Higher Dietary Quercetin Intake Is Associated with Lower Risk of Adverse Outcomes among Individuals with Inflammatory Bowel Disease in a Prospective Cohort Study.

BACKGROUND: Cumulative preclinical evidence reported quercetin, a major flavonoid, can attenuate the disease activity of inflammatory bowel diseases (IBD). However, there is limited evidence that supports the benefits of quercetin for patients with IBD. OBJECTIVES: To investigate whether dietary quercetin intake is associated with adverse outcomes among individuals with IBD in a prospective cohort study. METHODS: We included 2293 participants with IBD (764 Crohn's disease [CD] and 1529 ulcerative colitis [UC]) from the UK Biobank. Dietary information was collected using validated 24-h dietary assessments, and quercetin intake was estimated based on national nutrient databases. Two outcomes, enterotomy and all-cause mortality, were obtained based on the national data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a mean (standard deviation) follow-up of 9.6 (1.8) y, we documented 193 enterotomy events and 176 deaths. Compared with participants with the lowest quartile intake of quercetin, those in the highest quartiles were associated with lower risk of enterotomy (HR: 0.46; 95% CI: 0.28, 0.76) and all-cause mortality (HR: 0.53; 95% CI: 0.33, 0.83) in IBD. The inverse associations between quercetin and enterotomy were consistent in CD (HR: 0.30; 95% CI: 0.12, 0.78) but not UC (HR: 0.58; 95% CI: 0.32, 1.07), while the inverse associations between quercetin and mortality were consistent both in CD (HR: 0.37; 95% CI: 0.15, 0.92) and UC (HR: 0.55; 95% CI: 0.31, 0.95). CONCLUSIONS: Higher dietary intake of quercetin was associated with lower risk of enterotomy and all-cause mortality in IBD. Our study provides novel evidence that further suggests the benefits of quercetin for patients with IBD, while also calling for further validation in other cohorts and clinical trials.

Sales of antibiotics without a prescription in pharmacies, 2017 and 2021, China.

Objective: To measure sales of antibiotics without a prescription in pharmacies in China in 2017 and 2021, before and during the coronavirus disease 2019 (COVID-19) pandemic, and determine the factors associated with such sales. Methods: We conducted cross-sectional surveys using the simulated patient method in retail pharmacies in 13 provinces in eastern, central and western China in 2017 and 2021. At the pharmacies, the simulated patients (trained medical students) reported that they had mild respiratory tract symptoms and asked for treatment, using a three-stage process: (i) request some treatment; (ii) request antibiotics; (iii) request specific antibiotics. We used multivariable logistic regression analysis to determine factors associated with sale of antibiotics without a prescription. Findings: Of the pharmacies visited in 2017, 83.6% (925/1106) sold antibiotics without a prescription; this figure was 78.3% (853/1090) in 2021 (P-value: 0.002). After excluding pharmacies prohibited from selling antibiotics because of COVID-19, this difference was not significant (83.6% versus 80.9%; 853/1054; P-value: 0.11). Factors significantly associated with selling antibiotics without a prescription in both 2017 and 2019 were: location in central and western China compared with eastern China; being in a township or village compared with in a city; and presence of a counter where antibiotics were dispensed. Conclusion: Although laws became stricter between 2017 and 2021, antibiotic sales without a prescription were still common in pharmacies across China. Existing regulations need to be more strictly enforced, and pharmacy staff and the public should be made more aware of the risks of antibiotic misuse and dangers of antimicrobial resistance.

Higher Fiber Intake is Associated with Reduced Risk of Related Surgery among Individuals with Inflammatory Bowel Disease in a Prospective Cohort Study.

BACKGROUND: Evidence for the effects of dietary fiber on adverse outcomes in individuals with inflammatory bowel disease (IBD) is insufficient and controversial. OBJECTIVES: We aimed to prospectively explore the association between dietary fiber intake and the risk of IBD-related surgery. METHODS: We identified 5580 individuals with diagnosed IBD [Crohn disease (CD, n = 1908) and ulcerative colitis (UC, n = 3672)] at baseline in the UK Biobank via electronic medical records and self-reported information. Dietary fiber intake was estimated by a partial fiber score derived from a valid food frequency questionnaire. IBD-related surgery (enterotomy, perianal surgery, and others) was ascertained via inpatient data. Cox proportional model was applied to estimate hazard ratios with 95% confidence intervals (CIs) of dietary fiber in quartiles for the risk of IBD-related surgery. RESULTS: During a mean follow-up period of 11.2 y, we documented 624 IBD-related surgery among 5580 individuals with IBD (mean age, 57.3; 52.8% females). Compared with individuals in the lowest quartiles, those with second to fourth quartiles of fiber intake were associated with 23% (95% CI: 5%, 38%, P = 0.015), 29% (95% CI: 11%, 43%, P = 0.003), and 28% (95% CI: 10%, 43%, P = 0.005) reduced risk (P-trend = 0.002) of IBD-related surgery. Similar associations were observed in CD (P-trend = 0.005) but not UC (P-trend = 0.131). We observed inverse associations of fiber in vegetables and fruits (P-trend = 0.017 and 0.007) but positive associations of fiber in bread (P-trend = 0.046) with the risk of IBD-related surgery. CONCLUSIONS: Higher intake of fiber is associated with reduced IBD-related surgery risk in patients with IBD with CD but not UC.

