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1.
J Intern Med ; 286(5): 490-502, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31468640

RESUMEN

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that affects approximately 10% of the population. Diet triggers symptoms in the vast majority of individuals with IBS. In view of this, there has been a focus on the role of diet in IBS. The diets currently being headlined for IBS include (i) traditional dietary advice, (ii) the low fermentable oligo-, di-, mono- saccharides and polyols (FODMAPs) diet and (iii) the gluten-free diet (GFD). Although traditional dietary advice is considered as the first-line dietary therapy, its evidence base is variable, with a few randomized controlled trials (RCTs) exploring the efficacy of this approach, other than for fibre. There are now a growing number of RCTs demonstrating the efficacy of the low FODMAP diet in the short-term, with some emerging data on the long-term 'adapted' low FODMAP diet. There are also several RCTs showing the benefits of a GFD in IBS; however, this concept is hampered with uncertainty as to the mechanism of action. Nevertheless, all of these dietary therapies are viable options for individuals with IBS, with the dietitian and patient engagement at the forefront of achieving success. However, future pragmatic studies are needed to clarify the comparative efficacy and convenience of implementing these various diets into routine life. Moreover, it is imperative to better delineate the concern that restrictive diets - such as the low FODMAP and GFD - may promote nutritional inadequacies, disordered eating behaviours, and lead to detrimental alterations to the gut microbiota.


Asunto(s)
Dieta , Síndrome del Colon Irritable/etiología , Síndrome del Colon Irritable/terapia , Humanos
2.
Neurogastroenterol Motil ; 30(10): e13379, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29856100

RESUMEN

BACKGROUND: Among patients with irritable bowel syndrome (IBS), atopic disease has been proposed as a common comorbidity increasing the IBS symptom burden. We therefore assessed the prevalence of self-reported atopy among patients with IBS as compared to non-IBS controls, and whether atopy and higher serum IgE levels were associated with increased IBS symptom severity. METHODS: Levels of total and specific IgE in serum were measured and questionnaires assessing the presence of atopic disease (ie, eczema, asthma, rhinoconjunctivitis, and pollen allergy), gastrointestinal symptom burden, food intolerance, somatic, and psychological symptoms were completed. KEY RESULTS: In total, 223 patients with IBS and 47 controls participated. Presence of atopic disease was reported in 55% of patients with IBS compared to 40% of controls (P = .07). IBS patients with atopic manifestations (N = 123) had higher total serum IgE levels (median 31 vs 16 kUA /L, P < .001) and higher prevalence of self-reported food intolerance (28% vs 9%, P = .002) than non-atopic IBS patients (N = 100), respectively, but no major difference in gastrointestinal or psychological symptom burden was noted. However, severe somatic symptoms were more common among atopic than non-atopic patients with IBS (38% vs 27%, P = .028). We found no associations between self-reported atopy and IBS symptom severity using linear regression models. CONCLUSIONS & INFERENCES: Atopic disease is common in patients with IBS, but that is also true for subjects without IBS. The presence of atopic disease in IBS is associated with self-reported food intolerance and somatic symptom severity, but unrelated to IBS symptom severity.


Asunto(s)
Hipersensibilidad Inmediata/epidemiología , Síndrome del Colon Irritable/inmunología , Adolescente , Adulto , Anciano , Femenino , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Prevalencia , Autoinforme , Encuestas y Cuestionarios , Adulto Joven
3.
Neurogastroenterol Motil ; 30(10): e13378, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29797382

RESUMEN

BACKGROUND: Serum 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. METHODS: Serum levels of interleukin (IL)-1ß, 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 RESULTS: Irritable bowel syndrome patients (n = 246) had higher serum levels of IL-1ß, 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 & INFERENCES: Serum 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.


