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1.
  • Lagergren, Jesper, et al. (författare)
  • Gastroesophageal reflux does not alter effects of body mass index on risk of esophageal adenocarcinoma
  • 2014
  • Ingår i: Clinical Gastroenterology and Hepatology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1542-3565. ; 12:1, s. 45-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: A history of high body mass index (BMI) is strongly associated with risk of esophageal adenocarcinoma (EAC). We investigated whether gastroesophageal reflux is involved in this association. Methods: We analyzed data from a population-based Swedish nationwide study of patients with a new diagnosis of EAC (n=189) or gastroesophageal junction adenocarcinoma (n= 262), and matched controls (n=816), from 1995 through 1997. Our analysis included data on BMI 20 y before study inclusion; maximum adult BMI; frequency, severity and duration of gastroesophageal reflux symptoms; tumor features; and covariates (sex, age, smoking, alcohol, fruit and vegetables intake, and socio-economic status). We conducted stratified analyses and synergy tests, adjusting for covariates. Results: Odds ratios (ORs) for EAC among subjects with BMI ≥25 20 y before inclusion, compared with those with BMI <25, did not differ significantly, without or with adjustment for gastroesophageal reflux frequency (OR, 3.1; 95% confidence interval [CI], 2.2–4.4 and OR, 3.3; 95% CI, 2.2–4.8), severity (OR, 3.3; 95% CI, 2.2–4.8), or duration (OR, 3.2; 95% CI, 2.2–4.7). However, there were strong interactions and synergisms between BMI and gastroesophageal reflux categories. BMI appeared to have the largest effect on gastroesophageal reflux frequency (synergy index 8.9; 95% CI, 2.3–34.1 for maximum BMI and gastroesophageal reflux >3 times weekly). Conclusions: Based on a population-based study, the association between BMI and EAC does not appear to be affected by symptomatic gastroesophageal reflux, although BMI and reflux act synergistically.
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  • Ness-Jensen, Eivind, et al. (författare)
  • Lifestyle intervention in gastroesophageal reflux disease
  • 2016
  • Ingår i: Clinical Gastroenterology and Hepatology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1542-3565. ; 14:2, s. 175-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) affects up to 30% of adults in Western populations and is increasing in prevalence. GERD is associated with lifestyle factors, particularly obesity and tobacco smoking, which also threatens the patient's general health. GERD carries the risk of several adverse outcomes and there is widespread use of potent acid-inhibitors, which are associated with long-term adverse effects. The aim of this systematic review was to assess the role of lifestyle intervention in the treatment of GERD. METHODS: Literature searches were performed in PubMed (from 1946), EMBASE (from 1980), and the Cochrane Library (no start date) to October 1, 2014. Meta-analyses, systematic reviews, randomized clinical trials (RCTs), and prospective observational studies were included. RESULTS: Weight loss was followed by decreased time with esophageal acid exposure in 2 RCTs (from 5.6% to 3.7% and from 8.0% to 5.5%), and reduced reflux symptoms in prospective observational studies. Tobacco smoking cessation reduced reflux symptoms in normal-weight individuals in a large prospective cohort study (odds ratio, 5.67). In RCTs, late evening meals increased time with supine acid exposure compared with early meals (5.2% point change), and head-of-the-bed elevation decreased time with supine acid exposure compared with a flat position (from 21% to 15%). CONCLUSIONS: Weight loss and tobacco smoking cessation should be recommended to GERD patients who are obese and smoke, respectively. Avoiding late evening meals and head-of-the-bed elevation is effective in nocturnal GERD.
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3.
  • Xie, Shao-Hua, et al. (författare)
  • Association between levels of sex hormones and risk of esophageal adenocarcinoma and Barrett’s esophagus
  • 2019
  • Ingår i: Clinical Gastroenterology and Hepatology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1542-3565. ; 18:12, s. 2701-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones associated with risk of EAC or Barrett’s esophagus (BE). Methods: We conducted a Mendelian randomization analysis using data from patients with EAC (n=2488) or BE (n=3247) and control participants (n=2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs. Results: Higher genetically predicted levels of follicle stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01- 1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per standard deviation increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulphate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index. Conclusions: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle stimulating and luteinizing hormones and risk of BE and EAC.
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4.
  • Xie, Shao-Hua, et al. (författare)
  • The male predominance in esophageal adenocarcinoma
  • 2016
  • Ingår i: Clinical Gastroenterology and Hepatology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1542-7714 .- 1542-3565.
