| 1. |
- Clark, DW, et al.
(author)
-
Associations of autozygosity with a broad range of human phenotypes
- 2019
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
-
Journal article (peer-reviewed)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
|
|
| 2. |
- Wuttke, Matthias, et al.
(author)
-
A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
-
In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
-
Journal article (peer-reviewed)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
|
|
| 3. |
|
|
| 4. |
- Keqi, A., et al.
(author)
-
Electronic structure of the dilute magnetic semiconductor Ga1-xMnxP from hard x-ray photoelectron spectroscopy and angle-resolved photoemission
- 2018
-
In: Physical Review B. - 2469-9950 .- 2469-9969. ; 97:15
-
Journal article (peer-reviewed)abstract
- We have investigated the electronic structure of the dilute magnetic semiconductor (DMS) Ga0.98Mn0.02P and compared it to that of an undoped GaP reference sample, using hard x-ray photoelectron spectroscopy (HXPS) and hard x-ray angle-resolved photoemission spectroscopy (HARPES) at energies of about 3 keV. We present experimental data, as well as theoretical calculations, to understand the role of the Mn dopant in the emergence of ferromagnetism in this material. Both core-level spectra and angle-resolved or angle-integrated valence spectra are discussed. In particular, the HARPES experimental data are compared to free-electron final-state model calculations and to more accurate one-step photoemission theory. The experimental results show differences between Ga0.98Mn0.02P and GaP in both angle-resolved and angle-integrated valence spectra. The Ga0.98Mn0.02P bands are broadened due to the presence of Mn impurities that disturb the long-range translational order of the host GaP crystal. Mn-induced changes of the electronic structure are observed over the entire valence band range, including the presence of a distinct impurity band close to the valence-band maximum of the DMS. These experimental results are in good agreement with the one-step photoemission calculations and a prior HARPES study of Ga0.97Mn0.03As and GaAs [Gray et al., Nat. Mater. 11, 957 (2012)], demonstrating the strong similarity between these two materials. The Mn 2p and 3s core-level spectra also reveal an essentially identical state in doping both GaAs and GaP.
|
|
| 5. |
- Simrén, Magnus, 1966, et al.
(author)
-
Fecal incontinence in irritable bowel syndrome: Prevalence and associated factors in Swedish and American patients
- 2017
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 29:2
-
Journal article (peer-reviewed)abstract
- BackgroundFecal incontinence (FI) is a prevalent but poorly recognized problem in the general population with profound negative effects on daily life. The prevalence of FI in irritable bowel syndrome (IBS) and its association with clinical, demographic, and pathophysiological factors remain largely unknown. MethodsOne US (n=304) and one Swedish (n=168) patient cohort fulfilling Rome III criteria for IBS completed Rome III diagnostic questions on FI and IBS symptoms, and questionnaires on IBS symptom severity, quality of life, anxiety and depression, and work productivity impairment. The patients also underwent assessments of colorectal sensitivity and motility. Key ResultsFecal incontinence one day per month was reported by 19.7% (USA) and 13.7% (Sweden) of IBS patients. These proportions rose to 43.4% and 29.8% if patients with less frequent FI were included. Fecal incontinence prevalence was higher in older age groups, with a clear increase above age 40. Irritable bowel syndrome patients with FI reported greater overall IBS symptom severity, more frequent and loose stools, and greater urgency. Negative effects of FI on quality of life, psychological distress, and work productivity were demonstrated. No associations were found between colorectal physiology and FI. Conclusions & InferencesFecal incontinence is common in IBS patients, and similar to previous general population reports, the major risk factors for FI in IBS are older age, rectal urgency, and loose, frequent stools. When IBS patients have comorbid FI, the impact on quality of life, psychological symptoms, and work impairment appears greater.
|
|
| 6. |
- Aziz, Imran, et al.
(author)
-
Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults
- 2019
-
In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 17:5, s. 878-886
-
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
|
|
| 7. |
- Aziz, Imran, et al.
(author)
-
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
-
In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 3:4, s. 252-262
-
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.
|
|
| 8. |
- Aziz, Imran, et al.
(author)
-
How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors
- 2018
-
In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 113:7, s. 1017-1025
-
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.
|
|
| 9. |
- Aziz, Imran, et al.
(author)
-
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
-
In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 113:1, s. 86-96
-
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.
|
|
| 10. |
- Brunk, Elizabeth, et al.
(author)
-
Recon3D enables a three-dimensional view of gene variation in human metabolism
- 2018
-
In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 36:3, s. 272-281
-
Journal article (peer-reviewed)abstract
- Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures. These data provide a unique resource for investigating molecular mechanisms of human metabolism. Recon3D is available at http://vmh.life.
|
|
| 11. |
- Clevers, Egbert, et al.
(author)
-
Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study
- 2018
-
In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:8
-
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.
|
|
| 12. |
- Heymen, S., et al.