Asunto(s)
Citocinas/sangre , Síndrome del Colon Irritable/sangre , Síndrome del Colon Irritable/inmunología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
4.
Neurogastroenterol Motil ; 30(9): e13354, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29655299

RESUMEN

BACKGROUND: Gastrointestinal complications are common in hereditary transthyretin amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully elucidated, and the patients' small bowel function remains largely unexplored. The aim of the present study was to compare the small bowel motility in ATTRm amyloidosis patients with that in non-amyloidosis patient controls. METHODS: ATTRm amyloidosis patients undergoing evaluation for liver transplantation were consecutively investigated with 24-hour duodenojejunal manometry (n = 19). The somatostatin analogue octreotide was used to induce fasting motility. Patients with age at onset of ≥50 years were defined as late-onset cases. For each patient, three age- and sex-matched patient controls (n = 57) were selected from the total pool of investigated patients. KEY RESULTS: Manometry was judged as abnormal in 58% of the patients and in 26% of the patient controls (P = .01). Patients displayed significantly more daytime phase III migrating motor complexes than patient controls (median 4 vs 2, P < .01), and had a higher frequency of low-amplitude complexes (16% vs 4%; however, this difference did not reach statistical significance, P = .10). Furthermore, late-onset patients showed a delay in octreotide response (5.4 vs 3.8 minutes, P < .01), but this was not observed for early-onset patients or within the control group. CONCLUSIONS AND INFERENCES: Patients with ATTRm amyloidosis displayed abnormalities in their small bowel motility more frequently than non-amyloidosis patient controls, and the manometric pattern was probably best consistent with a combined neuromyopathic disorder. The delayed octreotide response in late-onset patients warrants further investigation.


Asunto(s)
Neuropatías Amiloides Familiares/complicaciones , Enfermedades Gastrointestinales/etiología , Motilidad Gastrointestinal/fisiología , Adulto , Anciano , Neuropatías Amiloides Familiares/fisiopatología , Femenino , Enfermedades Gastrointestinales/fisiopatología , Humanos , Intestino Delgado/fisiopatología , Masculino , Manometría , Persona de Mediana Edad
5.
Aliment Pharmacol Ther ; 47(10): 1349-1357, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29572885

RESUMEN

BACKGROUND: Associations between irritable bowel syndrome and other health problems have been described, but comprehensive reports are missing, especially in primary care. AIMS: To investigate which health problems are associated with irritable bowel syndrome, how they cluster together and when they are typically diagnosed relative to irritable bowel syndrome. METHODS: We used Intego, a general practice registry in Flanders, Belgium. Patients with an irritable bowel syndrome diagnosis (n = 13 701) were matched with controls without gastrointestinal diagnosis and controls with organic gastrointestinal disease. Long-term prevalences of 680 symptoms and diagnoses were compared between patients and controls. Results were summarised using functional enrichment analysis and visualised in a network and we calculated incidence rate ratios in the 10 years before and after the irritable bowel syndrome diagnosis for the network's key components. RESULTS: Various symptoms and infections, but not neoplasms, were enriched in irritable bowel syndrome patients compared to both control groups. We characterised the comorbidities of irritable bowel syndrome as psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms. These had a uniform incidence in the years around the irritable bowel syndrome diagnosis, and did not structurally precede or follow irritable bowel syndrome. CONCLUSIONS: Irritable bowel syndrome shares long-term associations with psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms in primary care. Clinicians are encouraged to take comorbidities into account when diagnosing and managing irritable bowel syndrome, as this may have important treatment implications.


Asunto(s)
Síndrome del Colon Irritable/fisiopatología , Atención Primaria de Salud , Comorbilidad , Femenino , Humanos , Incidencia , Síndrome del Colon Irritable/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Sistema de Registros
6.
Neurogastroenterol Motil ; 30(7): e13320, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29575352

RESUMEN

BACKGROUND: Disturbed brain-gut interactions are assumed to be of importance for symptom generation in patients with irritable bowel syndrome (IBS). The autonomic nervous system (ANS) is part of the bidirectional brain-gut communication, but previous studies in IBS show diverging results. We aimed to identify subgroups of IBS patients with distinct ANS characteristics differentiating them from healthy controls (HC), and to study associations between ANS status and symptoms. METHODS: Heart rate variability (HRV) was measured in IBS patients and HC (Holter monitoring: supine and standing positions with controlled respiration and ambulatory 24-hour period). Frequency (5 minutes, supine, standing) and time domains (24 hours, day, night) were analyzed. Validated questionnaires were used to measure gastrointestinal and psychological symptoms in patients. Patients and HC were compared on a univariate and multivariate level (principal component analysis [PCA] and orthogonal partial least squares discriminatory analysis (OPLS-DA)). KEY RESULTS: We analyzed 158 IBS patients (Rome III) and 39 HC. Patients differed significantly from HC in HRV parameters during daytime and in standing position. In the PCA, a majority of patients overlapped with HC, but the weighted means differed (P < .01). A subset of patients (n = 30; 19%) with an aberrant global HRV profile was identified through PCA and OPLS-DA; these patients reported more severe symptoms of frequent (P < .05) and loose stools (P = .03), as well as urgency (P = .01). CONCLUSIONS AND INFERENCES: Altered ANS function was demonstrated in patients with IBS, and this might be of particular relevance for symptoms in a subset of the patients.


