Screening behaviours, demographics, and stage at diagnosis in the publicly funded Ontario Breast Screening Program.

PURPOSE: The Ontario Breast Screening Program (OBSP) offers free screening mammograms every 2 years, to women aged 50-74. Study objectives were to determine demographic characteristics associated with the adherence to OBSP and if women screened in the OBSP have a lower stage at diagnosis than non-screened eligible women. METHODS: We used the Ontario cancer registry (OCR) to identify 48,927 women, aged 51-74 years, diagnosed with breast cancer between 2010 and 2017. These women were assigned as having undergone adherent screening (N = 26,108), non-adherent screening (N = 6546) or not-screened (N = 16,273) in the OBSP. We used multinomial logistic regression to investigate the demographic characteristics associated with screening behaviour, as well as the association between screening status and stage at diagnosis. RESULTS: Among women with breast cancer, those living in rural areas (versus the largest urban areas) had a lower odds of not being screened (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.68, 0.78). Women in low-income (versus high-income) communities were more likely not to be screened (OR 1.42, 95% CI 1.33, 1.51). When stratified, the association between income and screening status only held in urban areas. Non-screened women were more likely to be diagnosed with stage II (OR 1.91, 95% CI 1.82, 2.01), III (OR 2.96, 95% CI 2.76, 3.17), or IV (OR 8.96, 95% CI 7.94, 10.12) disease compared to stage I and were less likely to be diagnosed with ductal carcinoma in situ (DCIS) (OR 0.91, 95% CI 0.84-0.98). CONCLUSIONS: This study suggests that targeting OBSP recruitment efforts to lower income urban communities could increase screening rates. OBSP adherent women were more likely to be diagnosed with earlier stage disease, supporting the value of this initiative and those like it.

Validation of the International Breast Cancer Intervention Study (IBIS) model in the High Risk Ontario Breast Screening Program: A retrospective cohort study.

PURPOSE: Women with a remaining lifetime risk of breast cancer of ≥25%, estimated using the International Breast Cancer Intervention Study (IBIS) model, were eligible for the High Risk Ontario Breast Screening Program. This study examined the performance of IBIS 10-year risk estimates in the program. METHODS: This retrospective study included 7487 women aged 30 to 69 years referred to the High Risk Ontario Breast Screening Program between July 1, 2011, and December 31, 2016, with follow-up until December 31, 2018. Model calibration and discrimination were assessed. Analyses were conducted overall and stratified by age (< or ≥50 years). Different 10-year risk thresholds were compared with the current eligibility criteria. RESULTS: Overall, IBIS overestimated the risk of breast cancer with an expected vs observed case ratio of 1.17 (95% CI = 1.04-1.35). Overestimation was highest in women aged 50 to 69 years (expected vs observed case ratio = 1.29, 95% CI = 1.03-1.69) and for those in the top quartile of risk. Overall discrimination was fair with a concordance statistic of 0.66 (95% CI = 0.63-0.70). Furthermore, when using different 10-year risk eligibility thresholds, most cases would have been missed in the 30 to 49 age group using the 8% 10-year risk threshold, whereas relatively few women aged 50 to 69 would have been ineligible at any of the thresholds examined. CONCLUSION: We found that IBIS overestimated the risk of breast cancer in this screening cohort but had adequate discrimination. Age-specific risk thresholds should be considered to optimize the program eligibility criteria.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

Association between estimated cardiorespiratory fitness and breast cancer: a prospective cohort study.

OBJECTIVE: To examine the association between cardiorespiratory fitness (CRF) and the risk of breast cancer in postmenopausal women. METHODS: This study used data from 17 840 cancer-free postmenopausal women with a CRF assessment from the UK Biobank. High estimated CRF (eCRF) was categorised as being >80th percentile within 10-year age bands. Fine and Gray regression was used to examine the association between eCRF and breast cancer risk, accounting for both non-breast cancer diagnoses and all-cause mortality as competing risks. Age was used as the time scale. Several different models were produced, including those adjusting for known breast cancer risk factors, and stratified by measures of body fat (body mass index and per cent body fat). RESULTS: Over a median follow-up of 11.0 years there were 529 cases of invasive breast cancer, 1623 cases of non-breast cancer disease and 241 deaths. With adjustment for breast cancer risk factors, high eCRF was associated with a 24% (subdistribution HR (SDHR) 0.76, 95% CI 0.60 to 0.97) lower risk of breast cancer. When stratified by measures of body fat, we found evidence of effect measure modification. Mainly, having high eCRF was only associated with a lower risk of breast cancer among those classified as having overweight/obesity (SDHR 0.33, 95% CI 0.11 to 1.01) or percentage body fat above the 1st quintile (SDHR 0.65, 95% CI 0.45 to 0.94). CONCLUSION: Having higher CRF may be a protective factor against breast cancer in postmenopausal women but only for women with elevated body fat.

