| 1. |
- Ek, Weronica E, et al.
(author)
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Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux
- 2013
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:22, s. 1711-1718
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Journal article (peer-reviewed)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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| 2. |
- Tack, Jan, 1962, et al.
(author)
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A survey on the impact of the COVID-19 pandemic on motility and functional investigations in Europe and considerations for recommencing activities in the early recovery phase
- 2020
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:7
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Journal article (peer-reviewed)abstract
- Background The COVID-19 pandemic, declared by WHO on March 13, 2020, had a major global impact on the healthcare system and services. In the acute phase, the presence of the SARS-CoV-2 virus in the aerodigestive tract limited activities in the gastroenterology clinic and procedures to emergencies only. Motility and function testing was interrupted and as we enter the recovery phase, restarting these procedures requires a safety-focused approach with adequate infection prevention for patients and healthcare professionals. Methods We summarized knowledge on the presence of the SARS-CoV-2 virus in the aerodigestive tract and the risk of spread with motility and functional testing. We surveyed 39 European centers documenting how the pandemic affected activities and which measures they are considering for restarting these measurements. We propose recommendations based on current knowledge as applied in our center. Results Positioning of catheters for gastrointestinal motility tests carries a concern for aerosol-borne infection of healthcare workers. The risk is low with breath tests. The surveyed centers stopped almost all motility and function tests from the second half of March. The speed of restarting and the safety measures taken varied highly. Conclusions and Inferences Based on these findings, we provided recommendations and practical relevant information for motility and function test procedures in the COVID-19 pandemic era, to guarantee a high-quality patient care with adequate infection prevention.
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| 3. |
- Aziz, Imran, et al.
(author)
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Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults
- 2019
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In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 17:5, s. 878-886
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Journal article (peer-reviewed)abstract
- Background & Aims: Functional nausea and vomiting disorders (FNVDs) are classified as chronic nausea and vomiting syndrome (CNVS) or cyclic vomiting syndrome (CVS)—CVS includes cannabinoid hyperemesis syndrome. We investigated the population prevalence of FNVDs, their characteristics, and associated factors. Methods: In the year 2015, an Internet cross-sectional health survey was completed by 5931 adults in the general populations of 3 English-speaking countries; 2100 participants were in the United States, Canada, or the United Kingdom. Quota-based sampling was used to generate demographically balanced and population-representative samples. The survey collected data on demographics, health care visits, medications, somatic symptom severity, quality of life, and symptom-based diagnostic criteria for Rome IV FNVDs as well as for irritable bowel syndrome and functional dyspepsia. Subsequent comparisons were made between Rome IV FNVD subjects and individuals without FNVDs (controls). Results: Overall, 2.2% of the population (n = 131) fulfilled symptom-based diagnostic criteria for Rome IV FNVDs: the United States (3%) had a greater prevalence than Canada (1.9%) or the United Kingdom (1.8%) (P =.02). The prevalence of CNVS was similar among the countries, ranging from 0.8% to 1.2%. However, the prevalence of CVS was higher in the United States (2%) than in Canada (0.7%) or the United Kingdom (1%) (P =.03). The proportion of subjects with CVS taking cannabis did not differ significantly among countries (P =.31), although the 7 cases of cannabinoid hyperemesis syndrome were in the United States. A significantly higher proportion of subjects with CVS reported a compulsive need for hot water bathing to alleviate emetic symptoms than subjects with CNVS (44% vs 19%; P =.03); this behavior was independent of cannabis but augmented by its use. Subjects with FNVDs had significantly greater health impairment and health care utilization than controls. On multivariate analysis, independent factors associated with FNVDs were younger age, increasing somatic symptom severity, lower quality of life, presence of irritable bowel syndrome, and functional dyspepsia. However, on subgroup analysis, somatic symptom severity was associated with CVS but not CNVS, whereas poor quality of life was associated with CNVS but not CVS. Conclusions: Based on a cross-sectional health survey of adults in the general populations of 3 English-speaking countries, approximately 2% of subjects meet symptom-based criteria for Rome IV FNVDs and have considerable health impairments. Hot water bathing to alleviate emetic symptoms is reported for all FNVDs, and is perpetuated by cannabis use. © 2019 AGA Institute
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| 4. |
- Aziz, Imran, et al.
