Ileocecal Anastomosis Type Significantly Influences Long-Term Functional Status, Quality of Life, and Healthcare Utilization in Postoperative Crohn's Disease Patients Independent of Inflammation Recurrence.

OBJECTIVES: Anastomotic reconstruction following intestinal resection in Crohn's disease (CD) may employ side-to-side anastomosis (STSA; anti-peristaltic orientation) or end-to-end anastomosis (ETEA). Our aim was to determine the impact of these two anastomotic techniques on long-term clinical status in postoperative CD patients. METHODS: We performed a comparative effectiveness study of prospectively collected observational data from consented CD patients undergoing their first or second ileocolonic bowel resection and re-anastomosis between 2008 and 2012, in order to assess the association between anastomosis type and 2-year postoperative quality of life (QoL), healthcare utilization, disease clinical or endoscopic recurrence, use of medications, and need for repeat resection. RESULTS: One hundred and twenty eight postoperative CD patients (60 STSA and 68 ETEA) were evaluated. At 2 years postoperatively, STSA patients had higher rates of emergency department visits (33.3% vs. 14.7%; P=0.01), hospitalizations (30% vs. 11.8%; P=0.01), and abdominal computed tomography scans (50% vs. 13.2%; P<0.001) with lower QoL (mean short inflammatory bowel disease questionnaire 47.9 vs. 53.4; P=0.007). There was no difference among the two groups in the 30 day surgical complications and 2-year patterns of disease activity, CD medication requirement, endoscopic recurrence, and need for new surgical management (all P > 0.05). CONCLUSIONS: At 2 years postoperatively, CD patients with ETEA demonstrated better QoL and less healthcare utilization compared with STSA, despite having similar patterns of disease recurrence and CD treatment. These findings suggest that surgical reconstruction of the bowel as an intact tube (ETEA) contribute to improved functional and clinical status in patients with CD.

Peripheral Eosinophilia in Patients With Inflammatory Bowel Disease Defines an Aggressive Disease Phenotype.

OBJECTIVES: Peripheral blood eosinophilia (PBE) in inflammatory bowel disease (IBD) is associated with ulcerative colitis (UC) and active disease. Little data exist on the long-term impact of PBE on disease course. We aimed to investigate the multi-year patterns of PBE and its impact on disease severity in a large IBD cohort. METHODS: We performed a registry analysis of a consented, prospective, natural history IBD cohort at a tertiary center from 2009 to 2014. Demographics, comorbidities, disease activity, healthcare utilization, and time to hospitalization or surgical resection of patients who displayed PBE were compared to patients without PBE. RESULTS: Of the 2,066 IBD patients, 19.2% developed PBE. PBE was significantly associated with UC (P<0.001), extensive colitis (P<0.001), and shorter disease duration (P=0.03). Over six years, PBE patients had more active disease (Harvey-Bradshaw Index P=0.001; ulcerative colitis activity index P<0.001), concurrent C-reactive protein elevation (P<0.001), healthcare utilization (hospitalization P<0.001, IBD surgery P<0.001), and more aggressive medical therapy (prednisone P<0.001, anti-TNF P<0.001). Patients with PBE had a significantly reduced time to hospitalization in both UC (P<0.001) and Crohn's disease (CD) (P<0.001) and reduced time to colectomy in UC (P=0.003). On multivariable modeling, PBE remained significantly associated with hospitalization and surgery in both CD and UC. New diagnosis of UC with PBE was associated with increased steroid (P=0.007) and anti-TNF (P=0.001) requirement. CONCLUSION: This multi-year study of a large IBD cohort suggests that peripheral blood eosinophilia represents a biomarker of a distinct IBD subgroup, with a unique inflammatory signature, and at risk for worse clinical outcomes.

