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Spaghetti plots of mean arterial pressure (MAP) from clinical blood pressure measurements at three time points by study group.

Table showing descriptive statistics for three collagen features (length, width, and straightness) at the baseline measure.

Details on MRI Scanner information.

Purpose:To evaluate the effect of sulindac, a nonselective anti-inflammatory drug (NSAID), for activity to reduce breast density (BD), a risk factor for breast cancer.Experimental Design:An open-label phase II study was conducted to test the effect of 12 months' daily sulindac at 150 mg twice daily on change in percent BD in postmenopausal hormone receptor–positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by noncontrast magnetic resonance imaging (MRI) and reported as change in MRI percent BD (MRPD). A nonrandomized patient population on AI therapy (observation group) with comparable baseline BD was also followed for 12 months. Changes in tissue collagen after 6 months of sulindac treatment were explored using second-harmonic generated microscopy in a subset of women in the sulindac group who agreed to repeat breast biopsy.Results:In 43 women who completed 1 year of sulindac (86% of those accrued), relative MRPD significantly decreased by 9.8% [95% confidence interval (CI), −14.6 to −4.7] at 12 months, an absolute decrease of −1.4% (95% CI, −2.5 to −0.3). A significant decrease in mean breast tissue collagen fiber straightness (P = 0.032), an investigational biomarker of tissue inflammation, was also observed. MRPD (relative or absolute) did not change in the AI-only observation group (N = 40).Conclusions:This is the first study to indicate that the NSAID sulindac may reduce BD. Additional studies are needed to verify these findings and determine if prostaglandin E2 inhibition by NSAIDs is important for BD or collagen modulation.

Background Although exercise has been shown to improve cancer survivorship in other communities, cancer exercise studies among Native American communities are rare. We sought to adapt a Navajo-tailored cancer exercise pilot program to serve a broader Native American cancer community. Methods Tribal experts representing 10 different Tribal Nations were engaged in small focus groups (n=2–4) to assess program materials for cultural appropriateness and adaptation to expand tribal inclusiveness. Facilitated by a trained Native American interviewer, focus groups were provided a primer survey and then reviewed intervention materials (protocols, incentives, logo, flyers, etc.). Consensus was reached by the research team on all program adaptations. Results The program name, Restoring Balance, layout, graphics, and symbols were considered culturally appropriate overall. Program exercises and biomarker measurements were viewed as valuable to health improvements in the community. Important color, linguistic, and logistic program modifications were recommended to improve cultural alignment. The order of incentive items was revised to highlight restoration and the logo rotated to align with the four corners of the earth, an important cultural element. Linguistic modifications primarily related to prior traumatic research experiences in Native American communities where data had been taken without adequate community benefit or permission. Program emphasis should be on nurturing, added value and giving. Conclusion and Relevance The methodology used for cultural expert review was successful in eliciting adaptations to expand the tribal inclusiveness of Restoring Balance. Culture, as well as historically traumatic research experiences, among Native American populations must be considered when adapting health promotion programming.

Aim: To determine whether differences in joint and tendon stiffness as measured by ultrasound shear wave elastography are present in breast cancer patients with aromatase inhibitor- associated arthralgias compared to age-comparable healthy control women. Methods: Postmenopausal women with stage I–III breast cancer who were taking adjuvant aromatase inhibitors and complained of joint pain were enrolled (n = 6). Postmenopausal women with no history of breast cancer, hormone treatment, or joint pain served as controls (n = 7). All subjects had bilateral hands and wrists evaluated by gray-scale and power Doppler ultrasound, and shear wave elastography ultrasound. Results: Patients with AI-associated arthralgias had significantly stiffer tendons than controls in the 1st extensor compartment (long axis; p = 0.001), 4th extensor compartment (long axis; p = 0.014), 3rd metacarpophalangeal joint (p = 0.002), the pooled values of the extensor compartments, both long (p = 0.044) and short axes (p = 0.035), and the pooled values for the metacarpophalangeal joints (p = 0.002). On ultrasound, the patients (but not controls) presented with hyperemia and increased tenosynovial fluid in the flexor and extensor tendon sheaths, and the median nerves were symptomatic and bifid; however, these differences were not statistically significant. Conclusions: This is the first study to identify increased tendon stiffness as a putative physiological characteristic of aromatase inhibitor–associated arthralgias. Future studies should determine whether increased tendon stiffness is a risk factor for the development of aromatase inhibitor–associated arthralgias, or a result of aromatase inhibitor treatment.

PURPOSE: To examine benefit of sulindac for relief of musculoskeletal symptoms (MSS) in patients stable on aromatase inhibitors (AIs). METHODS: Sulindac was evaluated at 150 mg twice daily for effects on MSS at 3, 6, 9, and 12 months in 50 postmenopausal women stable on AI therapy for a median of 12.5 months for hormone receptor positive breast cancer. A separate, non-randomized group of 50 similar patients was observed for change in MSS over 12 months. MSS severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Brief Pain Inventory Short Form (BPI-SF). The Functional Assessment of Cancer Therapy – General form (FACT-G) measured quality of life (QOL). Change in MSS and QOL across time was assessed in each group using linear mixed effects models. RESULTS: Stiffness, not pain, was the main complaint at baseline. At 12 months, sulindac patients reported decreases (improvements) in mean [95% CI] Total WOMAC score (−5.85 [−9.73, −1.96]) and WOMAC pain (−5.40 [−10.64, −0.18]), Stiffness (−9.53 [−14.98, −4.08]) and Physical Function (−5.61 [−9.62, −1.60]) subscales, but not BPI-SF worst pain. Among sulindac patients with higher baseline MSS severity, 35% experienced ≥50% improvement in Total WOMAC, and Total FACT-G scores (6.18 [2.08, 10.27]; p = 0.003). For the observation group, MSS and QOL did not improve over 12 months, even among those with higher baseline MSS severity. CONCLUSIONS: Sulindac may relieve MSS in AI patients, especially physical function, and stiffness. Randomized controlled trials should further evaluate NSAIDs on AI-MSS and AI adherence.