(author)
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Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study
- 2018
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In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 3:4, s. 252-262
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Journal article (peer-reviewed)abstract
- Background The population prevalence, clinical characteristics, and associations for Rome IV functional dyspepsia are not known. Following the publication of the Rome IV criteria for functional gastrointestinal disorders, we aimed to assess the prevalence, characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults across the USA, Canada, and the UK. Methods We sent an internet-based cross-sectional health survey to adults in the general population of three English-speaking countries: the USA, Canada, and the UK. We used quota-based sampling to generate demographically balanced and population-representative samples. Individuals were invited to complete an online questionnaire on general health, without mention that the purpose of this survey was to examine gastrointestinal symptoms. We excluded participants who failed two attention-test questions or were excessively inconsistent on the three gastrointestinal questions that were presented twice in the survey for this particular purpose. The survey enquired about demographics, health-care visits, medications, somatisation, quality of life, and symptom-based criteria for Rome IV functional dyspepsia as well as for irritable bowel syndrome (IBS) and functional heartburn. We made subsequent comparisons between participants with Rome IV functional dyspepsia and controls without dyspepsia. The primary objective was to identify participants who fulfilled symptom-based criteria for Rome IV functional dyspepsia and categorise them into postprandial distress syndrome, epigastric pain syndrome, or overlapping subtypes. Findings 6300 general population adults completed the health survey; 2100 each from the USA, Canada, and the UK. 369 responses were deemed inconsistent, leaving data for 5931 adults. Rome IV functional dyspepsia was significantly more prevalent in the USA (232 [12%] of 1949) than in Canada (167 [8%] of 1988) and the UK (152 [8%] of 1994; p< 0 . 0001). The subtype distribution was 61% postprandial distress syndrome, 18% epigastric pain syndrome, and 21% overlapping variant with both syndromes; this pattern was similar across the countries. Participants with functional dyspepsia had significantly greater health impairment and health-care usage than those without dyspepsia. Participants with the overlapping variant showed greater somatisation and poorer quality-of-life scores than did individuals with either postprandial distress syndrome or epigastric pain syndrome alone. In multivariate analysis, independent factors associated with all functional dyspepsia subtypes included worsening quality of life and the presence of symptoms compatible with functional heartburn and IBS, with functional heartburn and IBS having the strongest association with overlapping postprandial distress syndrome and epigastric pain syndrome. Notably, somatisation showed a positive association with postprandial distress syndrome and the overlapping variant, and use of antidepressants showed a negative association with postprandial distress syndrome. Interpretation Approximately 10% of the adult population fulfils symptom-based criteria for Rome IV functional dyspepsia and incurs considerable associated health impairment. The functional dyspepsia subtypes show differing associations, suggesting differences in pathophysiological processes or influences.
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| 5. |
- Aziz, Imran, et al.
(author)
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How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors
- 2018
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 113:7, s. 1017-1025
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. METHODS: A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with >= 2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. RESULTS: Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. CONCLUSIONS: Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis.
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| 6. |
- Aziz, Imran, et al.
(author)
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The Prevalence and Impact of Overlapping Rome IV-Diagnosed Functional Gastrointestinal Disorders on Somatization, Quality of Life, and Healthcare Utilization: A Cross-Sectional General Population Study in Three Countries
- 2018
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 113:1, s. 86-96
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The population prevalence of Rome IV-diagnosed functional gastrointestinal disorders (FGIDs) and their cumulative effect on health impairment is unknown. METHODS: An internet-based cross-sectional health survey was completed by 5,931 of 6,300 general population adults from three English-speaking countries (2100 each from USA, Canada, and UK). Quota-based sampling was used to generate demographically balanced and population representative samples with regards to age, sex, and education level. The survey enquired for demographics, medication, surgical history, somatization, quality of life (QOL), doctor-diagnosed organic GI disease, and criteria for the Rome IV FGIDs. Comparisons were made between those with Rome IV-diagnosed FGIDs against non-GI (healthy) and organic GI disease controls. RESULTS: The number of subjects having symptoms compatible with a FGID was 2,083 (35%) compared with 3,421 (57.7%) non-GI and 427 (7.2%) organic GI disease controls. The most frequently met diagnostic criteria for FGIDs was bowel disorders (n = 1,665, 28.1%), followed by gastroduodenal (n = 627, 10.6%), anorectal (n = 440, 7.4%), esophageal (n = 414, 7%), and gallbladder disorders (n = 10, 0.2%). On average, the 2,083 individuals who met FGID criteria qualified for 1.5 FGID diagnoses, and 742 of them (36%) qualified for FGID diagnoses in more than one anatomic region. The presence of FGIDs in multiple regions was associated with increasing somatization, worse mental/physical QOL, more medical therapies, and a higher prevalence of abdominal surgeries; all P < 0.001. Notably, individuals with FGIDs in multiple regions had greater somatization and worse QOL than organic GI disease controls. CONCLUSIONS: Roughly a third of the general adult population fulfils diagnostic criteria for a Rome IV FGID. In a third of this subset multiple GI regions are involved and this overlap is associated with increased health impairment.
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| 7. |
- Bennet, Sean, et al.
