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1.
Scand J Gastroenterol ; 58(10): 1131-1138, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36987880

RESUMEN

BACKGROUND: The etiopathogenesis of diverticular disease is unknown. OBJECTIVE: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study. METHODS: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/-5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not. RESULTS: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027). CONCLUSIONS: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.


Asunto(s)
Enfermedades Diverticulares , Diverticulitis del Colon , Diverticulitis , Diverticulosis del Colon , Divertículo , Microbioma Gastrointestinal , Adulto , Humanos , Diverticulitis del Colon/complicaciones , Diverticulosis del Colon/complicaciones , Estudios de Cohortes , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Diverticulitis/complicaciones , Divertículo/complicaciones , Enfermedades Diverticulares/complicaciones , Colonoscopía/efectos adversos
2.
Am J Gastroenterol ; 116(1): 210-213, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33027078

RESUMEN

INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing. METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21-79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22-80 years, rr = 87%), 1995 (n = 1,139, 20-85 years, rr = 76%), and 2011 (n = 1,175, 20-93 years, rr = 63%). RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60-4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42-1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50-2.73). DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.


Asunto(s)
Dispepsia/epidemiología , Reflujo Gastroesofágico/epidemiología , Dolor Abdominal/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Pirosis/epidemiología , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Periodo Posprandial , Prevalencia , Suecia/epidemiología , Adulto Joven
3.
Gut ; 69(6): 1076-1084, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31601615

RESUMEN

OBJECTIVE: The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings. DESIGN: The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases). RESULTS: While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R²=0.255, p<3E-11) as was diversity (R²=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals. CONCLUSIONS: No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.


Asunto(s)
Microbioma Gastrointestinal/fisiología , Síndrome del Colon Irritable/microbiología , Estudios de Casos y Controles , Colonoscopía , Heces/microbiología , Microbioma Gastrointestinal/genética , Humanos , Mucosa Intestinal/microbiología , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Suecia
4.
Clin Gastroenterol Hepatol ; 18(4): 847-854.e1, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31323378

RESUMEN

BACKGROUND & AIMS: There is controversy about whether psychological factors (anxiety and depression) increase health care seeking by patients with irritable bowel syndrome (IBS). We investigated whether psychological factors increase health care seeking by patients with IBS and the effects of extragastrointestinal (extra-GI) symptoms. METHODS: We performed a population-based prospective study of health care use over a 12-year period in Sweden. From 2002 through 2006, 1244 subjects were selected randomly for an examination by a gastroenterologist and to complete questionnaires, including the Rome II modular questionnaire. Psychological factors were measured with the valid Hospital Anxiety and Depression scale and extra-GI symptoms were measured with a symptom checklist. Responses from 1159 subjects (57% female; mean age, 48.65 y) were matched with health records in 2016 (164 were classified as having IBS based on Rome II criteria). RESULTS: The overall association between depression or anxiety and health care use varied in subjects with and without IBS at baseline. The presence of extra-GI symptoms strengthened the relationship between anxiety and depression and prospective psychiatric visits for subjects with IBS and without IBS (incidence rate ratio, 1.14-1.26). Extra-GI symptoms did not alter the association of anxiety or depression with use of GI or extra-GI health care. CONCLUSIONS: In a population-based study in Sweden, we found that individuals with high baseline anxiety or depression were more likely to seek psychiatric health care, but not GI or extra-GI health care, in the presence of extra-GI symptoms at baseline. Patients with IBS might benefit from more thorough assessments that examine extra-GI and psychological symptoms, to reduce health care utilization.


Asunto(s)
Síndrome del Colon Irritable , Ansiedad/epidemiología , Femenino , Humanos , Síndrome del Colon Irritable/epidemiología , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Estudios Prospectivos , Encuestas y Cuestionarios
5.
J Bacteriol ; 201(21)2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31405919

