| 1. |
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| 2. |
- Tack, J., et al.
(författare)
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Plausibility criteria for putative pathophysiological mechanisms in functional gastrointestinal disorders: a consensus of experts
- 2018
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:8, s. 1425-1433
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims The functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances. Methods A group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs. Results Five criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism. Conclusion Evaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.
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| 3. |
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| 4. |
- Andreasson, Anna N., et al.
(författare)
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Prediction pathways for innate immune pathology, IBS, anxiety and depression in a general population (The POPCOL Study)
- 2013
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 32, s. e46-e46
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to ascertain whether low grade innate inflammation contributes to a pathway of depression and anxiety via irritable bowel syndrome (IBS). We evaluated innate immune cell counts in colonic mucosa in normal subjects and those with IBS (Rome III) from a population based study in which 745 randomly selected subjects had a colonoscopy (mean age 51 years;57% women). Intraepithelial lymphocytes (IELs) per 100 enterocytes and eosinophils (eos) per five non-overlapping high power fields (HPF) were counted in 90 controls and 100 cases; immunocytochemistry (CD117) was performed for mast cells per 5HPF in 80 controls and 81 cases. IELs, mast cells and eos were individually summed over 5 sites (terminal ileum, caecum, transverse colon, sigmoid colon and rectum). Anxiety and depression scores were calculated from HADS. A causal model path model which hypothesises immune cells being associated with IBS which, in turn, is associated with elevated anxiety and depression was tested using path analysis implemented in the MPlus software. All hypothesised paths reached statistical significance (p < .05) supporting the individual hypothesized pathways. The overall model fit was reasonable although imperfect. In conclusion, a significant contribution of innate immune inflammatory load leading to anxiety and depression via IBS was found. Whether therapy directed to decreasing this inflammatory load also lifts depression and anxiety should be further explored.
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| 5. |
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| 6. |
- Klaassen, T., et al.
(författare)
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Psychometric evaluation of an experience sampling method-based patient-reported outcome measure in functional dyspepsia
- 2021
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Due to important biases, conventional end-of-day and end-of-week assessment methods of gastrointestinal symptoms in functional dyspepsia (FD) are considered suboptimal. Real-time symptom assessment based on the experience sampling method (ESM) could be a more accurate measurement method. This study aimed to evaluate validity and reliability of an ESM-based patient-reported outcome measure (PROM) for symptom assessment in FD. Methods Thirty-five patients with FD (25 female, mean age 44.7 years) completed the ESM-based PROM (a maximum of 10 random moments per day) and an end-of-day symptom diary for 7 consecutive days. On day 7, end-of-week questionnaires were completed including the Nepean Dyspepsia Index (NDI) and Patient Assessment of Gastrointestinal Symptom Severity Index (PAGI-SYM). Key Results Experience sampling method and corresponding end-of-day scores for gastrointestinal symptoms were significantly associated (ICCs range 0.770-0.917). However, end-of-day scores were significantly higher (Delta 0.329-1.031) than mean ESM scores (p < 0.05). Comparing ESM with NDI and PAGI-SYM scores, correlations were weaker (Pearson's r range 0.467-0.846). Cronbach's alpha coefficient was good for upper gastrointestinal symptoms (alpha = 0.842). First half-week and second half-week scores showed very good consistency (ICCs range 0.913-0.975). Conclusion and Inferences Good validity and reliability of a novel ESM-based PROM for assessing gastrointestinal symptoms in FD patients was demonstrated. Moreover, this novel PROM allows to evaluate individual symptom patterns and can evaluate interactions between symptoms and environmental/contextual factors. ESM has the potential to increase patients' disease insight, provide tools for self-management, and improve shared decision making. Hence, this novel tool may aid in the transition toward personalized health care for FD patients.
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| 7. |
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| 8. |
- Smeets, F. G. M., et al.
