Association of Childhood Abuse with Incident Inflammatory Bowel Disease.

INTRODUCTION: A link between inflammatory bowel disease (IBD), stressful life events and psychological factors has previously been reported. Our objective was to examine the relationship between childhood emotional, physical, and sexual abuse and risk of IBD using a large cohort of female health professionals. METHODS: We included participants in the Nurses' Health Study II who completed the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale in 2001. Diagnosis of IBD was determined by self-report and confirmed independently by two physicians through review of medical records. We used Cox proportional hazard modeling to estimate the risk of Crohn's disease (CD) and ulcerative colitis (UC) while adjusting for covariates. RESULTS: Among 68,167 women followed from 1989 until 2017, there were 146 incident cases of CD and 215 incident cases of UC. Compared to women with no history of abuse, the adjusted hazard ratios of CD were 1.16 (95% CI 0.67 - 2.02) for mild, 1.58 (95% CI 0.92 - 2.69) for moderate, and 1.95 (95% CI 1.22 - 3.10) for severe abuse (Ptrend = 0.002). We did not observe an association between childhood abuse and risk of UC. CONCLUSIONS: Women who reported early life severe abuse had an increased risk of CD. These data add to the growing body of evidence on the critical role of early life stressors in development of CD.

Improving the Consent Process With an Informed Consent Video Prior to Outpatient Colonoscopy.

BACKGROUND AND AIMS: Informed consent should allow patients the appropriate time and conditions to make decisions about their care. However, consent is often obtained immediately prior to a colonoscopy. We conducted a quality improvement study to assess how a preprocedure consent video 2 days prior to an outpatient colonoscopy impacts patient satisfaction. METHODS: Patients undergoing outpatient colonoscopy at a large academic medical center opted in to a text messaging platform for procedural information. Our intervention was an informed consent video 2 days before the colonoscopy. Our primary outcome was a composite patient satisfaction score. Pre and postintervention scores were compared using ordinal or multinomial logistic models to calculate odds ratios (OR) or relative risk ratios and 95% confidence intervals (CI), adjusting for age and sex. RESULTS: 1109 and 1452 patients completed ≥1 survey question in the pre and postintervention phases, respectively. Overall patient satisfaction did not differ between groups [OR for a 1-point increment in satisfaction score between post- vs pre-intervention groups = 1.05; 95% CI: 0.90-1.22; P = .51]. Compared to preintervention, postintervention respondents were more likely to report higher satisfaction with time available to talk with their physician (OR of a 1-point increase in individual question response = 1.29; 95% CI: 1.09-1.54; P = .004). Compared to preintervention, more physicians in the postintervention phase rated satisfaction with consent process efficiency as "very satisfied" or "satisfied" (P < .001). CONCLUSION: An informed consent video prior to colonoscopy resulted in similar overall patient satisfaction. However, post-intervention, patients were more likely to report sufficient time to talk with their physician, and physicians reported higher satisfaction with consent efficiency.

Zn2+ is essential for Ca2+ oscillations in mouse eggs.

Changes in the intracellular concentration of free calcium (Ca2+) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca2+ release is periodical, known as Ca2+ oscillations, and mediated by the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). Another divalent cation, zinc (Zn2+), increases exponentially during oocyte maturation and is vital for meiotic transitions, arrests, and polyspermy prevention. It is unknown if these pivotal cations interplay during fertilization. Here, using mouse eggs, we showed that basal concentrations of labile Zn2+ are indispensable for sperm-initiated Ca2+ oscillations because Zn2+-deficient conditions induced by cell-permeable chelators abrogated Ca2+ responses evoked by fertilization and other physiological and pharmacological agonists. We also found that chemically or genetically generated eggs with lower levels of labile Zn2+ displayed reduced IP3R1 sensitivity and diminished ER Ca2+ leak despite the stable content of the stores and IP3R1 mass. Resupplying Zn2+ restarted Ca2+ oscillations, but excessive Zn2+ prevented and terminated them, hindering IP3R1 responsiveness. The findings suggest that a window of Zn2+ concentrations is required for Ca2+ responses and IP3R1 function in eggs, ensuring optimal response to fertilization and egg activation.

Periodontal disease is not associated with risk of inflammatory bowel disease: Results from two prospective cohort studies in the US.