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence of esophageal adenocarcinoma (EAC) has increased rapidly during the past four decades in many Western populations, including North America and Europe. The established etiological factors for EAC include gastro-esophageal reflux and obesity, Helicobacter pylori infection, tobacco smoking, and consumption of fruit and vegetables. There is a marked male predominance of EAC with a male-to-female ratio in incidence of up to 9-to-1. This review evaluates the available literature on the reasons for the male predominance, particularly an update on epidemiologic evidence from human studies during the past decade. The striking sex difference does not seem to be explained by established risk factors, given that the prevalence of the etiological factors and the strengths of associations between these factors and EAC risk are similar between the sexes. Sex hormonal factors may play a role in the development of EAC; estrogenic exposures may prevent such development, while androgens might increase the risk of EAC. However, continuing research efforts are still in need to fully understand the reasons for the male predominance of EAC.
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5.
  • Aglago, Elom K., et al. (författare)
  • Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
  • 2020
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
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  • Lynch, Kate D, et al. (författare)
  • Effects of Vedolizumab in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases.
  • 2020
  • Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n= 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P= .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P= .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.
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8.
  • Abdalla, Maie, et al. (författare)
  • Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study
  • 2017
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 15:7, s. 1055-1060
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND amp; AIMS: Patients with ulcerative colitis (UC) have an increased risk of rectal cancer, therefore reconstruction with an ileal pouch-anal anastomosis (IPAA) generally is preferred to an ileorectal anastomosis (IRA) after subtotal colectomy. Similarly, completion proctectomy is recommended for patients with ileostomy and a diverted rectum, although this approach has been questioned because anti-inflammatory agents might reduce cancer risk. We performed a national cohort study in Sweden to assess the risk of rectal cancer in patients with UC who have an IRA, IPAA, or diverted rectum after subtotal colectomy.METHODS: We collected data from the Swedish National Patient Register for a cohort of 5886 patients with UC who underwent subtotal colectomy with an IRA, IPAA, or diverted rectum from 1964 through 2010. Patients who developed rectal cancer were identified from the Swedish National Cancer Register. The risk of rectal cancer was compared between this cohort and the general population by standardized incidence ratio analysis.RESULTS: Rectal cancer occurred in 20 of 1112 patients (1.8%) who received IRA, 1 of 1796 patients (0.06%) who received an IPAA, and 25 of 4358 patients (0.6%) with a diverted rectum. Standardized incidence ratios for rectal cancer were 8.7 in patients with an IRA, 0.4 in patients with an IPAA, and 3.8 in patients with a diverted rectum. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio, 6.12), and colonic severe dysplasia or cancer before subtotal colectomy in patients with a diverted rectum (hazard ratio, 3.67).CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found that the risk for rectal cancer after colectomy in patients with UC is low, in relative and absolute terms, after reconstruction with an IPAA. An IRA and diverted rectum are associated with an increased risk of rectal cancer, compared with the general population, but the absolute risk is low. Patients and their health care providers should consider these findings in making decisions to leave the rectum intact, perform completion proctectomy, or reconstruct the colon with an IRA or IPAA.
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11.
  • Alexandersson, Bjarki, et al. (författare)
  • High-Definition Chromoendoscopy Superior to High-Definition White-Light Endoscopy in Surveillance of Inflammatory Bowel Diseases in a Randomized Trial
  • 2020
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:9, s. 2101-2107
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: There is debate over the optimal method for colonoscopic surveillance of patients with inflammatory bowel diseases. Guidelines recommend chromoendoscopy, but the value of chromoendoscopy in high-definition colonoscopy has not been proven. Furthermore, the value of random biopsies is controversial. METHODS: We performed a prospective study of 305 patients with ulcerative colitis or Crohn's colitis referred for surveillance colonoscopy at a university hospital in Sweden, from March 2011 through April 2016. Patients randomly assigned to a group that received high-definition chromoendoscopy with indigo carmine (HD-CE; n=152), collection of 32 random biopsies, and targeted biopsies or polypectomies or to a group that received high-definition white light endoscopy (HD-WLE; n=153), collection of 32 random biopsies, and targeted biopsies or polypectomies. The primary endpoint was number of patients with dysplastic lesions. RESULTS: Dysplastic lesions were detected in 17 patients with HD-CE and 7 patients with HD-WLE (P=.032). Dysplasias in random biopsies (n=9760) were detected in 9 patients: 6 (3.9%) in the HD-CE group and 3 (2.0%) in the HD-WLE group (P=.72). Of the 9 patients with dysplasia, 3 patients (33%) had primary sclerosing cholangitis-only 18% of patients (54/305) included in the study had primary sclerosing cholangitis. The number of dysplastic lesions per 10 min of withdrawal time was 0.066 with HD-CE and 0.027 with HD-WLE (P=.056). CONCLUSIONS: In a randomized trial, we found HD-CE with collection of random biopsies to be superior to HD-WLE with random biopsies for detection of dysplasia per colonoscopy. These results support the use of chromoendoscopy for surveillance of patients with inflammatory bowel diseases. ClinicalTrials.gov no: NCT01505842.
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12.
  • Anderson, Ryan T, et al. (författare)
  • Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic Hepatitis B Virus Infection : Systematic Review and Meta-analysis.
