Putting up with a pandemic

The COVID-19 pandemic created a unique opportunity to examine health as a function of multiple real-life stressors, especially in people with a chronic disease. Early studies indicated that the pandemic had an impact on social, physical and emotional aspects of life. This thesis examined mental and physical health during the COVID-19 pandemic in people with and without a chronic illness. Psychological flexibility is assumed to help dealing with adverse circumstances. We examined whether and to what extend psychological flexibility played a health-protecting role during the pandemic and whether the questionnaire that was used to assess psychological flexibility might be shortened. The five studies of this thesis yielded the following main findings: Although patients with an Inflammatory Rheumatic Disease (IRD) were more worried and stressed during the acute peak of the COVID-19 pandemic in 2020 compared to those without an IRD, their level of mental well-being was not lower compared to that of patients before the pandemic in 2018. There was no indication that psychological flexibility was a protective factor against a deterioration of health. Higher worry and stress during the pandemic, having a Central Sensitivity Syndrome (CSS) and lower psychological flexibility were all associated with more severe somatic symptoms. However, the association of stress with somatic symptoms was not particularly strong in people with a CSS and psychological flexibility did not buffer this association. The hypothesis that COVID-19 stress augments somatic symptoms particularly in people with a CSS, was not confirmed by our research. Although health of women with fibromyalgia was persistently low, mental health was not lower and pain and physical functioning were even better during, compared to before the COVID-19 pandemic. Especially during the prolonged phase of the pandemic in 2021, young adults’ mental and physical health was low, with one exception: in young adults with a chronic illness and low psychological flexibility, physical health was found to be better during the prolonged phase, compared to the acute and pre-pandemic phases. Factor analysis on the sixty items of the FIT-60 yielded a 2-factor solution, representing items of the ‘mindfulness and acceptance’ dimension of psychological inflexibility and of the ‘commitment and behavior change’ dimension of psychological flexibility, which were also represented in a succinct 18 item questionnaire: the FIT-18. Overall, this thesis implies that, with exception of young adults, people were perhaps mentally and physically healthier than expected during the pandemic. The expected larger health-preserving role of psychological flexibility, in worse times of the pandemic and in people with a chronic illness, was hardly confirmed. This suggests that more nuanced research is needed, regarding interventions that could support people with low flexibility in putting up with life after the pandemic

From Barrett's Esophagus towards Adenocarcinoma: Genetic and Clinical studies

Esophageal adenocarcinoma is a highly aggressive disease from which more than 80% of patients die within 5 years after diagnosis. Worldwide almost 400,000 new patients are diagnosed annually. Herewith esophageal cancer ranks eighth on the list of most common cancers, and sixth on the list of cancer mortality causes 1. More than 90% of esophageal cancers are either squamous cell carcinomas or adenocarcinomas 2. Esophageal cancer incidence has been rapidly increasing in Western Europe and the USA 3-5. This could be mainly ascribed to an increase in the rate of esophageal adenocarcinoma, which by now equals or even exceeds the rate of esophageal squamous cell carcinomas. Esophageal cancer incidence in the Netherlands is 10.2/100,000 for men and 3.2/100,000 for women with around 900 newly diagnosed patients annually 6. Adenocarcinomas of the gastric cardia and of the esophagus, commonly located in the distal esophagus, have several similarities. They show a parallel increase in incidence. Moreover, they show similarities in epidemiological and histomorphological features as well as in patterns of comorbidity 7-9. This thesis mainly deals with molecular biological aspects of adenocarcinomas of the distal esophagus and its precursor lesion, Barrett’s esophagus, but also includes work on adenocarcinomas of the gastric cardia. Adenocarcinomas from the distal third of the esophagus plus adenocarcinomas of the gastric cardia are in this thesis altogether mentioned by the description “gastro-esophageal junction (GEJ) adenocarcinomas”

Primate energy input and the evolutionary transition to energy-dense diets in humans

Humans and other large-brained hominins have been proposed to increase energy turnover during their evolutionary history. Such increased energy turnover is plausible, given the evolution of energy-rich diets, but requires empirical confirmation. Framing human energetics in a phylogenetic context, our meta-analysis of 17 wild non-human primate species shows that daily metabolizable energy input follows an allometric relationship with body mass where the allometric exponent for mass is 0.75 ± 0.04, close to that reported for daily energy expenditure measured with doubly labelled water in primates. Human populations at subsistence level (n = 6) largely fall within the variation of primate species in the scaling of energy intake and therefore do not consume significantly more energy than predicted for a non-human primate of equivalent mass. By contrast, humans ingest a conspicuously lower mass of food (−64 ± 6%) compared with primates and maintain their energy intake relatively more constantly across the year. We conclude that our hominin hunter–gatherer ancestors did not increase their energy turnover beyond the allometric relationship characterizing all primate species. The reduction in digestive costs due to consumption of a lower mass of high-quality food, as well as stabilization of energy supply, may have been important evolutionary steps enabling encephalization in the absence of significantly raised energy intakes

Validation, reproducibility and safety of trans dermal electrical stimulation in chronic pain patients and healthy volunteers

<p>Abstract</p> <p>Background</p> <p>Surrogate pain models have been extensively tested in Normal Human Volunteers (NHV). There are few studies that examined pain models in chronic pain patients. Patients are likely to have altered pain mechanisms. It is of interest to test patient pain responses to selective pain stimuli under controlled laboratory conditions.</p> <p>Methods</p> <p>The Institutional Ethic Committee approved the study. 16 patients with chronic neuropathic radiculopathy and 16 healthy volunteers were enrolled to the study after obtaining informed consent. During electrical stimulation (150 minutes for volunteers and 75 minutes for patients) the following parameters were measured every 10 minutes:</p> <p>Ongoing pain: Visual Analogue Scale (VAS) and Numeric Rate Scale (NRS)</p> <p>Allodynia (soft foam brush)</p> <p>Hyperalgesia (von Frey monofilament 20 g)</p> <p>Flare</p> <p>For each endpoint, the area under the curve (AUC) was estimated from the start of stimulation to the end of stimulation by the trapezoidal rule. The individual AUC values for both periods were plotted to show the inter- and intra-subject variability. For each endpoint a mixed effect model was fitted with random effect subject and fixed effect visit. The estimate of intra-subject variance and the mean value were then used to estimate the sample size of a crossover study required to have a probability of 0.80 to detect a 25% change in the mean value. Analysis was done using GenStat 8^thedition.</p> <p>Results</p> <p>Each endpoint achieved very good reproducibility for patients and NHV. Comparison between groups revealed trends towards:</p> <p>Faster habituation to painful stimuli in patients</p> <p>Bigger areas of hyperalgesia in patients</p> <p>Similar area of allodynia and flare (no statistical significance)</p> <p>Conclusion</p> <p>The differences demonstrated between patients and NHVs suggest that the electrical stimulation device used here may stimulate pathways that are affected in the pathological state.</p