AIM: To examine the relationship between periodontal disease and tooth loss and risk of inflammatory bowel disease (IBD). METHODS: We conducted a prospective cohort study of 86,602 women from the Nurses' Health Study (1992-2016) and 50,349 men from the Health Professionals Follow-up Study (1986-2016) with available data on periodontal disease and tooth loss. Cases of IBD were initially reported by participants and then confirmed by medical record review. We used Cox proportional hazards modelling to estimate multivariable-adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: Through the end of follow-up, we documented 175 cases of Crohn's disease (CD) and 209 cases of ulcerative colitis (UC). After adjustment for potential risk factors, there was no association between periodontal disease and risk of CD (pooled aHR: 0.99, 95% CI: 0.65-1.52, p = 0.970) or UC (aHR: 0.99, 95% CI: 0.68-1.45, p = 0.971). Similarly, we did not observe an association between tooth loss and risk of CD (aHR: 0.72, 95% CI: 0.43-1.21, p = 0.218) or UC (aHR: 0.89, 95% CI: 0.58-1.36, p = 0.581) in the pooled analysis. The associations were not modified by sex, age, body mass index (BMI), smoking status or NSAID use (all pinteraction > 0.87). CONCLUSION: In two large prospective cohort studies, we did not observe an association between periodontal disease and tooth loss and risk of CD or UC.

Zn2+ is Essential for Ca2+ Oscillations in Mouse Eggs.

Changes in the intracellular concentration of free calcium (Ca2+) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca2+ release is periodical, known as Ca2+ oscillations, and mediated by the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). Another divalent cation, zinc (Zn2+), increases exponentially during oocyte maturation and is vital for meiotic transitions, arrests, and polyspermy prevention. It is unknown if these pivotal cations interplay during fertilization. Here, using mouse eggs, we showed that basal concentrations of labile Zn2+ are indispensable for sperm-initiated Ca2+ oscillations because Zn2+-deficient conditions induced by cell-permeable chelators abrogated Ca2+ responses evoked by fertilization and other physiological and pharmacological agonists. We also found that chemically- or genetically generated eggs with lower levels of labile Zn2+ displayed reduced IP3R1 sensitivity and diminished ER Ca2+ leak despite the stable content of the stores and IP3R1 mass. Resupplying Zn2+ restarted Ca2+ oscillations, but excessive Zn2+ prevented and terminated them, hindering IP3R1 responsiveness. The findings suggest that a window of Zn2+ concentrations is required for Ca2+ responses and IP3R1 function in eggs, ensuring optimal response to fertilization and egg activation.

Association Between Opioid Use and Outpatient Visits for Dysphagia: An Analysis of the National Ambulatory Medical Care Survey in 2008-2018.

INTRODUCTION: Opioid-induced esophageal dysfunction has been described with characteristic manometric patterns, but the population burden of dysphagia attributable to opioid use remains unclear. METHODS: The National Ambulatory Medical Care Survey from 2008 to 2018 was used to assess the relationship between opioid use and outpatient visits for dysphagia. RESULTS: After controlling for potential confounders, there were no significant difference in ambulatory visits for dysphagia between opioid users and nonusers (adjusted odds ratio = 0.98, confidence interval: 0.59-1.65). DISCUSSION: No correlation between opioid use and ambulatory visits for dysphagia was found in a nationwide sample. Opioid-related manometric changes may be clinically relevant only in a small proportion of patients.

Diet Quality and Risk of Older-onset Crohn's Disease and Ulcerative Colitis.

BACKGROUND: We aimed to assess the relationship between diet quality and risk of older-onset Crohn's disease [CD] and ulcerative colitis [UC]. METHODS: We conducted a prospective cohort study of 83 147 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men. We used food frequency questionnaires to calculate adherence scores to multiple derived healthy diet patterns: Alternate Healthy Eating Index [AHEI], Healthy Eating Index-2015 [HEI-2015], Healthful Plant-Based Diet Index [HPDI], and modified Mediterranean Diet Score [mMED] at baseline in 1997 in both cohorts. Diagnoses of CD and UC were retrieved from the Swedish Patient Register. We used Cox proportional hazards modelling to estimate the adjusted hazard ratios [HRs] and 95% confidence intervals [CIs]. RESULTS: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC. Comparing the highest with the lowest quartiles, the adjusted HRs of CD were 0.73 [95% CI, 0.48, 1.12, ptrend = 0.123] for AHEI; 0.90 [0.57, 1.41, ptrend = 0.736] for HEI 2015; 0.52 [95% CI 0.32, 0.85, ptrend = 0.011] for HPDI; and 0.58 [95% CI 0.32, 1.06, ptrend = 0.044] for mMED. In contrast, we did not observe an association between any diet quality score and risk of UC. CONCLUSIONS: We found that several healthy eating patterns were associated with a lower risk of older-onset CD. Our findings provide a rationale for adapting different healthy dietary patterns based on individuals' food preferences and traditions in designing future prevention strategies for IBD.

Steroid Use and Risk of Nonalcoholic Fatty Liver Disease in Patients With Inflammatory Bowel Disease: Systematic Review and Meta-analysis.