  • 2021
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:3, s. 463-472
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is the desired end point of treatment for chronic hepatitis B virus (HBV) infection, according to guidelines. We performed a systematic review and meta-analysis to evaluate the strength of the association between HBsAg seroclearance and long-term clinical outcomes.METHODS: We performed a systematic review of the PubMed, EMBASE, and Cochrane Library databases for articles that assessed HBsAg status and reported the incidence of hepatocellular carcinoma (HCC), liver decompensation, liver transplantation, and/or all-cause mortality during follow-up evaluation. We performed a meta-analysis of rate ratios (RR) using a random-effects model independently for each end point and for a composite end point.RESULTS: We analyzed data from 28 studies, comprising a total of 188,316 patients with chronic HBV infection (treated and untreated), and 1,486,081 person-years (PY) of follow-up evaluation; 26 reported data on HCC, 7 on liver decompensation, and 13 on liver transplantation and/or death. The composite event rates were 0.19/1000 PY for the HBsAg seroclearance group and 2.45/1000 PY for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 for liver decompensation (95% CI, 0.13-0.59; P = .001), 0.30 for HCC (95% CI, 0.20-0.44; P < .001), 0.22 for liver transplantation and/or death (95% CI, 0.13-0.39; P < .001), and 0.31 for the composite end point (95% CI, 0.23-0.43; P < .001). No differences in RR estimates were observed among subgroups of different study or patient characteristics.CONCLUSIONS: In a systematic review and meta-analysis, we found seroclearance of HBsAg to be associated significantly with improved patient outcomes. The results are consistent among different types of studies, in all patient subpopulations examined, and support the use of HBsAg seroclearance as a primary end point of trials of patients with chronic HBV infection.
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  • Andreasson, Anna, et al. (författare)
  • Waist/Hip Ratio Better Predicts Development of Severe Liver Disease Within 20 Years Than Body Mass Index : A Population-based Cohort Study
  • 2017
  • Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 15:8, s. 1294-1301
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Obesity, commonly assessed based on body mass index (BMI), is associated with an increased risk for severe liver disease. It is not known if other measures of body composition are better determinants of risk for severe liver disease, and/or if these differ between women and men. We investigated the body composition measures that best predict the development of severe liver disease.METHODS: We collected data from the Malmo Diet and Cancer study in Sweden, comprising 16,784 women and 10,833 (mean age, 58.1 years at baseline), and followed patients for a median 19.8 years. We analyzed data on measures of body composition including BMI, waist/hip ratio, and others. We determined whether subjects were diagnosed with severe liver disease, or died from severe liver disease, until the end of 2014 using Swedish national registers. Associations between body composition measures and severe liver disease were assessed using Cox regression models, stratified by sex and adjusted for age, alcohol consumption, smoking, education, and physical activity.RESULTS: All studied measures of body composition were significantly associated with severe liver disease. Waist/hip ratio was the best predictor of severe liver disease in women (hazard ratio [HR] per standard deviation increment, 1.30; 95% confidence interval [CI], 1.16-1.46) and men (HR, 1.46; 95% CI, 1.31-1.63). BMI had the lowest HR in women (HR, 1.12; 95% CI, 1.00-1.27) and men (HR, 1.26; 95% CI, 1.12-1.42). The association between waist/hip ratio and development of liver disease was independent of BMI.CONCLUSIONS: In a Swedish population-based cohort study, we associated all measures of body composition with risk of severe liver disease. However, measures of abdominal obesity were best at predicting development of severe liver disease.
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  • Andrén Aronsson, Carin, et al. (författare)
  • Effects of Gluten Intake on Risk of Celiac Disease: a case-control study on a Swedish birth cohort.
  • 2016
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-7714 .- 1542-3565. ; 14:3, s. 403-409
  • Tidskriftsartikel (refereegranskat)abstract
    • It is not clear how intake of gluten during infancy affects subsequent risk of celiac disease. We investigated whether gluten intake before 2 years of age increases risk for celiac disease in genetically susceptible children.
