Effectiveness of a randomized intervention by a geriatric team in frail hospital inpatients in non-geriatric settings: FRAILCLINIC project.

BACKGROUND: Little research has been undertaken on the benefits of frailty management within different hospital settings. The objective of this study is to provide evidence on the viability and effectiveness of frailty management in non-geriatric hospital settings on mortality and functional decline after discharge. METHODS: Data from the FRAILCLINIC (NCT02643069) study were used. FRAILCLINIC is a randomized controlled trial developed in non-geriatric hospital inpatient settings (emergency room, cardiology and surgery) from Spain (2), Italy (2) and the United Kingdom (1). Inpatients must met frailty criteria (according to the Frailty Phenotype and/or FRAIL scale), ≥75 years old. The control group (CG) received usual care. The intervention group (IG) received comprehensive geriatric assessment (CGA) and a coordinated intervention consisting in recommendations to the treating physician about polypharmacy, delirium, falls, nutrition and physical exercise plus a discharge plan. The main outcomes included functional decline (worsening ≥5 points in Barthel Index) and mortality at 3 months. We used multivariate logistic regression models adjusted by age, gender and the Charlson index. Intention-to-treat (ITT) and per-protocol (PP) analyses were used. RESULTS: Eight hundred twenty one participants (IG: 416; mean age 83.00 ± 4.91; 51.44% women; CG: 405; mean age 82.46 ± 6.03; 52.35% women) were included. In the IG, 77.16% of the participants followed the geriatric team's recommendations as implemented by the treating physicians. The intervention showed a benefit on functional decline and mortality [OR: 0.67(0.47-0.96), P-value 0.027 and 0.29(0.14-0.57), P-value < 0.001, respectively) when fully followed by the treating physician. A trend to benefit (close to statistical significance) in functional decline and mortality were also observed when any of the recommendations were not followed [OR (95% CI): 0.72 (0.51-1.01), P-value: 0.055; and 0.64 (0.37-1.10), P-value: 0.105, respectively]. CONCLUSIONS: An individualized intervention in frail in-patients reduces the risk of functional deterioration and mortality at 3 months of follow-up when a care management plan is designed and followed.

Cancer-Related Fatigue and Circulating Biomarkers in Breast Cancer Survivors.

PURPOSE: Cancer-related fatigue (CRF) is the most common and disruptive symptom experienced by cancer survivors and because of its frequency and severity is especially worrisome in breast cancer survivors (BCS). Despite a great deal of research, the mechanisms underlying CRF have not been determined. The present study aims to describe associations between CRF in BCS and different blood biomarkers. METHODS: A descriptive and cross-sectional study was conducted. A set of biomarkers assessing inflammation were measured in BCS: C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), IL-1ß, IL-6, IL-8, IL-10, tumor necrosis factor (TNF); HPA axis dysfunction (cortisol), autonomic dysfunction (noradrenaline); oxidative stress (8-OH deoxyguanosine); insulin resistance markers (insulin, IGF-I, IGFBP3) and sexual hormones (estrogens, progesterone, testosterone). RESULTS: NLR (p = .00) and cortisol (p = .02) were positive and negatively associated with CRF, respectively. The rest of the blood markers were not associated with CRF. CONCLUSION: Our results increase the evidence on pathophysiological mechanisms driving CRF in BCS. However, longitudinal studies are needed to explore the role of these factors as potential causal mechanisms.

Differential utility of various frailty diagnostic tools in non-geriatric hospital departments of several countries: A longitudinal study.

BACKGROUND: There is limited knowledge on the performance of different frailty scales in clinical settings. We sought to evaluate in non-geriatric hospital departments the feasibility, agreement and predictive ability for adverse events after 1 year follow-up of several frailty assessment tools. METHODS: Longitudinal study with 667 older adults recruited from five hospitals in three different countries (Spain, Italy and United Kingdom). Participants were older than 75 years attending the emergency room, cardiology and surgery departments. Frailty scales used were Frailty Phenotype (FP), FRAIL scale, Tilburg and Groningen Frailty Indicators, and Clinical Frailty Scale (CFS). Analyses included the prevalence of frailty, degree of agreement between tools, feasibility and prognostic value for hospital readmission, worsening of disability and mortality, by tool and setting. RESULTS: Emergency Room and cardiology were the settings with the highest frailty prevalence, varying by tool between 40.4% and 67.2%; elective surgery was the one with the lowest prevalence (between 13.2% and 38.2%). The tools showed a fair to moderate agreement. FP showed the lowest feasibility, especially in urgent surgery (35.6%). FRAIL, CFS and FP predicted mortality and readmissions in several settings, but disability worsening only in cardiology. CONCLUSIONS: Frailty is a highly frequent condition in older people attending non-geriatric hospital departments. We recommend that based upon their current feasibility and predictive ability, the FRAIL scale, CFS and FP should be preferentially used in these settings. The low concordance among the tools and differences in prevalence reported and predictive ability suggest the existence of different subtypes of frailty.

