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Abstract Self-rated health is a common assessment used in epidemiological research and an independent predictor of morbidity and mortality. We investigate if a single measure of self-rated health in late adolescence predict mortality between 46 and 70 years of age. This study was based on 47 286 Swedish men that conscribed 1969–1970 at age 18–20 and that were still alive in 1997. Self-rated health and data on potential explanatory factors (psychological factors, health status markers and health behaviors) were collected at conscription. Adult socioeconomic position in 1990 was derived from registries. Death and cause of death (cancer, cardiovascular disease, violent and alcohol abuse related disorders) were derived from the Causes of Death Register between 1997 and 2019. Conscripts that rated their health as fair or poor/very poor had significantly higher hazard of all-cause mortality than conscript that rated their health as very good (HRfair = 1.27, 95%CI:1.18–1.37 and HRpoor = 1.25, 95%CI:1.11–1.41) and disease-specific mortality. Adjusting for all explanatory factors attenuated the risk estimates by 9–100%. In conclusion, poor self-rated health reported in late adolescence predicts all-cause and disease-specific mortality between the ages of 46 and 70 years. Psychological factors and health behaviors measured at conscription may serve as potential explanatory factors underlying the predictive ability of self-rated health in late adolescence.

Abstract The aim is to investigate the evidence for shared genetic architecture between each of asthma, allergic rhinitis and eczema with gastro-esophageal reflux disease (GERD). Structural equation models (SEM) and polygenic risk score (PRS) analyses are applied to three Swedish twin cohorts (n = 46,582) and reveal a modest genetic correlation between GERD and asthma of 0.18 and bidirectional PRS and phenotypic associations ranging between OR 1.09-1.14 and no correlations for eczema and allergic rhinitis. Linkage disequilibrium score regression is applied to summary statistics of recently published GERD and asthma/allergic disease genome wide association studies and reveals a genetic correlation of 0.48 for asthma and GERD, and Genomic SEM supports a single latent factor. A gene-/gene-set analysis using MAGMA reveals six pleiotropic genes (two at 12q13.2) associated with asthma and GERD. This study provides evidence that there is a common genetic architecture unique to asthma and GERD that may explain comorbidity and requires further investigation.

AbstractObjectives This study aimed to assess the impact of on-demand versus continuous prescribing of proton pump inhibitors (PPIs) on symptom burden and health-related quality of life in patients with gastroesophageal reflux disease (GERD) presenting to primary care.Methods Thirty-six primary care centres across Europe enrolled adult GERD patients from electronic health records. Participants were randomised to on-demand or continuous PPI prescriptions and were followed for 8 weeks. PPI intake, symptom burden, and quality of life were compared between the two groups using mixed-effect regression analyses. Spearman’s correlation was used to assess the association between changes in PPI dose and patient-reported outcomes.Results A total of 488 patients (median age 51 years, 58% women) completed the initial visit, with 360 attending the follow-up visit. There was no significant difference in PPI use between the continuous and on-demand prescription groups (b=.57, 95%CI:0.40-1.53), although PPI use increased in both groups (b = 1.33, 95%CI:0.65 − 2.01). Advice on prescribing strategy did not significantly affect patient-reported outcomes. Both symptom burden (Reflux Disease Questionnaire, b=-0.61, 95%CI:-0.73 − -0.49) and quality of life (12-item Short Form Survey physical score b = 3.31, 95%CI:2.17 − 4.45) improved from baseline to follow-up in both groups. Increased PPI intake correlated with reduced reflux symptoms (n = 347, ρ=-0.12, p = 0.02) and improved quality of life (n = 217, ρ = 0.16, p = 0.02).Conclusion In real-world settings, both continuous and on-demand PPI prescriptions resulted in similar increases in PPI consumption with no difference in treatment effects. Achieving an adequate PPI dose to alleviate reflux symptom burden improves quality of life in GERD patients. EudraCT number 2014-001314-25.