Higher Adherence to Cardioprotective Diet is Associated with Reduced Risk of Enterotomy and All-Cause Mortality among 5549 Individuals with Inflammatory Bowel Disease in a Prospective Cohort Study.

BACKGROUND: The cardioprotective diet has been previously reported to be inversely associated with the development of inflammatory bowel disease (IBD), but whether it is beneficial to improve adverse outcomes in IBD remains unknown. OBJECTIVES: We aimed to investigate whether the cardioprotective diet is associated with enterotomy and all-cause mortality among individuals with IBD. METHODS: We conducted a prospective cohort study of 5549 participants with IBD from the UK Biobank. Cardioprotective diet scores (range 0-7) were calculated based on the consumption of 7 common food groups collected by a validated food frequency questionnaire. Outcomes of interest were enterotomy and all-cause mortality, ascertained via inpatient data and death registry, respectively. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During an average follow-up duration of 12.0 y, we documented 506 enterotomy and 566 death events. Compared with participants with the lowest adherence to the cardioprotective diet (score of 0-2), participants with the highest adherence to the cardioprotective diet (score of 5-7) were observed to have a lower risk of enterotomy (HR: 0.60; 95% CI: 0.47, 0.76; P < 0.001; P-trend < 0.001) and all-cause mortality (HR: 0.77; 95% CI: 0.61, 0.98; P = 0.031; P-trend = 0.025). CONCLUSIONS: A greater adherence to the cardioprotective diet is associated with a lower risk of enterotomy and all-cause mortality among individuals with IBD.

Nonlinear Association between Serum 25-Hydroxyvitamin D and All-Cause Mortality in Adults with Inflammatory Bowel Disease in a Prospective Cohort Study.

BACKGROUND: Nonlinear association between serum 25-hydroxyvitamin D [25(OH)D] concentration and all-cause mortality has been widely reported for the general population, but this association has not been quantified for individuals with inflammatory bowel disease (IBD). OBJECTIVES: The aim was to explore the association between serum 25(OH)D and all-cause mortality in individuals with IBD. METHODS: We identified 2690 females and 2532 males aged 40-69 y with diagnosed IBD at baseline in the UK Biobank. Serum 25(OH)D concentration was measured by direct competitive chemiluminescent immunoassay. The outcome was all-cause mortality, ascertained via the death registry. Cox proportional hazard regression was used to evaluate associations between serum 25(OH)D in quintiles and all-cause mortality among individuals with IBD [Crohn disease (CD; n = 1760) and ulcerative colitis (UC; n = 3462)]. Restricted cubic splines were used to investigate potential nonlinearity. RESULTS: During the mean follow-up period of 11.9 y, 529 deaths (198 in CD and 331 in UC) were documented among 5222 individuals with IBD. Compared with the lowest quintile of serum 25(OH)D, HRs for the second to the highest quintiles were 0.82 (95% CI: 0.63, 1.06), 0.63 (95% CI: 0.47, 0.83), 0.64 (95% CI: 0.48, 0.85), and 0.74 (95% CI: 0.55, 0.99), respectively. Nonlinearity was detected in the dose-response association between serum 25(OH)D concentration and all-cause mortality (P-nonlinearity < 0.001), and 25(OH)D concentrations of 44-78 nmol/L were associated with a 50% lower risk of all-cause mortality (than 10 nmol/L). Subgroup analyses showed that the nonlinear association mostly applied to females (P-nonlinearity < 0.001 compared with 0.080 in males). CONCLUSIONS: We observed a nonlinear association, mostly applicable to females, between serum 25(OH)D concentrations and all-cause mortality among individuals with IBD. A 25(OH)D concentration range of 44-78 nmol/L can serve as a starting point for future research to confirm recommended 25(OH)D concentrations for individuals with IBD.

P003 Meat Consumption and All-Cause Mortality in 5763 Inflammatory Bowel Disease Patients: A Prospective Cohort Study.

