A national survey of caregiver's own experiences and perceptions of U.S. health care system when addressing their health and caring for an older adult.

BACKGROUND: Caregiving is a demanding role that can negatively impact a person's health and well-being. As such, adequate access to health care is important for maintaining the family caregiver's own personal health. The aims of this study were to identify if family caregivers of older adults had more difficulty accessing health care services than non-caregivers and to identify if family caregivers felt access to additional services would be beneficial for maintaining their own personal health care. METHODS: National survey of 3026 US adults aged 30 to 89 years old. Participants were grouped based on self-reported caregiving experience. Survey asked about access to care, importance of health care services and whether caregivers had support needed. Descriptive statistics were used to compare caregiver and non-caregiver's responses. Multivariate logistic regression model assessed correlates of caregivers not having the support they needed. RESULTS: Caregivers were older, female, lower educational attainment, lower income, had more multiple chronic health conditions and health condition or disability that impacts their daily life. Caregivers reported difficulty accessing mental health services, dental services, medications, and supportive services at home. Caregivers felt it was important to have care coordinator, long-term relationship with primary care provider and access to house calls, telemedicine, and medications delivered to the home. Age, ethnicity, chronic conditions and confidence in finances were factors influencing whether caregiver had support needed to provide assistance to older care recipient. CONCLUSION: Caregivers provide needed support and care to older adults while also needing support for themselves. Health care services delivered in the home were highly desirable to caregivers and could help them maintain their health and well-being.

Research-based PAM50 signature and long-term breast cancer survival.

PURPOSE: Multi-gene signatures provide biological insight and risk stratification in breast cancer. Intrinsic molecular subtypes defined by mRNA expression of 50 genes (PAM50) are prognostic in hormone-receptor positive postmenopausal breast cancer. Yet, for 25-40% in the PAM50 intermediate risk group, long-term risk remains uncertain. Our study aimed to (i) test the long-term prognostic value of the PAM50 signature in pre- and post-menopausal breast cancer; (ii) investigate if the PAM50 model could be improved by addition of other mRNAs implicated in oncogenesis. METHODS: We used archived FFPE samples from 1723 breast cancer survivors; high quality reads were obtained on 1253 samples. Transcript expression was quantified using a custom codeset with probes for > 100 targets. Cox models assessed gene signatures for breast cancer relapse and survival. RESULTS: Over 15 + years of follow-up, PAM50 subtypes were (P < 0.01) associated with breast cancer outcomes after accounting for tumor stage, grade and age at diagnosis. Results did not differ by menopausal status at diagnosis. Women with Luminal B (versus Luminal A) subtype had a > 60% higher hazard. Addition of a 13-gene hypoxia signature improved prognostication with > 40% higher hazard in the highest vs lowest hypoxia tertiles. CONCLUSIONS: PAM50 intrinsic subtypes were independently prognostic for long-term breast cancer survival, irrespective of menopausal status. Addition of hypoxia signatures improved risk prediction. If replicated, incorporating the 13-gene hypoxia signature into the existing PAM50 risk assessment tool, may refine risk stratification and further clarify treatment for breast cancer.

Continuous, objective measurement of physical activity during chemotherapy for breast cancer: the Activity in Treatment pilot study.

Despite many potential benefits of physical activity during and after breast cancer treatment, activity levels typically decline from pre- to posttreatment. Most previous research has relied on self-reported activity. The purpose of this study were to assess patterns of daily, to objectively measured physical activity throughout chemotherapy for breast cancer, and to identify predictors of physical activity patterns. Participants were given a Fitbit before starting chemotherapy and asked to wear it throughout chemotherapy. Restricted cubic splines assessed nonlinear patterns of Fitbit measured total physical activity (TPA) and moderate-to-vigorous physical activity (MVPA) throughout the duration of chemotherapy (mean = 17 weeks, standard deviation [SD] = 6.3). Mixed-effects regression models assessed the rate of physical activity decline. Regressions of subject-level random slope assessed predictors of the rate of physical activity decline on participant and cancer characteristics and self-reported physical and cognitive functioning. Participants (n = 32) were on average 50 years old; the majority had stage II breast cancer. MVPA declined linearly at a mean rate of 1.4 min/day (p = .002) for every 10% of chemotherapy completed, whereas TPA declined linearly at an average rate of 13.4 min/day (p = .0007) for every 10% of chemotherapy completed, until around halfway through chemotherapy, when activity rates leveled off. HER+ receptor status was associated with a greater rate of MVPA decline, ß = 13.3, p = .04. This novel study of objectively measured daily MVPA throughout chemotherapy showed that most reductions in activity occurred during the first half of a course of chemotherapy. Targeting this early period of chemotherapy may be important for preventing declines in activity levels throughout chemotherapy.

