Preventing Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: ALLO-Active Trial.

BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) is an efficacious treatment for hematologic malignancies but can be complicated by cardiac dysfunction and exercise intolerance impacting quality of life and longevity. We conducted a randomized controlled trial testing whether a multicomponent activity intervention could attenuate reductions in cardiorespiratory fitness and exercise cardiac function (co-primary end points) in adults undergoing allo-SCT. METHODS: Sixty-two adults scheduled for allo-SCT were randomized to a 4-month activity program (n=30) or usual care (UC; n=32). Activity comprised multicomponent exercise training (3 days/week) and sedentary time reduction (≥30 min/day) program and was delivered throughout hospitalization (≈4 weeks) and for 12 weeks after discharge. Physiological assessments conducted before admission and at 12 weeks after discharge included cardiopulmonary exercise testing to quantify peak oxygen uptake ([Formula: see text]), exercise cardiac magnetic resonance imaging for peak cardiac volume (CIpeak) and stroke volume (SVIpeak) index, echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and cardiac biomarkers (cTn-I [troponin-I] and BNP [B-type natriuretic peptide]). RESULTS: Fifty-two participants (84%) completed follow-up (25 activity and 27 UC); median (interquartile range [IQR]) adherence to the activity program was 74% (41-96%). There was a marked decline in [Formula: see text] in the UC program (-3.4 mL‧kg-1‧min-1 [95% CI, -4.9 to -1.8]) that was attenuated with activity (-0.9 mL‧kg-1‧min-1 [95% CI, -2.5 to 0.8]; interaction P=0.029). Activity preserved exercise cardiac function, with preservation of CIpeak (0.30 L‧min-1‧m-2 [95% CI, -0.34 to 0.41]) and SVIpeak (0.6 mL/m2 [95% CI, -1.3 to 2.5]), both of which declined with UC (CIpeak, -0.68 L‧min-1‧m-2 [95% CI, -1.3 to -0.32]; interaction P=0.008; SVIpeak, -2.7 mL/m2 [95% CI, -4.6 to -0.9]; interaction P=0.014). There were no treatment effects of activity on cardiac biomarkers or echocardiographic indices. CONCLUSIONS: Multicomponent activity intervention during and after allo-SCT is beneficial for preserving patient cardiorespiratory fitness and exercise cardiac function. These results may have important implications for cardiovascular morbidity and mortality after allo-SCT. REGISTRATION: URL: https://anzctr.org.au/; Unique identifier: ACTRN12619000741189.

Sustained Hypothetical Interventions on Midlife Alcohol Consumption in Relation to All-Cause and Cancer Mortality: The Australian Longitudinal Study on Women's Health.

No randomized controlled trial has evaluated the effect of long-term alcohol interventions on mortality. Results reported in existing observational studies may be subject to selection bias and time-varying confounding. Using data from the Australian Longitudinal Study on Women's Health 1946-1951 birth cohort, collected regularly from 1996-2016, we estimated all-cause and cancer mortality had women been assigned various alcohol interventions (in categories ranging from 0 to >30 g/day ethanol, or reduced to ≤20 g/day if higher) at baseline, and had they maintained these levels of consumption. The cumulative risks for all-cause and cancer mortality were 5.6% (10,118 women followed for 20 years) and 2.9% (18 years), respectively. For all-cause and cancer mortality, baseline ethanol up to 30 g/day showed lower risk and >30 g/day showed higher risk relative to abstention. Had women sustainedly followed the interventions, a similar relationship was observed for all-cause mortality. However, the negative association observed for intakes ≤30 g/day and positive association for intakes >30 g/day was not evident for cancer mortality. Our findings suggest that all-cause mortality could have been lower than observed if this cohort of women had consumed some alcohol (no more than 30 g/day) rather than no consumption, but cancer mortality might not.

Physical activity and pain in people with and without cancer.