Association Between Pulse Wave Velocity and Frailty, Disability, and Mortality in Community-Dwelling Older Adults.

Background: Arterial stiffness leads to several adverse events in the older population, but there is a lack of data on its association with frailty, disability, and mortality in the same population. Objectives: The purpose of this study was to evaluate the role of arterial stiffness in the loss of functional ability (frailty and disability) and mortality. Methods: Data were taken from community-dwelling aged 65 years participants without diabetes in the Toledo Study of Healthy Ageing cohort. Pulse wave velocity (PWV), assessed through SphygmoCor, was recorded at baseline. Median follow-up time were 2.99 years for frailty (frailty phenotype [FP] and Frailty Trait Scale-5 [FTS5]) and disability (Katz Index) and 6.2 for mortality. Logistic regressions models were built for disability and frailty and Cox proportional hazards model for death, adjusted by age and sex, comorbidity, cardiovascular risk factors, asymmetric dimethylarginine levels, and polypharmacy. Results: Overall, 978 (mean age 74.5 ± 5.6 years, 56.7% female) participants were included. Different cut-off points were shown for each outcome. PWV >11.5 m/s was cross-sectionally associated with frailty (FP: OR fully-adjusted model: 1.69, 95% CI: 1.45-1.97; FTS5: OR: 1.51, 95% CI: 1.22-1.87) and disability (OR: 1.51, 95% CI: 1.26-1.79); PWV >10 m/s with incident frailty by FP (OR: 1.36, 95% CI: 1.10-1.68) and FTS5 (OR: 1.40, 95% CI: 1.12-1.75), and PWV >11 m/s with death (HR: 1.28, 95% CI: 1.09-1.50). For incident (OR: 1.28, 95% CI: 1.06-1.55) and worsening disability (OR: 1.21, 95% CI: 1.02-1.45) the threshold was 12.5 m/s. Below these cut-off points, age was the best predictor of adverse outcomes. Conclusions: Arterial stiffness predicts frailty, disability, and mortality in older people, with different cut-off points, ie,severity degrees, for each of the assessed outcomes.

Role of sarcopenia in the frailty transitions in older adults: a population-based cohort study.

BACKGROUND: Frailty and sarcopenia are age-associated syndromes that have been associated with the risk of several adverse events, mainly functional decline and death, that usually coexist. However, the potential role of one of them (sarcopenia) in modulating some of those adverse events associated to the other one (frailty) has not been explored. The aim of this work is to assess the role of sarcopenia within the frailty transitions and mortality in older people. METHODS: Data from the Toledo Study of Healthy Aging (TSHA) were used. TSHA is a cohort of community-dwelling older adults ≥65. Frailty was assessed according with the Frailty Phenotype (FP) and the Frailty Trait Scale-5 (FTS5) at baseline and at follow-up. Basal sarcopenia status was measured with the standardized Foundation for the National Institutes of Health criteria. Fisher's exact test and logistic regression model were used to determine if sarcopenia modified the transition of frailty states (median follow-up of 2.99 years) and Cox proportional hazard model was used for assessing mortality. RESULTS: There were 1538 participants (74.73 ± 5.73; 45.51% men) included. Transitions from robustness to prefrailty and frailty according to FP were more frequent in sarcopenic than in non-sarcopenic participants (32.37% vs. 15.18%, P ≤ 0.001; 5.76% vs. 1.12%; P ≤ 0.001, respectively) and from prefrailty-to-frailty (12.68% vs. 4.27%; P = 0.0026). Improvement from prefrail-to-robust and remaining robust was more frequent in non-sarcopenic participants (52.56% vs. 33.80%, P ≤ 0.001; 80.18% vs 61.15%, P ≤ 0.001, respectively). When classified by FTS5, this was also the case for the transition from non-frail-to-frail (25.91% vs. 4.47%, P ≤ 0.001) and for remaining stable as non-frail (91.25% vs. 70.98%, P ≤ 0.001). Sarcopenia was associated with an increased risk of progression from robustness-to-prefrailty [odds ratio (OR) 2.34 (95% confidence interval, CI) (1.51, 3.63); P ≤ 0.001], from prefrailty-to-frailty [OR(95% CI) 2.50 (1.08, 5.79); P = 0.033] (FP), and from non-frail-to-frail [OR(95% CI) 4.73 (2.94, 7.62); P-value ≤ 0.001]. Sarcopenia does not seem to modify the risk of death associated with a poor frailty status (hazard ratios (HR, 95%) P > 0.05). CONCLUSIONS: Transitions within frailty status, but not the risk of death associated to frailty, are modulated by the presence of sarcopenia.