Mediators of a Physical Activity Intervention on Cognition in Breast Cancer Survivors: Evidence From a Randomized Controlled Trial.

BACKGROUND: Emerging research suggests that increasing physical activity can help improve cognition among breast cancer survivors. However, little is known about the mechanism through which physical activity impacts cancer survivors' cognition. OBJECTIVE: The objective of this secondary analysis examined physical and psychological function potentially linking physical activity with changes in cognition among breast cancer survivors in a randomized controlled trial where the exercise arm had greater improvements in cognition than the control arm. METHODS: A total of 87 sedentary breast cancer survivors were randomized to a 12-week physical activity intervention (n=43) or control condition (n=44). Objectively measured processing speed (National Institutes of Health Toolbox Oral Symbol Digit), self-reported cognition (patient-reported outcomes measurement information system [PROMIS] cognitive abilities), PROMIS measures of physical and psychological function (depression, anxiety, fatigue, and physical functioning), and plasma biomarkers (brain-derived neurotrophic factor, homeostatic model assessment 2 of insulin resistance, and C-reactive protein [CRP]) were collected at baseline and 12 weeks. Linear mixed-effects models tested intervention effects on changes in physical and psychological function variables and biomarkers. Bootstrapping was used to assess mediation. Exploratory analyses examined self-reported cognitive abilities and processing speed as mediators of the intervention effect on physical functioning. RESULTS: Participants in the exercise arm had significantly greater improvements in physical functioning (beta=1.23; 95% CI 2.42 to 0.03; P=.049) and reductions in anxiety (beta=-1.50; 95% CI -0.07 to -2.94; P=.04) than those in the control arm. Anxiety significantly mediated the intervention effect on cognitive abilities (bootstrap 95% CI -1.96 to -0.06), whereas physical functioning did not (bootstrap 95% CI -1.12 to 0.10). Neither anxiety (bootstrap 95% CI -1.18 to 0.74) nor physical functioning (bootstrap 95% CI -2.34 to 0.15) mediated the intervention effect on processing speed. Of the biomarkers, only CRP had greater changes in the exercise arm than the control arm (beta=.253; 95% CI -0.04 to 0.57; P=.09), but CRP was not associated with cognition; therefore, none of the biomarker measures mediated the intervention effect on cognition. Neither cognitive abilities (bootstrap 95% CI -0.06 to 0.68) nor processing speed (bootstrap 95% CI -0.15 to 0.63) mediated the intervention effect on physical function. CONCLUSIONS: Physical activity interventions may improve self-reported cognition by decreasing anxiety. If supported by larger studies, reducing anxiety may be an important target for improving self-reported cognition among cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT02332876; https://clinicaltrials.gov/ct2/show/NCT02332876.

miRNAs and Long-term Breast Cancer Survival: Evidence from the WHEL Study.

BACKGROUND: There is substantial variation in breast cancer survival rates, even among patients with similar clinical and genomic profiles. New biomarkers are needed to improve risk stratification and inform treatment options. Our aim was to identify novel miRNAs associated with breast cancer survival and quantify their prognostic value after adjusting for established clinical factors and genomic markers. METHODS: Using the Women's Healthy Eating and Living (WHEL) breast cancer cohort with >15 years of follow-up and archived tumor specimens, we assayed PAM50 mRNAs and 25 miRNAs using the Nanostring nCounter platform. RESULTS: We obtained high-quality reads on 1,253 samples (75% of available specimens) and used an existing research-use algorithm to ascertain PAM50 subtypes and risk scores (ROR-PT). We identified miRNAs significantly associated with breast cancer outcomes and then tested these in independent TCGA samples. miRNAs that were also prognostic in TCGA samples were further evaluated in multiple regression Cox models. We also used penalized regression for unbiased discovery. CONCLUSIONS: Two miRNAs, 210 and 29c, were associated with breast cancer outcomes in the WHEL and TCGA studies and further improved risk stratification within PAM50 risk groups: 10-year survival was 62% in the node-negative high miR-210-high ROR-PT group versus 75% in the low miR-210- high ROR-PT group. Similar results were obtained for miR-29c. We identified three additional miRNAs, 187-3p, 143-3p, and 205-5p, via penalized regression. IMPACT: Our findings suggest that miRNAs might be prognostic for long-term breast cancer survival and might improve risk stratification. Further research to incorporate miRNAs into existing clinicogenomic signatures is needed.

