| 1. |
- Keller, J., et al.
(författare)
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Advances in the diagnosis and classification of gastric and intestinal motility disorders
- 2018
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Ingår i: Nature Reviews Gastroenterology & Hepatology. - : Springer Science and Business Media LLC. - 1759-5045 .- 1759-5053. ; 15:5, s. 291-308
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Tidskriftsartikel (refereegranskat)abstract
- Disturbances of gastric, intestinal and colonic motor and sensory functions affect a large proportion of the population worldwide, impair quality of life and cause considerable health-care costs. Assessment of gastrointestinal motility in these patients can serve to establish diagnosis and to guide therapy. Major advances in diagnostic techniques during the past 5-10 years have led to this update about indications for and selection and performance of currently available tests. As symptoms have poor concordance with gastrointestinal motor dysfunction, clinical motility testing is indicated in patients in whom there is no evidence of causative mucosal or structural diseases such as inflammatory or malignant disease. Transit tests using radiopaque markers, scintigraphy, breath tests and wireless motility capsules are noninvasive. Other tests of gastrointestinal contractility or sensation usually require intubation, typically represent second-line investigations limited to patients with severe symptoms and are performed at only specialized centres. This Consensus Statement details recommended tests as well as useful clinical alternatives for investigation of gastric, small bowel and colonic motility. The article provides recommendations on how to classify gastrointestinal motor disorders on the basis of test results and describes how test results guide treatment decisions.
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| 2. |
- Ek, Weronica E, et al.
(författare)
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Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux
- 2013
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:22, s. 1711-1718
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Tidskriftsartikel (refereegranskat)abstract
- Background Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. Methods We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2 g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were twosided, except in the case of variance-explained estimation where one-sided tests were used. Results We estimated a statistically significant genetic variance explained for BE (h2 g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10-9) and for EA (h2 g = 25 %; SE = 5%; one-sided P = 2 × 10-7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10-6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. Conclusions We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases. © The Author 2013.
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| 3. |
- 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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| 4. |
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| 5. |
- Bonfiglio, F., et al.
(författare)
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A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population
- 2017
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes. MethodsWe performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap). Key resultsWe identified 30 GERD suggestive risk loci (P5x10(-5)), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds. ConclusionsWe report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.
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| 6. |
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| 7. |
- Vork, L., et al.
(författare)
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Patient-Specific Stress-Abdominal Pain Interaction in Irritable Bowel Syndrome: An Exploratory Experience Sampling Method Study
- 2020
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Ingår i: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION:Gastrointestinal symptoms in irritable bowel syndrome (IBS) have been correlated with psychological factors using retrospective symptom assessment. However, real-time symptom assessment might reveal the interplay between abdominal and affective symptoms more reliably in a longitudinal perspective. The aim was to evaluate the association between stress and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, repeated measurement method.METHODS:Thirty-seven patients with IBS (26 women; mean age 36.7 years) and 36 healthy controls (HC; 24 women; mean age 31.1 years) completed an electronic ESM during 7 consecutive days. Abdominal pain and stress were scored on an 11-point Numeric Rating Scale at a maximum of 10 random moments each day.RESULTS:Abdominal pain scores were 2.21 points higher in patients with IBS compared with those in HC (P < 0.001), whereas stress levels did not differ significantly (B: 0.250, P = 0.406). In IBS, a 1-point increase in stress was associated with, on average, 0.10 points increase in abdominal pain (P = 0.017). In HC, this was only 0.02 (P = 0.002). Stress levels at t = -1 were not a significant predictor for abdominal pain at t = 0 in both groups, and vice versa.DISCUSSION:Our results demonstrate a positive association between real-time stress and abdominal pain scores and indicate a difference in response to stress and not a difference in experienced stress per se. Furthermore, an in-the-moment rather than a longitudinal association is suggested. This study underlines the importance of considering the individual flow of daily life and supports the use of real-time measurement when interpreting potential influencers of abdominal symptoms in IBS.
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| 8. |
- Janssen, P., et al.
(författare)
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The Relation Between Symptom Improvement and Gastric Emptying in the Treatment of Diabetic and Idiopathic Gastroparesis
- 2013
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 108:9, s. 1382-1391
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The relationship between symptom improvement (SI) and acceleration of gastric emptying (GE) for different drugs used in the treatment of idiopathic and diabetic gastroparesis is uncertain. In this paper we examined the study-specific correlations between SI and GE, and we performed a meta-regression analysis of the association across multiple studies. METHODS: The MEDLINE database (1,946 to present) was searched, and only controlled trials or trials with an established effective comparator that compared both SI and GE were included. RESULTS: Studies were identified for metoclopramide (n = 6), domperidone (n = 6), cisapride (n = 14), erythromycin (n = 3), botulinum toxin (n = 2), and levosulpiride (n = 3). Even though most drugs concomitantly improved symptoms and accelerated GE, no study reported a significant correlation between SI and GE. Moreover, a correlation analysis over all studies using meta-regression did not show a significant relationship between SI and GE. Our findings need to be qualified by inconsistencies in study methods, which is a limitation but also suggests that our findings are robust to methodological factors. CONCLUSIONS: In this review, no evidence of a relationship between SI and GE was identified for different drugs used for the treatment of gastroparesis. This finding questions the use of GE measurement to direct drug development for gastroparesis.
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| 9. |
- Thind Tornkvist, Navkiran, et al.
(författare)
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Identification of irritable bowel syndrome in the Swedish National Patient Register: a validation study
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:7, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectiveNational patient registers are valuable in epidemiological studies. To ensure high-quality data for studies of irritable bowel syndrome (IBS), this study aimed to validate the ICD-10 code for IBS in the Swedish National Patient Register.MethodsThe positive predictive values (PPV) for IBS defined by the Rome criteria were calculated based on a review of medical records of randomly selected individuals with a first-ever diagnostic listing of IBS in the Swedish National Patient register in the year 2005 (Rome II criteria) or 2010 (Rome III criteria).Key results340 medical records were reviewed (172 from 2005 and 168 from 2010). The majority of patients were females (74%), and the mean age was 42 years. IBS used in any type of department had a PPV of 76% (95% confidence interval 71-80%), which increased to 80% (76-84%) when we included individuals likely to have IBS but where information about some aspects of the Rome criteria was lacking in the medical record. Two highly specialized gastroenterological departments had the best PPV, 96%, while departments of internal medicine in general had a PPV of 82% (80-95%). The PPV for the IBS subtype was 62% (55-67%). The PPVs were not significantly different comparing the two time periods investigated.Conclusion and inferencesThe validity of a register-based definition of IBS in the Swedish National Patient register is high and can be used to identify patients with IBS in observational research. The data source, i.e., type of hospital and department, influences reliability.
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| 10. |
- Vork, L., et al.
(författare)
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Development, content validity, and cross-cultural adaptation of a patient-reported outcome measure for real-time symptom assessment in irritable bowel syndrome
- 2018
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 30:3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEnd-of-day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient-reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross-cultural adaptation. MethodsFocus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward-and-back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients' understanding with the final items. Key resultsFocus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. Conclusions and InferencesAn ESM-based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross-cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow.
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