Effects of Vivifrail multicomponent intervention on functional capacity: a multicentre, randomized controlled trial.

BACKGROUND: Physical exercise is an effective strategy for preserving functional capacity and improving the symptoms of frailty in older adults. In addition to functional gains, exercise is considered to be a cornerstone for enhancing cognitive function in frail older adults with cognitive impairment and dementia. We assessed the effects of the Vivifrail exercise intervention for functional capacity, cognition, and well-being status in community-dwelling older adults. METHODS: In a multicentre randomized controlled trial conducted in three tertiary hospitals in Spain, a total of 188 older patients with mild cognitive impairment or mild dementia (aged >75 years) were randomly assigned to an exercise intervention (n = 88) or a usual-care, control (n = 100) group. The intervention was based on the Vivifrail tailored multicomponent exercise programme, which included resistance, balance, flexibility (3 days/week), and gait-retraining exercises (5 days/week) and was performed for three consecutive months (http://vivifrail.com). The usual-care group received habitual outpatient care. The main endpoint was change in functional capacity from baseline to 1 and 3 months, assessed with the Short Physical Performance Battery (SPPB). Secondary endpoints were changes in cognitive function and handgrip strength after 1 and 3 months, and well-being status, falls, hospital admission rate, visits to the emergency department, and mortality after 3 months. RESULTS: The Vivifrail exercise programme provided significant benefits in functional capacity over usual-care. The mean adherence to the exercise sessions was 79% in the first month and 68% in the following 2 months. The intervention group showed a mean increase (over the control group) of 0.86 points on the SPPB scale (95% confidence interval [CI] 0.32, 1.41 points; P < 0.01) after 1 month of intervention and 1.40 points (95% CI 0.82, 1.98 points; P < 0.001) after 3 months. Participants in the usual-care group showed no significant benefit in functional capacity (mean change of -0.17 points [95% CI -0.54, 0.19 points] after 1 month and -0.33 points [95% CI -0.70, 0.04 points] after 3 months), whereas the exercise intervention reversed this trend (0.69 points [95% CI 0.29, 1.09 points] after 1 month and 1.07 points [95% CI 0.63, 1.51 points] after 3 months). Exercise group also obtained significant benefits in cognitive function, muscle function, and depression after 3 months over control group (P < 0.05). No between-group differences were obtained in other secondary endpoints (P > 0.05). CONCLUSIONS: The Vivifrail exercise training programme is an effective and safe therapy for improving functional capacity in community-dwelling frail/prefrail older patients with mild cognitive impairment or mild dementia and also seems to have beneficial effect on cognition, muscle function, and mood status.

C-Reactive Protein Is Associated with Physical Fitness in Breast Cancer Survivors.