Development of an Inflammatory Bowel Disease Research Registry Derived from Observational Electronic Health Record Data for Comprehensive Clinical Phenotyping.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous collection of chronic inflammatory disorders of the digestive tract. Clinical, genetic, and pathological heterogeneity makes it increasingly difficult to translate efficacy studies into real-world practice. Our objective was to develop a comprehensive natural history registry derived from multi-year observational data to facilitate effectiveness and clinical phenotypic research in IBD. METHODS: A longitudinal, consented registry with prospectively collected data was developed at UPMC. All adult IBD patients receiving care at the tertiary care center of UPMC are eligible for enrollment. Detailed data in the electronic health record are accessible for registry research purposes. Data are exported directly from the electronic health record and temporally organized for research. RESULTS: To date, there are over 2565 patients participating in the IBD research registry. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, laboratory values, health-related questionnaires quantifying disease activity and quality of life, and analytical information on treatment, temporally organized for 6 years (2009-2015). The data have resulted in a detailed definition of clinical phenotypes suitable for association studies with parameters of disease outcomes and treatment response. We have established the infrastructure required to examine the effectiveness of treatment and disease course in the real-world setting of IBD. CONCLUSIONS: The IBD research registry offers a unique opportunity to investigate clinical research questions regarding the natural course of the disease, phenotype association studies, effectiveness of treatment, and quality of care research.

An Exposure-Based Video Game (Dr. Zoo) to Reduce Needle Phobia in Children Aged 3 to 6 Years: Development and Mixed Methods Pilot Study.

BACKGROUND: Needle phobia, which affects 19% of children aged 4 to 6 years, prevents many children from receiving necessary or preventive medical treatments. Digital interventions have been made to target needle phobia but currently rely on distraction rather than evidence-based exposure. OBJECTIVE: We designed and evaluated a serious exposure-based mobile game called Dr. Zoo to reduce the fear of needles in children aged 3 to 6 years, where players administered shots to cartoon animals. METHODS: We conducted a mixed methods study with 30 parents (mean age 35.87, SD 4.39 years) and their 36 children (mean age 4.44, SD 1.11 years) who played the game for 5 days leading to a scheduled appointment that included an injection (eg, influenza vaccination). After the study, parents completed exit surveys and participated in semistructured interviews to evaluate ease of use, acceptability, and preliminary effectiveness of the game and to provide insights on their experience with the game to inform future developments. Interview transcripts were analyzed by 3 independent coders following an open coding process and subsequently coded and discussed to reach consensus. RESULTS: Parents rated their child's difficulty in completing the game as very low on average (scale 1-5; mean 1.76, SD 0.82) and were highly likely to recommend Dr. Zoo to other parents (scale 1-5; mean 4.41, SD 0.87), suggesting Dr. Zoo's strong ease of use and high acceptability. In the exit survey, parents rated their child's fear as significantly lower after participating in the study (scale 1-5; mean 3.09, SD 1.17) compared with that before participating (scale 1-5; mean 4.37, SD 0.81; z score=-4.638; P<.001). Furthermore, 74% (26/35) of the parents reported that the game had a positive impact on their child's fear or perception of needles (only 2 parents reported a negative impact). Qualitative analysis of the interview transcripts revealed potentially important features of the game in this positive impact, such as the game's interactive design, as observed in 69% (24/35) of our participants. CONCLUSIONS: The results suggest that an evidence-based serious mobile game can be an easy-to-use, acceptable, and potentially effective intervention for changing young children's fear and perceptions of needles. Leveraging digital interventions may be a potential solution to needle anxiety as a public health concern.

Evaluating the Feasibility of a Multiplayer Role-Playing Game as a Behavioral Health Intervention in Adolescent Patients With Chronic Physical or Mental Conditions: Protocol for a Cohort Study.

