The impact of participation restrictions on everyday life in long-term colorectal cancer survivors in the EnCoRe study:A mixed-method study

Purpose: Knowledge about long-term colorectal cancer (CRC) or treatment related health and functioning problems and on its impact on participation of CRC survivors in domestic life and in society is limited. We aimed to explore the nature and impact of cancer (treatment) related participation restrictions on everyday life of long-term CRC survivors, their current satisfaction with participation, and associations of health and functioning problems with participation satisfaction, using the International Classification of Functioning, Disability and Health (ICF) to comprehensively study participation.Method: Mixed-method study in 2-10 years post-diagnosis stage I-III CRC survivors (n = 151) from the cross-sectional part of the EnCoRe study. Participation restrictions were explored by semi-structured interviews in a subsample reporting participation restrictions (n = 10). Role functioning (SF36-Health Survey), fatigue (Checklist Individual Strength), and peripheral neuropathy symptoms (EORTC QLQ-CIPN20) were assessed in all participants and associations with self-reported participation satisfaction were analyzed by multivariable logistic regression models.Results: 19% of CRC survivors reported dissatisfaction with participation. Participation restrictions were reported for interpersonal relationships, work/employment, and social/civic life. CRC survivors reporting better physical and emotional role functioning were significantly less likely to be dissatisfied with their participation, whereas survivors reporting higher levels of fatigue or more peripheral neuropathy symptoms were more likely to be dissatisfied with participation.Conclusions: Colorectal cancer (treatment) related health and functioning problems negatively impacts the ability of nearly 1 in 5 long-term CRC survivors to participate in everyday life situations and their satisfaction with participation. Follow-up care needs to be able to identify and address these problems.</p

Evaluating the Validity of a Food Frequency Questionnaire in Comparison with a 7-Day Dietary Record for Measuring Dietary Intake in a Population of Survivors of Colorectal Cancer

Background: Food frequency questionnaires (FFQs) are a commonly used method to assess dietary intake in epidemiological studies. It is important to evaluate the validity of FFQs in the population of interest. Objective: To evaluate the validity of an FFQ for measuring dietary intake in survivors of colorectal cancer (CRC), relative to a 7-day dietary record. Design: Dietary intake was assessed 1 year after the end of CRC treatment. Participants first completed a 7-day dietary record and 2 weeks later a 253-item FFQ that measured intake in the preceding month. Participants/setting: Data were used from a subsample of participants (n=100) enrolled in an ongoing prospective study (EnCoRe study) in the Netherlands, from 2015 to 2018. Main outcome measures: Estimated intakes of total energy, 19 nutrients, and 20 food groups as well as scoring adherence to the dietary recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) were compared between both dietary assessment methods. Statistical analyses performed: Means and standard deviations, Spearman rank correlations corrected for within-person variation and total energy, and κ agreement between quintiles were assessed. Results: The median Spearman correlation corrected for within-person variation for nutrients and total energy was 0.60. Correlations >0.50 were found for 15 of 19 nutrients, with highest agreement for vitamin B-12 (0.74), polysaccharides (0.75), and alcohol (0.91). On average, 73% (range=60% to 84%) of participants were classified into the exact same or adjacent nutrient quintile. The median Spearman correlation corrected for within-person variation for food groups was 0.62. Correlations >0.50 were found for 17 of 20 food groups, with highest agreement for cereals and cereal products (0.96), fish (0.96), and potatoes (0.99). The Spearman correlation between total scores of the WCRF/AICR dietary recommendations was 0.53. Conclusions: Relative to a 7-day dietary record, the validity of an FFQ for measuring dietary intake among survivors of CRC appeared moderate to good for most nutrients and food groups.</p

Associations between alcohol consumption and anxiety, depression, and health-related quality of life in colorectal cancer survivors

Purpose  Alcohol consumption is a major risk factor for colorectal cancer (CRC). It is currently poorly understood, however, how alcohol and different alcoholic beverage types are related to psychosocial outcomes in CRC survivors.  Methods  We used data of N = 910 CRC survivors from the pooled EnCoRe and PROCORE cohorts and harmonized them into five time points: at diagnosis and 3, 6, 12, and 24 months post-diagnosis. Generalized estimated equation models were used to examine longitudinal associations of alcohol consumption, including consumption of beer, wine, and liquor, with anxiety, depression, and health-related quality of life (HRQoL), while correcting for sociodemographic, lifestyle, and clinical factors.  Results  Survivors were on average 67 years and 37% was female. In the first 2 years post-diagnosis, survivors who consumed more alcoholic drinks/week reported lower anxiety and depressive symptoms and better HRQoL on all domains and symptom scales. This was the case for moderate and heavy amounts of alcohol and mostly for consuming beer and wine, but not for liquor. Associations were more often significant for men and for younger persons (< 67 years at baseline).  Conclusions  Generally, alcohol consumption was observed to be longitudinally related to less anxiety and depression and better HRQoL in CRC survivors. Implications for Cancer Survivors Although alcohol consumption is generally unfavorable due to increased risk of carcinogenesis and worse prognosis after CRC, it seems to be associated with better psychosocial outcomes in the first 2 years after diagnosis and treatment. More research is needed to gain knowledge about reasons for drinking and causality. Netherlands Trial Registry (www.trialregister.nl, NL6904

