessed the effect of the Women's Health Initiative Dietary Modification low-fat and increased fruit, vegetable, and grain intervention on incident hip, total, and site-specific fractures and self-reported falls, and, in a subset, on bone mineral density (BMD).

Design: Postmenopausal women (n = 48,835) aged 50-79 y (18.

Homocysteine levels and risk of hip fracture in postmenopausal women.

Background: Recent studies suggest that high homocysteine levels are associated with an increased risk of fractures. Homocysteine levels are known to be influenced by vitamin B and folate supply or status, and poor renal function can result in higher levels independent of nutritional adequacy.

Objective: The aim of the study was to determine the associations between fasting homocysteine levels and incident hip fractures, and the effects of other factors on hip fracture risk.

Conjugated equine estrogens and colorectal cancer incidence and survival: the Women's Health Initiative randomized clinical trial.

Background: In separate Women's Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine the survival of women following colorectal cancer diagnosis in the latter trial.

Participants And Methods: 10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.

Serum 25-hydroxyvitamin D concentrations and risk for hip fractures.

Background: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D] concentration and hip fractures is unclear.

Objective: To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women.

Design: Nested case-control study.

Cystatin-C, renal function, and incidence of hip fracture in postmenopausal women.

Objectives: To evaluate the association between chronic kidney disease and incident hip fracture using serum cystatin-C as a biomarker of renal function calculated without reference to muscle mass.

Design: Case-control study nested within a prospective study.

Setting: The Women's Health Initiative Observational Study conducted at 40 U.

Lipoprotein particle concentrations may explain the absence of coronary protection in the women's health initiative hormone trials.

Objective: The Women's Health Initiative randomized hormone trials unexpectedly demonstrated an increase in early coronary events. In an effort to explain this finding, we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case-control substudy.

Methods And Results: We randomized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.

Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal women.

Context: Endogenous estradiol, testosterone, and SHBG may influence the risk of hip fracture.

Design And Methods: From the Women's Health Initiative Observational Study, 39,793 eligible postmenopausal women did not have a previous hip fracture and were not using estrogen or other bone-active therapies. Of these, 400 who had a first-time nonpathological hip fracture (median follow-up, 7 yr) were matched to 400 controls by age, ethnicity, and baseline blood draw date.

Relation of demographic factors, menstrual history, reproduction and medication use to sex hormone levels in postmenopausal women.

In postmenopausal women, levels of estrogens, androgens, and perhaps prolactin have been related to risk of breast and other hormonal cancers in women. However, the determinants of these hormone concentrations have not been firmly established. Associations among various demographic, menstrual, and reproductive factors, medication use and endogenous sex hormone concentrations (estradiol, free estradiol, estrone, estrone sulfate, testosterone, free testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), dihydrotestosterone, and prolactin) were evaluated in a cross-sectional analysis from a simple random sample of 274 postmenopausal women selected from the Women's Health Initiative Dietary Modification Trial.

Clinical risk factors for fractures in multi-ethnic women: the Women's Health Initiative.

Unlabelled: To identify risk factors for fractures in multi-ethnic women, we studied 159,579 women enrolled in the Women's Health Initiative. In general, risk factors for fractures were similar across ethnic groups. However, irrespective of their ethnicity, women with multiple risk factors have a high risk of fracture.

Predictors of dietary change and maintenance in the Women's Health Initiative Dietary Modification Trial.

Objective: To identify predictors of dietary change to and maintenance of a low-fat eating pattern (<20% energy from fat, > or = 5 servings fruits/vegetables daily, and > or = 6 servings grains daily) among a cohort of postmenopausal women. Candidate predictors included intrapersonal, interpersonal, intervention program characteristics, and clinical center.

Design: Longitudinal study within the Women's Health Initiative Dietary Modification Trial.

Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause.

Context: The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.

Objective: To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.

Design, Setting, And Participants: Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo.

Prehypertension and cardiovascular disease risk in the Women's Health Initiative.

Background: Prehypertension is common and is associated with increased vascular mortality. The extent to which it increases risk of nonfatal myocardial infarction, stroke, and congestive heart failure is less clear.

Methods And Results: We determined the prevalence of prehypertension, its association with other coronary risk factors, and the risk for incident cardiovascular disease events in 60,785 postmenopausal women during 7.

Relation of BMI and physical activity to sex hormones in postmenopausal women.

Objective: Levels of estrogen, androgen, and prolactin have been related to risk of postmenopausal breast cancer. However, the determinants of these hormone concentrations are not established. The purpose of this study was to examine correlates of endogenous sex hormones.

Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative.

Objective: To determine the effect of hormone therapy on arthroplasty rates.

Methods: We examined data from the Women's Health Initiative placebo-controlled, double-blind, randomized trials. Community-dwelling women ages 50-79 years were enrolled at 40 US clinics.

The association between aspirin use and the incidence of colorectal cancer in women.

The purpose of this study was to test the hypothesis that aspirin use is associated with a decreased risk of incident colorectal cancer. From the Women's Health Initiative, 91,574 participants between the ages of 50 and 79 years at baseline in 1993-1998 provided details on aspirin use via interview using a standardized questionnaire and were subsequently followed annually for incident colorectal cancer during a period of over 6 years. For those persons who reported aspirin use, the type of compound, dose, and duration of use were recorded.

Conjugated equine estrogens and peripheral arterial disease risk: the Women's Health Initiative.

Background: Estradiol reduced progression of ultrasonographic carotid disease in a randomized trial. No trials of unopposed estrogen for prevention of lower extremity arterial disease or aortic aneurysm have been conducted.

Methods: The Estrogen Alone trial randomized 10739 postmenopausal women with prior hysterectomy, mean age 63.

The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature.

Study Objectives: Conditions that give rise to reduced lung function are frequently associated with low-grade systemic inflammation, which may lead to poor cardiovascular outcomes. We sought to determine the relationship between reduced FEV1 and cardiovascular mortality, independent of smoking.

Design: Longitudinal population-based study and a meta-analysis of literature.

Factors influencing in-hospital mortality in community-acquired pneumonia: a prospective study of patients not initially admitted to the ICU.

Purposes: To determine the factors that predict in-hospital mortality among patients who require hospitalization for the treatment of community-acquired pneumonia (CAP).

Study Design: Prospective observational study of all patients who were admitted to six hospitals in Edmonton, AL, Canada, with a diagnosis of CAP from November 15, 2000, to November 14, 2002. Pneumonia was defined as two or more respiratory symptoms and signs and an opacity on a chest radiograph as interpreted by the attending physician.

Comparing short form 6D, standard gamble, and Health Utilities Index Mark 2 and Mark 3 utility scores: results from total hip arthroplasty patients.

Objectives: The objectives are to compare SF-6D, standard gamble (SG), and Health Utilities Index (HUI) utility scores, compare change scores, and compare responsiveness.

Methods: A cohort of osteoarthritis patients referred for total hip arthroplasty (THA) were evaluated at the time of referral and followed until 3 months after THA. Patients were assessed using the SF-36, HUI2, HUI3, and the SG.