RESUMEN

Colonic spirochetosis, diagnosed based on the striking appearance in histological sections, still has an obscure clinical relevance, and only a few bacterial isolates from this condition have been characterized to date. In a randomized, population-based study in Stockholm, Sweden, 745 healthy individuals underwent colonoscopy with biopsy sampling. Of these individuals, 17 (2.3%) had colonic spirochetosis, which was associated with eosinophilic infiltration and a 3-fold-increased risk for irritable bowel syndrome (IBS). We aimed to culture the bacteria and perform whole-genome sequencing of the isolates from this unique representative population sample. From 14 out of 17 individuals with spirochetosis we successfully isolated, cultured, and performed whole-genome sequencing of in total 17 isolates, including the Brachyspira aalborgi type strain, 513A. Also, 16S analysis of the mucosa-associated microbiota was performed in the cases and nonspirochetosis controls. We found one isolate to be of the species Brachyspira pilosicoli; all remaining isolates were of the species Brachyspira aalborgi Besides displaying extensive genetic heterogeneity, the isolates harbored several mucin-degrading enzymes and other virulence-associated genes that could confer a pathogenic potential in the human colon. We also showed that 16S amplicon sequencing using standard primers for human microbiota studies failed to detect Brachyspira due to primer incompatibility.IMPORTANCE This is the first report of whole-genome analysis of clinical isolates from individuals with colonic spirochetosis. This characterization provides new opportunities in understanding the physiology and potentials of these bacteria that densely colonize the gut in the individuals infected. The observation that standard 16S amplicon primers fail to detect colonic spirochetosis may have major implications for studies searching for associations between members of the microbiota and clinical conditions such as irritable bowel syndrome (IBS) and should be taken into consideration in project design and interpretation of gastrointestinal tract microbiota in population-based and clinical settings.


Asunto(s)
Brachyspira/aislamiento & purificación , Colon/microbiología , Infecciones por Spirochaetales/microbiología , Brachyspira/genética , Genómica/métodos , Humanos , Microbiota/genética , ARN Ribosómico 16S/genética
6.
Gastroenterology ; 155(1): 168-179, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29626450

RESUMEN

BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 × 10-8) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0×10-6). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 × 10-10 in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKBKAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.


Asunto(s)
Cromosomas Humanos Par 9/genética , Estreñimiento/genética , Síndrome del Colon Irritable/genética , Menarquia/genética , Adulto , Anciano , Estreñimiento/etiología , Estreñimiento/fisiopatología , Europa (Continente) , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/fisiopatología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Autoinforme , Factores Sexuales , Suecia , Estados Unidos
7.
Am J Gastroenterol ; 114(3): 500-510, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30839393

RESUMEN

INTRODUCTION: Low-grade chronic inflammation has been suggested to play a role in uncomplicated asymptomatic and symptomatic diverticular disease. However, population-based studies are lacking. We investigated whether community participants with diverticulosis, with or without symptoms, would have colonic inflammation on histology and serology. METHODS: In a nested case-control study of 254 participants from the population-based colonoscopy (PopCol) study, colonic histological inflammatory markers and serological C-reactive protein levels were analyzed in cases with diverticulosis and controls without diverticulosis. Statistical methods included logistic and linear regression models. RESULTS: Background variables including age (P = 0.92), sex (P = 1.00), body mass index (P = 0.71), smoking (P = 0.34), and recent antibiotic exposure (P = 0.68) were similar between cases and controls. Cases reported more abdominal pain (P = 0.04) and diarrhea symptoms (mushy and high-frequency stools) than controls (P = 0.01 and P = 0.03, respectively) but were otherwise similar. The median C-reactive protein levels were similar among cases and controls [1.05 mg/L (0.3, 2.7) vs 0.8 (0.4, 2.2), P = 0.53]. There was a trend of increased numbers of cecal lymphoid aggregates in cases vs controls (P = 0.07), but no other associations between diverticulosis and inflammatory markers on histology were found. Similarly, no serological or mucosal inflammation was associated with symptomatic cases of diarrhea or abdominal pain vs asymptomatic controls. CONCLUSIONS: In a general community sample, both asymptomatic and symptomatic diverticulosis are not associated with colonic mucosal inflammation. Other explanations for symptomatic colonic diverticulosis need to be identified.


Asunto(s)
Ciego/patología , Colitis/patología , Divertículo del Colon/patología , Anciano , Proteína C-Reactiva/inmunología , Estudios de Casos y Controles , Ciego/inmunología , Colitis/inmunología , Colonoscopía , Divertículo/inmunología , Divertículo/patología , Divertículo/fisiopatología , Divertículo del Colon/inmunología , Divertículo del Colon/fisiopatología , Femenino , Humanos , Inflamación , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad
8.
Scand J Gastroenterol ; 54(9): 1065-1069, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31453726

RESUMEN

Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms. Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE ≥1 cm, The Prague C/M-classification with a minimum length of 1 cm. Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE ≥ 1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49-8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85-5.00), or CLE ≥1 cm (OR: 1.64, CI: 0.77-3.49). Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).


