Improving the promise of embedded pragmatic trials: Surmountable barriers encountered in an evaluation of home-based HPV self-sampling to increase cervical cancer screening in overdue women.

Despite increased attention on how to conduct pragmatic trials and their importance, there remains an under-appreciation for the reality of what they take to design, compete and secure funding and execute. Many barriers are surmountable through increased exposure to experiences from completed trials. This report summarizes our experience in designing, securing funding and implementing the Home-Based Options to Make screening Easier (HOME) pragmatic trial, which was designed to evaluate home human papillomavirus testing for cervical cancer screening in underscreened women (women who had not received a cervical cancer screening test in ≥3.5 years). This report highlights factors at the level of research teams, organizations seeking to conduct embedded research, reviewers and funding agencies that challenge pragmatic trial design and execution. There is an urgent need to train on peer-reviewers how to evaluate embedded trial grant proposals, for agencies to pursue more rapid and innovative funding strategies, and to consider strategies for reviewers and funders to evaluate stakeholder buy-in (beyond letters of support). These factors together are needed to realize the promise of pragmatic trials to more efficiently and effectively generate critical data that inform changes in health care delivery and benefit patients.

Preoperative breast MRI and mortality in older women with breast cancer.

PURPOSE: The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial. METHODS: We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I-III) from 2/2005-6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model. RESULTS: 917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72-1.12) compared to those without MRI. CONCLUSION: Our findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women's decision quality and confidence levels with decisions involving treatment choices.

Factors associated with non-compliance with hormone therapy cessation before screening mammography.

OBJECTIVES: To evaluate factors associated with non-compliance with discontinuation of hormone therapy (HT) within a study on the effect of HT cessation on mammography performance. METHODS: This randomized, controlled trial was conducted at Group Health, a health plan in Washington State, USA. Eligibility included: age 45-80 years; due for screening ('study') mammogram; and prior screening mammogram while using HT. We randomized 1704 women to no cessation (n = 567), 1-month (n = 570), or 2-month cessation (n = 567), and called participants before cessation to review instructions. We collected self-reported data at randomization (baseline) and before the study mammogram, including symptoms and compliance. This analysis includes women randomized to 1-month or 2-month cessation with complete baseline and follow-up questionnaires (n = 883). RESULTS: Most participants were using unopposed estrogen (63.3%) and intended to continue HT (90%); 9.6% were non-compliant with HT cessation. Comparing 2-month vs. 1-month cessation, the age and body mass index (BMI)-adjusted relative risk (RR) for non-compliance was 1.72 (95% confidence interval (CI) 1.12-2.60). Baseline variables associated with non-compliance included: age ≤55 vs. >55 years (RR 2.34; 95% CI 1.34-4.41); BMI < 25 vs. BMI ≥30 kg/m 2 (RR 1.63; 95% CI 1.01-2.63); unopposed estrogen vs. estrogen plus progestin (RR 1.59; 95% CI 1.01-2.51); using HT to manage sleep (RR 1.80; 95% CI 1.20-2.71); severe vs. no night sweats (RR 1.68; 95% CI 1.03-2.74); and night sweats that interfered with sleep (RR 1.78; 95% CI 1.02-3.11). CONCLUSIONS: Non-compliance with HT cessation before screening mammogram was associated with younger age, lower BMI, symptom severity and use of unopposed estrogen. Alternatives for menopause symptom management are needed to assist women with HT cessation.

Effect of previous benign breast biopsy on the interpretive performance of subsequent screening mammography.