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  • Axelrad, Jordan E., et al. (författare)
  • Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case-Control Study
  • 2019
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:7, s. 1311-1322
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Gastrointestinal infections have been associated with later development of inflammatory bowel diseases (IBD). However, studies have produced conflicting results. We performed a nationwide case-control study in Sweden to determine whether gastroenteritis is associated with the development of Crohn's disease (CD) or ulcerative colitis (UC).METHODS: Using the Swedish National Patient Register, we identified 44,214 patients with IBD (26,450 with UC; 13,387 with CD; and 4377 with IBD-unclassified) from 2002 to 2014 and matched them with 436,507 individuals in the general population (control subjects). We then identified patients and control subjects with reported episodes of gastroenteritis (from 1964 to 2014) and type of pathogen associated. We collected medical and demographic data and used logistic regression to estimate odds ratios (ORs) for IBD associated with enteric infection.RESULTS: Of the patients with IBD, 3105 (7.0%) (1672 with UC, 1050 with CD, and 383 with IBD-unclassified) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR, 1.64; 1.57-1.71), bacterial gastrointestinal infection (aOR, 2.02; 1.82-2.24), parasitic gastrointestinal infection (aOR, 1.55; 1.03-2.33), and viral gastrointestinal infection (aOR, 1.55; 1.34-1.79). Patients with UC had higher odds of previous infection with Salmonella, Escherichia coli, Campylobacter, or Clostridium difficile compared to control subjects. Patients with CD had higher odds of previous infection with Salmonella, Campylobacter, Yersinia enterocolitica, C difficile, amoeba, or norovirus compared to control subjects. Increasing numbers of gastroenteritis episodes were associated with increased odds of IBD, and a previous episode of gastroenteritis remained associated with odds for IBD more than 10 years later (aOR, 1.26; 1.19-1.33).CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found previous episodes of gastroenteritis to increase odds of later development of IBD. Although we cannot formally exclude misclassification bias, enteric infections might induce microbial dysbiosis that contributes to the development of IBD in susceptible individuals.
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  • Benito de Valle, Maria, et al. (författare)
  • Factors That Reduce Health-Related Quality of Life in Patients With Primary Sclerosing Cholangitis.
  • 2012
  • Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 10:7, s. 769-775
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Health-related quality of life (HRQL) is frequently reduced in patients with chronic liver disease, but there are limited data from patients with primary sclerosing cholangitis (PSC). We aimed to evaluate HRQL and its potential determinants in 2 population-based cohorts of patients with PSC and to study the prevalence of fatigue among these patients. METHODS: Validated questionnaires were used to measure quality of life (the Short-Form 36 [SF-36] and the chronic liver disease questionnaire), fatigue (the fatigue impact scale), and psychological distress (the hospital anxiety and depression scale) in 182 PSC patients residing in Sweden or England. Results were compared with those from the general population (controls). Regression analysis was performed to identify factors independently associated with HRQL. RESULTS: Patients with PSC had significantly lower scores from several areas of the SF-36, compared with controls (P < .05). Age (β = -0.62 to -0.21, P < .05) and systemic symptoms (β = 3.84-15.94, P < .05) such as pruritus were associated with lower scores from specific areas of the SF-36; serum level of alkaline phosphatase (β =-1.12 to -0.75, P < .05), and large-duct PSC (β = -15.35 to -10.05, P < .05) were associated with lower scores on mental health questionnaires. The proportion of patients with significant fatigue, depression, or anxiety did not differ between patients and controls (P > .05). CONCLUSIONS: Quality of life is impaired in unselected patients with PSC. Fatigue does not seem to be a specific symptom of PSC. Older age, large-duct disease, and systemic symptoms seem to reduce HRQL in patients with PSC.
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20.
  • Bergquist, Annika, et al. (författare)
  • Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis
  • 2008
  • Ingår i: Clinical Gastroenterology and Hepatology. - New York : Elsevier. - 1542-3565 .- 1542-7714. ; 6:8, s. 939-943
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6–84.4), 11.1 (3.3–37.8), and 2.3 (0.9–6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3–4.9) and for Crohn's disease 1.4 (0.8–2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9–18.9). Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC. 
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21.
  • Bergquist, A, et al. (författare)
  • Reply
  • 2020
  • Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 18:5, s. 1245-1246
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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22.
  • Bertilsson, Sara, et al. (författare)
  • Factors That Affect Disease Progression After First Attack of Acute Pancreatitis
  • 2015
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-7714 .- 1542-3565. ; 13:9, s. 1662-1669
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Little is known about recurrence of pancreatitis after an initial episode, and little is known about how the disease progresses or what factors affect progression. We performed a population-based study of patients with acute pancreatitis (AP) to determine their outcomes and associated factors. METHODS: We performed a retrospective study of patients with first-time AP from 2003 through 2012 in a well-defined area of Sweden. Data were collected from medical records on disease etiology, severity (according to the Atlanta classification), recurrence of AP, subsequent chronic pancreatitis, and mortality. Patients were followed up for a median time of 4.6 years, until death or the end of 2013. RESULTS: We identified 1457 patients with first-time AP (48% biliary disease, 17% alcohol-associated, 9.9% severe); 23% of patients had 1 or more recurrences. Risk for recurrence was significantly higher among smokers (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.03-1.95; P = .03), patients with alcohol-associated AP (HR, 1.58; 95% CI, 1.25-2.23; P < .01), after organ failure (HR, 1.46; 95% CI 1.05-2.03; P = .02), and in patients with systemic complications (HR, 1.88; 95% CI, 1.27-2.79; P < .01) or local complications (HR, 1.66; 95% CI, 1.22-2.27; P < .01). AP of all etiologies progressed to chronic pancreatitis, although alcohol-associated AP progressed most frequently (2.8/100 patient-years). Patients with recurrent AP were at the highest risk for chronic pancreatitis (HR, 6.74; 95% CI, 4.02-11.3; P < .01), followed by alcohol-associated AP (HR, 3.10; 95% CI, 2.05-5.87; P < .01), smoking (HR, 2.26; 95% CI, 1.12-4.58; P = .02), systemic complications (HR, 1.37; 95% CI, 1.06-4.62; P = .03), and peripancreatic necrosis (HR, 2.74; 95% CI, 1.7-4.43; P < .01). In-hospital mortality was 2.8%, and independently associated only with organ failure (odds ratio, 71.17; 95% CI, 21.14-239.60; P < .01). Fifty-three percent of patients who died during disease recurrence had biliary AP; a higher percentage of these patients died upon first recurrence (5.9%) than upon first attack of AP (2%; P = .01). CONCLUSIONS: The severity of first-time AP, smoking, and alcohol abuse are related to recurrence and subsequent chronic pancreatitis. Recurrence increases the risk for progression to chronic pancreatitis. Most patients who die upon disease recurrence have biliary AP.
