Heat-shock protein 90α in plasma reflects severity of fatigue in patients with Crohn’s disease

Heat-shock proteins (HSPs) are evolutionarily conserved proteins with important cellular homeostasis functions during harmful conditions, including inflammation. Some HSPs are secreted extracellularly and act on distant cells by downregulating inflammation and increasing cellular stress defence mechanisms. HSP90a has been postulated to signal fatigue in chronic inflammation. We investigated whether HSP90a is associated with fatigue in patients with Crohn’s disease. Fifty-three patients with newly diagnosed Crohn’s disease were included in a cross-sectional study. Data on demographics and disease distribution were obtained. Fatigue was measured by the fatigue visual analogue scale (fVAS). Disease activity was assessed by the Simple Endoscopic Score for Crohn’s disease and Harvey Bradshaw Index. C-reactive protein, faecal calprotectin and HSP90a were also measured. The median fVAS score was 52 mm, indicating significant fatigue. HSP90a scores correlated significantly with fVAS (r¼0.31, P¼0.03). In a multivariate regression model, HSP90a was the only significant contributor to fVAS scores (b¼0.31, P¼0.03). When patients were dichotomised into groups with high and low HSP90a concentrations, significantly higher fVAS scores were demonstrated in the group with high HSP90a (M¼62.4, confidence interval 53.0–71.8 vs. 43.3, 31.6–55.0; P¼0.01). Thus, HSP90a may contribute to fatigue generation and/or modulation in patients with Crohn’s disease.publishedVersio

A few more minutes make a difference? The relationship between content and length of GP consultations

Objectives. To investigate the relationship between the length of a medical consultation in a general practice setting and the biopsychosocial information obtained by the physician, and to explore the characteristics of young physicians obtaining comprehensive, especially psychosocial information. Design. A prospective, longitudinal follow-up study. Setting. Videotaped consultations with standardized patients on two occasions were scored for the amount of biopsychosocial information obtained. Consultation length was recorded in minutes. Subjects. Final-year (T-1) medical school students (n = 111) participated in the project. On completion of their internship one and a half years later (T-2), 62 attended a second time, as young physicians. Main outcome measures. Content lists. Results. Pearson's r correlations between content and length at T-1 and T-2 were 0.27 and 0.66, respectively (non-overlapping confidence intervals). Psychosocial content increased significantly when consultations exceeded 13 minutes (15 minutes scheduled). Physicians using more than 13 minutes had previously, as hospital interns, perceived more stress in the emergency room and had worked in local hospitals. Conclusions. A strong association was found between consultation length and information, especially psychosocial information, obtained by the physicians at internship completion. This finding should be considered by faculty members and organizers of the internship period. Further research is needed to detect when, during the educational process, increased emphasis on communication skills training would be most beneficial for students/residents, and how the medical curriculum and internship period should be designed to optimize young physicians’ use of time in consultations.publishedVersio

The Effect of Biological Treatment on Fatigue in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Background: Fatigue is a frequent complaint in patients with inflammatory bowel disease. Biological drugs have demonstrated beneficial effects on some extraintestinal manifestations, but the effect on fatigue is not clear. Objective: This study investigated the effects of biological and small molecule drugs approved for inflammatory bowel disease on fatigue. Methods: We performed a systematic review and meta-analysis of randomized, placebo-controlled trials reporting Federal Drug Agency (FDA)-approved biological and small molecule drugs for use in ulcerative colitis and Crohn’s disease in which measures of fatigue were recorded before and after treatment. Only induction studies were included. Maintenance studies were excluded. We searched Embase (Ovid), Medline (Ovid), PsycINFO (Ovid), Cinahl (EBSCOhost), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov in May 2022. Risk of bias was analyzed using the Cochrane risk-of-bias tool. Standardized mean difference was used to measure the treatment effect. Results: A total of seven randomized controlled trials composed of 3835 patients were included in the meta-analysis. All of the studies included patients with moderately to severely active ulcerative colitis or Crohn’s disease. The studies used three different generic fatigue instruments: the Functional Assessment of Chronic Illness Therapy-Fatigue and the Short Form 36 Health Survey Vitality Subscale versions 1 and 2. Overall treatment with biological or small molecule agents showed a beneficial effect compared with placebo, with a standardized mean difference of 0.25 (95% confidence interval 0.15–0.34, p < 0.001). The effect was independent of type of drug or subtype of inflammatory bowel disease. Discussion: The risk of bias was considered to be low for all domains except for missing outcome data. Even though the included studies were of high methodological quality, the review is limited by the small number of studies included and that the available studies were not designed to evaluate fatigue specifically. Conclusion: Biological and small molecule drugs used in inflammatory bowel disease have a consistent, though small, beneficial effect on fatigue.publishedVersio

High mobility group box 1 and a network of other biomolecules influence fatigue in patients with Crohn’s disease

