Substituting bouts of sedentary behavior with physical activity: adopting positive lifestyle choices in people with a history of cancer

Purpose: To determine in people with a history of cancer, whether substituting sitting time with other daily activities (i.e., sleeping, walking, moderate and vigorous physical activity) was associated with changes in waist circumference (WC), an important surrogate marker of cardiometabolic risk. Methods: Cross-sectional analyses from the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) cohort was conducted using isotemporal substitution models to explore the associations of substituting sedentary time, physical activity behavior (International Physical Activity Questionnaire), or sleep (Pittsburgh Sleep Quality Index) with changes in WC. Analyses were conducted using sex-specific WC classifications. Results: In 3,684 people with a history of cancer [mean age (SD) 58.2 (7.3) years; BMI 28.9 (5.2) kgm−2; 71% female], reallocating 10min of sleep or sedentary time for 10min of walking was associated with lower WC in women (p < 0.01). In men, PA intensity appeared to be more strongly associated with a reduced WC. Replacing 10min of sedentary time with 10min of moderate or vigorous PA and replacing 10min of sleep with moderate PA were associated with a significantly reduced WC (p < 0.001). The largest effect was when 10min of moderate PA was replaced with vigorous PA, a reduction in WC (p < 0.01) was evident. Conclusion: For people with a history of cancer, adopting small but positive changes in lifestyle behaviors could help reduce WC and potentially offset negative health-related outcomes associated with higher WC. Further research is required to examine whether such an intervention may be acceptable and manageable among this population

Fruit and vegetable intake and body adiposity among populations in Eastern Canada: The Atlantic Partnership for Tomorrow's Health Study

Objectives The prevalence of obesity among populations in the Atlantic provinces is the highest in Canada. Some studies suggest that adequate fruit and vegetable consumption may help body weight management. We assessed the associations between fruit and vegetable intake with body adiposity among individuals who participated in the baseline survey of the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) cohort study.Methods We carried out a cross-sectional analysis among 26 340 individuals (7979 men and 18 361 women) aged 35–69 years who were recruited in the baseline survey of the Atlantic PATH study. Data on fruit and vegetable intake, sociodemographic and behavioural factors, chronic disease, anthropometric measurements and body composition were included in the analysis.Results In the multivariable regression analyses, 1 SD increment of total fruit and vegetable intake was inversely associated with body mass index (−0.12 kg/m2; 95% CI −0.19 to –0.05), waist circumference (−0.40 cm; 95% CI −0.58 to –0.23), percentage fat mass (−0.30%; 95% CI −0.44 to –0.17) and fat mass index (−0.14 kg/m2; 95% CI −0.19 to –0.08). Fruit intake, but not vegetable intake, was consistently inversely associated with anthropometric indices, fat mass, obesity and abdominal obesity.Conclusions Fruit and vegetable consumption was inversely associated with body adiposity among the participant population in Atlantic Canada. This association was primarily attributable to fruit intake. Longitudinal studies and randomised trials are warranted to confirm these observations and investigate the underlying mechanisms

Adiposity Measures and Plasma Adipokines in Females with Rheumatoid and Osteoarthritis

The objective of this study was to examine the relationship between adipokines and adiposity in individuals with rheumatoid and osteoarthritis in the Atlantic PATH cohort. Using a nested case-control analysis, participants in the Atlantic PATH cohort with rheumatoid or osteoarthritis were matched for measures of adiposity with participants without a history of arthritis. Both measured and self-reported data were used to examine disease status, adiposity, and lifestyle factors. Immunoassays were used to measure plasma markers. BMI was positively correlated with percentage body fat, fat mass index (FMI), and a change in BMI from 18 years of age in all 3 groups. There were no statistical differences between levels of plasma adipokines; adiponectin levels were 6.6, 7.9, and 8.2 μg/ml, leptin levels were 10.3, 13.7, and 11.5 ng/ml, and resistin levels were 10.0, 12.1, and 10.8 ng/ml in participants without arthritis, with rheumatoid arthritis, and with osteoarthritis, respectively. Those with higher levels of adiponectin were more likely to have osteoarthritis (but not rheumatoid arthritis). No association was found between arthritis types and leptin or resistin. This study demonstrates differences in measures of adiposity and adipokines in specific types of arthritis and highlights the need for more research targeting specific adipokines during arthritic disease progression