Plasma and Interstitial Fluid Pharmacokinetics of Prophylactic Cefazolin in Elective Bariatric Surgery Patients.

Guidelines for surgical prophylactic dosing of cefazolin in bariatric surgery vary in terms of recommended dose. This study aimed to describe the plasma and interstitial fluid (ISF) cefazolin pharmacokinetics in patients undergoing bariatric surgery and to determine an optimum dosing regimen. Abdominal subcutaneous ISF concentrations (measured using microdialysis) and plasma samples were collected at regular time points after administration of cefazolin 2 g intravenously. Total and unbound cefazolin concentrations were assayed and then modeled using Pmetrics. Monte Carlo dosing simulations (n = 5,000) were used to define cefazolin dosing regimens able to achieve a fractional target attainment (FTA) of >95% in the ISF suitable for the MIC for Staphylococcus aureus in isolates of ≤2 mg · L-1 and for a surgical duration of 4 h. Fourteen patients were included, with a mean (standard deviation [SD]) bodyweight of 148 (35) kg and body mass index (BMI) of 48 kg · m-2. Cefazolin protein binding ranged from 14 to 36% with variable penetration into ISF of 58% ± 56%. Cefazolin was best described as a four-compartment model including nonlinear protein binding. The mean central volume of distribution in the final model was 18.2 (SD 3.31) L, and the mean clearance was 32.4 (SD 20.2) L · h-1. A standard 2-g dose achieved an FTA of >95% for all patients with BMIs ranging from 36 to 69 kg · m-2. A 2-g prophylactic cefazolin dose achieves appropriate unbound plasma and ISF concentrations in obese and morbidly obese bariatric surgery patients.

The effect of transnasal humidified rapid-insufflation ventilator exchange (THRIVE) versus nasal prongs on safe apnoea time in paralysed obese patients: a randomised controlled trial.

BACKGROUND: Evidence is lacking regarding the efficacy of Optiflow transnasal humidified rapid-insufflation ventilator exchange (THRIVE™) in obese patients. We compared the impact of this technique at 70 L min-1 with 4 L min-1 oxygen via nasal prongs on safe apnoea times of paralysed obese patients. METHODS: We randomised adults with a BMI >35 kg m-2 undergoing elective bariatric surgery. While apnoeic and paralysed, Group T received 70 L min-1 oxygen via Optiflow THRIVE™. Group N received nasal prong oxygen at 4 L min-1. The primary outcome was time to SpO2 ≤95% while apnoeic, with a 360 s cut-off. This was analysed by applying a time-to-event analysis. RESULTS: Forty-two patients were included. The median (inter-quartile range) BMI was 44.8 kg m-2 (40.0-50.0) in Group T and 42.0 kg m-2 (39.3-45.1) in Group N. Median (inter-quartile range) time to SpO2 ≤95% in Group T was 356 (165 to ≥360) s and in Group N, 210 (160-270) s. Using a survival analysis framework, median time-to-event in Group T was 356 s (95% confidence interval 165 s-upper limit not defined) and 210 s (95% confidence interval 160-242 s) (P=0.049) in Group N. CONCLUSIONS: Compared with oxygen delivered via nasal prongs at 4 L min-1, oxygen delivery via Optiflow THRIVE™ at a flow rate of 70 L min-1 can prolong safe apnoea time, however, the results are statistically inconclusive. Optiflow THRIVE™ did decrease the rate of reduction in Pao2 during apnoea. CLINICAL TRIAL REGISTRATION: ANZCTR 12618000445279.

Extended-release naltrexone/bupropion is safe and effective among subjects with type 2 diabetes already taking incretin agents: a post-hoc analysis of the LIGHT trial.