BACKGROUND: Performing physical activity may provide analgesic benefit, although this effect is more established for noncancer pain rather than cancer pain. The relationship between physical activity and pain outcomes in adults with and without a history of cancer was examined. METHODS: Totals of 51,439 adults without a cancer history and 10,651 adults with a cancer history from the Cancer Prevention Study II Nutrition Cohort were included. Exposures included self-reported moderate to vigorous physical activity (MVPA) as well as 2-year change in MVPA. Pain outcomes included pain intensity (primary outcome) and analgesic use (secondary outcome). RESULTS: MVPA was inversely associated with pain intensity for adults with (odds ratio [OR], 0.84 [≥15 metabolic equivalent of task (MET) h/week vs. <7.5 MET h/week]; 95% confidence interval [CI], 0.76-0.93) and without (OR, 0.79; 95% CI, 0.75-0.82) a history of cancer. Compared to remaining inactive, participants who became sufficiently active (cancer: OR, 0.76; 95% CI, 0.68-0.86; no cancer: OR, 0.73; 95% CI, 0.69-0.77), became inactive (cancer: OR, 0.79; 95% CI, 0.71-0.88; no cancer: OR, 0.84; 95% CI, 0.80-0.89), or remained sufficiently active (cancer: OR, 0.66; 95% CI, 0.60-0.72; no cancer: OR, 0.62; 95% CI, 0.60-0.65) also reported less pain. Physical activity was not related to analgesic use. CONCLUSIONS: The relationship between physical activity and pain intensity was not substantially different between people with and without a history of cancer. Cancer survivors who perform more activity, or who increase their activity, may experience less pain than cancer survivors who consistently perform less. PLAIN LANGUAGE SUMMARY: People who have had cancer often experience ongoing pain. Being physically active may help reduce the intensity of the pain they experience.

Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer.

BACKGROUND: This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks+ Escherichia coli (pks+E.coli+), pks+E.coli- (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum). METHODS: We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR. RESULTS: Pks+E.coli+ was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks+E.coli+ and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks+E.coli- (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01). CONCLUSION: Intratumoral pks+E.coli+ but not pks+E.coli- are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause.

Sex-steroid hormones and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis.

PURPOSE: Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways. METHODS: This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex-hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders. RESULTS: Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI 1.03 to 1.44), androstenedione (RR 1.20, 95% CI 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI 0.98 to 1.28), estrone (RR 1.21, 95% CI 0.99 to 1.48), total estradiol (RR 1.19, 95% CI 1.02 to 1.39) and free estradiol (RR 1.22, 95% CI 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR 0.83, 95% CI 0.66 to 1.05). CONCLUSION: Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex-hormone-driven nature of postmenopausal breast cancer.

Characterization of additive gene-environment interactions for colorectal cancer risk.

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

Dietary patterns derived by reduced rank regression, macronutrients as response variables, and variation by economic status: NHANES 1999-2018.

PURPOSE: Macronutrient intakes vary across people and economic status, leading to a disparity in diet-related metabolic diseases. This study aimed to provide insight into this by: (1) identifying dietary patterns in adults using reduced rank regression (RRR), with macronutrients as response variables, and (2) investigating the associations between economic status and macronutrient based dietary patterns, and between dietary patterns with central obesity (waist circumference) and systemic inflammation (C-reactive protein [CRP]). METHODS: 41,849 US participants from the National Health and Nutrition Examination Survey (NHANES), 1999-2018 were included. The percentages of energy from protein, carbohydrates, saturated fats, and unsaturated fats were used as response variables in RRR. Multivariable generalized linear models with Gaussian distribution were employed to investigate the associations. RESULTS: Four dietary patterns were identified. Economic status was positively associated with both the high fat, low carbohydrate [ßHighVsLow = 0.22; 95% CI: 0.16, 0.28] and high protein patterns [ßHighVsLow = 0.07; 95% CI: 0.03, 0.11], and negatively associated with both the high saturated fat [ßHighVsLow = -0.06; 95% CI: -0.08, -0.03] and the low alcohol patterns [ßHighVsLow = -0.08; 95% CI; -0.10, -0.06]. The high saturated fat pattern was positively associated with waist circumference [ßQ5VsQ1 = 1.71; 95% CI: 0.97, 2.44] and CRP [ßQ5VsQ1 = 0.37; 95% CI: 0.26, 0.47]. CONCLUSION: Macronutrient dietary patterns, which varied by economic status and were associated with metabolic health markers, may explain associations between economic status and health.

