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W Applegate

Publications and source records attributed to W Applegate.

15 recordsLinked to original sources
PubMed2001

Effects of hormone replacement therapy on clinical fractures and height loss: The Heart and Estrogen/Progestin Replacement Study (HERS).

PURPOSE: To determine if estrogen plus progestin reduces the incidence of fractures or height loss in postmenopausal women with coronary disease. SUBJECTS AND METHODS: We enrolled 2,763 postmenopausal women with coronary disease and with an intact uterus into the Heart Estrogen/progestin Replacement Study, a randomized double-blind, placebo-controlled secondary prevention trial of cardiovascular disease. Radiographically documented clinical fractures were a prespecified secondary endpoint. Height loss was used as a surrogate for vertebral fractures. The average age of the women was 66.7 +/- 6.7 years, and fewer than 15% of the women had osteoporosis based on their bone density. Women were randomly assigned to either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n = 1,380) or placebo (n = 1,383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 64% at the end of the study. RESULTS: During 10,554 person years of follow-up, 286 women experienced a fracture: 138 in the treatment group (26.3 per 1,000 person years) and 148 in the placebo group (28.0 per 1,000 person years); relative hazard, 0.94; 95% confidence interval 0.8 to 1.2, P = 0.61). These included 58 wrist fractures (1.01; 0.6 to 1.7); 27 hip fractures (1.09; 0.5 to 2.3); 32 spine fractures (0.69; 0.3 to 1.4), and 192 other fractures (0.91; 0.7 to 1.2). There was no difference in average height loss between the treatment and placebo groups or in the percent of women who lost more than 2 cm in height: 10.6% in the treatment group and 12.1% in the placebo group. CONCLUSIONS: There was no evidence of a reduction in the incidence of fractures or rate of height loss in older women not selected for osteoporosis. Randomized studies are needed to clarify the effect of hormone replacement therapy on fracture risk among women with and without osteoporosis.

Aged↗
PubMed2001

Postmenopausal hormones and incontinence: the Heart and Estrogen/Progestin Replacement Study.

OBJECTIVE: To determine whether postmenopausal hormone therapy improves the severity of urinary incontinence. METHODS: We included measures of incontinence and voiding frequency in the Heart and Estrogen/Progestin Replacement Study, a randomized, blinded trial of the effect of hormone therapy among 2763 postmenopausal women younger than 80 years with coronary disease and intact uteri. This report includes 1525 participants who reported at least one episode of incontinence per week at baseline. Participants were randomly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate in one tablet daily (n = 768) or placebo (n = 757) and were followed for a mean of 4.1 years. Severity of incontinence was classified as improved (decrease of at least two episodes per week), unchanged (change of at most one episode per week), or worsened (increase of at least two episodes per week). RESULTS: Incontinence improved in 26% of the women assigned to placebo compared with 21% assigned to hormones, while 27% of the placebo group worsened compared with 39% of the hormone group (P =.001). This difference was evident by 4 months of treatment and was observed for both urge and stress incontinence. The number of incontinent episodes per week increased an average of 0.7 in the hormone group and decreased by 0.1 in the placebo group (P <.001). CONCLUSION: Daily oral estrogen plus progestin therapy was associated with worsening urinary incontinence in older postmenopausal women with weekly incontinence. We do not recommend this therapy for the treatment of incontinence.

Drug Combinations↗
PubMed2000

Editor's note.

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Duplicate Publications as Topic↗
PubMed1999

Rationale and design of the Arterial Disease Multiple Intervention Trial (ADMIT) pilot study.

The primary objectives of the pilot study were to: (1) evaluate the feasibility of recruiting patients with peripheral arterial disease (PAD); (2) measure the efficacy and safety of high-density lipoprotein (HDL)-raising treatment, low-density lipoprotein (LDL)-lowering therapy, antioxidant therapy, antithrombotic therapy, and their combinations; and (3) assess adherence to a complex multiple drug regimen. Secondary objectives included measurement of the effect of the interventions on prespecified biochemical markers, maintenance of therapy masking (in particular with niacin), and measurement of the intervention's impact on functional status and on quality of life. To date, no secondary prevention trial has been conducted specifically among patients with PAD. Intermittent claudication affects about 0.5% to 1.0% of persons aged >35 years. There is a striking increase in incidence of PAD with age, particularly among those aged >50 years in both sexes, although men are twice as likely as women to develop PAD. The Arterial Disease Multiple Intervention Trial was a double-blind randomized pilot trial of 468 participants with documented PAD. A 2 x 2 x 2 factorial design was used to evaluate the effect of 3 interventions. The pilot incorporated several major novel design features: first, the use of a simple noninvasive method (measurement of ankle brachial index) to identify a population with either symptomatic or asymptomatic PAD; and second, a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as needed in the intervention and control group. Two other arms, the antioxidant arm (consisting of beta-carotene and vitamins E and C) and the antithrombotic arm (using warfarin) were also added. Adherence to therapy was measured by pill count, and success in treatment was measured by the proportion of values in target range for HDL, LDL, and the international normalized ratio.