Background: Physical fitness (PF) is an expression of the physiological functioning of multiple body components. PF is an important prognostic factor in terms of cardiovascular mortality, cancer mortality, and all-cause mortality. PF has been related to some biomarkers in the general population but not in breast cancer survivors (BCS). Purpose: To evaluate the effects of PF on biomarkers potentially related to physical activity (PA) in a sample of BCS. Methods: Cross-sectional study. A total of 84 BCS (mean age 54) who had finished their treatment were recruited. Different components of PF were evaluated, namely body composition (anthropometry), cardiorespiratory fitness (one-mile walk test), muscular (handgrip and sit-to-stand timed test), and motor (gait speed) components. Sexual hormones, inflammation, and insulin resistance biomarkers were measured. Results: C-Reactive Protein (CRP) was associated with every component of physical fitness: cardiorespiratory fitness (p-value = 0.002), muscular (sit-to-stand timed test, p-value = 0.002) and motor (gait speed, p-value = 0.004) components, and body composition (body mass index, p-value = 0.003; waist, p-value < 0.000; and waist-to-hip index, p-value = 0.012). CRP also was associated with "poor physical condition," a constructed variable that encompasses all components of physical fitness (p-value < 0.001). Insulin was associated with cardiorespiratory fitness and gait speed (p-values = 0.002 and 0.024, respectively). Insulin-like Growth Factor-1 was negatively associated with waist perimeter and waist-to-hip ratio. Conclusions: CRP can also be considered an indicator of poor PF in BCS. Implications for cancer survivors: in case of elevation of CRP indicating cardiovascular risk, health professionals should recommend lifestyle changes to improve BCS physical condition.

Associations between frailty trajectories and frailty status and adverse outcomes in community-dwelling older adults.

BACKGROUND: The association between frailty and adverse outcomes has been clearly defined. Frailty is associated with age, but different frailty evolution patterns might determine the incidence of adverse outcomes at older ages. So far, few observational studies have examined how distinct frailty trajectories could be associated with differences in the risk of adverse events and assessing whether frailty trajectories could define risk of death, hospitalization, worsening, and incident disability better than one-off assessment. Our hypothesis is that prospective increases in frailty levels are associated with higher risk of adverse events compared with subjects that prospectively decreased frailty levels. METHODS: Participants' data were taken from the Toledo Study of Healthy Ageing. Frailty was evaluated using the Frailty Trait Scale 5 (FTS5), being 0 the lower (the most robust) and 50 the highest (the frailest) score. FTS5 scores at baseline and follow-up (median 5.04 years) were used to construct frailty trajectories according to group-based trajectory modelling (GBTM). Multivariate Cox proportional hazard and logistic regression models were used to explore associations between frailty status and trajectory membership and the adverse outcomes. Deaths were ascertained through the Spanish National Death Index. Disability was evaluated through the Katz Index. Hospitalization was defined as first admission to Toledo Hospital. RESULTS: Nine hundred and seventy-five older adults (mean age 73.14 ± 4.69; 43.38% men) were included. GBTM identified five FTS5 trajectories: worsening from non-frailty (WNF), improving to non-frailty (INF), developing frailty (DF), remaining frail (RF), and increasing frailty (IF). Subjects belonging to trajectories of increasing frailty scores or showing consistently higher frailty levels presented with an increased risk of mortality {DF [hazard ratio (HR), 95% confidence interval (CI)] = 2.01 [1.21-3.32]; RF = 1.92 [1.18-3.12]; IF = 2.67 [1.48-4.81]}, incident [DF (HR, 95% CI) = 2.06 (1.11-3.82); RF = 2.29 (1.30-4.03); IF = 3.55 (1.37-9.24)], and worsening disability [DF (HR, 95% CI) = 2.11 (1.19-3.76); RF = 2.14 (1.26-3.64); IF = 2.21 (1.06-4.62)], compared with subjects prospectively showing decreases in frailty levels or maintaining low FTS5 scores. A secondary result was a significant dose-response relationship between baseline FTS5 score and adverse events. CONCLUSIONS: Belonging to trajectories of prospectively increasing/consistently high frailty scores over time are associated with an increased risk of adverse outcomes compared with maintaining low or reducing frailty scores. Our results support the dynamic nature of frailty and the potential benefit of interventions aimed at reducing its levels on relevant and burdensome adverse outcomes.

Changes in Health Behaviors, Mental and Physical Health among Older Adults under Severe Lockdown Restrictions during the COVID-19 Pandemic in Spain.