Physical activity and pain in people with cancer: a systematic review and meta-analysis.

PURPOSE: Physical activity can provide analgesic benefit but its effect on cancer-related pain is unclear. This review synthesised and appraised the evidence for the effect of physical activity on pain in people living with or beyond cancer. METHODS: A systematic search of Ovid Medline and Embase was performed to identify randomised controlled trials (RCTs), randomised cross-over studies (RXTs), and prospective observational studies that examined physical activity and pain outcomes in adults living with or beyond cancer. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to assess evidence quality. RESULTS: One hundred twenty-one studies (n = 13,806), including 102 RCTs, 6 RXTs, and 13 observational studies, met the criteria for inclusion. Meta-analyses of RCTs identified a decrease in pain intensity (n = 3734; standardised mean difference (SMD) - 0.30; 95% confidence interval (CI) - 0.45, - 0.15) and bodily pain (n = 1170; SMD 0.28; 95% CI 0.01, 0.56) but not pain interference (n = 207; SMD - 0.13, 95% CI - 0.42, 0.15) following physical activity interventions. Individual studies also identified a reduction in pain sensitivity but not analgesic use, although meta-analysis was not possible for these outcomes. High heterogeneity between studies, low certainty in some effect estimates, and possible publication bias meant that evidence quality was graded as very low to low. CONCLUSION: Physical activity may decrease pain in people living with and beyond cancer; however, high heterogeneity limits the ability to generalise this finding to all people with cancer or to specific types of cancer-related pain.

Healthy lifestyle is associated with reduced cardiovascular disease, depression and mortality in people at elevated risk of sleep apnea.

We assessed: (1) the independent and joint association of obstructive sleep apnea risk and healthy lifestyle with common consequences (excessive daytime sleepiness, depression, cardiovascular disease and stroke) of obstructive sleep apnea; and (2) the effect of healthy lifestyle on survival in people with increased obstructive sleep apnea risk. Data from 13,694 adults (median age 46 years; 50% men) were used for cross-sectional and survival analyses (mortality over 15 years). A healthy lifestyle score with values from 0 (most unhealthy) to 5 (most healthy) was determined based on diet, alcohol intake, physical activity, smoking and body mass index. In the cross-sectional analysis, obstructive sleep apnea risk was positively associated with all chronic conditions and excessive daytime sleepiness in a dose-response manner (p for trend < 0.001). The healthy lifestyle was inversely associated with all chronic conditions (p for trend < 0.001) but not with excessive daytime sleepiness (p for trend = 0.379). Higher healthy lifestyle score was also associated with reduced odds of depression and cardiovascular disease. We found an inverse relationship between healthy lifestyle score with depression (p for trend < 0.001), cardiovascular disease (p for trend = 0.003) and stroke (p for trend = 0.025) among those who had high obstructive sleep apnea risk. In the survival analysis, we found an inverse association between healthy lifestyle and all-cause mortality for all categories of obstructive sleep apnea risk (moderate/high- and high-risk groups [p for trend < 0.001]). This study emphasises the crucial role of a healthy lifestyle in mitigating the effects of obstructive sleep apnea risk in individuals with an elevated obstructive sleep apnea risk.

Associations between COVID-19 and hospitalisation with respiratory and non-respiratory conditions: a record linkage study.

