bluuebunny/crossref_metadata_2025_split huggingface dataset:
465 A Pharmacokinetic Bridging Study to Compare the Bioavailability of Budesonide Between Budesonide Oral Suspension and ENTOCORT EC in Healthy Subjects
Authors: Song Ivy , Finkelman Richard , Lan Lan 
Published: October 2019

INTRODUCTION:
Budesonide oral suspension (BOS; TAK-721) is a viscous formulation of budesonide that is in development for the treatment of eosinophilic esophagitis in adults and adolescents. BOS was granted Breakthrough Designation by the FDA and is currently being evaluated in phase 3 trials. Several budesonide products are approved in the US for other indications, including ENTOCORT EC for mild to moderate active Crohn's disease; thus, the safety of budesonide has been evaluated extensively. The present study compared the bioavailability of BOS with ENTOCORT EC, aiming to provide the pharmacokinetic (PK) bridge to the safety data of ENTOCORT EC.

METHODS:
Healthy adults (n=22) were enrolled in an open-label, single-center, crossover study. Subjects received two treatments in a randomized sequence with a 48 h washout period between treatments: a single oral dose of BOS 2 mg and a single oral dose of ENTOCORT EC 9 mg. Serial blood samples were collected in each treatment period to determine plasma budesonide concentrations. PK parameters were calculated by non-compartmental analysis and compared between treatments using a mixed effects model with sequence and treatment as fixed effects and subject within sequence as a random effect.

RESULTS:
Plasma budesonide concentrations showed a faster absorption from BOS compared with ENTOCORT EC. Peak plasma concentrations were achieved ∼1.5 h post-dose for BOS and ∼4 h post-dose for ENTOCORT EC. Systemic exposure to budesonide after a single dose of BOS 2 mg was lower than that observed after a single dose of ENTOCORT EC 9 mg: the geometric mean AUC0-t, AUC0-inf and Cmax of budesonide after BOS 2 mg were 33.6%, 32.9% and 71.1% of those after ENTOCORT EC 9 mg, respectively.

CONCLUSION:
ENTOCORT EC 9 mg once daily (qd) is approved for induction treatment of Crohn's disease. The proposed clinical dosing regimen for BOS for induction treatment of eosinophilic esophagitis is 2 mg twice daily (bid). When taking into account the different dosing frequencies, the daily AUC and the Cmax of budesonide from BOS 2 mg bid at steady state are estimated to be 67% and 71% of those from ENTOCORT EC 9 mg qd, respectively. These results provide PK bridging data to compare BOS 2 mg bid to ENTOCORT EC with respect to safety information.
466 Avoidant/Restrictive Food Intake Disorder (ARFID) Among Adult Gastroenterology Behavioral Health Patients: Comparison of ARFID vs. Non-ARFID Patients
Authors: Harer Kimberly N. , Jagielski Christina , Chey William D. , Riehl Megan 
Published: October 2019

INTRODUCTION:
Avoidant/Restrictive Food Intake Disorder (ARFID) is a feeding disorder characterized by avoidance or restriction of food associated with weight loss, nutritional deficiency, dependence on tube feeds/oral supplements, or significant psychosocial impairment. Emerging evidence has shown 6-19% of gastroenterology (GI) patients have concurrent ARFID; however, these patients have not been characterized.

METHODS:
Retrospective analysis of 223 adult GI patients seen by a gastroenterologist and GI psychologist at a tertiary care center from 2016 to 2018. ARFID diagnosis was based on chart review by a gastroenterologist and GI psychologist for evidence of DSM-5 ARFID criteria. Demographic, clinical, and questionnaire data were recorded.