Chemotherapy-induced peripheral neuropathy (CIPN) is caused by drug-induced damage to the axons which is not detected easily due to lack of reliable, clinically applicable modalities. Diffuse tensor imaging (DTI) allows for quantitative measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), which have been shown to detect nerve injury by Magnetic Resonance Imaging (MRI). We sought to evaluate if DTI could be used for detection of CIPN in patients with breast cancer treated with a taxane. Patients with h/o exposure to neurotoxic chemotherapy, diabetes, or peripheral neuropathy were excluded. Patients completed pre- and post-chemotherapy MRI of bilateral legs and FACT&GOG-Ntx. Genotyping of single-nucleotide variations (SNVs) was performed to detect known associations with CIPN. We had 14 evaluable patients in this prospective trial. Mean FA values post-chemotherapy were significantly lower than baseline at mid-calf (p

AIM: To investigate the association between dietary patterns and total and obesity-related cancers risk. Additionally, to examine if acculturation modifies this relationship. SUBJECT AND METHODS: Dietary intake of postmenopausal Hispanic women (N=5,482) enrolled in the Women’s Health Initiative was estimated from a Food Frequency Questionnaire and used to calculate dietary pattern scores; Healthy Eating Index-2015 (HEI-2015), Mexican Diet (MexD) score, alternate Mediterranean Diet Score (aMED), and the energy adjusted-Dietary Inflammatory Index (E-DII™). Associations were evaluated using Cox proportional hazards regression models. RESULTS: 631 cancers and 396 obesity-related cancers were diagnosed over a mean-follow up of 12 years. Across dietary scores, there were no significant associations with cancer risk or mortality. Trend analysis suggest a potentially lower risk for total cancer related to the highest MexD score (HR 0.68, 95% CI 0.45–1.04, P-trend=0.03), and lower risk for obesity-related cancer mortality related to the highest score category for MexD (HR 0.65, 95% CI 0.37–1.16, P-trend=0.02), and aMED (HR 0.87, 95% CI 0.45–1.67, P-trend=0.04). Further analysis suggests less acculturated women with higher MexD scores had 56% lower risk for any cancer (HR 0.44, 95% CI 0.22–0.88, P-trend=0.03) and 83% lower risk for cancer mortality (HR 0.17, 95% CI 0.04–0.76, P-trend=0.01) compared to more acculturated Hispanic women. CONCLUSIONS: Dietary patterns were not associated with cancer risk and mortality in postmenopausal Hispanic women. Less-acculturated, Spanish-preferred speakers, who reported consuming a more traditional Mexican diet may experience a lower risk for cancer and cancer mortality.

ObjectivesTo evaluate the efficacy of the Nurtured Heart Approach (NHA) to improve attention deficit hyperactivity disorder (ADHD) behaviors in children.MethodsIn 2017, we conducted a trial among parents (n = 104) with children ages 6–8 years diagnosed with ADHD/at risk for a diagnosis. Participants were randomly selected, but not blinded, to the immediate (NHA) or delayed (control) group. The NHA training was held online over 6 weeks.ResultsThe NHA group (−7.0 ± 8.1), but not the control group (0.2 ± 6.6), reported a decrease in inattention (p < .001). The NHA group (−7.9 ± 9.3), but not the control group (−0.5 ± 7.3), reported a decrease in hyperactivity/impulsivity (p < .001).ConclusionsThe study provides preliminary data of the NHA's potential to improve ADHD related behaviors.

Background. Preclinical and observational evidence supports cancer prevention activity of non-steroidal anti-inflammatory drugs (NSAIDs) in the breast via suppression of prostaglandin E2 (PGE2) synthesis by cyclooxygenase-2 (COX2). Evidence includes linking of PGE2 to aromatase activity and estrogen synthesis in breast adipose tissue, as well as effects on collagen and breast density (BD). Methods. In an open-label trial, we evaluated the effect of the non-selective NSAID sulindac at 150 mg bid for 12 months on BD in 52 postmenopausal women taking adjuvant aromatase inhibitors (AIs) for breast cancer. BD was measured using a fat-water decomposition MRI based BD measure (MRD) previously shown to be more quantitative than mammographic density. A non-randomized observation cohort of 46 postmenopausal women on AI without NSAID use was conducted in parallel to assess the effect of AI on MRD over 12 months. Eligible participants were recruited at two study sites and included women with an intact, unaffected contralateral breast and BI-RADS ≥ 2. Each subject’s MRI_BD measures at baseline and at 6 and 12 months were included in linear mixed models for longitudinal data. Log-transformation was applied to the outcome of BD. Covariates included log-transformed baseline BD, time on AI, and baseline body mass index (BMI) and change in BMI. Breast tissue collagen fiber alignment for 30 women with paired breast biopsies, before and after 6 months on sulindac, was examined using Second-Harmonic Generation (SHG) microscopy and analysis of the distribution (histogram) of ‘straight’ fibers in three randomly selected areas of breast tissue. Straightness of individual fibers was calculated as the linear length of a fiber divided by the distance along the fiber. Results. Participants on sulindac intervention had a significant change in BD relative to baseline BD at 6 (p=0.05) and 12 months (p Citation Format: Patricia Thompson, Chuan Huang, Betsy Wertheim, Christina Preece, Jie Yang, Jessica Martinez, Denise Roe, Pavani Chalasani, Alison Stopeck. Sulindac reduces breast density and alters collagen alignment in patients on aromatase inhibitors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-09.

BACKGROUND Myeloproliferative neoplasms (MPNs) are a group of myeloid malignancies associated with significant symptom burden. Despite pharmacological advances in therapies, inadequate management of MPN symptoms results in reduced quality of life. OBJECTIVE This study aims to determine the feasibility of a 12-week global wellness mobile app intervention in decreasing MPN symptom burden. The University of Arizona Andrew Weil Center for Integrative Medicine’s global wellness mobile app, My Wellness Coach (MWC), guides patients to improve their health and well-being through facilitating behavior changes. METHODS Of the 30 patients enrolled in a 12-week intervention, 16 (53%) were retained through the final assessment. Feasibility was assessed by the ease of recruitment, participant adherence, and mobile app acceptability. App acceptability was measured using the user version of the Mobile Application Rating Scale. MPN symptom burden was measured at baseline and 12 weeks after the intervention. RESULTS Recruitment was efficient, with the participant goal reached within a 60-day period, suggestive of a demand for such an intervention. Adherence was less than the target within study design (75%), although similar to mobile device app use in other studies (53%). The app was deemed acceptable based on the mean user version of the Mobile Application Rating Scale 3-star rating by participants. Finally, there were statistically significant improvements in several MPN symptoms, quality of life, and total score on the Myeloproliferative Neoplasm Symptom Assessment Form surveys. CONCLUSIONS Our 12-week intervention with the MWC app was feasible and was associated with a decrease in MPN symptom burden. Further investigation of the MWC app for use as a self-management strategy to reduce the symptom burden in patients with MPN is warranted.