Asunto(s)
Esófago de Barrett/diagnóstico , Esofagoscopía/métodos , Esófago/patología , Reflujo Gastroesofágico/diagnóstico , Adulto , Anciano , Esófago de Barrett/complicaciones , Esófago de Barrett/epidemiología , Femenino , Reflujo Gastroesofágico/complicaciones , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Suecia/epidemiología
9.
Gut ; 67(2): 263-270, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-27872184

RESUMEN

OBJECTIVE: IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. DESIGN: We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. RESULTS: CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). CONCLUSIONS: SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.


Asunto(s)
Síndrome del Colon Irritable/enzimología , Síndrome del Colon Irritable/genética , Complejo Sacarasa-Isomaltasa/genética , Complejo Sacarasa-Isomaltasa/metabolismo , Adulto , Animales , Errores Innatos del Metabolismo de los Carbohidratos/genética , Estudios de Casos y Controles , Línea Celular , Membrana Celular/enzimología , Análisis Mutacional de ADN , Defecación/genética , Diarrea/etiología , Exones , Heces/microbiología , Femenino , Dosificación de Gen , Genotipo , Haplorrinos , Humanos , Síndrome del Colon Irritable/complicaciones , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Complejo Sacarasa-Isomaltasa/deficiencia , Transfección
10.
Scand J Gastroenterol ; 53(6): 657-660, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29616831

RESUMEN

OBJECTIVES: The clinical relevance of small to moderate sliding hiatal hernias is controversial. The aims of the present study were to (1) investigate which symptoms are associated with sliding hiatal hernias and (2) define the length of a sliding hiatal hernia at which gastrointestinal symptoms occur. METHODS: A study population representative of the general Swedish population answered a questionnaire regarding gastrointestinal symptoms and was investigated with an upper endoscopy. The length of any sliding hiatal hernia was measured. RESULTS: Only reflux-related symptoms were associated with length of the hiatal hernia (acid regurgitation OR 1.46, CI 1.19-1.79, heartburn OR 1.27, CI 1.05-1.54), and the association did not become significant until an axial hiatal hernia length of 2 cm. CONCLUSIONS: Only reflux symptoms could be attributed to sliding hiatal hernias. Hiatal hernias less than 2 cm should be considered clinically insignificant.


Asunto(s)
Unión Esofagogástrica/fisiopatología , Reflujo Gastroesofágico/fisiopatología , Hernia Hiatal/diagnóstico , Hernia Hiatal/fisiopatología , Adulto , Anciano , Endoscopía del Sistema Digestivo , Femenino , Reflujo Gastroesofágico/complicaciones , Pirosis/etiología , Hernia Hiatal/complicaciones , Humanos , Concentración de Iones de Hidrógeno , Modelos Logísticos , Masculino , Manometría , Persona de Mediana Edad , Monitoreo Fisiológico , Análisis Multivariante , Suecia , Adulto Joven
11.
Gut ; 66(3): 421-428, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-26525574

RESUMEN

OBJECTIVE: Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role. DESIGN: Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin. RESULTS: Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10-10 for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10-11; OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis). CONCLUSIONS: HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.


Asunto(s)
Colitis Colagenosa/genética , Colitis Colagenosa/inmunología , Sitios Genéticos , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Antígenos HLA/inmunología , Anciano , Alelos , Estudios de Casos y Controles , Cromosomas Humanos Par 6 , Femenino , Técnicas de Genotipaje , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo
12.
Gut ; 65(8): 1242-51, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27196596

RESUMEN

The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between 1900 and September 2015. Evidence in retrieved reports was evaluated using the Grading of Recommendation Assessment, Development and Evaluation method. The current consensus report aims to help healthcare personnel manage CD in the adolescent and young adult and provide optimal care and transition into adult healthcare for patients with this disease. In adolescence, patients with CD should gradually assume exclusive responsibility for their care, although parental support is still important. Dietary adherence and consequences of non-adherence should be discussed during transition. In most adolescents and young adults, routine small intestinal biopsy is not needed to reconfirm a childhood diagnosis of CD based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) or North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria, but a biopsy may be considered where paediatric diagnostic criteria have not been fulfilled, such as, in a patient without biopsy at diagnosis, additional serology (endomysium antibody) has not been performed to confirm 10-fold positivity of tissue transglutaminase antibodies or when a no biopsy strategy has been adopted in an asymptomatic child.