Adult↗
PubMed1998

Heart and Estrogen/progestin Replacement Study (HERS): design, methods, and baseline characteristics.

The Heart and Estrogen/progestin Replacement Study (HERS) is a randomized, double-blind, placebo-controlled trial designed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease (CHD) events in women. The participants are postmenopausal women with a uterus and with CHD as evidenced by prior myocardial infarction, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or other mechanical revascularization or at least 50% occlusion of a major coronary artery. Between February 1993 and September 1994, 20 HERS centers recruited and randomized 2763 women. Participants ranged in age from 44 to 79 years, with a mean age of 66.7 (SD 6.7) years. Most participants were white (89%), married (57%), and had completed high school or some college (80%). As expected, the prevalence of coronary risk factors was high: 62% were past or current smokers, 59% had hypertension, 90% had serum LDL-cholesterol of 100 mg/dL or higher, and 23% had diabetes. Each woman was randomly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo. Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events (CHD death and nonfatal myocardial infarction). We will also assess other major CHD endpoints, including revascularization and hospitalization for unstable angina. The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo. The trial was designed to have power greater than 90% to detect a 35% reduction in the incidence of CHD events, assuming a 50% lag in effect for 2 years and a 5% annual event rate in the placebo group. The design, analysis, and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California, San Francisco. HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events.

Aged↗
PubMed1997

A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST).

OBJECTIVE: To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis. SETTING AND DESIGN: A randomized, single-blind clinical trial lasting 18 months conducted at 2 academic medical centers. PARTICIPANTS: A total of 439 community-dwelling adults, aged 60 years or older, with radiographically evident knee osteoarthritis, pain, and self-reported physical disability. INTERVENTIONS: An aerobic exercise program, a resistance exercise program, and a health education program. MAIN OUTCOME MEASURES: The primary outcome was self-reported disability score (range, 1-5). The secondary outcomes were knee pain score (range, 1-6), performance measures of physical function, x-ray score, aerobic capacity, and knee muscle strength. RESULTS: A total of 365 (83%) participants completed the trial. Overall compliance with the exercise prescription was 68% in the aerobic training group and 70% in the resistance training group. Postrandomization, participants in the aerobic exercise group had a 10% lower adjusted mean (+/- SE) score on the physical disability questionnaire (1.71 +/- 0.03 vs 1.90 +/- 0.04 units; P<.001), a 12% lower score on the knee pain questionnaire (2.1 +/- 0.05 vs 2.4 +/- 0.05 units; P=.001), and performed better (mean [+/- SE]) on the 6-minute walk test (1507 +/- 16 vs 1349 +/- 16 ft; P<.001), mean (+/-SE) time to climb and descend stairs (12.7 +/- 0.4 vs 13.9 +/- 0.4 seconds; P=.05), time to lift and carry 10 pounds (9.1 +/- 0.2 vs 10.0 +/- 0.1 seconds; P<.001), and mean (+/-SE) time to get in and out of a car (8.7 +/- 0.3 vs 10.6 +/- 0.3 seconds; P<.001) than the health education group. The resistance exercise group had an 8% lower score on the physical disability questionnaire (1.74 +/- 0.04 vs 1.90 +/- 0.03 units; P=.003), 8% lower pain score (2.2 +/- 0.06 vs 2.4 +/- 0.05 units; P=.02), greater distance on the 6-minute walk (1406 +/- 17 vs 1349 +/- 16 ft; P=.02), faster times on the lifting and carrying task (9.3 +/- 0.1 vs 10.0 +/- 0.16 seconds; P=.001), and the car task (9.0 +/- 0.3 vs 10.6 +/- 0.3 seconds; P=.003) than the health education group. There were no differences in x-ray scores between either exercise group and the health education group. CONCLUSIONS: Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability, physical performance, and pain from participating in either an aerobic or a resistance exercise program. These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis.

Activities of Daily Living↗
PubMed1996

Estimation of VO2 in older individuals with osteoarthritis of the knee and cardiovascular disease.