Background Myeloproliferative neoplasms (MPNs) are a group of myeloid malignancies associated with significant symptom burden. Despite pharmacological advances in therapies, inadequate management of MPN symptoms results in reduced quality of life. Objective This study aims to determine the feasibility of a 12-week global wellness mobile app intervention in decreasing MPN symptom burden. The University of Arizona Andrew Weil Center for Integrative Medicine’s global wellness mobile app, My Wellness Coach (MWC), guides patients to improve their health and well-being through facilitating behavior changes. Methods Of the 30 patients enrolled in a 12-week intervention, 16 (53%) were retained through the final assessment. Feasibility was assessed by the ease of recruitment, participant adherence, and mobile app acceptability. App acceptability was measured using the user version of the Mobile Application Rating Scale. MPN symptom burden was measured at baseline and 12 weeks after the intervention. Results Recruitment was efficient, with the participant goal reached within a 60-day period, suggestive of a demand for such an intervention. Adherence was less than the target within study design (75%), although similar to mobile device app use in other studies (53%). The app was deemed acceptable based on the mean user version of the Mobile Application Rating Scale 3-star rating by participants. Finally, there were statistically significant improvements in several MPN symptoms, quality of life, and total score on the Myeloproliferative Neoplasm Symptom Assessment Form surveys. Conclusions Our 12-week intervention with the MWC app was feasible and was associated with a decrease in MPN symptom burden. Further investigation of the MWC app for use as a self-management strategy to reduce the symptom burden in patients with MPN is warranted.

We evaluated the role of seasonality in self-reported diet quality among postmenopausal women participating in the Women’s Health Initiative (WHI). A total of 156,911 women completed a food frequency questionnaire (FFQ) at enrollment (1993–1998). FFQ responses reflected intake over the prior 3-month period, and seasons were defined as spring (March–May), summer (June–August), fall (September–November), and winter (December–February). FFQ data were used to calculate the Alternate Healthy Eating Index (AHEI), a measure of diet quality that has a score range of 2.5–87.5, with higher scores representing better diet quality. In multivariable linear regression models using winter as the reference season, AHEI scores were higher in spring, summer, and fall (all P values < 0.05); although significant, the variance was minimal (mean AHEI score: winter, 41.7 (standard deviation, 11.3); summer, 42.2 (standard deviation, 11.3)). Applying these findings to hypothesis-driven association analysis of diet quality and its relationship with chronic disease risk (cardiovascular disease) showed that controlling for season had no effect on the estimated hazard ratios. Although significant differences in diet quality across seasons can be detected in this population of US postmenopausal women, these differences are not substantial enough to warrant consideration in association studies of diet quality.

Purpose: To evaluate the effect of sulindac, a nonselective anti-inflammatory drug (NSAID), for activity to reduce breast density (BD), a risk factor for breast cancer. Experimental Design: An open-label phase II study was conducted to test the effect of 12 months' daily sulindac at 150 mg twice daily on change in percent BD in postmenopausal hormone receptor–positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by noncontrast magnetic resonance imaging (MRI) and reported as change in MRI percent BD (MRPD). A nonrandomized patient population on AI therapy (observation group) with comparable baseline BD was also followed for 12 months. Changes in tissue collagen after 6 months of sulindac treatment were explored using second-harmonic generated microscopy in a subset of women in the sulindac group who agreed to repeat breast biopsy. Results: In 43 women who completed 1 year of sulindac (86% of those accrued), relative MRPD significantly decreased by 9.8% [95% confidence interval (CI), −14.6 to −4.7] at 12 months, an absolute decrease of −1.4% (95% CI, −2.5 to −0.3). A significant decrease in mean breast tissue collagen fiber straightness (P = 0.032), an investigational biomarker of tissue inflammation, was also observed. MRPD (relative or absolute) did not change in the AI-only observation group (N = 40). Conclusions: This is the first study to indicate that the NSAID sulindac may reduce BD. Additional studies are needed to verify these findings and determine if prostaglandin E2 inhibition by NSAIDs is important for BD or collagen modulation.

Physical function is critical for mobility and quality of life. We hypothesized that higher total lean mass is associated with higher physical function, and body fat inversely associated, among postmenopausal women. Women's Health Initiative Observational Study participants at Pittsburgh, PA; Birmingham, AL; and Tucson-Phoenix, AZ (1993–1998) completed dual-energy X-ray absorptiometry scans and the Rand SF-36 questionnaire at baseline and 3 y (N = 4526). Associations between quartiles (Q1–4) of lean or fat mass and physical function were tested using linear regression, adjusted for demographics, lifestyle factors, medical history, and scanner serial number. At baseline, participants had a mean ± SD age of 63.4 ± 7.4 y and BMI of 27.4 ± 5.8 kg/m2. Higher percent lean mass was positively associated with physical function at baseline (Q4, 83.6 ± 0.6 versus Q1, 74.6 ± 0.7; p, Highlights • Lean mass (%) is positively associated with physical function in menopause. • Body fat is negatively associated with physical function in menopause. • Decline in physical function is more rapid with gains in fat during menopause. • Body composition influence on functional decline is more evident among women

BACKGROUND Increased breast density is a significant independent risk factor for breast cancer, and recent studies show that this risk is modifiable. Hence, breast density measures sensitive to small changes are desired. PURPOSE Utilizing fat-water decomposition MRI, we propose an automated, reproducible breast density measurement, which is nonionizing and directly comparable to mammographic density (MD). STUDY TYPE Retrospective study. POPULATION The study included two sample sets of breast cancer patients enrolled in a clinical trial, for concordance analysis with MD (40 patients) and reproducibility analysis (10 patients). FIELD STRENGTH/SEQUENCE The majority of MRI scans (59 scans) were performed with a 1.5T GE Signa scanner using radial IDEAL-GRASE sequence, while the remaining (seven scans) were performed with a 3T Siemens Skyra using 3D Cartesian 6-echo GRE sequence with a similar fat-water separation technique. ASSESSMENT After automated breast segmentation, breast density was calculated using FraGW, a new measure developed to reliably reflect the amount of fibroglandular tissue and total water content in the entire breast. Based on its concordance with MD, FraGW was calibrated to MR-based breast density (MRD) to be comparable to MD. A previous breast density measurement, Fra80-the ratio of breast voxels with