(författare)
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Development of a real-time patient-reported outcome measure for symptom assessment in patients with functional dyspepsia using the experience sampling method
- 2019
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Patient-reported outcome measures (PROMs) are used to assess symptoms in patients with functional dyspepsia (FD). Current end-of-day questionnaires have several limitations including sensitivity to recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments across momentary states in daily life and therefore less sensitive to these limitations. This study describes the development of a novel PROM based on ESM technology. Methods An initial draft of the PROM was developed based on literature. Focus group interviews with FD patients according to Rome IV criteria, and an expert meeting with international opinion leaders in the field of functional gastrointestinal disorders were conducted in order to select items for the PROM. Cognitive interviews were performed to evaluate patients' understanding of the selected items and to create the definitive PROM. Key results A systematic literature search revealed 59 items across four domains (ie, physical status; mood and psychological factors; context and environment; and nutrition, medication, and substance use). After patient focus group interviews and an international expert meeting, the number of items was reduced to 33. Cognitive interviews resulted in some minor linguistic changes in order to improve patients' understanding. Conclusions and inferences A novel digital ESM-based PROM for real-time symptom assessment in patients with functional dyspepsia was developed. This novel PROM has the potential to identify individual symptom patterns and specific triggers for dyspeptic symptoms, and optimize treatment strategies.
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| 9. |
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| 10. |
- Zuzek, Rachael, et al.
(författare)
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Prevalence of Histological Gastritis in a Community Population and Association with Epigastric Pain
- 2024
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Ingår i: Digestive Diseases and Sciences. - 0163-2116 .- 1573-2568. ; 69, s. 528-537
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Gastritis is a common histological diagnosis, although the prevalence is decreasing in developed populations, alongside decreasing prevalence of H. pylori infection. We sought to determine the prevalence of the etiology of gastritis in a Swedish population sample and to analyze any associations with symptoms, an area of clinical uncertainty. Methods Longitudinal population-based study based in osthammar, Sweden. A randomly sampled adult population completed a validated gastrointestinal symptom questionnaire (Abdominal Symptom Questionnaire, ASQ) in 2011 (N = 1175). Participants < 80 years of age and who were eligible were invited to undergo esophagogastroduodenoscopy (EGD) (N = 947); 402 accepted and 368 underwent EGD with antral and body biopsies (average 54.1 years, range 20-79 years; 47.8% male) with H. pylori serology. Results Gastritis was found in 40.2% (148/368; 95% CI 35.2-45.2%). By rank, the most common histological subtype was reactive (68/148; 45.9%), then H. pylori (44/148; 29.7%), chronic non-H. pylori (29/148; 19.6%), and autoimmune (4/148; 2.7%). Gastritis was significantly associated with older age and H. pylori status (p < 0.01). Gastritis subjects were divided into three histological categories: chronic inactive inflammation, autoimmune gastritis, and active inflammation; there was no difference in the presence of upper gastrointestinal symptoms when categories were compared to cases with no pathological changes. Functional dyspepsia or gastroesophageal reflux were reported in 25.7% (38/148) of those with gastritis (any type or location) versus 34.1% (75/220) with no pathological changes (p = 0.32). Epigastric pain was more common in chronic H. pylori negative gastritis in the gastric body (OR = 3.22, 95% CI 1.08-9.62). Conclusion Gastritis is common in the population with a prevalence of 40% and is usually asymptomatic. Chronic body gastritis may be associated with epigastric pain, but independent validation is required to confirm these findings. Clinicians should not generally ascribe symptoms to histological gastritis.
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| 11. |
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| 12. |
- Andreasson, Anna, et al.
(författare)
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An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years : A Prospective Population-Based Study in Sweden
- 2021
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 116:1, s. 210-213
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing.METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21–79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22–80 years, rr = 87%), 1995 (n = 1,139, 20–85 years, rr = 76%), and 2011 (n = 1,175, 20–93 years, rr = 63%).RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60–4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42–1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50–2.73).DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Stolte, M, et al.
(författare)
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In patients with Helicobacter pylori gastritis and functional dyspepsia, a biopsy from the incisura angularis provides useful diagnostic information
- 2006
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Ingår i: Pathology, Research and Practice. - : Elsevier BV. - 0344-0338 .- 1618-0631. ; 202:6, s. 405-413
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess whether the taking of an additional biopsy from the incisura angularis increases the chance of detecting maximal degrees of atrophy and intestinal metaplasia (IM) in patients with Helicobacter pylori gastritis and functional dyspepsia. At entry into a randomised trial, biopsies were taken from 328 patients (mean age 48 years), two from both the gastric antrum and corpus, and one from the incisura angularis, and comparative grading of gastritis variables was carried out. Biopsy material from the gastric antrum, corpus, and the incisura angularis revealed no notable differences in atrophy or an incidence of IM and mucosa-associated lymphatic tissue. However, when the incisura biopsies were classified histologically, 58% contained antral mucosa (AM), 18% corpus mucosa (CM), and 24% intermediate zone mucosa. AM at the incisura was associated with considerably more severe gastritis in both the incisura and antrum (14% atrophy, 20% IM) than in CM of incisura (2% atrophy, 6% IM). Corpus atrophy and IM were rare in the AM group and absent from the CM group. Incisura angularis biopsy in patients with H. pylori gastritis and functional dyspepsia does give additional information regarding the severity of gastritis expected in the corpus and antrum. Antral-type mucosa in the incisura angularis region seems to indicate an increased risk for the development of atrophy and/or IM. (c) 2006 Elsevier GmbH. All rights reserved.