RESULTS:
Of 223 patients, 28 (12.6%) met criteria for ARFID. Concern for ARFID was raised in 0% of cases. There was no difference between ARFID and non-ARFID patient gender, age, educational level, GI diagnosis, GI symptom severity, mean BMI, or frequency of nutrition referral (Table 1). ARFID patients were less likely to be using a psychotropic medication (17.9% vs 50%, P < 0.01). There was no difference in eating disorder history (ARFID 3.6% vs non-ARFID 8.7%, P = 0.12). On the IBS-QOL questionnaire, ARFID patients reported more severe food avoidance concerns, more frustration with not being able to eat what they wanted, and less severe body image concerns (all P< 0.5). Following completion of GI-directed psychological therapies, IBS-QOL scores improved less in ARFID patients (Table 2). There was no difference between groups in Brief Symptoms Inventory scores or sleep quality scores (Table 3).

CONCLUSION:
This is the first study comparing ARFID vs non-ARFID adult GI behavioral health patients. Of 223 patients, 12.6% met ARFID criteria. ARFID and non-ARFID patients were clinically indistinguishable based on age, gender, BMI, GI diagnosis, or GI symptom severity. Although ARFID is often associated by gastroenterologists with underlying psychiatric or eating disorders, ARFID patients were less likely to be using psychotropic agents, reported lower body image concerns, and reported increased frustration with not being able to eat than non-ARFID patients. ARFID patients had decreased improvement in post-behavioral health therapy IBS-QOL scores. This data demonstrates the need to appropriately screen patients for ARFID and raises concern regarding the need utilize a multidisciplinary treatment approach that takes into account GI, psychological, and nutritional needs.
470 Nutritional Deficiencies in Irritable Bowel Syndrome: A North American Population-Based Study
Authors: Hujoel Isabel A. 
Published: October 2019

INTRODUCTION:
Irritable bowel syndrome (IBS) is common, affecting 12% of the population. However, the quality of evidence in support of current medical interventions has been rated as very low, and the majority of those with IBS report their symptoms as being unchanged or worsened over time. Diet is thought to play a significant role in IBS, and there is increasing focus on the therapeutic benefit of diet and supplementation. This study aims to compare dietary composition and serologic markers of nutritional status in those with and without IBS to determine potential targets for therapeutic supplementation.

METHODS:
All 17 national surveys between 1959 and 2019 were screened and only one, the Second National Health and Nutrition Examination Survey (NHANES II) (1976-1980), provided comprehensive data on IBS. We performed a cross-sectional analysis of serology and dietary composition of 12,295 individuals, aged 18 to 74 in NHANES II. Dietary composition was drawn from dietary recall questionnaires, and the diagnosis of IBS was based on self-reporting.

RESULTS:
Individuals with IBS had significantly higher copper-zinc ratios (1.70 versus 1.55, P = 0.048) and were more likely to have ratios above 1.8 (odds ratio 1.79, 95% confidence interval 1.02-3.13), suggestive of an underlying zinc deficiency. This deficiency may be due to their avoidance of milk, which was the largest source of dietary zinc in the study population. While they were significantly more likely to report dietary avoidances, they had no other serologic evidence of nutritional deficiencies. Additionally, dietary recall showed that they consumed significantly more daily calories (P = 0.02), were more likely to take vitamin supplements (P = 0.003) and that their macro and micronutrient intake was not significantly different.

CONCLUSION:
The findings suggest that individuals with IBS should be screened for zinc deficiency. Zinc deficiency may perpetuate the underlying pathophysiology of IBS and may contribute to the associated psychiatric conditions through zinc's role in the immune system, “brain-gut” axis, and gastrointestinal barrier integrity. This suggests that zinc supplementation may be a potential therapy both to mitigate underlying pathology as well as improve symptoms. Our findings should be confirmed in future studies, and the association of copper-zinc ratios with symptom severity, and the response of symptoms to supplementation could be investigated.
471 Investigating the Tissue Distribution of [14C]-Prucalopride Following a Single Oral Dose in Rats
Authors: Lou Zhen , Welty Devin 
Published: October 2019

INTRODUCTION:
Prucalopride is a selective, high-affinity agonist of the 5-hydroxytryptamine-4 (5-HT4) receptor and is indicated for the treatment of adult patients with chronic constipation. In humans, prucalopride is rapidly absorbed and extensively distributed, reaching maximum plasma concentration 2–3 h after a 2 mg oral dose. We report three studies investigating tissue distribution of prucalopride in rats.