The relationship between anthropometric measures and cardiometabolic health in shift work: findings from the Atlantic PATH Cohort Study

PurposeTo evaluate the relationship between anthropometric measures and cardiometabolic health in shift workers compared to non-shift workers.MethodsA population health study was conducted with 4155 shift workers and 8258 non-shift workers from the Atlantic Partnership for Tomorrow’s Health (PATH) cohort. Linear and logistic regression models were used to assess the differences in anthropometric measures (body adiposity) and self-reported cardiometabolic disease outcomes (obesity, diabetes, and cardiovascular disease) between shift workers and non-shift workers.ResultsThere was a significant increased risk of cardiovascular disease, obesity, and diabetes among shift workers compared to matched controls despite higher levels of physical activity and lower levels of sedentary behaviour. Shift workers were 17% more likely to be obese (95% CI 7–27) and 27% more likely to have diabetes (95% CI 8–51). The strength of this association was demonstrated by also controlling for body mass index and fat mass index.ConclusionsShift work is associated with obesity, cardiovascular disease, and diabetes despite higher levels of physical activity and lower levels of sedentary behaviour. The association between shift work and cardiometabolic health was independent of body mass index for cardiovascular disease and diabetes, and independent of fat mass index for diabetes

Relationship between Adiponectin and apoB in individuals with diabetes in the Atlantic PATH Cohort

ContextThe increasing prevalence of obesity and diabetes greatly influences the risk for cardiovascular (CV) comorbidities and affects the quality of life of many people. However, the relationship among diabetes, obesity, and cardiovascular risk is complex and requires further investigation to understand the biological milieu connecting these conditions.ObjectiveThe aim of the current study was to explore the relationship between biological markers of adipose tissue function (adiponectin) and CV risk (apolipoprotein B) in body mass index (BMI)–matched participants with and without diabetes.DesignNested case-control study.SettingThe Atlantic Partnership for Tomorrow’s Health (PATH) cohort represents four Atlantic Canadian provinces: Newfoundland and Labrador, New Brunswick; Nova Scotia; and Prince Edward Island.ParticipantsThe study population (n = 480) was aged 35 to 69 years, 240 with diabetes and 240 without diabetes.Main Outcome MeasuresGroups with and without diabetes were matched for sex and BMI. Both measured and self-reported data were used to examine disease status, adiposity, and lifestyle factors. Immunoassays were used to measure plasma markers.ResultsIn these participants, plasma adiponectin levels were lower among those with diabetes than those without diabetes; these results were sex-specific, with a strong relationship seen in women. In contrast, in participants matched for sex and adiposity, plasma apoB levels were similar between participants with and those without diabetes.ConclusionMeasures of adiposity were higher in participants with diabetes. However, when matched for adiposity, the adipokine adiponectin exhibited a strong inverse association with diabetes

Dietary t10,c12-CLA but not c9,t11 CLA Reduces Adipocyte Size in the Absence of Changes in the Adipose Renin–Angiotensin System in fa/fa Zucker Rats

In obesity, increased activity of the local renin–angiotensin system (RAS) and enlarged adipocytes with altered adipokine production are linked to the development of obesity-related health problems and cardiovascular disease. Mixtures of conjugated linoleic acid (CLA) isomers have been shown to reduce adipocyte size and alter the production of adipokines. The objective of this study was to investigate the effects of feeding individual CLA isomers on adipocyte size and adipokines associated with the local adipose RAS. Male fa/fa Zucker rats received either (a) control, (b) cis(c)9,trans(t)11-CLA, or (c) t10,c12-CLA diet for 8 weeks. The t10,c12-CLA isomer reduced adipocyte size and increased cell number in epididymal adipose tissue. RT-PCR and Western blot analysis revealed that neither CLA isomer altered mRNA or protein levels of angiotensinogen or AngII receptors in adipose tissue. Likewise, levels of the pro-inflammatory cytokines TNF-α and IL-6 or the anti-inflammatory cytokine IL-10 were unchanged in adipose tissue. Similarly, neither CLA isomer had any effect on phosphorylation nor DNA binding of NF-κB. Our results suggest that although the t10,c12-CLA isomer had beneficial effects on reducing adipocyte size in obese rats, this did not translate into changes in the local adipose RAS or associated adipokines