BACKGROUND: Meat consumption was found to be associated with the incidence and developmental course of inflammatory bowel diseases (IBD), but its roles in the risk of all-cause mortality in IBD patients remained unknown. The aim of this study (UK Biobank Resource under application number 73595) was to assess the associations between meat consumption and all-cause mortality among IBD patients. METHODS: We leveraged data of 5763 IBD patients in the UK Biobank recruited from 2007 to 2010 and followed up to March 13, 2021. Dietary information was collected using a simplified food frequency questionnaire (FFQ) in the touchscreen questionnaire at baseline recruitment. Death events were ascertained from the death registry. Cox proportional hazards models were used to estimate potential associations of each meat consumption with mortality in IBD patients, 0.1-0.9 time per week was seen as the reference, and hazard ratios (HRs) and 95% confidence interval (CIs) were reported. Moreover, we conducted a series of subgroup and sensitivity analyses. RESULTS: During an average follow-up of 11.7 years, we documented 590 deaths over 67,095 person-years. Of the 5763 IBD patients with a mean (SD) age of 57.3 (7.9) years, 3028 (52.5%) were female and 2735 (47.5%) were male, 1834 were with Crohn's diseases (CD) and 3929 were with ulcerative colitis (UC). Consuming processed meat more than 4 times per week (>4 times/week) was associated with an increased risk of mortality in IBD patients (HR 1.53, 95%CI 1.06-2.23, P = 0.025) compared with consumption of less than once per week (0.1-0.9 time/week), while consumptions of fish, unprocessed poultry, or unprocessed red meat were not found to be related to mortality. The association of processed meat with mortality was also observed in CD patients (HR 2.01, 95%CI 1.12-3.62, P = 0.020), but not significantly in UC patients (HR 1.27, 95% CI 0.77-2.09, P = 0.346). In subgroup analyses, we also observed the associations in IBD patients with diseases duration more than 10 years (HR 1.67, 95%CI 1.03-2.69) or patients who had high physical activities (HR 2.21, 95%CI 1.13-4.33), but was not significant in other subgroup analyses, also, the associations manifested robust in sensitivity analyses. CONCLUSION: In this study, more frequent consumption of processed meat was found to be associated with the increased risk of mortality in IBD patients, while no such associations were observed in IBD patients who consuming fish, unprocessed poultry meat or unprocessed red meat. Therefore, based on the results above, we recommend a remodified diet with restricting processed meat as well as supplying an additional healthy diet for IBD patients, using alone or in combination with pharmacotherapy.

Dietary quercetin intake is associated with lower ulcerative colitis risk but not Crohn's disease in a prospective cohort study and in vivo experiments.

Objectives: Previous preclinical evidence indicates a protective role of quercetin against inflammatory bowel disease (IBD). However, there is no evidence from human populations, resulting in knowledge gaps regarding the role of quercetin in the IBD development. We aimed to prospectively evaluate the associations between dietary quercetin intake and IBD in humans and in vivo animal models. Methods: We included 187 709 IBD-free participants from the UK Biobank. Dietary information was collected using validated 24-hour dietary recalls and the quercetin intake was estimated based on national nutrient databases. Incident IBD was ascertained via inpatient and primary care data. Cox proportional hazard models were used to estimate the multi-variable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Experiments were conducted in two chemical-induced (dextran sulfate sodium salt and trinitro-benzene-sulfonic acid) mouse models orally pretreated with quercetin (CAS number: 117-39-5) solution to evaluate the effects of quercetin at physiological levels. Results: After a mean follow-up of 9.7 years, we documented 863 incident IBD. Compared to participants with the lowest quintile intake of quercetin, those in the highest quintiles were associated with a lower risk of IBD (aHR 0.76, 95% CI 0.60-0.95; P-trend = 0.004) and ulcerative colitis (aHR 0.69, 95% CI 0.53-0.91; P-trend = 0.001), but not Crohn's disease (aHR 0.95, 95% CI 0.62-1.45; P-trend = 0.765). Mouse models showed that pretreatment with quercetin could attenuate the chemically induced colitis. Conclusions: Higher quercetin intake was associated with a lower risk of IBD, especially UC. The protective role of quercetin is promising in humans and warrants further investigation into downstream mechanisms.

Associations between meat consumption and all-cause and cause-specific mortality in middle-aged and older adults with frailty.