METHODS:
A single oral dose of 14C-labelled prucalopride at 5mg base-equivalent(eq)/kg was administered to 30 SPF Wistar rats (5 males, seven groups of 3 non-pregnant females and 4 pregnant females [dose administered on day 18 of gestation]). Total radioactivity (TR) in various tissues was measured up to 96h. In females, the area under the TR concentration curve for up to 8h (AUC0–8h) and the AUC0–8h tissue:plasma ratio was calculated. The tissue concentration of unchanged drug (UD) was measured up to 48 h.

RESULTS:
The highest mean TR for all rats was detected in the pancreas (8.9µg-eq/g within 30 min of dosing; below the limit of detection [LOD] after 24 h), the liver (12.5 µg-eq/g within 20 min; 0.3 µg-eq/g after 96 h) and the small intestine (15.6µg-eq/g within 30 min; below the LOD after 24 h). The highest mean concentration of UD in non-pregnant females was detected in the small intestine (10.1 µg-eq/g within 20 min; below the LOD after 24 h). The lowest mean TR was detected in the brain, in males (0.12 µg-eq/g within 30 min), non-pregnant females (0.21 µg-eq/g within 1 h) and pregnant females (0.21 µg-eq/g within 30 min). TR in the brain was below the LOD within 2, 24 and 8 h of dosing, respectively. In non-pregnant females, the highest AUC0–8h and AUC0–8h tissue:plasma ratios of TR were observed in the small intestine (75.3 and 31.3, respectively); the lowest values were observed in the brain (0.85 and 0.35, respectively). Findings were similar for UD. In pregnant females the highest AUC0–8h and AUC0–8h tissue:plasma ratios of TR were observed in rectal (mucosa) and salivary gland tissue (122 and 20.5, respectively, for both); the lowest values were observed in the brain (0.33 and 0.17 [AUC0–2h], respectively).

CONCLUSION:
After a single oral dose of prucalopride, high concentrations were detected in the pancreas, liver and small intestine, and very low concentrations in the brain (∼0.05% of the dose in non-pregnant female rats). Mean concentrations of TR and UD in the brain were below the LOD within 24h of dosing, suggesting prucalopride is not unduly retained in the brain.
475 The Fragility Index of the Randomized Trials for Irritable Bowel Syndrome With Constipation
Authors: Takakura Will , Rezaie Ali 
Published: October 2019

INTRODUCTION:
In the age of frequentist analyses and standardized threshold P-values (<0.05); fragility index (FI), the minimum number of patients that needs to change from “non-responder” to “responder” for the P-value to become >0.05, has been suggested to aid our interpretation of the robustness of the “positive” large randomized control trials (RCTs) (Walsh, M. et al. JCE 2014). This number allows the reader to quickly know the number of patients that the study relies on for its significance, hence a higher index suggests a higher confidence in the results. Based on all available RCTs, we aimed to calculate the FI of medications that are approved by Food and Drug Association (FDA) for (Irritable bowel syndrome with constipation) IBS-C.

METHODS:
Data from 13 double-blind RCTs on linaclotide, plecanatide, lubiprostone and tegaserod were analyzed. FI was calculated by converting the number of “non-responders” in a dichotomized data to a “responders” to get a P-value > 0.05 by using the Fisher's exact test. We calculated the FI for the FDA endpoint if it was reported, otherwise the dichotomized endpoint evaluating its efficacy was used. A similar calculation was done for diarrhea as the most common side effect in RCTs on IBS-C in each respective study by converting those without diarrhea to those with diarrhea to calculate its FI.