BACKGROUND: Numerous studies have revealed that adolescents with chronic physical or mental conditions (CPMCs) are at an increased risk for depression and anxiety, with serious direct and indirect negative effects on treatment adherence, family functioning, and health-related quality of life. As game-based approaches are effective interventions in treating anxiety and depression, we propose to explore the use of a multiplayer role-playing game (RPG) as a potential intervention for social isolation, anxiety, and depression. OBJECTIVE: The objectives of this study were to (1) determine the feasibility of using Masks, a multiplayer RPG, as an intervention for social isolation, anxiety, and depression in adolescents with CPMCs; (2) evaluate the viability of the research process; and (3) gauge participation in and engagement with RPG-based interventions. METHODS: This study is a remote synchronous game-based intervention for adolescents with CPMCs aged 14-19 years. Eligible participants completed a web-based baseline survey to assess anxiety, depression, and social isolation and to identify their gaming habits. After completing the baseline survey, they participated in 5 moderated Masks game sessions. In Masks, players assume the roles of young superheroes; select their character types, superpowers; and perform actions determined by the game's rule system and dice rolls. All game sessions were played using Discord, a communication platform commonly used by gaming communities. Games were led and moderated by game masters (GMs). After each game session, participants completed surveys to assess changes in anxiety, depression, and social isolation, and their attitude toward the game and the user experience. The participants also completed an exit survey after all 5 game sessions (modified version of the Patient Health Questionnaire and the Generalized Anxiety Disorder Questionnaire, and 17 open-ended questions). The GMs rated each game session and reported on gameplay, player behavior, comfort, and engagement levels of the players. RESULTS: As of March 2020, six participants were recruited for the pilot study to participate in moderated web-based game sessions of Masks; 3 completed all game sessions and all required assessments. Although the number of participants was too low to draw generalizable conclusions, self-reported clinical outcomes did seem to indicate a positive change in depression, anxiety, and social isolation symptoms. Qualitative analysis of postgame survey data from participants and GMs indicated high levels of engagement and enjoyment. Furthermore, the participants provided feedback about improved mood and engagement related to weekly participation in Masks. Lastly, responses to the exit survey showed interest in future RPG-related studies. CONCLUSIONS: We established a workflow for gameplay and evaluated a research protocol for evaluating the impact of RPG participation on isolation, anxiety, and depression symptoms in adolescents with CPMCs. Preliminary data collected from the pilot study support the validity of the research protocol and the use of RPG-based interventions in larger clinical studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/43987.

Testing the effects of the Strong Together self-advocacy serious game among women with advanced cancer: Protocol for the STRONG randomized clinical trial.

BACKGROUND: Women with advanced cancer experience significant barriers to achieving high-quality care and maximizing their physical and emotional health. Our novel serious game, Strong Together, aims to teach women with advanced cancer self-advocacy skills needed to improve their symptom burden, quality of life, and patient-centered care. METHODS: This is a single-center, multi-site randomized clinical trial of the Strong Together intervention among 336 women within three months of an advanced breast or gynecologic cancer diagnosis. Randomization occurs to the 3-month Strong Together serious game or enhanced care as usual group. The aims are to: (1) evaluate the effects of the intervention on patient self-advocacy (primary outcome); (2) evaluate the effects of the intervention on quality of life, symptom burden, and patient-centered care (secondary outcomes); and (3) evaluate the behavioral and game mechanisms that influence the efficacy of the intervention. ELIGIBILITY CRITERIA: female, age ≥ 18 years; diagnosis of advanced breast or gynecologic cancer within the past 3 months; Eastern Cooperative Oncology Group score of 0-2; English literacy; and ≥ 6-month life expectancy. Patient-reported outcome measures are collected at baseline, 3-months, and 6-months. CONCLUSION: This protocol is the first large-scale intervention aimed at promoting self-advocacy in women with advanced cancer. Understanding the ability of serious games to impact patient outcomes provides critical information for researchers, clinicians, and stakeholders aiming to improve patient-centered care. TRIAL REGISTRATION: NCT04813276.

A systematic comparison of the accuracy of monocular RGB tracking and LiDAR for neuronavigation.