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23.
  • Bhoo-Pathy, Nirmala, et al. (författare)
  • Intake of Coffee, Decaffeinated Coffee, or Tea Does Not Affect Risk for Pancreatic Cancer : Results From the European Prospective Investigation into Nutrition and Cancer Study
  • 2013
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 11:11, s. 1486-1492
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer.METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire, and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression.RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers.CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.
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25.
  • Bjorkstrom, K., et al. (författare)
  • Risk Factors for Severe Liver Disease in Patients With Type 2 Diabetes
  • 2019
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 17:13, s. 2769-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Type 2 diabetes is a risk factor for development of cirrhosis and hepatocellular carcinoma. However, risk factors that identify persons with the highest risk for these outcomes are missing from unselected, population-based cohorts. METHODS: The National Diabetes Register contains data on about 90% of persons in Sweden with type 2 diabetes. In this cohort study, persons with type 2 diabetes listed in the National Diabetes Register were compared with 5 individuals from the general population (controls), matched for age, sex, and county. In total, 406 770 persons with type 2 diabetes and 2 033 850 controls were included and followed for 21 596 934 person-years. We used population-based registers to determine the incidence of severe liver disease, defined as a diagnosis of hepatocellular carcinoma, cirrhosis, decompensation, liver failure and/or death due to liver disease during follow up. Cox regression was performed to estimate the risk of severe liver disease and to examine risk factors in persons with type 2 diabetes. RESULTS: Risk for severe liver disease was increased in patients with type 2 diabetes compared to controls (hazard ratio, 2.28; 95% CI, 2.21-2.36). Risk factors associated with severe liver disease in persons with type 2 diabetes were higher age, male sex, hypertension, higher body mass index, lower glomerular filtration rate, microalbuminuria, and smoking. Statins were associated with a decreased risk of severe liver disease. CONCLUSIONS: Persons with type 2 diabetes have an increased risk for severe liver disease. Knowledge of risk factors can be helpful in identifying persons with type 2 diabetes who have a high risk for severe liver disease.
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26.
  • Bozorg, Soran R., 1993-, et al. (författare)
  • Work loss in patients with celiac disease : A population-based longitudinal study
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:5, s. 1068-1076.e6
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Celiac disease (CD) affects around 1% of the population worldwide. Data on work disability in celiac patients remain scarce. We estimated work loss in celiac patients including its temporal relationship to diagnosis.METHODS: Through biopsy reports from Sweden's 28 pathology departments, we identified 16,005 working-aged patients with prevalent CD (villus atrophy) as of January 1, 2015, and 4,936 incident patients diagnosed with CD in 2008-2015. Each patient was matched to up to 5 general-population comparators. Using nationwide social insurance registers, we retrieved prospectively-recorded data on compensation for sick leave and disability leave to assess work loss in patients and comparators.RESULTS: In 2015, patients with prevalent CD had a mean of 42.5 lost work days as compared with 28.6 in comparators (mean difference: 14.7, 95%CI: 13.2-16.2), corresponding to a relative increase of 49%. More than half of the work loss (60.1%) in celiac patients was derived from a small subgroup (7%) while 75.4% had no work loss. Among incident patients, the annual mean difference between patients and comparators was 8.0 (5.4-10.6) lost work days 5 years before CD diagnosis, which grew to 13.7 (9.1-18.3) days 5 years after diagnosis. No difference in work loss was observed between patients with or without mucosal healing at follow-up.CONCLUSIONS: Celiac patients lost more work days than comparators before their diagnosis, and this loss increased after diagnosis. Identifying patients with an increased risk of work loss may serve as a target to mitigate work disability, and thereby reduce work loss, in CD.
