Effect modification and interaction are key concepts within epidemiologic research. They refer to situations where the magnitude and/or direction of the causal effect of some exposure variable on an ...outcome depends on the level of a second variable (effect modification) or on the effect of a second variable (interaction). Interest in case of effect modification is primarily in one exposure variable, with its effects varying across subgroups, whereas primary interest in case of interaction is in the interplay of effects of two exposure variables. Distinctions between the concepts of effect modification and interaction are subtle. The goal of this article is to clarify these distinctions by using the concept of mediation, which focuses on elucidating mechanisms of causal effects.
Since colorectal cancer (CRC) survivors often suffer from long-term adverse health effects of the cancer and its treatment, having a negative impact on their health-related quality of life (HRQL), ...this study focuses on the association between adherence to WCRF/AICR recommendations and HRQL among CRC survivors. In a cross-sectional PROFILES registry study in 1096 CRC survivors (mean time since diagnosis 8.1 years), WCRF/AICR adherence scores (range 0–8, with a higher score for better adherence) were calculated, and HRQL was assessed using the EORTC QLQ-C30. Associations between adherence scores and HRQL scores were investigated using linear regression analyses. Additionally, associations with adherence to guidelines for body mass index (BMI) (normal weight, overweight and obese), physical activity (PA) (score 0/1) and diet (score < 3, 3– < 4 and > 4) were evaluated separately. Mean adherence score was 4.81 ± 1.04. Higher WCRF/AICR scores were associated with better global health status (
β
1.64; 95%CI 0.69/2.59), physical functioning (
β
2.71; 95%CI 1.73/3.68), role functioning (
β
2.87; 95%CI 1.53/4.21), cognitive functioning (
β
1.25; 95%CI 0.19/2.32), social functioning (
β
2.01; 95%CI 0.85/3.16) and fatigue (
β
− 2.81; 95%CI − 4.02/− 1.60). Adherence versus non-adherence PA was significantly associated with better physical, role, emotional and social functioning, global health status and less fatigue. Except for the association between being obese and physical functioning (
β
− 4.15; 95%CI − 47.16/− 1.15), no statistically significant associations with physical functioning were observed comparing adherence to non-adherence to BMI and dietary recommendations. Better adherence to the WCRF/AICR recommendations was positively associated with global health status, most functioning scales and less fatigue among CRC survivors. PA seemed to be the main contributor.
There is a growing population of survivors of colorectal cancer (CRC). Fatigue and insomnia are common symptoms after CRC, negatively influencing health-related quality of life (HRQoL). Besides ...increasing physical activity and decreasing sedentary behavior, the timing and patterns of physical activity and rest over the 24-h day (i.e. diurnal rest-activity rhythms) could also play a role in alleviating these symptoms and improving HRQoL. We investigated longitudinal associations of the diurnal rest-activity rhythm (RAR) with fatigue, insomnia, and HRQoL in survivors of CRC.
In a prospective cohort study among survivors of stage I-III CRC, 5 repeated measurements were performed from 6 weeks up to 5 years post-treatment. Parameters of RAR, including mesor, amplitude, acrophase, circadian quotient, dichotomy index, and 24-h autocorrelation coefficient, were assessed by a custom MATLAB program using data from tri-axial accelerometers worn on the upper thigh for 7 consecutive days. Fatigue, insomnia, and HRQoL were measured by validated questionnaires. Confounder-adjusted linear mixed models were applied to analyze longitudinal associations of RAR with fatigue, insomnia, and HRQoL from 6 weeks until 5 years post-treatment. Additionally, intra-individual and inter-individual associations over time were separated.
Data were available from 289 survivors of CRC. All RAR parameters except for 24-h autocorrelation increased from 6 weeks to 6 months post-treatment, after which they remained relatively stable. A higher mesor, amplitude, circadian quotient, dichotomy index, and 24-h autocorrelation were statistically significantly associated with less fatigue and better HRQoL over time. A higher amplitude and circadian quotient were associated with lower insomnia. Most of these associations appeared driven by both within-person changes over time and between-person differences in RAR parameters. No significant associations were observed for acrophase.