With the advent of augmented reality (AR), the use of AR-guided systems in the field of medicine has gained traction. However, the wide-scale adaptation of these systems requires highly accurate and reliable tracking. In this work, the tracking accuracy of two technology platforms, LiDAR and Vuforia, are developed and rigorously tested for a catheter placement neurological procedure. Several experiments (900) are performed for each technology across various combinations of catheter lengths and insertion trajectories. This analysis shows that the LiDAR platform outperformed Vuforia; which is the state-of-the-art in monocular RGB tracking solutions. LiDAR had 75% less radial distance error and 26% less angle deviation error. Results provide key insights into the value and utility of LiDAR-based tracking in AR guidance systems.

High Sugar-Sweetened Beverage Consumption Is Associated with Increased Health Care Utilization in Patients with Inflammatory Bowel Disease: A Multiyear, Prospective Analysis.

BACKGROUND: Dietary factors like sugar-sweetened beverage (SSB) consumption are known to influence disease course in a variety of illnesses; however, long-term outcomes are not well documented for inflammatory bowel disease. OBJECTIVE: Does high consumption of SSBs lead to high healthcare utilization (ie, hospitalizations and emergency department visits), inflammation, and disease severity in patients with inflammatory bowel disease? DESIGN: A prospective cohort study was conducted from 2015 to 2019. Patients enrolled in the discovery study cohort were followed for 3 years, whereas patients in the validation cohort were followed for 2 years. They underwent nutrition assessment and received routine care. Dietary intakes of SSBs and fiber were quantified by a validated, self-reported questionnaire. PARTICIPANTS/SETTING: For the discovery study cohort, 1133 adult patients were recruited from the University of Pittsburgh Medical Center Digestive Disease Clinic in Pittsburgh, PA. Eligible patients had a preexisting diagnosis of Crohn's disease or ulcerative colitis and had at least annual follow-up at this tertiary referral center. High SSB consumption was defined as 7 or more SSBs per week. Moderate was defined as > 2 but < 7 SSBs per week. Low SSB consumption was defined as 2 or fewer SSBs per week. MAIN OUTCOME MEASURES: Primary outcome was time to hospitalization and emergency department visits. Secondary outcomes assessed laboratory markers of disease severity and inflammation. Tertiary outcomes assessed time to hospitalization and emergency department visits in a subsequent independent cohort of patients. STATISTICAL ANALYSIS PERFORMED: Multivariable logistic regression, Kaplan-Meier, and Cox proportional hazards modeling RESULTS: The discovery cohort included of 1,133 adult patients with inflammatory bowel disease (58% women, 70% with Chron's disease, 30% with ulcerative colitis, median age 46 years). Low SSB consumption, moderate SSB consumption, and high SSB consumption occurred in 57%, 17%, and 26% in the discovery cohort, respectively. Among patients without active disease at enrollment, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption (hazard ratio 1.55, 95% CI 1.06 to 2.27; and hazard ratio 1.53, 95% CI 1.10 to 2.13). In terms of disease severity and inflammatory biomarkers, high SSB consumption was associated with increase odds of elevated erythrocyte sedimentation rate (odds ratio 2.04, 95% CI 1.31 to 3.18), elevated C-reactive protein level (odds ratio 1.60, 95% CI, 1.07-2.37), eosinophilia (odds ratio 1.88, 95% CI 1.06 to 3.335), and monocytosis (odds ratio 1.81, 95% CI 1.18 to 2.79) when compared with low SSB consumption after adjusting for baseline differences. Lastly, the validation cohort produced similar results to our primary outcome (ie, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption). CONCLUSIONS: High SSB consumption was associated with decreased time to hospitalization and emergency department visits. Furthermore, high SSB consumption is associated with disease severity biomarkers and inflammation. Prospective studies assessing the therapeutic influence of nutrition counseling and decreased SSB consumption on long-term inflammatory bowel disease clinical course are warranted.

