Publications by authors named "Hamed Khalili"

145 Publications

Interventions to decrease unplanned healthcare utilization and improve quality of care in adults with IBD: A systematic review.

Clin Gastroenterol Hepatol 2021 Sep 2. Epub 2021 Sep 2.

Division of Gastroenterology, Massachusetts General Hospital, Harvard University.

Background And Aims: Inflammatory bowel disease (IBD) care and outcomes exhibit substantial variability, suggesting quality gaps. We aimed to identify interventions to narrow these gaps.

Methods: We performed a systematic review of Medline, Embase and Web of Science through May 2021 to find manuscripts and abstracts reporting quality improvement (QI) interventions in IBD. We included studies with interventions that addressed acute care utilization, vaccination, or Crohn's and Colitis Foundation quality indicators for care processes, including pre-therapy testing, tobacco cessation, colorectal cancer surveillance, C. difficile infection screening in flares, sigmoidoscopy in patients hospitalized with ulcerative colitis, and use of steroid-sparing therapy. The primary objective was to identify successful QI interventions. Risk of bias assessment was conducted using the Joanna Briggs Institute critical appraisal checklist.

Results: Twenty-three manuscripts and 23 meeting abstracts met inclusion criteria. Influenza and pneumococcal vaccination were the most studied indicators (24 references), followed by ER and/or hospital utilization, tobacco cessation, and pre-therapy testing (17, 11 and 10 references, respectively). Electronic medical record-based interventions were the most frequent, while other initiatives employed strategies that included changes to care structure or delivery, vaccination protocols, or physician and patient education. Successful interventions matched the complexity of the metric to the intervention including making changes to care structure or delivery, empowered non-physician staff, and utilized electronic medical record changes to prompt clinicians.

Conclusions: The quality of IBD care can be improved with diverse interventions that range from simple to complex. However, these interventions are not universally successful. Clinicians should emulate successful interventions and design new initiatives to narrow gaps in care quality.
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http://dx.doi.org/10.1016/j.cgh.2021.08.048DOI Listing
September 2021

Alcohol Consumption is Associated With An Increased Risk of Microscopic Colitis: Results From 2 Prospective US Cohort Studies.

Inflamm Bowel Dis 2021 Sep 2. Epub 2021 Sep 2.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Background: No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC.

Methods: We conducted a prospective cohort study of 209,902 participants (age range, 28.5-66.7 years) enrolled in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Results: Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (Ptrend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86-1.67) for consumers of 0.1-4.9 g/day of alcohol, 1.90 (95% CI, 1.34-2.71) for consumers of 5-14.9 g/day, and 2.31 (95% CI, 1.54-3.46) for consumers of ≥15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (Pheterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04-1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91-1.12) or liquor (aHR, 1.00; 95% CI, 0.92-1.09).

Conclusions: Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC.
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http://dx.doi.org/10.1093/ibd/izab220DOI Listing
September 2021

Ultra-processed Foods and Risk of Crohn's Disease and Ulcerative Colitis: A Prospective Cohort Study.

Clin Gastroenterol Hepatol 2021 Aug 28. Epub 2021 Aug 28.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

Background & Aims: The rising incidence of inflammatory bowel disease in regions undergoing Westernization has coincided with the increase in ultra-processed food (UPF) consumption over the past few decades. We aimed to examine the association between consumption of UPFs and the risk of Crohn's disease (CD) and ulcerative colitis (UC).

Methods: We performed a prospective cohort study of 3 nationwide cohorts of health professionals in the United States-the Nurses' Health Study (1986-2014), the Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2012). We employed Cox proportional hazards models with adjustment for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CD and UC according to self-reported consumption of UPFs.

Results: The study included 245,112 participants. Over 5,468,444 person-years of follow-up, we documented 369 incident cases of CD and 488 incident cases of UC. The median age at diagnosis was 56 years (range, 29-85 years). Compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (HR, 1.70; 95% CI, 1.23-2.35; P = .0008). Among different UPF subgroups, ultra-processed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies showed the strongest positive associations with CD risk (HR per 1 standard deviation increase in intake, 1.18 [95% CI, 1.07-1.29], 1.11 [95% CI, 1.01-1.22], and 1.14 [95% CI, 1.02-1.27], respectively). There was no consistent association between UPF intake and UC risk.