We used data from 3041 participants in four cohorts of community-dwelling individuals aged ≥65 years in Spain collected through a pre-pandemic face-to-face interview and a telephone interview conducted between weeks 7 to 15 after the beginning of the COVID-19 lockdown. On average, the confinement was not associated with a deterioration in lifestyle risk factors (smoking, alcohol intake, diet, or weight), except for a decreased physical activity and increased sedentary time, which reversed with the end of confinement. However, chronic pain worsened, and moderate declines in mental health, that did not seem to reverse after restrictions were lifted, were observed. Males, older adults with greater social isolation or greater feelings of loneliness, those with poorer housing conditions, as well as those with a higher prevalence of chronic morbidities were at increased risk of developing unhealthier lifestyles or mental health declines with confinement. On the other hand, previously having a greater adherence to the Mediterranean diet and doing more physical activity protected older adults from developing unhealthier lifestyles with confinement. If another lockdown were imposed during this or future pandemics, public health programs should specially address the needs of older individuals with male sex, greater social isolation, sub-optimal housing conditions, and chronic morbidities because of their greater vulnerability to the enacted movement restrictions.

Prevalence and correlates of cancer-related fatigue in breast cancer survivors.

PURPOSE: To identify potential correlates of cancer-related fatigue (CRF) after curative breast cancer (BC) treatment. The hypothesis was that fatigue would be more severe among women treated with cardiotoxic drugs, with poor physical condition and those who exercised less. METHODS: Observational cross-sectional design. Fatigue was evaluated through PERFORM Questionnaire (multi-item, multi-dimensional). Patient-reported assessments and objective information regarding clinical data, physical activity (PA) and physical condition were analysed as potential correlates of CRF. RESULTS: One hundred eighty women who remained free of disease were recruited. The prevalence of fatigue interfering with quality of life was 43%. Weight, resting and recovery heart rate were positively associated with fatigue. Age and time from diagnosis were negatively associated. Previous therapies, objectively assessed weekly PA, cardiorespiratory condition, muscular strength and adherence to Mediterranean diet were not associated with CRF. CONCLUSIONS: CRF is a prevalent problem after BC treatment. Objectively assessed PA, cardiorespiratory fitness and muscular strength did not predict CRF. The association of heart rate and fatigue deserves a further insight. Future research should include longitudinal studies and determination of biomarkers. IMPLICATIONS FOR CANCER SURVIVORS: BC survivors, especially younger and overweight women, should be informed about fatigue as a potential persistent symptom through all stages of the cancer trajectory and into survivorship. They also should be routinely screened for CRF.

Cancer-related Fatigue in Breast Cancer Survivors: A Review.

Fatigue has been the most distressing and frequent symptom in breast cancer (BC) survivors after treatment. Although fatigue can occur in other cancer survivors, women with a history of BC might share some distinctive features. The present study aimed to recapitulate the knowledge about risk factors and correlates of cancer-related fatigue (CRF) in BC survivors after oncologic therapy. An electronic data search was conducted in PubMed using the terms "fatigue," "breast," "cancer," and "survivors." Records were included if they were original articles, available in English, had used a quantitative scale, had > 100 participants, and had excluded women with BC relapse. BC survivors were required to have finished their treatments ≥ 2 months before, except for hormonal therapy. The physiopathology and other interventions were considered beyond the scope of our review. The correlates were subsequently classified into 7 main categories: (1) sociodemographic data, (2) physical variables, (3) tumor- and treatment-related variables, (4) comorbidities, (5) other symptoms, (6) psychological issues, and (7) lifestyle factors. Fatigue was consistently greater in younger, obese, and diabetic women. Women reporting fatigue often communicated symptoms such as pain, depression, insomnia, and cognitive dysfunction. Coping strategies such as catastrophizing could play an important role in the persistence of fatigue. However, tumor characteristics, previous treatments received, and physical activity were not consistently reported. CRF was a strong predictor of the quality of life of BC survivors after treatment. In conclusion, we found CRF was a frequent and serious symptom that severely affects the quality of life of BC survivors after treatment. Health practitioners require more awareness and information about CRF.

Rapid Assessment at Hospital Admission of Mortality Risk From COVID-19: The Role of Functional Status.

