Predictors of adherence in the Women's Health Initiative Calcium and Vitamin D Trial.

The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking > or = 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial.

Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models.

Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD+/-/human APOE ɛ3 or ɛ4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral ß-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aß deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aß oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aß production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.

Profile of men randomized to the prostate cancer prevention trial: baseline health-related quality of life, urinary and sexual functioning, and health behaviors.

PURPOSE: To describe men who agreed to be randomized to the Prostate Cancer Prevention Trial (PCPT), a 7-year, double-blind placebo-controlled study of the efficacy of finasteride in preventing prostate cancer. METHODS: Comprehensive health-related quality-of-life data are presented for 18,882 randomized PCPT participants. RESULTS: PCPT participants are highly educated, middle to upper income, and primarily white (92%). Participants reported healthy lifestyles. The mean American Urological Association Symptom Index score was well below the maximum entry score of less than 19; existing urinary symptoms were generally not bothersome. The scores for two sexual functioning scales could range from 0 to 100, with higher scores reflecting worse sexual functioning. The mean score for the Sexual Problem Scale was 19.2 out of 100, and the mean Sexual Activities Scale was 44.1 out of 100. Scores for seven of the eight Medical Outcomes Study 36-item Short-Form Health Survey scales (higher scores are better) were 10 to 20 points higher than those reported by a general population sample and differed minimally by race but not by age. Previously reported associations between sexual dysfunction and hypertension, diabetes, and depression were also observed. Men who never smoked reported less sexual dysfunction than did those who either had quit or still smoked. CONCLUSION: Individuals who are likely to enroll in primary prevention trials have a high socioeconomic status, healthy lifestyle behaviors, and better health than the general population. These data help oncologists design chemoprevention trials with respect to the selection of health-related quality-of-life assessments and recruitment strategies.

Quality of life among 5,025 patients with left ventricular dysfunction randomized between placebo and enalapril: the Studies of Left Ventricular Dysfunction. The SOLVD Investigators.

OBJECTIVES: This study was performed to assess the quality of life of patients with left ventricular dysfunction for up to 2 years after randomization to enalapril or placebo. BACKGROUND: Previous reports have documented that survival of patients with congestive heart failure can be extended by the angiotensin-converting enzyme inhibitor enalapril. However, it is unknown whether enalapril has a long-term favorable impact on the quality of life in patients with heart failure. METHODS: A brief quality of life questionnaire assessing the quality of life was administered at baseline and at 6 weeks, 1 year and 2 years of follow-up to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). Participants had an ejection fraction < or = 0.35, no other serious illnesses and either symptomatic heart failure (treatment trial, n = 2,465) or asymptomatic left ventricular dysfunction (prevention trial, n = 2,560). RESULTS: Among the 14 scales of quality of life, better scores at one or more follow-up intervals were noted in 6 scales in the treatment trial and in 1 scale in the prevention trial among patients assigned to enalapril. Consistent superiority with enalapril at two consecutive follow-up intervals was noted in the treatment trial for social functioning and dyspnea but for no scale in the prevention trial. However, an average of 40% of quality of life responses were missing at 2 years of follow-up because of death or failure to complete the questionnaire. In the treatment trial, survivors with more severe heart failure were less likely to complete the questionnaire. CONCLUSIONS: Modest benefits in quality of life for > or = 1 year occurred when patients with left ventricular dysfunction and symptomatic heart failure were treated with enalapril. No apparent beneficial or adverse effect on quality of life was observed with enalapril in asymptomatic patients with left ventricular dysfunction.

Hormone replacement therapy and other potential treatments for dementias.