Physical Activity Change in an RCT: Comparison of Measurement Methods.

Objectives: We aimed to quantify the agreement between self-report, standard cut-point accelerometer, and machine learning accelerometer estimates of physical activity (PA), and exam- ine how agreement changes over time among older adults in an intervention setting. Methods: Data were from a randomized weight loss trial that encouraged increased PA among 333 postmenopausal breast cancer survivors. PA was estimated using accelerometry and a validated questionnaire at baseline and 6-months. Accelerometer data were processed using standard cut-points and a validated machine learning algorithm. Agreement of PA at each time-point and change was assessed using mixed effects regression models and concordance correlation. Results: At baseline, self-report and machine learning provided similar PA estimates (mean dif- ference = 11.5 min/day) unlike self-report and standard cut-points (mean difference = 36.3 min/ day). Cut-point and machine learning methods assessed PA change over time more similarly than other comparisons. Specifically, the mean difference of PA change for the cut-point versus machine learning methods was 5.1 min/day for intervention group and 2.9 in controls, whereas it was ≥ 24.7 min/day for other comparisons. Conclusions: Intervention researchers are facing the issue of self-report measures introducing bias and accelerometer cut-points being insensi- tive. Machine learning approaches may bridge this gap.

Breast cancer survivors reduce accelerometer-measured sedentary time in an exercise intervention.

PURPOSE: Cancer survivors are highly sedentary and have low physical activity. How physical activity interventions impact sedentary behavior remains unclear. This secondary analysis examined changes in sedentary behavior among breast cancer survivors participating in a physical activity intervention that significantly increased moderate-to-vigorous physical activity (MVPA). METHODS: Insufficiently active breast cancer survivors were randomized to a 12-week physical activity intervention (exercise arm) or control arm. The intervention focused solely on increasing MVPA with no content targeting sedentary behavior. Total sedentary behavior, light physical activity (LPA), and MVPA were measured at baseline and 12 weeks (ActiGraph GT3X+ accelerometer). Separate linear mixed-effects models tested intervention effects on sedentary behavior, intervention effects on LPA, the relationship between change in MVPA and change in sedentary behavior, and potential moderators of intervention effects on sedentary behavior. RESULTS: The exercise arm had significantly greater reductions in sedentary behavior than the control arm (mean - 24.9 min/day (SD = 5.9) vs. - 4.8 min/day (SD = 5.9), b = - 20.1 (SE = 8.4), p = 0.02). Larger increases in MVPA were associated with larger decreases in sedentary behavior (b = - 1.9 (SE = 0.21), p < 0.001). Women farther out from surgery had significantly greater reductions in sedentary behavior than women closer to surgery (b = - 0.91 (SE = 0.5), p = 0.07). There was no significant group difference in change in LPA from baseline to 12 weeks (b = 5.64 (SE = 7.69), p = 0.48). CONCLUSIONS: Breast cancer survivors in a physical activity intervention reduced total sedentary time in addition to increasing MVPA. IMPLICATIONS FOR CANCER SURVIVORS: Both increasing physical activity and reducing sedentary behavior are needed to promote optimal health in cancer survivors. These results show that MVPA and sedentary behavior could be successfully targeted together, particularly among longer-term cancer survivors. CLINICAL TRIAL REGISTRATION: This study is registered at www.ClinicalTrials.gov (NCT02332876).

The effects of weight loss and metformin on cognition among breast cancer survivors: Evidence from the Reach for Health study.

