The Role of Diet in Inflammatory Bowel Disease Onset, Disease Management, and Surgical Optimization.

The concept of using diet as therapy in inflammatory bowel disease is of interest to clinicians and patients. Once considered to play a minor role, diet is now known to not only affect disease onset but may also serve as a therapeutic tool for inducing and maintaining remission and improving surgical outcomes. Further research is needed to fully elucidate how, when, and in whom diet therapies may be best applied to improve clinical and disease outcomes. The aim of this review was to summarize current research findings and serve as a tool to help facilitate patient-clinician conversations.

Immunosuppression regimen and latitude impact keratinocyte carcinoma risk in U.S. liver transplant recipients.

Immunosuppression after solid organ transplantation is associated with an increased risk of keratinocyte carcinoma (KC). Despite its established morbidity, KC risk in liver transplant (LT) recipients is understudied, including the contribution of immunosuppression regimen and latitude. A retrospective cohort of 9,966 adult first LT alone recipients alive with their native allograft at 1-year post-LT without prior KC between 2007 and 2016 were identified using linked data from the Organ Procurement and Transplantation Network and Medicare administrative claims. The primary exposures were immunosuppression regimen and latitude of residence. The primary outcome was incident, de novo KC occurring at least 1-year after LT. Adjusted Cox regression analysis stratified by transplant center was used in all analyses. The cohort was 63.4% male, 70.2% White and with median age 61 years (interquartile range, IQR, 54-66) at transplant. Calcineurin inhibitor (CNI) with anti-metabolite combination was independently associated with incident KC when measured as intention-to-treat (adjusted hazard ratio (aHR) 1.21 vs. CNI monotherapy, 95% CI 1.02-1.43, p = 0.026), in a time-updating as-treated analysis (aHR 1.61, 95% CI 1.34-1.93; p < 0.001) and when measured as cumulative exposure (aHR 1.13 per 6-month increase, 95% CI: 1.02-1.33; p = 0.027). More southern latitude of residence was also independently associated with incident KC with an aHR of 1.26 per 5°N decrease towards the Equator (95% CI: 1.08-1.47, p = 0.003). We demonstrate independent effects of CNI with antiM immunosuppression regimen and latitude of residence on the risk of post-LT KC, which will better inform screening practices and immunosuppression management.

Hospital readmission for acute kidney injury is independently associated with de novo end-stage renal disease after liver transplantation.

End-stage renal disease (ESRD) after liver transplantation (LT) is associated with high morbidity and mortality. The consequences of hospitalizations for post-LT acute kidney injury (AKI) are poorly understood. Using linked Medicare claims and transplant registry data, we analyzed adult liver alone recipients not receiving pre-transplant dialysis between 1/1/2007-12/31/2016. Covariate-adjusted Cox proportional hazards models stratified by center evaluated factors associated with AKI readmission during the first post-LT year, and whether AKI readmission was associated with de novo early (<1 y) or late (≥1 y) ESRD post-LT. The cohort included 10,559 patients and was 64.5% male, 72.5% White, 8.1% Black and 14.0% Hispanic with median age 62 years. Overall, 2,875 (27.2%) patients had ≥1 AKI hospitalization during the first year. eGFR at LT was associated with AKI readmission (aHR 1.16 per 10 mL/min/1.73m2 decrease; p<0.001). The aHR for early ESRD in patients with ≥1 AKI readmission <90 days post-LT was 1.90 (p<0.001). The aHRs for late ESRD with 1 and ≥2 prior AKI readmissions were 1.57 and 2.80 respectively (p<0.001). AKI readmissions in the first post-LT year impact over one-quarter of recipients. These increase the risk of subsequent ESRD, but may represent an opportunity to intervene and mitigate further renal dysfunction.

Travel Time to Treating Center is Associated With Diagnostic Delay in Pediatric Inflammatory Bowel Disease.