The past decade has seen a substantial increase in the number of individuals affected by dementia. Dementia places a tremendous personal and economic burden on millions of patients and caregivers annually. Consequently, many scientists have been searching for a treatment for dementia to avoid the imminent public health crisis that will occur if this trend continues. Primary and secondary prevention studies, as well as animal research, demonstrate the potential for hormone replacement therapy (HRT) as an efficacious treatment for dementia. Recently, the Women's Health Initiative-Memory Study began the first randomized, longterm clinical trial to test the hypothesized role of HRT at the onset and in the progression of dementia in women. Researchers also are investigating the potential of other treatments for dementias, such as nonsteroidal anti-inflammatory drugs and free radical scavengers.

Assessment of quality of life as observed from the baseline data of the Studies of Left Ventricular Dysfunction (SOLVD) trial quality-of-life substudy.

The improvement of aspects of a patient's quality of life may be as important as prolonging survival in evaluating clinical trials of heart failure. The purpose of this study was to analyze the psychometric properties of the baseline measures from the quality-of-life substudy from the Studies of Left Ventricular Dysfunction (SOLVD) trial. The measures included the 6-Minute Walk Test, Dyspnea Scale, Living with Heart Failure, Physical Limitations, Psychologic Distress and Health Perceptions, as reported by both patients and staff. Cognitive functioning, such as Vocabulary, Digit Span and Trails Making, was also assessed. Patients were classified as New York Heart Association class I (n = 158) versus II or III (n = 150). The internal consistencies (i.e., reliabilities) of the self-report measures were high, except for the Health Perceptions of Class II or III patients. Reliability of the SOLVD quality-of-life battery was confirmed by significantly better life quality among New York Heart Association class I patients versus class II or III patients combined on the Walk Test, Physical Limitations, Dyspnea, Living with Heart Failure, Psychologic Distress and staff perceptions of patient health. In accordance with prior studies, the measures were uncorrelated with left ventricular ejection fraction. By demonstrating strong internal consistencies, reliability based on physician reports, and independence of ejection fraction levels, use of this quality-of-life assessment battery in this and other clinical trials of compromised ventricular functioning is supported.

Comparison of preoperative characteristics of men and women undergoing coronary artery bypass grafting (the Post Coronary Artery Bypass Graft [CABG] Biobehavioral Study).

A cohort of 759 coronary artery bypass grafting (CABG) patients (269 women and 490 men) was enrolled in the prospective POST CABG Biobehavioral Study at 5 clinical centers in the United States and Canada. Sociodemographic and medical data were obtained by interview and from medical charts. Health-related quality of life and psychosocial data were ascertained preoperatively by interview and questionnaire for those patients whose condition allowed preoperative assessment and was compared among patients from hospitals enrolling both male and female patients (143 women and 267 men). Women enrolled in the Biobehavioral Study were older than men (65.4 +/- 9.0 vs 61.8 +/- 9.7 years, p < 0.001) and more likely to have a preoperative medical condition which precluded biobehavioral evaluation (47% vs 34%, p < 0.001). Women were less likely to be high school graduates (59% vs 74%, p < 0.001), were less likely to be earning > or = $25,000 per year (39% vs 69%, p < 0.001), and were married less often at the time of surgery (59% vs 85%, p < 0.001). Fewer women than men were able to perform basic self-care activities (p < 0.001) and social activities (p < 0.001). Women were also less able to perform the more demanding activities required for independent living, recreation, and maintaining a household (p < 0.001). Women were also more anxious (p = 0.01) and reported more depressive symptoms (p < 0.001) than men. These data suggest that plans for perioperative and convalescent care for women undergoing CABG should take into account their less favorable medical and psychosocial status relative to men.

The Kidney Outcomes Prediction and Evaluation (KOPE) study: a prospective cohort investigation of patients undergoing hemodialysis. Study design and baseline characteristics.