OBJECTIVE: Breast cancer survivors experience problems with cognition that interfere with daily life and can last for years. In the general population, obesity and diabetes are risk factors for cognitive decline, and weight loss can improve cognition; however, the impact of intentional weight loss on cancer survivors' cognition has not been tested. We investigated the impact of weight loss and metformin on changes in cognitive function in a sample of breast cancer survivors. METHODS: Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomized to a weight loss intervention versus control and metformin versus placebo in a 2 × 2 factorial design. Outcomes were changes in five cognitive domains from baseline to 6 months measured by objective neurocognitive tests. RESULTS: There were no statistically significant intervention effects for the metformin or weight loss interventions in five neurocognitive domains. Baseline body mass index (BMI) was a significant effect modifier of the changes in verbal functioning for the weight loss (P = 0.009) and metformin interventions (P = 0.0125). These effect modifications were independent of percent weight loss achieved during the 6-month study period. CONCLUSIONS: This randomized controlled trial of weight loss and metformin interventions that examined changes to cognition among breast cancer survivors suggests that these interventions may not improve cognitive functioning among breast cancer survivors in general. However, weight loss may improve verbal functioning among individuals with a higher BMI.

Dimensions of sedentary behavior and objective cognitive functioning in breast cancer survivors.

PURPOSE: To examine associations between dimensions of sedentary behavior and cognitive function in breast cancer survivors. METHODS: Sedentary behavior variables were measured using thigh-worn activPALs, and included total daily sitting time, time in long sitting bouts, sit-to-stand transitions, and standing time. Cognitive function was assessed using the NIH Toolbox Cognitive Domain. Separate multivariable linear regression models were used to examine associations between sedentary behavior variables with the cognitive domain scores of attention, executive functioning, episodic memory, working memory, and information processing speed. RESULTS: Thirty breast cancer survivors with a mean age of 62.2 (SD = 7.8) years who were 2.6 (SD = 1.1) years since diagnosis completed study assessments. In multivariable linear regression models, more time spent standing was associated with faster information processing (b: 5.78; p = 0.03), and more time spent in long sitting bouts was associated with worse executive function (b: -2.82; p = 0.02), after adjustment for covariates. No other sedentary behavior variables were statistically significantly associated with the cognitive domains examined in this study. CONCLUSIONS: Two important sedentary constructs that are amenable to intervention, including time in prolonged sitting bouts and standing time, may be associated with cognitive function in breast cancer survivors. More research is needed to determine whether modifying these dimensions of sedentary behavior will improve cognitive function in women with a history of breast cancer, or prevent it from declining in breast cancer patients.

Patterns of Fitbit Use and Activity Levels Throughout a Physical Activity Intervention: Exploratory Analysis from a Randomized Controlled Trial.

BACKGROUND: There has been a rapid increase in the use of technology-based activity trackers to promote behavior change. However, little is known about how individuals use these trackers on a day-to-day basis or how tracker use relates to increasing physical activity. OBJECTIVE: The aims were to use minute level data collected from a Fitbit tracker throughout a physical activity intervention to examine patterns of Fitbit use and activity and their relationships with success in the intervention based on ActiGraph-measured moderate to vigorous physical activity (MVPA). METHODS: Participants included 42 female breast cancer survivors randomized to the physical activity intervention arm of a 12-week randomized controlled trial. The Fitbit One was worn daily throughout the 12-week intervention. ActiGraph GT3X+ accelerometer was worn for 7 days at baseline (prerandomization) and end of intervention (week 12). Self-reported frequency of looking at activity data on the Fitbit tracker and app or website was collected at week 12. RESULTS: Adherence to wearing the Fitbit was high and stable, with a mean of 88.13% of valid days over 12 weeks (SD 14.49%). Greater adherence to wearing the Fitbit was associated with greater increases in ActiGraph-measured MVPA (binteraction=0.35, P<.001). Participants averaged 182.6 minutes/week (SD 143.9) of MVPA on the Fitbit, with significant variation in MVPA over the 12 weeks (F=1.91, P=.04). The majority (68%, 27/40) of participants reported looking at their tracker or looking at the Fitbit app or website once a day or more. Changes in Actigraph-measured MVPA were associated with frequency of looking at one's data on the tracker (b=-1.36, P=.07) but not significantly associated with frequency of looking at one's data on the app or website (P=.36). CONCLUSIONS: This is one of the first studies to explore the relationship between use of a commercially available activity tracker and success in a physical activity intervention. A deeper understanding of how individuals engage with technology-based trackers may enable us to more effectively use these types of trackers to promote behavior change. TRIAL REGISTRATION: ClinicalTrials.gov NCT02332876; https://clinicaltrials.gov/ct2/show/NCT02332876?term=NCT02332876 &rank=1 (Archived by WebCite at http://www.webcitation.org/6wplEeg8i).