GOALS: We sought to evaluate the association of steroids with nonalcoholic fatty liver disease (NAFLD) among patients with inflammatory bowel disease (IBD). BACKGROUND: Patients with IBD are at increased risk of NAFLD. Steroids may have a role in the pathogenesis of NAFLD. STUDY: We searched MEDLINE (through PubMed) and Embase for studies from inception to July 2021. We included published interventional and observational studies of adults 18 years or older with ulcerative colitis or Crohn's disease. We reported odds ratios, 95% confidence intervals, and generated forest plots. A random effects model generated a summary effect estimate. Publication bias was assessed by funnel plot and Egger's test. Study quality was examined using modified Newcastle-Ottawa scale (NOS) and Agency for Healthcare Research and Quality (AHRQ). RESULTS: A total of 12 observational studies with 3497 participants were included. NAFLD was identified in 1017 (29.1%) patients. The pooled odds ratio for the development of NAFLD in steroid users versus non-users was 0.87 (95% confidence interval: 0.72-1.04). There was no significant heterogeneity between studies ( I ²=0.00%, P =0.13). No publication bias was detected by funnel plot or Egger's test ( P =0.24). Findings were consistent among subgroup analyses stratified by study quality. CONCLUSION: In this meta-analysis, steroids were not associated with NAFLD in patients with IBD. Steroids may not need to be withheld from patients with IBD for the purposes of preventing NAFLD. Additional prospective studies that systematically document steroid exposure and important confounders among patients with IBD are warranted.

Endogenous Levels of Circulating Androgens Are Not Associated with Risk of Microscopic Colitis.

BACKGROUND: Microscopic colitis is a chronic inflammatory disease that most commonly affects post-menopausal women. Exogenous hormone use has recently been linked with increased risk of microscopic colitis. Yet, it is unclear whether levels of endogenous sex hormones are also associated with risk of microscopic colitis. AIM: To evaluate the association between prediagnostic plasma androgens and subsequent risk of microscopic colitis. METHODS: We conducted a case-control study nested within prospective cohort studies of the Nurses' Health Study (NHS) and NHSII. Cases of microscopic colitis were each matched to two controls according to age, cohort, menopause status, fasting status, and season of plasma collection. Prediagnosis plasma levels of androgens including dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of microscopic colitis using conditional logistic regression models. RESULTS: Our study included 96 cases of microscopic colitis matched to 190 controls. Plasma levels of testosterone were not associated with risk of microscopic colitis (Ptrend = 0.70). Compared to participants in the lowest quartile of plasma testosterone levels, the aOR of microscopic colitis for women in the highest quartile was 0.88, 95% CI 0.45-1.71. Similarly, we did not observe an association between dehydroepiandrosterone sulfate and sex hormone-binding globulin and risk of microscopic colitis (all Ptrend > 0.52). CONCLUSION: Among women, prediagnostic circulating levels of testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin are not associated with risk of microscopic colitis.

Smoking Behaviour Changes After Diagnosis of Inflammatory Bowel Disease and Risk of All-cause Mortality.

BACKGROUND AND AIMS: We examined smoking behaviour changes after diagnoses of Crohn's disease [CD] and ulcerative colitis [UC] and evaluated their impact on mortality. METHODS: Study population included incident CD or UC cases from three cohorts of the Nurses' Health Study [NHS], NHSII, and Health Professionals Follow-up Study. Smoking and other risk factors were prospectively assessed. Smoking behaviour changes were categorised as never, former [i.e., quit smoking before diagnosis], quitters [i.e., quit smoking after diagnosis], and current [i.e., continue smoking after diagnosis]. Follow-up for date and cause of death was completed through linkage to the National Death Index. Cox proportional hazard regression was used to estimate hazard ratios [HRs] and 95% confidence intervals [CIs]. RESULTS: Among 909 eligible CD and UC cases, 45% were never smokers, 38% were past smokers, and 16% were active smokers at the time of diagnosis. Among active smokers, 70% of patients with CD and 44% of patients with UC continued to smoke after diagnosis. In patients with CD, compared with current smokers, the multivariable-adjusted HRs [95% CI] of death were 0.19 [0.10 to 0.38] for never smokers, 0.31 [0.16 to 0.57] for former smokers, and 0.41 [0.18 to 0.93] for quitters. Similarly for UC, compared with current smokers, we observed a reduced risk of mortality for never smokers [HR = 0.23, 95% CI 0.10 to 0.51], former smokers [HR = 0.23, 95% CI 0.11 to 0.48], and quitters [HR = 0.28, 95% CI 0.11 to 0.72]. CONCLUSIONS: In three cohorts of health professionals, a substantial proportion of patients with new diagnosis of CD and UC and history of smoking continued to smoke after diagnosis. Smoking cessation around the time of diagnosis was associated with a significant reduction in mortality.

Risk Factors for Incident Inflammatory Bowel Disease According to Disease Phenotype.

