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1.
Artigo em Inglês | MEDLINE | ID: mdl-33627380

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among IBD patients. METHODS: This Swedish/Danish population-based cohort study (1969-2017) followed IBD patients and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up. RESULTS: Among the 97,496 ulcerative colitis patients/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall HRs were 1.83 (95%CI: 1.41-2.38) for HCC-, 7.33 (95%CI: 5.81-9.25) for ICC-, and 4.46 (95%CI: 3.49-5.70) for ECC-death. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among ulcerative colitis patients with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 Crohn's disease patients (median follow-up 11 years), 10-year-mortality from HCC (n=28), ICC (n=28), and ECC (n=24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95%CI: 1.31-2.93), 3.33 (95%CI: 2.19-5.09), and 3.10 (95%CI: 1.97-4.87). 1/28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC. CONCLUSIONS: Risk of HCC-, ICC-, and ECC-death was low in IBD patients and decreased over time. However, a large proportion of deaths occurred after PSC. IMPACT: Guidelines on specific surveillance strategies for IBD patients with PSC, but not those without PSC, are needed.

2.
Scand J Gastroenterol ; : 1-12, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632044

RESUMO

BACKGROUND: It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). METHODS: A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. RESULTS: Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. CONCLUSIONS: The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

5.
J Pediatr Gastroenterol Nutr ; Publish Ahead of Print2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33416269

RESUMO

OBJECTIVES: A foreign body impacted in the esophagus could be a sign of eosinophilic esophagitis (EoE). Our aim was to investigate if children previously diagnosed with a foreign body in the esophagus had a missed diagnosis of EoE. METHODS: In this population-based longitudinal study, all children (0-18 years) diagnosed with a foreign body in the esophagus in Stockholm, Sweden 2006 to 2016, were identified. In addition to a review of medical files, each family was contacted (n = 325) and asked standardized questions. Children with symptoms indicating EoE were offered esophagogastroduodenoscopy (EGD). RESULTS: We found 325 pediatric cases of foreign body. Two hundred and seven (64%) underwent an endoscopy at the event, 3 of these had biopsies taken, whereby 2 were diagnosed with EoE. Six additional patients were diagnosed with EoE between the initial event and the study follow-up. Children with persisting symptoms suggestive of EoE at the follow-up (n = 21), were offered EGD whereof 7 accepted. Four new cases of EoE were found. Hence, 12 (3.7%) of the children with a previous foreign body, either spontaneously released or endoscopically removed, were diagnosed with EoE. In the structured interview, dysphagia, food impactions and drinking excessively with meals, as well as food allergies, were significantly more common in EoE patients. CONCLUSIONS: Children with a foreign body in the esophagus are at risk of having EoE. Biopsies should be taken during foreign body removal and questions about swallowing problems and allergic diseases should be carefully explored also in children who do not need EGD because of spontaneous release.