OBJECTIVES: This study aimed to explore the associations between different types of meat consumption and mortality risk among people with frailty. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: We included 19,913 physically frail participants from the UK Biobank. MEASUREMENTS: We used the validated brief food frequency questionnaire (FFQ) to measure meat consumption. Baseline diet data from 2006 to 2010 were collected, and participants were followed up until March 23, 2021. Cox proportional hazards regression models were conducted to examine the associations of meat consumption with mortality risk. RESULTS: We identified 3,622 all-cause deaths, 1,453 cancer deaths, and 1,663 cardiovascular deaths during a median follow-up time of 11.2 years. Higher consumption of unprocessed poultry (per 25 g/day increment) was associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.75-0.88), cancer mortality (HR 0.84, 95% CI 0.74-0.96), and cardiovascular mortality (HR 0.72, 95% CI 0.63-0.81). Consumption of unprocessed red meat had a U-shaped relationship with mortality. Moderate consumption of unprocessed red meat 1.0-1.9 times/week was associated with a 14% (95% CI: 3 %-24%) lower risk of all-cause mortality than the lowest consumption frequency group (0-0.9 times/week). The hazard of cancer and CV mortality was also lower in the 1.0-1.9 times/week group, though the associations were not statistically significant. More frequent consumption of processed meat was associated with an increased risk of all-cause mortality (HR 1.20, 95% CI 1.07-1.34) and cardiovascular mortality (HR 1.20, 95% CI 1.02-1.42). Fish consumption was not associated with all types of mortality. CONCLUSIONS: Higher consumption of processed meat, not fish, was associated with increased all-cause and cardiovascular mortality. In contrast, higher consumption of unprocessed poultry and moderate consumption of unprocessed red meat was associated with reduced all-cause, cancer, and cardiovascular mortality. These findings warrant further investigation to establish optimal dietary patterns for frail individuals.

Digestive System Diseases, Genetic Risk, and Incident Dementia: A Prospective Cohort Study.

INTRODUCTION: Although digestive system disease affects gut microbiota and their metabolites associated with dementia risk, the association between digestive system diseases and incident dementia has not yet been established. METHODS: This cohort analysis included 458,181 participants free of baseline dementia in the UK Biobank (2006-2021). The associations of 14 digestive system diseases with dementia incidence were examined in 2022 using Cox proportional hazards regression models. Analyses were performed to differentiate the associations for early-onset (age <65 years) and late-onset (age ≥65 years) dementia. Interaction and stratification analyses were performed for polygenic risk score and APOE. RESULTS: During a median follow-up of 12.4 years, 6,415 incident dementia cases were diagnosed. Eleven digestive system diseases showed significant associations with an increased risk of dementia after controlling for covariates and multiple testing. Compared with hazard ratios for individuals without digestive system diseases, the hazard ratios of dementia increased from 1.15 (95% confidence interval=1.09, 1.23) for patients with intestinal diverticular disease to 2.31 (95% confidence interval=1.98, 2.70) for patients with cirrhosis. The associations were different between certain digestive system diseases and dementia by onset age. The associations appeared to be stronger for cirrhosis (Q=0.001), irritable bowel syndrome (Q<0.001), gastritis and duodenitis (Q=0.002), gastroesophageal reflux disease (Q<0.001), ulcerative colitis (Q=0.047), gallbladder disease (Q=0.012), and peptic ulcer (Q=0.030) with early-onset dementia. There were no interactions for polygenic risk score or APOE (p>0.05). CONCLUSIONS: These findings suggest an increased need for dementia prevention among patients with digestive system diseases.

Greater adherence to the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet is associated with lower risk of inflammatory bowel disease: a prospective cohort study.

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is emerging as a promising candidate for preventive measures against inflammatory bowel disease (IBD), though there is currently no direct evidence from population-based studies. This study aims to bridge the gap in understanding of the association of the MIND diet with IBD risk. Methods: We utilized data from 187 490 participants in the UK Biobank who provided dietary information and were free of IBD at baseline. Dietary information was obtained using a validated web-based 24-hour dietary recall questionnaire. A MIND diet score was evaluated based on the intake of ten beneficial and five unhealthy food groups and the scores were further grouped into tertiles. The outcome of interest was incident IBD, Crohn's disease (CD), and ulcerative colitis (UC). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models adjusted for demographic characteristics, lifestyle factors, cancer history, and other dietary factors. Mediation analyses were performed to evaluate the role of systemic inflammation and metabolic disorders represented by the integrated biomarkers in the MIND diet-IBD association. Results: After a mean follow-up of 10.7 years, we documented 825 incident IBD cases (250 CD and 575 UC). The average age of the participants was 56.2 years, of which 55.0% were females. We found that greater adherence to the MIND diet, represented by a higher diet score, was associated with a lower risk of IBD (HRcomparing extreme tertiles 0.74, 95% CI 0.62-0.90, p = 0.002; p for trend = 0.005), CD (HR 0.66, 95% CI 0.47-0.94, p = 0.022; p for trend = 0.023), and UC (HR 0.78, 95% CI 0.62-0.98, p = 0.031; p for trend = 0.022). The associations were partially mediated by metabolic and inflammation status (mediation proportion: 5.5-15.9%). Conclusion: We found higher adherence to the MIND diet was associated with a lower risk of IBD, and that inflammatory and metabolic conditions may play an important role in the underlying mechanistic pathways.