BACKGROUND: Extended-release naltrexone/bupropion (NB) is indicated for chronic weight management. Incretin agents are recommended for patients with type 2 diabetes. This analysis looked at the add-on of NB to incretins to see if weight loss could occur in patients already stabilized on incretin agents. METHODS: This was a post-hoc analysis of NB vs. placebo (PL) among subjects with type 2 diabetes stable on an incretin agent prior to randomization in a double-blind, PL-controlled cardiovascular outcome trial (N = 1317). RESULTS: Over 1 year, mean weight loss was significantly greater among NB patients vs. PL among those taking DPP-4i (mean absolute difference 4.6% [p < 0.0001]) and those taking GLP-1RAs (mean absolute difference 5.2%, p < 0.0001). Proportions of subjects achieving 5% weight loss were significantly greater for NB vs. PL at weeks 26 and 52 among those taking DPP-4is or GLP-1RAs. There were no significant differences in effectiveness observed between NB + DPP-4i and NB + GLP-1RA or between PL + DPP-4i and PL + GLP-1RA in any of the analyses. Serious adverse events were reported by 9.1% and 11.1% for PL + DPP-4i and PL + GLP-1RA, respectively, and 13.3% and 12.4% of NB + DPP-4i and NB + GLP-1RA, respectively. CONCLUSION: NB appears to be effective in reducing weight in patients with T2DM and obesity/overweight who are taking DPP-4ihibitors or GLP-1RA. The SAE rates in all arms of this analysis were lower than have been reported in other cardiovascular outcome trials in type 2 diabetes.

ClearSight™ finger cuff versus invasive arterial pressure measurement in patients with body mass index above 45 kg/m2.

BACKGROUND: Measuring blood pressure in patients with obesity is challenging. The ClearSight™ finger cuff (FC) uses the vascular unloading technique to provide continuous non-invasive blood pressure measurements. We aimed to test the agreement of the FC with invasive radial arterial monitoring (INV) in patients with obesity. METHODS: Participants had a body mass index (BMI) ≥45 kg/m2 and underwent laparoscopic bariatric surgery. FC and INV measurements were obtained simultaneously every 5 min on each patient, following induction of anesthesia. Agreement over time was assessed using modified Bland-Altman plots and error grid analysis permitted clinical interpretation of the results. Four-quadrant plots allowed assessment of concordance in blood pressure changes. RESULTS: The 30 participants had a median (IQR) BMI of 50.2 kg/m2 (IQR 48.3-55.3). The observed bias (SD, 95% limits of agreement) for systolic blood pressure (SBP) was 14.3 mmHg (14.1, -13.4 - 42.0), 5.2 mmHg (10.9, -16.0 - 26.5) for mean arterial pressure (MAP) and 2.6 mmHg (10.8, -18.6 - 23.8) for diastolic blood pressure (DBP). Error grid analysis showed that the proportion of readings in risk zones A-E were 90.8, 6.5, 2.7, 0 and 0% for SBP and 91.4, 4.3, 4.3, 0 and 0% for MAP, respectively. Discordance occurred in ≤8% of pairs for consecutive change in SBP, MAP and DBP. CONCLUSIONS: The vascular unloading technique was not adequately in agreement with radial arterial monitoring. Evaluation in a larger sample is required before recommending this technique for intraoperative monitoring of patients with BMI ≥45 kg/m2.

The safety and effectiveness of commonly-marketed natural supplements for weight loss in populations with obesity: A critical review of the literature from 2006 to 2016.

Objective: To evaluate the evidence published from 2006 to 2016 on the effectiveness and safety of commonly used natural supplements for weight loss in individuals with obesity.Methods: Amazon and Google were searched for names of mono-agent natural supplements marketed for weight loss and a list of the 10 supplements was created. Google Scholar, Pubmed, Science Direct, and the Cochrane Library were searched for articles that met inclusion.Results: At least one article was published on the effectiveness or safety of bitter orange, capsinoid, carnitine, chromium picolinate, Coleus forskohlii, conjugated linoleic acid, glucomannan, green tea and psyllium for weight loss in populations with obesity from 2006 to 2016. There was insufficient evidence to suggest that the natural supplements examined contribute to significant weight loss, with the exception of perhaps glucomannan in the form of PGX. In general, the majority of side-effects reported were minor to moderate, and gastrointestinal-related. However, in some cases extreme side-effects such as liver and kidney failure were observed.Conclusion: Contrary to popular belief, results of this review suggest that the use of natural supplements for weight loss are unlikely to contribute to meaningful weight loss and in some cases may contribute to harm.

Prophylactic Cefazolin Dosing in Women With Body Mass Index >35 kg·m-2 Undergoing Cesarean Delivery: A Pharmacokinetic Study of Plasma and Interstitial Fluid.