RESULTS:
All 13 studies had a positive FI except for Johanson et al. studying lubiprostone since the study itself reported a nonsignificant outcome, as well as Novick at al. studying tegaserod (Table 1). The FI for diarrhea was positive for those in linaclotide and 2 studies for plecanatide and tegaserod but not in lubiprostone. The median (mean) FI for efficacy was 27 (28.5), 13 (17.7), 2 (2), and 6 (11) events and the median (mean) FI for diarrhea was 31.5 (29.3), 2 (3), 0 (0), and 8 (5.7) events for linaclotide, plecanatide, lubiprostone and tegaserod respectively. Linear regression showed a significant positive correlation between FI for efficacy and diarrhea with R2 = 0.54 (P = 0.004) (Figure 1).

CONCLUSION:
Median FI is appropriately positive for RCTs assessing IBS-C on medications currently approved by FDA. We recommend considering the addition of FI, as a simple and useful tool, in future systematic reviews to assist in appropriate and optimal decision making in patient care.
477 Abdominal Herniation and Gastrointestinal Symptoms in Patients With Loey Dietz Syndrome and Vascular Ehlers Danlos Syndrome
Authors: Wang Xiao Jing , Babameto Mary , Babovic-Vuksanovic Dusica , Camilleri Michael 
Published: October 2019

INTRODUCTION:
Loey Dietz syndrome (LDS) is an autosomal dominant disorder caused by a mutation in TGFBR1- or TGFBR2. LDS is characterized by distinctive facies, tortuous arteries and aortic aneurysms predisposition to eosinophilic allergic disorders including eosinophilic esophagitis and gastritis, and other systemic findings including inflammatory bowel disease. Patients with vascular Ehlers Danlos Syndrome (vEDS) have deficiency in type III collagen and have similar vascular laxity and concomitant GI manifestations. This connective tissue vulnerability contributes to increased post-operative wound dehiscence and development of hernias. Our aim was to summarize abdominal wall and GI tract manifestations in these two rare vascular disorders at a tertiary referral center.

METHODS:
Data were collected via Advanced Cohort Explorer (ACE) application at Mayo Clinic. A chart review was undertaken on patients with a confirmed diagnosis of vEDS or LDS seen at Mayo Clinic in Rochester from 1994 to 2018. Diagnoses were confirmed by genetic testing and/or clinical review through the specialized medical genetics clinic. Information was extracted on vascular complications of disease, prevalence of abdominal hernias, and gastrointestinal symptoms. The study was reviewed and exempted by the Mayo Clinic IRB.

RESULTS:
We identified and reviewed records of 50 vEDS and 13 LDS patients; data are summarized in Tables 1 and 2. Patients were similar in age at diagnosis and gender distribution. Hernias were present in similar proportions of patients with vEDS and LDS, although ventral hernias were more frequent and the hernias were more likely to be post-operative in vEDS than in LDS. LDS patients had more aneurysms (58% vEDS vs. 76.9% LDS, P = 0.02) with higher proportion requiring arterial repair (32.7% vEDS vs. 69.2% LDS, P = 0.03). Co-morbidities more prevalent in LDS than vEDS were autonomic dysfunction, psychopathology and allergy. We did not note increase in symptoms suggestive of eosinophilic esophagitis/gastritis in the LDS patients. GI symptoms were prevalent in both disorders and largely similar, except for diarrhea and constipation which were both significantly more prevalent in LDS patients.