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Investigating the oral microbiome in retrospective and prospective cases of prostate, colon, and breast cancer

Abstract The human microbiome has been proposed as a potentially useful biomarker for several cancers. To examine this, we made use of salivary samples from the Atlantic Partnership for Tomorrow’s Health (PATH) project and Alberta’s Tomorrow Project (ATP). Sample selection was divided into both a retrospective and prospective case control design examining prostate, breast, and colon cancer. In total 89 retrospective and 260 prospective cancer cases were matched to non-cancer controls and saliva samples were sequenced using 16S rRNA gene sequencing. We found no significant differences in alpha diversity. All beta diversity measures were insignificant except for unweighted UniFrac profiles in retrospective breast cancer cases and weighted UniFrac, Bray-Curtis and Robust Atchinson’s distances in colon cancer after testing with age and sex adjusted MiRKAT models. Differential abundance (DA) analysis showed several taxa that were associated with previous cancer in all three groupings. Only one genus (Clostridia UCG-014) in breast cancer and one ASV (Fusobacterium periodonticum) in colon cancer was identified by more than one DA tool. In prospective cases three ASVs were associated with colon cancer, one ASV with breast cancer, and one ASV with prostate cancer. Random Forest classification showed low levels of signal in both study designs in breast and prostate cancer. Contrastingly, colon cancer did show signal in our retrospective analysis (AUC: 0.737) and in one of two prospective cohorts (AUC: 0.717). Our results indicate that it is unlikely that reliable microbial oral biomarkers for breast and prostate cancer exist.. However, further research into the oral microbiome and colon cancer could be fruitful

Assessing the Variation within the Oral Microbiome of Healthy Adults

More than 1,000 different species of microbes have been found to live within the human oral cavity, where they play important roles in maintaining both oral and systemic health. Several studies have identified the core members of this microbial community; however, the factors that determine oral microbiome composition are not well understood. In this study, we exam the salivary oral microbiome of 1,049 Atlantic Canadians using 16S rRNA gene sequencing to determine which dietary, lifestyle, and anthropometric features play a role in shaping microbial community composition. Features that were identified as being significantly associated with overall composition then were additionally examined for genera, amplicon sequence variants, and predicted pathway abundances that were associated with these features. Several associations were replicated in an additional secondary validation data set. Overall, we found that several anthropometric measurements, including waist-hip ratio (WHR), height, and fat-free mass, as well as age and sex, were associated with overall oral microbiome structure in both our exploratory and validation data sets. We were unable to validate any dietary impacts on overall taxonomic oral microbiome composition but did find evidence to suggest potential contributions from factors such as the number of vegetable and refined grain servings an individual consumes. Interestingly, each one of these factors on its own was associated with only minor shifts in the overall taxonomic composition of the oral microbiome, suggesting that future biomarker identification for several diseases associated with the oral microbiome can be undertaken without the worry of confounding factors obscuring biological signals.IMPORTANCE The human oral cavity is inhabited by a diverse community of microbes, known as the human oral microbiome. These microbes play a role in maintaining both oral and systemic health and, as such, have been proposed to be useful biomarkers of disease. However, to identify these biomarkers, we first need to determine the composition and variation of the healthy oral microbiome. In this report, we investigate the oral microbiome of 1,049 healthy individuals to determine which genera and amplicon sequence variants are commonly found between individual oral microbiomes. We then further investigate how lifestyle, anthropometric, and dietary choices impact overall microbiome composition. Interestingly, the results from this investigation showed that while many features were significantly associated with oral microbiome composition, no single biological factor explained a variation larger than 2%. These results indicate that future work on biomarker detection may be encouraged by the lack of strong confounding factors