Randomized controlled trial of increasing physical activity on objectively measured and self-reported cognitive functioning among breast cancer survivors: The memory & motion study.

BACKGROUND: Increasing physical activity can improve cognition in healthy and cognitively impaired adults; however, the benefits for cancer survivors are unknown. The current study examined a 12-week physical activity intervention, compared with a control condition, on objective and self-reported cognition among breast cancer survivors. METHODS: Sedentary breast cancer survivors were randomized to an exercise arm (n = 43) or a control arm (n = 44). At baseline and at 12 weeks, objective cognition was measured with the National Institutes of Health Cognitive Toolbox, and self-reported cognition using the Patient-Reported Outcomes Measurement Information System scales. Linear mixed-effects regression models tested intervention effects for changes in cognition scores. RESULTS: On average, participants (n = 87) were aged 57 years (standard deviation, 10.4 years) and were 2.5 years (standard deviation, 1.3 years) post surgery. Scores on the Oral Symbol Digit subscale (a measure of processing speed) evidenced differential improvement in the exercise arm versus the control arm (b = 2.01; P < .05). The between-group differences in improvement on self-reported cognition were not statistically significant but were suggestive of potential group differences. Time since surgery moderated the correlation, and participants who were ≤2 years post surgery had a significantly greater improvement in Oral Symbol Digit score (exercise vs control (b = 4.00; P < .01), but no significant improvement was observed in patients who were >2 years postsurgery (b = -1.19; P = .40). A significant dose response was observed with greater increased physical activity associated with objective and self-reported cognition in the exercise arm. CONCLUSIONS: The exercise intervention significantly improved processing speed, but only among those who had been diagnosed with breast cancer within the past 2 years. Slowed processing speed can have substantial implications for independent functioning, supporting the potential importance of early implementation of an exercise intervention among patients with breast cancer. Cancer 2018;124:192-202. © 2017 American Cancer Society.

Transfusion practices at end of life for hematopoietic stem cell transplant patients.

PURPOSE: Limited data exist regarding transfusion practices at end of life (EOL) for hematopoietic stem cell transplant (HSCT) patients. The purpose of this study was to examine red blood cell (RBC) and platelet transfusion practices in HSCT patients who enrolled or did not enroll in hospice. METHODS: This was a single-center, retrospective chart review in deceased HSCT patients. The primary objective was to determine the mean difference between the last transfusion and death in HSCT patients (n = 116) who enrolled or did not enroll in hospice. RESULTS: Sixteen (14%) and 100 (86%) patients were enrolled in hospice and not enrolled in hospice, respectively. Hospice patients observed a larger mean difference between death and last transfusion (45.9 ± 66.7 vs. 14.6 ± 48.1 days, p < 0.0001). A higher amount of platelet, but not RBC, transfusions occurred in patients not enrolled in hospice (p = 0.04). The last transfusion that occurred more than 96 h before death was observed in 12 (75%) and 22 (22%) in hospice and non-hospice patients, respectively. For HSCT patients not enrolled in hospice, 17 patients received a transfusion on the same day of death and 31 patients received the last transfusion 24 h before death. CONCLUSIONS: Blood transfusion practices differed in HSCT patients enrolled and not enrolled in hospice. For most patients not enrolled in hospice, the last transfusion occurred 24 h before death. Future efforts should explore if limited access to blood products is a barrier to hospice enrollment for HSCT patients.

Advance Care Planning and Palliative Care Integration for Patients Undergoing Hematopoietic Stem-Cell Transplantation.