Background Fatigue is common in patients with chronic inflammatory and autoimmune diseases, often with a severe impact on the patient’s daily life. From a biological point of view, fatigue can be regarded as an element of the sickness behavior response, a coordinated set of responses induced by pathogens to enhance survival during an infection and immunological danger. The mechanisms are not fully understood but involve activation of the innate immune system, with pro-inflammatory cytokines, in particular interleukin (IL)-1β, acting on cerebral neurons. These mechanisms are also active during chronic inflammatory conditions. High mobility group box 1 (HMGB1) protein has interleukin-1 like properties and is a strong inducer of innate immune responses. Its role in generation of fatigue is not clarified. Emerging evidence indicates that also other biomolecules may influence sickness behavior. We aimed to elucidate how HMGB1 influences fatigue in patients with Crohn’s disease, and how the protein interacts with other candidate biomarkers of fatigue. Methods In 56 patients with newly diagnosed Crohn’s disease, fatigue was evaluated using three different fatigue instruments: the fatigue visual analog scale (fVAS), Fatigue Severity Scale (FSS), and the vitality subscale of Medical Outcomes Study Short-Form Health Survey (SF-36vs). The biochemical markers IL-1 receptor antagonist (RA), soluble IL-1 receptor type 2 (sIL-RII), heat shock protein 90 alpha (HSP90α), HMGB1, anti-fully reduced (fr)HMGB1 antibodies (abs), hemopexin (HPX), and pigment epithelium-derived factor (PEDF) were measured in plasma. Multivariable regression and principal component analyses (PCA) were applied. Results Multivariable regression analyses revealed significant contributions to fatigue severity for HMGB1 in the FSS model, HSP90α in the fVAS model and IL-1RA in the SF-36vs model. Depression and pain scores contributed to all three models. In PCA, two components described 53.3% of the variation. The “inflammation and cellular stress dimension” was dominated by IL-1RA, sIL-1RII, HSP90α, HPX, and PEDF scores, where the “HMGB1 dimension” was dominated by HMGB1, anti-frHMGB1 abs, and fVAS scores. Conclusion This study supports the hypothesis that HMGB1 and a network of other biomolecules influence fatigue severity in chronic inflammatory conditions. The well-known association with depression and pain is also acknowledged.publishedVersio

The multidimensional fatigue inventory (MFI-20): psychometrical testing in a Norwegian sample of inflammatory bowel disease (IBD) patients

OBJECTIVES To evaluate the psychometric properties of the Norwegian version of the multidimensional fatigue inventory (MFI-20) in patients with inflammatory bowel disease. METHODS Participants were recruited from nine hospitals in the southeastern and western parts of Norway. Clinical and sociodemographic data were collected, and participants completed the MFI-20, as well as the Fatigue Questionnaire (FQ). In addition to a confirmatory factor analysis, validity, reliability, test-retest and responsiveness were evaluated. RESULTS In total, 410 patients were included. The Norwegian MFI-20 had an acceptable model fit when compared to the original five-dimensional structure. A positive correlation was observed between the dimensions of MFI-20 and the FQ. MFI-20 scores increased according to subjective disease activity, but no differences were observed when using a calprotectin cut-off  =250 µg/g mg/kg. All MFI-20 dimensions except ‘reduced motivation’ in both ulcerative colitis (UC) and Crohn’s disease (CD) patients had alpha Cronbach alpha values ≥70, and test-retest reliability revealed good to excellent values. Merely one dimension (Reduced activity) in UC patients reporting improvement did not reach the threshold for acceptable responsiveness according to Guyatt statistics. CONCLUSIONS The Norwegian version of MFI-20 is valid, reliable and responsive. The instrument can safely be used in studies using fatigue as an endpoint.publishedVersio

Fatigue: a frequent and biologically based phenomenon in newly diagnosed celiac disease

Fatigue is increasingly recognized as a major complaint in patients with chronic inflammatory and autoimmune diseases. Although fatigue is assumed to represent a significant problem in celiac disease, existing knowledge is scarce, and opinions are conflicting. This study aimed to investigate the prevalence and severity of fatigue in patients with newly diagnosed celiac disease and compare it with healthy control subjects. Ninety patients with newly diagnosed celiac disease were compared with 90 age- and sex-matched healthy subjects. The primary endpoints were fatigue severity as measured by: the fatigue Visual Analog Scale (fVAS), the Fatigue Severity Scale (FSS), and the inverted Vitality subscale of the MOS36 (SF-36vs). Higher scores indicate more severe fatigue. Clinically relevant fatigue was determined using predefined cut-off values. Secondary endpoints were the associations between fatigue, and sex, age, depression, pain, and selected biochemical variables. The median (IQR) fVAS-scores were 43.0 (18.0–64.5) in patients, and 9.0 (2.0–16.0) in the control group (p < 0.001); and the FSS scores 3.8 (2.0–4.8) in patients, and 1.4 (1.0–1.9) in control subjects (p < 0.001). Inverted SF-36vs scores had a mean (SD) value of 58.8 (23.6) in patients, and 29.7 (14.3) in healthy subjects (p < 0.001). The presence of clinically relevant fatigue ranged from 41 to 50% in patients. Increased fatigue severity was associated with female sex, younger age, and elevated pain and depression scores, but not with levels of selected biochemical variables, including hemoglobin. Fatigue is a severe and frequent phenomenon in patients with untreated celiac disease.publishedVersio