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| 19. |
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| 20. |
- Talley, Nicholas J., et al.
(författare)
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Role of smoking in functional dyspepsia and irritable bowel syndrome : three random population-based studies
- 2021
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 54:1, s. 32-42
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients.Aim: To assess if smoking is an independent risk factor for FD and IBS.Methods: Three population-based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta-analysis using mixed effect logistic regression, adjusted for snuffing, age and sex.Results: Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD-PDS) (OR 10-19 cig/day = 1.42, 95% CI 1.04-1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38-3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS-diarrhoea (OR = 2.40, 95% CI 1.12-5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28-3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41-3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14-2.76, P = 0.012) than non-smokers. Smoking was not associated with IBS-constipation or IBS-mixed.Conclusion: Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS-diarrhoea, but not constipation, is also likely important.
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| 21. |
- Thorell, Kaisa, 1983, et al.
(författare)
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Isolates from Colonic Spirochetosis in Humans Show High Genomic Divergence and Potential Pathogenic Features but Are Not Detected Using Standard Primers for the Human Microbiota
- 2019
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Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 201:21
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Tidskriftsartikel (refereegranskat)abstract
- Colonic spirochetosis, diagnosed based on the striking appearance in histological sections, still has an obscure clinical relevance, and only a few bacterial isolates from this condition have been characterized to date. In a randomized, population-based study in Stockholm, Sweden, 745 healthy individuals underwent colonoscopy with biopsy sampling. Of these individuals, 17 (2.3%) had colonic spirochetosis, which was associated with eosinophilic infiltration and a 3-fold-increased risk for irritable bowel syndrome (IBS). We aimed to culture the bacteria and perform whole-genome sequencing of the isolates from this unique representative population sample. From 14 out of 17 individuals with spirochetosis we successfully isolated, cultured, and performed whole-genome sequencing of in total 17 isolates, including the Brachyspira aalborgi type strain, 513A. Also, 16S analysis of the mucosaassociated microbiota was performed in the cases and nonspirochetosis controls. We found one isolate to be of the species Brachyspira pilosicoli; all remaining isolates were of the species Brachyspira aalborgi. Besides displaying extensive genetic heterogeneity, the isolates harbored several mucin-degrading enzymes and other virulenceassociated genes that could confer a pathogenic potential in the human colon. We also showed that 16S amplicon sequencing using standard primers for human microbiota studies failed to detect Brachyspira due to primer incompatibility. IMPORTANCE This is the first report of whole-genome analysis of clinical isolates from individuals with colonic spirochetosis. This characterization provides new opportunities in understanding the physiology and potentials of these bacteria that densely colonize the gut in the individuals infected. The observation that standard 16S amplicon primers fail to detect colonic spirochetosis may have major implications for studies searching for associations between members of the microbiota and clinical conditions such as irritable bowel syndrome (IBS) and should be taken into consideration in project design and interpretation of gastrointestinal tract microbiota in population-based and clinical settings.
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| 22. |
- Wallner, Bengt, 1962-, et al.
(författare)
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Identifying clinically relevant sliding hiatal hernias : a population-based endoscopy study
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 53:6, s. 657-660
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The clinical relevance of small to moderate sliding hiatal hernias is controversial. The aims of the present study were to (1) investigate which symptoms are associated with sliding hiatal hernias and (2) define the length of a sliding hiatal hernia at which gastrointestinal symptoms occur.Methods: A study population representative of the general Swedish population answered a questionnaire regarding gastrointestinal symptoms and was investigated with an upper endoscopy. The length of any sliding hiatal hernia was measured.Results: Only reflux-related symptoms were associated with length of the hiatal hernia (acid regurgitation OR 1.46, CI 1.19–1.79, heartburn OR 1.27, CI 1.05–1.54), and the association did not become significant until an axial hiatal hernia length of 2 cm.Conclusions: Only reflux symptoms could be attributed to sliding hiatal hernias. Hiatal hernias less than 2 cm should be considered clinically insignificant.