(author)
-
Patient preferences for endpoints in fecal incontinence treatment studies
- 2017
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 29:5
-
Journal article (peer-reviewed)abstract
- Background: Randomized controlled trials of treatments for fecal incontinence (FI) are difficult to compare because case definitions and study endpoints vary. Our aims were to assess patient perspectives on the case definition for FI and how treatment success should be measured. Methods: In Phase 1, 28 FI patients participated in anonymous on-line focus groups, and in Phase 2, 186 people with FI, stratified by gender, race, and age completed an online survey. Key Results: Focus group participants described frequency and urgency as the most important characteristics for defining FI. Most (80%) thought staining of underwear constitutes FI, but only 33% thought gas leakage was FI. When asked how the success of treatment should be defined, 77% said by a reduction in frequency or complete cure, but less than half thought a 50% reduction in frequency was enough. When asked how much reduction would be needed, responses averaged 80%. The Phase 2 survey confirmed that frequency, urgency, and intestinal discomfort are the most important characteristics for case definition, and that success should be defined by at least a 75% decrease in frequency. A 50% reduction was an acceptable endpoint for 58% overall but only 26% for those aged 65. Adequate relief was acceptable to 78%. Conclusions and Inferences: Inclusion criteria for trials should specify a minimum frequency of FI. Most patients would require a 75% reduction in FI frequency to call a treatment successful but young adults and those with more severe FI would accept a 50% reduction as meaningful.
|
|
| 13. |
- Polster, Annikka, et al.
(author)
-
Subgroups of IBS patients are characterized by specific, reproducible profiles of GI and non-GI symptoms and report differences in healthcare utilization: A population-based study
- 2019
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:1
-
Journal article (peer-reviewed)abstract
- Background In a previous clinical sample of IBS patients, subgroups characterized by profiles of GI and non-GI symptoms were identified. We aimed to replicate these subgroups and symptom associations in participants fulfilling IBS diagnostic criteria from a population-based study and relate them to healthcare utilization. Methods An Internet-based health survey was completed by general population adults from United States, Canada, and UK. Respondents fulfilling IBS diagnosis (Rome III and IV) were analyzed for latent subgroups using Gaussian mixture model analysis. Symptom measures were derived from validated questionnaires: IBS-related GI symptoms (Rome IV), extraintestinal somatic symptoms (PHQ-12), and psychological symptoms (SF-8). Key Results A total of 637 respondents fulfilled Rome III criteria (average age 46 years, range 18-87, 66% females) and 341 Rome IV criteria (average age 44, range 18-77, 64% female) for IBS. Seven subgroups were identified in the Rome III cohort, characterized by profiles of GI symptoms (constipation-related, diarrhea-related, and mixed, respectively), and further distinguished by the presence or absence of non-GI comorbidities. The Rome IV cohort showed five similar but less distinct subgroups with a preponderance of mixed symptom profiles. Higher severity of non-GI comorbidities was associated with more frequent healthcare visits and medication usage. Conclusions and Inferences In line with previous findings in a clinical IBS cohort, we were able to identify population-based subgroups characterized by a combination of GI symptoms with the additional distinction made by varying severity of non-GI symptoms and with differences in healthcare utilization.
|
|
| 14. |
- Simrén, Magnus, 1966, et al.
(author)
-
Cumulative Effects of Psychologic Distress, Visceral Hypersensitivity, and Abnormal Transit on Patient-reported Outcomes in Irritable Bowel Syndrome
- 2019
-
In: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 157:2, s. 391-402
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Little is known about the link between pathophysiologic factors and symptoms of irritable bowel syndrome (IBS), or whether these factors have cumulative effects on patient-reported outcomes (PROs). We investigated whether pathophysiologic alterations associated with IBS have cumulative or independent effects on PROs. METHODS: We performed a retrospective analysis of data from 3 cohorts of patients with IBS (n = 407; 74% female; mean age, 36 +/- 12 years), based on Rome II or Rome III criteria, seen at a specialized unit for functional gastrointestinal disorders in Sweden from 2002 through 2014. All patients underwent assessments of colonic transit time (radiopaque markers); compliance, allodynia, and hyperalgesia (rectal barostat); anxiety and depression (Hospital Anxiety and Depression scale), as pathophysiologic factors. Dysfunction was defined by available normal values. PROs included IBS symptom severity, somatic symptom severity, and disease-specific quality of life. RESULTS: Allodynia was observed in 36% of patients, hyperalgesia in 22%, accelerated colonic transit in 18%, delayed transit in 7%, anxiety in 52%, and depression in 24%: each of these factors was associated with severity of at least 1 symptom of IBS. Rectal compliance was not associated with more severe symptoms of IBS. At least 3 pathophysiologic factors were present in 20% of patients, 2 in 30%, 1 in 31%, and none in 18%. With increasing number of pathophysiologic abnormalities, there was a gradual increase in IBS symptom severity (P < .0001) and somatic symptom severity (P < .0001), and a gradual reduction in quality of life (P < .0001). CONCLUSION: Visceral hypersensitivity, including allodynia and hyperalgesia, abnormal colonic transit, and psychologic factors are all associated with IBS symptoms. These factors have a cumulative effect on gastrointestinal and non-gastrointestinal symptoms, as well as on quality of life, in patients with IBS and are therefore relevant treatment targets.
|
|
| 15. |
- Simrén, Magnus, 1966, et al.