AbstractThe ‘Oslo Chronic Fatigue Consortium’ consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

The Sickness Questionnaire (SicknessQ) is a questionnaire developed to assess symptoms of sickness behavior, including somatic, behavioral, and affective dimensions. To promote cross-cultural assessments of sickness behavior, we aim to expand the use of this questionnaire to other populations and languages. The aim of the present study was to evaluate the French translation of SicknessQ in a French-speaking general population during the COVID-19 pandemic. One hundred and thirty-nine individuals completed the SicknessQ online, along with the construct criteria measures of self-rated health, state anxiety (STAI-S), and depressive symptoms (PHQ-9). The principal component analyses revealed two components: the first component included seven items concerning mood, motivation and experiences of fatigue and pain; the second component included three items concerning somatic sickness symptoms. Higher scores on the total scale and the two component subscales were associated with poorer self-rated health and higher STAI-S and PHQ-9 scores. Since the associations with construct criteria variables were relatively similar between the single- and the two-dimensional solutions, both the total scale and the subscales of the two components of the French SicknessQ can be used in future studies to measure sickness behavior in French-speaking populations.

IntroductionLynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC). In order to detect CRCs amongst LS patients, regular colonoscopies are recommended. However, an international agreement on an optimal surveillance interval has not yet been reached. In addition, few studies have investigated factors that could potentially increase the CRC risk amongst LS patients.AimsThe primary aim was to describe the frequency of CRCs detected during endoscopic surveillance and to estimate the interval from a clean colonoscopy to CRC detection amongst LS patients. The secondary aim was to investigate individual risk factors, including sex, LS genotype, smoking, aspirin use and body mass index (BMI), on CRC risk amongst patients that develop CRC before and during surveillance.Material and methodsClinical data and colonoscopy findings from 366 LS patients’ 1437 surveillance colonoscopies were collected from medical records and patient protocols. Logistic regression and Fisher’s exact test were used to investigate associations between individual risk factors and CRC development. Mann-Whitney U test was used to compare the distribution of TNM stages of CRC detected before surveillance and after index.ResultsCRC was detected in 80 patients before surveillance and in 28 patients during surveillance (10 at index and 18 after index). During the surveillance programme, CRC was detected within 24 months in 65% of the patients, and after 24 months within 35% of the patients. CRC was more common amongst men, previous and current smokers, and the odds of developing CRC also increased with an increasing BMI. CRCs were more often detected amongst MLH1 and MSH2 carriers during surveillance, compared to the other genotypes.ConclusionsWe found that 35% of the CRC cases detected during surveillance were found after 24 months. MLH1 and MSH2 carriers were at higher risk of developing CRC during surveillance. Additionally, men, current or previous smokers, and patients with a higher BMI were at higher risk of developing CRC. Currently, LS patients are recommended a “one-size-fits-all” surveillance program. The results support the development of a risk-score whereby individual risk factors should be taken into consideration when deciding on an optimal surveillance interval.

Abstract Background FODMAPs (Fermentable Oligo-, Di-, Monosaccharides And Polyols) are known for their health benefits but their fermentation may trigger gastrointestinal symptoms and a low-FODMAP diet is a commonly used intervention for functional gastrointestinal disorders. The use of direct measures of FODMAP is labor intensive and expensive and to facilitate the assessment of FODMAP intake in research and clinical work, a nutritional content database with good quality estimates on FODMAP values is needed. Further, the average intake of FODMAP in a general population would be a useful reference and knowledge of the most commonly eaten foods containing FODMAPs would facilitate clinical work utilizing FODMAP diet interventions. Methods A nutritional content database was extended with published FODMAP content data. The database was used to calculate FODMAP intake from four-day food diaries from 117 individuals from the general population in Sweden and the most common food items containing FODMAPs were identified. Results FODMAP content for 1060 food items was added to the database resulting in 1805 listed FODMAP values. Mean intake of total FODMAP in the diaries was 19 g (fructose: 15.2 g; fructan: 3.5 g; lactose: 14.1 g; galacto-oligosaccharides (GOS) 0.43 g and polyols 1.3 g per day). Overall the most common eaten food items containing FODMAPs were rye and wheat based foods. Conclusion Intake of FODMAPs as calculated using the extended database were in line with previous studies supporting its use of the database in both research and clinical interventions. The lists of the most commonly eaten FODMAP food items are provided and may be used to facilitate FODMAP diet interventions.

Summary: Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10−8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.