BACKGROUND & AIMS: Delayed diagnosis of inflammatory bowel disease (IBD) leads to prolonged symptoms and worse long-term outcomes. We sought to evaluate whether race, ethnicity, disease type, and social factors are associated with delayed diagnosis of pediatric IBD. METHODS: We performed a cross-sectional study of newly diagnosed pediatric patients with IBD at 22 United States sites from 2019 to 2022. Parents/guardians reported race, ethnicity, time between symptom onset and diagnosis, and other social determinants of health. Through bivariate and multivariable analyses using generalized estimating equations, we evaluated associations between these factors and diagnosis time defined as ≤60 days, 61 to 180 days, 181 to 365 days, and >365 days. RESULTS: We enrolled 869 participants (mean age at diagnosis, 13.1 years; 52% male; 57% Crohn's disease [CD]; 34% ulcerative colitis [UC]; 8% Hispanic; 30% non-White). Overall, the mean time to diagnosis was 265.9 days. After adjustment, factors associated with longer diagnosis time included CD vs UC (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.9-3.5), 2 or more other health conditions (OR, 1.7; 95% CI, 1.1-2.7), and longer travel time to clinic (>1 hour [OR, 1.7; 95% CI, 1.2-2.4], >2 hours (OR, 1.8; 95% CI, 1.2-2.9] each vs <30 minutes). There was no association with race, ethnicity, birth country, sex, parent education, household income, insurance type, health literacy, and health system distrust. CONCLUSIONS: Consistent with prior literature, diagnostic delay is longer for CD than UC. Reassuringly, time to diagnosis is equitable across racioethnic groups. New models of diagnostic care are needed for communities affected by longer travel times.

Meta-analysis of the Therapeutic Impact of Cannabinoids in Inflammatory Bowel Disease.

BACKGROUND: With the increasing legalization of medical and recreational cannabis, patients and providers have growing interest in the role of cannabinoids in treating inflammatory bowel disease. Prior meta-analysis has shown inconclusive evidence for efficacy of cannabinoids. We sought to produce an up-to-date meta-analysis that pools new data to evaluate the therapeutic effects of cannabinoids in both Crohn's disease (CD) and ulcerative colitis (UC). METHODS: PubMed, Embase, CENTRAL and CINAHL were queried for randomized-controlled trials evaluating the impact cannabinoids in CD or UC. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. RESULTS: Eight studies, including 4 studies of CD, 3 studies of UC, and 1 study of both diseases met inclusion criteria. Among 5 studies of CD, a statistically significant decrease in clinical disease activity following intervention was observed (risk ratios [RR],  -0.91; 95% CI, CI:1.54 to CI:0.28, I2 = 71.9%). Clinical disease activity in UC was not significantly lower in the pooled analysis (RR, -2.13; 95% CI, -4.80 to 0.55; I2 = 90.3%). Improvement in quality of life (QoL) was observed in both CD and UC combined (RR, 1.79; 95% CI, 0.92-0.2.66; I2 = 82.8%), as well as individually. No differences were observed in the analysis on endoscopic disease activity and inflammatory markers. CONCLUSIONS: This meta-analysis of clinical trials suggests that cannabinoids are associated with improved quality of life in both CD and UC, as well as improved disease activity but not inflammation.

This updated systematic review and meta-analysis suggests that cannabis for inflammatory bowel disease may improve quality of life and disease activity but not inflammation.

Association of fatigue with disease activity and clinical manifestations in patients with Crohn's disease and ulcerative colitis: an observational cross-sectional study in the United States.

BACKGROUND: Fatigue imposes a socioeconomic burden on patients with Crohn's disease (CD) and ulcerative colitis (UC). We assessed the prevalence of fatigue among patients with CD or UC and identified disease activity measures associated with fatigue. METHODS: Data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD) were analyzed separately for CD and UC. Fatigue was defined based on a subjective and dichotomic questionnaire. Patients indicated if they experienced fatigue within the last week. The overall prevalence of fatigue was analyzed using descriptive and contingency tables. Demographics, clinical characteristics, disease activity (measures include Physician's Global Assessment for both CD and UC, short CD Activity Index for CD, and Ulcerative Colitis Disease Activity Index for UC), symptoms, and patient-reported outcomes were compared between patients with and without fatigue. Multivariable logistic regression models were constructed to identify symptoms and disease activity measures associated with fatigue. RESULTS: The study included 903 patients with CD and 443 patients with UC. Fatigue was reported in 47.7% of patients with CD and 40.9% of patients with UC. In patients with CD, abdominal pain, bowel incontinence, depressive symptoms, reduced general well-being, and night-time bowel movements were associated with fatigue. In patients with UC, depressive symptoms, reduced general well-being, moderate or severe disease activity by the physician's global assessment, and night-time bowel movements were significantly associated with fatigue. CONCLUSIONS: Fatigue is a common symptom among patients with CD or UC and is associated with higher levels of disease activity and reduced general well-being.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), can lead to fatigue in many patients regardless of their disease severity. Fatigue not only affects patients' quality-of-life but also their ability to work and their mental health. However, research specific to the IBD related symptoms that contribute to fatigue in these patients is not currently available, especially in the United States (US). To address this gap, real-world data was analyzed to understand how common fatigue is among patients with CD and UC in the US and clinical symptoms that co-occur with fatigue. We found that fatigue affects more than 40% of the patients. Our results suggest that fatigue is correlated with more severe disease symptoms and overall lower well-being among patients with CD and UC.

