| 1. |
- Mårild, Karl, 1982, et al.
(författare)
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Histological remission in inflammatory bowel disease and female fertility : A nationwide study
- 2024
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Ingår i: Gastroenterology. - : American Gastroenterology Association Institute. - 0016-5085 .- 1528-0012. ; 166:5, s. 802-814.e18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histological disease activity.METHODS: Nationwide IBD cohort of Swedish women aged 15-44 years. We examined fertility rates during periods with vs. without histological inflammation (n=21,046; follow-up: 1990-2016) and during periods with vs. without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n=24,995; follow-up: 2006-2020). Accounting for socio-demographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live-births conceived during 12-month-periods of histological inflammation (vs. histological remission) and 3-month-periods of clinically active IBD (vs. quiescent IBD).RESULTS: During periods with vs. without histological inflammation, there were 6.35 (95%CI=5.98-6.73) and 7.09 (95%CI=6.48-7.70) live-births conceived per 100 person-years of follow-up, respectively, or one fewer child per fourteen women with 10 years of histological inflammation (aFRR=0.90; 95%CI=0.81-1.00). In women with histological inflammation fertility was similarly reduced in ulcerative colitis (UC, aFRR=0.89 [95%CI=0.78-1.02]) and Crohn's disease (CD, aFRR=0.86 [95%CI=0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95%CI=0.72-0.79) or one fewer child per six women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR=0.75 [95%CI=0.70-0.81]) and CD (aFRR=0.76 [95%CI=0.70-0.82]). Finally, also among women with clinically quiescent IBD, histological inflammation (vs. histological remission) was associated with reduced fertility (aFRR=0.85 [95%CI=0.73-0.98]).CONCLUSIONS: An association between histological and clinical activity and reduced female fertility in CD and UC was found. Notably, histological inflammation was linked to reduced fertility also in women with clinically quiescent IBD.
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| 2. |
- Emilsson, Louise, et al.
(författare)
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The characterisation and risk factors of ischaemic heart disease in patients with coeliac disease
- 2013
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 37:9, s. 905-914
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies have shown an increased risk of ischaemic heart disease (IHD) in patients with coeliac disease (CD), despite the patients' lack of traditional IHD risk factors.Aim: To characterise IHD according to CD status.Methods: Data on duodenal or jejunal biopsies were collected in 20062008 from all 28 pathology departments in Sweden and were used to define CD (equal to villous atrophy; Marsh stage 3). We used the Swedish cardiac care register SWEDEHEART to identify IHD and to obtain data on clinical status and risk factors at time of first myocardial infarction for this case-only comparison. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). CD patients were compared with general population reference individuals.Results: We identified 1075 CD patients and 4142 reference individuals with subsequent IHD. CD patients with myocardial infarction had lower body mass index (P<0.001) and cholesterol values (P<0.001) and were less likely to be active smokers (OR=0.74; 95% CI=0.560.98) than reference individuals with myocardial infarction. CD patients had less extensive coronary artery disease at angiography (any stenosis: OR=0.80; 95% CI=0.660.97; three-vessel disease: OR=0.73; 95% CI=0.570.94); but there was no difference in the proportions of CD patients with positive biochemical markers of myocardial infarction (CD: 92.2% vs. reference individuals: 91.5%, P=0.766).Conclusion: Despite evidence of an increased risk of IHD and higher cardiovascular mortality, patients with coeliac disease with IHD have a more favourable cardiac risk profile compared with IHD in reference individuals.
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| 3. |
- Lebwohl, Benjamin, et al.
(författare)
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Mucosal healing and the risk of ischemic heart disease or atrial fibrillation in patients with celiac disease : a population-based study
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF.Methods: We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF.Results: Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were >= 60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73-1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73-1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74-1.30).Conclusions: In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events.
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| 4. |
- Uusijärvi, A., et al.