In the first five years after CRC treatment, adhering to a generally more active (mesor) and consistent (24-h autocorrelation) RAR, with a pronounced peak activity (amplitude) and a marked difference between daytime and nighttime activity (dichotomy index) was found to be associated with lower fatigue, lower insomnia, and a better HRQoL. Future intervention studies are needed to investigate if restoring RAR among survivors of CRC could help to alleviate symptoms of fatigue and insomnia while enhancing their HRQoL.
EnCoRe study NL6904 ( https://www.onderzoekmetmensen.nl/ ).
Purpose
Previous research indicates that sedentary behavior is unfavorably associated with health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. Using isotemporal substitution ...modeling, we studied how substituting sedentary behavior with standing or physical activity was associated with HRQoL in CRC survivors, 2–10 years post-diagnosis.
Methods
A cross-sectional study was conducted in stage I–III CRC survivors (
n
= 145) diagnosed at Maastricht University Medical Center+, the Netherlands (2002–2010). Sedentary, standing, and physical activity time were measured by the thigh-mounted MOX activity monitor. HRQoL outcomes comprised global quality of life, physical, role, and social functioning, and disability (scales: 0–100), fatigue (20–140), and depression and anxiety (0–21). Isotemporal substitution modeling was applied to analyze associations with HRQoL of substituting sedentary time with equal time in standing or physical activity.
Results
On average, participants spent 10.2 h/day sedentary (SD, 1.7), 3.4 h/day standing (1.3), and 1.7 h/day in physical activity (0.8). In confounder-adjusted isotemporal models, substituting sedentary time with standing or with physical activity was associated with significantly better physical functioning (regression coefficient β, i.e., difference in outcome score per 1 h/day of sedentary time substituted with standing or physical activity, 3.1; 95 % confidence interval CI 0.5, 5.7; and 5.6; 0.7, 10.6, respectively). Substituting sedentary time with standing was also associated with significantly lower disability (β, −3.0; 95 % CI −4.9, −1.1) and fatigue (−4.0; −7.6, −0.3).
Conclusions
Our results suggest that substituting sedentary behavior with standing or physical activity may be beneficially associated with certain HRQoL outcomes in CRC survivors. Prospective studies are warranted to confirm whether actual substitution of sedentary behavior with these activities may improve HRQoL in CRC survivors.
Abstract
Colorectal cancer (CRC) survivors need evidence-based guidelines pertaining to post-treatment body composition, which could benefit health-related quality of life (HRQoL). We aimed to ...describe the course of several body composition measures, and to assess longitudinal associations of these measures with HRQoL, fatigue and chemotherapy-induced peripheral neuropathy (CIPN). In a prospective cohort among stage I–III CRC survivors (n = 459), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Body mass index (BMI), waist circumference and fat percentage were assessed as measures of adiposity, and muscle arm circumference and handgrip strength as measures of muscle mass and function. We applied linear mixed-models to describe changes in body composition over time and to analyze overall longitudinal associations. Of included participants, 44% was overweight and 31% was obese at diagnosis. All body composition measures followed similar trends, decreasing from diagnosis to 6 weeks and then increasing up to 24 months post-treatment. In confounder-adjusted mixed models, increases in adipose tissue and muscle function were longitudinally associated with better HRQoL and less fatigue, regardless of pre-treatment body composition. With regards to improving HRQoL, decreasing fatigue and CIPN, clinical practice should also focus on restoring body tissues after CRC treatment.
Trial registration:
NTR7099.
Statistical analyses of randomized controlled trials (RCTs) yield a causally valid estimate of the overall treatment effect, which is the contrast between the outcomes in two randomized treatment ...groups commonly accompanied by a confidence interval. In addition, the trial investigators may want to examine whether the observed treatment effect varies across patient subgroups (also called ‘heterogeneity of treatment effects’), i.e. whether the treatment effect is modified by the value of a variable assessed at baseline. The statistical approach for this evaluation of potential effect modifiers is a test for statistical interaction to evaluate whether the treatment effect varies across levels of the effect modifier. In this article, we provide a concise and nontechnical explanation of the use of simple statistical tests for interaction to identify effect modifiers in RCTs. We explain how to calculate the test of interaction by hand, applied to a dataset with simulated data on 1,000 imaginary participants for illustration.
The increasing colorectal cancer (CRC) survivor population highlights the need for dietary recommendations in order to enhance health-related quality of life (HRQoL) and alleviate symptoms of ...fatigue, chemotherapy-induced peripheral neuropathy (CIPN), and gastrointestinal problems.