PURPOSE: Advance care planning (ACP) in hematopoietic stem-cell transplantation (HSCT) is challenging, given the potential for cure despite increased morbidity and mortality risk.The aim of this study was to evaluate ACP and palliative care (PC) integration for patients who underwent HSCT. METHODS: A retrospective analysis was conducted and data were extracted from electronic medical records of patients who underwent HSCT between January 2011 and December 2015. Patients who received more than one transplant and who were younger than 18 years of age were excluded. The primary objective was to determine the setting and specialty of the clinician who documented the initial and final code status. Secondary objectives included evaluation of advance directive and/or completion of the Physician Orders for Life-Sustaining Treatment form, PC consultation, hospice enrollment, and location of death. RESULTS: The study sample comprised 39% (n = 235) allogeneic and 61% (n = 367) autologous HSCTs. All patients except one (n = 601) had code status documentation, and 99.2% (n = 596) were initially documented as full code. Initial and final code status documentation in the outpatient setting was 3% (n = 17) and 24% (n = 143), respectively. PC consultation occurred for 19% (n = 114) of HSCT patients, with 83% (n = 95) occurring in the hospital. Allogeneic transplant type and age were significantly associated with greater rates of advance directive and/or Physician Orders for Life-Sustaining Treatment completion. Most patients (85%, n = 99) died in the hospital, and few were enrolled in hospice (15%, n = 17). CONCLUSION: To our knowledge, this is the largest single-center study of ACP and PC integration for patients who underwent HSCT. Code status documentation in the outpatient setting was low, as well as utilization of PC and hospice services.

The Association of the C-Reactive Protein Inflammatory Biomarker with Breast Cancer Incidence and Mortality in the Women's Health Initiative.

Purpose: To examine associations of prediagnosis high-sensitivity C-reactive protein (hsCRP) with breast cancer incidence and postdiagnosis survival and to assess whether associations are modified by body mass index (BMI).Methods: A prospective analysis of the Women's Health Initiative was conducted among 17,841 cancer-free postmenopausal women with baseline hsCRP measurements. Cox proportional hazards models were used to examine associations between hsCRP concentrations and (i) breast cancer risk (n cases = 1,114) and (ii) all-cause mortality after breast cancer diagnosis. HRs are per 1 SD in log hsCRP.Results: hsCRP was not associated with breast cancer risk overall [HR = 1.05; 95% confidence interval (CI), 0.98-1.12]; however, an interaction between BMI and hsCRP was observed (Pinteraction = 0.02). A 1 SD increase in log hsCRP was associated with 17% increased breast cancer risk (HR = 1.17; 95% CI, 1.03-1.33) among lean women (BMI < 25), whereas no association was observed among overweight/obese (BMI ≥ 25) women. Prediagnosis hsCRP was not associated with overall mortality (HR, 1.04; 95% CI, 0.88-1.21) after breast cancer diagnosis; however, an increased mortality risk was apparent among leaner women with higher hsCRP levels (HR, 1.39, 95% CI, 1.03-1.88).Conclusions: Prediagnosis hsCRP levels are not associated with postmenopausal breast cancer incidence or survival overall; however, increased risks are suggested among leaner women. The observed effect modification is in the opposite direction of a previous case-control study finding and warrants further investigation.Impact: Associations of higher CRP levels with incident breast cancer and survival after breast cancer may depend on BMI. Cancer Epidemiol Biomarkers Prev; 26(7); 1100-6. ©2017 AACR.

Sleep duration and breast cancer prognosis: perspectives from the Women's Healthy Eating and Living Study.

PURPOSE: To examine whether baseline sleep duration or changes in sleep duration are associated with breast cancer prognosis among early-stage breast cancer survivors in the multi-center Women's Healthy Eating and Living Study. METHODS: Data were collected from 1995 to 2010. Analysis included 3047 women. Sleep duration was self-reported at baseline and follow-up intervals. Cox proportional hazard models were used to investigate whether baseline sleep duration was associated with breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality. Time-varying models investigated whether changes in sleep duration were associated with breast cancer prognosis. RESULTS: Compared to women who slept 7-8 h/night at baseline, sleeping ≥9 h/night was associated with a 48% increased risk of breast cancer recurrence (Hazard ratio [HR] 1.48, 95% Confidence interval [CI] 1.01, 2.00), a 52% increased risk of breast cancer-specific mortality (HR 1.52, 95% CI 1.09, 2.13), and a 43% greater risk of all-cause mortality (HR 1.43, 95% CI 1.07, 1.92). Time-varying models showed analogous increased risk in those who inconsistently slept ≥9 h/night (all P < 0.05), but not in those who consistently slept ≥9 h/night. CONCLUSIONS: Consistent long or short sleep, which may reflect inter-individual variability in the need for sleep, does not appear to influence prognosis among early-stage breast cancer survivors.