(författare)
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Use of antibiotics in infancy and childhood and risk of recurrent abdominal pain-a Swedish birth cohort study
- 2014
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Ingår i: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 26:6, s. 841-850
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Tidskriftsartikel (refereegranskat)abstract
- Background: The etiology of recurrent abdominal pain of functional origin (AP) is largely unknown. Antibiotic treatment influences the intestinal microbiota, and a few studies have indicated an increased risk of AP in adults after antibiotic treatment. Corresponding data in children are lacking. The aim of this study was to explore the association between antibiotic treatment during childhood and AP at 12years.Methods: Two thousand seven hundred and thirty-two children from a Swedish, population-based birth cohort. Parents reported antibiotic use for the children between birth and 2years. Antibiotic use between 9 and 12years was collected from the Swedish Prescribed Drug Register. The children answered questionnaires regarding AP at age 12. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for AP at 12years as a function of antibiotic use.Key Results: Antibiotic treatment between 9 and 12years was not associated with AP at 12. Children who had received 3 courses, or broad-spectrum antibiotics between 9 and 12years had an increased risk of AP at 12, but these associations failed to reach statistical significance. Antibiotic treatment during both the first and the second year of life increased the risk of AP in girls at 12 (OR 1.65; 95% CI: 1.09-2.49), but not in boys or the whole cohort.Conclusions & Inferences: Antibiotic treatment does not seem to be a major risk factor for AP at 12years. However, we cannot exclude that repeated courses, especially to infant girls, or use of broad-spectrum antibiotics between 9 and 12years may be associated with an increased risk of AP.
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| 5. |
- Lebwohl, Benjamin, et al.
(författare)
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Cancer Risk in 47,241 Individuals with Celiac Disease : A Nationwide Cohort Study
- 2022
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:2, s. e111-e131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Celiac disease (CD) is associated with increased mortality, in part due to cancer. Most studies investigating this cancer risk involved patients diagnosed before widespread increases in CD diagnosis rates and access to gluten-free food. We performed a population-based study of the risk of cancer in CD.METHODS: We identified all patients in Sweden with CD as defined as duodenal villus atrophy, using the ESPRESSO cohort. Each patient was matched to ≤5 controls by age, sex, and county. We used stratified Cox proportional-hazards model, following patients from diagnosis until first cancer, or by December 31, 2016.RESULTS: Among 47,241 patients with CD, 30,080 (64%) were diagnosed since 2000. After a median follow-up of 11.5 years, the incidence of cancer was 6.5 and 5.7 per 1000 person-years in CD patients and controls, respectively. The overall risk of cancer was increased (hazard ratio[HR] 1.11; 95%CI 1.07-1.15), but was only significantly elevated in the first year after CD diagnosis (HR 2.47; 95%CI 2.22-2.74), and not subsequently (HR 1.01; 95%CI 0.97-1.05), though the risks of hematologic, lymphoproliferative, hepatobiliary, and pancreas cancers persisted. The overall risk was highest in those diagnosed with CD after age 60 years (HR 1.22; 95%CI 1.16-1.29) and was not increased in those diagnosed before age 40. The cancer risk was similar among those diagnosed with CD before or after the year 2000.CONCLUSIONS: There is an increased risk of cancer in CD, even in recent years, but this risk increase is confined to those diagnosed with CD after age 40, and is primarily present within the first year of diagnosis.
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| 6. |
- Lebwohl, Benjamin, et al.