OBJECTIVE: To evaluate the role of functional status along with other used clinical factors on the occurrence of death in patients hospitalized with COVID-19. DESIGN: Prospective cohort study. SETTING: Public university hospital (Madrid). PARTICIPANTS AND METHODS: A total of 375 consecutive patients with COVID-19 infection, admitted to a Public University Hospital (Madrid) between March 1 and March 31, 2020, were included in the Prospective Cohort study. Death was the main outcome. The main variable was disability in activities of daily living (ADL) assessed with the Barthel Index. Covariates included sex, age, severity index (Quick Sequential Organ Failure Assessment, qSOFA), polypharmacy (≥5 drugs in the month before admission), and comorbidity (≥3 diseases). Multivariable logistic regression was used to identify risk factors for adverse outcomes. Estimated model coefficients served to calculate the expected probability of death for a selected combination of 5 variables: Barthel Index, sex, age, comorbidities, and severity index (qSOFA). RESULTS: Mean age was 66 years (standard deviation 15.33), and there were 207 (55%) men. Seventy-four patients died (19.8%). Mortality was associated with low Barthel Index (odds ratio per 5-point decrease 1.11, 95% confidence interval 1.03-1.20), male sex (0.23, 0.11-0.47), age (1.07, 1.03-1.10), and comorbidity (2.15, 1.08-4.30) but not with qSOFA (1.29, 0.87-1.93) or polypharmacy (1.54, 0.77-3.08). Calculated mortality risk ranged from 0 to 0.78. CONCLUSIONS AND IMPLICATIONS: Functional status predicts death in hospitalized patients with COVID-19. Combination of 5 variables allows to predict individual probability of death. These findings provide useful information for the decision-making process and management of patients.

Concurrent Exercise Interventions in Breast Cancer Survivors with Cancer-related Fatigue.

This study compared the effects of two supervised concurrent training interventions in breast cancer survivors with cancer-related fatigue at baseline. Twenty-three female breast cancer survivors (50±8 years) were randomized to a high- (n=13) or a moderate-intensity (n=10) training program. Both interventions lasted 16 weeks and included the same resistance exercises, but the aerobic component was supervised and more intense in the former (i.e., rating of perceived exertion of 7-8 vs. 6 on a 1-10 scale for the high and moderate-intensity intervention, respectively). The primary endpoint was fatigue perception. Endpoints were assessed at baseline and after 16 weeks. The p-value for statistical significance was set at 0.004 after Bonferroni correction for multiple comparisons. The high-intensity training program increased lower-limb muscle strength significantly (p=0.002) and tended to improve fatigue perception (p=0.006), waist circumference (p=0.013), neutrophil-to-lymphocyte ratio (p=0.028) and some quality of life items (p=0.011). Although the moderate-intensity training program did not provide such benefits in general (i.e., higher p-values for pre vs post-intervention comparisons), no significant differences were found between interventions (all p>0.004). Further research is needed to elucidate if the benefits provided by high-intensity concurrent training are superior to those elicited by moderate-intensity training in breast cancer survivors.

Cardiorespiratory fitness and adiposity in breast cancer survivors: is meeting current physical activity recommendations really enough?

PURPOSE: Breast cancer (BC) survivors are becoming increasingly predisposed to cardiovascular disease (CVD) mortality. Low cardiorespiratory fitness and physical activity (PA) levels, as well as high values of adiposity indices, contribute to CVD risk. We evaluated adiposity, cardiorespiratory profile, and PA levels in two independent cohorts of BC survivors. METHODS: Data were collected from two groups (99% women) from different areas of Madrid (Spain): group 1, n = 110, age 51.4 ± 9.7 years, median time from diagnosis 365 days (95% confidence interval [CI], 354-401), and group 2, n = 93, age 54.7 ± 8.9 years, 1714 days (95% CI, 1502-1938). We estimated peak oxygen uptake (VO2peak) and measured body mass index (BMI), waist circumference (WC), waist-to-hip index, and accelerometry-determined PA. RESULTS: Both groups had values of BMI in the overweight range (25.3 ± 4.3 and 27.1 ± 5.1 kg/m2, p = 0.003). Estimated VO2peak levels were lower in group 2 than in group 1 (28.1 ± 9.1 and 23.7 ± 8.8 ml/kg/min, p < 0.001), although levels in both groups were low. Yet, the majority of participants in both groups (81 and 88%, p = 0.234) met international PA recommendations (235 ± 196 and 351 ± 173 min/week of moderate-vigorous PA, p < 0.001). Both groups had very low levels of vigorous PA. These results were essentially independent of type of treatment (anthracycline/radiotherapy). CONCLUSIONS: We found a poor cardiorespiratory profile in two independent BC cohorts that differed in median time from diagnosis (as well in socioeconomic status), supporting the notion that implementation of PA (possibly focusing on vigorous PA) and dietary intervention is urgently needed in this patient population.