Weight loss versus muscle loss: re-evaluating inclusion criteria for future cancer cachexia interventional trials.

PURPOSE: Participation in cancer cachexia clinical trials requires a defined weight loss (WL) over time. A loss in skeletal muscle mass, measured by cross-sectional computed tomography (CT) image analysis, represents a possible alternative. Our aim was to compare WL versus muscle loss in patients who were screened to participate in a cancer cachexia clinical trial. METHODS: This was a single-center, retrospective analysis in metastatic colorectal cancer patients screened for an interventional cancer cachexia trial requiring a ≥5 % WL over the preceding 6 months. Concurrent CT images obtained as part of standard oncology care were analyzed for changes in total muscle and fat (visceral, subcutaneous, and total). RESULTS: Of patients screened (n = 36), 3 (8 %) enrolled in the trial, 17 (47 %) were excluded due to insufficient WL (<5 %), 3 (8 %) were excluded due to excessive WL (>20 %), and 16 (44 %) met inclusion criteria for WL. Patients who met screening criteria for WL (5-20 %) had a mean ± SD of 7.7 ± 8.7 % muscle loss, 24.4 ± 37.5 % visceral adipose loss, 21.6 ± 22.3 % subcutaneous adipose loss, and 22.1 ± 24.7 % total adipose loss. Patients excluded due to insufficient WL had 2 ± 6.4 % muscle loss, but a gain of 8.5 ± 39.8 % visceral adipose, and 4.2 ± 28.2 % subcutaneous adipose loss and 0.8 ± 28.4 % total adipose loss. Of the patients excluded due to WL <5 % (n = 17), 7 (41 %) had a skeletal muscle loss >5 %. CONCLUSIONS: Defining cancer cachexia by WL over time may be limited as it does not capture skeletal muscle loss. Cross-sectional CT body composition analysis may improve early detection of muscle loss and patient participation in future cancer cachexia clinical trials.

When are CT angiograms indicated for patients with lower extremity fractures? A review of 275 extremities.

BACKGROUND: Computed tomography angiogram (CTA) is frequently utilized to detect vascular injuries even without examination findings indicating a vascular injury. We had the following hypotheses: (1) a CTA for lower extremity fractures with no clinical signs of a vascular injury is not indicated, and (2) fracture location and pattern would correlate with the risk of a vascular injury. METHODS: A retrospective review was conducted on patients who had an acute lower extremity fracture(s) and a CTA. Their charts were reviewed for multiple factors including the presence or absence of hard or soft signs of a vascular injury, soft tissue status, and fracture location/pattern. Every CTA radiology report was reviewed and any vascular intervention or amputation resulting from a vascular injury was recorded. Statistical analysis was performed. RESULTS: Of the 275 CTAs of fractured extremities reviewed, 80 (29%) had a positive CTA finding and 16 (6%) required treatment. A total of 109 (40%) of the extremities had no hard or soft signs; all had normal CTAs. Having at least one hard or soft sign was a significant risk factor for having a positive CTA. An open fracture, isolated proximal third fibula fracture, distal and shaft tibia fractures, and the presence of multiple fractures in one extremity were also associated with an increased risk for having a positive CTA. CONCLUSION: We found no evidence to support the routine use of CTAs to evaluate lower extremity fractures unless at least one hard or soft sign is present. The presence of an open fracture, distal tibia or tibial shaft fractures, multiple fractures in one extremity, and/or an isolated proximal third fibula fracture increases the risk of having a finding consistent with a vascular injury on a CTA. Only 6% of the cases required treatment, and all of them had diminished or absent distal pulses on presentation. LEVEL OF EVIDENCE: Diagnostic test, level III.

Technology- and Phone-Based Weight Loss Intervention: Pilot RCT in Women at Elevated Breast Cancer Risk.