BACKGROUND: Dietary energy density (DED) is the ratio of energy [kilocalories (kcal) or kilojoules (kJ)] intake to food weight (grams, g) and is a measure of diet quality. Consumption of foods high in DED has been associated with weight gain in adults. OBJECTIVE: To investigate the association between baseline DED and incident obesity-associated cancers in the Women’s Health Initiative (WHI). DESIGN: Prospective cohort study of clinical trial and observational study participants. PARTICIPANTS/SETTING: Postmenopausal women ages 50–79 years (n = 92,295) enrolled in the observational study or the calcium and vitamin D trial and hormone replacement therapy trials. MAIN OUTCOME MEASURES: Incident, medical record-adjudicated, obesity-related cancers during follow-up. Exposure variable was DED (kcal/g for the total diet) from self-reported dietary intake at baseline using a food frequency questionnaire. STATISTICAL ANALYSES PERFORMED: The associations between DED and each incident cancer, or any obesity-related cancer, were examined using competing-risks regression models, with death as a competing risk. Body mass index (BMI)-stratified models were generated to investigate BMI as a potential modifying factor. RESULTS: DED was associated with higher BMI (mean ± standard deviation: 28.9 ± 6.0 versus 26.3 ± 4.9 kg/m(2)) and waist circumference (89.3 ± 14.2 versus 82.4 ± 12.4 cm) for DED quintiles 5 versus 1, respectively. DED was associated with a 10% increased risk of any obesity-related cancer (subhazard ratio(Q5 vs Q1): 1.1; 95% confidence interval, 1.03–1.2; P = 0.004). This increased risk appeared limited to women who were normal-weight at enrollment. CONCLUSIONS: Higher DED may be a contributing factor for obesity-related cancers, especially among normal-weight postmenopausal women and, as such, could serve as a modifiable behavior for dietary intervention to reduce obesity-associated cancer risk.

Purpose: To investigate how mode of entry into a quitline influences program utilization and quit outcomes among clients seeking cessation services. Design: This is a retrospective analysis of clients receiving quitline services from January 2011 to June 2016. Setting: The study was conducted at the Arizona Smokers’ Helpline. Participants: Enrolled clients completed a 7-month follow-up (N = 18 650). Measures: The independent variable was referral mode of entry (ie, proactive, passive, and self-referral). Outcome variables included tobacco cessation medication use, number of coaching sessions completed, and 30-day tobacco abstinence at 7 months. Analysis: Logistic regression was used to analyze tobacco abstinence after controlling for potential confounders. Results: Compared to self-referred clients, proactively referred clients were least likely (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.81-0.97), whereas passively referred clients were most likely (OR: 1.14; 95% CI: 1.00-1.30) to report tobacco abstinence. Proactively referred (OR: 0.79; 95% CI: 0.70-0.88), but not passively referred, clients were 21% less likely to report tobacco cessation medication use than self-referred clients. Conclusion: Proactive referrals are associated with lower utilization of tobacco cessation medication and less successful quit outcomes; however, provider referrals are critical to reaching tobacco users who may have more significant health risks and barriers to quitting. Examining potential barriers among both providers and provider-referred clients is needed to inform improvements in training providers on brief interventions for tobacco cessation.

Introduction: Integrative hematology oncology (IHO), the combination of complementary medicine in conjunction with conventional cancer treatments, is emerging as an important supportive care modality. Formal education programs, such as IHO fellowship programs, are not currently available. We conducted a national survey to gauge interest and investigate barriers to the development of IHO training programs in the US. Methods: An 18-question survey was sent to hematology/oncology, radiation oncology, and palliative care program directors, physicians, and fellows, and internal medicine residents planning to enter into any of the above fellowship programs. Recruitment was national with use of public email list servs and social media. Program directors and fellowship programs were identified through the Accreditation Council for Graduate Medical Education (ACGME). Participant informed consent was completed online and, Qualtrics survey links were shared weekly via email in two 4-week sessions. Results: Participants (n=208) included physicians from: Hematology/Oncology 65.9% (n=137), Radiation Oncology 8.6%(n=18) and Palliative Care 25.4% (n=53). Hematology oncology respondents included physicians 47.4% (n=65), fellows 33.6% (n=46), and residents planning to enter into a hematology oncology fellowship 3.6% (n=5). Program directors (n=69) from each specialty included: 15.3% (n=21) from hematology/oncology, 61.1% (n=11) from radiation oncology, and 69.8% (n=37) from palliative care. Interestingly, palliative care had the highest response rate in this category. Survey respondents were mostly aged 31-40 y (38.4%), 41-50 y (23.8%), or 51-60 y (21.5%). Participant genders were male (45.7%), female (50.9%), or prefer not to identify (3.5%). There was diverse regional participation across the United States. Overall participant responses revealed significant interest for an IHO training program, despite little (36.0%) to no (49.4%) previous training in integrative medicine (Table 1). Curriculum topics of primary interest were physician/provider wellness, stress reduction techniques, off-label use of medication, exercise/physical activity, nutrition, and lifestyle counseling. The preferred education delivery was didactic lectures and clinical practice exposure. Barriers to implementation included lack of good curriculum and inadequate budget/time/faculty experience to implement the program. Need for IHO training was based on perceived benefit to patients in 39 participants (73.6%), and patient request for services in 37 participants (68.8%). Conclusion: In this national survey of 208 physicians, the majority (64%) expressed interest in IHO education programs. Barriers included lack of curriculum, expertise, budget, and time. Education preference for fellowship track and certificate programs were similar, suggesting interest of both available options. Most participants (87%) felt fellows should participate in IHO research. In conclusion, IHO training is perceived as valuable and desirable. Thus, the development and dissemination of IHO training programs is needed. Figure 1 Figure 1. Disclosures Gowin: Incyte: Speakers Bureau.

e20044 Background: Recent advancements in the treatment of plasma cell disorders (PCD) have led to a revolution in treatment options. Despite improved outcomes, patients have unmet symptom management needs. Integrative medicine (IM) is a method for addressing symptoms in cancer, but its use and efficacy is poorly defined in PCD patients. This analysis describes the utilization of IM among myeloma patients and explores associations with symptom burden. Methods: For 3 months, a 70-question online survey was hosted on HealthTree.org, an online resource for myeloma patients and researchers created by the HealthTree Foundation. The survey included questions about demographics, PCD type, disease stage, complementary practice use, PHQ-2 score (depression screen), and quality of life (sum of 6 interference items; possible score range 0-6). Mean outcome values were compared between IM users and non-users using two-sample t-tests. Proportions of supplement users and IM users were compared between patients currently on myeloma-specific treatment and patients not currently on treatment using chi-square tests. Results: Of 195 total respondents, 17 were excluded for not completing the survey section on IM practices. Median age range was 60-69 years old, 61% were female, 91% were non-Hispanic white, and 57% were overweight or obese. Plasma cell subtypes were active myeloma (81%), smoldering myeloma (12%), MGUS (3%), amyloidosis (2%), and plasmacytoma (1%), and 72% of patients were currently on cancer-specific treatment. On a scale of 1-10 (1=very uncomfortable; 10=very comfortable), patients reported a mean score of 3.7 when discussing IM therapies with their oncologist. The top 10 IM modalities reported were aerobic exercise (83%), nutrition (67%), natural products (60%), strength exercise (52%), support groups (48%), breathing exercises (44%), meditation (42%), yoga (40%), mindfulness-based stress reduction (38%), and massage (38%). Those who participated in meditation had significantly higher PHQ-2 scores (worse depression) than non-participants (1.1 vs. 0.8; p=0.05). Users of support groups (3.4 vs. 2.7; p=0.04), medicinal marijuana (4.0 vs. 2.9; p=0.03), or vitamin C (3.6 vs. 2.7; p=0.01) reported higher mean interference (worse quality of life) than non-users. Compared to patients currently on cancer treatment for PCD, untreated patients were significantly more likely to use curcumin (58% vs. 41%; p=0.04) or green tea (44% vs. 17%; p