Provider Specialization in Inflammatory Bowel Diseases: Quality of Care and Outcomes.

BACKGROUND & AIMS: Management of inflammatory bowel diseases (IBD) is complex and variation in care has been well-documented. However, the drivers of practice variation remain unexplored. We examined variation based on the treating gastroenterologist's IBD focus (proportion of outpatient visits for IBD). METHODS: We conducted a retrospective cohort of newly diagnosed patients with IBD using data from Optum's deidentified Clinformatics Data Mart Database (2000-2020). The exposure variable was whether the treating gastroenterologist had an IBD focus (>90th percentile of IBD visits/total outpatient visits). We used adjusted regression models to evaluate associations between provider IBD focus and process measures (use of mesalamine, corticosteroid, biologic, and narcotic medications and endoscopic or radiographic imaging) and clinical outcomes (time to IBD-related hospitalization and bowel resection surgery). We tested for change in treatment patterns over time by including an interaction term for study era (2004-2012 vs 2013-2020). RESULTS: The study included 772 children treated by 493 providers and 2864 adults treated by 2076 providers. In children, none of the associations between provider focus and process or outcome measures were significant. In adults, care from an IBD-focused provider was associated with more use of biologics, combination therapy, and imaging and endoscopy, and less mesalamine use for Crohn's disease (P < .05 for all comparisons) but not with other process measures. Biologics were prescribed more frequently and narcotics less frequently during the later era (P < .05 for both). Hospitalization and surgery rates were not associated with IBD focus or era. CONCLUSIONS: IBD care for adults varies by provider specialization. Given the evolving complexity, novel methods may be needed to standardize care.

Hospitalizations for opportunistic infections following transplantation and associated risk factors: A national cohort study of Medicare beneficiaries.

BACKGROUND: Opportunistic infections (OIs) are a significant cause of morbidity and mortality after organ transplantation, though data in the liver transplant (LT) population are limited. METHODS: We performed a retrospective cohort study of LT recipients between January 1, 2007 and Deceber 31, 2016 using Medicare claims data linked to the Organ Procurement and Transplantation Network database. Multivariable Cox regression models evaluated factors independently associated with hospitalizations for early (≤1 year post transplant) and late (>1 year) OIs, with a particular focus on immunosuppression. RESULTS: There were 11 320 LT recipients included in the study, of which 13.2% had at least one OI hospitalization during follow-up. Of the 2638 OI hospitalizations, 61.9% were early post-LT. Cytomegalovirus was the most common OI (45.4% overall), although relative frequency decreased after the first year (25.3%). Neither induction or maintenance immunosuppression were associated with early OI hospitalization (all p > .05). The highest risk of early OI was seen with primary sclerosing cholangitis (aHR 1.74; p = .003 overall). Steroid-based and mechanistic target of rapamycin inhibitor-based immunosuppression at 1 year post LT were independently associated with increased late OI (p < .001 overall). CONCLUSION: This study found OI hospitalizations to be relatively common among LT recipients and frequently occur later than previously reported. Immunosuppression regimen may be an important modifiable risk factor for late OIs.

Differential effects of mass-loading the eardrum and stiffening the middle ear on wideband absorbance.