The American College of Sports Medicine (ACSM) equation for estimating oxygen consumption (VO2) is often inappropriately applied to non-steady-state treadmill exercise. Therefore, it was the purpose of this investigation to develop an equation to estimate VO2 that could be applied to non-steady-state treadmill exercise in a population of patients with osteoarthritis of the knee, and to assess the generalizability of this equation for estimating VO2peak in patients with cardiovascular disease. Subjects for the investigation were 414 participants in the Fitness and Arthritis in Seniors Trial (FAST), and 362 patients with cardiovascular disease. Results from the FAST subjects showed that the ACSM equation was inappropriate for estimating VO2 during non-steady-state incremental treadmill walking. We developed the following equation (FAST) using speed and the interaction between speed and grade as the predictor variables during treadmill walking: VO2(ml.kg-1.min-1) = 0.0698 x speed(m.min-1) + 0.8147 x grade(%) x speed(m.min-1) + 7.533 ml.kg-1.min-1 The generalizability of the FAST equation for estimating VO2peak was evaluated in the patients with cardiovascular disease. The measured VO2peak of these patients was 23.7 +/- 0.3 ml.kg-1.min-1, whereas the VO2peak values estimated from the FAST equation and the ACSM equation were 24.1 +/- 0.3 and 33.2 +/- 0.5 ml.kg-1.min-1, respectively. No significant differences were found between the measured VO2peak and that estimated from the FAST equation. The VO2peak estimated from the ACSM equation was significantly greater than the measured VO2peak. These results suggest it is more appropriate to use the FAST equation rather than the ACSM equation to estimate VO2 in older patients with either osteoarthritis of the knee or cardiovascular disease.

Age Factors↗
PubMed1995

Estrogen replacement therapy and progression of intimal-medial thickness in the carotid arteries of postmenopausal women. ACAPS Investigators. Asymptomatic Carotid Atherosclerosis Progression Study.

The effect of estrogen replacement therapy (ERT) on 3-year changes in carotid intimal-medial thickness (IMT) was explored using serial B-mode ultrasound measurements collected during 1989-1993 as part of the Asymptomatic Carotid Atherosclerotic Progression Study (ACAPS). Eligibility included increased IMT and elevated low density lipoprotein cholesterol. Of the 186 postmenopausal ACAPS women randomly assigned to receive either placebo or lovastatin, 34% reported use of ERT. Users tended to be younger than nonusers by an average of 3 years, to have more favorable high and low density lipoprotein cholesterol levels, and to be more likely to have had hysterectomies. Baseline blood pressure, body mass index, and cross-sectional IMT were similar among ERT users and nonusers. In the placebo group, IMT tended to progress among ERT nonusers but to regress among ERT users: Mean covariate-adjusted progression rates were 0.015 +/- 0.007 mm/year versus -0.012 +/- 0.012 mm/year, respectively (p = 0.05). This difference appeared to be independent of lipoprotein concentrations. Lovastatin was associated with an approximately 25% lowering of low density lipoprotein cholesterol among both ERT users and nonusers and had a marked impact on IMT progression (p = 0.004) in these women. ERT appeared to have little additional effect on IMT in women assigned to lovastatin. ERT may reduce or halt the progression of early atherosclerosis in women not receiving active lipid-lowering medication.

Adult↗
PubMed1994

Cholesterol lowering in the elderly. Results of the Cholesterol Reduction in Seniors Program (CRISP) pilot study.

BACKGROUND: Total and lipoprotein cholesterol levels continue to be predictors of coronary heart disease risk in men and women over 65 years old. Cholesterol-lowering trials, however, while sometimes including such subjects, have not concentrated on this age group. The Cholesterol Reduction in Seniors Program was a five-center pilot study to assess feasibility of recruitment and efficacy of cholesterol lowering in this age group. METHODS: The study was a randomized, double-masked clinical trial with placebo, 20-mg lovastatin, and 40-mg lovastatin arms. Major efforts were made to recruit women and minorities. Participants were followed up for 1 year on a cholesterol-lowering diet plus placebo or study drug. End points were changes in blood lipid levels. Data on other blood chemistry values, as well as quality-of-life measures and coronary heart disease morbidity and mortality, were also collected. RESULTS: Four hundred thirty-one subjects with low-density lipoprotein cholesterol levels greater than 4.1 and less than 5.7 mmol/L (159 and 221 mg/dL) were randomized, of whom 71% were women and 21% were African Americans; the mean age was 71 years. In the 20- and 40-mg lovastatin groups, total cholesterol levels fell 17% and 20%; low-density lipoprotein cholesterol levels fell 24% and 28%; triglyceride levels fell 4.4% and 9.9%, respectively. High-density lipoprotein cholesterol levels rose 7.0% and 9.0%, respectively. No changes were observed in the placebo group. Gender, race, and age did not significantly affect responses. Coronary heart disease morbidity and mortality data were collected but not analyzed for this study. CONCLUSION: Older subjects of both genders and a variety of racial and ethnic groups can be successfully recruited into a cholesterol-lowering trial. Lovastatin has effects similar to those reported in younger subjects in previous controlled trials. There is little advantage to the higher lovastatin daily dose. Side effects were remarkably low in all groups.

