Cross-Sectional Survey of Factors Contributing to COVID-19 Testing Hesitancy Among US Adults at Risk of Severe Outcomes from COVID-19.

INTRODUCTION: The United States Centers for Disease Control and Prevention (CDC) advises testing individuals for COVID-19 after exposure or if they display symptoms. However, a deeper understanding of demographic factors associated with testing hesitancy is necessary. METHODS: A US nationwide cross-sectional survey of adults with risk factors for developing severe COVID-19 ("high-risk" individuals) was conducted from August 18-September 5, 2023. Objectives included characterizing demographics and attitudes associated with COVID-19 testing. Inverse propensity weighting was used to weight the data to accurately reflect the high-risk adult US population as reflected in IQVIA medical claims data. We describe here the weighted results modeled to characterize demographic factors driving hesitancy. RESULTS: In the weighted sample of 5019 respondents at high risk for severe COVID-19, 58.2% were female, 37.8% were ≥ 65 years old, 77.1% were White, and 13.9% had a postgraduate degree. Overall, 67% were Non-testers (who indicated that they were unlikely or unsure of their likelihood of being tested within the next 6 months); these respondents were significantly more likely than Testers (who indicated a higher probability of testing within 6 months) to be female (60.2 vs. 54.1%; odds ratio [OR] [95% confidence interval (CI)], 1.3 [1.1‒1.4]), aged ≥ 65 years old (41.5 vs. 30.3%; OR [95% CI] compared with ages 18‒34 years, 0.6 [0.5‒0.7]), White (82.1 vs. 66.8%; OR [95% CI], 1.4 [1.1‒1.8]), and to identify as politically conservative (40.9 vs. 18.1%; OR [95% CI], 2.6 [2.3‒2.9]). In contrast, Testers were significantly more likely than Non-testers to have previous experience with COVID-19 testing, infection, or vaccination; greater knowledge regarding COVID-19 and testing; greater healthcare engagement; and concerns about COVID-19. CONCLUSIONS: Older, female, White, rural-dwelling, and politically conservative high-risk adults are the most likely individuals to experience COVID-19 testing hesitancy. Understanding these demographic factors will help guide strategies to improve US testing rates.

Developing, optimizing, and evaluating patient infographics for diagnosing cardiac amyloidosis.

Objective: Advancements in diagnostics and treatment options for cardiac amyloidosis have improved patient outcomes, yet few patient education materials exist to help patients understand the disease and diagnosis process. We sought to develop and evaluate a set of plain language, patient-centered infographics describing the condition and common diagnostic tests. Methods: Using health literacy best practices, we developed 7 infographics which were further revised based on multilevel stakeholder feedback. To evaluate the materials, we recruited 100 patients from healthcare settings in Chicago, IL; participants completed a web-assisted interview during which they were randomized 1:1 to first view either our infographics or a standard material. Participants completed a knowledge assessment on their assigned material and subsequently reported impressions of both materials. Results: No differences were found between study arms in knowledge. The infographics took significantly less time to read and were more highly rated by participants in terms of appearance and understandability. Over two-thirds of participants preferred the infographics to the standard. Conclusions: The infographics created may improve the learning process about a complex condition and diagnosis process unknown to most adults. Innovation: These infographics are the first of their kind for cardiac amyloidosis and were created using health literacy best practices.

Towards a more patient-centered clinical trial process: A systematic review of interventions incorporating health literacy best practices.

BACKGROUND: A 2019 public workshop convened by the National Academies of Sciences, Engineering and Medicine (NASEM) Roundtable on Health Literacy identified a need to develop evidence-based guidance for best practices for health literacy and patient activation in clinical trials. PURPOSE: To identify studies of health literacy interventions within medical care or clinical trial settings that were associated with improved measures of health literacy or patient activation, to help inform best practices in the clinical trial process. DATA SOURCES: Literature searches were conducted in PubMed, the Cumulative Index to Nursing and Allied Health Literature, SCOPUS, Cochrane, and Web of Science from January 2009 to June 2021. STUDY SELECTION: Of 3592 records screened, 22 records investigating 27 unique health literacy interventions in randomized controlled studies were included for qualitative synthesis. DATA EXTRACTION: Data screening and abstraction were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. DATA SYNTHESIS: Types of health literacy interventions were multimedia or technology-based (11 studies), simplification of written material (six studies) and in-person sessions (five studies). These interventions were applied at various stages in the healthcare and clinical trial process. All studies used unique outcome measures, including patient comprehension, quality of informed consent, and patient activation and engagement. CONCLUSIONS: The findings of our study suggest that best practice guidelines recommend health literacy interventions during the clinical trial process, presentation of information in multiple forms, involvement of patients in information optimization, and improved standardization in health literacy outcome measures.

