bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHARACTERIZING THE JOHNS HOPKINS INFLAMMATORY BOWEL DISEASE COHORT USING OMOP CDM
Authors: Haas Leonard , Nagy Paul , Bowring Mary , Cook Michael , Magen-Rimon Ramit , Weisshof Roni , Yanover Chen , Miller Steven 
Published: January 2023

Abstract

BACKGROUND
Inflammatory Bowel Disease (IBD) is an increasingly prevalent condition that results in weight loss, bloody diarrhea, and poor quality of life. Traditional population-based research on patients with IBD has involved use of relatively shallow claims data that is deficient in precise demographics. IBD research using richly detailed electronic health record (EHR) data has been difficult due to the need for laborious manual chart review to extract information, but new methods and technology allow for rapid EHR data extraction. We present here the results of the extraction of IBD patient data from our EHR into the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM).

METHODS
This study is an observational cohort study using patient health care data from our EHR extracted into the OMOP CDM. Transforming data into the standard CDM format allows for information from different databases and coding schema to be compared and aggregated. We used a de-identified dataset of all patients seen at Johns Hopkins Medicine since 2016. Our cohort of IBD, Crohn’s disease (CD), and Ulcerative Colitis (UC) patients were stratified by age, sex, race, weight, and pregnancy status. Within the cohorts, we obtained demographics, comorbidities, symptoms, labs, medications, and other data. We validated the extraction by comparison with EHR queries using Slicer/Dicer (SD).

RESULTS
There were 11,357 IBD patients including 6,512 CD patients and 4,224 UC patients. There were more female patients for both CD and UC (56.4% v 57.5%) and more white patients for both CD and UC (55.4% v 56.7%) compared to black (23.5% v 22.6%) and Asian patients (5.6% v 4.9%). CD and UC patients were treated with systemic steroids (49.1% v 51.5%), 5-ASA (24.9% v 47.2%) anti-TNF inhibitors (24.0% v 12%), IL12/23 inhibitors (8.4% v 2.7%), and JAK inhibitors (0.3% v 1.8%). Using SD queries, the percent differences were determined between the OMOP and EHR data, revealing a 0.54% difference in the number of CD patients and 10.36% difference in the number of UC patients (Table 1).

CONCLUSION
Using OMOP CDM to analyze clinical characteristics and outcomes for patients with IBD is a valuable method for obtaining de-identified patient data, reducing patient risk, and facilitating rapid creation of on-demand cohorts for multi-institutional research studies. This advantage is balanced by the lack of access to row-level data to validate cohorts. Local validation of data extraction through SD queries can allow for rapid creation of cohorts for big data research. The most significant differences between SD queries and OMOP CDM was in the calculation of prevalence of medications and race, suggesting that differing data extraction coding methods could result in queries that underestimate rates of treatment due to proprietary local coding schema.
PERSISTENCE WHILE ON LABELED MAINTENANCE DOSE AMONG BIO-EXPERIENCED PATIENTS WITH CROHN'S DISEASE INITIATED ON USTEKINUMAB COMPARED TO ADALIMUMAB
Authors: Zhdanava Maryia , Ding Zhijie , Manceur Ameur , Kachroo Sumesh , Holiday Christopher , Zhao Ruizhi , Pilon Dominic 
Published: January 2023

Abstract

BACKGROUND
In Crohn’s disease (CD), dose escalation on biologic therapy may be required to maintain effectiveness, while adverse events or non-response, among other factors, may lead to lack of persistence. Understanding persistence while on labeled maintenance dose is particularly important in bio-experienced patients with CD, as they may have reduced response to subsequent lines of therapy. This analysis compared persistence while on labeled maintenance dose among bio-experienced patients on ustekinumab versus adalimumab in the United States (US).