PURPOSE: The purpose of the Kidney Outcomes Prediction and Evaluation (KOPE) study, was to more fully characterize the end-stage renal disease (ESRD) population with respect to social, psychological, and clinical characteristics, and to prospectively study the biomedical, social, and psychological factors that influence a range of ESRD outcomes in a large observational study of black and white patients on hemodialysis. This paper focuses on the KOPE study design as well as characteristics of patients at baseline. METHODS: KOPE was a prospective cohort investigation of patients treated at four dialysis centers in Forsyth County, North Carolina. Participants were interviewed at the dialysis centers, semi-annually over a 3 1/2 year period. Prevalent cases who were being treated with hemodialysis at the initiation of the study were enrolled into KOPE. Incident cases were subsequently enrolled as they presented to the participating units for hemodialysis. A total of 304 prevalent and 162 incident cases were enrolled into the study. The baseline health and sociodemographic characteristics of KOPE participants reported in this paper were obtained from medical records and Southeast Kidney Council data. Laboratory values taken within a 30-day interval around the baseline interview are also reported. RESULTS: KOPE participants differ from national statistics on race, age, and gender. Differences between KOPE participants and patients living in the region, but who did not participate in the study, can be explained by our recruitment criteria. CONCLUSIONS: KOPE will enable the characterization of the ESRD population, identification of factors related to poor outcomes, and identification of opportunities for interventions to prevent death and morbidity.

Factors related to sleep disturbance in older adults experiencing knee pain or knee pain with radiographic evidence of knee osteoarthritis.

OBJECTIVES: To describe the types and frequencies of sleep complaints and the biopsychosocial factors associated with sleep disturbance in a large community sample of older adults experiencing knee pain or knee pain with radiographic evidence of knee osteoarthritis (OA). DESIGN: Baseline analyses of an observational prospective study. SETTING AND PARTICIPANTS: Participants were 429 men and women aged 65 years and older experiencing knee pain or knee pain with radiographic evidence of OA enrolled in the Observational Arthritis Study in Seniors (OASIS). MEASUREMENTS: Demographic variables (age, gender, ethnicity, education), health (X-rays of knee rated for OA severity, medical conditions, medication use, smoking status, body mass index, self-rated health), physical functioning (self-rated physical functioning, physical performance), knee pain, and psychosocial functioning (social support, depression) were measured. RESULTS: Problems with sleep onset, sleep maintenance, and early morning awakenings occurred at least weekly among 31%, 81%, and 51% of participants, respectively. Bivariate correlates of greater sleep disturbance in those with OA were less education, cardiovascular disease, more arthritic joints, poorer self-rated health, poorer physical functioning, poorer physical performance, knee pain, depression, and less social support. In regression analyses, each set of variables representing the domains of health, physical functioning, pain, and psychosocial functioning contributed to the prediction of sleep disturbance beyond the demographic set. Finally, in a simultaneous model, white race (trend, P = .06), poorer self-rated health, poorer physical functioning, and depressive symptoms were predictive of sleep disturbance. CONCLUSIONS: Sleep disturbance is common in older adults experiencing knee pain or knee pain with radiographic evidence of OA and is best understood through the consideration of demographic, physical health, physical functioning, pain, and psychosocial variables. Interventions that take into account the multidetermined nature of sleep disturbance in knee pain or knee OA are most likely to be successful.

Baseline correlates with quality of life among men and women with medication-controlled hypertension. The trial of nonpharmacologic interventions in the elderly (TONE).

OBJECTIVES: To examine Quality of Life (QOL) and its correlates among older adults with medication-controlled hypertension. DESIGN: Baseline data from the TONE clinical trial. MEASUREMENTS: Demographic variables (age, race, income), hypertension treatment (medication class, years treated), health status (obesity, physical symptoms), and QOL status (MOS-Short-Form 36, Jenkins Sleep Disturbance, and CES-D Depression). PARTICIPANTS: A total of 975 men and women, aged 60 to 81 years and free of major diseases and disability, with a screening blood pressure (BP) of < or = 145/85 mm Hg, treated medically for hypertension with antihypertensive medication. RESULTS: On average, TONE participants reported a QOL level on the SF-36 that was similar to or better than that reported by older adults in the general population. However, there was a strikingly high prevalence of physical complaints or symptoms: 90.3% of men and 93.3% of women experienced one or more physical symptoms or complaints, and nearly 50% reported that such symptoms had disrupted their daily functioning. Among variables-considered, only the physical symptoms index score, number of severe symptoms, and obesity status were correlated consistently with QOL among TONE men and women. Lower QOL scores were associated with higher symptom scores and with obesity. Neither medication class nor age were appreciably associated with QOL status. CONCLUSIONS: Physical symptoms, rather than medication class and age, were the strongest correlates of QOL in TONE. This underscores the importance of identifying the etiology of symptoms as a means to improve the QOL of order hypertensive persons rather than substituting medication. The association of poorer physical well-being with obesity suggests that weight reduction to manage BP may also improve QOL for some individuals.