Peripheral inflammation has been found associated with psychiatric disorders. However, results are inconclusive as to its role in common mental disorders (CMDs), i.e., depression, anxiety, insomnia and stress-related disorders. Further, some research suggests that cognitive behavior therapy (CBT) could reduce inflammatory markers in CMDs. In the present study, we measured pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6] and IL-8) pre- and post-treatment in two clinical trials (N ​= ​367) investigating CBT for patients with CMDs in primary care. We hypothesized that higher levels of these cytokines would be associated with more severe psychiatric symptoms (i.e., symptoms of depression, stress and anxiety). We also hypothesized that level of cytokines would decrease after CBT and that the reduced levels would correlate with a reduction in symptoms. Results showed that in men, higher levels of TNF-α were associated with more severe psychiatric symptoms. Further, age moderated the association between TNF-α, as well as IL-6, and stress, and exploratory stratified analyses revealed significant associations in subgroups. No other significant associations between cytokines and psychiatric symptoms were found. None of the cytokines were reduced following CBT, and the marked improvements in psychiatric symptoms after treatment were not associated with changes in cytokines. In conclusion, although inflammation might be of relevance in subgroups, it seems to be of limited importance for clinical improvements across mild to moderate CMDs.

Sickness behavior including malaise, fatigue and increased pain sensitivity is thought to be adaptive and facilitate recovery from disease. However, it may also reduce functioning and health if symptoms persists, which is why validated instruments for its assessment are needed. We evaluated the English translation of the Sickness Questionnaire (SicknessQ) in an Australian population of 156 participants with high level of persistent musculoskeletal pain and/or gastrointestinal symptoms without an organic explanation. The SicknessQ total score had an adequate model fit and no other models were found to fit data better. The SicknessQ correlated most strongly with fatigue, stress, anxiety and depression, which explained 62% of the variance in SicknessQ, but not with physical functioning. The mean score (8.9; 95 %CI: 8.0–9.8) was in between those previously reported in a general population sample and in primary care patients. In conclusion, the evaluation of the English version of the SicknessQ in an Australian sample with significant, chronic unexplained medical symptoms supports the use of the English version of the total SicknessQ score as an overall measure of sickness behavior.

Background: Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain. The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects. In addition, we wanted to explore how sickness behavior is related to self-rated health and health-related functioning. Methods: Sickness behavior was quantified using the sickness questionnaire (SicknessQ). Self-ratings were collected at one time-point in 6 different samples. Levels of sickness behavior in patients with ME/CFS (n ​= ​38) and patients with chronic pain (n ​= ​190) were compared to healthy subjects with lipopolysaccharide(LPS)-induced inflammation (n ​= ​29), primary care patients (n ​= ​163), individuals from the general population (n ​= ​155) and healthy subjects (n ​= ​48), using linear regression. Correlations and moderated regression analyses were used to investigate associations between sickness behavior and self-rated health and health-related functioning in ME/CFS, chronic pain and the general population. Results: LPS-injected individuals (M ​= ​16.3), patients with ME/CFS (M ​= ​16.1), chronic pain (M ​= ​16.1) and primary care patients (M ​= ​10.7) reported significantly higher SicknessQ scores than individuals from the general population (M ​= ​5.4) and healthy subjects (M ​= ​3.6) all p’s ​

This study investigated associations between inflammatory markers, sickness behaviour, health anxiety and self-rated health in 311 consecutive primary care patients. Poor self-rated health was associated with high sickness behaviour ( ρ = 0.28, P

BACKGROUND:Patient-reported outcomes predict mortality and play increasingly important roles in care, but factors that modify central measures such as health ratings have been little investigated. Building on designated immune-to-brain pathways, we aimed to determine how a short-term induced inflammation response impacts self-reported health status. METHODS:Lipopolysaccharide injections were used to provoke acute systemic inflammatory responses in healthy men and women and were compared to placebo in two double-blind randomized experiments. In Experiment 1, 8 individuals (mean 24 years; SD = 3.7) received lipopolysaccharide 0.8 ng/kg once and placebo once in a cross-over design, and in Experiment 2, 52 individuals received either lipopolysaccharide 0.6 ng/kg or placebo once (28.6 years; SD = 7.1). Main outcomes were perceived health (general and current), sickness behaviour (like fatigue, pain and negative affect), and plasma interleukin-6, interleukin-8 and tumour necrosis factor-α, before and after injection. RESULTS:Compared to placebo, lipopolysaccharide lead to a deterioration in both self-rated general (Experiment 1, b = 1.88 for 0.8 ng/kg) and current health (Experiment 1 b = -3.00; and Experiment 2 b = -1.79) 1.5h after injection (p's

High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmö Diet and Cancer study conducted in Sweden between 1991-1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.