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| 23. |
- Xia, H.H.-X., et al.
(författare)
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Clinical and pathological implications of IgG antibody responses to Helicobacter pylori and its virulence factors in non-ulcer dyspepsia
- 2003
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 17:7, s. 935-943
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To determine whether pre-treatment antibody response to Helicobacter pylori virulence factors predicts eradication success and symptom relief 12 months after triple therapy in non-ulcer dyspepsia. Methods: H. pylori-positive patients with non-ulcer dyspepsia received 1-week omeprazole-based triple therapy, or omeprazole plus placebos. Symptoms were assessed using a validated Likert scale. Gastric biopsies taken before and 12 months after treatment were used for histological examination. Pre-treatment blood samples were used for the detection of anti-H. pylori immunoglobulin G (IgG) antibodies, and specific IgG antibodies to 19.5-, 26.5-, 30-, 35-, 89- (VacA) and 116-KDa (CagA) antigens of H. pylori. Results: IgG antibodies to the six antigens were detected in 62%, 96%, 88%, 47%, 54% and 78% of patients, respectively. The presence of antibody to 19.5-, 26.5- or 30-kDa antigen was associated with an increased anti-H. pylori IgG absorbance index. IgG absorbance indices were greater in those with H. pylori eradication (vs. persistent infection). The prevalence of antibodies to the six antigens was not significantly different between those with symptom relief vs. those without. The 19.5kDa antigen (P = 0.018) and VacA (P = 0.001) were independent risk factors for body gastritis. Conclusions: An increased pre-treatment anti-H. pylori IgG absorbance index may be a useful predictor of the success of eradication therapy. Although the 19.5-kDa antigen and VacA were associated with body gastritis, none of the six antigens tested predicted symptom relief after triple therapy.
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| 24. |
- Agreus, Lars, et al.
(författare)
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Towards a healthy stomach? : Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community
- 2016
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Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 4:5, s. 686-696
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Tidskriftsartikel (refereegranskat)abstract
- Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden.Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status.Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old.Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Bosman, M., et al.
(författare)
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Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis
- 2023
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:2
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Forskningsöversikt (refereegranskat)abstract
- Background Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response. Methods We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined. Key Results We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms. Conclusions and Inferences The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.
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| 29. |
- Cameron, Raquel, et al.
(författare)
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Mortality risk increased in colonic diverticular disease : a nationwide cohort study
- 2022
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Ingår i: Annals of Epidemiology. - : Elsevier. - 1047-2797 .- 1873-2585. ; 76, s. 39-49
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: There are limited population cohort data on overall and cause-specific mortality in colonic diverticular disease.Objective: To measure overall and cause-specific mortality in colonic diverticular disease, compared to matched reference individuals and siblings.Methods: Population-based cohort study ("the ESPRESSO study") in Sweden. There were 97,850 cases with a medical diagnosis of diverticular disease (defined by international classification of disease codes) and colorectal histology identified in 1987-2017 from histopathology reports. The mortality risk between individuals with colonic diverticular disease and matched reference individuals ( n = 453/634) from the general population was determined. Cox regression models adjusted for comorbidity estimated hazard ratios (HRs) for all-cause mortality.
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| 30. |
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| 31. |
- Enck, P, et al.
(författare)
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Functional dyspepsia
- 2017
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Ingår i: Nature reviews. Disease primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 3, s. 17081-
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Tidskriftsartikel (refereegranskat)
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| 32. |
- Flook, N. W., et al.