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29.
  • Caron, Bénédicte, et al. (författare)
  • IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis : the PROCTRIAL Consensus
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:11, s. 2169-2627.e1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the PROCTRIAL (Definition and endpoints for ulcerative PROCtitis in clinical TRIALs) initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults.METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters.RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity is proposed. Secondary endpoints which should be evaluated include endoscopic remission, histological remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life.CONCLUSION: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the PROCTRIAL consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.
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30.
  • Castro, Felipe A., et al. (författare)
  • Increased Risk of Hepatobiliary Cancers After Hospitalization for Autoimmune Disease
  • 2014
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-7714 .- 1542-3565. ; 12:6, s. 1038-1045
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Some autoimmune diseases are associated with increased risk of liver cancer. However, there has been no comprehensive evaluation of autoimmune diseases among patients who develop different subtypes of hepatobiliary cancer. We examined the association between autoimmune diseases and cancers of the liver and biliary tract in the Swedish population. METHODS: We analyzed data from national datasets at the Center for Primary Health Care Research (Lund University, Sweden). Data on patients with autoimmune disorders were retrieved from the Swedish Hospital Discharge Register, from 1964 through 2008; 33 diseases were evaluated. Hepatobiliary cancer cases were retrieved from the Swedish Cancer Registry. We calculated standardized incidence ratios (SIRs) and hazard ratios for incident cancers and deaths from hepatobiliary cancers. RESULTS: Among 402,462 patients with autoimmune disorders, 582 were diagnosed with primary liver cancer, 330 with gallbladder cancer, 115 with extrahepatic bile duct cancer, and 43 with ampulla of Vater cancers. We identified 14 autoimmune conditions that were significantly associated with increased risk of primary liver cancer (overall SIR [any autoimmune disease], 2.1; 95% confidence interval [CI], 2.0-2.3), 5 conditions associated with gallbladder cancer (overall SIR, 1.3; 95% CI, 1.1-1.4), and 3 associated with extrahepatic bile duct cancer (overall SIR, 1.6; 95% CI, 1.3-1.9). The autoimmune disorders with the strongest association with primary liver cancer were primary biliary cirrhosis (SIR, 39.5; 95% CI, 28.2-53.8) and autoimmune hepatitis (SIR, 29.0; 95% CI, 9.1-68.2); ulcerative colitis was strongly associated with extrahepatic bile duct cancer (SIR, 5.6; 95% CI, 3.6-8.4). Celiac disease, Crohn's disease, systemic sclerosis, and ulcerative colitis were associated with at least 2 types of cancer. Increased hazard ratios were observed only for patients with biliary tract cancer who had been hospitalized for autoimmune conditions. CONCLUSIONS: In a study of the Swedish population, we identified an increased risk of hepatobiliary cancers among individuals diagnosed with autoimmune disease. Associations among different cancer types indicate that shared immunomodulatory mechanisms determine susceptibility to hepatobiliary cancer.
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31.
  • Chan, Simon S. M., et al. (författare)
  • Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis : A Pooled Analysis of Five Prospective Cohort Studies
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:5, s. 1048-1058
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC).METHODS: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs).RESULTS: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI >= 30 kg/m(2)) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I-2 = 0%) compared with normal BMI (18.5 to <25 kg/m(2)). Each 5 kg/m(2) increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I-2 = 0%). Similarly, with each 5 kg/m(2) increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I-2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I-2 = 0%). No associations were observed between measures of obesity and risk of UC.CONCLUSIONS: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.
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32.
  • De Vincentis, Antonio, et al. (författare)
  • A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores.
  • 2022
  • Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 20:3, s. 658-673
  • Tidskriftsartikel (refereegranskat)abstract
    • A polygenic risk score based on well-known genetic variants in PNPLA3, TM6SF2, MBOAT7 and GCKR predicts hepatic fat content (PRS-HFC). Here we hypothesize that the addition of PRS-HFC to clinical fibrosis scores may improve risk stratification and prediction of severe liver disease (SLD).We used data from 266,687 individuals in the UK Biobank, evaluating the incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation during a median follow-up of 9 years. NAFLD fibrosis score (NFS), FIB-4, APRI, BARD and Forns scores, and PRS-HFC, were computed. All analyses were stratified according to the presence of diabetes, obesity and positive fatty liver index (FLI≥60).Unfavorable genetics (PRS-HFC≥0.396) further stratified the risk of SLD in subjects in intermediate/high risk classes of fibrosis scores, with higher effect in those with metabolic risk factors, and the prediction was improved by integrating PRS-HFC (AUROCs increased for all scores with p∼10-2-10-4, except for APRI in the overall population and in subjects with obesity. PRS-HFC improved diagnostic accuracies and positive predictive values for SLD in intermediate-high clinical score risk classes. Risk stratification and prediction were not/poorly affected by unfavorable genetics in subjects without metabolic risk factors.Integration of genetics with clinical fibrosis scores refines individual risk and prediction for SLD, mainly in individuals at risk for NAFLD. These data provide first evidence from a prospective cohort that common genetic variants capture additional prognostic insights not conveyed by validated clinical/biochemical parameters.