The Relative Burden of Menopausal and Postmenopausal Symptoms versus Other Major Conditions: A Retrospective Analysis of the Medical Expenditure Panel Survey Data.

BACKGROUND: The direct costs associated with menopausal and postmenopausal symptoms (hereafter "menopausal symptoms") may include the costs of physician and emergency department visits, medications, laboratory testing, and the management of side effects. However, much remains unknown about the costs related to menopausal symptoms, including how they compare with the costs of other diseases that are common among menopausal women. OBJECTIVE: To compare the economic burden of menopausal symptoms with other select prevalent chronic conditions among a nationally representative sample of US menopausal women aged 45 to 65 years. METHODS: Women aged 45 to 65 years who have not had a hysterectomy and who participated in the 2010-2012 Medical Expenditure Panel Survey Household Component were included in the analysis. We estimated the direct costs of care associated with the management of menopausal symptoms and compared them with the direct costs of care for other indications, including osteoporosis, influenza, disorders of lipid metabolism, essential hypertension, mood disorders, esophageal disorders, headache, osteoarthritis, urinary tract infections, asthma, glaucoma, anxiety disorder, diabetes, chronic obstructive pulmonary disease/bronchiectasis, and cataract. Regression analyses were used to estimate the differences in direct costs, which included total expenditures and charges for inpatient, outpatient, and emergency department visits. RESULTS: The annual per-patient direct cost of menopausal symptoms was $248 in 2010-2012 dollars. Based on the modeled costs, menopausal symptoms were associated with significantly higher annual costs than osteoporosis, disorders of lipid metabolism, and esophageal disorders; and these annual costs were comparable to those of influenza, asthma, anxiety disorder, essential hypertension, and headache. The direct costs associated with the management of menopausal symptoms were significantly lower than the direct costs associated with osteoarthritis, mood disorders, chronic obstructive pulmonary disease/bronchiectasis, urinary tract infections, diabetes, glaucoma, and cataract. CONCLUSION: The direct costs of care for menopausal symptoms are substantial and are similar to or greater than the direct healthcare costs associated with a number of medical conditions often requiring medical attention in menopausal women.

Low-Fat Dietary Pattern Intervention and Health-Related Quality of Life: The Women's Health Initiative Randomized Controlled Dietary Modification Trial.

BACKGROUND: Intensive dietary intervention programs may lead to benefits in vitality and other components of health quality. The Women's Health Initiative Dietary Modification (DM) intervention includes a large randomized controlled trial of an intensive intervention. OBJECTIVE: To evaluate whether the intervention is associated with improved health-related quality of life (HRQoL) subscales, overall self-reported health, depression symptoms, cognitive functioning, and sleep quality. DESIGN: This randomized controlled trial was analyzed as intent to treat. PARTICIPANTS: Between 1993 and 1998, 48,835 women aged 50 to 79 years were recruited by 40 clinical centers across the United States. Eligibility included having fat intake at baseline ≥32% of total calories, and excluded women with any prior colorectal or breast cancer, recent other cancers, type 1 diabetes, or medical conditions with predicted survival <3 years. INTERVENTION: Goals were to reduce calories from fat to 20%, increase vegetables and fruit to 5+ servings, and increase grain servings to 6+ servings a day. During the first year, 18 group sessions were held, with quarterly sessions thereafter. MAIN OUTCOME MEASURES: The RAND 36-Item Health Survey was used to assess HRQoL at baseline, Year 1, and close-out (about 8 years postrandomization), and estimate differential HRQoL subscale change scores. STATISTICAL ANALYSES PERFORMED: Mean change in HRQoL scores (Year 1 minus baseline) were compared by randomization group using linear models. RESULTS: At 1 year, there was a differential change between intervention and comparison group of 1.7 units (95% CI 1.5, 2.0) in general health associated with the intervention. DM intervention improved physical functioning by 2.0 units (95% CI 1.7, 2.3), vitality by 1.9 units (95% CI 1.6, 2.2), and global quality of life by 0.09 units (95% CI 0.07, 0.12). With the exception of global quality of life, these effects were significantly modified by body mass index at baseline. CONCLUSIONS: DM intervention was associated with small, but significant improvements in three HRQoL subscales: general health, physical functioning, and vitality at 1 year follow-up, with the largest improvements seen in the women with the greatest baseline body mass index.