OBJECTIVES: To assess associations between SARS-CoV-2 infection and the incidence of hospitalisation with selected respiratory and non-respiratory conditions in a largely SARS-CoV-2 vaccine-naïve population . DESIGN, SETTING, PARTICIPANTS: Self-control case series; analysis of population-wide surveillance and administrative data for all laboratory-confirmed COVID-19 cases notified to the Victorian Department of Health (onset, 23 January 2020 - 31 May 2021; ie, prior to widespread vaccination rollout) and linked hospital admissions data (admission dates to 30 September 2021). MAIN OUTCOME MEASURES: Hospitalisation of people with acute COVID-19; incidence rate ratios (IRRs) comparing incidence of hospitalisations with defined conditions (including cardiac, cerebrovascular, venous thrombo-embolic, coagulative, and renal disorders) from three days before to within 89 days of onset of COVID-19 with incidence during baseline period (60-365 days prior to COVID-19 onset). RESULTS: A total of 20 594 COVID-19 cases were notified; 2992 people (14.5%) were hospitalised with COVID-19. The incidence of hospitalisation within 89 days of onset of COVID-19 was higher than during the baseline period for several conditions, including myocarditis and pericarditis (IRR, 14.8; 95% CI, 3.2-68.3), thrombocytopenia (IRR, 7.4; 95% CI, 4.4-12.5), pulmonary embolism (IRR, 6.4; 95% CI, 3.6-11.4), acute myocardial infarction (IRR, 3.9; 95% CI, 2.6-5.8), and cerebral infarction (IRR, 2.3; 95% CI, 1.4-3.9). CONCLUSION: SARS-CoV-2 infection is associated with higher incidence of hospitalisation with several respiratory and non-respiratory conditions. Our findings reinforce the value of COVID-19 mitigation measures such as vaccination, and awareness of these associations should assist the clinical management of people with histories of SARS-CoV-2 infection.

Diverse strategies are needed to support physical activity engagement in women who have had breast cancer.

PURPOSE: Physical activity can improve health in people living with and beyond breast cancer; however, how to best support physical activity participation in this population is unclear. This qualitative study sought to identify important physical activity program components for breast cancer. METHODS: Women with previous breast cancer (n = 11) and allied health professionals (n = 7) participated in one-on-one semi-structured interviews (n = 15) or focus groups (n = 1). Qualitative data were analyzed using reflexive thematic analysis methods. RESULTS: Four main themes were generated including (1) the need for physical activity programs; (2) person-centered programs; (3) flexible physical activity programs; and (4) systems factors. These reflected the health and non-health benefits of physical activity, the need to facilitate agency, the diversity in individual characteristics, preferences, abilities, and commitments of people with lived experience of cancer, as well as the need for physical activity programs to be integrated within the broader health system. CONCLUSION: Strategies to support physical activity engagement for breast cancer should embrace the diversity of those who are diagnosed with cancer as well as the diversity in which physical activity can be achieved.

Can mat Pilates and belly dance be effective in improving body image, self-esteem, and sexual function in patients undergoing hormonal treatment for breast cancer? A randomized clinical trial.

The purpose of this study is to examine the effects of a 16-week exercise intervention (mat Pilates or belly dance) on body image, self-esteem and sexual function in breast cancer survivors receiving hormone therapy. Seventy-four breast cancer survivors were randomly allocated into mat Pilates, belly dance, or control group. The physical activity groups received a 16-week intervention, delivered 3 days a week, and 60 min a session. The control group received three education sessions. Data collection occurred at baseline, post-intervention, 6 and 12 months of follow-up with a questionnaire including body image (Body Image After Breast Cancer Questionnaire), self-esteem (Rosenberg Self-Esteem Scale), and sexual function (Female Sexual Function Index) measures. The belly dance group significantly improved body image on limitations scale in the short term and long term, the mat Pilates significantly improved body image on limitations only in the long term, and the control group significantly decreased body image on limitations in the long term. The belly dance group experienced reduced discomfort and pain during sexual relations in the short and long term. All groups showed a significant improvement in self-esteem, but orgasm sub-scale scores declined over time. No adverse events were found for any of the exercise intervention groups. Belly dance seem to be more effective than mat Pilates and control group in improving limitations of body image and sexual discomfort in the short term for breast cancer survivors. ClinicalTrials.gov (NCT03194997) - "Pilates and Dance to Breast Cancer Patients Undergoing Treatment".

The Relationship Between Psychological Distress and Physical Activity Is Non-linear and Differs by Domain: a Cross-Sectional Study.