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38.
  • Efe, C., et al. (författare)
  • Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis
  • 2017
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 15:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Predniso(lo) ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo) ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.
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39.
  • Elfström, Peter, et al. (författare)
  • Low Risk of Gastrointestinal Cancer Among Patients With Celiac Disease, Inflammation, or Latent Celiac Disease
  • 2012
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 10:1, s. 30-36
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Celiac disease has been associated with gastrointestinal (GI) cancers in small studies; risks have not been estimated from large populations or based on histopathology analyses.METHODS: We examined the risk of GI cancers by using data from cohorts of patients with celiac disease (villous atrophy, Marsh score of 3; n = 28,882) or inflammation (Marsh score of 1-2; n = 12,860); biopsy samples were evaluated at 28 pathology centers. A third cohort included 3705 individuals with latent celiac disease (normal mucosa, but positive serology results). Data were compared with those from an age-and sex-matched population.RESULTS: Of patients with celiac disease, 372 developed incident GI cancers; 347 patients with inflammation and 38 with latent celiac disease developed GI cancers. In the first year after diagnosis and initial biopsy, celiac disease was associated with 5.95-fold increase in risk of incident GI cancer (95% confidence interval [ CI], 4.64-7.64); the hazard ratio [HR] for inflammation was 9.13 (95% CI, 7.19-11.6) and for latent celiac disease was 8.10 (95% CI, 4.69-14.0). After the first year, patients were at no significant increase in risk for GI cancers; the HR for celiac disease was 1.07 (95% CI, 0.93-1.23), for inflammation it was 1.16 (95% CI, 0.98-1.37), and for latent celiac disease it was 0.96 (95% CI, 0.56-1.66). The absolute risk for any GI cancer in patients with celiac disease was 101/100,000 person-years, with an excess risk of 2/100,000 person-years.CONCLUSIONS: Although celiac disease, inflammation, and latent disease all increase risk for GI cancers in the first year after diagnosis, there is no increase in risk thereafter.
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40.
  • Elmunzer, B. Joseph, et al. (författare)
  • Prolonged Gastrointestinal Manifestations After Recovery From COVID-19
  • 2024
  • Ingår i: Clinical Gastroenterology and Hepatology. - 1542-3565 .- 1542-7714. ; 22:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19. Methods: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12–18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events–Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up. Results: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P <. 0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events–Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events–Revised) was the strongest predictor of GI symptom severity at follow-up. Conclusions: In this follow-up survey of patients 12–18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.
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41.
  • Emilsson, Louise, et al. (författare)
  • Autoimmune Disease in First-Degree Relatives and Spouses of Individuals With Celiac Disease
  • 2015
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 13:7, s. 1271-1277.e2
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease. METHODS: We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n = 29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n = 84,648) and controls (n = 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups. RESULTS: During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P =.11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation. CONCLUSIONS: First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.
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42.
  • Flack, Kathryn F., et al. (författare)
  • Major Gastrointestinal Bleeding Often Is Caused by Occult Malignancy in Patients Receiving Warfarin or Dabigatran to Prevent Stroke and Systemic Embolism From Atrial Fibrillation
  • 2017
  • Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 15:5, s. 682-690
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Gastrointestinal (GI) bleeding in patients receiving anticoagulation agents can be caused by occult malignancies. We investigated the proportions and features of major GI bleeding (MGIB) events related to occult GI cancers in patients receiving anticoagulation therapy.METHODS: We analyzed data from the Randomized Evaluation of Long Term Anticoagulant Therapy study (conducted between December 2005 and March 2009 in 951 clinical centers in 44 countries worldwide), which compared the abilities of dabigatran vs warfarin to prevent stroke and systemic embolism in 18,113 patients with atrial fibrillation. Two blinded gastroenterologists independently reviewed source documents of MGIB events (n = 595) that occurred during the study period. We collected data on MGIB events caused by previously unidentified GI malignancies, and compared characteristics of MGIB events in patients who received dabigatran vs warfarin (primary end point), and in patients with bleeding from cancer, vs patients bleeding from a nonmalignant or unidentified source.RESULTS: Of 546 unique MGIB events, 44 (8.1%) were found to be from GI cancers (34 of 398 MGIB events in dabigatran users and 10 of 148 MGIB events in warfarin users; P = .60). Colorectal cancer accounted for 35 of 44 of all cancers identified. There were more colorectal cancer-associated MGIB events in the dabigatran group (30 of 34) than in the warfarin group (5 of 10) (P = .02), but more gastric cancer-associated MGIB events in the warfarin group (5 of 10) than in the dabigatran group (1 of 34) (P = .001). There were no differences in the short-term outcomes of cancer-related MGIB events in the dabigatran vs the warfarin group, but 75% of all cancer-related MGIB events required at least 1 blood transfusion and the mean hospital stay was 10.1 days. Compared with MGIB events from a nonmalignant or unidentified source, MGIB from cancer occurred sooner (343.0 vs 223.1 d; P = .003), but the bleeding was more likely to be chronic (for > 7 d) (27.3% vs 63.6%; P < .001).CONCLUSIONS: In evaluating data from a study of the effects of anticoagulation therapy, we found approximately 1 of every 12 MGIB events to be related to an occult cancer. Approximately two thirds of cancer-related MGIB presents with chronic bleeding, and morbidity, and resource utilization is high.