Conclusions: Higher UPF intake was associated with an increased risk of incident CD. Further studies are needed to identify specific contributory dietary components.
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http://dx.doi.org/10.1016/j.cgh.2021.08.031DOI Listing
August 2021

Diagnostic yield of endoscopy in irritable bowel syndrome: A nationwide prevalence study 1987-2016.

Eur J Intern Med 2021 Aug 19. Epub 2021 Aug 19.

Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, United States; Department of Paediatrics, Örebro University Hospital, Sweden. Electronic address:

Introduction: Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures. We examined the yield of colonoscopy and upper endoscopy in IBS for several organic diseases.

Methods: Matched population-based prevalence study in Sweden. We identified 21,944 participants diagnosed with IBS from 1987 to 2016 undergoing colonoscopy with a biopsy from all of Sweden's 28 pathology departments within 6 months of diagnosis. We compared prevalence of histopathology-proven diagnoses of inflammatory bowel disease (IBD), colorectal cancer, precancerous polyps, and microscopic colitis between patients recently diagnosed with IBS and matched controls without IBS (n = 81,101) undergoing colonoscopy. We also compared prevalence of celiac disease between patients diagnosed with IBS (n = 9,965) and matched controls (n = 45,584) undergoing upper endoscopy with biopsy. IBS patients were also compared to their siblings. Conditioned logistic regression estimated adjusted odds ratios (aORs).

Results: Biopsy-proven IBD was seen in 1.6% of IBS and in 5.9% of controls (aOR=0.21; 95%CI=0.19-0.24). The prevalence of precancerous polyps was 4.1% vs. 13.0% (aOR=0.28; 95%CI=0.26-0.30), colorectal cancer 0.8% vs. 6.3% (aOR=0.17; 95%CI=0.14-0.20) and celiac disease 1.9% vs. 3.4% (aOR=0.54; 95%CI=0.47-0.63). Conversely, the prevalence of microscopic colitis was 2.9% vs. 1.7% (aOR=1.77; 95%CI=1.61-1.95), with higher prevalence in older patients and patients with IBS with diarrhea. Yield of colonoscopy for precancerous polyps, colorectal cancer, and microscopic colitis increased by age. Our findings were consistent using unaffected siblings as the comparator group.

Discussion: The diagnostic yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS, though increases with age.
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http://dx.doi.org/10.1016/j.ejim.2021.08.001DOI Listing
August 2021

Multi-omics reveal microbial determinants impacting responses to biologic therapies in inflammatory bowel disease.

Cell Host Microbe 2021 Aug 22;29(8):1294-1304.e4. Epub 2021 Jul 22.

Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:

The intestinal microbiome is a key determinant of responses to biologic therapy in inflammatory bowel disease (IBD). However, diverse therapeutics and variable responses among IBD patients have posed challenges in predicting clinical therapeutic success. In this prospective study, we profiled baseline stool and blood in patients with moderate-to-severe Crohn's disease or ulcerative colitis initiating anti-cytokine therapy (anti-TNF or -IL12/23) or anti-integrin therapy. Patients were assessed at 14 weeks for clinical remission and 52 weeks for clinical and endoscopic remission. Baseline microbial richness indicated preferential responses to anti-cytokine therapy and correlated with the abundance of microbial species capable of 7α/β-dehydroxylation of primary to secondary bile acids. Serum signatures of immune proteins reflecting microbial diversity identified patients more likely to achieve remission with anti-cytokine therapy. Remission-associated multi-omic profiles were unique to each therapeutic class. These profiles may facilitate a priori determination of optimal therapeutics for patients and serve as targets for newer therapies.
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http://dx.doi.org/10.1016/j.chom.2021.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366279PMC
August 2021

Clinical Characteristics and Treatment Response in Microscopic Colitis Based on Age at Diagnosis: A Multicenter Retrospective Study.

Dig Dis Sci 2021 Jul 20. Epub 2021 Jul 20.

Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, MA, USA.

Background: Microscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce.

Aims: To compare clinical characteristics and treatment response by age at diagnosis.

Methods: This retrospective cohort study was performed at Mayo Clinic and Massachusetts General Hospital. Patients were chosen consecutively using established databases. Patients were 'younger' if age at diagnosis was ≤ 50 years and 'older' if age > 50 years. Treatment outcomes were captured for induction (12 ± 4 weeks), based on the total number of daily stools, and defined as remission (complete resolution), response (≥ 50% improvement), non-response (< 50% improvement), and intolerance. Patients were considered 'responders' if they had remission or response and 'non-responders' if they had non-response or intolerance.