Higher Serum Vitamin D Concentrations Are Longitudinally Associated with Better Global Quality of Life and Less Fatigue in Colorectal Cancer Survivors up to 2 Years after Treatment

BACKGROUND: Vitamin D status may be an important determinant of health-related quality of life of colorectal cancer survivors. The current study investigated longitudinal associations between serum 25-hydroxyvitamin D3 (25OHD3) concentrations and quality of life in stage I-III colorectal cancer survivors up to 2 years after treatment. METHODS: Patients with colorectal cancer (n = 261) were included upon diagnosis. Home visits (including blood sampling) were performed at diagnosis and at 6 weeks, 6 months, 1 year, and 2 years after treatment. Serum 25OHD3 concentrations were measured using LC/MS-MS and adjusted for season. Validated questionnaires were used to assess global quality of life and cognitive functioning (EORTC-QLQ-C30), fatigue (EORTC-QLQ-C30 and Checklist Individual Strength, CIS), and depression and anxiety (Hospital Anxiety and Depression Scale). Statistical analyses were performed using linear mixed models and adjusted for sex, age, time since diagnosis, therapy, comorbidities, physical activity, and body mass index. RESULTS: At diagnosis, 45% of patients were vitamin D deficient (<50 nmol/L). After treatment, 25OHD3 concentrations increased on average with 3.1 nmol/L every 6 months. In confounder-adjusted models, 20 nmol/L increments in 25OHD3 were longitudinally associated with increased global quality of life [β 2.9; 95% confidence interval (CI), 1.5-4.3] and reduced fatigue (EORTC-QLQ-C30 subscale: β -3.5; 95% CI, -5.3 to -1.8 and CIS: β -2.8; 95% CI, -4.7 to -0.9). Observed associations were present both within and between individuals over time. CONCLUSIONS: Higher concentrations of 25OHD3 were longitudinally associated with better global quality of life and less fatigue in colorectal cancer survivors. IMPACT: This study suggests that higher 25OHD3 concentrations may be beneficial for colorectal cancer survivors. Future intervention studies are needed to corroborate these findings

A Comparative Study on the WCRF International/University of Bristol Methodology for Systematic Reviews of Mechanisms Underpinning Exposure-Cancer Associations

The World Cancer Research Fund (WCRF) International and the University of Bristol have developed a novel framework for providing an overview of mechanistic pathways and conducting a systematic literature review of the biologically plausible mechanisms underlying exposure-cancer associations. Two teams independently applied the two-stage framework on mechanisms underpinning the association between body fatness and breast cancer to test the framework feasibility and reproducibility as part of a WCRF-commissioned validation study. In stage I, a "hypothesis-free" approach was used to provide an overview of potential intermediate mechanisms between body fatness and breast cancer. Dissimilar rankings of potential mechanisms were observed between the two teams due to different applications of the framework. In stage II, a systematic review was conducted on the insulin-like growth factor 1 receptor (IGF1R) chosen as an intermediate mechanism. Although the studies included differed, both teams found inconclusive evidence for the body fatness-IGF1R association and modest evidence linking IGF1R to breast cancer, and therefore concluded that there is currently weak evidence for IGF1R as mechanism linking body fatness to breast cancer. The framework is a good starting point for conducting systematic reviews by integrating evidence from mechanistic studies on exposure-cancer associations. On the basis of our experience, we provide recommendations for future users. (C) 2017 AACR

Effects of oral adenosine 5'-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: a randomized cross-over study

<p>Abstract</p> <p>Background</p> <p>It is well-known that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the small bowel associated with disruption of mucosal barrier function. In healthy human volunteers, we showed previously that topical administration of adenosine 5'-triphosphate (ATP) by naso-intestinal tube attenuated a rise in small intestinal permeability induced by short-term challenge with the NSAID indomethacin. This finding suggested that ATP may be involved in the preservation of intestinal barrier function. Our current objective was to corroborate the favourable effect of ATP on indomethacin-induced permeability changes in healthy human volunteers when ATP is administered via enteric-coated capsules, which is a more practically feasible mode of administration. Since ATP effects may have been partly mediated through its breakdown to adenosine, effects of encapsulated adenosine were tested also.</p> <p>Methods</p> <p>By ingesting a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by five-hour collection of total urine, small intestinal permeability was assessed in 33 healthy human volunteers by measuring the urinary lactulose/rhamnose excretion ratio. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC). Basal permeability of the small intestine was assessed as a control condition (no indomethacin, no ATP/adenosine). As a model of increased small intestinal permeability, two dosages of indomethacin were ingested at 10 h (75 mg) and 1 h (50 mg) before ingesting the lactulose/rhamnose test drink. At 1.5 h before indomethacin ingestion, two dosages of placebo, ATP (2 g per dosage) or adenosine (1 g per dosage) were administered via enteric-coated hydroxypropyl methylcellulose (HPMC) capsules with Eudragit^©L30D-55.</p> <p>Results</p> <p>Median urinary lactulose/rhamnose excretion ratio (g/g) in the control condition was 0.032 (interquartile range: 0.022–0.044). Compared to the control condition, lactulose/rhamnose ratio after ingestion of indomethacin plus placebo was significantly increased to 0.039 (0.035–0.068); P < 0.01). The indomethacin-induced increase was neither affected by administration of encapsulated ATP (0.047 (0.033–0.065)) nor adenosine (0.050 (0.030–0.067)). Differences in L/R ratios between the conditions with indomethacin plus placebo, ATP or adenosine were not significant.</p> <p>Conclusion</p> <p>In this study, either ATP or adenosine administered via enteric-coated capsules had no effect on indomethacin-induced small intestinal permeability changes in healthy human volunteers. The observed lack of effect of encapsulated ATP/adenosine may have been caused by opening of the enteric-coated supplement at a site distal from the indomethacin-inflicted site. Further studies on site-specific effectiveness of ATP/adenosine on intestinal permeability changes are warranted.</p