Because of the therapeutic potential of dietary fiber on the gut, we aim to assess longitudinal associations of postdiagnostic dietary fiber, fruit, and vegetable intake, a major source of dietary fiber, with HRQoL, fatigue, CIPN, and gastrointestinal symptoms in CRC survivors from 6 wk to 24 mo posttreatment.
In a prospective cohort among stage I–III CRC survivors (n = 459), 5 repeated study measurements between diagnosis and 24 mo posttreatment were executed. Dietary fiber intake and fruit and vegetable intake were measured by 7-d dietary records. HRQoL, fatigue, CIPN, and gastrointestinal symptoms were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyze longitudinal associations from 6 wk until 24 mo posttreatment and used hybrid models to disentangle the overall association into intraindividual changes and interindividual differences over time.
Higher dietary fiber intake and fruit and vegetable intake were longitudinally associated with statistically significant better physical functioning and less fatigue. Intraindividual analyses showed that an increase of 10 g/d in dietary fiber within individuals over time was associated with better physical functioning (β: 2.3; 95% CI: 0.1, 4.4), role functioning (ability to perform daily activities; 5.9; 1.5, 10.3), and less fatigue (−4.1; −7.7, −0.5). An average increase in fruit and vegetable intake of 100 g/d between individuals over time was predominantly associated with less fatigue (−2.2; −4.2, −0.3). No associations were found with CIPN and gastrointestinal symptoms.
Our results suggest that increasing dietary fiber, fruit, and vegetable intake is related to better physical and role functioning and less fatigue in the first 2 y after the end of treatment for CRC.
Purpose
In the general population, poor sleep quality and short sleep duration are associated with a higher body mass index (BMI) and waist circumference (WC), and an unhealthy diet. The aim of this ...study was to assess if the association between sleep quality and duration and BMI, WC, and diet quality also exists among colorectal cancer (CRC) survivors, as many CRC survivors have an unhealthy weight and diet.
Methods
Cross-sectional data from a longitudinal CRC cohort were used. In this study, survivors were 4–13 years post diagnosis. The Pittsburgh Sleep Quality Index (PSQI) was used to assess both sleep quality and sleep duration. Diet quality was assessed by scoring adherence (low, moderate, high) to the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations of five food groups and nutrients: fruit and vegetables, dietary fiber, red and processed meat, alcoholic beverages, and sugary drinks, using a brief diet screener. BMI and WC were self-measured. Associations were analyzed by multivariable linear and multinomial logistic regression analyses.
Results
Among 1002 CRC survivors, 23% reported poor sleep quality (PSQI score ≥ 8) and 24% reported short sleep duration (≤ 6 h). No associations between sleep and BMI, WC, and diet quality were found.
Conclusion
Sleep problems are common in long-term CRC survivors; however, sleep quality and duration was not associated with BMI, WC, and diet quality in this population. It is unknown why the results differ from findings in the general population.
Colorectal cancer is one of the most common lifestyle-related types of cancer. The exact pathophysiologic mechanism in the relation between (visceral) adipose tissue, systemic inflammation and ...colorectal cancer remains unknown. This study aimed to assess the association of lifestyle with markers of systemic inflammation at the time of diagnosis in stage I-III colorectal cancer patients. Patients (n = 298) with stage I-III colorectal cancer from three Dutch hospitals were included at diagnosis. Several lifestyle-related variables (MUST nutritional status score, WCRF/AICR healthy lifestyle score, active smoking, alcohol consumption and BMI) and inflammatory markers (plasma levels of IL-6, IL-8, IL-10, TNFα and ‘high sensitive’ hsCRP) were measured at the time of diagnosis. Confounder-adjusted multivariable linear regression models were used to analyse how the lifestyle variables were associated with the inflammatory markers. Statistically significant associations were found between a better WCRF/AICR lifestyle score and lower levels of IL-6 and hsCRP. A medium and high risk of malnutrition according to the MUST score was associated with elevated levels of both IL-8 and hsCRP. An overall unhealthier lifestyle indicated by a lower WCRF/AICR lifestyle score and a higher risk of malnutrition according to the MUST score at the time of diagnosis was associated with elevated levels of inflammatory markers. These findings can contribute to formulating lifestyle advice to improve treatment outcomes and prognosis in patients having CRC in the future.
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