BACKGROUND: Obesity is a risk factor for surgical site infection after cesarean delivery. There is inadequate pharmacokinetic data available regarding prophylactic cefazolin dosing in obese pregnant women. We aimed to describe the plasma and interstitial fluid (ISF) pharmacokinetics of cefazolin in obese women undergoing elective cesarean delivery and use dosing simulations to predict optimal dosing regimens. METHODS: Eligible women were scheduled for elective cesarean delivery at term, with a body mass index (BMI) of >35 kg·m. Plasma and ISF samples were collected following 2 g of intravenous cefazolin. Concentrations were determined using liquid chromatography-mass spectrometry. Population pharmacokinetic modeling and Monte Carlo dosing simulations were performed using Pmetrics. Total and unbound cefazolin concentrations in plasma and ISF were compared with the minimum inhibitory concentration at which 90% of isolates are inhibited (MIC90) of cefazolin for Staphylococcus aureus, 2 mg·L. The fractional target attainment (FTA) of dosing regimens to achieve a pre-established target of 95% unbound ISF concentrations >2 mg·L throughout a 3-hour duration of the surgery was calculated. RESULTS: The 12 women recruited had a median (interquartile range [IQR]) BMI of 41.5 (39.7-46.6) kg·m and a median (IQR) gestation of 38.7 weeks (37.9-39.0). For each timepoint up to 180 minutes, the median across subjects of total and unbound plasma concentration of cefazolin remained above 2 mg·L. The minimum observed total plasma concentration was 31.7 mg·L and plasma unbound concentration was 7.7 mg·L (observed in the same participant). For each timepoint up to 150 minutes, the median across subjects of unbound ISF concentrations remained above 2 mg·L. The minimum observed unbound ISF concentration was 0.7 mg·L (observed in 1 participant). In 2 participants, the ISF concentration of cefazolin was not maintained above 2 mg·L. The mean (± standard error [SE]) penetration of cefazolin (calculated as area under the concentration-time curve for the unbound fraction of drug [fAUC]tissue/fAUCplasma) into the ISF was 0.884 ± 1.11. Simulations demonstrated that FTA >95% was achieved in patients weighing 90-150 kg by an initial 2 g dose with redosing of 2 g at 2 hours. FTA was improved to >99% when an initial 3 g dose was repeated at 2 hours. CONCLUSIONS: To maintain adequate ISF antibiotic concentrations in obese pregnant women, our results suggest that redosing of cefazolin may be required. When wound closure has not occurred within 2 hours, redosing is suggested, following either a 2 or 3 g initial bolus. These preliminary results require validation in a larger population.

Perioperative Blood Pressure Monitoring in Patients With Obesity.

Blood pressure monitoring plays a key part in the preoperative, intraoperative, and postoperative care of all patients. In patients with obesity, hypertension indicates increased metabolic and surgical risk and may signal the presence of significant medical comorbidities, including obstructive sleep apnea. Avoidance of hypertension postoperatively is necessary to minimize bleeding risk after surgery. Hypotension in the postoperative period may be the first sign of significant complications that require urgent management. With the problem of being overweight or obese now affecting two-thirds of adults in Western countries, the proportion of patients with obesity in perioperative environments is similarly increasing. Detection of aberrations in blood pressure is contingent on the accuracy of blood pressure measurement methods. Patients with obesity tend to have a large arm circumference and "cone-shaped arms." Standard blood pressure cuffs fit such patients poorly, and this compromises the accuracy of measurements. Alternatives to arm blood pressure cuffs, some made specifically for individuals with obesity, have been evaluated but are not widely available to clinicians. This focused narrative review will discuss the relevance of hypertension management in the care of patients with obesity, highlight the currently available methods for perioperative monitoring of blood pressure, and explore the opportunities that exist to improve the perioperative blood pressure care in patients with obesity undergoing surgical procedures.

Modeling Human Exposure to Indoor Contaminants: External Source to Body Tissues.

Information on human indoor exposure is necessary to assess the potential risk to individuals from many chemicals of interest. Dynamic indoor and human physicologically based pharmacokinetic (PBPK) models of the distribution of nonionizing, organic chemical concentrations in indoor environments resulting in delivered tissue doses are developed, described and tested. The Indoor model successfully reproduced independently measured, reported time-dependent air concentrations of chloroform released during showering and of 2-butyoxyethanol following use of a volatile surface cleaner. The Indoor model predictions were also comparable to those from a higher tier consumer model (ConsExpo 4.1) for the surface cleaner scenario. The PBPK model successful reproduced observed chloroform exhaled air concentrations resulting from an inhalation exposure. Fugacity based modeling provided a seamless description of the partitioning, fluxes, accumulation and release of the chemical in indoor media and tissues of the exposed subject. This has the potential to assist in health risk assessments, provided that appropriate physical/chemical property, usage characteristics, and toxicological information are available.

Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression.

Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the IDC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum.

Sugar, non-nutritive sweetener intake and obesity risk in college students.

OBJECTIVE: The purpose of this study was to investigate the association between sugar and NNS consumption with body fat percentage in young adults. METHODS: 524 college students were asked to complete the Web-based National Institutes of Health (NIH) Diet History Questionnaire II and had their body fat percentage measured using a bioelectrical impedance analysis scale. RESULT: One-fourth of the participants were classified as overfat/obese and of those overfat or obese, 49% of them were African American. Overfat/obese participants consumed significantly more sugar than the heathy group and the underfat group (p < 0.001). Saccharin consumption was significantly higher in the overfat/obese group compare to the underfat and normal groups (p < 0.001). The odds of becoming overfat/obese increased 1.2 times for excessive total sugar consumption (95% CI: 1.0-1.8, p < 0.05). CONCLUSION: Excessive sugar and saccharin consumption were associated with higher body fat percentage in young adults.

A Comparison of Experiences with Factors Related to Food Insecurity between College Students Who Are Food Secure and Food Insecure: A Qualitative Study.

BACKGROUND: Previous research has reported negative health consequences and poor academic achievement among college students who are food insecure. It is unknown if students with food insecurity's experiences qualitatively differ from students who are food secure. OBJECTIVE: To qualitatively evaluate experiences of students who are food secure and food insecure with internal and external factors related to food insecurity. DESIGN: Trained interviewers conducted in-person qualitative interviews from February to August 2018 to gain insights about eating patterns, food environment, financial situation, and ideas for addressing food insecurity on college campuses with students who are food secure and food insecure. PARTICIPANTS AND SETTING: Students from three universities in the western United States (N = 58) who were classified as food secure (n = 28) and food insecure (n = 30) using the US Department of Agriculture's 6-item Food Security Module participated in this study. STATISTICAL ANALYSES PERFORMED: Interviews were recorded and transcribed verbatim. Data were analyzed using a conventional content analysis. A random sample of transcripts were independently coded to determine interrater reliability. Researchers divided transcripts for final coding and overarching themes were discussed. Descriptive statistics were used. RESULTS: Students who were both food secure and food insecure obtained food from similar sources (eg, grocery stores); had unexpected expenses that led to financial constraints; indicated transportation barriers altered the amount or package size of food purchased; and reported similar knowledge, attitudes, use, and familial history of food assistance. Students with food insecurity uniquely reported prioritizing rent or other living expenses over food, and when funds were low, reducing food intake, experiencing a variable food supply throughout the month, or using strategies like donating plasma or selling possessions to enhance financial stability. CONCLUSIONS: This study helps nutrition and dietetics practitioners better understand how college students' experiences with factors related to food insecurity differ by food security status. Future quantitative research is needed to confirm the coping strategies identified among students with food insecurity in this study.

MRI background parenchymal enhancement, breast density and breast cancer risk factors: A cross-sectional study in pre- and post-menopausal women.

Breast tissue enhances on contrast MRI and is called background parenchymal enhancement (BPE). Having high BPE has been associated with an increased risk of breast cancer. We examined the relationship between BPE and the amount of fibroglandular tissue on MRI (MRI-FGT) and breast cancer risk factors. This was a cross-sectional study of 415 women without breast cancer undergoing contrast-enhanced breast MRI at Memorial Sloan Kettering Cancer Center. All women completed a questionnaire assessing exposures at the time of MRI. Prevalence ratios (PR) and 95% confidence intervals (CI) describing the relationship between breast cancer risk factors and BPE and MRI-FGT were generated using modified Poisson regression. In multivariable-adjusted models a positive association between body mass index (BMI) and BPE was observed, with a 5-unit increase in BMI associated with a 14% and 44% increase in prevalence of high BPE in pre- and post-menopausal women, respectively. Conversely, a strong inverse relationship between BMI and MRI-FGT was observed in both pre- (PR = 0.66, 95% CI 0.57, 0.76) and post-menopausal (PR = 0.66, 95% CI 0.56, 0.78) women. Use of preventive medication (e.g., tamoxifen) was associated with having low BPE, while no association was observed for MRI-FGT. BPE is an imaging marker available from standard contrast-enhanced MRI, that is influenced by endogenous and exogenous hormonal exposures in both pre- and post-menopausal women.