CONCLUSION/DISCUSSION:
While vEDS and LDS are both connective tissue disorders with propensity for GI symptoms, abdominal hernias and aneurysm formation, the risk of arterial rupture and co-morbidity of autonomic dysfunction, psychopathology and allergy are greater in LDS than vEDS.
482 Prevalence and Predictors of Symptom Complexes Commonly Seen in Acute Hepatic Porphyria in the General Population
Authors: Lakhoo Krutika , Almario Christopher , Ko John J. , Wei Alex , Meninger Stephen , Spiegel Brennan 
Published: October 2019

INTRODUCTION:
Acute hepatic porphyria (AHP), a family of rare genetic disorders, can present with life-threatening attacks with a predominant symptom of abdominal pain. Literature states that patients with AHP have been misdiagnosed with other conditions such as irritable bowel syndrome, functional abdominal pain, and endometriosis, among others. We aimed to determine the prevalence and predictors of symptom complexes commonly seen in AHP among community-dwelling adults in the US.

METHODS:
We partnered with Cint, an online survey research firm, to recruit a representative sample of US adults aged ≥18 y with abdominal pain. We asked if they had recurrent episodes of excruciating belly pain lasting ≥1 day with any of these co-occurring symptoms: urine color change to dark red/brown; skin blisters on sun-exposed areas; peripheral (e.g., muscle weakness, extremity pain), central (e.g., depression, seizures), or autonomic (e.g., tachycardia, hypertension) nervous system manifestations. Multivariable logistic regression models were used to adjust for confounding.

RESULTS:
24,932 individuals accessed the survey, with 10,300 (41.3%) reporting abdominal pain (Table 1). Of those with abdominal pain, 23.4% had symptoms consistent with AHP (≥2 episodes of excruciating abdominal pain and ≥2 concomitant symptoms). Those with AHP-like symptoms experienced the following: autonomic (97.7%), central (96.5%), and peripheral (58.8%) nervous system manifestations; urine color change (21.9%); and skin blisters (6.6%). Most (90.9%) sought medical care for their symptoms: emergency room (57.6%), doctor's office (52.1%); urgent care facility (29.4%); clinic/health center (19.1%); hospital admission (18.4%). Table 2 shows results of the regression analysis on presence of AHP-like symptoms. Younger individuals, Latinos, those who identified as other race, and those with a usual source of care, comorbidities, lower locus of control, more severe pain, and worse physical health were more likely to have AHP-like symptoms.

CONCLUSION:
In this population-based survey, 1 of 4 individuals with prior abdominal pain had symptoms consistent with AHP manifestations. Although AHP prevalence is very low, clinicians should ask those experiencing multiple episodes of severe abdominal pain about concomitant neurologic, psychiatric, skin, and urologic symptoms. This practice may prompt earlier testing for AHP, decreasing the delay to diagnosis and improving outcomes.
488 National Trends and Outcomes of Irritable Bowel Syndrome Presenting to Emergency Departments: Results From the Nationwide Emergency Department Sample (NEDS) Database
Authors: Tariq Tooba , Sieloff Martin , Irfan Furqan 
Published: October 2019

INTRODUCTION:
Irritable bowel syndrome (IBS) is a chronically relapsing disease that causes gastrointestinal discomfort with diarrhea and/or constipation in a large group of Americans. Estimates of IBS disease burden in emergency departments (ED) are lacking. We sought to investigate IBS emergency department visits nationally, patient demographics and hospitalization trends from 2009-2014 using Nationwide Emergency Department Sample (NEDS) database.

METHODS:
The Nationwide Emergency Department Sample database was used to extract data from 2009 to 2014 for patients who visited the ED with a primary diagnosis of irritable bowel syndrome. International Classification of Diseases (ICD-9-CM) were used to identify patients; Irritable bowel syndrome (ICD-9-CM: 564.1). The 2009-2014 NEDS data was used to study the incidence of ED visits, patient/hospital factors, inpatient charges, length of hospitalization and discharge from hospital to home.