Results: We included 295 patients (52 younger, 243 older). There were no differences in sex, race, MC subtype, and diarrhea severity between groups (all P > 0.05). Younger patients were more likely to have celiac disease (17.3% vs. 5.8%, P = 0.01), while older patients had higher BMI (mean 25.0 vs. 23.8 kg/m, P = 0.04) were more likely smokers (53.9% vs. 34.6%, P = 0.01) and use NSAIDs (48.6% vs. 15.4%, P < 0.01) and statins (22.6% vs. 3.8%, P < 0.01). Overall treatment response was highest for budesonide (88.3%) and did not differ when comparing older to younger patients (90.6% vs. 77.8%, P = 0.12) or by MC subtype (LC, 81.5% vs. CC, 92.9%, P = 0.07).

Conclusions: There are no significant differences in MC treatment response based on age or disease subtype. These findings support treating patients with MC based on symptom severity rather than age.
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http://dx.doi.org/10.1007/s10620-021-07162-4DOI Listing
July 2021

Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies.

Clin Gastroenterol Hepatol 2021 Jul 7. Epub 2021 Jul 7.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

Background And Aims: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC).

Methods: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs).

Results: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I = 0%) compared with normal BMI (18.5 to <25 kg/m). Each 5 kg/m increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I = 0%). Similarly, with each 5 kg/m increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I = 0%). No associations were observed between measures of obesity and risk of UC.

Conclusions: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.
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http://dx.doi.org/10.1016/j.cgh.2021.06.049DOI Listing
July 2021

Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality.

J Hepatol 2021 Jul 3. Epub 2021 Jul 3.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Orebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.

Background & Aims: Longitudinal data are scarce regarding the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD).

Methods: This nationwide, matched cohort study included all Swedish children and young adults (≤25 years) with biopsy-confirmed NAFLD (1966-2017; n = 718). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, and further categorized as simple steatosis or steatohepatitis (NASH). Patients with NAFLD were matched to ≤5 general population controls by age, sex, calendar year and county (n = 3,457). To account for shared genetic and early-life factors, we also matched patients with NAFLD to full-sibling comparators. Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% CIs.

Results: Over a median of 15.8 years, 59 patients with NAFLD died (5.5/1,000 person-years [PY]) compared to 36 population controls (0.7/1,000 PY; difference = 4.8/1,000 PY; multivariable aHR 5.88; 95% CI 3.77-9.17), corresponding to 1 additional death per 15 patients with NAFLD, followed for 20 years. The 20-year absolute risk of overall mortality was 7.7% among patients with NAFLD, and 1.1% among controls (difference = 6.6%; 95% CI 4.0-9.2). Findings persisted after excluding those who died within the first 6 months (aHR 4.65; 95% CI 2.92-7.42), and after using full-sibling comparators (aHR 11.72; 95% CI 3.18-43.23). Simple steatosis was associated with a 5.26-fold higher adjusted rate of mortality compared to controls (95% CI 3.05-9.07), and this was amplified with NASH (aHR 11.51, 95% CI 4.77-27.79). Most of the excess mortality was from cancer (1.67 vs. 0.07/1,000PY; aHR 15.60; 95% CI 4.97-48.93), liver disease (0.93 vs. 0.04/1,000PY; aHR 16.46; 95% CI 2.75-98.43) and cardiometabolic disease (1.12 vs. 0.14/1,000PY; aHR 4.32, 95% CI 1.73-10.79).

Conclusions: Swedish children and young adults with biopsy-confirmed NAFLD have significantly higher rates of overall, cancer-, liver- and cardiometabolic-specific mortality compared to matched general population controls.

Lay Summary: Currently, the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) is unknown. This nationwide cohort study compared the risk of all-cause and cause-specific mortality in pediatric and young adult patients in Sweden with biopsy-confirmed NAFLD to matched general population controls. We found that compared to controls, children and young adults with biopsy-confirmed NAFLD and NASH have significantly higher rates of overall, cancer-, liver- and cardiometabolic-specific mortality.
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http://dx.doi.org/10.1016/j.jhep.2021.06.034DOI Listing
July 2021

Microscopic colitis.

Nat Rev Dis Primers 2021 06 10;7(1):39. Epub 2021 Jun 10.

Gastroenterology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Microscopic colitis (MC) is an inflammatory disease of the large intestine associated with urgent watery diarrhoea. MC may occur in people of all ages, although the disease primarily affects older women. Once believed to be rare, MC is now known to be a common cause of chronic watery diarrhoea in high-income countries, affecting 1 in 115 women and 1 in 286 men during their lifetime in Swedish population-based estimates. An inappropriate immune response to disturbances in the gut microenvironment is implicated in the pathogenesis of MC. Evidence also supports an underlying genetic basis for disease. The diagnosis of MC relies on clinical symptoms and microscopic assessment of colonic biopsy samples. MC is categorized histologically into collagenous colitis, lymphocytic colitis and their incomplete forms. The mainstay of treatment includes the use of budesonide, with or without adjunctive therapies, and withdrawal of offending drugs. Emerging studies suggest a role for biologicals and immunosuppressive therapies for the management of budesonide-refractory or budesonide-dependent disease. MC can have a substantial negative effect on patient quality of life. The outlook for MC includes a better understanding of the immune response, genetics and the microbiome in disease pathogenesis along with progress in disease management through robust clinical trials.
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http://dx.doi.org/10.1038/s41572-021-00273-2DOI Listing
June 2021

Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study.

Hepatology 2021 Apr 3. Epub 2021 Apr 3.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Background And Aims: Recent studies link NAFLD to an increased incidence of HCC and extrahepatic cancers. However, earlier studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity.

Approach And Results: We conducted a population-based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N = 8,892). NAFLD was defined from prospectively recorded liver histopathology submitted to all 28 Swedish pathology departments and categorized as simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis. NAFLD patients were individually matched to ≤5 general population controls without NAFLD by age, sex, calendar year, and county (N = 39,907). Using Cox proportional hazards modeling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs. Over a median of 13.8 years, we documented 1,691 incident cancers among NAFLD patients and 6,733 among controls. Compared with controls, NAFLD patients had significantly increased overall cancer incidence (10.9 vs. 13.8 per 1,000 person-years [PYs]; difference = 2.9 per 1,000 PYs; aHR, 1.27 [95% CI, 1.18-1.36]), driven primarily by HCC (difference = 1.1 per 1,000 PYs; aHR, 17.08 [95% CI, 11.56-25.25]). HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; P  < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively). In contrast, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma (differences = 0.2 per 1,000 PYs, 0.1 per 1,000 PYs, and 0.2 per 1,000 PYs, respectively), but no other cancers.

Conclusions: Compared with controls, patients with biopsy-proven NAFLD had significantly increased cancer incidence, attributable primarily to HCC, whereas the contribution of extrahepatic cancers was modest. Although HCC risk was highest with cirrhosis, substantial excess risk was also found with noncirrhotic fibrosis and comorbid diabetes.
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http://dx.doi.org/10.1002/hep.31845DOI Listing
April 2021

Dietary Gluten Intake Is Not Associated With Risk of Inflammatory Bowel Disease in US Adults Without Celiac Disease.

Clin Gastroenterol Hepatol 2021 Mar 26. Epub 2021 Mar 26.

Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Clinical and Translation Epidemiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts. Electronic address:

Background & Aims: Diet is thought to play a role in the development of inflammatory bowel disease (IBD), although the relationship between gluten intake and risk of IBD has not been explored. The aim of this study was to determine the relationship between gluten intake and risk of incident Crohn's disease (CD) and ulcerative colitis (UC).

Methods: We performed a prospective cohort study of 208,280 US participants from the Nurses' Health Study (1986-2016), Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2016) who did not have IBD at baseline or celiac disease, and who completed semiquantitative food frequency questionnaires. We used Cox proportional hazards modeling to estimate the risk of IBD according to quintiles of cumulative average energy-adjusted dietary gluten intake over the follow-up period.

Results: We documented 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up evaluation. Dietary gluten intake was not associated with risk of IBD. Compared with participants in the lowest quintile of gluten intake, the adjusted hazard ratios and 95% CIs for participants in the highest quintile of gluten intake were 1.16 (95% CI, 0.82-1.64; P = .41) for CD and 1.04 (95% CI, 0.75-1.44; P = .64) for UC. Adjusting for primary sources of gluten intake did not materially change our estimates.

Conclusions: In 3 large adult US prospective cohorts, gluten intake was not associated with risk of CD or UC. Our findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.
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http://dx.doi.org/10.1016/j.cgh.2021.03.029DOI Listing
March 2021

Association Between Microscopic Colitis and Parkinson's Disease in a Swedish Population.

Mov Disord 2021 08 25;36(8):1919-1926. Epub 2021 Mar 25.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Gastrointestinal inflammation has been linked with Parkinson's disease (PD). Microscopic colitis (MC) is an intestinal inflammatory disease with unknown relationship with PD.