Tutorial: A nontechnical explanation of the counterfactual definition of effect modification and interaction

Effect modification and interaction are important concepts for answering causal questions about interdependent effects of two (or more) exposures on some outcome of interest. Although conceptually alike and often mistakenly regarded as synonymous, effect modification and interaction actually refer to slightly different concepts when considered from a causal perspective. Their subtle yet relevant distinction lies in how the interplay between exposures is defined and the causal roles attributed to the exposures involved in the effect modification and interaction. To gain more insight into similarities and differences between the concepts of effect modification and interaction, the counterfactual theory of causation, albeit complicated, can be very helpful. Therefore, this article presents a nontechnical explanation of the counterfactual definition of effect modification and interaction. Essentially, effect modification and interaction are reflections of the reality and complexity of multicausality. The causal effect of an exposure of interest often depends on the levels of other exposures (effect modification) or causal effects of other exposures (interaction). Consequently, exposure effects should not be regarded in isolation but in combination. Understanding the underlying principles of effect modification and interaction on a conceptual level enables researchers to better anticipate, detect, and interpret these causal phenomena when setting up, analyzing, and reporting findings of (clinical) epidemiological studies. Effect modification and interaction are not biases to be avoided but properties of causal effects that ought to be unveiled. Hence, evidence for effect modification and interaction needs to be shown in order to delineate in whom and which instances causal effects occur. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/

Tutorial: A nontechnical explanation of the counterfactual definition of effect modification and interaction

Effect modification and interaction are important concepts for answering causal questions about interdependent effects of two (or more) exposures on some outcome of interest. Although conceptually alike and often mistakenly regarded as synonymous, effect modification and interaction actually refer to slightly different concepts when considered from a causal perspective. Their subtle yet relevant distinction lies in how the interplay between exposures is defined and the causal roles attributed to the exposures involved in the effect modification and interaction. To gain more insight into similarities and differences between the concepts of effect modification and interaction, the counterfactual theory of causation, albeit complicated, can be very helpful. Therefore, this article presents a nontechnical explanation of the counterfactual definition of effect modification and interaction. Essentially, effect modification and interaction are reflections of the reality and complexity of multicausality. The causal effect of an exposure of interest often depends on the levels of other exposures (effect modification) or causal effects of other exposures (interaction). Consequently, exposure effects should not be regarded in isolation but in combination. Understanding the underlying principles of effect modification and interaction on a conceptual level enables researchers to better anticipate, detect, and interpret these causal phenomena when setting up, analyzing, and reporting findings of (clinical) epidemiological studies. Effect modification and interaction are not biases to be avoided but properties of causal effects that ought to be unveiled. Hence, evidence for effect modification and interaction needs to be shown in order to delineate in whom and which instances causal effects occur. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/

A nontechnical explanation of the counterfactual definition of confounding

In research addressing causal questions about relations between exposures and outcomes, confounding is an issue when effects of interrelated exposures on an outcome are confused. For making valid inferences about cause-and-effect relationships, the biasing influence of confounding must be controlled by design or eliminated during data analysis. Consequently, researchers require a sound understanding of the concept of confounding to adequately deal with this type of bias when setting up and conducting (clinical) epidemiological research. For explaining confounding on a conceptual level, the counterfactual framework for causal inference is invaluable but can be very complicated. In this article, therefore, a nontechnical explanation of the counterfactual definition of confounding is presented. When considering confounding in a counterfactual way, the principle of exchangeability plays a pivotal role. Causal effects of an exposure on an outcome can be evaluated only when different exposure groups have comparable background risks of the outcome. Then, exposure groups are exchangeable and thus unconfounded. By providing a simplified explanation of the counterfactual principles of exchangeability, and consequences of nonexchangeability, this article aims to increase understanding of confounding on a conceptual level as well as the rationale underlying design and analytic strategies for dealing with confounding in (clinical) epidemiological research. (C) 2020 Elsevier Inc. All rights reserved