The effect of conjugated estrogens/bazedoxifene therapy on body weight of postmenopausal women: pooled analysis of five randomized, placebo-controlled trials.

OBJECTIVE: This post hoc analysis compared body weight, body mass index (BMI), and BMI category changes in postmenopausal women treated with conjugated estrogens/bazedoxifene (CE/BZA) versus placebo in the Selective Estrogens, Menopause, and Response to Therapy (SMART) trials. METHODS: Data were pooled from five randomized, double-blind, placebo- and active-controlled studies in postmenopausal women aged 40 to 75 years with a uterus given CE 0.45 mg/BZA 20 mg (n = 1,607), CE 0.625 mg/BZA 20 mg (n = 1,598), or placebo (n = 1,256) for at least 12 weeks and up to 2 years. Changes from baseline in body weight, BMI (kg/m(2)), and World Health Organization BMI category (underweight <18.5; normal 18.5 to <25; overweight 25 to <30; obese ≥30) during treatment were evaluated. RESULTS: Mean body weight increased less than 0.9 kg and mean BMI increased less than 0.4 kg/m(2) in all treatment groups at all time points. There were no statistically significant between-group differences, except for significantly greater increases in weight (P = 0.015) and BMI (P = 0.014) with placebo versus CE 0.625 mg/BZA 20 mg at month 12. Approximately, 10% of women in the CE/BZA groups and 11% in the placebo group had increases in body weight greater than 7% of baseline. The majority of BMI changes were within ±7%, and there were no statistically significant between-group differences in BMI category distributions during treatment. CONCLUSIONS: Significant increases in body weight or BMI were not observed in postmenopausal women receiving CE 0.45 mg/BZA 20 mg or CE 0.625 mg/BZA 20 mg for up to 2 years in the Selective Estrogens, Menopause, and Response to Therapy trials.

The Comparative Burden of Chronic Widespread Pain and Fibromyalgia in the United States.

BACKGROUND/PURPOSE: Little information exists on the comparative patient and economic burden of chronic widespread pain (CWP) and fibromyalgia (FM) in the United States. METHODS: This multistage, observational study included an online screening survey of a large geographically diverse US sample to assess CWP status, a physician/site visit to determine FM diagnosis, and an online subject questionnaire to capture clinical characteristics, pain, health status, functioning, sleep, healthcare resource use (HRU), productivity, and costs. Based on the screener and physician evaluation, mutually exclusive groups of subjects without CWP (CWP-), with CWP but without FM (CWP+), and with confirmed FM were identified. RESULTS: Disease burden was examined in 472 subjects (125 CWP-, 176 CWP+, 171 FM). Age, race, and ethnicity were similar across groups. Mean body mass index and number of comorbidities increased from CWP- to CWP+ to FM (P = 0.0044, P < 0.0001, respectively). From CWP- to CWP+ to FM, there were reductions in health status (EQ-5D, SF-12) and sleep outcomes (MOS-SS, SSQ) (all P < 0.05). Pain severity, interference with function (BPI-SF), and overall work impairment (WPAI:SHP) increased from CWP- to CWP+ to FM (all P < 0.0001). Higher proportions of CWP+ (52.8%) and FM subjects (62.6%) were taking pain-related prescription medications relative to CWP- subjects (32.8%; P < 0.0001). Significant differences in total direct and indirect costs across the three groups (both P < 0.0001) were observed, with highest costs among FM subjects. CONCLUSION: Fibromyalgia subjects were characterized by the greatest disease burden with more comorbidities and pain-related medications, poorer health status, function, sleep, lower productivity, and higher costs.