The current work investigated the effects of mass-loading the eardrum on wideband absorbance in humans. A non-invasive approach to mass-loading the eardrum was utilized in which water was placed on the eardrum via ear canal access. The mass-loaded absorbance was compared to absorbance measured for two alternative middle ear states: normal and stiffened. To stiffen the ear, subjects pressurized the middle ear through either exsufflation or insufflation concurrent with Eustachian tube opening. Mass-loading the eardrum was hypothesized to reduce high-frequency absorbance, whereas pressurizing the middle ear was hypothesized to reduce low- to mid-frequency absorbance. Discriminant linear analysis classification was performed to evaluate the utility of absorbance in differentiating between conditions. Water on the eardrum reduced absorbance over the 0.7- to 6-kHz frequency range and increased absorbance at frequencies below approximately 0.5 kHz; these changes approximated the pattern of changes reported in both hearing thresholds and stapes motion upon mass-loading the eardrum. Pressurizing the middle ear reduced the absorbance over the 0.125- to 4-kHz frequency range. Several classification models based on the absorbance in two- or three-frequency bands had accuracy exceeding 88%.

The Clinical Course of Bowel Urgency Severity Among Patients with Inflammatory Bowel Disease-A Real-World Study.

BACKGROUND: Bowel urgency is a highly burdensome symptom among patients with inflammatory bowel disease (IBD). OBJECTIVES: To assess changes in severity of bowel urgency and identify predictors of worsening or improvement among patients with Crohn's disease (CD) and ulcerative colitis (UC) at 6 months from their enrollment visit. METHODS: Data from patients in the Study of a Prospective Adult Research Cohort with IBD were analyzed. Enrolled patients with CD or UC with 6-month visits were included. Changes and predictors of bowel urgency severity over 6 months in patients with CD or UC were examined using two separate analyses: (a) "worsening" versus "no change" excluding those with moderate-to-severe bowel urgency at enrollment, and (b) "improvement" versus "no change" excluding those with no bowel urgency at enrollment. The enrollment characteristics were compared within these groups. RESULTS: At baseline, in both CD and UC, use of biologics and/or immunomodulators at enrollment was similar across cohorts. Among patients with CD, 206 of 582 (35.4%) reported worsening, and 195 of 457 (42.7%) reported improvement in bowel urgency. Younger age (P = 0.013) and moderate-to-severe bowel urgency (P < 0.001) were associated with improvement. Moderate bowel urgency (P = 0.026) and bowel incontinence while awake (P = 0.022) were associated with worsening. Among patients with UC, 84 of 294 (28.6%) reported worsening, and 111 of 219 (50.7%) reported improvement in bowel urgency. Higher symptomatic disease severity (P = 0.011) and more severe bowel urgency (P < 0.001) were associated with improvement. CONCLUSIONS: Bowel urgency is an unpredictable and unstable symptom among patients with IBD. Over 50% of patients with CD or UC experienced either worsening or improvement at 6 months postenrollment.

WHAT IS KNOWN ABOUT BOWEL URGENCY IN INFLAMMATORY BOWEL DISEASE (IBD)?: Around six to eight in every ten patients with inflammatory bowel disease suffer from bowel urgency, a sudden need to have bowel movement. Many patients with IBD perceive bowel urgency as a bothersome symptom impacting their everyday activities. WHY DID WE DO THIS STUDY?: Despite the importance of bowel urgency, the changes in bowel urgency severity among the IBD-affected US population are yet to be fully known. We aimed to assess changes in severity of bowel urgency in patients with Crohn's disease (CD) or ulcerative colitis (UC) at 6 months. WHAT HAVE WE FOUND FROM THIS STUDY?: Bowel urgency is a common and unpredictable symptom among patients with CD and UC. Over 50% of patients reported that the severity of bowel urgency has either worsened or improved at the 6 months postenrollment. While about 40­50% of IBD patients reported improvement, about 30% reported worsening, suggesting a lack of effective therapies to treat bowel urgency. FUTURE IMPLICATION: There is a need for advanced therapies to resolve bowel urgency in patients with CD and UC.

Real-world evidence for factors associated with maintenance treatment practices among US adults with autoimmune hepatitis.

BACKGROUND AND AIMS: While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in US patients with AIH. APPROACH AND RESULTS: A retrospective cohort of adults with the incident and prevalent AIH was identified from Optum's deidentified Clinformatics Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic, and with a median age of 61 years. Among 2203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone, and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination and 1.9% monotherapy). Hispanic ethnicity (aOR: 0.56; p = 0.006), cirrhosis (aOR: 0.73; p = 0.019), osteoporosis (aOR: 0.54; p =0.001), and top quintile of provider AIH experience (aOR: 0.66; p = 0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/y; p = 0.004), osteoporosis (+749 mg/y; p < 0.001), and highly experienced providers (+556 mg/y; p < 0.001). CONCLUSIONS: Long-term prednisone therapy remains common and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.