BACKGROUND: Most breast biopsies will be negative for cancer. Benign breast biopsy can cause changes in the breast tissue, but whether such changes affect the interpretive performance of future screening mammography is not known. METHODS: We prospectively evaluated whether self-reported benign breast biopsy was associated with reduced subsequent screening mammography performance using examination data from the mammography registries of the Breast Cancer Surveillance Consortium from January 2, 1996, through December 31, 2005. A positive interpretation was defined as a recommendation for any additional evaluation. Cancer was defined as any invasive breast cancer or ductal carcinoma in situ diagnosed within 1 year of mammography screening. Measures of mammography performance (sensitivity, specificity, and positive predictive value 1 [PPV1]) were compared both at woman level and breast level in the presence and absence of self-reported benign biopsy history. Referral to biopsy was considered a positive interpretation to calculate positive predictive value 2 (PPV2). Multivariable analysis of a correct interpretation on each performance measure was conducted after adjusting for registry, year of examination, patient characteristics, months since last mammogram, and availability of comparison film. Accuracy of the mammogram interpretation was measured using area under the receiver operating characteristic curve (AUC). All statistical tests were two-sided. RESULTS: A total of 2,007,381 screening mammograms were identified among 799,613 women, of which 14.6% mammograms were associated with self-reported previous breast biopsy. Multivariable adjusted models for mammography performance showed reduced specificity (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.73 to 0.75, P < .001), PPV2 (OR = 0.85, 95% CI = 0.79 to 0.92, P < .001), and AUC (AUC 0.892 vs 0.925, P < .001) among women with self-reported benign biopsy. There was no difference in sensitivity or PPV1 in the same adjusted models, although unadjusted differences in both were found. Specificity was lowest among women with documented fine needle aspiration-the least invasive biopsy technique (OR = 0.58, 95% CI = 0.55 to 0.61, P < .001). Repeating the analysis among women with documented biopsy history, unilateral biopsy history, or restricted to invasive cancers did not change the results. CONCLUSIONS: Self-reported benign breast biopsy history was associated with statistically significantly reduced mammography performance. The difference in performance was likely because of tissue characteristics rather than the biopsy itself.

Lone mothers are at higher risk for cardiovascular disease compared with partnered mothers. Data from the National Health and Nutrition Examination Survey III (NHANES III).

Lone mothers are a disadvantaged population, with research in several countries indicating that they experience low levels of physical and mental health. While research has demonstrated a socioeconomic gradient for cardiovascular disease (CVD), little research has explored lifestyle and clinical risk for CVD and prevalence of CVD events in lone mothers. The purpose of this study is (1) to compare select CVD lifestyle risks (smoking, obesity, physical activity), health, and relevant sociodemographic variables in partnered versus lone mothers; (2) to examine the relationship between partner status and having experienced a CVD event (myocardial infarction [MI], congestive heart failure [CHF], stroke). Data from the U.S. National Health and Nutrition Examination Survey III (NHANES III) included 1,446 women over 60 years with one or more children less than 17 years old. Lone mothers included women who were widowed, divorced, separated, never married, or married without the spouse living in the household (n = 623; weighted sample represents n = 3,904,450). Partnered mothers included women who reported living as married or married with the spouse in the household (n = 832; weighted sample represents n = 8,614,362). Weighted logistic regression was used to compare the prevalence of CVD risk factors in lone (43%) ver sus partnered (57%) mothers. Multivariate modeling was used to examine the relationship between partner status, CVD risks, and Coronary Heart Disease (CHD) events. Compared with partnered mothers, lone mothers were less educated and reported lower levels of income, health, and social support; and they were more likely to report non-White ethnicity. Lone mothers were more likely to be current smokers, overweight or obese, and physically active than partnered mothers. Those with clinical risks for CVD, including diabetes, elevated C-reactive protein, hypercholesterolemia, or hypertension, or all of these were more likely to be lone mothers. After adjusting for age, we found that mothers who had experienced a CVD event (MI, CHF, or stroke) were 3.3 times more likely to be a lone mother than a partnered mother (95% confidence interval (CI) 3.24, 3.31). Lone mothers are at increased risk for CVD. Health professionals and lone mothers should collaborate in the development of programs and policies not only to reduce lone mothers' risk for CVD, but also improve their conditions of living.