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44.
  • Forss, Anders, et al. (författare)
  • Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events : A Matched Cohort Study
  • 2023
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:13
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Inflammatory diseases are associated with an increased risk of incident major adverse cardiovascular events (MACE). However, data on MACE are lacking in large population-based histopathology cohorts of microscopic colitis (MC).METHODS: This study included all Swedish adults with MC without previous cardiovascular disease (1990- 2017; N = 11,018). MC and subtypes (collagenous colitis and lymphocytic colitis) were defined from prospectively recorded intestinal histopathology reports from all pathology departments (n = 28) in Sweden. MC patients were matched for age, sex, calendar year, and county with up to 5 reference individuals (N = 48,371) without MC or cardiovascular disease. Sensitivity analyses included full sibling comparisons, and adjustment for cardiovascular medication and healthcare utilization. Multivariable-adjusted hazard ratios for MACE (any of ischemic heart disease, congestive heart failure, stroke, and cardiovascular mortality) were calculated using Cox proportional hazards modelling. RESULTS: Over a median of 6.6 years of follow-up, 2181 (19.8%) incident cases of MACE were confirmed in MC patients and 6661 (13.8%) in reference individuals. MC patients had a higher overall risk of MACE outcomes compared with reference individuals (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.21-1.33) and higher risk of its components: ischemic heart disease (aHR, 1.38; 95% CI, 1.28-1.48), congestive heart failure (aHR, 1.32; 95% CI, 1.22-1.43), and stroke (aHR, 1.12; 95% CI, 1.02-1.23) but not cardiovascular mortality (aHR, 1.07; 95% CI, 0.98-1.18). The results remained robust in the sensitivity analyses.CONCLUSIONS: Compared with reference individuals, MC patients had a 27% higher risk of incident MACE, equal to 1 extra case of MACE for every 13 MC patients followed for 10 years.
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47.
  • Frudinger, Andrea, et al. (författare)
  • Skeletal muscle–derived cell implantation for the treatment of fecal incontinence : a randomized, placebo-controlled study
  • 2023
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:2, s. 476-486.e8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Fecal incontinence (FI) improvement following injection of autologous skeletal muscle–derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy.Methods: Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months.Results: Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. Conclusions: Injection of a high dose of autologous skeletal muscle–derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32).
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48.
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49.
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50.
  • Gruneau, Lina, et al. (författare)
  • Disease Progression Modeling for Economic Evaluation in Nonalcoholic Fatty Liver Disease-A Systematic Review
  • 2023
  • Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 21:2, s. 283-298
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND & AIMS: Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease progression, long-term impact of pharmacologic treatments can be assessed only by complementing emerging clinical trial evidence with data from other sources in disease progression modeling. Although this modeling is crucial for economic evaluation studies assessing the clinical and economic con-sequences of new treatments, the approach to modeling the natural history of NAFLD differs in contemporary research. This systematic literature review investigated modeling of the natural history of NAFLD.METHODS: A systematic literature review was conducted searching PubMed, Scopus, Cochrane, and the National Health Service Economic Evaluation Database to identify articles focusing on modeling of the natural history of NAFLD. Model structure and transition probabilities were extracted from included studies.RESULTS: Of the 28 articles identified, differences were seen in model structure and data input. Clear definitions of nonalcoholic steatohepatitis and NAFLD often were lacking; differences in the granularity of modeling fibrosis progression, the approach to disease regression, and modeling of advanced liver disease varied across studies. Observed transition probabilities for F0 to F1, F1 to F2, F2 to F3, and F3 to compensated cirrhosis varied between 0.059 to 0.095, 0.023 to 0.140, 0.018 to 0.070, and 0.040 to 0.118, respectively.CONCLUSIONS: The difference in disease progression modeling for seemingly similar models warrants further inquiry regarding how to model the natural course of NAFLD. Such differences may have a large impact when assessing the value of emerging pharmacologic treatments.
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