The cross-sectional relationship of hemoglobin levels and functional outcomes in women with self-reported osteoarthritis: results from the Women's Health Initiative.

OBJECTIVES: Gastrointestinal blood loss is a recognized complication of the use of nonsteroidal anti-inflammatory drugs (NSAIDS) in patients with arthritis. We examined the cross-sectional relationship of patient-reported outcomes of overall health, physical function, vitality, and quality of life to hemoglobin (hgb) levels in postmenopausal women with self-reported osteoarthritis to determine whether hgb levels as potential markers of chronic blood loss were associated with these functional outcomes. METHODS: Postmenopausal women (N = 64,850) with self-reported osteoarthritis (srOA) at baseline in the Women's Health Initiative study, excluding participants with chronic or hemolytic diseases associated with anemia, had hgb levels measured and completed Short-Form Health Surveys. General linear models analysis adjusting for potential confounders was performed. RESULTS: A nonlinear plateauing relationship between hgb levels and functional outcomes was found. Participants with srOA had statistically significantly worse overall health, physical function, and vitality, but not quality of life, for each gram of hgb below 14 g/dL, compared with those with hgb 14 g/dL (P < 0.001). Participants with srOA taking NSAIDS had worse functional outcomes for each level of hgb compared with those not reporting NSAIDS use. CONCLUSIONS: In cross-sectional analyses of postmenopausal women with srOA, differences in hgb levels are related to differences in functional outcomes of overall health, physical function, and vitality at clinically important levels. Prospective studies evaluating whether changes in hgb levels result in changes in functional outcomes in participants with osteoarthritis are needed to confirm of our findings and before any changes in therapeutics based on hemoglogin levels are considered in the care of patients with osteoarthritis.

Impact of upper and lower gastrointestinal blood loss on healthcare utilization and costs: a systematic review.

OBJECTIVES: Gastrointestinal (GI) blood loss is a common medical condition which can have serious morbidity and mortality consequences and may pose an enormous burden on healthcare utilization. The purpose of this study was to conduct a systematic review to evaluate the impact of upper and lower GI blood loss on healthcare utilization and costs. METHODS: We performed a systematic search of peer-reviewed English articles from MEDLINE published between 1990 and 2010. Articles were limited to studies with patients ≥18 years of age, non-pregnant women, and individuals without anemia of chronic disease, renal disease, cancer, congestive heart failure, HIV, iron-deficiency anemia or blood loss due to trauma or surgery. Two reviewers independently assessed abstract and article relevance. RESULTS: Eight retrospective articles were included which used medical records or claims data. Studies analyzed resource utilization related to medical care although none of the studies assessed indirect resource use or costs. All but one study limited assessment of healthcare utilization to hospital use. The mean cost/hospital admission for upper GI blood loss was reported to be in the range $3180-8990 in the US, $2500-3000 in Canada and, in the Netherlands, the mean hospital cost/per blood loss event was €11,900 for a bleeding ulcer and €26,000 for a bleeding and perforated ulcer. Mean cost/ hospital admission for lower GI blood loss was $4800 in Canada, and $40,456 for small bowel bleeding in the US. CONCLUSIONS: Our findings suggest that the impact of GI blood loss on healthcare costs is substantial but studies are limited. Additional investigations are needed which examine both direct and indirect costs as well as healthcare costs by source of GI blood loss focusing on specific populations in order to target treatment pathways for patients with GI blood loss.

Alcohol and folate intake and breast cancer risk in the WHI Observational Study.