METHODS
Adults with CD initiated on ustekinumab or adalimumab (index date) between 09/23/2016 (ustekinumab approval for CD in the US) and 08/01/2019 were selected from IBM® MarketScan® Commercial Database. Patients were bio-experienced (≥1 claim for another CD-indicated biologic in the 12 months baseline period pre-index date). Patients with other auto-immune diseases at baseline were excluded. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Persistence to the index agent while on labeled maintenance dose was defined as (1) no gaps between days of therapy supply &gt;120 days for ustekinumab (2 x 8-week on-label maintenance dose interval) or &gt;60 days for adalimumab (2 x days of supply mode) and (2) no dose change relative to the US label maintenance dose. It was assessed from index date until the earliest of discontinuation (event), dose change during maintenance phase (censoring), or last day of supply (censoring). Weighted Kaplan-Meier and Cox proportional hazards models adjusted for baseline classes of biologics were used to assess the outcome at 12 months post-index.

RESULTS
903 bio-experienced patients with CD were included in the ustekinumab cohort (mean age 40.9 years old; 57.1% female) and 525 in the adalimumab cohort (mean age 41.3; 56.3% female). During the baseline period, 71.1% and 72.6% used corticosteroids, 41.2% and 40.8% used immunomodulators, and 11.1% and 12.6% had a prior CD-related surgery, in the ustekinumab and adalimumab cohorts, respectively. At 12 months post-index, the probability of persisting on the index biologic while on labeled maintenance dose was higher in the ustekinumab cohort versus adalimumab cohort (78.8% vs. 67.8%; Fig. 1). Patients in the ustekinumab versus adalimumab cohort had a 71% higher rate of persistence while on labeled maintenance dose (hazard ratio [HR] 1.71; 95% confidence interval: 1.31-2.23; P-value: &lt;0.001*).

CONCLUSIONS
Bio-experienced patients with CD initiated on ustekinumab were significantly more persistent while on labeled maintenance dose compared to patients initiated on adalimumab. These results confirm results on persistence to biologics in bio-experienced patients with CD from a prior study.
ASSESSMENT OF THE IMMUNE CELL LANDSCAPE IN INFLAMMATORY BOWEL DISEASE
Authors: Martinez Evelyn Calderon , Zevallos-Delgado Christian , Ng Wern Lynn , Gautam Seema Sharma , Joseph Maria 
Published: January 2023

Abstract

INTRODUCTION
Inflammatory Bowel Disease (IDB) is a chronic and sometimes refractory group of gastrointestinal conditions that can cause enormous medical and socioeconomic burdens. [1] Both, innate and adaptive immune cells play a crucial role in the pathogenesis of IBD, but the exact mechanisms are not totally well understood [2] An improved understanding of the immune cell landscape behind IBD is necessary for identifying novel diagnostic and therapeutic targets.

OBJECTIVE
The aim of this study was to evaluate and compare the immune cell composition between healthy patients and patients with Ulcerative Colitis (UC) and Chron’s Disease (CD) in peripheral blood and colon biopsy samples.

METHODOLOGY
The immune cell landscape in peripheral blood and colon biopsy samples was determined using CIBERSORT and gene expression data from the study submitted by Argmann et al obtained via Gene Expression Omnibus (peripheral blood: GSE186507 and colon biopsies: GSE193677). In this study the biopsies were obtained from ileum, colon, and rectum. T-test was used to estimate the differences among the groups.

RESULTS
The immune cell landscape of peripheral blood showed more resting T CD4 memory cells in the control group (p=0.009), while the number of activated T CD4 memory cells was greater in IBD patients (p= 0.01). The frequency of B cells naïve was higher in CD than in UC (p= 0.03), and CD8 T cells were more in UC (p=0.04). In terms of biopsies, the samples from the rectum showed the highest infiltration of immune cells. Macrophages M1 are present with higher numbers in rectum samples from CD vs UC (p=0.0026) and CD vs control group (p=8e-10).

CONCLUSIONS
The results showed significant differences in the immune cell composition among the control group, UC, and CD patients, not only in peripheral blood but also in biopsy samples. In both cases, Macrophages M1 were the most common cells found. These findings suggest that immune cell landscape could be used as a potential biomarker of the progression of IBD.
A NURSE LED INTERVENTION TO IMPROVE ACCESS TO CARE USING A TELEPHONE TRIAGE ALGORITHM
Authors: Banty Andrea , Solomon Theodore , Lee Susie , Castelan Viankail Cedillo , Parry Alyssa , Davey Joseph , Paredes Jovina , Farrior Sharmayne , Torres Daisy , Savoy Rochelle , Martirosyan Lilly , Melmed Gil 
Published: January 2023

Abstract

BACKGROUND
Inflammatory bowel disease is a chronic inflammatory condition for which patients may require care on a more urgent basis. Response times can be delayed when clinics are inundated with calls or when providers are not available for immediate patient care. We developed and tested an algorithm to empower nurses to effectively triage phone calls and improve access.