Objective: This study aimed to examine the association of MC with PD risk.

Methods: In this nationwide matched cohort study in Sweden, PD incidence was compared between 12,609 patients with histologically confirmed MC and a matched population cohort of 58,879 MC-free individuals and a sibling cohort comprising all unaffected siblings of the MC patients (N /N  = 6281/12,351). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models.

Results: During a mean follow-up of ~7 years, we identified 449 incident PD diagnoses among the MC patients and the population cohort. Overall, MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up. In the time-varying effects model, PD hazard was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals but was not different beyond 5 years after biopsy (HR: 1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted when comparing MC patients to their siblings. In a post hoc case-control analysis, we also detected a strong association between MC and preexisting PD (odds ratio: 3.46; 95% CI: 2.91, 4.12).

Conclusions: Our findings suggest that MC may not be a risk factor for PD; instead, it may co-occur with PD as a comorbidity or develop after a diagnosis of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28594DOI Listing
August 2021

Inflammatory bowel disease and risk of severe COVID-19: A nationwide population-based cohort study in Sweden.

United European Gastroenterol J 2021 03 11;9(2):177-192. Epub 2021 Mar 11.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Background: There are concerns that individuals with chronic immune-mediated diseases are at increased risk of COVID-19 and related severe adverse outcome, including intensive care admission or death. We aimed to explore the absolute and relative risk of severe COVID-19 in inflammatory bowel disease (IBD).

Methods: This population-based cohort study used nationwide registers in Sweden, with 67,292 individuals with a diagnosis of IBD 1969-2017 (Crohn's disease, n = 21,599; ulcerative colitis: n = 43,622; IBD-unclassified: n = 2071) and alive on 1 February 2020. Patients with IBD were matched to up to five controls from the general population (n = 297,910). Cox regression estimated hazard ratios (HRs) for (i) hospital admission with laboratory-confirmed COVID-19 as the primary diagnosis, and (ii) severe COVID-19 (composite outcome consisting of (a) COVID-19 intensive care admission, or (b) death from COVID-19 or (c) death within 30 days of COVID-19 hospital admission), were calculated. Analyses were conditioned on age, sex, calendar period, and county and adjusted for other comorbidities.

Results: Between 1 February and 31 July 2020, 179 (0.27%) IBD patients and 500 (0.17%) general population controls were admitted to hospital with COVID-19 (adjusted HR [aHR] = 1.43; 95% CI = 1.19-1.72). The corresponding numbers for severe COVID-19 was 65 (0.10%) and 183 (0.06%; aHR = 1.11; 95% CI = 0.81-1.52). Adjusted HRs were similar in Crohn's disease and ulcerative colitis. In a propensity score-matched model taking comorbidity into account until 2016, the increased risk for COVID-19 hospital admission remained (aHR = 1.32; 1.12-1.56), but there was no increased risk of severe COVID-19 (aHR = 1.12; 0.85-1.47).

Conclusions: While individuals with IBD were more likely to be admitted to hospital for COVID-19 than the general population, the risk of severe COVID-19 was not higher.
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http://dx.doi.org/10.1002/ueg2.12049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014882PMC
March 2021

Association Between Collagenous and Lymphocytic Colitis and Risk of Severe Coronavirus Disease 2019.

Gastroenterology 2021 06 19;160(7):2585-2587.e3. Epub 2021 Feb 19.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2021.02.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892313PMC
June 2021

P044 Designing Interventions to Elevate the Quality of IBD Care: A Systematic Review of Quality Improvement Initiatives.

Am J Gastroenterol 2020 Dec;115(Suppl 1):S12

Division of Gastroenterology and Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard University, Boston, United States.

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http://dx.doi.org/10.14309/01.ajg.0000722972.32480.f7DOI Listing
December 2020

Statin Use and Risk of Inflammatory Bowel Diseases: Authors' Reply.

J Crohns Colitis 2021 08;15(8):1403-1404

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1093/ecco-jcc/jjab015DOI Listing
August 2021

Gastrointestinal Infection and Risk of Microscopic Colitis: A Nationwide Case-Control Study in Sweden.

Gastroenterology 2021 04 6;160(5):1599-1607.e5. Epub 2021 Jan 6.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Orebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York.