Objectives To examine prospective associations between changes in physical activity (PA) and changes in physical performance measures (PPMs) over 6 years in older women. Design Prospective cohort study. Setting Forty clinical centers in the United States. Participants Women aged 65 and older (mean age 69.8) enrolled in the Women's Health Initiative Clinical Trials with gait speed, timed chair stand, grip strength, and self-reported recreational PA data assessed at baseline (1993–98) and follow-up Years 1, 3, and 6 (N = 5,092). Measurements Mixed-effects linear regression models were used to determine the association between time-varying PA and change in each PPM. Potential interactions between time-varying PA and age (

Objective: Tamoxifen (TAM) lowers breast cancer recurrence by 40-50% with evidence of individual variability in responsiveness. A ≥10% decrease in mammography-determined breast density (BD) after 12–18 months of TAM use has been associated with clinical benefit. Early determination of changes in BD may offer a strategy to tailor hormone therapy in non-responders; for responders, it may encourage adherence. Fat-water decomposition MRI (FWD-MRI) is an accurate and fast (< 5 minutes) method for measuring BD without ionizing radiation or contrast agent. Here, we examined whether change in FWD-MRI-derived BD predicts decrease in BD at earlier time points than observable with a 12-month measure of BD. Methods: The study population included a subset of 44 pre- and post-menopausal women receiving TAM for treatment of early-stage breast cancer or prevention who were enrolled in a randomized, placebo-controlled trial of diindolylmethane. Eligibility for this analysis included participants with FWD-MRI scans at baseline, 6 and 12 months. Median time on TAM at baseline was 13 months (IQR, 5–26 months). All MRI images were acquired on a 1.5T GE Signa NV-CV/i scanner. Automated breast segmentation was performed using MATLAB software and validated against manual ROI drawings. MRI-based BD was calculated as the ratio of breast voxels with 2 times the test-retest variability of Fra80 (0.032). McNemar's test was used to test the association between change from baseline to 6 months and change from baseline to 12 months. Results and Discussion: At 12 months, 15 (34%) participants had a decrease in BD, whereas 29 (66%) remained unchanged or increased. Of these 29, 28 also had no decrease at 6 months (specificity = 97%), and 9 of the 15 women who showed a decrease at 12 months had a decrease at 6 months (sensitivity = 60%; McNemar's test, P = 0.06). Conversely, for those women with a measured decrease in BD from baseline to 6 months, 9 of 10 had a measured decrease at 12 months. A study limitation is inclusion of participants on TAM for varying duration as the greatest change in BD likely would have occurred earlier. Ongoing efforts will focus on FWD-MRI for measures of change in BD in patients initiating TAM. Conclusion: Use of the specified cut point would fail to detect a decrease in BD at 12 months in 40% of women. However, a decrease in BD from baseline to 6 months was highly associated with decrease from baseline to 12 months and in some women may be useful as an early biomarker of effect. Ongoing effort is needed to determine the impact of factors such as baseline BD, menopausal status, and time on TAM in misclassification of BD change using the 6-month measure. Acknowledgement: NIH grants CA149417, CA161534.Objective: Tamoxifen (TAM) lowers breast cancer recurrence by 40-50% with evidence of individual variability in responsiveness. A ≥10% decrease in mammography-determined breast density (BD) after 12–18 months of TAM use has been associated with clinical benefit. Early determination of changes in BD may offer a strategy to tailor hormone therapy in non-responders; for responders, it may encourage adherence. Fat-water decomposition MRI (FWD-MRI) is an accurate and fast (< 5 minutes) method for measuring BD without ionizing radiation or contrast agent. Here, we examined whether change in FWD-MRI-derived BD predicts decrease in BD at earlier time points than observable with a 12-month measure of BD. Methods: The study population included a subset of 44 pre- and post-menopausal women receiving TAM for treatment of early-stage breast cancer or prevention who were enrolled in a randomized, placebo-controlled trial of diindolylmethane. Eligibility for this analysis included participants with FWD-MRI scans at baseline, 6 and 12 months. Median time on TAM at baseline was 13 months (IQR, 5–26 months). All MRI images were acquired on a 1.5T GE Signa NV-CV/i scanner. Automated breast segmentation was performed using MATLAB software and validated against manual ROI drawings. MRI-based BD was calculated as the ratio of breast voxels with 2 times the test-retest variability of Fra80 (0.032). McNemar's test was used to test the association between change from baseline to 6 months and change from baseline to 12 months. Results and Discussion: At 12 months, 15 (34%) participants had a decrease in BD, whereas 29 (66%) remained unchanged or increased. Of these 29, 28 also had no decrease at 6 months (specificity = 97%), and 9 of the 15 women who showed a decrease at 12 months had a decrease at 6 months (sensitivity = 60%; McNemar's test, P = 0.06). Conversely, for those women with a measured decrease in BD from baseline to 6 months, 9 of 10 had a measured decrease at 12 months. A study limitation is inclusion of participants on TAM for varying duration as the greatest change in BD likely would have occurred earlier. Ongoing efforts will focus on FWD-MRI for measures of change in BD in patients initiating TAM. Conclusion: Use of the specified cut point would fail to detect a decrease in BD at 12 months in 40% of women. However, a decrease in BD from baseline to 6 months was highly associated with decrease from baseline to 12 months and in some women may be useful as an early biomarker of effect. Ongoing effort is needed to determine the impact of factors such as baseline BD, menopausal status, and time on TAM in misclassification of BD change using the 6-month measure. Acknowledgement: NIH grants CA149417, CA161534. Citation Format: Ding J, Thompson PA, Wertheim BC, Roe DJ, Marron MT, Altbach MI, Galons J-P, Wang F, Thomson CA, Huang C, Stopeck A. Breast density change at 6 months is associated with change at 12 months as measured by fat-water decomposition MRI in women on tamoxifen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-19.