Risk of subsequent gastrointestinal disease assessed by skeletal muscle strength and mass in a prospective cohort study.

Skeletal muscle may mutually interact with gastrointestinal disease through metabolic homeostasis and nutritional status and therefore may be a marker for early risk detection. We conducted a prospective cohort analysis including 393,606 participants (mean age 56.0 years, 53.9% female) from the UK Biobank. The exposures were grip strength and skeletal muscle mass (SMM). The primary outcomes were 24 incident gastrointestinal diseases. During a mean follow-up of 12.1 years, we found that one sex-specific SD increase in grip strength and SMM were associated with reduced risk of 16 and 19 gastrointestinal diseases, respectively. For grip strength, the HRs ranged from 0.94 (for ulcerative colitis) to 0.80 (for liver cancers). For SMM, the HRs ranged from 0.92 (for colorectal cancer) to 0.51 (for non-alcoholic fatty liver disease). Our finding suggested that grip strength and SMM might be significant indicators for gastrointestinal diseases risk screen.

Risk Assessment for Gastrointestinal Diseases via Clinical Dimension and Genome-Wide Polygenic Risk Scores of Type 2 Diabetes: A Population-Based Cohort Study.

OBJECTIVE: We aimed to evaluate whether individuals with type 2 diabetes (T2D) were at higher risk of developing a wide range of gastrointestinal diseases based on a population-based cohort study. RESEARCH DESIGN AND METHODS: This study included 374,125 participants free of gastrointestinal disorders at baseline; of them, 19,719 (5.27%) with T2D were followed-up by linking to multiple medical records to record gastrointestinal disease diagnoses. Multivariable Cox models were used to estimate the hazard ratios (HRs) and CIs. Logistic models were used to examine the associations between polygenic risk scores (PRS) and clinical gastrointestinal phenotypes. RESULTS: During a median follow-up of 12.0 years, we observed the new onset of 15 gastrointestinal diseases. Compared with nondiabetes, participants with T2D had an increased risk of gastritis and duodenitis (HR 1.58, 95% CI 1.51-1.65), peptic ulcer (HR 1.56, 95% CI 1.43-1.71), diverticular disease (HR 1.19, 95% CI 1.14-1.24), pancreatitis (HR 1.45, 95% CI 1.24-1.71), nonalcoholic fatty liver disease (HR 2.46, 95% CI 2.25-2.69), liver cirrhosis (HR 2.92, 95% CI 2.58-3.30), biliary disease (HR 1.18, 95% CI 1.10-1.26), gastrointestinal tract cancers (HR 1.28, 95% CI 1.17-1.40), and hepatobiliary and pancreatic cancer (HR 2.32, 95% CI 2.01-2.67). Positive associations of PRS of T2D with gastritis, duodenitis, and nonalcoholic fatty liver disease were also observed. CONCLUSIONS: In this large cohort study, we found that T2D was associated with increased risks of a wide range of gastrointestinal outcomes. We suggest the importance of early detection and prevention of gastrointestinal disorders among patients with T2D.

Circulating 25-hydroxyvitamin D concentration can predict bowel resection risk among individuals with inflammatory bowel disease in a longitudinal cohort with 13 years of follow-up.

BACKGROUND: Although the beneficial properties of vitamin D in anti-inflammation and immunity-modulation are promising in the management of inflammatory bowel disease (IBD), data were limited for the critical IBD prognosis. The association between serum vitamin D levels and the risk of bowel resection in individuals with IBD remains largely unknown. MATERIALS AND METHODS: We performed a longitudinal cohort study among 5474 individuals with IBD in the UK Biobank. Serum 25-hydroxyvitamin D [25(OH)D] was measured using direct competitive chemiluminescent immunoassay. Bowel resection events were ascertained via national inpatient data. Multivariable-adjusted Cox proportional hazard regression was used to examine the association between serum 25(OH)D and bowel resection risk, presented with hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) was used to evaluate dose-response associations. RESULTS: During a mean follow-up of 13.1 years, we documented 513 incident bowel resection cases. Compared to participants with vitamin D deficiency, non-deficient participants showed a significantly reduced bowel resection risk in IBD (HR 0.72, 95% CI 0.59-0.87, P=0.001), Crohn's disease (CD, HR 0.74, 95% CI 0.56-0.98, P=0.038), and ulcerative colitis (UC, HR 0.73, 95% CI 0.57-0.95, P=0.020). When comparing extreme quintiles of 25(OH)D level, participants with IBD showed a 34% reduced risk of bowel resection (95% CI 11%-51%, P=0.007) and participants with UC showed a 46% reduced risk (95% CI 19%-64%, P=0.003), while this association was not significant in CD (HR 0.93, 95% CI 0.59-1.45, P=0.740). Linear dose-response associations were observed using the RCS curve (all P-nonlinearity>0.05). CONCLUSION: Increased serum level of 25(OH)D is independently associated with reduced bowel resection risk in IBD. This association was significant in UC but may not be stable in CD. Vitamin D deficiency is a risk factor for bowel resection in individuals with IBD, and may be an effective metric in predicting and risk-screening surgical events.