(author)
-
Management of the multiple symptoms of irritable bowel syndrome
- 2017
-
In: The Lancet Gastroenterology and Hepatology. ; 2:2, s. 112-122
-
Research review (peer-reviewed)abstract
- Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. A stepwise management approach is advocated for patients with IBS. For a substantial proportion of patients with mild symptoms, general management principles, including making a confident diagnosis and offering explanation, reassurance, and dietary and lifestyle advice, are sufficient. However, many patients continue to have moderate-to-severe symptoms and are not satisfied solely with this approach. In these patients, use of pharmacotherapy on the basis of the predominant symptom (constipation, diarrhoea, pain, or bloating) or combination of symptoms is the next step. For patients with symptoms that are refractory to these initial treatment options and those who have comorbid conditions or psychological symptoms, a combination of therapies should be used, and the use of psychotropic drugs and psychological treatment alternatives is often effective. Finally, the key to successful treatment of patients with IBS is a good physician–patient relationship and use of person-centred care principles. © 2017 Elsevier Ltd
|
|
| 16. |
- Simrén, Magnus, 1966, et al.
(author)
-
Update on Rome IV Criteria for Colorectal Disorders: Implications for Clinical Practice
- 2017
-
In: Current Gastroenterology Reports. - : Springer Science and Business Media LLC. - 1522-8037 .- 1534-312X. ; 19:4
-
Journal article (peer-reviewed)abstract
- Purpose of Review: The purpose of the review was to provide an update of the Rome IV criteria for colorectal disorders with implications for clinical practice. Recent Findings: The Rome diagnostic criteria are expert consensus criteria for diagnosing functional gastrointestinal disorders (FGIDs). The current version, Rome IV, was released in May of 2016 after Rome III had been in effect for a decade. It is the collective product of committees that included more than 100 leading functional GI experts. For functional bowel and anorectal disorders, the majority of changes relative to Rome III are relatively minor and will have little impact on clinical practice. However, notable changes with potential impact on clinical practice and research include the changes in the diagnostic criteria for IBS, the modified approach for subtyping of IBS, the view on functional bowel disorders as a spectrum of disorders, and the new definition of fecal incontinence. Summary: New features in the Rome IV diagnostic criteria for functional bowel and anorectal disorders will likely have modest influence on clinical practice, with a few exceptions. © 2017, The Author(s).
|
|
| 17. |
- Simrén, Magnus, 1966, et al.
(author)
-
Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts
- 2018
-
In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 255-262
-
Journal article (peer-reviewed)abstract
- Objective Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms. Design We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression. Results In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial eta(2): 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05). Conclusions A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.
|
|
| 18. |
- Whitehead, W. E., et al.
(author)
-
Biomarkers to distinguish functional constipation from irritable bowel syndrome with constipation
- 2016
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:6, s. 783-792
-
Journal article (peer-reviewed)abstract
- Treatments for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) differ, but symptom criteria do not reliably distinguish between them; some regard FC and IBS-C as parts of a single constipation spectrum. Our goal was to review studies comparing FC and IBS-C to identify possible biomarkers that separate them. A systematic review identified 15 studies that compared physiologic tests in FC vs IBS-C. Pain thresholds were lower in IBS-C than FC for 3/5 studies and not different in 2/5. Colonic motility was decreased more in FC than IBS-C for 3/3 studies, and whole gut transit was delayed more in FC than IBS-C in 3/8 studies and not different in 5/8. Pelvic floor dyssynergia was unrelated to diagnosis. Sympathetic arousal, measured in only one study, was greater in IBS-C than FC. The most reliable separation of FC from IBS-C was shown by a novel new magnetic resonance imaging technique described in this issue of the journal. These authors showed that drinking one liter of polyethylene glycol laxative significantly increased water content in the small intestine, volume of contents in the ascending colon, and time to first evacuation in FC vs IBS-C; and resulted in less colon motility and delayed whole gut transit in FC compared to IBS-C. Although replication is needed, this well-tolerated, non-invasive test promises to become a new standard for differential diagnosis of FC vs IBS-C. These data suggest that FC and IBS-C are different disorders rather than points on a constipation spectrum. © 2016 John Wiley & Sons Ltd.
|
|
