Summary Background Data for front-line health-care workers and risk of COVID-19 are limited. We sought to assess risk of COVID-19 among front-line health-care workers compared with the general community and the effect of personal protective equipment (PPE) on risk. Methods We did a prospective, observational cohort study in the UK and the USA of the general community, including front-line health-care workers, using self-reported data from the COVID Symptom Study smartphone application (app) from March 24 (UK) and March 29 (USA) to April 23, 2020. Participants were voluntary users of the app and at first use provided information on demographic factors (including age, sex, race or ethnic background, height and weight, and occupation) and medical history, and subsequently reported any COVID-19 symptoms. We used Cox proportional hazards modelling to estimate multivariate-adjusted hazard ratios (HRs) of our primary outcome, which was a positive COVID-19 test. The COVID Symptom Study app is registered with ClinicalTrials.gov , NCT04331509 . Findings Among 2 035 395 community individuals and 99 795 front-line health-care workers, we recorded 5545 incident reports of a positive COVID-19 test over 34 435 272 person-days. Compared with the general community, front-line health-care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% CI 10·93–12·33). To account for differences in testing frequency between front-line health-care workers and the general community and possible selection bias, an inverse probability-weighted model was used to adjust for the likelihood of receiving a COVID-19 test (adjusted HR 3·40, 95% CI 3·37–3·43). Secondary and post-hoc analyses suggested adequacy of PPE, clinical setting, and ethnic background were also important factors. Interpretation In the UK and the USA, risk of reporting a positive test for COVID-19 was increased among front-line health-care workers. Health-care systems should ensure adequate availability of PPE and develop additional strategies to protect health-care workers from COVID-19, particularly those from Black, Asian, and minority ethnic backgrounds. Additional follow-up of these observational findings is needed. Funding Zoe Global, Wellcome Trust, Engineering and Physical Sciences Research Council, National Institutes of Health Research, UK Research and Innovation, Alzheimer's Society, National Institutes of Health, National Institute for Occupational Safety and Health, and Massachusetts Consortium on Pathogen Readiness.

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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 (β = −0.37; 95% CI, −0.72 to −0.01) and a longer duration of nighttime sleep (β = 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.

Background Serum C-reactive protein (CRP) is a marker of acute inflammatory response and has been associated with health outcomes in some studies. Inflammation and immune response may have potential prognostic implications for breast cancer survivors. Methods The Women’s Healthy Eating and Living (WHEL) Study includes 2919 early stage breast cancer survivors with serum collected 2 years post-diagnosis and follow-up for clinical outcomes over approximately 7 years. CRP concentrations were measured using high-sensitivity electrochemiluminescence assay. Outcomes, including all-cause mortality, breast cancer-specific mortality, and additional breast cancer events were oncologist verified from medical records and death certificates. Cox proportional hazards models were conducted with adjustment for potential confounding factors to generate hazard ratios (HR) and 95% confidence intervals (CI). Results CRP concentrations in women diagnosed with breast cancer were associated with death due to any cause, death due to breast cancer, and additional breast cancer events, after adjustment for sociodemographic and cancer characteristics (lnCRP: P<0.05 for all three outcomes). The HR for women with (versus without) acute inflammation suggests a threshold effect on overall survival, rather than a dose-response relationship (≥10.0 mg/L v <1 mg/L: HR 1.96; 95% CI, 1.22–3.13). Associations were similar for breast cancer-specific mortality (HR 1.91; 95% CI, 1.13–3.23) and any additional breast cancer-related event (HR 1.69; 95% CI, 1.17–2.43). Conclusions Acute inflammation status (CRP ≥10 mg/L) may be an important independent biomarker for long-term survival in breast cancer survivors. Impact Interventions to decrease circulating CRP concentrations in breast cancer survivors with acute inflammation may improve prognosis.

Background/Objectives To explore the relationship between cognitive functioning and the time spent at different intensities of physical activity (PA) in free-living older adults. Design, Setting Cross sectional analyses of participants enrolled in a randomized controlled trial set in continuing care retirement communities. Participants 215 older adults residing in 7 continuing care retirement communities in San Diego County: average age 83 years, 70% female and 35% with graduate level education. Measurements PA was measured objectively by hip worn accelerometers with data aggregated to the minute level. Three cut points were used to assess low-light, high-light, and moderate-to-vigorous intensity PA (MVPA). Trail Making Tests A and B were completed and time for each test (sec) and test B-minus- A time (sec) were used as measures of cognitive functioning. Variables were log transformed and entered into linear regression models adjusting for demographic factors (age, education, gender) and other PA intensity variables. Results Low-light PA was not related to any Trails test score. High-light PA was significantly related to Trails A, B and B-minus-A; but only in unadjusted models. MVPA was related to Trails B and B-minus-A after adjusting for demographic variables. Conclusion These data suggest there may be a dose response between PA intensity and cognitive functioning in older adults. The stronger findings supporting a relationship between MVPA and cognitive functioning are consistent with previous observational and intervention studies.