Effects of Tympanic Membrane Electrodes on Sound Transmission From the Ear Canal to the Middle and Inner Ears.

OBJECTIVES: The first objective of the study was to compare approaches to eardrum electrode insertion as they relate to the likelihood of introducing an acoustic leak between the ear canal and eartip. A common method for placing a tympanic membrane electrode involves securing the electrode in the canal by routing it underneath a foam eartip. This method is hypothesized to result in a slit leak between the canal and foam tip due to the added bulk of the electrode wire. An alternative approach involves creating a bore in the wall of the foam tip that the electrode can be threaded through. This method is hypothesized to reduce the likelihood of a slit leak before the electrode wire is integrated into the foam tip. The second objective of the study was to investigate how sound transmission in the ear is affected by placing an electrode on the eardrum. It was hypothesized that an electrode in contact with the eardrum increases the eardrum's mass, with the potential to reduce sound transmission at high frequencies. DESIGN: Wideband acoustic immittance and distortion product otoacoustic emissions (DPOAEs) were measured in eight human ears. Measurements were completed for five different conditions: (1) baseline with no electrode in the canal, (2) dry electrode in the canal but not touching the eardrum, secured underneath the eartip, (3) dry electrode in the canal not touching the eardrum, secured through a bore in the eartip (subsequent conditions were completed using this method), (4) hydrated electrode in the canal but not touching the eardrum, and (5) hydrated electrode touching the eardrum. To create the bore, a technique was developed in which a needle is heated and pushed through the foam eartip. The electrode is then thread through the bore and advanced slowly by hand until contacting the eardrum. Analysis included comparing absorbance, admittance phase angle, and DPOAE levels between measurement conditions. RESULTS: Comparison of the absorbance and admittance phase angle measurements between the electrode placement methods revealed significantly higher absorbance and lower admittance phase angle from 0.125 to 1 kHz when the electrode is routed under the eartip. Absorbance and admittance phase angle were minimally affected when the electrode was inserted through a bore in the eartip. DPOAE levels across the different conditions showed changes approximating test-retest variability. Upon contacting the eardrum, the absorbance tended to decrease below 1 kHz and increase above 1 kHz. However, changes were within the range of test-retest variability. There was evidence of reduced levels below 1 kHz and increased levels above 1 kHz upon the electrode contacting the eardrum. However, differences between conditions approximated test-retest variability. CONCLUSIONS: Routing the eardrum electrode through the foam tip reduces the likelihood of incurring an acoustic leak between the canal walls and eartip, compared with routing the electrode under the eartip. Changes in absorbance and DPOAE levels resulting from electrode contact with the eardrum implicate potential stiffening of eardrum; however, the magnitude of changes suggests minimal effect of the electrode on sound transmission in the ear.

Surgery for Crohn's Disease Is Associated With a Dysbiotic Microbiome and Metabolome: Results From Two Prospective Cohorts.

BACKGROUND & AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery. METHODS: Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies. Stool samples were analyzed with shotgun metagenomics sequencing. Fecal butyrate was measured with 1H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry. RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, Egerthella lenta, Adlercreutzia equalofaciens, and Gordonibacter pamelaeae were lower in abundance among patients with prior surgery in both cohorts. CONCLUSIONS: In 2 different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria and secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.

Validation of new medication use algorithms as proxies for worsening disease activity in patients with juvenile idiopathic arthritis.

PURPOSE: To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity. METHODS: Using electronic health record data from three pediatric centers, we defined new JIA medication use as (re)initiation of disease-modifying antirheumatic drugs or glucocorticoids (oral or intra-articular). Data were collected from 201 randomly selected subjects with (101) or without (100) new medication use. We assessed the positive predictive value (PPV) and negative predictive value (NPV) based on a reference standard of documented worsening of JIA disease activity. The algorithm was refined to optimize test characteristics. RESULTS: Overall, the medication-based algorithm had suboptimal performance in representing worsening JIA disease activity (PPV 69.3%, NPV 77.1%). However, algorithm performance improved for definitions specifying longer times after JIA diagnosis (≥1-year post-diagnosis: PPV 82.9%, NPV 80.0%) or after initiation of prior JIA treatment (≥1-year post-treatment: PPV 89.7%, NPV 80.0%). CONCLUSION: An algorithm for new JIA medication use appears to be a reasonable proxy for worsening JIA disease activity, particularly when specifying new use ≥1 year since initiating a prior JIA medication. This algorithm will be valuable for conducting research on JIA populations within administrative claims databases.