Monocytosis Is a Biomarker of Severity in Inflammatory Bowel Disease: Analysis of a 6-Year Prospective Natural History Registry.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with alterations of the innate and adaptive immune systems. Monocytes respond to inflammation and infection, yet the relationship between monocytosis and IBD severity is not fully understood. We aimed to characterize the prevalence of monocytosis in IBD and the association between monocytosis and disease severity and IBD-related health care utilization. METHODS: We used a multiyear, prospectively collected natural history registry to compare patients with IBD with monocytosis to those without monocytosis, among all patients and by disease type. RESULTS: A total of 1290 patients with IBD (64.1% with Crohn disease; 35.9% with ulcerative colitis) were included (mean age 46.4 years; 52.6% female). Monocytosis was found in 399 (30.9%) of patients with IBD (29.3% with Crohn disease; 33.9% with ulcerative colitis). Monocytosis was significantly associated with abnormal C-reactive protein level and erythrocyte sedimentation rate, anemia, worse quality of life, active disease, and increased exposure to biologics (all P < 0.001). Compared with patients without monocytosis, patients with monocytosis had a 3-fold increase in annual financial health care charges (median: $127,013 vs. $32,925, P < 0.001) and an increased likelihood of hospitalization (adjusted odds ratio [AOR], 4.5; P < 0.001), IBD-related surgery (AOR, 1.9; P = 0.002), and emergency department (ED) use (AOR, 2.8; P < 0.001). Patients with monocytosis had a shorter time to surgery, hospitalization, and ED visit after stratifying by disease activity (all P < 0.05). CONCLUSIONS: Patients with IBD with monocytosis, regardless of disease type, are at increased risk for worse clinical outcomes, hospitalization, surgery, and ED use. Peripheral monocytosis may represent a routinely available biomarker of a distinct subgroup with severe disease.

Elevated serum globulin fraction as a biomarker of multiyear disease severity in inflammatory bowel disease.

Background: Serum protein reflects albumin and globulin levels, both of which can be altered in inflammatory bowel disease (IBD). The implications of a high globulin fraction in IBD are unknown. We hypothesized that a high globulin fraction may function independently of albumin as a biomarker of disease severity in IBD patients over a multiyear period. Methods: This was an observational study from a prospective IBD registry of a tertiary care center. High globulin fraction was defined as an elevated globulin level >4 g/dL. Data collected included patient demographics, medication exposures, quality-of-life scores, disease activity, emergency department visits, telephone calls, hospitalizations, and IBD-related surgeries over a 4-year period. Comparisons between patients with a high globulin fraction and those without were performed using Pearson's chi-squared, Student's and Mann-Whitney tests. Multivariate analyses were used to assess the relationship between high globulin fraction and healthcare utilization. Results: A total of 1767 IBD patients with a 4-year follow up were included: 53.5% female, mean age 48.4±15.1 years, and 65.4% with Crohn's disease. Of these patients, 446 (25.2%) presented with elevated globulin fraction. Patients with a high globulin fraction were more likely to be hospitalized during the study period. This result remained significant after multivariate analysis for both Crohn's disease patients and those with ulcerative colitis. Conclusion: A high globulin fraction is independently associated with greater disease severity and healthcare utilization in IBD patients, and may function as a routinely available biomarker of a more severe future disease trajectory.

The Impact of Cholecystectomy on Long-Term Disease Outcomes and Quality of Life in Patients with Crohn's Disease.