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%, P < .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; P = .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).
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http://dx.doi.org/10.1053/j.gastro.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035297PMC
April 2021

Immune-mediated diseases and risk of Crohn's disease or ulcerative colitis: a prospective cohort study.

Aliment Pharmacol Ther 2021 03 5;53(5):598-607. Epub 2020 Dec 5.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

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 (P  < 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 (P 0.16) (P 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.
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http://dx.doi.org/10.1111/apt.16210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082435PMC
March 2021

Association Between Statin Use and Inflammatory Bowel Diseases: Results from a Swedish, Nationwide, Population-based Case-control Study.

J Crohns Colitis 2021 May;15(5):757-765

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

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 = 7637] or ulcerative colitis [UC, n = 15 652] from 2006 to 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 with no statin use, any statin use was associated with a lower risk of CD (OR = 0.71; 95% confidence interval [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 of UC. The association with CD risk appeared strongest for current statin use. Our findings suggest that statin use may influence the development of CD.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247597PMC
May 2021

Immunosuppressive Therapy and Risk of COVID-19 Infection in Patients With Inflammatory Bowel Diseases.

Inflamm Bowel Dis 2021 01;27(2):155-161

Crohn's and Colitis Center, Massachusetts General Hospital, Boston, MA.

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.
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http://dx.doi.org/10.1093/ibd/izaa278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665507PMC
January 2021

Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort.

Gut 2021 Jul 9;70(7):1375-1382. Epub 2020 Oct 9.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Stockholm County, Sweden

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)(p <0.01). This dose-dependent gradient was similar when simple steatosis was the reference (p <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.
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http://dx.doi.org/10.1136/gutjnl-2020-322786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185553PMC
July 2021

Healthcare use, work loss and total costs in incident and prevalent Crohn's disease and ulcerative colitis: results from a nationwide study in Sweden.

Aliment Pharmacol Ther 2020 08 3;52(4):655-668. Epub 2020 Jul 3.

Stockholm, Sweden.

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.
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http://dx.doi.org/10.1111/apt.15889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490827PMC
August 2020

Opioid Use Among Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Clin Gastroenterol Hepatol 2021 05 21;19(5):895-907.e4. Epub 2020 Aug 21.

Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts; Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden. Electronic address:

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 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.
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http://dx.doi.org/10.1016/j.cgh.2020.08.041DOI Listing
May 2021

Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden.

Lancet Gastroenterol Hepatol 2020 11 17;5(11):986-995. Epub 2020 Aug 17.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/S2468-1253(20)30267-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034612PMC
November 2020

Effect of Low-dose and Standard-dose Aspirin on PGE Biosynthesis Among Individuals with Colorectal Adenomas: A Randomized Clinical Trial.

Cancer Prev Res (Phila) 2020 10 27;13(10):877-888. Epub 2020 Jul 27.

Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.

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 PGE, 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 ( = 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 ( = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; = 0.018) or 325 mg/day (-28%; < 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.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541643PMC
October 2020

Microscopic colitis and risk of cancer - a population-based cohort study.

J Crohns Colitis 2020 Jul 25. Epub 2020 Jul 25.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa156DOI Listing
July 2020

Fruit and vegetable consumption is associated with lower prevalence of asymptomatic diverticulosis: a cross-sectional colonoscopy-based study.

BMC Gastroenterol 2020 Jul 11;20(1):221. Epub 2020 Jul 11.

Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.

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 (P = 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 P > 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.
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http://dx.doi.org/10.1186/s12876-020-01374-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353809PMC
July 2020

Assessment of Body Weight Changes in Patients with Inflammatory Bowel Diseases Initiating Biologic Therapy: A Prospective Cohort Study.

Dig Dis Sci 2020 12 2;65(12):3672-3678. Epub 2020 Jul 2.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

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.
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http://dx.doi.org/10.1007/s10620-020-06442-9DOI Listing
December 2020

Acid-suppressive medications and risk of colorectal cancer: results from three large prospective cohort studies.

Br J Cancer 2020 09 16;123(5):844-851. Epub 2020 Jun 16.

Dana-Farber Cancer Institute, Boston, MA, USA.

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.
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http://dx.doi.org/10.1038/s41416-020-0939-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462971PMC
September 2020

Dietary Inflammatory Potential and Risk of Crohn's Disease and Ulcerative Colitis.

Gastroenterology 2020 09 7;159(3):873-883.e1. Epub 2020 May 7.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address:

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; P = .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 (P = .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.
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http://dx.doi.org/10.1053/j.gastro.2020.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502466PMC
September 2020
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