Active surveillance pharmacovigilance for Clostridioides difficile infection and gastrointestinal bleeding: an analytic framework based on case-control studies.

BACKGROUND: Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called pharmacopeia-wide association studies (PharmWAS) that limits false positive medication associations through high-dimensional confounding adjustment and set enrichment. We aimed to assess the transportability and generalizability of the PharmWAS framework by using medical claims data to reproduce known medication associations with Clostridioides difficile infection (CDI) or gastrointestinal bleeding (GIB). METHODS: We conducted case-control studies using Optum's de-identified Clinformatics Data Mart Database of individuals enrolled in large commercial and Medicare Advantage health plans in the United States. Individuals with CDI (from 2010 to 2015) or GIB (from 2010 to 2021) were matched to controls by age and sex. We identified all medications utilized prior to diagnosis and analysed the association of each with CDI or GIB using conditional logistic regression adjusted for risk factors for the outcome and a high-dimensional propensity score. FINDINGS: For the CDI study, we identified 55,137 cases, 220,543 controls, and 290 medications to analyse. Antibiotics with Gram-negative spectrum, including ciprofloxacin (aOR 2.83), ceftriaxone (aOR 2.65), and levofloxacin (aOR 1.60), were strongly associated. For the GIB study, we identified 450,315 cases, 1,801,260 controls, and 354 medications to analyse. Antiplatelets, anticoagulants, and non-steroidal anti-inflammatory drugs, including ticagrelor (aOR 2.81), naproxen (aOR 1.87), and rivaroxaban (aOR 1.31), were strongly associated. INTERPRETATION: These studies demonstrate the generalizability and transportability of the PharmWAS pharmacovigilance framework. With additional validation, PharmWAS could complement traditional passive surveillance systems to identify medications that unexpectedly provoke or prevent high-impact conditions. FUNDING: U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

The Role of Hospital Characteristics in Clinical and Quality Outcomes for Gastrointestinal Bleeding in a National Cohort.

INTRODUCTION: There is substantial variability in patient outcomes for gastrointestinal bleeding (GIB) across hospitals. This study aimed to identify hospital factors associated with GIB outcomes. METHODS: This was a retrospective cohort study of Medicare fee-for-service beneficiaries hospitalized for GIB from 2016 to 2018. These data were merged with the American Hospital Association Annual Survey data to incorporate hospital characteristics. We used generalized linear mixed-effect models to estimate the effect of hospital-level characteristics on patient outcomes after adjusting for patient risk factors including anticoagulant and antiplatelet use, recent GIB, and comorbidities. The primary outcome was 30-day mortality, and secondary outcomes included length of stay and a composite outcome of 30-day readmission or mortality. RESULTS: Factors associated with improved GIB 30-day mortality included large hospital size (defined as beds >400, odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90-0.97), greater case volume (OR 0.97, 95% CI 0.96-0.98), increased resident and nurse staffing (OR 0.88, 95% CI 0.83-0.94), and blood donor center designation (OR 0.93, 95% CI 0.88-0.99). Patients treated at a hospital with multiple advanced capabilities, such as availability of advanced endoscopy, advanced intensive care unit (ICU) capabilities (both a medical-surgical ICU and cardiac ICU), blood donor center, and liver transplant center, had a 22% reduction in 30-day mortality risk, compared with those hospitalized in a hospital with none of these services (OR 0.78, 95% CI 0.68-0.91). However, length of stay increased with additional services. DISCUSSION: Patients hospitalized for GIB at hospitals with multiple advanced specialized capabilities have lower mortality but longer lengths of stay. Further research should examine the processes of care linked to these services that contribute to improved mortality in GIB.

AGA Clinical Practice Update on Diet and Nutritional Therapies in Patients With Inflammatory Bowel Disease: Expert Review.