(författare)
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Psychiatric disorders in patients with a diagnosis of celiac disease during childhood from 1973 to 2016
- 2021
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:10, s. 2093-2101.e13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Few studies have explored the link between childhood celiac disease and long-term psychiatric comorbidities. We performed a population-based cohort study of associations between childhood celiac disease and psychiatric disorders and investigated whether risk persists into adulthood.METHODS: We performed a nationwide study in Sweden using data from the ESPRESSO cohort. In this cohort, 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016 were identified from Sweden's 28 pathology departments. Each patient was matched with as many as 5 reference children (controls, n=94,249). Data on psychiatric disorders were obtained from the patient register. We used Cox proportional modeling to estimate hazard ratios (HRs).RESULTS: During a median follow-up time of 12.3 years, 3174 children (16.5%) with celiac disease received a new diagnosis of a psychiatric disorder, compared with 13,286 controls (14.1%). Corresponding incidence rates were 12.2 per 1000 person-years (95% Cl, 11.8-12.7) vs 10.3 per 1000 person-years (95% Cl, 10.2-10.5). Childhood celiac disease was associated with a 19% increase in risk of any psychiatric disorder (95% Cl, 1.14-1.23); the increase in risk was observed in all childhood age groups. The highest HRs were seen in the first year after celiac diagnosis (HR, 1.70; 95% Cl, 1.41-2.05). The risk increase persisted into adulthood (older than 18 years: HR, 1.11; 95% Cl, 1.04-1.17). We found increased risks of mood disorders (HR, 1.20; 95% CI, 1.12-1.28), anxiety disorders (HR, 1.12; 95% CI, 1.06-1.19), eating disorders (HR, 1.34; 95% CI, 1.18-1.51), attention deficit hyperactivity disorder (HR, 1.29; 95% CI, 1.20-1.39), and autism spectrum disorder (HR, 1.47; 95% CI, 1.32-1.64). We found no statistically significant risk increase for psychotic disorders, psychoactive substance misuse, behavioral disorders, personality disorders, suicide attempt, or suicide. Celiac disease was also linked to an increased use of psychiatric drugs (HR, 1.34; 95% CI, 1.24-1.43). A conditional logistic regression found that psychiatric disorders were also more common prior to diagnosis of celiac disease (odds ratio, 1.56; 95% Cl, 1.39-1.76).CONCLUSIONS: Childhood celiac disease is associated with increased risk of subsequent psychiatric disorders, which persists into adulthood. Mental health surveillance should be integral in the care of celiac disease.
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| 7. |
- Ugalde-Morales, Emilio, et al.
(författare)
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Common shared genetic variation behind decreased risk of breast cancer in celiac disease
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- There is epidemiologic evidence showing that women with celiac disease have reduced risk of later developing breast cancer, however, the etiology of this association is unclear. Here, we assess the extent of genetic overlap between the two diseases. Through analyses of summary statistics on densely genotyped immunogenic regions, we show a significant genetic correlation (r = -0.17, s.e. 0.05, P < 0.001) and overlap (Ppermuted < 0.001) between celiac disease and breast cancer. Using individuallevel genotype data from a Swedish cohort, we find higher genetic susceptibility to celiac disease summarized by polygenic risk scores to be associated with lower breast cancer risk (ORper-SD, 0.94, 95% CI 0.91 to 0.98). Common single nucleotide polymorphisms between the two diseases, with low P-values (P-CD < 1.00E-05, P-BC <= 0.05), mapped onto genes enriched for immunoregulatory and apoptotic processes. Our results suggest that the link between breast cancer and celiac disease is due to a shared polygenic variation of immune related regions, uncovering pathways which might be important for their development.
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| 8. |
- Lebwohl, B., et al.
(författare)
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Mucosal healing and mortality in coeliac disease
- 2013
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 37:3, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coeliac disease (CD), characterised by the presence of villous atrophy (VA) in the small intestine, is associated with increased mortality, but it is unknown if mortality is influenced by mucosal recovery.AIMS: To determine whether persistent VA is associated with mortality in CD.METHODS: Through biopsy reports from all pathology departments (n = 28) in Sweden, we identified 7648 individuals with CD (defined as VA) who had undergone a follow-up biopsy within 5 years following diagnosis. We used Cox regression to examine mortality according to follow-up biopsy.RESULTS: The mean age of CD diagnosis was 28.4; 63% were female; and the median follow-up after diagnosis was 11.5 years. The overall mortality rate of patients who underwent follow-up biopsy was lower than that of those who did not undergo follow-up biopsy (Hazard Ratio 0.88, 95% CI: 0.80-0.96). Of the 7648 patients who underwent follow-up biopsy, persistent VA was present in 3317 (43%). There were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared with those with mucosal healing (HR: 1.01; 95% CI: 0.86-1.19). Mortality was not increased in children with persistent VA (HR: 1.09 95% CI: 0.37-3.16) or adults (HR 1.00 95% CI: 0.85-1.18), including adults older than age 50 years (HR: 0.96 95% CI: 0.80-1.14).CONCLUSIONS: Persistent villous atrophy is not associated with increased mortality in coeliac disease. While a follow-up biopsy will allow detection of refractory disease in symptomatic patients, in the select population of patients who undergo repeat biopsy, persistent villous atrophy is not useful in predicting future mortality.