METHODS
We created an algorithm for nurses handling phone calls and electronic messages to a tertiary care IBD clinic. Calls were divided into four categories: Needs Immediate Response, Disease Flare, Routine and Other. IBD nurses triaged calls to facilitate urgent visits with a nurse practitioner (NP) when deemed appropriate, bypassing physician review or response. We compared the time from call-to-visit during the 3 months before and 3 months after implementation of the algorithm. We also assessed clinical outcomes of these urgently scheduled visits including visit type (in-person or virtual), and whether there was a change in dose or type of therapy, new prescription of steroids, or emergency room referral. We used the Mann Whitney U Test to assess for pre-post changes.

RESULTS
We randomly assessed 60 visits per month in the 3 months before and 3 months after the algorithm was implemented (June 1, 2022), for a total of 360 visits. The median time from call-to-visit improved from 5 days during the 3 months prior to the algorithm implementation to 3.5 days during the 3 months after algorithm implementation (p=0.016). There was no significant change in visit type pre- and post-intervention. Overall clinical interventions during these visits included therapy change (36%), a new prescription of corticosteroids (9%), new diagnostic testing ordered (67%) and ER referral (1%); these did not significantly differ in the pre- and post-intervention periods.

CONCLUSION
Utilization of a phone call triage algorithm by nurses can help improve the time from call-to-visit without involvement of a physician. Urgently scheduled NP visits result in important clinical interventions including changes to therapy and diagnostic testing. Implementation of nurse-led triage algorithms can improve access to care in a tertiary IBD clinic.
THE ONSET AND SEVERITY OF ULCERATIVE COLITIS IN IL-10 -/- MICE IS NOT DEPENDENT ON FECAL MICROBIOTA TRANSPLANTATION FROM ULCERATIVE COLITIS PATIENTS
Authors: Roy Kayla , Moncada Edward , Reddivari Lavanya 
Published: January 2023

Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects around 1% of the U.S population. IBD is comprised of Chron’s Disease and Ulcerative Colitis (UC), with UC having a higher incidence rate. IBD is believed to be caused by immune dysfunction and several environmental factors. Specifically in UC, bacterial dysbiosis is positively correlated with colitis severity and incidence. Thus, we propose that genetically susceptible mice colonized with human colitis-associated bacteria will exhibit early onset and increased colitis severity compared to mice colonized with fecal microbiota from healthy individuals. To test this hypothesis, germ-free IL-10-/- mice of an average age of 20 weeks were gavaged orally with fecal samples from healthy individuals and a severe colitis patient with a fecal calprotectin level of 1947 ug/mg. The Disease Activity Index (DAI) was calculated based on occult blood, weight loss, stool consistency, and grimace. DAI was used to assess colitis severity weekly in transplanted mice for eight weeks.16S rRNA sequencing analysis showed a significant difference in alpha (Shannon Index) and beta diversity (unweighted UniFrac) between the colitis patient and healthy donors indicating dysbiosis (p=.0001; p=.001). The colitis donor had a reduction in species richness. Furthermore, recipient mice clustered with the donors in their bacterial composition. Compared to mice with healthy individual-associated bacteria, colitic-associated bacteria did not significantly increase the colitis incidence or severity in IL-10 -/- mice. Furthermore, there were no significant differences in DAI scores, organ weights, and gut permeability between the treatments. Thus, this study demonstrates that bacterial dysbiosis alone is not sufficient to induce colitis in genetically predisposed mice.
REAL-WORLD EXPERIENCE FOR BIOLOGIC USE IN IBD IN THAI: A SINGLE-CENTER EXPERIENCE
Authors: Limsrivilai Julajak , Chaemsupaphan Thanaboon , Sattayalertyanyong Onuma , Subdee Nichcha , Permpim Parinya , Pausawasdi Nonthalee 
Published: January 2023

Abstract

BACKGROUND
Biologics have been used for the treatment of inflammatory bowel disease (IBD) worldwide; however, their use is still limited in Southeast Asia. This study aimed to describe the pattern of biologic use and outcomes in a tertiary referral center in Thailand.

