PURPOSE: Fatigue is a common and potentially disabling symptom in patients with cancer. It can often be effectively reduced by exercise. Yet, effects of exercise interventions might differ across subgroups. We conducted a meta-analysis using individual patient data of randomized controlled trials (RCTs) to investigate moderators of exercise intervention effects on cancer-related fatigue.METHODS: We used individual patient data from 31 exercise RCTs worldwide, representing 4,366 patients, of whom 3,846 had complete fatigue data. We performed a one-step individual patient data meta-analysis, using linear mixed-effect models to analyze the effects of exercise interventions on fatigue (z-score) and to identify demographic, clinical, intervention- and exercise-related moderators. Models were adjusted for baseline fatigue and included a random intercept on study level to account for clustering of patients within studies. We identified potential moderators by testing their interaction with group allocation, using a likelihood ratio test.RESULTS: Exercise interventions had statistically significant beneficial effects on fatigue (β= -0.17 [95% confidence interval (CI) -0.22;-0.12]). There was no evidence of moderation by demographic or clinical characteristics. Supervised exercise interventions had significantly larger effects on fatigue than unsupervised exercise interventions (βdifference= -0.18 [95%CI -0.28;-0.08]). Supervised interventions with a duration ≤12 weeks showed larger effects on fatigue (β= -0.29 [95% CI -0.39;-0.20]) than supervised interventions with a longer duration. CONCLUSIONS: In this individual patient data meta-analysis, we found statistically significant beneficial effects of exercise interventions on fatigue, irrespective of demographic and clinical characteristics. These findings support a role for exercise, preferably supervised exercise interventions, in clinical practice. Reasons for differential effects in duration require further exploration.
Background Ethnic differences in colon cancer (CC) care were shown in the United States, but results are not directly applicable to European countries due to fundamental healthcare system differences. This is the first study addressing ethnic differences in treatment and survival for CC in the Netherlands. Methods Data of 101,882 patients diagnosed with CC in 1996–2011 were selected from the Netherlands Cancer Registry and linked to databases from Statistics Netherlands. Ethnic differences in lymph node (LN) evaluation, anastomotic leakage and adjuvant chemotherapy were analysed using stepwise logistic regression models. Stepwise Cox regression was used to examine the influence of ethnic differences in adjuvant chemotherapy on 5-year all-cause and colorectal cancer-specific survival. Results Adequate LN evaluation was significantly more likely for patients from ‘other Western’ countries than for the Dutch (OR 1.09; 95% CI 1.01–1.16). ‘Other Western’ patients had a significantly higher risk of anastomotic leakage after resection (OR 1.24; 95% CI 1.05–1.47). Patients of Moroccan origin were significantly less likely to receive adjuvant chemotherapy (OR 0.27; 95% CI 0.13–0.59). Ethnic differences were not fully explained by differences in socioeconomic and hospital-related characteristics. The higher 5-year all-cause mortality of Moroccan patients (HR 1.64; 95% CI 1.03–2.61) was statistically explained by differences in adjuvant chemotherapy receipt. Conclusion These results suggest the presence of ethnic inequalities in CC care in the Netherlands. We recommend further analysis of the role of comorbidity, communication in patient-provider interaction and patients’ health literacy when looking at ethnic differences in treatment for CC.
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Enhancing sweetness of vegetables by addition of sucrose or sweeteners can increase acceptance but is not necessarily desirable. An alternative strategy could be to combine vegetables with other vegetables. By offering combinations of vegetables it might be possible to suppress bitterness, enhance sweetness and provide texture variety leading to increased acceptance. The aim of this study was to determine the influence of combining vegetables with other vegetables on sensory properties and acceptance. Carrot (sweet), cucumber (neutral), green bell pepper (bitter) and red bell pepper (sour) were assessed individually and in combination with the other three vegetables in two mixing ratios (1:2 and 2:1). Additionally, four combinations of three vegetables (mixing ratio 1:1:1) were assessed. A trained panel (n = 24) evaluated taste, flavour and texture and a consumer panel (n = 83) evaluated acceptance of all vegetables and combinations. Combining green bell pepper with carrot (1:2 and 2:1) increased sweetness and decreased bitterness. Combining cucumber, carrot or red bell pepper with green bell pepper (1:2) increased bitterness. Mainly sweetness and bitterness were associated with acceptance whereas texture (crunchiness, firmness and juiciness) did not strongly influence acceptance. Cucumber was the most accepted vegetable followed by carrot, red bell pepper and green bell pepper. Acceptance of vegetable combinations can differ from acceptance of individual vegetables depending on vegetable type and mixing ratio. Only 3 of 16 vegetable combinations had higher acceptance compared to the least accepted vegetable in the combination and similar acceptance as the more accepted vegetable in the combination. For 13 of 16 vegetable combinations acceptance did not increase compared to acceptance of individual vegetables. These findings suggest that strategies aimed at increasing vegetable consumption can be devised using specific combinations of vegetables.