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| 9. |
- Olen, O., et al.
(författare)
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Allergy-related diseases and recurrent abdominal pain during childhood - a birth cohort study
- 2014
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Ingår i: Alimentary Pharmacology & Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 40:11, s. 1349-1358
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAllergy and immune dysregulation may have a role in the pathophysiology of recurrent abdominal pain of functional origin, but previous studies of allergy-related diseases and abdominal pain have contradictory results. AimTo examine the association between allergy-related diseases or sensitisation during childhood and abdominal pain at age 12years. MethodsIn this birth cohort study of 4089 children, parents answered questionnaires regarding asthma, allergic rhinitis, eczema and food hypersensitivity (allergy-related diseases') at ages 0,1,2,4,8 and 12years. Blood for analyses of allergen-specific IgE was sampled at 4 and 8years. At 12years, the children answered questions regarding abdominal pain. Children with coeliac disease or inflammatory bowel disease were excluded. Associations were examined using multivariable logistic regression. ResultsAmong 2610 children with complete follow-up, 9% (n=237) reported abdominal pain at 12years. All allergy-related diseases were associated with concurrent abdominal pain at 12years and the risk increased with increasing number of allergy-related diseases (P for trend <0.001). Asthma at 1 and 2years and food hypersensitivity at 8years were significantly associated with abdominal pain at 12years. There was an increased risk of abdominal pain at 12years in children sensitised to food allergens at 4 or 8years, but in stratified analyses, this was confined to children whose parents had not reported food hypersensitivity at time of sensitisation. ConclusionAllergy-related diseases as well as sensitisation to food allergens were associated with an elevated risk of abdominal pain, and the risk increased with the number of allergy-related diseases.
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| 10. |
- Eberhardson, M., et al.
(författare)
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Anti-TNF treatment in Crohn's disease and risk of bowel resection-a population based cohort study
- 2017
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 46:6, s. 589-598
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Tidskriftsartikel (refereegranskat)abstract
- Background: TNF inhibitors (TNFi) have been shown to reduce the need for surgery in Crohn's disease, but few studies have examined their effect beyond the first year of treatment.Aim: To conduct a register-based observational cohort study in Sweden 2006-2014 to investigate the risk of bowel resection in bowel surgery naive TNFi-treated Crohn's disease patients and whether patients on TNFi >= 12 months are less likely to undergo bowel resection than patients discontinuing treatment before 12 months.Methods: We identified all individuals in Sweden with Crohn's disease through the Swedish National Patient Register 1987-2014 and evaluated the incidence of bowel resection after first ever dispensation of adalimumab or infliximab from 2006 and up to 7 years follow-up.Results: We identified 1856 Crohn's disease patients who had received TNFi. Among these patients, 90% treatment retention was observed at 6 months after start of TNFi and 65% remained on the drug after 12 months. The cumulative rates of surgery in Crohn's disease patients exposed to TNFi years 1-7 were 7%, 13%, 17%, 20%, 23%, 25% and 28%. Rates of bowel resection were similar between patients with TNFi survival < 12 months and >= 12 months respectively (P=.27). No predictors (eg, sex, age, extension or duration of disease) for bowel resection were identified.Conclusions: The risk of bowel resection after start of anti-TNF treatment is higher in regular health care than in published RCTs. Patients on sustained TNFi treatment beyond 12 months have bowel resection rates similar to those who discontinue TNFi treatment earlier.
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