DESCRIPTION: Diet plays a critical role in human health, but especially for patients with inflammatory bowel disease (IBD). Guidance about diet for patients with IBD are often controversial and a source of uncertainty for many physicians and patients. The role of diet has been investigated as a risk factor for IBD etiopathogenesis and as a therapy for active disease. Dietary restrictions, along with the clinical complications of IBD, can result in malnutrition, an underrecognized condition among this patient population. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice statements, primarily to clinical gastroenterologists, covering the topics of diet and nutritional therapies in the management of IBD, while emphasizing identification and treatment of malnutrition in these patients. We provide guidance for tailored dietary approaches during IBD remission, active disease, and intestinal failure. A healthy Mediterranean diet will benefit patients with IBD, but may require accommodations for food texture in the setting of intestinal strictures or obstructions. New data in Crohn's disease supports the use of enteral liquid nutrition to help induce remission and correct malnutrition in patients heading for surgery. Parenteral nutrition plays a critical role in patients with IBD facing acute and/or chronic intestinal failure. Registered dietitians are an essential part of the interdisciplinary team approach for optimal nutrition assessment and management in the patient population with IBD. METHODS: This expert review was commissioned and approved by the AGA Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. The best practice advice statements were drawn from reviewing existing literature combined with expert opinion to provide practical advice on the role of diet and nutritional therapies in patients with IBD. Because this was not a systematic review, formal rating of the quality of evidence or strength of the presented considerations was not performed. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Unless there is a contraindication, all patients with IBD should be advised to follow a Mediterranean diet rich in a variety of fresh fruits and vegetables, monounsaturated fats, complex carbohydrates, and lean proteins and low in ultraprocessed foods, added sugar, and salt for their overall health and general well-being. No diet has consistently been found to decrease the rate of flares in adults with IBD. A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn's disease. BEST PRACTICE ADVICE 2: Patients with IBD who have symptomatic intestinal strictures may not tolerate fibrous, plant-based foods (ie, raw fruits and vegetables) due to their texture. An emphasis on careful chewing and cooking and processing of fruits and vegetables to a soft, less fibrinous consistency may help patients with IBD who have concomitant intestinal strictures incorporate a wider variety of plant-based foods and fiber in their diets. BEST PRACTICE ADVICE 3: Exclusive enteral nutrition using liquid nutrition formulations is an effective therapy for induction of clinical remission and endoscopic response in Crohn's disease, with stronger evidence in children than adults. Exclusive enteral nutrition may be considered as a steroid-sparing bridge therapy for patients with Crohn's disease. BEST PRACTICE ADVICE 4: Crohn's disease exclusion diet, a type of partial enteral nutrition therapy, may be an effective therapy for induction of clinical remission and endoscopic response in mild to moderate Crohn's disease of relatively short duration. BEST PRACTICE ADVICE 5: Exclusive enteral nutrition may be an effective therapy in malnourished patients before undergoing elective surgery for Crohn's disease to optimize nutritional status and reduce postoperative complications. BEST PRACTICE ADVICE 6: In patients with IBD who have an intra-abdominal abscess and/or phlegmonous inflammation that limits ability to achieve optimal nutrition via the digestive tract, short-term parenteral nutrition may be used to provide bowel rest in the preoperative phase to decrease infection and inflammation as a bridge to definitive surgical management and to optimize surgical outcomes. BEST PRACTICE ADVICE 7: We suggest the use of parenteral nutrition for high-output gastrointestinal fistula, prolonged ileus, short bowel syndrome, and for patients with IBD with severe malnutrition when oral and enteral nutrition has been trialed and failed or when enteral access is not feasible or contraindicated. BEST PRACTICE ADVICE 8: In patients with IBD and short bowel syndrome, long-term parenteral nutrition should be transitioned to customized hydration management (ie, intravenous electrolyte support and/or oral rehydration solutions) and oral intake whenever possible to decrease the risk of developing long-term complications. Treatment with glucagon-like peptide-2 agonists can facilitate this transition. BEST PRACTICE ADVICE 9: All patients with IBD warrant regular screening for malnutrition by their provider by means of assessing signs and symptoms, including unintended weight loss, edema and fluid retention, and fat and muscle mass loss. When observed, more complete evaluation for malnutrition by a registered dietitian is indicated. Serum proteins are no longer recommended for the identification and diagnosis of malnutrition due to their lack of specificity for nutritional status and high sensitivity to inflammation. BEST PRACTICE ADVICE 10: All patients with IBD should be monitored for vitamin D and iron deficiency. Patients with extensive ileal disease or prior ileal surgery (resection or ileal pouch) should be monitored for vitamin B12 deficiency. BEST PRACTICE ADVICE 11: All outpatients and inpatients with complicated IBD warrant co-management with a registered dietitian, especially those who have malnutrition, short bowel syndrome, enterocutaneous fistula, and/or are requiring more complex nutrition therapies (eg, parenteral nutrition, enteral nutrition, or exclusive enteral nutrition), or those on a Crohn's disease exclusion diet. We suggest that all newly diagnosed patients with IBD have access to a registered dietitian. BEST PRACTICE ADVICE 12: Breastfeeding is associated with a lower risk for diagnosis of IBD during childhood. A healthy, balanced, Mediterranean diet rich in a variety of fruits and vegetables and decreased intake of ultraprocessed foods have been associated with a lower risk of developing IBD.