Huntington’s disease (HD) and various spinocerebellar ataxias (SCA) are autosomal dominantly inherited neurodegenerative disorders caused by a CAG repeat expansion in the disease-related gene1. The impact of HD and SCA on families and individuals is enormous and far reaching, as patients typically display first symptoms during midlife. HD is characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. SCAs are mainly characterized by ataxia but also other symptoms including cognitive deficits, similarly affecting quality of life and leading to disability. These problems worsen as the disease progresses and affected individuals are no longer able to work, drive, or care for themselves. It places an enormous burden on their family and caregivers, and patients will require intensive nursing home care when disease progresses, and lifespan is reduced. Although the clinical and pathological phenotypes are distinct for each CAG repeat expansion disorder, it is thought that similar molecular mechanisms underlie the effect of expanded CAG repeats in different genes. The predicted Age of Onset (AO) for both HD, SCA1 and SCA3 (and 5 other CAG-repeat diseases) is based on the polyQ expansion, but the CAG/polyQ determines the AO only for 50% (see figure below). A large variety on AO is observed, especially for the most common range between 40 and 50 repeats11,12. Large differences in onset, especially in the range 40-50 CAGs not only imply that current individual predictions for AO are imprecise (affecting important life decisions that patients need to make and also hampering assessment of potential onset-delaying intervention) but also do offer optimism that (patient-related) factors exist that can delay the onset of disease.To address both items, we need to generate a better model, based on patient-derived cells that generates parameters that not only mirror the CAG-repeat length dependency of these diseases, but that also better predicts inter-patient variations in disease susceptibility and effectiveness of interventions. Hereto, we will use a staggered project design as explained in 5.1, in which we first will determine which cellular and molecular determinants (referred to as landscapes) in isogenic iPSC models are associated with increased CAG repeat lengths using deep-learning algorithms (DLA) (WP1). Hereto, we will use a well characterized control cell line in which we modify the CAG repeat length in the endogenous ataxin-1, Ataxin-3 and Huntingtin gene from wildtype Q repeats to intermediate to adult onset and juvenile polyQ repeats. We will next expand the model with cells from the 3 (SCA1, SCA3, and HD) existing and new cohorts of early-onset, adult-onset and late-onset/intermediate repeat patients for which, besides accurate AO information, also clinical parameters (MRI scans, liquor markers etc) will be (made) available. This will be used for validation and to fine-tune the molecular landscapes (again using DLA) towards the best prediction of individual patient related clinical markers and AO (WP3). The same models and (most relevant) landscapes will also be used for evaluations of novel mutant protein lowering strategies as will emerge from WP4.This overall development process of landscape prediction is an iterative process that involves (a) data processing (WP5) (b) unsupervised data exploration and dimensionality reduction to find patterns in data and create “labels” for similarity and (c) development of data supervised Deep Learning (DL) models for landscape prediction based on the labels from previous step. Each iteration starts with data that is generated and deployed according to FAIR principles, and the developed deep learning system will be instrumental to connect these WPs. Insights in algorithm sensitivity from the predictive models will form the basis for discussion with field experts on the distinction and phenotypic consequences. While full development of accurate diagnostics might go beyond the timespan of the 5 year project, ideally our final landscapes can be used for new genetic counselling: when somebody is positive for the gene, can we use his/her cells, feed it into the generated cell-based model and better predict the AO and severity? While this will answer questions from clinicians and patient communities, it will also generate new ones, which is why we will study the ethical implications of such improved diagnostics in advance (WP6).
