bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMPACT OF TIMING OF INITIATION OF INFLIXIMAB ON THE RISK OF IBD-RELATED SURGERY AND COMPLICATIONS
Authors: Young Denise , Thavamani Aravind , