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3.
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).

4.
Artigo em Inglês | MEDLINE | ID: mdl-33280139

RESUMO

BACKGROUND: Although immune-mediated diseases (IMDs) including inflammatory bowel diseases (IBDs) are known to cluster, to what extent this is due to common environmental influences is unknown. AIM: To examine the incidence of IBD in individuals with another IMD. METHODS: We used data from the prospective Nurses' Health Study II cohort (1995-2017) to examine the effect of diagnoses of several common IMDs on subsequent risk of Crohn's disease (CD) or ulcerative colitis (UC) using Cox proportional hazards models, adjusting for detailed diet and lifestyle confounders. RESULTS: We documented 132 cases of CD and 186 cases of UC over 2 016 163 person-years of follow-up (median age at IBD diagnosis 50 years). Compared to participants with no history of IMD, the HRs of CD for those with 1 and ≥ 2 IMDs were 2.57 (95% CI 1.77-3.74) and 2.74 (95% CI 1.36 to 5.49), respectively (Ptrend  < 0.0001). This association was only modestly attenuated by adjustment for environmental risk factors (HR 2.35 and 2.46, respectively). The risk of UC was not increased, with multivariable-adjusted HRs of 1.22 (95% CI 0.85-1.76) and 1.33 (95% CI 0.67-2.65) for those with 1 and ≥ 2 IMDs, respectively, compared to those with none (Ptrend 0.16) (Pheterogeneity comparing CD and UC 0.037). Asthma, atopic dermatitis, psoriasis and rosacea were individually associated with higher risk of CD (HR ranging from 2.15 to 3.39) but not UC. CONCLUSIONS: Individuals with one or more IMDs are at an increased risk for CD but not UC.

5.
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.

6.
Inflamm Bowel Dis ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089863

RESUMO

BACKGROUND: The effect of immunosuppressive treatment for immune-mediated diseases on risk of the novel coronavirus disease 2019 (COVID-19) has not been established. We aimed to define the effect of targeted biologic and immunomodulator therapy on risk of COVID-19 in a multi-institutional cohort of patients with inflammatory bowel disease (IBD). METHODS: We identified patients 18 years and older who received care for IBD at Partners Healthcare between January 2019 and April 2020. The primary outcome was development of COVID-19 defined as a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2. Multivariable regression models were used to examine the effect of immunosuppression on risk of COVID-19 and its outcomes. RESULTS: In a cohort of 5302 IBD patients, 39 (0.7%) developed COVID-19. There was no difference in age, sex, or race between IBD patients with and without COVID-19. The rate of COVID-19 was similar between patients treated with immunosuppression (0.8%) compared with those who were not (0.64%; P = 0.55). After adjusting for age, sex, race, and comorbidities, use of immunosuppressive therapy was not associated with an increased risk of COVID-19 (odds ratio, 1.73; 95% confidence interval, 0.82-3.63). The presence of obesity was associated with a higher risk of COVID-19 (odds ratio, 8.29; 95% confidence interval, 3.72-18.47). There were 7 hospitalizations, 3 intensive care unit stays, and 1 death. Older age and obesity but not immunosuppressive treatment were associated with severe COVID-19 infection. CONCLUSIONS: The use of systemic immunosuppression was not associated with an increased risk of COVID-19 in a multi-institutional cohort of patients with IBD.

7.
Gut ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037056

RESUMO

OBJECTIVE: Population-based data are lacking regarding the risk of overall and cause-specific mortality across the complete histological spectrum of non-alcoholic fatty liver disease (NAFLD). DESIGN: This nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD (1966 to 2017; n=10 568). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, after excluding other etiologies of liver disease, and further categorised as, simple steatosis, non-fibrotic steatohepatitis (NASH), non-cirrhotic fibrosis and cirrhosis. NAFLD cases were matched to ≤5 general population comparators by age, sex, calendar year and county (n=49 925). Using Cox regression, we estimated multivariable-adjusted HRs (aHRs) and 95% CIs. RESULTS: Over a median of 14.2 years, 4,338 NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (16.9 vs 28.6/1000 PY; difference=11.7/1000 PY; aHR=1.93, 95% CI=1.86 to 2.00). Compared with controls, significant excess mortality risk was observed with simple steatosis (8.3/1000 PY, aHR=1.71, 95% CI=1.64 to 1.79), non-fibrotic NASH (13.4/1000 PY, aHR=2.14, 95% CI=1.93 to 2.38), non-cirrhotic fibrosis (18.4/1000 PY, aHR=2.44, 95% CI=2.22 to 2.69) and cirrhosis (53.6/1000 PY, aHR=3.79, 95% CI=3.34 to 4.30)(ptrend <0.01). This dose-dependent gradient was similar when simple steatosis was the reference (ptrend <0.01). The excess mortality associated with NAFLD was primarily from extrahepatic cancer (4.5/1000 PY, aHR=2.16, 95% CI=2.03 to 2.30), followed by cirrhosis (2.7/1000 PY, aHR=18.15, 95% CI=14.78 to 22.30), cardiovascular disease (1.4/1000 PY, aHR=1.35, 95% CI=1.26 to 1.44) and hepatocellular carcinoma (HCC) (1.2/1000 PY, aHR=11.12, 95% CI=8.65 to 14.30). CONCLUSION: All NAFLD histological stages were associated with significantly increased overall mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.