Gender differences in social support and physical health.

A large body of prospective data has accumulated linking social support to health, and most social scientists agree that low levels of support are associated with poor physical and mental health. Unfortunately, most of the research has been limited to White men. When women and people of color are included in the designs, the relationships between social support and physical health are more complicated. Prospective population-based studies provide evidence that low support is associated with increased risk of mortality in women. However, in several studies, results indicated that, for specific age groups, women with high social support have increased risk of mortality. Factors that may contribute to the observed gender differences in the social support-physical health relationship are discussed. Future research should include adequate numbers of women and more sophisticated measures of social support to move the field forward.

Psychosocial interventions in adult patients with coronary heart disease and cancer. A literature review.

A growing body of evidence suggests that chronic medical illness is associated with an increased prevalence and incidence of psychiatric and psychological disturbances. The present literature review is based on two theses: first, that chronic illness is viewed as a stressor and is associated with increased psychological distress, and secondly, that interventions can minimize the distress. A review of the studies conducted with adult patients diagnosed either with coronary heart disease or cancer suggests that psychosocial interventions are, in general, efficacious in relieving self-reported psychological distress. The review also recommends psychosocial interventions for high-risk patients rather than all patients, and that researchers need to identify other outcomes such as health care costs, disability, days in hospital, morbidity, and mortality in order to convince policy makers that these interventions are worthwhile. Recommendations for future research are also discussed.

Women's health initiative. Why now? What is it? What's new?

Studies collectively named the Women's Health Initiative (WHI) are currently enrolling 164,500 postmenopausal women in several overlapping clinical trials and an observational study. The overall goals of WHI are to understand the determinants of postmenopausal women's health and to evaluate the efficacy of practical interventions in preventing the major causes of morbidity and mortality in older women. This article reviews the research leading to the WHI studies; describes the study designs and protocols, with an emphasis on what's new about WHI from a psychological perspective; and outlines the major psychosocial hypotheses under investigation and the major challenges WHI presents to psychological science.

No effect of HRT on health-related quality of life in postmenopausal women with heart disease.

AIM: Previous clinical studies suggest hormone replacement therapy (HRT) alleviates menopausal symptoms and may improve health-related quality of life (HRQL). Most studies on HRT and HRQL were limited in duration (12 months or less) and scope (few and non-standard HRQL measures). The aim of this paper is to assess HRQL in the Estrogen Replacement and Atherosclerosis (ERA) trial. METHODS: A subset of women within a randomized, blinded, placebo-controlled secondary prevention trial has been studied in outpatient and community settings at 5 US sites. A total of 246 postmenopausal women with angiographically documented heart disease (mean age 66 years, 83% Caucasian) were enrolled in the ERA trial. Participants received either 0.625 mg/day conjugated equine estrogen only, estrogen plus 2.5 mg/day medroxyprogesterone acetate, or placebo. HRQL was assessed using validated questionnaire instruments at baseline and follow-up (mean 3.2 years of trial). Physical and mental functioning, life satisfaction, depressive symptoms, urinary incontinence, sleep disturbance, and frequency and intensity of physical symptoms were evaluated. RESULTS: In this group of women with established coronary disease, active therapy was not significantly associated with more favorable outcomes for any HRQL. The estrogen-only group reported more urinary incontinence than the placebo group (p<0.05). Analyses restricted to adherent women (those who took > or = 80% of pills) showed a similar pattern of results, showing that the estrogen only group reported significantly higher urinary incontinence compared to placebo (p<0.01). CONCLUSION: The hormone replacement regimens in the ERA trial did not improve HRQL of postmenopausal women with heart disease.