METHOD
All patients with IBD who used biologics from the first case in 2012 to present in our center were enrolled. The data were prospectively collected since 2017; the data of patients before 2017 were retrospectively reviewed. The treatment outcomes comprised cumulative clinical, endoscopic, radiologic response or remission, and quality of life assessed by SIBDQ. Furthermore, the biologic persistence was reported.

RESULTS
Of 296 cases currently in the IBD clinic, 85 used biologics, including infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST). The mean age was 44.4 years, and 62% were male. Fifty-eight (68.2%) had Crohn’s disease (CD) and 27 (31.8%) had ulcerative colitis (UC). In CD, 58% had ileocolonic disease, 48% had bowel stricture, 29% had fistula, and 19% had perianal diseases. In UC, 19% had left-sided colitis, and 81% had extensive colitis. Most patients (97%) failed conventional treatment. In CD, 60%, 31%, and 8.6% use IFX, VDZ, and UST as the first biologic, respectively. While 81.5% of UC used VDZ and 18.5% used IFX. Concomitant immunomodulator was used in 77.6%. The median duration of the first biologic use was 12.6 months. The outcomes of the treatment were shown in Table 1. The overall cumulative clinical response and remission at 1 year were 94% and 63%, respectively, without significant differences among each biologic. The cumulative rate of endoscopic remission was 29%, 64%, and 82% at 1, 3, and 5 years, respectively, also without significant differences among each biologic (p=0.21). However, subgroup analysis in Crohn’s disease showed a trend of a better endoscopic remission rate for IFX and UST when compared to VDZ (p=0.15). The radiologic remission rate was only 12% of 25 patients who underwent CT enterography. The SIBDQ increased from 52.0 to 57.4 after 1 year of treatment. Thirty-six (42%) stopped the medicine. As shown in Figure 1, the overall cumulative rate of biologic discontinuation was 19% and 39% in the first and second year, respectively, without significant differences among biologics. However, the reason for drug discontinuation was different as all adverse events occurred in only patients using IFX.

CONCLUSION
Biologics were mostly used in refractory patients in this cohort. The outcomes were comparable to those previously reported in western. Current biologics could significantly improve patients’ symptoms, quality of life, and mucosal healing, but not transmural healing. The adverse events were less in newer biologics.
HLA-DQA1*05 ASSOCIATES WITH IMMUNOGENICITY AND LOSS OF RESPONSE TO ANTI-TNF THERAPY IN THE IBD POPULATION: A META-ANALYSIS
Authors: Bergstein Suzannah , Spencer Elizabeth 
Published: January 2023

Abstract

BACKGROUND
The human leukocyte antigen (HLA) allele group HLA-DQA1*05 has been associated with the development of antidrug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF)1 in the inflammatory bowel disease (IBD) population, except in the setting of proactive optimization2. We performed a meta-analysis to determine the prevalence of HLADQA1*05 carriage, to define the association of HLA-DQA1*05 on immunogenicity and loss of response (LOR) to anti-TNF, and to explore the impact of therapeutic drug monitoring (TDM) on this association.

METHODS
A systematic search of EMBASE, MEDLINE, Web of Science, and SCOPUS was conducted and identified 49 studies. Fourteen studies were included in the meta-analysis according to our inclusion and exclusion criteria. Two reviewers independently assessed eligibility and extracted data. Data extraction focused on the prevalence of HLADQA1*05 carriage, management style of the subjects (proactive TDM vs not), use of combination therapy with immunomodulators (IMM), and association of the variant with ADA and LOR. To examine the potential mitigating effect of management style, three forest plots were generated for each outcome including: 1. all studies, 2. studies using solely proactive TDM, and 3. studies where TDM was either not defined or not performed.