Asunto(s)
Electrocardiografía Ambulatoria/tendencias , Frecuencia Cardíaca/fisiología , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/fisiopatología , Análisis de Componente Principal/métodos , Adulto , Estudios de Cohortes , Electrocardiografía Ambulatoria/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
7.
Neurogastroenterol Motil ; 30(6): e13284, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29315999

RESUMEN

BACKGROUNDS: Acotiamide is a novel acetylcholinesterase inhibitor for treatment of postprandial distress syndrome (PDS) symptoms of functional dyspepsia (FD). This European phase 3 open-label safety trial has been conducted to evaluate the long-term safety of acotiamide and explore the efficacy of acotiamide on PDS symptoms using the validated LPDS, quality of life using SF-36 and SF-NDI, and work productivity using WPAI. METHODS: FD-PDS patients (defined by ROME III criteria) aged ≥18 years with active PDS symptoms and without predominant overlapping symptoms of epigastric pain syndrome and related disorders were enrolled to receive 100 mg acotiamide three times daily for 1 year. Patients' safety profile and efficacy of acotiamide were monitored. KEY RESULTS: The majority of patients (81.6%) maintained exposure to acotiamide for >50 weeks, with a mean duration of 320.3 days. No specific clinically significant safety concerns have been shown, with no deaths, treatment-related severe/serious adverse events, or any clinically significant laboratory test results. Although being an open-label trial, acotiamide showed a change in severity larger than the minimum clinically important difference at weeks 1 and 2 for postprandial fullness and early satiation (meal-related symptoms), and showed improvement of quality of life and work productivity from the first measurement (at week 12) up to 1 year. CONCLUSIONS & INFERENCES: The long-term safety of acotiamide treatment was confirmed. A clinically important change for PDS symptoms, QoL, and work productivity was suggested; however a controlled trial is required to confirm this hypothetic efficacy of acotiamide. (NCT01973790).


Asunto(s)
Benzamidas/uso terapéutico , Dispepsia/tratamiento farmacológico , Dispepsia/epidemiología , Fármacos Gastrointestinales/uso terapéutico , Periodo Posprandial/efectos de los fármacos , Tiazoles/uso terapéutico , Adulto , Benzamidas/farmacología , Dispepsia/fisiopatología , Europa (Continente)/epidemiología , Femenino , Fármacos Gastrointestinales/farmacología , Humanos , Masculino , Persona de Mediana Edad , Periodo Posprandial/fisiología , Tiazoles/farmacología , Factores de Tiempo , Resultado del Tratamiento
8.
Artículo en Inglés | MEDLINE | ID: mdl-29106029

RESUMEN

BACKGROUND: End-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. METHODS: Focus 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 RESULTS: Focus 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 INFERENCES: An 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.


Asunto(s)
Adaptación Psicológica , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/embriología , Medición de Resultados Informados por el Paciente , Adolescente , Adulto , Anciano , Comparación Transcultural , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
10.
Aliment Pharmacol Ther ; 46(5): 529-539, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28671338

RESUMEN

BACKGROUND: Current subgrouping of Irritable Bowel Syndrome (IBS) is exclusively based on stool consistency without considering other relevant gastrointestinal (GI), extraintestinal somatic or psychological features. AIM: To identify subgroups based on a comprehensive set of IBS-related parameters. METHODS: Mixture model analysis was used, with the following input variables: 13 single-item scores from the IBS-specific Gastrointestinal Symptom Rating Scale, average stool consistency and frequency from a 7-day Bristol Stool Form diary, 12 single-item extraintestinal symptom scores from the Patient Health Questionnaire-12, and anxiety and depression subscale scores from the Hospital Anxiety and Depression scale. The resulting latent subgroups were compared regarding symptom profiles using analysis of variance followed by pair-wise comparisons. RESULTS: One hundred and seventy-two IBS patients (Rome III; 69% female; mean age 33.7 [range 18-60] years) were included. The optimal subgrouping showed six latent groups, characterised by: (I) constipation with low comorbidities, (II) constipation with high comorbidities, (III) diarrhoea with low comorbidities, (IV) diarrhoea and pain with high comorbidities, (V) mixed GI symptoms with high comorbidities, (VI) a mix of symptoms with overall mild severity. The subgroups showed differences in the distribution of Rome III-subtypes, IBS severity, presence of anxiety and depression, and gender, but not regarding age, IBS duration or reported post-infectious onset of IBS. CONCLUSIONS: This model-based subgrouping of IBS partly supports the distinction of subgroups based on bowel habits, but additionally distinguishes subgroups with or without co-morbid extraintestinal somatic and psychological symptoms. The resulting groups show specific profiles of symptom combinations.