BACKGROUND: Alcohol increases breast cancer risk. Epidemiological studies suggest folate may modify this relationship. OBJECTIVE: To examine the relationship among breast cancer, alcohol and folate in the Women's Health Initiative-Observational Study (WHI-OS). METHODS: 88,530 postmenopausal women 50-79 years completed baseline questionnaires between October 1993 and December 1998, which addressed alcohol and folate intake and breast cancer risk factors. Cox proportional hazards analysis examined the relationship between self-reported baseline alcohol and folate intake and incident breast cancer. RESULTS: 1,783 breast cancer cases occurred over 5 years. Alcohol was associated with increased risk of breast cancer (RR = 1.005, 95%CI 1.001-1.009). Risk increased with consumption of alcohol (up to 5 g/d, adjusted HR = 1.10, 95%CI 0.96-1.32; >5-15 g/d HR = 1.14, 95%CI 0.99-1.31; and >15 g/d HR = 1.13 95%CI 0.96-1.32). We found no significant interaction between alcohol and folate in our adjusted model. CONCLUSIONS: We found no evidence for folate attenuating alcohol's effect on breast cancer risk in postmenopausal women. Our results may be due to misclassification of folate intake or the relatively short follow-up period.

Use of recovery biomarkers to calibrate nutrient consumption self-reports in the Women's Health Initiative.

Underreporting of energy consumption by self-report is well-recognized, but previous studies using recovery biomarkers have not been sufficiently large to establish whether participant characteristics predict misreporting. In 2004-2005, 544 participants in the Women's Health Initiative Dietary Modification Trial completed a doubly labeled water protocol (energy biomarker), 24-hour urine collection (protein biomarker), and self-reports of diet (assessed by food frequency questionnaire (FFQ)), exercise, and lifestyle habits; 111 women repeated all procedures after 6 months. Using linear regression, the authors estimated associations of participant characteristics with misreporting, defined as the extent to which the log ratio (self-reported FFQ/nutritional biomarker) was less than zero. Intervention women in the trial underreported energy intake by 32% (vs. 27% in the comparison arm) and protein intake by 15% (vs. 10%). Younger women had more underreporting of energy (p = 0.02) and protein (p = 0.001), while increasing body mass index predicted increased underreporting of energy and overreporting of percentage of energy derived from protein (p = 0.001 and p = 0.004, respectively). Blacks and Hispanics underreported more than did Caucasians. Correlations of initial measures with repeat measures (n = 111) were 0.72, 0.70, 0.46, and 0.64 for biomarker energy, FFQ energy, biomarker protein, and FFQ protein, respectively. Recovery biomarker data were used in regression equations to calibrate self-reports; the potential application of these equations to disease risk modeling is presented. The authors confirm the existence of systematic bias in dietary self-reports and provide methods of correcting for measurement error.

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. Dietary change was evaluated after 1 year of participation in the Women's Health Initiative Dietary Modification Trial, and dietary maintenance after 3 years. SUBJECTS: Postmenopausal women aged 50 to 79 years at baseline who were randomized to the intervention arm of the Women's Health Initiative Dietary Modification Trial (n=19,541). STATISTICAL ANALYSIS: Univariate and multivariate linear regression analysis was performed and associations evaluated between candidate predictors and each of the three dietary goals: percent energy from fat, fruit/vegetable servings, and grain servings. RESULTS: Year 1 (change) predictors of percent energy from fat (P<0.005) included being younger (beta=2.12; 70 to 79 years vs 50 to 59 years), more educated (beta=-.69; college vs high school), more optimistic (beta=-.07), attending more sessions (beta=-.69), and submitting more self-monitoring records (beta=-.74). At year 3 (maintenance), the predictors of percent energy from fat (P<0.005) included attending more sessions (beta=-.65) and submitting more self-monitoring scores (beta=-.71). The analytic model predicted 22% of the variance in fat intake at year 1 and 27% at year 3 (P<0.01). CONCLUSIONS: The strongest predictors of dietary change and maintenance were attending intervention sessions and self-monitoring dietary intake. Novel was the finding that optimism predicted dietary change.

Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy.