Time-Restricted Eating: A Novel and Simple Dietary Intervention for Primary and Secondary Prevention of Breast Cancer and Cardiovascular Disease.

There is substantial overlap in risk factors for the pathogenesis and progression of breast cancer (BC) and cardiovascular disease (CVD), including obesity, metabolic disturbances, and chronic inflammation. These unifying features remain prevalent after a BC diagnosis and are exacerbated by BC treatment, resulting in elevated CVD risk among survivors. Thus, therapies that target these risk factors or mechanisms are likely to be effective for the prevention or progression of both conditions. In this narrative review, we propose time-restricted eating (TRE) as a simple lifestyle therapy to address many upstream causative factors associated with both BC and CVD. TRE is simple dietary strategy that typically involves the consumption of ad libitum energy intake within 8 h, followed by a 16-h fast. We describe the feasibility and safety of TRE and the available evidence for the impact of TRE on metabolic, cardiovascular, and cancer-specific health benefits. We also highlight potential solutions for overcoming barriers to adoption and adherence and areas requiring future research. In composite, we make the case for the use of TRE as a novel, safe, and feasible intervention for primary and secondary BC prevention, as well as tertiary prevention as it relates to CVD in BC survivors.

The association of sex and calendar month with changes in weight: A retrospective cohort study of a community-based weight management clinic.

OBJECTIVE: To assess changes in weight by calendar month and sex in patients enrolled in a weight loss intervention. METHODS: Adults participating in a lifestyle weight loss intervention at the Wharton Medical Clinic from January 1st, 2007 to July 4th, 2019 were examined (N = 19,153). A linear generalized estimating equation was used to examine the association between weight change (baseline, month 1, month 2) and calendar month with adjustment for age, sex and baseline body mass index. A first order interaction between sex and calendar was included to assess if the association between calendar month and weight loss differs by sex. RESULTS: Patients lost 1.3 ± 2.0 kg (1.2 ± 1.8%) of their body weight per month. As compared to the mean monthly weight loss, patients lost slightly less weight in September (mean, 95% confidence interval (CI): -0.3, -0.4 to -0.2 kg) and slightly more weight in October (0.2, 0.1-0.3 kg). With adjustment for age, body mass index and calendar month, men lost 0.4 kg/month (95% CI: 0.3, 0.5 kg/month) than women. There were no other significant differences in the monthly weight change between men and women (sex*calendar month P-value = 0.24). CONCLUSION: While there were slight differences in the amount of weight change achieved by patients in September, and October, it was not of a magnitude that is likely clinically relevant. In addition, men consistently lost more weight than women across all calendar months. Taken together, this suggest that calendar month is not associated with differences in weight loss for men and women enrolled in a structured weight management program.

The association of estimated cardiorespiratory fitness with COVID-19 incidence and mortality: A cohort study.

BACKGROUND: It has been suggested that cardiorespiratory fitness (CRF) may be used to identify those at greatest risk for severe COVID-19 illness. However, no study to date has examined the association between CRF and COVID-19. The objectives of this study were to determine whether CRF is independently associated with testing positive with or dying from COVID-19. METHODS: This is a prospective cohort study of 2,690 adults from the UK Biobank Study that were followed from March 16th, 2020 to July 26th, 2020. Participants who were tested for COVID-19 and had undergone CRF assessment were examined. CRF was estimated (eCRF) and categorized as low (<20th percentile), moderate (20th to 80th percentile) and high (≥80th percentile) within sex and ten-year age groups (e.g. 50-60 years). Participants were classified as having COVID-19 if they tested positive (primarily PCR tests) at an in-patient or out-patient setting as of July 26, 2020. Participants were classified as having died from COVID-19 if the primary or underlying cause of death was listed ICD-10 codes U071 or U072 by June 30th, 2020. Adjusted risk ratios (aRR) and 95% confidence intervals (CI) were estimated and a forward model building approach used to identify covariates. FINDINGS: There was no significant association between eCRF and testing positive for COVID-19. Conversely, individuals with moderate (aRR = 0.43, 95% CI: 0.25, 0.75) and high fitness (aRR = 0.37, 95% CI: 0.16, 0.85) had a significantly lower risk of dying from COVID-19 than those with low fitness. CONCLUSIONS: While eCRF was not significantly associated with testing positive for COVID-19, we observed a significant dose-response between having higher eCRF and a decreased risk of dying from COVID-19. This suggests that prior gains in CRF could be protective against dying from COVID-19 should someone develop the virus.