[This corrects the article DOI: 10.1371/journal.pone.0185019.].

Asthma is a chronic inflammatory respiratory disorder associated with reduced lung function and poor quality of life. The condition is also associated with poor self-rated health, a major predictor of objective health trajectories. Of biological correlates to self-rated health, evidence suggests a role for inflammatory cytokines and related sickness behaviours. However, this is mainly based on cross-sectional data, and the relation has not been investigated in patients with chronic inflammatory conditions.To investigate inflammatory cytokines, lung function, sickness behaviour and asthma-related quality of life as determinants of self-rated health in patients with asthma, and to investigate if these variables co-vary over time.Plasma cytokines (IL-5, IL-6), lung function (FEV1), sickness behaviour, asthma-related quality of life and self-rated health were assessed in 181 patients with allergic asthma aged 18-64 years in a one-year longitudinal study. Mixed effect regression models and Spearman's correlation were performed to analyse the associations between repeated measurements.More sickness behaviour and poorer asthma-related quality of life were associated with poorer self-rated health (p's

Objective Self-rated health is a powerful predictor of long-term health and mortality, hence the importance of a better understanding of its biological determinants. Previous studies have shown that low-grade inflammation is associated with poor self-rated health in clinical and healthy populations, but the evidence is sparse in men and completely lacking for men in late adolescence. The aim of this study was to investigate the association between low-grade inflammation and self-rated health among conscripts. It was hypothesised that high levels of inflammatory factors would be associated with poor self-rated health.Design Data from 49 321 men (18–21 years) conscripted for military service in 1969 and 1970 were used. Inflammation had been measured through erythrocyte sedimentation rate (ESR). Self-rated health had been assessed on a five-point scale, and was dichotomised into Good (‘Very good’/‘Good’/‘Fair’) versus Poor (‘Poor’/‘Very poor’). Data from 43 110 conscripts with normal levels of ESR, and who reported self-rated health remained after exclusion of those with ESR 11 mm/h. Associations were calculated using logistic regression analyses. Adjustments were made for body mass index, socioeconomic position, inflammatory disease, emotion regulation, smoking, risky use of alcohol and physical activity.Results High levels of ESR were associated with higher odds for poor self-rated health (OR: 1.077 for each unit mm/h increase in ESR, 95% CI 1.049 to 1.105).Conclusions The present study shows for the first time a significant association between a marker of inflammation and self-rated health in late adolescent men, adding to evidence of an association between low-grade inflammation and subjective health perception also in men, as previously demonstrated in women. Further support for inflammation as part of a general psychobiological process that underpins subjective health perception is hereby provided.

Background and study aims: The pathogenesis of gastroesophageal reflux disease (GERD) is multifactorial, including the mechanical anti-reflux barrier of the gastroesophageal junction. This barrier can be evaluated endoscopically in two ways: by measuring the axial length of any hiatal hernia present or by assessing the gastroesophageal flap valve. The endoscopic measurement of axial length is troublesome because of the physiological dynamics in the area. Grading the gastroesophageal flap valve is easier and has proven reproducible. The aim of the present study was to compare the two endoscopic grading methods with regard to associations with GERD. Patients and methods: Population-based subjects underwent endoscopic examination assessing the axial length of hiatus hernia, the gastroesophageal flap valve using the Hill classification, esophagitis using the Los Angeles (LA) classification, and columnar metaplasia using the Z-line appearance (ZAP) classification. Biopsies were taken from the squamocolumnar junction to assess the presence of intestinal metaplasia. Symptoms were recorded with the validated Abdominal Symptom Questionnaire. GERD was defined according to the Montreal definition. Results: In total, 334 subjects were included in the study and underwent endoscopy; 86 subjects suffered from GERD and 211 presented no symptoms or signs of GERD. Based on logistic regression, the estimated area under the curve statistic (AUC) for Hill (0.65 [95 %CI 0.59 – 0.72]) was higher than the corresponding estimate for the axial length of a hiatal hernia (0.61 [95 %CI 0.54 – 0.68]), although the difference was not statistically significant (P = 0.225). Conclusion: From our data, and in terms of association with GERD, the Hill classification was slightly stronger compared to the axial length of a hiatal hernia, but we could not verify that the Hill classification was superior as a predictor. The Hill classification may replace the axial length of a hiatal hernia in the endoscopic assessment of the mechanical anti-reflux barrier of the gastroesophageal junction.