6.
Dis Colon Rectum ; 64(3): 301-312, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395139

RESUMO

BACKGROUND: To avoid a permanent stoma, restorative surgery is performed after the colectomy. Previous studies have shown that less than half of patients with ulcerative colitis undergo restorative surgery. OBJECTIVE: The primary aim was to explore the association between socioeconomic status and restorative surgery after colectomy. DESIGN: This was a nationwide register-based cohort study. SETTINGS: The study was conducted in Sweden. PATIENTS: All Swedish patients with ulcerative colitis who underwent colectomy between 1990 and 2017 at the age of 15 to 69 years were included. MAIN OUTCOME MEASURES: The main outcome was restorative surgery, and the secondary outcome was failure of the reconstruction (defined as the need for a new ileostomy after the reconstruction or nonreversal of a defunctioning stoma within 2 years of the reconstruction). To calculate HRs for restorative surgery after colectomy, as well as failure after restorative surgery, multivariable Cox regression models were performed (adjusted for sex, year of colectomy, colorectal cancer diagnosis, education, civil status, country of birth, income (quartiles 1 to 4, where Q4 represents highest income), hospital volume, and stratified by age). RESULTS: In all, 5969 patients with ulcerative colitis underwent colectomy, and of those, 2794 (46.8%) underwent restorative surgery. Restorative surgery was more common in patients with a high income at the time of colectomy (quartile 1, reference; quartile 2, 1.09 (0.98-1.21); quartile 3, 1.20 (1.07-1.34); quartile 4, 1.27 (1.13-1.43)) and less common in those born in a Nordic country than in immigrants born in a non-Nordic country (0.86 (0.74-0.99)), whereas no association was seen with educational level and civil status. There was no association between socioeconomic status and the risk of failure after restorative surgery. LIMITATIONS: The study was restricted to register data. CONCLUSIONS: Restorative surgery in ulcerative colitis appears to be more common in patients with a high income and patients born in a non-Nordic country, indicating inequality in the provided care. See Video Abstract at http://links.lww.com/DCR/B433. LA CIRUGA RESTAURADORA ES MS COMN EN PACIENTES CON COLITIS ULCEROSA CON INGRESOS ALTOS UN ESTUDIO POBLACIONAL: ANTECEDENTES:Para evitar un estoma permanente, se realiza una cirugía reparadora después de la colectomía. Estudios anteriores han demostrado que menos de la mitad de los pacientes con colitis ulcerosa se someten a cirugía reconstituyente.OBJETIVO:El objetivo principal fue explorar la asociación entre el nivel socioeconómico y la cirugía reconstituyente después de la colectomía.DISEÑO:Estudio de cohorte basado en registros a nivel nacional.MARCO:Suecia.PACIENTES:Todos los pacientes Suecos con colitis ulcerosa que se sometieron a colectomía desde el 1990 a 2017 a la edad de 15 a 69 años.MEDIDAS DE RESULTADOS PRINCIPALES:El resultado principal fue la cirugía restaurativa y el resultado secundario fue el fracaso de la reconstrucción (definida como la necesidad de una nueva ileostomía después de la reconstrucción o la no-reversión de un estoma disfuncional dentro de los dos años posteriores a la reconstrucción). Para calcular los cocientes de riesgo para la cirugía restauradora después de la colectomía, así como el fracaso después de la cirugía restauradora, se realizaron modelos de regresión de Cox multivariables (ajustados por sexo, año de colectomía, diagnóstico de cáncer colorrectal, educación, estado civil, país de nacimiento e ingresos (cuartiles 1- 4; donde Q4 representa los mayores ingresos), volumen de hospitales y estratificado por edad).RESULTADOS:En total 5969 pacientes con colitis ulcerosa se sometieron a colectomía, y de ellos 2794 (46,8%) se sometieron a cirugía restauradora. La cirugía restauradora fue más común en pacientes con altos ingresos en el momento de la colectomía (referencia del cuartil 1, cuartil 2: 1,09 (0,98-1,21), cuartil 3: 1,20 (1,07-1,34), cuartil 4: 1,27 (1,13-1,43)), y menos común en los nacidos en un país nórdico que en los inmigrantes nacidos en un país no-nórdico (0,86 (0,74-0,99)), mientras que no se observó asociación con el nivel educativo y el estado civil. No hubo asociación entre el nivel socioeconómico y el riesgo de fracaso después de la cirugía reparadora.LIMITACIONES:Restricción para registrar datos.CONCLUSIONES:La cirugía reparadora en colitis ulcerosa parece ser más común en pacientes con ingresos altos y en pacientes nacidos en un país no-nórdico, lo que indica desigualdad en la atención brindada. Consulte Video Resumen en http://links.lww.com/DCR/B433.