Serum 25-hydroxyvitamin D, type 2 diabetes, and liver-related outcomes: Secondary data analysis of a prospective recruited cohort.

BACKGROUND: The association of vitamin D deficiency, which is prevalent in type 2 diabetes mellitus (T2DM), with liver disease and related mortality has not been quantified. Our study aimed to (1) investigate whether there is a synergistic association of vitamin D deficiency and T2DM with liver-related outcomes and (2) explore whether high 25-hydroxyvitamin D [25(OH)D] concentrations are associated with a lower risk of liver-related outcomes in T2DM. METHOD: Leveraging the data from UK Biobank, we conducted 2 studies: study I assessed the joint associations of vitamin D deficiency [25(OH)D <50 nmol/L] and T2DM with liver-related outcomes among 439,276 participants, and study II explored the associations of vitamin D status with liver-related outcomes among 21,519 individuals with T2DM. Baseline T2DM was identified through medication, laboratory test, and electronic health-related records. Serum 25(OH)D was measured by direct competitive chemiluminescent immunoassay. Liver-related outcomes included 6 liver disease end points and mortality by overall liver disease, chronic liver disease, and severe liver disease. RESULTS: During an average follow-up duration of 11.6 years, we observed a significant positive additive interaction effect (all synergy index>1.0) of T2DM and vitamin D deficiency on the risk of liver-related outcomes. Compared with participants without either T2DM or vitamin D deficiency, the multivariable-adjusted HRs of overall liver diseases were 1.29 for participants without T2DM but with vitamin D deficiency, 1.73 for participants with T2DM but without vitamin D deficiency, and 2.19 for participants with both T2DM and vitamin D deficiency. In individuals with T2DM, we observed that participants without vitamin D deficiency were inversely associated with incident liver disease and related mortality (multivariable-adjusted HRs 0.41-0.81) when compared with individuals with vitamin D deficiency. CONCLUSIONS: There are positive synergistic associations of vitamin D deficiency and T2DM with liver-related outcomes. Inverse associations between serum 25(OH)D concentrations and liver-related outcomes were observed in individuals with T2DM.

Higher dietary fibre intake is associated with lower risk of inflammatory bowel disease: prospective cohort study.

BACKGROUND: Limited prospective studies that have examined the association of dietary fibre with IBD have provided inconsistent evidence. AIM: To examine any associations between dietary fibre intake and subsequent incidence of IBD, Crohn's disease (CD) and ulcerative colitis (UC) METHODS: We conducted a prospective cohort study of 470,669 participants from the UK Biobank and estimated dietary fibre intake from a valid food frequency questionnaire at baseline. Incident IBD was ascertained from primary care data and inpatient data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between dietary fibre intake and the risk of IBD, CD and UC. RESULTS: During an average follow-up of 12.1 years, we ascertained 1473 incident IBD cases, including 543 cases of CD and 939 cases of UC. Comparing the lowest quintiles, an inverse association was observed between dietary fibre intake and risk of IBD (HR 0.74, 95% CI 0.58-0.93, p = 0.011) and CD (HR 0.48, 95% CI 0.32-0.72, p < 0.001), but not UC (HR 0.92, 95% CI 0.69-1.24, p = 0.595). For specified sources, dietary fibre intake from fruit and bread decreased the risk of CD, while dietary fibre intake from cereal decreased the risk of UC. CONCLUSIONS: Higher consumption of dietary fibre was associated with a lower risk of IBD and CD, but not UC. Our findings support current recommendations to increase the intake of dietary fibre.

Associations of sugar-sweetened beverages, artificially sweetened beverages, and natural juices with cardiovascular disease and all-cause mortality in individuals with inflammatory bowel disease in a prospective cohort study.