(författare)
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Acid-Suppressive Therapy With Esomeprazole for Relief of Unexplained Chest Pain in Primary Care: A Randomized, Double-Blind, Placebo-Controlled Trial
- 2013
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 108:1, s. 56-64
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: High-quality data regarding the efficacy of acid-suppressive treatment for unexplained chest pain are lacking. The aim of this study was to evaluate the efficacy of esomeprazole in primary-care treatment of patients with unexplained chest pain stratified for frequency of reflux/regurgitation symptoms. METHODS: Patients with a ≥2-week history of unexplained chest pain (unrelated to gastroesophageal reflux) who had at least moderate pain on ≥2 of the last 7 days were stratified by heartburn/regurgitation frequency (≤1 day/week (stratum 1) vs. ≥2 days/week (stratum 2)) and randomized to 4 weeks of double-blind treatment with twice-daily esomeprazole 40mg or placebo. Chest pain relief during the last 7 days of treatment (≤1 day with minimal symptoms assessed daily using a 7-point scale) was analyzed by stratum in keeping with the predetermined analysis plan. RESULTS: Overall, 599 patients (esomeprazole: 297, placebo: 302) were randomized. In stratum 1, more esomeprazole than placebo recipients achieved chest pain relief (38.7% vs. 25.5%; P=0.018); no between-treatment difference was observed in stratum 2 (27.2% vs. 24.2%; P=0.54). However, esomeprazole was superior to placebo in a post-hoc analysis of the whole study population (combined strata; 33.1% vs. 24.9%; P=0.035). CONCLUSIONS: A 4-week course of high-dose esomeprazole provided statistically significant relief of unexplained chest pain in primary-care patients who experienced infrequent or no heartburn/regurgitation, but there was no such significant reduction in patients with more frequent reflux symptoms.
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| 33. |
- Forsberg, Anna M., et al.
(författare)
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Prevalence of colonic neoplasia and advanced lesions in the normal population : a prospective population-based colonoscopy study
- 2012
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:2, s. 184-90
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Tidskriftsartikel (refereegranskat)abstract
- Objective. There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. Methods. A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19-70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. Results. Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. Conclusion. One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.
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| 34. |
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| 35. |
- Hugerth, Luisa W., et al.
(författare)
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No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population
- 2020
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 69:6, s. 1076-1084
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Tidskriftsartikel (refereegranskat)abstract
- Objective The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings.Design The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases).Results While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R-2=0.255, p<3E-11) as was diversity (R-2=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals.Conclusions No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.
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| 36. |
- Irani, Mudar Zand, et al.
(författare)
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Neutrophils, eosinophils, and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms
- 2021
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Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 115, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32–37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13–2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.
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| 37. |
- Jarbrink-Sehgal, ME, et al.
(författare)
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Response to Tursi
- 2019
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Ingår i: The American journal of gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 114:8, s. 1350-1351
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 38. |
- Jarbrink-Sehgal, ME, et al.
(författare)
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Response to Zidar et al
- 2019
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Ingår i: The American journal of gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 114:8, s. 1348-1349
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 39. |
- Jones, Michael P., et al.
(författare)
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Clusters of community-dwelling individuals empirically derived from stool diaries correspond with clinically meaningful outcomes
- 2021
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Ingår i: European Journal of Gastroenterology and Hepathology. - : Lippincott Williams & Wilkins. - 0954-691X .- 1473-5687. ; 33:1S, s. e740-e745
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Tidskriftsartikel (refereegranskat)abstract
- Background Functional gastrointestinal disorders (FGIDs) are diagnosed according to expert consensus criteria based on recall of symptoms over periods of 3 months or longer. Whether the expert opinion concords with underlying disease process and whether individual recall is accurate are both in doubt. This study aimed to identify naturally occurring clusters of individuals with respect to symptom pattern, evaluate their significance, compare cluster profiles with expert opinion and evaluate their temporal stability.Methods As part of a random population study of FGID-related symptoms, we first explored the use of prospective stool and symptom diaries combined with empirical grouping of individuals into clusters using nonhierarchical cluster analysis.Results The analysis identified two clusters of individuals, one of which was characterized by elevated scores on all domains of symptoms (26% of the sample) and one that was low to average on all domains (74% of the sample). Cluster membership was found to be stable over a long interval. Clusters were found to differ on most domains of quality-of-life (d = 0.46–0.74), self-rated health (d = −0.42) and depression (d = −0.42) but not anxiety. Prevalence of clinically diagnosed irritable bowel syndrome (IBS) was higher in the more impacted cluster (33%) compared with the healthy cluster (13%; P < 0.0001).Conclusion A naturalistic classification of individuals challenges consensus criteria in showing that some IBS individuals have a symptom experience not unlike health. The proposed approach has demonstrated temporal stability over time, unlike consensus criteria. A naturalistic disease classification system may have practical advantages over consensus criteria when supported by a decision-analytic system.
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| 40. |
- Järbrink-Sehgal, Maria Ellionore, et al.