8.
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
9.
Artigo em Inglês | MEDLINE | ID: mdl-32835841

RESUMO

BACKGROUND AND AIMS: Despite reported adverse effects of opioids in patients with inflammatory bowel disease (IBD), the burden of opioid use in this population appears to be high. We performed a systematic review and meta-analysis of prior studies to determine the prevalence of opioid use among patients with IBD as well as risk factors and outcomes associated with opioid use in this population. METHODS: We conducted a systematic search of the MEDLINE, Embase, Web of Science, and the Cochrane Library through November of 2019. Primary outcomes included the prevalence of opioid use and demographic and clinical variables associated with opioid use in patients with IBD. Quality was assessed using the Newcastle-Ottawa scale. We used random-effect meta-analysis to estimate pooled relative risks (RRs) and 95% CIs. RESULTS: Of 780 citations identified, 31 were included in our study. The prevalence of opioid use was 21% (95% CI, 13%-30%) in the outpatient setting. Likewise, 62% (95% CI, 25%-92%) of patients received opioids while hospitalized for IBD. Opioid use was associated with female sex (RR 1.20; 95% CI 1.03-1.40), depression (1.99; 95% CI 1.80-2.19), substance abuse (4.67; 95% CI 2.87-7.60), prior gastrointestinal surgery (2.33; 95% CI 1.66-3.26), biologic use (1.36; 95% CI 1.06-1.74), and steroid use (1.41; 95% CI 1.04-1.91). Based on the systematic review, opioid use also appeared to be associated with increased IBD activity, healthcare use, infection, and mortality. CONCLUSION: In a systematic review and meta-analysis, we found that 21% of outpatients with IBD (and 62% of hospitalized patients) are opioid users; use is associated with more severe IBD and increased healthcare use. Further studies are required to determine whether opioids are the cause or an effect of these associations. Nonetheless, urgent interventions are needed to reduce opioid use, improve disease-related outcomes and reduce healthcare costs.

10.
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
11.
Cancer Prev Res (Phila) ; 13(10): 877-888, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32718943

RESUMO

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8-12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (-4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; P = 0.018) or 325 mg/day (-28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

12.
BMC Gastroenterol ; 20(1): 221, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32652931

RESUMO

BACKGROUND: Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis. METHODS: Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDER), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: Among 549 participants with a mean age of 61 years enrolled in GIDER, we confirmed diverticulosis in 245 (44.6%). The prevalence of diverticulosis appeared to decrease with higher consumption of fruit and vegetables (Ptrend = 0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60-1.17) with five to seven servings per week and 0.62 (95% CI, 0.44-0.89) with greater than one serving per day. Similarly, compared to participants with less than five servings per week of fruit, the multivariable-adjusted PR of diverticulosis was 0.60 (95% CI, 0.41-0.87) with greater than one serving per day. These associations were not modified by age, BMI, smoking, or red meat intake (All Pinteraction > 0.055). CONCLUSION: In a colonoscopy-based longitudinal cohort study, we show that higher consumption of fruit and vegetables is associated with lower risk of prevalent diverticulosis.