Asunto(s)
Estreñimiento/epidemiología , Diarrea/epidemiología , Síndrome del Colon Irritable/diagnóstico , Adolescente , Adulto , Ansiedad/psicología , Comorbilidad , Defecación , Depresión/psicología , Femenino , Humanos , Síndrome del Colon Irritable/fisiopatología , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
12.
Artículo en Inglés | MEDLINE | ID: mdl-27401139

RESUMEN

BACKGROUND: Fatigue is a frequent symptom in patients with irritable bowel syndrome (IBS), and is associated with poor quality of life. However, few studies have evaluated its impact on daily life or the perceived distress it can cause. Using a multi-methods approach, this study describes the impact and manifestations of fatigue in patients with IBS and investigates the relationship between fatigue severity and illness-related and health-promoting factors. METHODS: A total of 160 patients with IBS completed self-reported questionnaires assessing fatigue, gastrointestinal symptoms, psychological distress, and sense of coherence. Fatigue was assessed with the Fatigue Impact Scale, which also includes structured and open-ended questions which were analyzed with a deductive qualitative analysis. Patients were classified as having severe, moderate, or mild fatigue based on frequency, distress and impact on daily life. KEY RESULTS: The open-ended questions revealed a multidimensional impact on life. Fatigue mainly interfered with the ability to perform physical activities, work, and domestic work, and the ability to interact socially. Decreased stamina was evident, along with strategies to limit the bodily consequences of tiredness. Severe fatigue was accompanied by more severe IBS symptoms, anxiety and depression and lower sense of coherence. CONCLUSIONS & INFERENCES: Fatigue is a distressing symptom which occurs in a sizeable proportion of patients with IBS. It affects life in a multidimensional way, with poor bodily stamina being the most prominent feature. Fatigue, along with sense of coherence, depression and anxiety, needs to be assessed, confirmed and targeted for interventions.


Asunto(s)
Fatiga/diagnóstico , Fatiga/epidemiología , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/epidemiología , Autoinforme , Adolescente , Adulto , Estudios Transversales , Fatiga/psicología , Femenino , Humanos , Síndrome del Colon Irritable/psicología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
13.
Am J Gastroenterol ; 112(1): 132-140, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27958284