BACKGROUND: There is increasing evidence for the relationship between physical activity (PA), sedentary behaviour and mental health. Limited data exists on sex-specific associations. We aimed to identify associations between PA dose and domain and television time with psychological distress, including sex-stratified models. METHODS: A total of 22,176 adults from the Melbourne Collaborative Cohort Study follow-up 2 cohort (2003-2007) participated in this cross-sectional study. Occupational, household, transport, leisure PA, hours watching television and psychological distress were assessed. Restricted cubic splines were used to examine the relationships between PA domains, television viewing time and psychological distress. RESULTS: The relationships between PA and psychological distress were non-linear (p < 0.05) and differed by PA domain. There were dose-dependent, inverse associations between distress with transport (B[95% CI] = -0.39[-0.49, -0.30]) and leisure PA (B[95% CI] = -0.35[-0.46, -0.25]). The effect estimates for transport and leisure PA with distress were larger for women. For household domain, a U-shaped curve with an elongated tail was seen. Median PA was associated with lower distress compared with lower quantities (B[95% CI] = -0.12[-0.22, -0.03]); however, this association was not evident with increasing household PA. There were no clear associations between occupational PA and distress. Higher television viewing was associated with higher distress (B[95% CI] = 0.16[0.02, 0.30]). CONCLUSIONS: Increasing PA and reducing television viewing may contribute to reduced psychological distress, particularly in women. Future interventions should incorporate leisure and transport PA and decrease television viewing to assess the impact on mental health.

Alcohol intake trajectories during the life course and risk of alcohol-related cancer: A prospective cohort study.

We examined associations between sex-specific alcohol intake trajectories and alcohol-related cancer risk using data from 22 756 women and 15 701 men aged 40 to 69 years at baseline in the Melbourne Collaborative Cohort Study. Alcohol intake for 10-year periods from age 20 until the decade encompassing recruitment, calculated using recalled beverage-specific frequency and quantity, was used to estimate group-based sex-specific intake trajectories. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for primary invasive alcohol-related cancer (upper aerodigestive tract, breast, liver and colorectum). Three distinct alcohol intake trajectories for women (lifetime abstention, stable light, increasing moderate) and six for men (lifetime abstention, stable light, stable moderate, increasing heavy, early decreasing heavy, late decreasing heavy) were identified. 2303 incident alcohol-related cancers were diagnosed during 485 525 person-years in women and 789 during 303 218 person-years in men. For men, compared with lifetime abstention, heavy intake (mean ≥ 60 g/day) at age 20 to 39 followed by either an early (from age 40 to 49) (early decreasing heavy; HR = 1.75, 95% CI: 1.25-2.44) or late decrease (from age 60 to 69) (late decreasing heavy; HR = 1.94, 95% CI: 1.28-2.93), and moderate intake (mean <60 g/day) at age 20 to 39 increasing to heavy intake in middle-age (increasing heavy; HR = 1.45, 95% CI: 1.06-1.97) were associated with increased risk of alcohol-related cancer. For women, compared with lifetime abstention, increasing intake from age 20 (increasing moderate) was associated with increased alcohol-related cancer risk (HR = 1.25, 95% CI: 1.06-1.48). Similar associations were observed for colorectal (men) and breast cancer. Heavy drinking during early adulthood might increase cancer risk later in life.

Physical activity and glioma: a case-control study with follow-up for survival.

PURPOSE: High-grade disease accounts for ~ 70% of all glioma, and has a high mortality rate. Few modifiable exposures are known to be related to glioma risk or mortality. METHODS: We examined associations between lifetime physical activity and physical activity at different ages (15-18 years, 19-29 years, 30-39 years, last 10 years) with the risk of glioma diagnosis, using data from a hospital-based family case-control study (495 cases; 371 controls). We followed up cases over a median of 25 months to examine whether physical activity was associated with all-cause mortality. Physical activity and potential confounders were assessed by self-administered questionnaire. We examined associations between physical activity (metabolic equivalent [MET]-h/wk) and glioma risk using unconditional logistic regression and with all-cause mortality in cases using Cox regression. RESULTS: We noted a reduced risk of glioma for the highest (≥ 47 MET-h/wk) versus lowest (< 24 METh/wk) category of physical activity for lifetime activity (OR = 0.58, 95% CI: 0.38-0.89) and at 15-18 years (OR = 0.57, 95% CI: 0.39-0.83). We did not observe any association between physical activity and all-cause mortality (HR for lifetime physical activity = 0.91, 95% CI: 0.64-1.29). CONCLUSION: Our findings are consistent with previous research that suggested physical activity during adolescence might be protective against glioma. Engaging in physical activity during adolescence has many health benefits; this health behavior may also offer protection against glioma.