(author)
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Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics
- 2018
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:10
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Journal article (peer-reviewed)abstract
- BackgroundSerum levels of pro-inflammatory cytokines tend to be increased in irritable bowel syndrome (IBS) patients, or subgroups thereof. Still, the link between cytokine levels and IBS symptoms is unclear. We aim to determine systemic cytokine levels in IBS patients and healthy subjects (HS), confirm the presence of a subset of patients with an increased immune activity and to establish if cytokines are linked to IBS symptoms and pathophysiological factors. MethodsSerum levels of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF), and IL-10 were measured. All subjects reported IBS symptoms using validated questionnaires and underwent colonic sensorimotor testing. Multivariate supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and unsupervised principal component analysis (PCA) and hierarchical cluster analysis (HCA) were implemented. Key ResultsIrritable bowel syndrome patients (n=246) had higher serum levels of IL-1, IL-6, IL-8, TNF, and IL-10 compared to HS (n=21); however, serum cytokine profiles could not discriminate patients from HS. Moreover, cytokine levels were not correlated with symptoms among patients. Supervised OPLS-DA identified 104 patients (40% of patients) and unsupervised HCA analysis identified 49 patients (20%) with an increased immune activity indicated by elevated levels of serum cytokines compared to HS and the other patients. However, irrespective of how patients with increased immune activity were identified they were symptomatically similar to patients with no indication of increased immune activity. Conclusions & InferencesSerum cytokines are elevated in IBS patients compared to HS. Immune activation characterizes a subset of patients, but modest associations between cytokine profile and symptoms suggest immune activity does not directly influence symptoms in IBS.
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| 8. |
- Clevers, Egbert, et al.
(author)
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Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study
- 2018
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In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:8
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV questionnaire using factor analysis of a population-based sample. METHODS: The Rome IV questionnaire was completed online in English by 5931 respondents from the United Kingdom, United States, and Canada (49% female, age range, 18-92 years). We performed an exploratory factor analysis on the Rome IV questions. Next, we performed a confirmatory factor analysis to compare the exploratory factor result to that of the Rome IV criteria. RESULTS: The exploratory factor analysis identified 8 factors that accounted for 45% of the variance in response: constipation, diarrhea, irritable bowel syndrome, abdominal pain, heartburn, nausea or vomiting, globus, and other upper GI symptoms. Most factors corresponded to distinct functional GI disorders defined by the Rome IV criteria-exceptions included abdominal pain and upper GI symptoms. In confirmatory factor analysis, the exploratory model fitted slightly better than that based on the Rome IV criteria (root mean square error of approximation, 0.063 vs 0.077). CONCLUSIONS: We used factor analysis to identify distinct upper and lower GI symptom groups that are compatible with the Rome IV criteria. Our findings support the use of the Rome IV criteria in research and clinical practice as a basis for development of diagnostics and management of patients.
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| 9. |
- Drossman, D. A., et al.
(author)
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Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut−Brain Interaction): A Rome Foundation Working Team Report
- 2018
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 154:4
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Journal article (peer-reviewed)abstract
- Background & Aims: Central neuromodulators (antidepressants, antipsychotics, and other central nervous system−targeted medications) are increasingly used for treatment of functional gastrointestinal disorders (FGIDs), now recognized as disorders of gut−brain interaction. However, the available evidence and guidance for the use of central neuromodulators in these conditions is scanty and incomplete. In this Rome Foundation Working Team report, a multidisciplinary team summarized available research evidence and clinical experience to provide guidance and treatment recommendations. Methods: The working team summarized the literature on the pharmacology of central neuromodulators and their effects on gastrointestinal sensorimotor function and conducted an evidence-based review on their use for treating FGID syndromes. Because of the paucity of data for FGIDs, we included data for non-gastrointestinal painful disorders and specific symptoms of pain, nausea, and vomiting. This information was combined into a final document comprising a synthesis of available evidence and recommendations for clinical use guided by the research and clinical experience of the experts on the committee. Results: The evidence-based review on neuromodulators in FGID, restricted by the limited available controlled trials, was integrated with open-label studies and case series, along with the experience of experts to create recommendations using a consensus (Delphi) approach. Due to the diversity of conditions and complexity of treatment options, specific recommendations were generated for different FGIDs. However, some general recommendations include: (1) low to modest dosages of tricyclic antidepressants provide the most convincing evidence of benefit for treating chronic gastrointestinal pain and painful FGIDs and serotonin noradrenergic reuptake inhibitors can also be recommended, though further studies are needed; (2) augmentation, that is, adding a second treatment (adding quetiapine, aripiprazole, buspirone α2δ ligand agents) is recommended when a single medication is unsuccessful or produces side effects at higher dosages; (3) treatment should be continued for 6−12 months to potentially prevent relapse; and (4) implementation of successful treatment requires effective communication skills to improve patient acceptance and adherence, and to optimize the patient−provider relationship. Conclusions: Based on systematic and selectively focused review and the consensus of a multidisciplinary panel, we have provided summary information and guidelines for the use of central neuromodulators in the treatment of chronic gastrointestinal symptoms and FGIDs. Further studies are needed to confirm and refine these recommendations.
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| 10. |
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