Aged↗
PubMed1991

Geriatric evaluation and management: current status and future research directions.

In the last decade the concept of geriatric evaluation and management (GEM) has been widely discussed in the literature. Studies of GEM have occurred primarily in three settings: inpatient units, outpatient clinics, and specialized types of home care. We have reviewed the literature, focusing on randomized trials, to determine the strength of the evidence for the efficacy of these interventions. Two single-site randomized controlled trials of inpatient GEM units have been conducted and indicate that such units that provide care to targeted disabled older patients probably have a favorable impact on subsequent physical function, rates of institutionalization, and mortality. Two randomized trials of inpatient GEM consultation teams have been conducted. The trial that did not target high-risk individuals showed no benefit while the trial that did target an at-risk group showed that those receiving the service had improvements in mental status and short-term mortality. The results of randomized trials of outpatient GEM clinics to date have been unimpressive. Two trials of in-home GEM by a trained observer tended to show that the service resulted in a reduction in mortality. To date randomized trials of GEM have been very heterogeneous in terms of the type of assessment and subsequent care, the site in which services are delivered, and the manner in which patients are selected for the studies. This limits the ability to compare and extrapolate across studies. In the future there is a need to better clarify the selection of study participants, the exact structure of the assessment intervention provided, and the elements of successful interventions that may be most critical to insuring a good outcome.

Aged↗
PubMed1991

Research strategies for geriatric evaluation and management: conference summary and recommendations.

In this paper, we present the consensus statement from a national conference on research priorities and methodologies for studying geriatric evaluation and management (GEM) programs. These conclusions, discussion points, and recommendations resulted from discussions of plenary papers, working group deliberations, and a final session in which findings were synthesized by the conference co-chairmen and presented to conference participants for final review. Major conclusions included: (1) The importance of linking geriatric evaluation with care management in future studies; (2) The need for multi-center trials of inpatient units to establish efficacy; (3) The importance of studying criteria for targeting GEM care on patients who are most likely to benefit; (4) The need for further developmental studies of outpatient GEM clinics; (5) The importance of assessing a range of outcomes including mortality, patient function, satisfaction, caregiver burden, and cost; and (6) The need to define more carefully the nature of the intervention that is being studied to aid in comparing and extrapolating findings. The following research priorities for GEMS were formulated based on the conference: (1) Within the VA health care system, a multi-site randomized trial of inpatient GEM units should be initiated; (2) Multi-site studies of inpatient GEM units and consultation teams linked to outpatient care should be initiated in non-VA settings; (3) Studies should identify the components of GEM that are most critical to outcome; (4) Studies should explore efficacy of GEM in settings that have not been well studied to date such as nursing homes; and (5) Studies are needed to test screening methods and targeting criteria for GEM in all settings.

Geriatric Assessment↗
PubMedDate not supplied

Long-term effectiveness of enalapril plus extended-release diltiazem in essential hypertension.

STUDY OBJECTIVE: To evaluate the efficacy and safety of a new combination product, enalapril-diltiazem ER, when administered over the long term. DESIGN: Open-label, titration to response, with treatment lasting 46 weeks after a 6-week, double-blind phase. SETTING: Medical clinics in the private and academic sectors. PATIENTS: Of 265 patients (68% men, 83% Caucasian, mean age 54.9 yrs) with essential hypertension (sitting diastolic blood pressure 95-115 mm Hg) enrolled, 167 completed the trial. INTERVENTIONS: Patients received either the dosage of enalapril-diltiazem ER that they were given during the double-blind phase, or were prescribed enalapril 5 mg-diltiazem ER 120 mg once/day. The dosage was increased until blood pressure was controlled or to a maximum of enalapril 10-diltiazem ER 360 mg/day. MEASUREMENTS AND MAIN RESULTS: Combination therapy decreased sitting blood pressures by -11.1/-10.6 mm Hg. Overall, 58% of the patients achieved a sitting diastolic blood pressure of 90 mm Hg or below at the end of the study. There was no evidence of tolerance to the agents' antihypertensive effects. The most common drug-related adverse events were cough, headache, dizziness, and asthenia or fatigue. CONCLUSION: The combination effectively managed essential hypertension when administered on a long-term basis and was generally well tolerated. It should improve both compliance and management of hypertension.

Adult↗