Background: Beverage consumption was found to be associated with cardiovascular disease and mortality in the general population. However, it is unclear whether this association still exists in individuals with inflammatory bowel disease (IBD). Objectives: To investigate the associations of sugar-sweetened beverages, artificially sweetened beverages, and natural juices with cardiovascular disease and all-cause mortality among individuals with IBD. Design: Prospective cohort study. Methods: We included 1981 participants with IBD in the UK Biobank. Consumption of beverages was measured using a validated 24-h diet recall. Outcomes of interest were overall cardiovascular disease and all-cause mortality. Cox proportional hazard models were used to estimate the hazard ratios and 95% confidence intervals (CIs). Results: During a mean (SD) follow-up of 10.1 (1.7) years, we documented 205 cardiovascular events and 133 deaths. Compared to non-consumers, those consuming sugar-sweetened beverages more than 1 unit/day (reported in glasses/cans/250 ml/cartons) were associated with 64% (95% CI: 5-155, p = 0.030) and 97% (95% CI: 16-233, p = 0.012) increased risk of cardiovascular disease and all-cause mortality, respectively. We also observed a 78% (95% CI: 3-205, p = 0.038) increased risk of cardiovascular disease in participants who consumed artificially sweetened beverages more than 1 unit/day when compared with non-consumers. We did not observe significant associations between natural juice consumption and the two outcomes in IBD. Conclusion: Higher sugar- and artificially sweetened beverage consumption were associated with adverse cardiovascular and mortality outcomes in IBD. These exploratory results were consistent with the evidence in the general population and highlighted the importance of diet management in individuals with IBD.

Ambient Air Pollution and Risk of Enterotomy, Gastrointestinal Cancer, and All-Cause Mortality among 4,708 Individuals with Inflammatory Bowel Disease: A Prospective Cohort Study.

BACKGROUND: Previous studies indicated that air pollution plausibly increases the risk of adverse outcomes in inflammatory bowel disease (IBD) via proinflammatory mechanisms. However, there is scant epidemiological data and insufficient prospective evidence assessing associations between ambient air pollution and clinical outcomes of IBD. OBJECTIVES: We aimed to investigate the associations between ambient air pollution and clinical outcomes among individuals with IBD. METHODS: Leveraging data from the UK Biobank, we included 4,708 individuals with IBD recruited in the period 2006-2010 in this study. A land use regression model was used to assess annual mean concentrations of ambient air pollutants nitrogen including oxides (NOx), nitrogen dioxide (NO2), and particulate matter (PM) with aerodynamic diameter ≤10µm (PM10) and PM with aerodynamic diameter ≤2.5µm (PM2.5). Individuals with IBD were followed up for incident clinical outcomes of enterotomy, gastrointestinal cancer, and all-cause mortality, ascertained via death registry, inpatient, primary care, and cancer registry data. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the magnitude of the associations. RESULTS: During a mean follow-up of 12.0 y, 265 enterotomy events, 124 incident gastrointestinal cancer, and 420 death events were documented among individuals with IBD. We found that each interquartile range (IQR) increase in exposure to PM2.5 was associated with increased risk of enterotomy (HR=1.16; 95% CI: 1.00, 1.34, p=0.043), whereas an IQR increase in exposure to NOx (HR=1.10; 95% CI: 1.01, 1.20, p=0.016), NO2 (HR=1.16; 95% CI: 1.03, 1.29, p=0.010), PM10 (HR=1.15; 95% CI: 1.03, 1.30, p=0.015), and PM2.5 (HR=1.14; 95% CI: 1.02, 1.28, p=0.019) was associated with increased risk of all-cause mortality among individuals with IBD. We did not observe any significant associations between air pollutants and gastrointestinal cancer in the primary analyses. Consistent results were observed in subgroup and sensitivity analyses. CONCLUSIONS: Ambient pollution exposure was associated with an increased risk of enterotomy and all-cause mortality among individuals with IBD, highlighting the important role of environmental health in improving the prognosis of IBD. https://doi.org/10.1289/EHP12215.

Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn's disease but not Ulcerative Colitis: a prospective cohort study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently recognized as a condition featured with metabolic dysfunctions in liver. It has been supposed that MAFLD might contribute to the development of IBD, but evidence from prospective cohort studies is lacking and inconclusive. METHODS: A total of 221,546 females and 183,867 males from the UK Biobank cohort enrolled in 2006-2010 were included to examine whether MAFLD and liver function markers were related to incident IBD. MAFLD was identified based on hepatic steatosis defined by fatty liver index plus the prevalence of overweight, type 2 diabetes mellitus, or at least two metabolic abnormalities. Biomarker related to liver function (albumin [ALB], alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]; gamma-glutamyl transferase [GGT], total bilirubin [TB], total protein [TP]) was measured using colorimetric or enzymatic assays. The incidence of IBD was ascertained based on primary care and inpatient records. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for the magnitude of their associations. RESULTS: With a mean follow-up of 12.1 years, 2228 incident IBD cases were documented. We identified 150,385 individuals with MAFLD at baseline and 86% participants' circulating liver function markers were within the normal range. Participants with MAFLD were associated with a 12% (HR 1.12, 95% CI 1.03, 1.23, p = 0.012) increased risk of IBD compared with those without MAFLD at baseline; the association was stronger (p-Heterogeneity = 0.006) with Crohn's disease (HR 1.35, 95% CI 1.15, 1.59, p < 0.001) than ulcerative colitis (HR 1.03, 95% CI 0.93, 1.15, p = 0.57). As for the serum liver function markers, the HRs of IBD for per 1-SD increment in ALB, ALP, AST, and TB concentration were 0.86 (95% CI 0.83, 0.90, p < 0.001), 1.18 (95% CI 1.13, 1.24, p < 0.001), 0.95 (95% CI 0.91, 0.99, p = 0.027), 0.92 (95% CI 0.87, 0.96, p < 0.001), respectively. We did not observe significant associations of GGT and TP with IBD. CONCLUSIONS: Individuals with MAFLD were at increased risk of developing IBD, especially CD, but not UC. Circulating levels of liver function biomarkers as the surrogate indicators of MAFLD were also associated with IBD risk.

Meat consumption and all-cause mortality in 5763 patients with inflammatory bowel disease: A retrospective cohort study.

Background: Whether meat consumption is related to risk of mortality in patients with inflammatory bowel disease (IBD) remains poorly understood. Methods: In the UK Biobank, 5763 patients with IBD were recruited from 2007 to 2010 and finished a brief food frequency questionnaire at baseline. We followed them until March 13, 2021 to document all-cause death events. Cox proportional hazard models were used to estimate hazard ratios (HRs) for all-cause mortality associated with consumptions of fish, unprocessed poultry, unprocessed red meat, and processed meat among the patients. Findings: During 67,095 person-years (mean follow-up 11·7 years, mean age 57·3, 52·5% female), we documented 590 death events. Higher consumption of processed meat was associated with an increased risk of all-cause mortality in patients with IBD (HR comparing >4·0 with 0-0·9 time/week=1·52, 95% confidence interval (CI) 1·05-2·19), but the P-trend for each 25 g increment was 0·075. This association remained significant in patients with Crohn's disease (HR 1·77, 95% CI 1·01-3·10) but not in patients with ulcerative colitis (HR 1·34, 95% CI 0·82-2·20). Consumptions of fish (HR 1·27, 95% CI 0·84-1·91), unprocessed poultry (HR 0·59, 95% CI 0·28-1·21), or unprocessed red meat (HR 0·87, 95% CI 0·60-1·26) were not significantly associated with the mortality of patients with IBD. Interpretation: More frequent consumption of processed meat was associated with an increased risk of mortality in patients with IBD, while no associations were observed for consumption of other types of meat. Our exploratory and speculative findings should be cautiously interpreted and need further replication in other cohorts. Funding: The National Natural Science Foundation of China (81,970,494); Key Project of Research and Development Plan of Hunan Province (2019SK2041).

Effectiveness of Educational Interventions for Health Workers on Antibiotic Prescribing in Outpatient Settings in China: A Systematic Review and Meta-Analysis.

Educational interventions are considered an important component of antibiotic stewardship, but their effect has not been systematically evaluated in outpatient settings in China. This research aims to evaluate the effectiveness of educational interventions for health workers on antibiotic prescribing rates in Chinese outpatient settings. Eight databases were searched for relevant randomized clinical trials, non-randomized trials, controlled before-after studies and interrupted time-series studies from January 2001 to July 2021. A total of 16 studies were included in the systematic review and 12 in the meta-analysis. The results showed that educational interventions overall reduced the antibiotic prescription rate significantly (relative risk, RR 0.72, 95% confidence interval, CI 0.61 to 0.84). Subgroup analysis demonstrated that certain features of education interventions had a significant effect on antibiotic prescription rate reduction: (1) combined with compulsory administrative regulations (RR With: 0.65 vs. Without: 0.78); (2) combined with financial incentives (RR With: 0.51 vs. Without: 0.77). Educational interventions can also significantly reduce antibiotic injection rates (RR 0.83, 95% CI 0.74 to 0.94) and the inappropriate use of antibiotics (RR 0.61, 95% CI 0.51 to 0.73). The limited number of high-quality studies limits the validity and reliability of the results. More high-quality educational interventions targeting the reduction of antibiotic prescribing rates are needed.