BACKGROUND: Cholecystectomy (CCY) is one of the most frequently performed abdominal surgeries. However, the impact of CCY in clinical settings with altered gastrointestinal physiology and anatomy, such as Crohn's disease (CD), has not been fully characterized. We sought to investigate clinical outcomes, disease severity, and quality of life of CD patients after CCY. METHODS: We utilized a prospective, longitudinal registry of consented CD patients followed at a tertiary center. Crohn's disease patients that had or had not undergone CCY formed the 2 study groups. The absence or presence of gallbladder was confirmed with abdominal CT scans obtained during routine care. Multiyear clinical, biochemical, and histologic data were collected and analyzed. RESULTS: Among 834 CD patients, 151 (18%) had undergone CCY. History of CCY was associated with higher disease activity (median Harvey-Bradshaw index; P < 0.001), more years with anemia (P = 0.048), lower albumin (P = 0.001), worse quality of life (mean Short Inflammatory Bowel Disease Questionnaire; P < 0.001), chronic abdominal pain (P < 0.001), higher risk for incident colonic dysplasia (P = 0.011), higher rates of annual hospital admissions (P = 0.004), and opioid use (P < 0.001). In multivariate analysis, CCY remained associated with higher disease activity (P < 0.001), lower albumin (P = 0.008), lower quality of life (P < 0.001), and more hospital admissions (P = 0.008), whereas CD patients with diseased ileum had higher risk for colonic dysplasia (P = 0.031). CONCLUSIONS: CCY in CD patients was associated with multiple markers of disease activity and worse quality of life during multiyear follow up. This data suggests that CCY in CD patients may adversely impact the long-term clinical course.

Serum IgG4 Subclass Deficiency Defines a Distinct, Commonly Encountered, Severe Inflammatory Bowel Disease Subtype.

BACKGROUND: Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity. METHODS: We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period. Patients with IBD with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. We stratified patients with IBD with low, normal, or high serum IgG4 levels. RESULTS: We found IgG4 characterized in 1193 patients with IBD and low IgG4 levels in 233 patients (20%) and elevated IgG4 levels in 61 patients (5%). An IgG4 deficiency did not significantly correlate with other antibody deficiencies. In a multiple Poisson regression analysis, low IgG4 was associated with more years on biologic agents (P = 0.002) and steroids (P = 0.049) and more hospital admissions (P < 0.001), clinic visits (P = 0.010), outpatient antibiotic prescriptions (P < 0.001), and CD-related surgeries (P = 0.011) during the study period after controlling for certain confounders. Elevated IgG4 was only associated with primary sclerosing cholangitis (P = 0.011). A cohort of patients with IgG4-deficient severe IBD received intravenous Ig replacement therapy, which benefited and was continued in 10 out of 11 individuals. CONCLUSIONS: An IgG4 subclass deficiency, distinct from other antibody deficiencies, occurred commonly in a referral IBD population and was associated with multiple markers of disease severity. This is the first association of IgG4 subclass deficiency with an inflammatory disease process. Further work is needed to define the mechanistic role of IgG4 deficiency in this severe IBD subgroup.

Mapping Behavioral Health Serious Game Interventions for Adults With Chronic Illness: Scoping Review.

BACKGROUND: Serious games for health are increasingly being used to address health outcomes in patients with chronic illnesses. These studies vary in their study designs, patient populations, frameworks, outcome variables, and degree of specificity of the serious game intervention. OBJECTIVE: This scoping review aims to clarify the conceptual features of the existing research related to serious games designed to improve cognitive and behavioral outcomes in adults with chronic illness. METHODS: We applied the Preferred Reporting Items of Systematic Reviews and Meta-Analysis for scoping reviews (PRISMA-ScR) methodology, including an a priori research question. We searched 4 electronic databases to identify articles published through November 2019. Inclusion criteria encompassed (1) adults 18 years or older; (2) patients with a diagnosis of chronic illness; (3) a serious game intervention; and (4) defined patient outcomes that assess patients' behavioral, cognitive, or health outcomes. RESULTS: Of the 3305 articles identified, 38 were included in the review. We charted and analyzed the theoretical frameworks, key concepts, and outcome variables of these studies with summaries of features across articles. The majority of studies used a randomized controlled trial design (23/38, 61%), included a custom serious game intervention (22/38, 58%), and lacked a theoretical framework (25/38, 66%). Common outcome variables included quality of life (16/38, 42%), mood (15/38, 39%), cognitive function (13/38, 34%), symptoms (12/38, 32%), and physical activity (9/38, 24%). Key differences between studies included whether or not serious games aimed to train versus teach patients, be widely accessible versus tailored interventions, or replace versus complement current treatments. CONCLUSIONS: This scoping review defines the current landscape of research in serious games for health research targeting behavioral and cognitive outcomes in adults with chronic disease. Studies have addressed a variety of patient populations and diverse patient outcomes. Researchers wanting to build on the current research should integrate theoretical frameworks into the design of the intervention and trial to more clearly articulate the active ingredients and mechanisms of serious games.