INTRODUCTION: For women with an increased breast cancer risk, reducing excess weight and increasing physical activity are believed to be important approaches for reducing their risk. This study tested a weight loss intervention that combined commercially available technology-based self-monitoring tools with individualized phone calls. DESIGN: Women were randomized to a weight loss intervention arm (n=36) or a usual care arm (n=18). SETTING/PARTICIPANTS: Participants were women with a BMI ≥ 27.5 kg/m2 and elevated breast cancer risk recruited from the mammography clinic at the Moores Cancer Center at the University of California San Diego. INTERVENTION: Intervention participants used the MyFitnessPal website and phone app to monitor diet and a Fitbit to monitor physical activity. Participants received 12 standardized coaching calls with trained counselors over 6 months. Usual care participants received the U.S. Dietary Guidelines for Americans at baseline and two brief calls over the 6 months. MAIN OUTCOME MEASURES: Weight and accelerometer-measured physical activity were assessed at baseline and 6 months. Data were collected in San Diego, CA, from 2012 to 2014 and analyzed in 2015. RESULTS: Participants (n=54) had a mean age of 59.5 (SD=5.6) years, BMI of 31.9 (SD=3.5), and a mean Gail Model score of 2.5 (SD=1.4). At 6 months, intervention participants had lost significantly more weight (4.4 kg vs 0.8 kg, p=0.004) and a greater percentage of starting weight (5.3% vs 1.0%, p=0.005) than usual care participants. Across arms, greater increases in moderate-to-vigorous physical activity resulted in greater weight loss (p=0.01). CONCLUSIONS: Combining technology-based self-monitoring tools with phone counseling supported weight loss over 6 months in women at increased risk for breast cancer.

Thirty-Six-Month Outcomes of a Generalist Paraprofessional Perinatal Home Visiting Intervention in South Africa on Maternal Health and Child Health and Development.

Almost all pregnant women (98 %) in 24 Cape Town neighborhoods were randomized by neighborhood to (1) the standard care (SC) condition (n = 12 neighborhoods; n = 594 pregnant women) or (2) the Philani Intervention Program (PIP) in which home visits by Community Health Workers (CHW) were conducted (n = 12 neighborhoods; n = 644 pregnant women). At 36 months post-birth (84.6 % follow-up), PIP mothers were significantly less depressed compared to the SC mothers. Children in PIP were significantly less likely to be stunted (24.3 vs 18.1 %, p = 0.013), to have better vocabularies, and were less likely to be hospitalized than children in the SC condition. These data suggest home visits may need to continue for several years post-birth. Sustainable, scalable perinatal intervention models are needed in LMIC.

Prolonged Nightly Fasting and Breast Cancer Prognosis.

IMPORTANCE: Rodent studies demonstrate that prolonged fasting during the sleep phase positively influences carcinogenesis and metabolic processes that are putatively associated with risk and prognosis of breast cancer. To our knowledge, no studies in humans have examined nightly fasting duration and cancer outcomes. OBJECTIVE: To investigate whether duration of nightly fasting predicted recurrence and mortality among women with early-stage breast cancer and, if so, whether it was associated with risk factors for poor outcomes, including glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein), obesity, and sleep. DESIGN, SETTING, AND PARTICIPANTS: Data were collected from 2413 women with breast cancer but without diabetes mellitus who were aged 27 to 70 years at diagnosis and participated in the prospective Women's Healthy Eating and Living study between March 1, 1995, and May 3, 2007. Data analysis was conducted from May 18 to October 5, 2015. EXPOSURES: Nightly fasting duration was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4. MAIN OUTCOMES AND MEASURES: Clinical outcomes were invasive breast cancer recurrence and new primary breast tumors during a mean of 7.3 years of study follow-up as well as death from breast cancer or any cause during a mean of 11.4 years of surveillance. Baseline sleep duration was self-reported, and archived blood samples were used to assess concentrations of hemoglobin A1c and C-reactive protein. RESULTS: The cohort of 2413 women (mean [SD] age, 52.4 [8.9] years) reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21; 95% CI, 0.91-1.60) or a statistically significant higher risk of all-cause mortality (hazard ratio, 1.22; 95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower hemoglobin A1c levels (ß = -0.37; 95% CI, -0.72 to -0.01) and a longer duration of nighttime sleep (ß = 0.20; 95% CI, 0.14-0.26). CONCLUSIONS AND RELEVANCE: Prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence. Improvements in glucoregulation and sleep may be mechanisms linking nightly fasting with breast cancer prognosis.