RESUMEN

OBJECTIVES: The Rome III criteria proposed to subdivide functional dyspepsia (FD) into a postprandial distress syndrome (PDS) group, characterized by the presence of postprandial fullness and/or early satiety, and an epigastric pain syndrome (EPS) group, characterized by the presence of epigastric pain and/or epigastric burning. It has been suggested that different pathophysiological mechanisms underlie the symptom presentations in these subgroups that might determine treatment choices. The aim of this study was to investigate the prevalence of gastric sensorimotor dysfunction in the PDS, EPS, and overlap groups and to evaluate potential differential associations with dyspeptic symptom scores. METHODS: Consecutive FD patients fulfilling Rome III criteria were recruited and they scored frequency of dyspeptic symptoms (postprandial fullness, early satiety, nausea, bloating, epigastric pain, and epigastric burning) over the past 3 months (0-5; 1=once a month or less, 2=two or three times a month, 3=once a week, 4=several times a week, 5=every day). The cumulative symptom score was calculated by adding up the score of these dyspeptic symptoms. Based on these symptom scores, the patients were subdivided into subgroups according to the Rome III consensus: (i) PDS, characterized by postprandial fullness and/or early satiety at least several times a week, (ii) EPS, characterized by epigastric pain and/or epigastric burning at least once a week, and (iii) overlap, fulfilling the criteria for both PDS and EPS. Gastric sensitivity and gastric accommodation were measured using barostat testing, and solid gastric emptying was determined using the [14C]octanoate breath test. RESULTS: A total of 560 FD patients (165 men, age 41.8±0.7 years) were classified into PDS (n=131), EPS (n=50), and overlap (n=379) groups. The prevalence of gastric hypersensitivity, impaired gastric accommodation, and delayed gastric emptying were 37%, 37%, and 23%, respectively, without any differential distribution in Rome III subgroups (P=0.16, P=0.27, and P=0.39 respectively). Comparing the physiological parameters for these gastric sensorimotor functions, there was only a significant difference in the gastric half emptying time between subgroups, with the overlap group having a higher t1/2 (P<0.05) compared with the EPS group. In the overlap group, gastric hypersensitivity was associated with the severity of PDS symptoms (P=0.03), EPS symptoms (P=0.02), and the cumulative symptom score (P=0.02), whereas delayed gastric emptying was associated with nausea (P=0.02) and the cumulative symptom score (P=0.02). CONCLUSIONS: Except for gastric emptying in the overlap group, FD subgroups as defined by the Rome III criteria are not differentially associated with putative pathophysiological mechanisms. These observations question the utility of this classification for guiding therapeutic choices in clinical practice.


Asunto(s)
Dolor Abdominal/fisiopatología , Dispepsia/fisiopatología , Náusea/fisiopatología , Estómago/fisiopatología , Dolor Abdominal/etiología , Adulto , Pruebas Respiratorias , Caprilatos , Radioisótopos de Carbono , Dispepsia/clasificación , Dispepsia/complicaciones , Femenino , Vaciamiento Gástrico/fisiología , Humanos , Masculino , Náusea/etiología , Periodo Posprandial
14.
Artículo en Inglés | MEDLINE | ID: mdl-27581702

RESUMEN

BACKGROUND: Fecal 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. METHODS: One 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 RESULTS: Fecal 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 & INFERENCES: Fecal 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.


Asunto(s)
Incontinencia Fecal/epidemiología , Incontinencia Fecal/psicología , Síndrome del Colon Irritable/epidemiología , Síndrome del Colon Irritable/psicología , Calidad de Vida/psicología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Incontinencia Fecal/diagnóstico , Femenino , Humanos , Síndrome del Colon Irritable/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Suecia/epidemiología , Estados Unidos/epidemiología , Adulto Joven
15.
Artículo en Inglés | MEDLINE | ID: mdl-27485664

RESUMEN

BACKGROUND: Gastroesophageal 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. METHODS: We 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 RESULTS: We identified 30 GERD suggestive risk loci (P≤5×10-5 ), 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. CONCLUSIONS: We 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.


Asunto(s)
Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/genética , Estudio de Asociación del Genoma Completo/métodos , Vigilancia de la Población/métodos , Finlandia/epidemiología , Reflujo Gastroesofágico/diagnóstico , Humanos , Suecia/epidemiología , Estudios en Gemelos como Asunto/métodos , Reino Unido/epidemiología
17.
Neurogastroenterol Motil ; 28(8): 1279, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27440497
18.
Neurogastroenterol Motil ; 28(5): 613-9, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27106677

RESUMEN

Chronic nausea and vomiting are common and debilitating symptoms in adults. There are some fundamental problems that make our understanding of mechanisms difficult, diagnostic definitions of patient-cohorts being central. As there is no unifying mechanism with a direct link to chronic nausea or vomiting, it is most likely that several mechanisms interact, e.g., pylorus function and its relation to gastric emptying, or gastric sensory and motor function. In this mini-review, we highlight the roles and evidence for brain-gut interactions as well as gastrointestinal neurophysiologic, motor, sensory, and hormonal factors involved in the pathophysiology of chronic nausea and vomiting. There are factors not mentioned in the text, mostly as they are not well characterized in the setting of chronic symptoms or only in animal models.