Asunto(s)
Enfermedad Celíaca , Transición a la Atención de Adultos/organización & administración , Adolescente , Adulto , Biopsia/métodos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/terapia , Consenso , Europa (Continente) , Humanos , Cooperación Internacional , Pruebas Serológicas/métodos , Evaluación de Síntomas/métodos , Estados Unidos
13.
Gastroenterology ; 148(5): 928-37, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25644097

RESUMEN

BACKGROUND & AIMS: Functional dyspepsia (FD) is associated with anxiety but it is not clear if one causes the other. We investigated whether anxiety and depression precede the onset of FD (based on the modified Rome III criteria) and gastroesophageal reflux symptoms (GERS) in a population-based follow-up study. METHODS: Participants from the Kalixanda study (n = 3000), randomly selected from the national population register of Sweden, were given the validated Abdominal Symptom Questionnaire 1998-2001; 1000 of these participants then were selected randomly to undergo esophagogastroduodenoscopy and were given the Abdominal Symptom Questionnaire along with the Hospital Anxiety and Depression Scale questionnaire. All eligible subjects who underwent endoscopy (n = 887) were invited to participate in a follow-up study in June-August 2010 and were given the same questionnaires. Data were analyzed by logistic regression. RESULTS: Of the 703 subjects who completed the follow-up questionnaires (79.3%); 110 were found to have FD at baseline (15.6%) and 93 at the follow-up examination (13.3%); 48 of these were new cases of FD. GERS without organic disease was reported by 273 individuals (38.8%) at baseline and by 280 at follow-up examination (39.8%); 93 cases were new. Major anxiety was associated with FD at the follow-up evaluation (odds ratio [OR], 6.30; 99% confidence interval [CI], 1.64-24.16). Anxiety was associated with postprandial distress syndrome at baseline (OR, 4.83; 99% CI, 1.24-18.76) and at the follow-up examination (OR, 8.12; 99% CI, 2.13-30.85), but not with epigastric pain syndrome. Anxiety at baseline was associated with new-onset FD at the follow-up examination (OR, 7.61; 99% CI, 1.21-47.73), but not with GERS. CONCLUSIONS: In a study of the Swedish population, anxiety at baseline, but not depression, increased the risk for development of FD by 7.6-fold in the next 10 years. Anxiety did not affect risk for GERS.


Asunto(s)
Ansiedad/epidemiología , Dispepsia/epidemiología , Reflujo Gastroesofágico/epidemiología , Ansiedad/diagnóstico , Ansiedad/psicología , Distribución de Chi-Cuadrado , Depresión/diagnóstico , Depresión/epidemiología , Depresión/psicología , Dispepsia/diagnóstico , Dispepsia/psicología , Endoscopía Gastrointestinal , Femenino , Estudios de Seguimiento , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/psicología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Suecia/epidemiología , Factores de Tiempo
14.
Clin Gastroenterol Hepatol ; 14(12): 1763-1770.e1, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27353142

RESUMEN

BACKGROUND & AIMS: Symptomatic uncomplicated diverticular disease is considered to be a discreet clinical entity distinct from irritable bowel syndrome (IBS), but population-based data are unavailable. We aimed to investigate the prevalence and location of diverticulosis in the general population, and its association with colonic symptoms and mental health. We propose that individuals with diverticulosis would report more constipation and IBS. METHODS: We performed a population-based study of randomly selected adults born in Sweden (age, 18-70 y; 57.2% women); 745 received a gastroenterology consultation, completed validated abdominal symptom and mental health questionnaires, and were examined by colonoscopy. Logistic regression was used to calculate the associations between diverticulosis and age, sex, gastrointestinal symptoms, anxiety, depression, and self-rated health. RESULTS: Among the 742 participants (54.6% women), 130 (17.5%) had diverticulosis. Age was the strongest predictor of diverticulosis (P < .001), and diverticulosis was rare in participants younger than 40 years (0.7%). All participants with diverticulosis had sigmoid involvement. Participants with diverticulosis were more likely to report loose stools (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.20-2.96), urgency (OR, 1.64; 95% CI, 1.02-2.63), passing mucus (OR, 2.26; 95% CI, 1.08-4.72), and a high stool frequency (OR, 2.02; 95% CI, 1.11-3.65). Diverticulosis was associated with abdominal pain (OR, 2.10; 95% CI, 1.01-4.36; P = .047) and diarrhea-predominant IBS (OR, 9.55; 95% CI, 1.08-84.08; P = .04) in participants older than 60 years. The presence of anxiety and depression and self-rated health were similar in participants with and without diverticulosis. CONCLUSIONS: The prevalence of diverticulosis is age-dependent. Diverticulosis is associated with diarrhea in subjects across all age ranges. In subjects older than age 60, diverticulosis is associated with abdominal pain and diarrhea-predominant IBS.