RESULTS
The prevalence of HLADQA1*05 carriage was 43.3% across the 14 manuscripts. Ten studies used data from adult populations, 2 reported on pediatrics only, and 2 reported on a mix of pediatrics and adults. Nine studies took place in Europe, and 5 occurred in North America. A little over half (57%) were abstracts. All studies included some patients on combination therapy with IMM. Data analysis confirmed that possessing the HLADQA1*05 variant leads to an increased ADA risk (OR 1.63 [95% CI: 1.35 - 1.98]). When focusing on the studies that used proactive optimization of anti-TNF therapy, the variant was no longer a risk factor for developing ADA (OR 0.37 [95% CI: 0.19 - 0.70]). Without proactive optimization, the carriage of HLADQA1*05 appears to consistently be associated with a higher risk of immunogenicity (OR 1.93 [95% CI: 1.58 - 2.36]) (Figure 1). HLADQA1*05 was also found to be a risk factor for LOR (HR 1.84 [95% CI: 1.53 - 2.22]) (Figure 2); insufficient data were available for the studies with proactive TDM on LOR.

CONCLUSION
Prevalence of HLADQA1*05 carriage is consistent across studies from both North America and Europe. This variant increases the risk of ADA and LOR to anti-TNF. However, in studies that used solely proactive TDM, variant carriage no longer conferred a risk for ADA.
1. Sazonovs A, et al. Gastro. 2020;158(1):189-199.
2. Spencer EA, et al. Gastro. 2022;162(6):1746-1748.e1743.
SPATIAL CONCORDANCE OF LEFT AND RIGHT COLON FINDINGS IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS AFTER TREAMTENT
Authors: Thadasina Meenal , Ammoun Alwalid , Perry Sharon , Patil Nirav , Young Denise , Saab Shahrazad , Moses Jonathan 
Published: January 2023

Abstract

OBJECTIVES
Achieving endoscopic remission has become the preferred clinical endpoint in the care of inflammatory bowel disease (IBD) patients. This requires repeat colonoscopy in patients with ulcerative colitis (UC) after initiation of therapy. Recent adult data suggests findings in the left colon on flexible sigmoidoscopy can be highly predictive of the findings if a full colonoscopy was performed; however, pediatric data is lacking for this association. The primary aim our study to assess the accuracy of findings on the left colon with the right colon for repeat endoscopy in pediatric patients with UC.

METHODS
This was a retrospective chart review of pediatric patients with UC seen at a single, academic center between 2010-2021. Patient demographics, clinical disease activity, laboratory values and endoscopic findings were collected. The Mayo Endoscopy Score (MES) was used to assess the findings in the right and left colon by a single reader (JM). Histologic findings were assessed using the Geobes index by a pathology resident (AKA) and over-read by an attending pathologist (SS). Weighted kappa correlation was used to assess concordance between left and right colon endoscopic and histologic findings. Receiver operator curve (ROC) analysis was used to assess the accuracy of left-sided findings predicting right-sided findings.

RESULTS
We analyzed repeat endoscopies from 57 patients, of which 31 (54.4%) were male, mean age at UC diagnosis was 13.5 ± 4.1 years, 53 (93%) were Caucasian. Most common medication was oral mesalamine (67.2%) and most common distribution was pancolitis (53.4%). Mean time between index and repeat colonoscopy was 11.3 months. On repeat colonoscopy, endoscopic findings on the left colon moderately correlated with findings on the right colon [(κ = 0.53 (0.30-0.75)], similarly histologic findings for the left and right colon had a moderate correlation [(κ = 0.41 (0.17-0.64)]. Area under the ROC (AUC) was 0.89 for endoscopic remission anywhere in the colon and 0.98 for complete endoscopic healing anywhere in the colon. Longer interval between the index and follow-up colonoscopy did not affect odds of concordance.

CONCLUSIONS
We found that endoscopic and histologic severity correlated between the right and left colon for repeat assessment after initiation of biologic therapy. Left sided findings were highly accurate for endoscopic remission and complete endoscopic healing anywhere in the colon. This data suggest a flexible sigmoidoscopy could be feasible in lieu of full colonoscopy when assessing for endoscopic remission in pediatric patients with UC, to reduce the burden to the family and healthcare system. Further, prospective studies with a central reading component for histology and endoscopy are needed to validate these findings.