It has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3‐year intervention in a subset of participants randomized to oral UDCA at 8‐10 mg/kg of body weight per day (n = 198) or placebo (n = 203). Study participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This reflected a UDCA‐associated shift in microbial community composition (P < 0.001), independent of sex, with no evidence of a UDCA effect on microbial richness (P > 0.05). These UDCA‐associated shifts in microbial community distance metrics from baseline to end‐of‐study were not associated with risk of any or advanced adenoma (all P > 0.05) in men or women. Separate analyses of microbial networks revealed an overrepresentation of Faecalibacterium prausnitzii in the post‐UDCA arm and an inverse relationship between F prausnitzii and Ruminococcus gnavus. In men who received UDCA, the overrepresentation of F prausnitzii and underrepresentation of R gnavus were more prominent in those with no adenoma recurrence at follow‐up compared to men with recurrence. This relationship was not observed in women. Daily UDCA use modestly influences the relative abundance of microbial species in stool and affects the microbial network composition with suggestive evidence for sex‐specific effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk. ISSN:2045-7634

Type 2 diabetes is typified by insulin-resistance in adipose tissue, skeletal muscle, and liver, leading to chronic hyperglycemia. Additionally, obesity and type 2 diabetes are characterized by chronic low-grade inflammation. Membrane-associated RING-CH-1 (MARCH1) is an E3 ubiquitin ligase best known for suppression of antigen presentation by dendritic and B cells. MARCH1 was recently found to negatively regulate the cell surface levels of the insulin receptor via ubiquitination. This, in turn, impaired insulin sensitivity in mouse models. Here, we report that MARCH1-deficient (knockout; KO) female mice exhibit excessive weight gain and excessive visceral adiposity when reared on standard chow diet, without increased inflammatory cell infiltration of adipose tissue. By contrast, male MARCH1 KO mice had similar weight gain and visceral adiposity to wildtype (WT) male mice. MARCH1 KO mice of both sexes were more glucose tolerant than WT mice. The levels of insulin receptor were generally higher in insulin-responsive tissues (especially the liver) from female MARCH1 KO mice compared to males, with the potential to account in part for the differences between male and female MARCH1 KO mice. We also explored a potential role for MARCH1 in human type 2 diabetes risk through genetic association testing in publicly-available datasets, and found evidence suggestive of association. Collectively, our data indicate an additional link between immune function and diabetes, specifically implicating MARCH1 as a regulator of lipid metabolism and glucose tolerance, whose function is modified by sex-specific factors.

Background Over 23 million Americans have type 2 diabetes (T2D). Eating habits such as breakfast consumption, time-restricted eating, and limiting daily eating occasions have been explored as behaviors for reducing T2D risk, but prior evidence is inconclusive. Objectives Our objectives were to examine associations between number of daily eating occasions and T2D risk in the Women's Health Initiative Dietary Modification Trial (WHI-DM) and whether associations vary by BMI, age, or race/ethnicity. Methods Participants were postmenopausal women in the WHI-DM who comprised a 4.6% subsample completing 24-h dietary recalls (24HRs) at years 3 and 6 as part of trial adherence activities (n = 2159). Numbers of eating occasions per day were obtained from the year 3 24HRs, and participants were grouped into approximate tertiles as 1–3 (n = 795), 4 (n = 713), and ≥5 (n = 651) daily eating occasions as the exposure. Incident diabetes was self-reported on semiannual questionnaires as the outcome. Results Approximately 15% (15.4%, n = 332) of the WHI-DM 24HR cohort reported incident diabetes at follow-up. Cox proportional hazards regression tested associations of eating occasions with T2D adjusted for neighborhood socioeconomic status, BMI, waist circumference, race/ethnicity, family history of T2D, recreational physical activity, Healthy Eating Index-2005, 24HR energy intake, and WHI-DM arm. Compared with women reporting 1–3 meals/d, those consuming 4 meals/d had a T2D HR = 1.38 (95% CI: 1.03, 1.84) without further increases in risk for ≥5 meals/d. In stratified analyses, associations for 4 meals/d compared with 1–3 meals/d were stronger in women with BMI, Four meals/day compared to fewer meals may increase the risk of Type 2 diabetes in older women but no dose response effect seen for higher frequency.

Physical activity has been shown to improve quality of life, body composition, metabolic and physical function, and survival among cancer survivors. However, no studies have focused on Native American cancer survivors. Methods: Native cancer survivors and family members were enrolled in a 12-week multi-site, randomized supervised and home-based physical activity intervention (n = 63). The intervention includes 1d/wk supervised resistance, aerobic, flexibility, and balance and 2-3 days/wk of home-based exercise. National guidelines for survivorship exercise training were culturally tailored based focus groups and interviews, as well as cultural expert program review by representatives from 10 tribes. Preliminary descriptive statistics (mean, SD) and six and twelve week changes in weight (kg), fat mass (%), HbA1c (%), fitness by 6min walk test (meters), and quality of life by PROMIS10 questionnaire score have been assessed by paired t-test for survivors only (n = 30). Though currently under powered, data collection is ongoing and will be updated as participants complete the 12-week intervention. Results: Participants were 58.4 ± 12.2 years of age. Tumor types were breast (n = 7), colorectal (n = 7), stomach (n = 2), lung (n = 2), and other varied cancers. Reasons for loss to follow-up were: repeat surgeries or change in clinical care plan (n=3), loss of family members (n=1), and loss of contact (n=3). Comorbidities for cancer survivors included: diabetes (n=7), cardiovascular disease (N=13). Twenty-two Native cancer survivors have completed six weeks of intervention and 14 Native cancer survivors have completed twelve weeks of intervention thus far. Weight loss was significant at six weeks (-1.0 ± 2.2kg; p=0.04), but not twelve weeks. Fitness and quality of life were improved by twelve weeks, 31.9 ± 132m and 1.6±0.4, respectively, though not significant. Conclusions: Tailored exercise programs present opportunities to restore health and balance among Native cancer survivors. This ongoing trial will provide important information on the effects of physical activity in Native cancer survivorship, unaddressed to date. Citation Format: Jennifer W Bea, Hendrik de Heer, Taylor Lane, Brenda Charley, Etta Yazzie, Jennifer Hudson, Mishayla Mitchell, Betsy Wertheim, Anna Schwartz. Restoring Balance, a physical activity intervention for Native cancer survivors, preliminary analysis (NNR.14.192) [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B002.