7.
Gastroenterology ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33421519

RESUMO

BACKGROUND AND AIMS: Gastrointestinal infections have been linked to changes in the composition and function of gut microbiome and development of inflammatory bowel diseases. We therefore sought to examine the relationship between gastroenteritis and risk of microscopic colitis (MC). METHODS: We conducted a case-control study of all adult patients with MC diagnosed between 1990 and 2016 in Sweden matched to up to 5 general population controls according to age, sex, calendar year, and county. Cases of MC were identified using Systematized Nomenclature of Medicine codes from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, a cohort of gastrointestinal pathology reports from all 28 pathology centers in Sweden. We used logistic regression modeling to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Through December of 2016, we matched 13,468 MC cases to 64,479 controls. The prevalence of previous diagnosed gastrointestinal infection was 7.5% among patients with MC, which was significantly higher than in controls (3.0%, Pcomparison < .001). After adjustment, gastroenteritis was associated with an increased risk of MC (aOR 2.63; 95% CI 2.42-2.85). Among specific pathogens, Clostridioides difficile (aOR 4.39; 95% CI 3.42-5.63), Norovirus (aOR 2.87; 95% CI 1.66-4.87), and Escherichia species (aOR 3.82; 95% CI 1.22-11.58), but not Salmonella species, were associated with an increased risk of MC. The association between gastrointestinal infections and risk of MC was stronger for collagenous subtype (aOR 3.23; 95% CI 2.81-3.70) as compared with lymphocytic colitis (aOR 2.51; 95% CI 2.28-2.76; Pheterogeneity = .005). The associations remained significant after adjustment for immune-mediated conditions and polypharmacy and when compared with unaffected siblings. CONCLUSION: In a nationwide study, we found that gastrointestinal infection, particularly Clostridioides difficile, is associated with an increased risk of subsequent MC. This study was approved by the Regional Ethics Committee, Stockholm, Sweden (Protocol no. 2014/1287-31/4).

8.
Aliment Pharmacol Ther ; 53(4): 471-483, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33340426

RESUMO

BACKGROUND: Comparisons of second-line anti-tumour necrosis factor (TNF) agents and vedolizumab are sparse. AIM: To evaluate the effectiveness of anti-TNF agents compared to vedolizumab as second-line biologics in inflammatory bowel disease (IBD). METHODS: A propensity score-matched cohort was created using Swedish nationwide registers. Patients with Crohn's disease or ulcerative colitis, exposed to first-line anti-TNF treatment, who initiated a second anti-TNF agent or vedolizumab in 2014-2016 (N = 1363) were included. The primary outcome was drug survival at 12 months. Secondarily, we assessed survival without IBD-related hospitalisation, IBD-related surgery, antibiotics, or hospitalisation because of infection, and also corticosteroid exposure. RESULTS: After 1:1 propensity score matching, 400 patients (Crohn's disease, N = 198; ulcerative colitis, N = 202) remained. For Crohn's disease, drug survival was 73% in the vedolizumab group vs 74% in the anti-TNF group (difference: 1 percentage point; 95% confidence interval [CI]:-11-13; P = 0.87). Survival without IBD-related hospitalisation (82% vs 88%), surgery (82% vs 89%), antibiotics (65% vs 71%), hospitalisation due to infection (95% vs 88%) and corticosteroids (58% vs 48%) were not statistically significantly different between groups. For ulcerative colitis, drug survival was 69% in the vedolizumab group vs 62% in the anti-TNF group (difference: -7 percentage points; 95% CI: -20 to 6; P = 0.30). Vedolizumab-treated patients had lower survival without IBD-related hospitalisation (82% vs 93%, P = 0.02). Survival without colectomy (93% vs 97%), antibiotics (81% vs 70%), hospitalisation due to infection (92% vs 92%) and corticosteroids (58% vs 48%) were not statistically significantly different. CONCLUSIONS: Based on Swedish clinical practice, the effectiveness and safety of second-line anti-TNF and vedolizumab at 12 months appeared largely similar.