Preventing the adverse cardiovascular consequences of allogeneic stem cell transplantation with a multi-faceted exercise intervention: the ALLO-Active trial protocol.

BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) is a potentially lifesaving treatment for high-risk hematological malignancy, but survivors experience markedly elevated rates of cardiovascular disease and associated functional impairment. Mounting evidence suggests regular exercise, combined with a reduction in sedentary time through replacement with light exercise may be a useful therapeutic strategy for the prevention of cardiovascular comorbidities. However, this type of intervention has yet to be evaluated in patients undergoing allo-SCT. The ALLO-Active study will evaluate the efficacy of a ~ 4 month multi-faceted exercise intervention, commenced upon admission for allo-SCT, to preserve peak oxygen uptake (VO2peak) and peak cardiac output, compared with usual care. The study will also evaluate the effect of the intervention on functional independence, quality of life, and symptoms of fatigue. METHODS: Sixty adults with hematological malignancy scheduled for allo-SCT will be randomly assigned to usual care (n = 30) or the exercise and sedentary behaviour intervention (n = 30). Participants assigned to the intervention will complete a thrice weekly aerobic and progressive resistance training program and concomitantly aim to reduce daily sedentary time by 30 min with short, frequent, light-intensity exercise bouts. Participants will undergo testing prior to, immediately after inpatient discharge, and 12 weeks after discharge. To address aim 1, VO2peak and peak cardiac output (multiple primary outcomes, p < 0.025) will be assessed via cardiopulmonary exercise testing and exercise cardiac magnetic resonance imaging, respectively. Secondary outcomes include functional independence (defined as VO2peak ≥ 18.mL.kg-1.min-1), quality of life, and fatigue (assessed via validated questionnaire). Exploratory outcomes will include indices of resting cardiac, vascular, and skeletal muscle structure and function, cardiovascular biomarkers, anxiety and depression, transplant outcomes (e.g., engraftment, graft-versus-host disease), and habitual physical activity, sedentary time, and sleep. DISCUSSION: Multi-faceted exercise programs are a promising approach for ameliorating the cardiovascular consequences of allo-SCT. If this intervention proves to be effective, it will contribute to the development of evidence-based exercise guidelines for patients undergoing allo-SCT and assist with optimising the balance between acute cancer management and long-term health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ID: 12619000741189 . Registered 17 May 2019.

Television viewing time and all-cause mortality: interactions with BMI, physical activity, smoking, and dietary factors.

BACKGROUND: Higher levels of time spent sitting (sedentary behavior) contribute to adverse health outcomes, including earlier death. This effect may be modified by other lifestyle factors. We examined the association of television viewing (TV), a common leisure-time sedentary behavior, with all-cause mortality, and whether this is modified by body mass index (BMI), physical activity, smoking, alcohol intake, soft drink consumption, or diet-associated inflammation. METHODS: Using data from participants in the Melbourne Collaborative Cohort Study, flexible parametric survival models assessed the time-dependent association of self-reported TV time (three categories: < 2 h/day, 2-3 h/day, > 3 h/day) with all-cause mortality. Interaction terms were fitted to test whether there was effect modification of TV time by the other risk factors. RESULTS: From 19,570 participants, 4,417 deaths were reported over a median follow up of 14.5 years. More TV time was associated with earlier mortality; however, this relationship diminished with increasing age. The hazard ratio (HR) and 95% confidence interval (95% CI) for > 3 h/day compared with < 2 h/day of TV time was 1.34 (1.16, 1.55) at 70 years, 1.14 (1.04, 1.23) at 80 years, and 0.95 (0.84, 1.06) at 90 years. The TV time/mortality relationship was more evident in participants who were physically inactive (compared with active; p for interaction < 0.01) or had a higher dietary inflammatory index score (compared with a lower score; p for interaction = 0.03). No interactions were detected between TV time and BMI, smoking, alcohol intake, nor soft-drink consumption (all p for interaction > 0.16). CONCLUSIONS: The relationship between TV time and all-cause mortality may change with age. It may also be more pronounced in those who are otherwise inactive or who have a pro-inflammatory diet.