This project aims to develop a measurement tool to assess the inclusivity of experiences for people with varying challenges and capabilities on the auditory spectrum. In doing so, we performed an in-depth exploration of scientific literature and findings from previous projects by Joint Projects. Based on this, we developed an initial conceptual model that focuses on sensory perception, emotion, cognition, and e[ort in relation to hearing and fatigue. Within, this model a visitor attraction is seen as an “experienscape” with four key elements: content, medium, context, and individual. In co-creative interviews with experts by experience with varying challenges on the auditory spectrum, they provided valuable insights that led to a significant expansion of this initial model. This was a relevant step, as in the scientific and professional literature, little is known about the leisure experiences of people with troubled hearing. For example, personal factors such as a person’s attitude toward their own hearing loss and the social dynamics within their group turned out to greatly influence the experience. The revised model was then applied in a case study at Apenheul, focusing on studying differences in experience of their gorilla presentation amongst people with varying challenges on the auditory spectrum.Societal issueThe Netherlands is one of the countries in Europe with the highest density of visitor attractions. Despite this abundance, many visitor attractions are not fully accessible to everyone, particularly to visitors with disabilities who sometimes are not eligible to ride due to safety concerns, yet when eligible generally still encounter numerous barriers. Accessibility of visitor attractions can be approached in various ways. However, because the focus often lies on operational and technical aspects (e.g., reducing stimuli at certain times of the day by turning o[ music, o[ering alternative wheelchair entrances), strategic and community-focused approaches are often overlooked. More importantly, there is also a lack of attention to the experience of visitors with disabilities. This becomes apparent from several studies from Joint Projects, where visitor attractions are being visited together with experts by experience with various disabilities. Nevertheless, experience is often being regarded as the 'core product' of the leisure sector. The right to meet, discover, develop, relax and thus enjoy this core product is hindered for many people with disabilities due to a lack of knowledge, inaccessibility (physical, digital, social, communicative as well as financial) and discrimination in society. Additionally, recreation entrepreneurs still face a significant gap in reaching the potential market of guests with disabilities and their networks. Thus, despite the numerous initiatives in the leisure sector aimed at improving accessibility on technical and operational fronts, often people with disabilities are still not being able to experience the same kind of enjoyment as those without. These observations form the pressing impetus for initiating the current research project, tapping into the numerous opportunities for learning, development and growth on making leisure offer more inclusive.Benefit to societyIn total, the current project approach comes with a number of enrichments in terms of both knowledge and methodology: a mixed-methods approach that allows for comparing data from different sources to obtain a more complete picture of the experience; a methodological co-design process that honours the 'nothing about us without us' principle; and benchmarking for a group (i.e., people with challenges on the auditory spectrum) that despite the size of its population has thus far mostly been overlooked.
Wheelchair users with a spinal cord injury (SCI) or amputation generally lead an inactive lifestyle, associated with reduced fitness and health. Digital interventions and sport and lifestyle applications (E-platforms) may be helpful in achieving a healthy lifestyle. Despite the potential positive effects of E-platforms in the general population, no studies are known investigating the effects for wheelchair users and existing E-platforms can not be used to the same extent and in the same manner by this population due to differences in physiology, body composition, exercise forms and responses, and risk injury. It is, therefore, our aim to adapt an existing E-platform (Virtuagym) within this project by using existing data collections and new data to be collected within the project. To reach this aim we intend to make several relevant databases from our network available for analysis, combine and reanalyze these existing databases to adapt the existing E-platform enabling wheelchair users to use it, evaluate and improve the use of the adapted E-platform, evaluate changes in healthy active lifestyle parameters, fitness, health and quality of life in users of the E-platform (both wheelchair users and general population) and identify determinants of these changes, identify factors affecting transitions from an inactive lifestyle, through an intermediate level, to an athlete level, comparing wheelchair users with the general population, and comparing Dutch with Brazilian individuals. The analysis of large datasets of exercise and fitness data from various types of individuals with and without disabilities, collected over the last years both in the Netherlands and Brazil, is an innovative and potentially fruitful approach. It is expected that the comparison of e.g. wheelchair users in Amsterdam vs. Sao Paulo or recreative athletes vs. elite athletes provides new insight in the factors determining a healthy and active lifestyle.