CONTEXT: The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis. OBJECTIVE: To determine the effects of CEE on breast cancers and mammographic findings. DESIGN, SETTING, AND PARTICIPANTS: Following breast cancer risk assessment, 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included. INTERVENTION: A dose of 0.625 mg/d of CEE or an identical-appearing placebo. MAIN OUTCOME MEASURES: Breast cancer incidence, tumor characteristics, and mammogram findings. RESULTS: After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up. CONCLUSIONS: Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.

Calcium plus vitamin D supplementation and the risk of fractures.

BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

Calcium plus vitamin D supplementation and the risk of colorectal cancer.

BACKGROUND: Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study. RESULTS: The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. CONCLUSIONS: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).

Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

CONTEXT: The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial. OBJECTIVE: To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence. DESIGN AND SETTING: A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005. PARTICIPANTS: A total of 48,835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled. INTERVENTIONS: Women were randomly assigned to the dietary modification intervention group (40% [n = 19,541]) or the comparison group (60% [n = 29,294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes. MAIN OUTCOME MEASURE: Invasive breast cancer incidence. RESULTS: Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor. CONCLUSIONS: Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.

Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

CONTEXT: Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial. OBJECTIVE: To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States. INTERVENTIONS: Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern. MAIN OUTCOME MEASURE: Invasive colorectal cancer incidence. RESULTS: A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention. CONCLUSION: In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.

Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

CONTEXT: Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed. OBJECTIVE: To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years. INTERVENTION: Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials. MAIN OUTCOME MEASURES: Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke). RESULTS: By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits. CONCLUSIONS: Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.

Community interventions for cardiovascular disease.

Review of the community-based CVD intervention programs suggests that a number of components have been successful using varying methods and materials for CVD risk reduction. It should be noted, however, that in multi-intervention programs it is often difficult to determine which components of the intervention were responsible for the overall success of the study. The community-based approach to CVD prevention is generalizable, cost-effective (because of the use of mass communication methods), and has the potential for modifying the environment and influencing health policies. Based on the experiences and successes of a number of community projects, recommendations have been proposed for developing future programs. Although they are not totally comprehensive, it has been suggested that a community-based intervention program should consider the following recommendations: 1) An understanding of the community: the needs and priorities of the community should be assessed, and close collaboration with individuals from the community, including community leaders, opinion leaders, community health care providers, and community organizations from various sectors of the community, should be consulted. Efforts should be focused on underserved and vulnerable populations. 2) Inclusion of community activities: these activities should be integrated within the context of the community environment, including primary health care services, voluntary organizations, grocery stores, restaurants, work sites, schools, and local media. 3) Inclusion mass media messages: the mass media can provide information and reinforcement of the behavior change. 4) Develop cost-effective interventions to assure that the community is exposed to an effective dose of the intervention. 5) Work with community organizations to help change social and physical environments to make them more conducive to health and healthy life-styles changes. 6) Develop a reliable monitoring and evaluation system: monitor the change process and conduct summary evaluations. 7) Disseminate the results to ensure that the benefits from the community program reach all communities. 8) For national implementation, the intervention program should work closely with national policy makers throughout the project.

Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial.

BACKGROUND: The Women's Health Initiative (WHI) clinical trial of conjugated equine estrogens (CEEs), involving 10,739 postmenopausal women with hysterectomy, aged 50 to 79 years, was stopped early owing to lack of overall health benefit and increased risk of stroke. Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis, it is important to understand the overall impact of this therapy on health-related quality of life (HRQOL). METHODS: All participants completed 6 specific measures of quality of life at baseline and 1 year, and a subsample (n = 1189) also completed the questions 3 years after randomization. Changes in scores were analyzed for treatment effect. RESULTS: Randomization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline (mean benefit, 0.4 points on a 20-point scale) and a statistically significant but small negative effect on social functioning (mean effect, -1.3 points on a 100-point scale). There were no significant improvements due to CEE in the areas of general health, physical functioning, pain, vitality, role functioning, mental health, depressive symptoms, cognitive function, or sexual satisfaction at year 1. A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes. Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline, CEE did not improve any of the HRQOL variables at year 1. CONCLUSION: In this trial of postmenopausal women with prior hysterectomy, oral CEE did not have a clinically meaningful effect on HRQOL.