Disease Characteristics and Severity in Patients With Inflammatory Bowel Disease With Coexistent Diabetes Mellitus.

BACKGROUND: Given the rising prevalence of diabetes mellitus (DM) and the limited data on its effect on the course of inflammatory bowel disease (IBD), we characterized multiyear patterns of disease severity in a cohort of IBD patients with coexistent DM. METHODS: Data of consented IBD patients followed prospectively in a natural history registry at a tertiary center between 2009 and 2017 were analyzed. Patients with ≥3 years of clinical follow-up were included. Patients identified with a diagnosis of DM were compared with 400 consecutive IBD controls without a diagnosis of DM, no laboratory evidence of hyperglycemia, and no history of antihyperglycemic treatment. RESULTS: Out of 2810 IBD patients, 141 (5%) had DM (IBD DM; 44% ulcerative colitis, 56% Crohn's disease, 48.2% female). IBD DM had higher use of 5-aminosalicylic acid (5ASA) agents (P = 0.04), narcotics (P < 0.001), and antibiotics (P = 0.007) but not immunomodulators and/or biologics compared with IBD controls. When analyzing biomarkers of severity, IBD DM demonstrated higher frequencies of elevated C-reactive protein (CRP; P = 0.006), elevated erythrocyte sedimentation rate (ESR; P = 0.001), eosinophilia (P = 0.004), monocytosis (P = 0.02), and hypoalbuminemia (P = 0.001). IBD DM had worse quality of life (mean Short Inflammatory Bowel Disease Questionnaire; P < 0.001). IBD DM had increased health care utilization compared with controls (emergency room usage P = 0.008, hospitalizations P < 0.001, gastroenterology clinic visits P < 0.001, and median annual charges P < 0.001). Among IBD DM patients, the use of immunomodulators and/or biologics was not associated with further complications as measured by antibiotic use or hospitalizations. CONCLUSIONS: This study of a large IBD cohort suggests that DM in IBD may be associated with increased disease severity and that there may be room for increasing use of highly effective immunomodulator and/or biologic agents in this group.

Peripheral Blood Eosinophilia and Long-term Severity in Pediatric-Onset Inflammatory Bowel Disease.

BACKGROUND: Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS: We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS: Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS: Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.

Lasting Impact of Clostridium difficile Infection in Inflammatory Bowel Disease: A Propensity Score Matched Analysis.

BACKGROUND: Patients with inflammatory bowel disease are at an increased risk of Clostridium difficile infection (CDI), but the impact of CDI on disease severity is unclear. The aim of this study was to determine the effect of CDI on long-term disease outcome in a matched cohort of patients with inflammatory bowel disease. METHODS: Patients who tested positive for infection formed the CDI-positive group. We generated a 1:2 propensity matched case to control cohort based on risk factors for CDI in the year before infection. Health care utilization data (emergency department use, hospitalizations, and telephone encounters), medications, laboratories, disease activity, and quality-of-life metrics were compared by CDI status. RESULTS: A total of 198 patients (66 CDI and 132 matched controls) were included (56.6% women; 60.1% Crohn's disease, and 39.9% ulcerative colitis). In the year of infection, having CDI was significantly associated with more steroid and antibiotic exposure, elevated C-reactive protein or erythrocyte sedimentation rate, low vitamin D, increased disease activity, worse quality of life, and increased health care utilization (all P < 0.01). During the next year after infection, patients with CDI continued to have increased exposure to CDI-targeted antibiotics (P < 0.001) and other antibiotics (P = 0.02). They also continued to have more clinic visits (P = 0.02), telephone encounters (P = 0.001), and increased health care financial charges (P = 0.001). CONCLUSIONS: CDI in inflammatory bowel disease is significantly associated with markers of disease severity, increased health care utilization and poor quality of life during the year of infection, and a 5-fold increase in health care charges in the year after infection (see Video Abstract, Supplemental Digital Content, http://links.lww.com/IBD/B658).