e15546 Background: Pancreatic cancer (PC) is a high mortality malignancy typically found when curative surgery is not an option. Liquid biopsies are a minimally invasive option that may allow earlier detection of PC. Using a bioinformatic analysis of TCGA and GEO we identified a novel set of blood-based biomarkers to detect PC with high sensitivity and specificity (AUROC = 0.999) (Vrba et al, Epigenetics 2019). Here we tested the ability of this DNA methylation signature (MS) to distinguish metastatic PC from pancreatic cysts (Cy) and healthy controls (HC) through quantitative DNA methylation analysis of cell free DNA (cfDNA). Methods: A 10 gene DNA methylation marker set that identifies PC was used to evaluate the cfDNA component of the plasma of PC patients, Cy patients and HC. The ROC analysis and AUC calculations were performed using the R library pROC (Robin et al, BMC Bioinformatics 2011). Plasma samples were collected in cfDNA collection tubes from patients with benign Cy, PC, and HC. Clinical information was collected including age, gender, smoking history, CA 19-9 level, cyst size, presence of liver metastases, and survival status. After processing and cfDNA extraction, qRT-PCR methylation analysis was performed on these prospectively collected samples. The difference in median DNA MS per marker of the full 10-gene marker set between the above groups was analyzed by Wilcoxon rank sum test and ROC analysis. A Cox proportional hazard regression model was used to test the association between MS and survival. Results: A total of 66 samples were collected (PC = 10, Cy = 12, HC = 44). Clinical information was collected on all patients included in the analysis. Using liquid biopsies for cfDNA analysis and a novel set of DNA methylation biomarkers, MS was substantially stronger in PC (median, 13.2) patients than Cy (median, 3.5) patients (p = 0.0001). Importantly, while there was no clear association between MS and age, gender, smoking status, CA 19-9 levels, or presence of liver metastases, higher methylation levels were non-significantly associated with worse overall survival in PC patients (HR, 1.29; 95% CI, 0.97–1.72; p = 0.082). Conclusions: While this is a small sample size, early findings suggest that a DNA MS may reliably distinguish PC from benign Cy. The strength of signal may be a prognostic marker that could play a role in determining treatment approaches. Given its utility in predicting PC, future directions include testing this tool as a blood-based early detection mechanism as well as a predictor for recurrence or response to PC treatment.

The purpose of this study was to determine if oxylipins – oxygenated bioactive lipid metabolites of ω-3 and ω-6 fatty acids with varying roles in inflammation and pain – correlate with aromatase inhibitor-associated arthralgia (AIA) and quality of life (QOL) in early stage breast cancer (ESBC) patients. Methods: ESBC patients on AI therapy were enrolled to an open-label study of sulindac, a non-steroidal anti-inflammatory drug (NSAID), for 12 months (n = 47). Pre-intervention arthralgia and physical function were assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire, where higher scores indicate worse symptoms. The Functional Assessment of Cancer Therapy – General (FACT-G) questionnaire was used to assess QOL, where higher scores indicate better QOL. A total of 53 plasma oxylipins in plasma were quantified by mass spectrometry. Pearson's correlation was used to measure the association between pre-intervention oxylipin concentrations, arthralgias and QOL. Results: Prior to initiating sulindac, baseline levels of 17 oxylipins were found to be significantly correlated with QOL scales. This included inverse associations between QOL and seven pro-inflammatory products of ω-6 fatty acid metabolism. Notably, prostaglandin E2, the primary target of NSAIDs, was negatively correlated with Social Well-Being (rho = −0.30; P = 0.04). Conversely, resolvin D1, a potent anti-inflammatory lipid, was positively associated with Total FACT-G (rho = 0.31; P = 0.03) and Emotional Well-Being (rho = 0.37; P = 0.01). Two ω-3 metabolites with unknown mechanisms were correlated with both QOL and WOMAC; 19,20-DiHDPE was positively correlated with Total (rho = 0.34; P = 0.02) and Social FACT-G (rho = 0.32; P = 0.03), and inversely with Total WOMAC (rho = -0.303; P = 0.04) and Stiffness (rho = −0.32; P = 0.03); and 5(6)-DiHETE was inversely correlated with Social FACT-G (rho = −0.33; P = 0.02) and positively with Total WOMAC (rho = 0.31; P = 0.04). Conclusions: This is the first evidence that plasma oxylipin metabolites of ω-3/ω-6 fatty acids correlate with QOL and arthralgia symptoms in patients on AIs and suggests oxylipins as a potential novel target for improving QOL and adherence to AI therapy in patients with ESBC.

Study Objectives To evaluate the associations between sedentary time, total (total-PA), light (light-PA), moderate (MOD-PA), and vigorous (VIG-PA) physical activity with indices of sleep in postmenopausal women. Methods Baseline self-reported data from the Women’s Health Initiative Observational Study (n = 75 074) were used in this cross-sectional analysis. Total-PA, light-PA, MOD-PA, and VIG-PA were categorized by metabolic equivalents of the activity (MET-hour [hr]/week [wk]) and were estimated using validated questionnaires. Sedentary time was categorized by hr/day and was estimated via questionnaire. Logistic regression was used to examine the associations between these variables and short sleep (≤6 hr/night), long sleep (≥10 hr/night), poor sleep quality, and insomnia symptoms after adjustment for age, race, socioeconomic status, body mass index, health status, depressive symptoms, smoking status, alcohol use, hormone therapy, and comorbidities. Results Higher sedentary time (>11 hr/day) was associated with higher odds of short sleep (odds ratio [OR] = 1.80, 95% confidence interval [CI]: 1.72–1.88), poor sleep quality (OR = 1.85, 95% CI: 1.74–1.97), and insomnia symptoms (OR = 1.56, 95% CI: 1.49–1.64). Light-PA (>0 MET-hr/wk) was associated with lower odds of short sleep (OR = 0.96, 95% CI: 0.92–1.00), and higher amounts of total-PA (OR = 0.90, 95% CI: 0.84–0.97), light-PA (OR = 0.94, 95% CI: 0.89–1.00), and MOD-PA (OR = 0.91, 95% CI: 0.86–0.97) were associated with lower odds of poor sleep quality. Conclusions Our findings suggest that higher levels of light and moderate intensity physical activity are associated with better sleep quality, whereas higher amounts of sedentary time are associated with short sleep and lower quality sleep. Future studies should investigate the directionality of these associations and potential causal pathways.

Research suggests that women may have poorer tobacco cessation outcomes than men; however, the literature is somewhat mixed. Less is known about gender differences in cessation within quitline settings. This study examined gender differences in the utilization of services (i.e., coaching sessions, pharmacotherapy) and tobacco cessation among callers to the Arizona Smokers’ Helpline (ASHLine). The study sample included callers enrolled in ASHLine between January 2011 and June 2016. We tracked number of completed coaching sessions. At the 7-month follow-up, callers retrospectively reported use of cessation pharmacotherapy (gum, patch, or lozenge), as well as current tobacco use. Associations between gender and tobacco cessation were tested using logistic regression models. At month 7, 36.4% of women (3,277/9,004) and 40.3% of men (2,960/7,341) self-reported 30-day point prevalence abstinence. Compared to men, fewer women reported using pharmacotherapy (women: 71.4% vs. men: 73.6%, p = .01) and completed at least five coaching sessions (women: 35.1% vs. men: 38.5%, p < .01). After adjusting for baseline characteristics, women had significantly lower odds of reporting tobacco cessation than men (OR = 0.91, 95% CI: 0.84 to 0.99). However, after further adjustment for use of pharmacotherapy and coaching, there was no longer a significant relationship between gender and tobacco cessation (OR: 0.96, 95% CI: 0.87 to 1.06). Fewer women than men reported tobacco cessation. Women also had lower utilization of quitline cessation services. Although the magnitude of these differences were small, future research on improving the utilization of quitline services among women may be worth pursuing given the large-scale effects of tobacco.

Objective: Smokers with comorbid health conditions have a disproportionate burden of tobacco-related death and disease. A better understanding of differences in quit rates among smokers with comorbid health conditions can guide tailoring of quitline services for subgroups. The objective of this study was to examine self-reported tobacco cessation rates among Arizona Smokers’ Helpline callers with chronic health conditions (CHCs) and/or a mental health condition (MHC). Methods: We analyzed data from quitline telephone callers (n = 39 779) who enrolled in and completed at least 1 behavioral counseling session (ie, coaching call). We categorized callers as CHC only (cardiovascular disease/respiratory-related/cancer; 32%), MHC only (eg, mood/anxiety/substance dependence; 13%), CHC + MHC (25%), or no comorbid condition (30%). We assessed 30-day abstinence at 7-month follow-up for 16 683 clients (41.9%). We used logistic regression analysis to test associations between comorbidity and quit outcomes after controlling for relevant variables (eg, nicotine dependence). Results: Overall quit rates were 45.4% for those with no comorbid condition, 43.3% for those with a CHC only, 37.0% for those with an MHC only, and 33.3% for those with CHC + MHC. Compared with other groups, the CHC + MHC group had the lowest odds of quitting (adjusted odds ratio = 0.60; 95% confidence interval, 0.52-0.69). Conclusion: Having a comorbid condition was associated with lower quit rates, and smokers with co-occurring CHCs and MHCs had the lowest quit rates. Quitlines should evaluate more intensive, evidence-driven, tailored services for smoking cessation among callers with comorbid conditions.

Objectives To compare the value of clinically measured gait speed with that of the self‐reported Medical Outcomes Study 36‐item Short‐Form Survey Physical Function Index (SF‐36 PF) in predicting future preclinical mobility disability (PCMD) in older women. Design Prospective cohort study. Setting Forty clinical centers in the United States. Participants Women aged 65 to 79 enrolled in the Women's Health Initiative Clinical Trials with gait speed and SF‐36 assessed at baseline (1993–1998) and follow‐up Years 1, 3, and 6 (N = 3,587). Measurements Women were categorized as nondecliners or decliners based on changes (from baseline to Year 1) in gait speed and SF‐36 PF scores. Logistic regression models were used to estimate incident PCMD (gait speed

Drugs that inhibit cyclooxygenase (COX)-2 and the metabolism of arachidonic acid (ARA) to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins) by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel) trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90) or placebo (n = 95). We assessed the effect of celecoxib (with and without low dose aspirin) on circulating oxylipins and systolic blood pressure (SBP). Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P

Studies suggest that ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) may preserve skeletal muscle with aging. We evaluated longitudinal differences in lean body mass (LBM) among women diagnosed with hypertension and classified as ACE-I/ARB users and nonusers among Women’s Health Initiative participants that received dual energy X-ray absorptiometry scans to estimate body composition (n=10,635) at baseline and at years 3 and 6 of follow-up. Of those, 2642 were treated for hypertension at baseline. Multivariate linear regression models, adjusted for relevant demographics, behaviors, and medications, assessed ACE-I/ARB use/nonuse and LBM associations at baseline, as well as change in LBM over 3 and 6 years. Although BMI did not differ by ACE-I/ARB use, LBM (%) was significantly higher in ACE-I/ARB users versus nonusers at baseline (52.2% versus 51.3%, resp., p=0.001). There was no association between ACE-I/ARB usage and change in LBM over time. Reasons for higher LBM with ACE-I/ARB use cross sectionally, but not longitundinally, are unclear and may reflect a threshold effect of these medications on LBM that is attenuated over time. Nevertheless, ACE-I/ARB use does not appear to negatively impact LBM in the long term.

ObjectiveWe previously reported that Ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduces risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colon cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies.DesignUsing banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal neoplasia, we compared change in the microbiome composition after 3 years intervention in a subset of participants randomized to 8–10 mg/kg of body weight UDCA (n=198) to placebo (n=203). UDCA effects on the microbiome, sex and adenoma outcome were investigated.ResultsStudy participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This change reflected an UDCA-associated shift in microbial community distance metrics (P 0.05). These UDCA-associated shifts in microbial community distance metrics from baseline to end-of-study were not associated with risk of any or advanced adenoma (all P> 0.05) in men or women.ConclusionDespite a large sampling of randomized clinical trial participants, daily UDCA use only modestly influenced the relative abundance of microbial species in stool with no evidence for effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk.SUMMARYWhat is already known about this subject?Ursodeoxycholic acid (UDCA) is a therapeutic bile acid used in the treatment of primary biliary cirrhosis (PBC) and investigated for anti-cancer activity in the colonIn humans, UDCA is produced in the colon from the conjugation of primary bile acids by intestinal bacteriaIntestinal bacteria play a critical role in human intestinal health and disease including a hypothesized role in the development of colorectal cancer.UDCA was found to reduce the risk of more advanced colorectal adenoma with effects present in men but not women.Therapeutic UDCA was recently shown to reduce the extent of bacterial dysbiosis in patients with PBCWhat are the new findings?Among a population of patients with colorectal adenoma, low dose oral UDCA taken daily produced modest changes in fecal bacterial compositionUDCA associated changes in the gut microbiome were similar in men and women.UDCA associated changes in the gut micobiome were not associated with risk of any or advanced colorectal adenoma in the patient population.How might it impact on clinical practice in the foreseeable future?These findings confirm effects of oral UDCA on the microbiome that may be beneficial for patients with PBC.These findings suggest that the anti-cancer effects of UDCA for colorectal adenoma prevention are not due to major effects of UDCA on the gut microbiome.