RESULTS:
There were 189,210 (0.02%) ED visits identified with a diagnosis of IBS among a total of 795,980,104 ED visits between 2009-2014 in the NEDS database. Most patients were female (n = 143247.6, 75.8%) with a mean age of 42.4 years. The rate of ED visits decreased from 10.2 per 100,000 in 2009, to 9.4 per 100,000 in 2014 (decrease of 8%; z = -1.691, P = 0.091). The majority of patients had private insurance (n = 68687, 36.3%) followed by Medicare (n = 43272, 22.9%) and Medicaid (n = 41737, 22.1%). Uninsured patients presenting with IBS to the ED constituted 15% (n = 28392) of the study population. Patients presented with IBS in far greater numbers to urban EDs (n = 150148, 79.4%) compared to rural EDs (n = 39062, 20.6%). Most were discharged from the ED (n = 134616.9, 71.1%) while 28.9% (n = 54593.5) patients were admitted. Hospitalized patients had a decrease in mean length of stay from 3.64 days in 2009 to 3.53 days in 2014; however, the mean inpatient charges increased from $20,823 in 2009 to $27,649 in 2014 (increase of 32.8%).

CONCLUSION:
Irritable bowel syndrome emergency department visits remained relatively constant between 2009 and 2014 while nearly 30% of patients were admitted. Despite unchanged hospital length of stay, hospitalization costs appear to be increasing. Better outpatient management of irritable bowel syndrome is needed to avoid emergency department visits and rising inpatient costs.
490 High-Resolution Electrogastrogram Identifies Disturbed Gastric Slow Waves and Dysautonomia in Subjects With Dumping Syndrome
Authors: Kabadi Alisha , Coleman Todd P. , Greenwald Holly S. , Kunkel David C. 
Published: October 2019

INTRODUCTION:
Rapid gastric emptying is the sine qua non of Dumping Syndrome (DS), which can arise from multiple etiologies including gastric surgery and diabetes mellitus. The relationship between DS and gastric myoelectric activity is unknown, but dysautonomia may play a role. We sought to characterize features of gastric slow waves and autonomic indices among subjects with DS using the ambulatory high-resolution electrogastrogram (HR-EGG).

METHODS:
Eleven subjects completed 24-hour ambulatory HR-EGG. Fasting abdominal computed tomography scan was utilized for stomach localization and placement of the ambulatory HR-EGG array, consisting of 10 skin mounted electrodes. Subjects were divided into two groups: DS (4F, age 53.2 ± 9.3, BMI 31.7 ± 11, 79-93% gastric emptying at 1 hour on scintigraphy, two diabetics, one prior gastric surgery, one gastrointestinal amyloidosis) and healthy age-matched controls (4M/3F, age 47.6 ± 28, BMI 24.5 ± 3.7). All subjects completed the PAGI-SYM foregut symptom questionnaire and a diary capturing all meals and sleep/wake times.

RESULTS:
Subjects with DS had significantly higher mean PAGI-SYM foregut symptom severity scores (1.9 ± 1.0 vs 0.1 ± 0.1; P = 0.0007). HR-EGG showed that DS subjects had a significantly lower slow wave speed (4.6 vs 5.9 ± 0.4; P = 0.0003) and higher post-prandial power change (11 vs 3.5 ± 3.6; P = 0.002) compared to healthy controls. The global percent stomach activity throughout the 24-hour ambulatory recordings was not different between groups. DS subjects trended towards higher post-prandial area under the curve EGG activity at both the 1-hour (261.9 ± 360.7 vs 172.9 ± 137.5) and 4-hour marks (1108.8 ± 1589.4 vs 656.3 ± 442.2). In addition, subjects with DS had significantly lower heart rate variability than controls: RMSDD (39.9 ± 9.7 vs 58.1 ± 7.8) and SDNN (12.6 ± 4.2 vs 23.7 ± 3.2); no differences were noted in mean heart rate (Table 1).

CONCLUSION:
Ambulatory HR-EGG clearly identifies that there are spatial abnormalities of the gastric slow wave present among subjects with DS. Moreover, reduced heart rate variability - a marker of autonomic dysfunction - was observed among subjects with DS. These findings suggest that gastric dysrhythmias and autonomic disturbances should be given important consideration in the pathogenesis of Dumping Syndrome.