13.
Dig Dis Sci ; 65(12): 3672-3678, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32617768

RESUMO

BACKGROUND: Prior studies have inconsistently suggested that biologic therapy may be associated with weight gain in inflammatory bowel disease patients (IBD). Our aim was to compare weight gain across different biologic therapy classes with distinct mechanisms of action. METHODS: This prospective cohort study recruited patients with moderate to severe IBD initiating outpatient biologic therapy with anti-TNF (infliximab, adalimumab), vedolizumab, or ustekinumab. Weight measurements were performed at weeks 0, 14, 30, and 54. Changes in weight between baseline and each of the follow-up visits were modeled as a continuous variable, and multivariate regression assessed the independent effect of therapeutic class on this outcome. RESULTS: Our study enrolled 269 patients (163 CD, 106 UC) initiating biologic therapy [99 anti-TNF (37%), 122 vedolizumab (45%), 48 ustekinumab (18%)]. From baseline, the weight significantly increased at week 14 with a mean of 0.36 kg (± 3.8 kg, p = 0.004) and continued to increase compared to baseline with 0.96 kg (± 3.9 kg, p < 0.001) and 1.29 kg (± 4.2 kg, p < 0.001) at week 30 and 54, respectively. On univariate and multivariable analysis, no significant differences between any of the biologic therapies for weight gain were seen at any time point (weight gain anti-TNF: 0.31 kg, 1.06 kg, 1.33 kg; VDZ: 0.30 kg, 0.83 kg, 1.10 kg; UST: 0.63 kg, 1.21 kg, 2.31 kg at wk 14, wk 30, and wk 54, respectively). None of the disease activity parameters showed any statistical association with weight gain. CONCLUSION: There was no difference in weight gain among the different biologic therapeutic classes.

14.
J Crohns Colitis ; 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32710780

RESUMO

BACKGROUND AND AIMS: The association between microscopic colitis (MC) and cancer risk is unclear. Large, population-based studies are lacking. METHODS: We conducted a nationwide cohort study of 11,758 patients with incident MC (diagnosed 1990-2016 in Sweden), 50,828 matched reference individuals and 11,614 siblings to MC patients. Data were obtained through Sweden´s pathology departments and from the Swedish Cancer Register. Adjusted hazard ratios (aHRs) were calculated using Cox proportional hazards models. RESULTS: At the end of follow up (mean: 6.7 years), 1,239 (10.5%) of MC patients had received a cancer diagnosis, compared to 4,815 (9.5%) of reference individuals (aHR 1.08 (95%CI=1.02-1.16)). The risk of cancer was highest during the first year of follow up. The absolute excess risks for cancer at 5, 10 and 20 years after MC diagnosis were +1.0% (95%CI=0.4%-1.6%), +1.5% (0.4%-2.6%) and +3.7% (-2.3-9.6%), respectively, equivalent to one extra cancer event in every 55 individuals with MC followed for ten years.MC was associated with an increased risk of lymphoma (aHR 1.43, 1.06-1.92) and lung cancer (aHR 1.32, 1.04-1.68) but with decreased risks of colorectal (aHR 0.52, 0.40-0.66) and gastrointestinal cancers (aHR 0.72, 0.60-0.85). We found no association with breast or bladder cancer. Using siblings as reference group to minimize the impact of shared genetic and early environmental factors, patients with MC were still at an increased risk of cancer (HR=1.20; 95%CI=1.06-1.36). CONCLUSIONS: This nationwide cohort study demonstrated an 8% increased risk of cancer in MC patients. The risk was highest during the first year of follow up.

15.
Br J Cancer ; 123(5): 844-851, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32541871

RESUMO

BACKGROUND: Despite several plausible biological mechanisms linking proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) with colorectal tumorigenesis, their association with risk of colorectal cancer (CRC) has not been adequately assessed in prospective epidemiological studies. METHODS: We evaluated the association of acid-suppressive medication use with CRC risk among 175,871 (PPI) and 208,831 (H2RA) participants from three large prospective cohort studies. Medication use was assessed at baseline and updated biennially. The association was evaluated using multivariate Cox proportional hazards regression models. RESULTS: There was no significant association between baseline PPI use (hazard ratio (HR) = 0.89, 95% confidence interval (CI), 0.71-1.12) or PPI use after a lag of 8-10 years (HR = 1.12, 95% CI, 0.78-1.59) with CRC risk. We observed no significant association between H2RA use after a lag of 8-10 years and CRC risk (HR = 1.02, 95% CI, 0.81-1.28), while risk was lower for participants with baseline H2RA use (HR = 0.76, 95% CI, 0.60-0.95). Duration of PPI use or H2RA use was not associated with CRC risk (P-trend = 0.21 and 0.95, respectively). CONCLUSIONS: Among participants from three large prospective cohorts, use of PPI or H2RA was not associated with higher risk of colorectal cancer.