Associations between baseline demographic, clinical and lifestyle factors, and changes in fatigue, depression, and health-related quality of life in long-term cancer survivors: a cohort study.

PURPOSE: To investigate the longitudinal associations between demographic, clinical and lifestyle factors, and changes in patient-reported outcomes (PROs) in cancer survivors 6-9 years post-diagnosis in Western Australia. METHODS: A total of 290 individuals participated in this study. Three-quarters of participants were female, and 55%, 31%, and 14% were survivors of breast cancer, colon cancer, and non-Hodgkin lymphoma (NHL), respectively. PROs (fatigue, depression, and health-related quality of life (HRQOL)) were reported at two time points (2012-13 and 2017). Descriptive statistics were used to assess the overall changes over time and linear mixed models were used to identify factors associated with changes over time, after adjusting for confounders. RESULTS: No significant changes were observed in PROs between time point 1 and follow-up at the population level, yet a notable proportion of participants (23% for fatigue, 10% for depression, and 39% for HRQOL) reported a negative minimal clinically important difference (MCID). Being non-Caucasian and having had NHL were associated with negative changes over time. Being obese and having had radiotherapy were related to improved outcomes. CONCLUSION: Cancer survivors whose levels of fatigue, depression, and quality of life are compromised during cancer treatment may require intervention even 6-9 years post-treatment. Our results suggest particular attention should be paid to those who are non-Caucasian and who have had NHL. This is crucial for providing appropriate care and to support those who are at increased risk of deteriorating naturally over time.

Adiposity and estrogen receptor-positive, postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol.

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case-cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case-control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m2 compared to women with BMI 18.5-25 kg/m2 , the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05-2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43-2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11-2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68-1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity-breast cancer relationship but does not explain all of the association.

Social connectedness and mortality after prostate cancer diagnosis: A prospective cohort study.

Men with prostate cancer experience side effects for which a supportive social environment may be beneficial. We examined the association between four measures of social connectedness and mortality after a prostate cancer diagnosis. Male participants in the Melbourne Collaborative Cohort Study in 1990-1994, who developed incident prostate cancer and attended follow-up in 2003-2007, were eligible for the study. Information on social connectedness, collected at follow-up, included (i) living arrangement; (ii) frequency of visits to friends/relatives and (iii) from friends/relatives; (iv) weekly hours of social activities. A total of 1,421 prostate cancer cases was observed (338 all-cause deaths, 113 from prostate cancer), including 867 after follow-up (150 all-cause deaths, 55 from prostate cancer) and 554 before follow-up (188 all-cause deaths, 58 from prostate cancer). Cox models stratified by tumour Gleason score and stage, and sequentially adjusted for socioeconomic, health- and lifestyle-related confounders, were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between social connectedness and all-cause mortality after prostate cancer. Men who reported living alone before diagnosis had higher overall mortality (HR = 1.6, 95% CI: 1.0-2.5), after adjustment for socioeconomic, health and lifestyle confounders. Lower mortality was observed for men with more social activities (p-trend = 0.07), but not in comprehensively adjusted models. Consistent with these findings, men living alone after prostate cancer diagnosis had higher mortality (HR = 1.3, 95% CI: 0.9-1.9). Lower mortality was observed with increasing socializing hours in the age-adjusted model (p-trend = 0.06) but not after more comprehensive adjustment. Our findings suggest that living with someone, but not other aspects of social connectedness, may be associated with decreased mortality for men with prostate cancer.