Have medical students’ attitudes towards clinical communication skills changed over a 12- year period? A comparative long-term study

Background Attitudes towards learning clinical communication skills at the end of medical school are likely to reflect the students’ training and motivation for the continued development of their skills as doctors. Students from two Norwegian medical schools, one with a traditional, and the other with an integrated curriculum, were approached in 2003 and 2015; with regard to changes in students’ attitudes towards acquiring communication skills in two diverse learning environments. This comparison might reveal the effects of the training programs from a long-term perspective, as neither of the medical schools made any major curriculum changes within the study period. Methods The samples comprised final-year medical students. Two separate cross-sectional surveys performed 12 years apart (2003 and 2015) used items from the Communication Skills Attitude Scale in addition to age and gender. The traditional curriculum included only theoretical teaching and no contact with patients was made during the first 2 to 2.5 years of medical school. However, the integrated curriculum combined training in theoretical and clinical communication skills with early patient contact from the beginning. Results Attitudes improved from the first to the second survey at both schools, however, students from the integrated school reported more positive attitudes than those from the traditional school. Female students from the integrated school contributed the most to the difference in attitudes in both surveys. Conclusions Students in both traditional and integrated curricula improved their attitudes from the first to the second assessment. However, compared with the traditional curriculum, the integrated one fostered even higher levels of positive attitudes towards acquiring communication skills, and a pronounced influence was observed on female students. These findings suggest that an educational program with greater emphasis on improving attitudes among male students may be required.publishedVersio

Self-esteem in patients with inflammatory bowel disease

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A salmon peptide diet alleviates experimental colitis as compared with fish oil

Fish oil (FO) has been shown to have anti-inflammatory properties in animal models of inflammatory bowel disease, but how fish peptides (FP) influence intestinal inflammation has been less studied. Male Wistar rats, divided into five groups, were included in a 4-week dietary intervention study. Of the groups, four were exposed in the fourth week to 5 % dextran sulfate sodium (DSS) to induce colitis, while one group was unexposed. The diets were: (1) control, (2) control + DSS, (3) FO (5 %) + DSS, (4) FP (3·5 %) + DSS, (5) FO + FP + DSS. Following DSS intake, weight and disease activity index (DAI) were assessed, and histological combined score (HCS), selected colonic PG, cytokines, oxidative damage markers and mRNA levels were measured. FP reduced HCS, tended to lower DAI (P = 0·07) and reduced keratinocyte chemoattractant/growth-regulated oncogene levels, as compared with the FO diet. FP also reduced mRNA levels of Il-6 and Cxcl1, although not significantly. FO intake increased the DAI as compared with DSS alone. PGE3 levels increased after the FO diet, and even more following FO + FP intake. The FP diet seems to have a protective effect in DSS-induced colitis as compared with FO. A number of beneficial, but non-significant, changes also occurred after FP v. DSS. A combined FO + FP diet may influence PG synthesis, as PGE3 levels were higher after the combined diet than after FO alone

A salmon peptide diet alleviates experimental colitis as compared with fish oil

Fish oil (FO) has been shown to have anti-inflammatory properties in animal models of inflammatory bowel disease, but how fish peptides (FP) influence intestinal inflammation has been less studied. Male Wistar rats, divided into five groups, were included in a 4-week dietary intervention study. Of the groups, four were exposed in the fourth week to 5 % dextran sulfate sodium (DSS) to induce colitis, while one group was unexposed. The diets were: (1) control, (2) control + DSS, (3) FO (5 %) + DSS, (4) FP (3·5 %) + DSS, (5) FO + FP + DSS. Following DSS intake, weight and disease activity index (DAI) were assessed, and histological combined score (HCS), selected colonic PG, cytokines, oxidative damage markers and mRNA levels were measured. FP reduced HCS, tended to lower DAI (P = 0·07) and reduced keratinocyte chemoattractant/growth-regulated oncogene levels, as compared with the FO diet. FP also reduced mRNA levels of Il-6 and Cxcl1, although not significantly. FO intake increased the DAI as compared with DSS alone. PGE3 levels increased after the FO diet, and even more following FO + FP intake. The FP diet seems to have a protective effect in DSS-induced colitis as compared with FO. A number of beneficial, but non-significant, changes also occurred after FP v. DSS. A combined FO + FP diet may influence PG synthesis, as PGE3 levels were higher after the combined diet than after FO alone.publishedVersio