16.
Gastroenterology ; 159(3): 873-883.e1, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32389666

RESUMO

BACKGROUND & AIMS: Inflammation is a potential mechanism through which diet modulates the onset of inflammatory bowel disease. We analyzed data from 3 large prospective cohorts to determine the effects of dietary inflammatory potential on the risk of developing Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We collected data from 166,903 women and 41,931 men in the Nurses' Health Study (1984-2014), Nurses' Health Study II (1991-2015), and Health Professionals Follow-up Study (1986-2012). Empirical dietary inflammatory pattern (EDIP) scores were calculated based on the weighted sums of 18 food groups obtained via food frequency questionnaires. Self-reported CD and UC were confirmed by medical record review. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 328 cases of CD and 428 cases of UC over 4,949,938 person-years of follow-up. The median age at IBD diagnosis was 55 years (range 29-85 years). Compared with participants in the lowest quartile of cumulative average EDIP score, those in the highest quartile (highest dietary inflammatory potential) had a 51% higher risk of CD (HR 1.51; 95% CI 1.10-2.07; Ptrend = .01). Compared with participants with persistently low EDIP scores (at 2 time points, separated by 8 years), those with a shift from a low to high inflammatory potential of diet or persistently consumed a proinflammatory diet had greater risk of CD (HR 2.05; 95% CI 1.10-3.79 and HR 1.77; 95% CI 1.10-2.84). In contrast, dietary inflammatory potential was not associated with the risk of developing UC (Ptrend = .62). CONCLUSIONS: In an analysis of 3 large prospective cohorts, we found dietary patterns with high inflammatory potential to be associated with increased risk of CD but not UC.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32142939

RESUMO

BACKGROUND & AIMS: It is not clear whether a healthy lifestyle affects mortality of patients with inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We collected data form the Nurses' Health Study (1986-2014), Nurses' Health Study II (1991-2015), and Health Professionals Follow-up Study (1986-2014), which assess lifestyles with serial questionnaires. We estimated joint and individual associations between 5 healthy lifestyle factors after IBD diagnosis (never smoking, body mass index 18.5-24.9 kg/m2, vigorous physical activity in the highest 50% with non-zero value, alternate Mediterranean diet score ≥4, and light drinking [0.1-5.0 g/d]) and mortality using Cox proportional hazards models. RESULTS: We documented 83 deaths in 363 patients with CD during 4741 person-years and 80 deaths in 465 patients with UC during 6061 person-years. The median age of IBD diagnosis was 55 y. Compared to patients with IBD with no healthy lifestyle factors, patients with IBD with 3-5 healthy lifestyle factors had a significant reduction in all-cause mortality (hazard ratio [HR], 0.29; 95% CI, 0.16-0.52; Ptrend < .0001). This reduction was significant in patients with CD (Ptrend = .003) as well as in patients with UC (Ptrend = .0003). Individual associations were more than 25 pack-years (HR, 1.92; 95% CI, 1.24-2.97; Ptrend < .0001), physical activity (HR according to quintiles, 0.55-0.31; Ptrend = .001), Mediterranean diet (HR, 0.69; 95% CI, 0.49-0.98), and alcohol consumption (HR0.1-5 g/d 0.61; 95% CI, 0.39-0.95 vs HR>15 g/d 1.84; 95% CI, 1.02-3.32). The findings did not change when we adjusted for family history of IBD, immunomodulator use, and IBD-related surgery. CONCLUSIONS: In an analysis of data from 3 large cohort studies, we associated adherence to a healthy lifestyle with reduced mortality in patients with CD or UC.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32184182

RESUMO

BACKGROUND & AIMS: Fatigue is frequent and disabling in patients with inflammatory bowel diseases (IBD) but its mechanisms are poorly understood. We investigated alterations in fecal microbiomes and serum metabolomes and proteomes in patients with quiescent IBD, with vs without fatigue. METHODS: We performed a prospective observational study of patients (44% women; mean age, 39.8 y) with clinically and endoscopically quiescent Crohn's disease (n = 106) or ulcerative colitis (n = 60) at a tertiary hospital, from March 2016 through December 2018. Fatigue was assessed using the functional assessment of chronic illness therapy-fatigue scoring system and defined as a score of 43 or less. We performed metabolomic analysis of serum samples using liquid chromatography-mass spectrometry methods and proteomic analysis using multiplex proximity extension assay (PEA) technology. Stool samples were obtained from 50 patients and analyzed by shotgun metagenomic sequencing on Illumina HiSeq platform. RESULTS: Of the 166 study participants, 91 (55%) were fatigued. Serum samples from patients with fatigue (n = 59) did not have significant increases in levels of inflammatory cytokines compared with serum samples from nonfatigued patients (n = 72). We found a statistically significant difference in a cluster of 18 serum metabolites between patients with fatigue (n = 84) vs without fatigue (n = 72) (P = .033); serum samples from patients with fatigue had significant reductions in levels of methionine (P = .020), tryptophan (P = .042), proline (P = .017), and sarcosine (P = .047). Fecal samples from patients with fatigue had a less diverse gut microbiome, with significant reductions in butyrate-producing bacteria, including Faecalibacterium prausnitzii (P = .0002, q =.007) and Roseburia hominis (P = .0079, q = 0.105). This fatigue-like microbiome was associated with fatigue scales and correlated with progressive depletion of metabolites from serum samples. CONCLUSIONS: In an analysis of fecal and serum samples from 166 patients with IBD, we found alterations in serum metabolites and fecal microbes that were associated with fatigue.