Emerging evidence suggests that there is interplay between the frequency and circadian timing of eating and metabolic health. We examined the associations of eating frequency and timing with metabolic and inflammatory biomarkers putatively associated with breast cancer risk in women participating in the National Health and Nutrition Examination 2009–2010 Survey. Eating frequency and timing variables were calculated from 24-hour food records and included (1) proportion of calories consumed in the evening (5pm-midnight), (2) number of eating episodes per day, and (3) nighttime fasting duration. Linear regression models examined each eating frequency and timing exposure variable with C-reactive protein (CRP) concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP. There was a significant interaction between proportion of calories consumed in the evening and fasting duration with CRP (p = 0.02). A longer nighttime fasting duration was associated with an 8 percent lower CRP only among women who ate less than 30% of their total daily calories in the evening (p = 0.01). None of the eating frequency and timing variables were significantly associated with HOMA-IR. These findings suggest that eating more frequently, reducing evening energy intake, and fasting for longer nightly intervals may lower systemic inflammation and subsequently reduce breast cancer risk. Randomized trials are needed to validate these associations.

Background A novel line of research has emerged suggesting that daily feeding-fasting schedules that are synchronized with sleep-wake cycles have metabolic implications that are highly relevant to breast cancer. We examined associations of nighttime fasting duration with biomarkers of breast cancer risk among women in the 2009-2010 U.S. National Health and Nutrition Examination Survey. Methods Dietary, anthropometric and HbA1c data were available for 2,212 women, and 2-hour postprandial glucose concentrations were available for 1,066 women. Nighttime fasting duration was calculated using 24-hour food records. Separate linear regression models examined associations of nighttime fasting with HbA1c and 2-hour glucose concentrations. Logistic regression modeled associations of nighttime fasting with elevated HbA1c (HbA1c ≥ 39 mmol/mol or 5.7%) and elevated 2-hour glucose (glucose ≥ 140 mg/dL). All models adjusted for age, education, race/ethnicity, BMI, total kcal intake, evening kcal intake, and the number of eating episodes per day. Results Each 3-hour increase in nighttime fasting (roughly one standard deviation) was associated with a 4% lower 2-hour glucose measurement (β 0.96, 95% CI 0.93-1.00; p<0.05), and a non-statistically significant decrease in HbA1c. Logistic regression models indicate that each 3-hour increase in nighttime fasting duration was associated with roughly a 20% reduced odds of elevated HbA1c (OR 0.81, 95% CI 0.68, 0.97; p<0.05) and non-significantly reduced odds of elevated 2-hour glucose. Conclusions A longer nighttime duration was significantly associated with improved glycemic regulation. Impact Randomized trials are needed to confirm whether prolonged nighttime fasting could improve biomarkers of glucose control, thereby reducing breast cancer risk.

Rest-activity patterns provide an indication of circadian rhythmicity in the free-living setting. We aimed to describe the distributions of rest-activity patterns in a sample of adults and children across demographic variables. A sample of adults (N=590) and children (N=58) wore an actigraph on their non-dominant wrist for 7 days and nights. We generated rest-activity patterns from cosinor analysis (MESOR, acrophase and magnitude) and non-parametric circadian rhythm analysis (IS: intradaily stability; IV: interdaily variability; L5: least active 5-hour period; M10: most active 10-hour period; and RA: relative amplitude). Demographic variables included age, sex, race, education, marital status, and income. Linear mixed effects models were used to test for demographic differences in rest-activity patterns. Adolescents, compared to younger children, had: 1) later M10 midpoints (β=1.12 hours [95% CI: 0.43, 1.18] and lower M10 activity levels; 2) later L5 midpoints (β=1.6 hours [95% CI: 0.9, 2.3]) and lower L5 activity levels; 3) less regular rest-activity patterns (lower IS and higher IV); and 4) lower magnitudes (β=−0.95 [95% CI: −1.28, −0.63]) and relative amplitudes (β=−0.1 [95% CI: −0.14, −0.06]). Mid-to-older adults, compared to younger adults (ages 18 to 29 years), had: 1) earlier M10 midpoints (β=−1.0 hours [95% CI: −1.6, −0.4]; 2) earlier L5 midpoints (β=−0.7 hours [95% CI: −1.2, −0.2]); and 3) more regular rest-activity patterns (higher IS and lower IV). The magnitudes and relative amplitudes were similar across the adult age categories. Sex, race and education level rest-activity differences were also observed. Rest-activity patterns vary across the lifespan, and differ by race, sex and education. Understanding population variation in these patterns provides a foundation for further elucidating the health implications of rest-activity patterns across the lifespan.