The integration of health quality of life in clinical research: experiences from cardiovascular clinical trials.

Health Quality of Life (HQL) assessment in clinical trial and epidemiological research is necessary to determine the efficacy of treatments and interventions. A definition of HQL is presented with the following dimensions of HQL identified: social, physical, and neuropsychological functioning; emotional stability; personal productivity; and intimacy. A strategy for selecting HQL dimensions and measures is discussed and includes consideration of the study population, the intervention(s), and the clinical trial design. Examples from NHLBI-sponsored clinical trials illustrate how HQL measures are selected as well as the goals that HQL assessment can address. That is, the authors discuss how HQL data can be used to characterize the study populations, determine the effects of HQL on critical outcomes, and assess how treatment affects overall HQL and specific dimensions of HQL.

Cognitive function and retinal and ischemic brain changes: the Women's Health Initiative.

OBJECTIVE: To examine the association between retinopathy and cognitive decline or brain lesions and volumes in older women. METHODS: This study included 511 women aged 65 and older who were simultaneously enrolled in the Women's Health Initiative Memory Study and the Sight Examination Study. In this analysis, we examined the link between retinopathy, assessed using fundus photography (2000-2002), cognitive performance over time assessed by the modified Mini-Mental State Examination (3MSE) (1996-2007), and white matter hyperintensities and lacunar infarcts in the basal ganglia. RESULTS: Presence of retinopathy was associated with poorer 3MSE scores (mean difference = 1.01, SE: 0.43) (p = 0.019) over a 10-year follow-up period and greater ischemic volumes in the total brain (47% larger, p = 0.04) and the parietal lobe (68% larger, p = 0.01) but not with measures of regional brain atrophy. CONCLUSIONS: The correspondence we found between retinopathy and cognitive impairment, along with larger ischemic lesion volumes, strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes. Retinopathy may be useful as a clinical tool if it can be shown to be an early marker related to neurologic outcomes.

Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study.

OBJECTIVE: The Women's Health Initiative Memory Study (WHIMS) hormone therapy (HT) trials reported that conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) increases risk for all-cause dementia and global cognitive decline. WHIMS MRI measured subclinical cerebrovascular disease as a possible mechanism to explain cognitive decline reported in WHIMS. METHODS: We contacted 2,345 women at 14 WHIMS sites; scans were completed on 1,424 (61%) and 1,403 were accepted for analysis. The primary outcome measure was total ischemic lesion volume on brain MRI. Mean duration of on-trial HT or placebo was 4 (CEE+MPA) or 5.6 years (CEE-Alone) and scans were conducted an average of 3 (CEE+MPA) or 1.4 years (CEE-Alone) post-trial termination. Cross-sectional analysis of MRI lesions was conducted; general linear models were fitted to assess treatment group differences using analysis of covariance. A (two-tailed) critical value of alpha = 0.05 was used. RESULTS: In women evenly matched within trials at baseline, increased lesion volumes were significantly related to age, smoking, history of cardiovascular disease, hypertension, lower post-trial global cognition scores, and increased incident cases of on- or post-trial mild cognitive impairment or probable dementia. Mean ischemic lesion volumes were slightly larger for the CEE+MPA group vs placebo, except for the basal ganglia, but the differences were not significant. Women assigned to CEE-Alone had similar mean ischemic lesion volumes compared to placebo. CONCLUSIONS: Conjugated equine estrogen-based hormone therapy was not associated with a significant increase in ischemic brain lesion volume relative to placebo. This finding was consistent within each trial and in pooled analyses across trials.