19.
Clin Epidemiol ; 12: 273-285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210631

RESUMO

Purpose: Patients with Crohn's disease have increased work loss. We aimed to describe changes in work ability in relation to pharmacological and surgical treatments. Patients and Methods: We linked data from the Swedish National Patient Register, The Swedish Quality Register for Inflammatory Bowel Disease SWIBREG, The Prescribed Drug Register, The Longitudinal Integrated Database for Health Insurance and Labour Market Studies, and the Social Insurance Database. We identified working-age (19-59 years) patients with incident Crohn's disease 2006-2013 and population comparator subjects matched by sex, birth year, region, and education level. We assessed the number of lost workdays due to sick leave and disability pension before and after treatments. Results: Of 3956 patients (median age 34 years, 51% women), 39% were treated with aminosalicylates, 52% with immunomodulators, 22% with TNF inhibitors, and 18% with intestinal surgery during a median follow-up of 5.3 years. Most patients had no work loss during the study period (median=0 days). For all treatments, the mean number of lost workdays increased during the months before treatment initiation, peaked during the first month of treatment and decreased thereafter, and was heavily influenced by sociodemographic factors and amount of work loss before first Crohn's disease diagnosis. The mean increase in work loss days compared to pre-therapeutic level was ~3 days during the first month of treatment for all pharmacological therapies and 11 days for intestinal surgery. Three months after treatment initiation, 88% of patients treated surgically and 90-92% of patients treated pharmacologically had the same amount of work loss as before treatment start. Median time to return to work was 2 months for all treatments. Conclusion: In this regular clinical setting, patients treated surgically had more lost workdays than patients treated pharmacologically, but return to work was similar between all treatments.

20.
Am J Gastroenterol ; 115(5): 746-755, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32108661

RESUMO

INTRODUCTION: Mortality concern is a frequent driver of care seeking in patients with irritable bowel syndrome (IBS). Data on mortality in IBS are scarce, and population-based studies have been limited in size. We examined mortality in IBS. METHODS: A nationwide, matched, population-based cohort study was conducted in Sweden. We identified 45,524 patients undergoing a colorectal biopsy at any of Sweden's 28 pathology departments and with a diagnosis of IBS from 2002 to 2016 according to the National Patient Register, a nationwide registry of inpatient and outpatient specialty care. We compared the mortality risk between these individuals with IBS and age- and sex-matched reference individuals (n = 217,316) from the general population and siblings (n = 53,228). In separate analyses, we examined the role of mucosal appearance for mortality in IBS. Finally, we examined mortality in 41,427 patients with IBS not undergoing a colorectal biopsy. Cox regression estimated hazard ratios (HRs) for death. RESULTS: During follow-up, there were 3,290 deaths in individuals with IBS (9.4/1,000 person-years) compared with 13,255 deaths in reference individuals (7.9/1,000 person-years), resulting in an HR of 1.10 (95% confidence interval [CI] = 1.05-1.14). After adjustment for confounders, IBS was not linked to mortality (HR = 0.96; 95% CI = 0.92-1.00). The risk estimates were neutral when patients with IBS were compared with their siblings. The underlying mucosal appearance on biopsy had only a marginal impact on mortality, and patients with IBS not undergoing a colorectal biopsy were at no increased risk of death (HR = 1.02; 95% CI = 0.99-1.06). DISCUSSION: IBS does not seem to confer an increased risk of death.


Assuntos
Síndrome do Intestino Irritável/mortalidade , Medição de Risco/métodos , Adulto , Biópsia , Causas de Morte/tendências , Feminino , Seguimentos , Humanos , Síndrome do Intestino Irritável/diagnóstico , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Suécia/epidemiologia
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