9.
J Psychosom Res ; 140: 110287, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33227558

RESUMO

OBJECTIVES: Exposure-based cognitive behavioral therapy via internet (Internet-CBT) has been shown to reduce symptoms and increase quality of life for children with functional abdominal pain disorders (FAPDs), but the mechanisms of change are unknown. The objective was to examine whether a change in symptom-specific fear and avoidance, i.e., gastrointestinal-specific anxiety (GI-anxiety) and gastrointestinal-specific avoidance (GI-avoidance), mediated changes in parent-reported abdominal symptoms for children receiving Internet-CBT compared with children receiving treatment as usual. A further aim was to assess if baseline levels of the proposed mediators moderated the mediation. METHODS: Weekly assessments of child-reported mediators and parent-reported outcome from 90 children aged 8-12 who were included in a randomized controlled trial were used in univariate and multivariate growth models to test the direct effect of treatment on outcome and the indirect effects via mediators and moderated mediation. RESULTS: Treatment condition significantly predicted the slope of the mediators (a-path), in favor of Internet-CBT, and mediators were correlated with the outcome (b-path). The indirect effects of the mediators on the outcome (cross-product of the a and b-paths) were significantly different from zero for both GI-avoidance, ab = 1.43, 95%CI [0.42, 3.23]; and GI-anxiety ab = 1.58, 95%CI [0.43, 3.62]. Baseline levels of the proposed mediators moderated the size of the mediation. CONCLUSIONS: GI-anxiety and GI-avoidance were mediators of change in Internet-CBT and high levels of the mediators at baseline were associated with larger mediated effects. Healthcare professionals should be aware of, and inform families about, the potential benefits of reducing symptom-specific fear and avoidance.

10.
J Crohns Colitis ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216873

RESUMO

BACKGROUND: In addition to their potent lipid-lowering action, statins may modulate inflammation. However, data on statin use and the risk of inflammatory bowel diseases (IBD) have been inconsistent. METHODS: We searched the Nationwide Swedish Patient Register (inpatient and non-primary outpatient care) to identify adults diagnosed with Crohn's disease (CD, n=7,637) or ulcerative colitis (UC, n=15,652) from 2006-2014. Each case was matched to 10 general population controls (n=232,890). Data on dispensed statin prescriptions were extracted from the Prescribed Drug Register. Conditional logistic regression models estimated odds ratios (ORs) for risk of IBD according to statin exposure while controlling for potential confounders, including indications for statin therapy. RESULTS: In multivariable adjusted models, compared to no statin use, any statin use was associated with a lower risk of CD (OR=0.71; 95% CI, 0.63-0.79), but not UC (OR=1.03; 95% CI, 0.96-1.11). The lowest OR for CD was seen for current statin use (OR=0.67; 95% CI, 0.60-0.75). For CD, the lowest category of cumulative statin dose (31-325 defined daily dose, DDD) was associated with an OR of 0.73 (95% CI, 0.61-0.88) and the highest category (>1500 DDD) with an OR of 0.66 (95% CI, 0.55-0.80), Ptrend=0.10. For UC, the lowest and highest dose categories yielded ORs of 1.12 (95% CI, 1.00-1.25) and 0.99 (95% CI, 0.88-1.13), respectively, Ptrend=0.13. CONCLUSIONS: Statin use was associated with a lower risk of CD, but not UC. The association with CD risk appeared strongest for current statin use. Our findings suggest that statin use may influence the development of CD.

11.
J Crohns Colitis ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245360

RESUMO

BACKGROUND/AIM: Patients with inflammatory bowel disease (IBD) have more work disability than the general population. We aimed to estimate the monetary cost of IBD for the individual through assessment of earnings in relation to diagnosis. METHODS: Through linkage of national registers we identified patients aged 30-55 years at first IBD diagnosis in Sweden 2002-2011, and same-sex IBD-free siblings. We estimated taxable earnings and disposable income from 5 years before to 5 years after diagnosis. RESULTS: The 5,961 patients (27% Crohn's disease, 68% ulcerative colitis, 4.3% IBD unclassified) had similar taxable earnings as their 7,810 siblings until the year of diagnosis, when earnings decreased and remained lower than in siblings during follow-up. The adjusted difference in earnings over the entire 5-year period after diagnosis was -5% (-8,212€; 95%CI: -11,458 to-4,967). The difference was larger in women than in men, and larger in Crohn's disease than in ulcerative colitis. When stratifying for sex and IBD subtype and comparing earnings during each year of follow-up, the median annual earnings were lower in women with Crohn's disease and ulcerative colitis than in their sisters during all years of follow-up, whereas the men had similar annual taxable earnings as their brothers. The disposable income was similar between patients and siblings during the investigated time period. CONCLUSION: From the year of diagnosis and at least 5 years onwards, patients with IBD had 5% lower earnings than siblings, mainly explained by differences between women with IBD and their sisters. However, there were no differences in disposable income.