Asunto(s)
Encéfalo/fisiología , Motilidad Gastrointestinal/fisiología , Tracto Gastrointestinal/fisiología , Náusea/fisiopatología , Vómitos/fisiopatología , Enfermedad Crónica , Vaciamiento Gástrico/fisiología , Hormonas Gastrointestinales/fisiología , Humanos , Náusea/diagnóstico , Vías Nerviosas/fisiología , Vómitos/diagnóstico
19.
Neurogastroenterol Motil ; 27(12): 1772-82, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26467837

RESUMEN

BACKGROUND: Visceral hypersensitivity and psychological symptoms are frequent features in irritable bowel syndrome (IBS). Exploring mechanistic pathways leading to visceral hypersensitivity is of importance to direct future studies and treatment options. In this study, we evaluated the contribution of psychological factors to the perception of painful and non-painful rectal sensations in hyper- vs normosensitive IBS patients. METHODS: We included 138 IBS patients (Rome II criteria) who underwent an ascending method of limited rectal balloon distension paradigm. At the end of each distension step, subjects rated the perceived intensity of non-painful ('unpleasantness') and painful rectal sensations on visual analog scales. Sensitivity status was determined based on pain thresholds. Anxiety, depression and somatization were assessed by questionnaires. Mixed models were used to test the relationship between sensitivity status, psychological variables, and pain & unpleasantness ratings upon increasing distension. KEY RESULTS: Hypersensitive IBS patients had lower sensory thresholds for pain, first perception, urge to defecate, and discomfort (p < 0.0001). Upon increasing distension, they rated both painful and non-painful sensations as more intense than normosensitive patients (p < 0.0001). Psychological factors were associated with higher pain ratings during distension in hypersensitive (p < 0.006-0.0001), but not in normosensitive patients. Anxiety, but not depression or somatization, was associated with increased intensity ratings of non-painful sensations (p < 0.001), independent of sensitivity status. CONCLUSIONS & INFERENCES: Hypersensitive IBS patients are characterized by increased perception of pain, but also of non-painful sensations. Psychological factors increase the perception of painful sensations in hypersensitive patients only, whereas non-painful visceral sensations were exaggerated in anxious patients regardless of the sensitivity status.


Asunto(s)
Hiperalgesia/psicología , Síndrome del Colon Irritable/psicología , Percepción del Dolor/fisiología , Umbral del Dolor/psicología , Adulto , Femenino , Humanos , Hiperalgesia/complicaciones , Masculino , Manometría , Pruebas Neuropsicológicas , Dimensión del Dolor , Recto
20.
Neurogastroenterol Motil ; 27(6): 796-804, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25817301

RESUMEN

BACKGROUND: Differences regarding symptoms, coping abilities, and quality of life (QOL) between men and women with irritable bowel syndrome (IBS) have been reported but data are sparse and sometimes conflicting. The aim of present study was to investigate gender differences in gastrointestinal, extra-intestinal, and psychological symptoms, and sense of coherence (SOC) and QOL in a large group of patients diagnosed with IBS. METHODS: We analyzed questionnaire data from 557 patients (152 men) diagnosed with IBS consecutively included in studies at an outpatient clinic for functional bowel disorders between 2002 and 2010. Following questionnaires were included: IBS severity scoring system (IBS-SSS), Hospital Anxiety and Depression Scale (HAD), IBSQOL Scale, Visceral Sensitivity Index (VSI), SOC Scale, Bristol Stool Form Scale (BSFS), and Patient Health Questionnaire (PHQ-15). KEY RESULTS: Women had harder stools (FDR-adjusted p-value: q = 0.033), more severe bloating (q = 0.020), higher symptom severity (q = 0.042), higher total somatic symptom burden (q = 0.035), lower SOC (q = 0.042), and lower QOL. Women rated more general anxiety (q = 0.017) and gastrointestinal-specific anxiety (q = 0.042), but there were no group differences in depression, pain, stool frequency, impact on daily life, dissatisfaction with bowel habit, or extra-colonic symptoms. The differences found were small (effect sizes: r < 0.3). CONCLUSIONS & INFERENCES: In this study, we demonstrated more similarities than differences between men and women with IBS. The largest difference were seen for QOL which might reflect certain structural stressors to which women in general are more exposed than men.


Asunto(s)
Ansiedad/psicología , Depresión/psicología , Síndrome del Colon Irritable/fisiopatología , Calidad de Vida , Sentido de Coherencia , Dolor Visceral/fisiopatología , Adaptación Psicológica , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Síndrome del Colon Irritable/psicología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factores Sexuales , Encuestas y Cuestionarios , Dolor Visceral/psicología , Adulto Joven
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