(författare)
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Diverticulosis, Symptoms and Colonic Inflammation : A Population-Based Colonoscopy Study
- 2019
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 114:3, s. 500-510
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Low-grade chronic inflammation has been suggested to play a role in uncomplicated asymptomatic and symptomatic diverticular disease. However, population-based studies are lacking. We investigated whether community participants with diverticulosis, with or without symptoms, would have colonic inflammation on histology and serology.METHODS: In a nested case-control study of 254 participants from the population-based colonoscopy (PopCol) study, colonic histological inflammatory markers and serological C-reactive protein levels were analyzed in cases with diverticulosis and controls without diverticulosis. Statistical methods included logistic and linear regression models.RESULTS: Background variables including age (P = 0.92), sex (P = 1.00), body mass index (P = 0.71), smoking (P = 0.34), and recent antibiotic exposure (P = 0.68) were similar between cases and controls. Cases reported more abdominal pain (P = 0.04) and diarrhea symptoms (mushy and high-frequency stools) than controls (P = 0.01 and P = 0.03, respectively) but were otherwise similar. The median C-reactive protein levels were similar among cases and controls [1.05 mg/L (0.3, 2.7) vs 0.8 (0.4, 2.2), P = 0.53]. There was a trend of increased numbers of cecal lymphoid aggregates in cases vs controls (P = 0.07), but no other associations between diverticulosis and inflammatory markers on histology were found. Similarly, no serological or mucosal inflammation was associated with symptomatic cases of diarrhea or abdominal pain vs asymptomatic controls.CONCLUSIONS: In a general community sample, both asymptomatic and symptomatic diverticulosis are not associated with colonic mucosal inflammation. Other explanations for symptomatic colonic diverticulosis need to be identified.
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| 41. |
- Järbrink-Sehgal, M. Ellionore, et al.
(författare)
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Symptomatic Diverticulosis Is Characterized By Loose Stools
- 2016
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 14:12, s. 1763-1770
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Symptomatic uncomplicated diverticular disease is considered to be a discreet clinical entity distinct from irritable bowel syndrome (IBS), but population-based data are unavailable. We aimed to investigate the prevalence and location of diverticulosis in the general population, and its association with colonic symptoms and mental health. We propose that individuals with diverticulosis would report more constipation and IBS.METHODS: We performed a population-based study of randomly selected adults born in Sweden (age, 18-70 y; 57.2% women); 745 received a gastroenterology consultation, completed validated abdominal symptom and mental health questionnaires, and were examined by colonoscopy. Logistic regression was used to calculate the associations between diverticulosis and age, sex, gastrointestinal symptoms, anxiety, depression, and self-rated health.RESULTS: Among the 742 participants (54.6% women), 130 (17.5%) had diverticulosis. Age was the strongest predictor of diverticulosis (P < .001), and diverticulosis was rare in participants younger than 40 years (0.7%). All participants with diverticulosis had sigmoid involvement. Participants with diverticulosis were more likely to report loose stools (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.20-2.96), urgency (OR, 1.64; 95% CI, 1.02-2.63), passing mucus (OR, 2.26; 95% CI, 1.08-4.72), and a high stool frequency (OR, 2.02; 95% CI, 1.11-3.65). Diverticulosis was associated with abdominal pain (OR, 2.10; 95% CI, 1.01-4.36; P = .047) and diarrhea-predominant IBS (OR, 9.55; 95% CI, 1.08-84.08; P = .04) in participants older than 60 years. The presence of anxiety and depression and self-rated health were similar in participants with and without diverticulosis.CONCLUSIONS: The prevalence of diverticulosis is age-dependent. Diverticulosis is associated with diarrhea in subjects across all age ranges. In subjects older than age 60, diverticulosis is associated with abdominal pain and diarrhea-predominant IBS.
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| 42. |
- Ludvigsson, Jonas F., et al.