12.
Clin Epidemiol ; 12: 1059-1072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116900

RESUMO

Background: The Swedish Quality Register for Inflammatory Bowel Disease (SWIBREG) contains clinical data for the study of inflammatory bowel disease (IBD). The Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort was recently established for the study of gastrointestinal histopathology. We aimed to develop and validate a histology score from ESPRESSO using clinical information from SWIBREG, and secondarily, to evaluate the association of the score on IBD-related hospitalization. Methods: In a nationwide, population-based cohort study of patients with IBD during 1969-2017, we linked endoscopic inflammation in SWIBREG with histologic inflammation in ESPRESSO. We established a clinically interpretable model for predicting the endoscopic score from histology using scalable Bayesian rule lists to define a SNOMED-based histology score applicable to the ESPRESSO cohort. We also assessed the impact of baseline endoscopic and histology scores on time to IBD-related hospitalization. Results: We identified 5225 individuals with IBD comprising 11,051 endoscopic assessments in SWIBREG linked to a histopathology record in ESPRESSO. We created predictive models to calculate a SNOMED-based histology score which predicted the endoscopic score. Split-sample validated areas under the ROC curves for the score predicting a non-zero endoscopic score were 0.80 (0.78-0.81) in UC, 0.70 (0.68-0.72) in CD, and 0.76 (0.73-0.78) in IBD-U. In a subset of 2741 individuals with an initial IBD diagnosis and a corresponding record in ESPRESSO with an endoscopic assessment in SWIBREG, the baseline endoscopic and histology scores were associated with time to IBD-related hospitalization (endoscopy log-rank UC p<0.001, CD p=0.020, IBD-U p<0.001; histology log-rank UC p=0.018, CD p=0.960, IBD-U p=0.034). Conclusion: Histopathology data in ESPRESSO accurately predict endoscopic scores in SWIBREG. Baseline endoscopic and histologic scores were associated with time to IBD-related hospitalization, particularly in UC. The SNOMED-based histology score can be used as a measure of disease activity in future register-based IBD studies.

14.
Aliment Pharmacol Ther ; 52(4): 655-668, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32902894

RESUMO

BACKGROUND: There are limited data on population-wide assessment of cost in Crohn's disease (CD) and ulcerative colitis (UC). AIM: To estimate the societal cost of actively treated CD and UC in Sweden. METHODS: We identified 10 117 prevalent CD and 19 762 prevalent UC patients, aged ≥18 years on 1 January 2014 and 4028 adult incident CD cases and 8659 adult incident UC cases (2010-2013) from Swedish Patient Register. Each case was matched to five population comparators. Healthcare costs were calculated from medications, outpatient visits, hospitalisations and surgery. Cost of productivity losses was derived from disability pension and sick leave. RESULTS: The mean annual societal costs per working-age patient (18-64 years) with CD and UC were $22 813 (vs $7533 per comparator) and $14 136 (vs $7351 per comparator), respectively. In patients aged ≥65 years, the mean annual costs of CD and UC were $9726 and $8072 vs $3875 and $4016 per comparator, respectively. The majority of cost for both CD (56%) and UC (59%) patients originated from productivity losses. Higher societal cost of working-age CD patients as compared to UC patients was related to greater utilisation of anti-TNF (22.2% vs 7.4%) and increased annual disability pension (44 days vs 25 days). Among incident CD and UC patients, the mean total cost over the first year per patient was over three times higher than comparators. CONCLUSION: In Sweden, the societal cost of incident and prevalent CD and UC patients was consistently two to three times higher than the general population.


Assuntos
Colite Ulcerativa , Doença de Crohn , Custos de Cuidados de Saúde , Recursos em Saúde , Licença Médica , Absenteísmo , Adolescente , Adulto , Colite Ulcerativa/economia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/terapia , Doença de Crohn/economia , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Licença Médica/economia , Licença Médica/estatística & dados numéricos , Suécia/epidemiologia , Fator de Necrose Tumoral alfa/uso terapêutico , Trabalho/economia , Trabalho/estatística & dados numéricos , Adulto Jovem
15.
Lancet Gastroenterol Hepatol ; 5(11): 986-995, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32818437