BACKGROUND & AIMS: We examined whether relationships between known risk factors for Crohn's disease (CD) and ulcerative colitis (UC) differ according to disease phenotype, defined by Montreal classification, at the time of diagnosis. METHODS: We performed a prospective cohort study of 208,070 adults from the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS). Dietary, lifestyle, and medical data were obtained at baseline and every 2-4 years. We confirmed cases of inflammatory bowel disease (IBD) and their phenotypes via medical record review. We tested for heterogeneity across CD subtypes using the likelihood ratio test and for linear heterogeneity across UC subtypes using the meta-regression method. RESULTS: We ascertained 346 cases of CD and 456 cases of UC over 5,117,021 person-years of follow-up (1986-2016 for NHS and HPFS; 1991-2017 for NHSII). Fiber intake was associated with decreased risk for ileocolonic but not ileal or colonic CD (Pheterogeneity = .04). Physical activity was associated with decreased risk of nonstricturing and nonpenetrating CD but not of penetrating CD (Pheterogeneity = .02). Higher body mass index and current smoking were associated with decreased risk of proctitis and left-sided UC but not of pan-UC (Plinear heterogeneity= .004 and .02, respectively). The associations between other risk factors examined and risk of CD and UC did not differ by disease phenotype (all Pheterogeneity > .06). CONCLUSIONS: In 3 large prospective cohorts, we observed that dietary and lifestyle risk factors for IBD may differ according to disease phenotype. These findings highlight the need for disease stratification in future epidemiologic studies.

Alcohol consumption and risk of inflammatory bowel disease among three prospective US cohorts.

BACKGROUND AND AIMS: There are limited data on alcohol dose and types and risk of Crohn's Disease (CD) and Ulcerative Colitis (UC). We therefore sought to comprehensively examine the association between alcohol consumption and risk of CD and UC. METHODS: We conducted a prospective cohort study of 237,835 participants from the Nurses' Health Study, Nurses' Health Study II, and Health Professional Follow-Up Study. Alcohol consumption was obtained through questionnaires submitted every four years; additional covariates were obtained at two or four-year intervals. Cases were confirmed independently by two physicians through medical record review. We used Cox proportional hazards regression to estimate age and multivariable-adjusted hazards ratios and 95% confidence intervals. RESULTS: Across 5,170,474 person-years of follow-up, 370 cases of CD and 486 cases of UC were documented. Increased consumption of alcohol intake was not associated with CD (Ptrend = 0.455) or UC (Ptrend = 0.745). Compared to non-users, the MV-adjusted HRs for 15.0 + g/day of alcohol intake group were 0.84 (95% CI 0.56, 1.24) for CD and 1.08 (95% CI 0.77, 1.51) for UC. In analyses of alcohol subtypes, we observed that only moderate consumption of beer (>1-4 servings/week) was marginally associated with reduced risk of CD, while consumption of >4 servings/week of liquor was associated with an increased risk of UC. CONCLUSION: This prospective study did not identify a relationship between overall alcohol consumption and risk of CD or UC. Our suggestive associations between alcohol types and risk of CD and UC deserve additional investigation.

Lifestyle factors for the prevention of inflammatory bowel disease.

OBJECTIVE: To estimate the proportion of cases of Crohn's disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors. DESIGN: In a prospective cohort study of US adults from the Nurses' Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable risk scores (MRS; 0-6) for CD and UC based on established lifestyle risk factors, and healthy lifestyle scores (HLS; 0-9) derived from American healthy lifestyle recommendations. We calculated the population attributable risk by comparing the incidence of CD and UC between low-risk (CD-MRS≤1, UC-MRS≤2, HLS≥7) and high-risk groups. We externally validated our findings in three European cohorts: the Swedish Mammography Cohort (n=37 275), Cohort of Swedish Men (n=40 810) and European Prospective Investigation into Cancer and Nutrition (n=404 144). RESULTS: Over 5 117 021 person-years of follow-up (NHS, HPFS: 1986-2016; NHSII: 1991-2017), we documented 346 CD and 456 UC cases. Adherence to a low MRS could have prevented 42.9% (95% CI 12.2% to 66.1%) of CD and 44.4% (95% CI 9.0% to 69.8%) of UC cases. Similarly, adherence to a healthy lifestyle could have prevented 61.1% (95% CI 16.8% to 84.9%) of CD and 42.2% (95% CI 1.7% to 70.9%) of UC cases. In our validation cohorts, adherence to a low MRS and healthy lifestyle could have, respectively, prevented 43.9%-51.2% and 48.8%-60.4% of CD cases and 20.6%-27.8% and 46.8%-56.3% of UC cases. CONCLUSIONS: Across six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification.

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

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; Ptrend = .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.

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

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.