Preoperative Exclusive Enteral Nutrition Is Associated With Reduced Skin and Soft Tissue and Intra-abdominal Infections in Patients With Crohn's Disease Undergoing Intestinal Surgery: Results from a Meta-Analysis.

BACKGROUND: Malnutrition is an independent risk factor for adverse postoperative outcomes and is common among patients with Crohn's disease (CD). The objective of this meta-analysis was to precisely quantify the association of preoperative exclusive enteral nutrition (EEN) and total parenteral nutrition (TPN) with surgical outcomes in patients undergoing intestinal surgery for CD. METHODS: PubMed, Embase, and Scopus were queried for comparative studies evaluating the impact of preoperative nutritional support on postoperative outcomes in patients undergoing surgery for CD. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. RESULTS: Fourteen studies, all nonrandomized cohort studies, met inclusion criteria for studying EEN. After pooling data from 14 studies (874 EEN treated and 1044 control patients), the relative risk of intra-abdominal septic complications was decreased 2.1-fold in patients receiving preoperative EEN (relative risk 0.47, 95% confidence interval [CI], 0.35-0.63, I2 = 0.0%). After pooling data from 9 studies (638 EEN treated and 819 control patients), the risk of skin and soft tissue infection was decreased 1.6-fold (relative risk 0.63; 95% CI, 0.42-0.94, I2 = 42.7%). No significant differences were identified in duration of surgery, length of bowel resected, or operative blood loss. Among the 9 studies investigating TPN, no significant differences were identified in infectious outcomes. CONCLUSIONS: Preoperative nutritional optimization with EEN was associated with reduced risk of infectious complications in CD patients undergoing intestinal surgery. Preoperative nutritional support with EEN should be considered for optimizing outcomes in CD patients requiring bowel resection surgery.

Pooled data from this meta-analysis demonstrated significantly decreased rates of skin/soft tissue and intra-abdominal infections following intestinal surgery for Crohn's disease after preoperative treatment with exclusive enteral nutrition.

Effectiveness and safety of prophylactic anticoagulation among hospitalized patients with inflammatory bowel disease.

ABSTRACT: Hospitalized patients with inflammatory bowel disease (IBD) are at increased risk of venous thromboembolism (VTE). We aimed to evaluate the effectiveness and safety of prophylactic anticoagulation compared with no anticoagulation in hospitalized patients with IBD. We conducted a retrospective cohort study using a hospital-based database. We included patients with IBD who had a length of hospital stay ≥2 days between 1 January 2016 and 31 December 2019. We excluded patients who had other indications for anticoagulation, users of direct oral anticoagulants, warfarin, therapeutic-intensity heparin, and patients admitted for surgery. We defined exposure to prophylactic anticoagulation using charge codes. The primary effectiveness outcome was VTE. The primary safety outcome was bleeding. We used propensity score matching to reduce potential differences between users and nonusers of anticoagulants and Cox proportional-hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The analysis included 56 194 matched patients with IBD (users of anticoagulants, n = 28 097; nonusers, n = 28 097). In the matched sample, prophylactic use of anticoagulants (vs no use) was associated with a lower rate of VTE (HR, 0.62; 95% CI, 0.41-0.94) and with no difference in the rate of bleeding (HR, 1.05; 95% CI, 0.87-1.26). In this study of hospitalized patients with IBD, prophylactic use of heparin was associated with a lower rate of VTE without increasing bleeding risk compared with no anticoagulation. Our results suggest potential benefits of prophylactic anticoagulation to reduce the burden of VTE in hospitalized patients with IBD.