(författare)
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Celiac disease, eosinophilic esophagitis and gastroesophageal reflux disease, an adult population-based study
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 48:7, s. 808-814
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Celiac disease (CD) has been linked to gastroesophageal reflux disease (GORD) and eosinophilic esophagitis (EoE), but population-based studies of the prevalence of CD in these conditions are lacking, that is, the aim of this study. Materials and methods. An endoscopic study was carried out in 1000 randomly selected adults from the general population. CD was defined on the basis of positive serology in parallel with mucosal abnormalities of the small intestine. Any eosinophil infiltration of the esophageal epithelium was defined as esophageal eosinophilia and EoE was defined as having at least 15 eosinophils/high-power field in biopsies from the distal esophagus. We used Fisher's exact test to compare the prevalence of GORD, esophageal eosinophilia, and EoE in subjects with CD versus controls. Results. Four hundred subjects (40%) had gastroesophageal reflux symptoms (GORS), 155 (15.5%) had erosive esophagitis, 16 (1.6%) had Barrett's esophagus, 48 (4.8%) had esophageal eosinophilia, and 11 (1.1%) had EoE. CD was diagnosed in 8/400 (2.0%) individuals with GORS (vs. controls: 10/600 (1.7%), p = 0.81), in 3/155 (1.9%) with erosive esophagitis (vs. 15/845 controls (1.8%), p = 0.75), and in 2/48 (4.2%) individuals with esophageal eosinophilia (controls: 16/952 (1.7%), p = 0.21), but in none of those 16 with Barrett's esophagus (vs. 18/984 controls (1.8%), p = 1.0) or of the 11 individuals with EoE (controls: 18/989 (1.8%), p = 1.0). Conclusions. This population-based study found no increased risk of CD among individuals with GORD, esophageal eosinophilia, or EoE. CD screening of individuals with GORD or EoE of individuals with CD cannot be recommended.
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| 43. |
- McNaughton, David T., et al.
(författare)
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Effects of Psychology and Extragastrointestinal Symptoms on Health Care Use by Subjects With and Without Irritable Bowel Syndrome
- 2020
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:4, s. 847-852
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: There is controversy about whether psychological factors (anxiety and depression) increase health care seeking by patients with irritable bowel syndrome (IBS). We investigated whether psychological factors increase health care seeking by patients with IBS and the effects of extragastrointestinal (extra-GI) symptoms.Methods: We performed a population-based prospective study of health care use over a 12-year period in Sweden. From 2002 through 2006, 1244 subjects were selected randomly for an examination by a gastroenterologist and to complete questionnaires, including the Rome II modular questionnaire. Psychological factors were measured with the valid Hospital Anxiety and Depression scale and extra-GI symptoms were measured with a symptom checklist. Responses from 1159 subjects (57% female; mean age, 48.65 y) were matched with health records in 2016 (164 were classified as having IBS based on Rome II criteria).Results: The overall association between depression or anxiety and health care use varied in subjects with and without IBS at baseline. The presence of extra-GI symptoms strengthened the relationship between anxiety and depression and prospective psychiatric visits for subjects with IBS and without IBS (incidence rate ratio, 1.14-1.26). Extra-GI symptoms did not alter the association of anxiety or depression with use of GI or extra-GI health care.Conclusions: In a population-based study in Sweden, we found that individuals with high baseline anxiety or depression were more likely to seek psychiatric health care, but not GI or extra-GI health care, in the presence of extra-GI symptoms at baseline. Patients with IBS might benefit from more thorough assessments that examine extra-GI and psychological symptoms, to reduce health care utilization.
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| 44. |
- McNaughton, David T., et al.
(författare)
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Limited evidence of moderation of the association between gastrointestinal symptoms and prospective healthcare utilisation by quality of life
- 2022
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 55:3, s. 311-317
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Tidskriftsartikel (refereegranskat)abstract
- Background: An individual’s drive to seek medical help remains a complex behavioural process, incorporating psychological, social and symptom-specific factors. Within irritable bowel syndrome (IBS), gastrointestinal symptoms only predict a small portion of the high healthcare-seeking experienced.Aim: To examine the moderating role of quality of life (QoL) domains on this relationship to help explain the variance observed.Methods: This is an analysis of a Swedish population-based prospective study of healthcare use over a 12-year period. At baseline, gastrointestinal symptoms were measured with the valid Gastrointestinal Symptom Rating Scale, and QoL via the SF-36. 1159 subjects (57% female; mean age 48.6 years) had their health records matched with the initial survey. 164 were classified as IBS by Rome II criteria. Negative binomial or logistic models were fit to evaluate the moderating effect of particular QoL domains on the relationship between gastrointestinal symptoms and prospective healthcare utilisation.Results: Gastrointestinal symptoms were associated with prospective healthcare use, but moderation in this relationship by particular QoL domains was not supported; most models did not reach statistical significance. Furthermore, the impact of IBS status did not alter the moderation hypotheses.Conclusions: Particular QoL domains did not impact the relationship between gastrointestinal symptoms on prospective healthcare seeking. Future research should continue to examine other psychological, social and symptom variables to identify predictors of high healthcare consumers in IBS.
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| 45. |
- Nordenfelt, Pontus, et al.