RESUMO

BACKGROUND: Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study. METHODS: In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD. FINDINGS: We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1·88 (95% CI 1·79-1·98) for diagnosis of incident IBD, 1·74 (1·64-1·85) for ulcerative colitis, and 2·27 (2·06-2·49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1·11, 1·07-1·15), two antibiotic dispensations (1·38, 1·32-1·44), and three or more antibiotic dispensations (1·55, 1·49-1·61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1·47, 95% CI 1·40-1·54) and Crohn's disease (1·64, 1·53-1·76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1·35 (95% CI 1·28-1·43) for patients who had received three or more dispensations, compared with general population controls. INTERPRETATION: Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD. FUNDING: National Institutes of Health. Crohn's and Colitis Foundation.


Assuntos
Antibacterianos , Disbiose , Doenças Inflamatórias Intestinais , Adolescente , Adulto , Idade de Início , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Biópsia/estatística & dados numéricos , Estudos de Casos e Controles , Sistemas de Informação em Farmácia Clínica/estatística & dados numéricos , Disbiose/induzido quimicamente , Disbiose/prevenção & controle , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Irmãos , Suécia/epidemiologia
17.
Gut ; 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474410

RESUMO

OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD). DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs). RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32). CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

18.
Aliment Pharmacol Ther ; 52(1): 143-154, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32412143

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of cancer. AIM: To assess the risk of pancreatic cancer in IBD compared to the general population. METHODS: Patients with incident IBD 1969-2017 were identified in Danish and Swedish National Patient Registers and through biopsy data, and were matched to IBD-free reference individuals by sex, age, place of residence and year of IBD diagnosis. We linked data to Cancer and Causes of Death Registers and examined the absolute and relative risks of pancreatic cancer and pancreatic cancer death. RESULTS: Among 161 926 patients followed for 2 000 951 person years, 442 (0.27%) were diagnosed with pancreatic cancer compared to 3386 (0.21%) of the 1 599 024 reference individuals. The 20-year cumulative incidence was 0.34% (95% confidence interval 0.30-0.38) vs 0.29% (0.28-0.30). The incidence rate was 22.1 (20.1-24.2)/100 000 person years in the patients (excluding the first year of follow-up: 20.8 [18.8-23.0]), and 16.6 (16.0-17.2) in the reference individuals. The hazard ratio (HR) for pancreatic cancer was increased overall: 1.43 (1.30-1.58), in subtypes (Crohn's disease: 1.44 [1.18-1.74]; ulcerative colitis: 1.35 [1.19-1.53]; IBD unclassified: 1.99 [1.50-2.64]) and especially in IBD patients with primary sclerosing cholangitis: 7.55 (4.94-11.5). Patients and reference individuals with pancreatic cancer did not differ in cancer stage (P = 0.17) or pancreatic cancer mortality (HR 1.07 [0.95-1.21]). CONCLUSIONS: Patients with IBD had an excess risk of pancreatic cancer, in particular patients with primary sclerosing cholangitis. However, the cumulative incidence difference after 20 years was small: 0.05%, that is, one extra pancreatic cancer per 2000 IBD patients.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Suécia/epidemiologia , Adulto Jovem
19.
Scand J Gastroenterol ; 55(4): 430-435, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32370571

RESUMO

Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown.Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals.Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis.Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.

20.
Aliment Pharmacol Ther ; 51(11): 1022-1030, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32319125

RESUMO

BACKGROUND: The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties. AIMS: To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC). METHODS: A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index. RESULTS: We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person-years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time-dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40-2.31) at year 5 and 1.49 (1.14-1.96) at year 10 post-vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94-6.80] for truncal and 2.06 [1.49-2.84] for selective vagotomy) but not UC (1.36 [0.71-2.62] for truncal and 1.25 [0.95-1.63] for selective vagotomy). CONCLUSIONS: We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.


Assuntos
Doenças Inflamatórias Intestinais/etiologia , Complicações Pós-Operatórias/etiologia , Vagotomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/etiologia , Doença de Crohn/epidemiologia , Doença de Crohn/etiologia , Feminino , Humanos , Incidência , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Vagotomia/estatística & dados numéricos
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