Asunto(s)
Diarrea/epidemiología , Diarrea/etiología , Divertículo/epidemiología , Divertículo/patología , Dolor Abdominal/epidemiología , Dolor Abdominal/etiología , Adolescente , Adulto , Factores de Edad , Anciano , Divertículo/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Suecia/epidemiología , Adulto Joven
15.
Helicobacter ; 21(3): 186-91, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26347458

RESUMEN

BACKGROUND AND AIM: In populations with a low prevalence rate of Helicobacter pylori (H. pylori) infection from Western countries, guidelines for the management of uninvestigated dyspepsia generally recommend that the "test and treat" strategy should be avoided in favor of empiric proton-pump inhibitor therapy in younger patients (on average < 50 years of age) without alarm symptoms and signs. The prevalence of H. pylori infection has fallen from about 30% to about 10% in Sweden and other countries. We aimed to explore whether the rationale for test and treat is relevant in contemporary clinical practice. MATERIALS AND METHODS: In settings with an infection rate in the adult population of 30% and 10%, we modeled the positive and negative predictive values for indirect (nonendoscopy) tests on current H. pylori infection with a presumed sensitivity and specificity of 95%. We then calculated the difference in false-negative and false-positive test outcome, and eradication prescription rates in the two scenarios. RESULTS: While the positive predictive value for the test decreased from 0.89 to 0.68 when the prevalence of H. pylori fell from 30% to 10%, there were only 1% more false-negative tests and 1% less false-positive tests. The eradication prescription rate would decrease by 18% with a 10% prevalence rate. CONCLUSION: The recommendation to stop applying "test and treat" at lower prevalence rates of H. pylori should be reconsidered. The test and treat strategy is the preferred approach for most patients who present with dyspepsia.


Asunto(s)
Antibacterianos/uso terapéutico , Dispepsia/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Adulto , Dispepsia/diagnóstico , Dispepsia/epidemiología , Reacciones Falso Negativas , Reacciones Falso Positivas , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Sensibilidad y Especificidad
16.
Gut ; 64(11): 1774-82, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25248455

RESUMEN

OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11,326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.


Asunto(s)
Estudio de Asociación del Genoma Completo , Síndrome del Colon Irritable/genética , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad
17.
Scand J Gastroenterol ; 50(7): 866-74, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25762374

RESUMEN

BACKGROUND AND AIMS: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. METHODS: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. RESULTS: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. CONCLUSIONS: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.


Asunto(s)
Adenoma/diagnóstico , Colonoscopía/métodos , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Pólipos/patología , Adenoma/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , Suecia , Adulto Joven
18.
Gut ; 63(7): 1103-11, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24041540

RESUMEN

OBJECTIVE: The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS. DESIGN: 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with Puncorrected<0.05 were validated in an independent set of 497 patients and 887 controls. Genotype distributions of single SNPs were assessed using an additive genetic model in IBS and clinical subtypes, IBS-C and IBS-D, both in individual and combined cohorts. Trait anxiety (N=614 patients, 533 controls), lifetime depression (N=654 patients, 533 controls) and mRNA expression in rectal biopsies (N=22 patients, 29 controls) were correlated with SNP genotypes. RESULTS: Two SNPs associated independently in the exploratory and validation cohort: rs17837965-CDC42 with IBS-C (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42 (1.08 to 1.88)). When combining both cohorts, the association of rs2349775 withstood post hoc correction for multiple testing in the IBS-D subgroup. Additionally, three SNPs in immune-related genes (rs1464510-LPP, rs1881457-IL13, rs2104286-IL2RA), one SNP in a neuronal gene (rs2349775-NXPH1) and two SNPs in epithelial genes (rs245051-SLC26A2, rs17837965-CDC42) were weakly associated with total-IBS (Puncorrected<0.05). At the functional level, rs1881457 increased IL13 mRNA levels, whereas anxiety and depression scores did not correlate with rs2349775-NXPH1. CONCLUSIONS: Rs2349775 (NXPH1) and rs17837965 (CDC42) were associated with IBS-D and IBS-C, respectively, in two independent cohorts. Further studies are warranted to validate our findings and to determine the mechanisms underlying IBS pathophysiology.


Asunto(s)
Estreñimiento/genética , Diarrea/genética , Predisposición Genética a la Enfermedad , Glicoproteínas/genética , Síndrome del Colon Irritable/genética , Neuropéptidos/genética , Polimorfismo de Nucleótido Simple , Proteína de Unión al GTP cdc42/genética , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Genotipo , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad
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