(författare)
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Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin, when engaged to an extracellular ligand and the cytoskeleton, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid, ligand-binding head of the integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin head, and measure orientation with fluorescence polarization microscopy. Cytoskeleton and ligand-bound integrins orient in the same direction as retrograde actin flow with their cytoskeleton-binding β-subunits tilted by applied force. The measurements demonstrate that intracellular forces can orient cell surface integrins and support a molecular model of integrin activation by cytoskeletal force. Our results place atomic, Å-scale structures of cell surface receptors in the context of functional and cellular, μm-scale measurements.
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| 46. |
- Rana, Brinda K., et al.
(författare)
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Natural variation within the neuronal nicotinic acetylcholine receptor cluster on human chromosome 15q24 : influence on heritable autonomic traits in twin pairs
- 2009
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 331:2, s. 419-428
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Tidskriftsartikel (refereegranskat)abstract
- Nicotinic acetylcholine receptors (nAChRs) are combinations of subunits arranged as pentamers encircling a central cation channel. At least nine α and four β subunits are expressed in the central and peripheral nervous systems; their presence in autonomic ganglia, the adrenal medulla, and central nervous system, with accompanying responses elicited by nicotinic agonists, point to their involvement in cardiovascular homeostasis. nAChRs formed by α3, α5, and β4 subunits may regulate blood pressure (BP) by mediating release of catestatin, the endogenous nicotinic antagonist fragment of chromogranin A (CHGA) and potent inhibitor of catecholamine secretion. Genes encoding these subunits (CHRNA3, CHRNA5, and CHRNB4) are clustered on human chromosome 15q24. Because variation in this cluster may alter autonomic regulation of BP, we sequenced ∼15 kilobase pairs in 15q24 containing their coding and 5′- and 3′-untranslated regions in 80 individuals. We identified 63 variants: 25 in coding regions of CHRNA3, CHRNA5, and CHRNB4 and 48 noncoding single-nucleotide polymorphisms (SNPs). Haplotype frequencies varied across ethnic populations. We assessed the contribution of six SNPs in the putative catestatin binding region of CHRNA3 and CHRNB4 to autonomic traits. In twins, catestatin and BP were heritable. CHRNA3 SNPs and haplotypes containing K95K (G285A) associated with circulating plasma catestatin, epinephrine levels, as well as systolic BP, suggesting altered coupling of the nAChRs to BP. Studies of chromaffin cells in vitro reveal that nicotinic agonist stimulation releases catecholamines and CHGA, a process augmented by overexpression of CHRNA3 and blocked by catestatin. These cellular events suggest a homeostatic mechanism underlying the pleiotropic actions of CHRNA3 genetic variation on autonomic function observed in twins.
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| 47. |
- Ronkainen, Jukka, et al.
(författare)
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Duodenal eosinophilia and the link to anxiety : A population-based endoscopic study
- 2021
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The concept of gut-to-brain communication via microbial or inflammatory pathways is gaining increased attention but genuine pathology directly linking gut perturbation to anxiety is lacking. We hypothesized that duodenal eosinophilia, as known to occur in functional dyspepsia (FD), may be an underlying cause of anxiety and may help explain the striking association between FD and anxiety.Methods: Randomly selected subjects from the national population register of Sweden completed the validated Abdominal Symptom Questionnaire; 1000 completed esophagogastroduodenoscopy and the Hospital Anxiety and Depression Scale questionnaire. Duodenal biopsies were obtained from 1(st) (D1) and 2(nd) portion (D2). Eligible subjects who underwent endoscopy (n = 887) were invited to participate in a 10-year follow-up study with the same questionnaires. Among endoscopy normal subjects, FD was identified by Rome criteria, and controls were symptom free. Duodenal eosinophilia was based on pre-defined cut-offs. Finding are reported as odds ratios (ORs) with 95% confidence interval and p-value.Results: The study population comprised 89 cases with FD and 124 healthy controls (mean age 62 years, SD 12, 34% male). Clinical anxiety at follow-up was elevated in those with D1 eosinophilia at baseline considering either new-onset anxiety (OR = 4.5, 95% CI 0.8, 23.8; p = 0.08) or follow-up anxiety adjusting for baseline anxiety (OR = 4.51 (95% CI 1.03, 19.81; p = 0.046).Conclusion: Duodenal eosinophilia may potentially be a mechanism linked to anxiety independent of FD.
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| 48. |
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