Demographic and Clinical Predictors of High Healthcare Use in Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory condition requiring significant healthcare expenditure. Subgroups of individuals contribute disproportionately to spending. We aimed to determine demographic and clinical factors predictive of high healthcare expenditures for IBD patients followed over a multiyear period. METHODS: This was a registry analysis using a prospective observational, consented, natural history registry from a tertiary IBD center and associated medical charges, not including pharmacy expenses. The 100 patients with the highest medical charges (top 5%) were compared with the median 300 patients. Logistic regression determined demographic and clinical factors associated with high charge patients. RESULTS: IBD patients in the high charge group had significantly more unemployment (P < 0.0001), were of black race (P = 0.013), comorbid psychiatric illness (P = 0.002), hypertension (P = 0.01), diabetes (P = 0.004), opiate use (P < 0.0001), perianal involvement (P = 0.002), penetrating disease (P < 0.0001), and extensive colitis (P = 0.01). In multivariate analysis, unemployment (Crohn's disease [CD]: odds ratio [OR], 3.04; 95% confidence interval [CI], 1.32-7.02; ulcerative colitis [UC]: OR, 2.68; 95% CI, 1.20-5.99), psychiatric illness (UC: OR, 2.08; 95% CI, 1.03-4.19), opiates (CD: OR, 5.61; 95% CI, 2.67-11.82; UC: OR, 5.14; 95% CI, 2.52-10.48), prior surgery (CD: OR, 3.29; 95% CI, 1.59-6.82; UC: OR, 2.72; 95% CI, 1.39-5.32), penetrating CD (OR, 3.29; 95% CI, 1.02-10.62), and corticosteroid requirement (CD: OR, 3.78; 95% CI, 1.86-7.65; UC: OR, 2.98; 95% CI, 1.51-5.90) remained independently associated with high charges. CONCLUSIONS: High expenditure IBD patients were affected by more severe disease. The high prevalence of depression, anxiety, and chronic pain in these patients suggests the need for focused treatment of these comorbidities ultimately to reduce financial burden.

Silent Crohn's Disease Predicts Increased Bowel Damage During Multiyear Follow-up: The Consequences of Under-reporting Active Inflammation.

BACKGROUND: Patients with Crohn's disease (CD) in clinical remission with elevated C-reactive protein (CRP) have been labeled "silent CD" and have increased 2-year hospitalization rates when compared with asymptomatic patients with no biochemical evidence of inflammation. The risk of cumulative bowel damage in patients with silent CD is unknown. METHODS: Observational study of patients with CD prospectively followed in a tertiary referral natural history registry. Consecutive patients with CD in clinical remission (Harvey-Bradshaw Index ≤ 4) with good quality of life (short inflammatory bowel disease questionnaire score ≥ 50), and same day CRP measurement at first encounter, followed for a minimum of 4 years formed the study population. Disease trajectory was determined using change in Lémann Index as a measure of bowel damage. RESULTS: A total of 185 patients with CD (median age 42 years; 51.4% men) were included in the study. CRP elevation was observed in 43 (23%) patients (Silent CD cohort). Majority of them showed worsening disease trajectories based on change in Lémann Index when compared with asymptomatic patients with normal CRP (65% versus 36%, P < 0.0001). Multinomial logistic regression analysis demonstrated that elevated CRP was independently associated with 7-fold higher odds (odds ratio = 6.93, P < 0.0001) of having worse disease trajectories when compared with stable disease trajectories. CONCLUSIONS: Two-thirds of patients with CD in clinical remission, while demonstrating elevated CRP, will develop bowel damage over the ensuing years, despite feeling well. These patients with silent CD are an "at-risk" group who warrant further investigation to prevent development of disease-related complications.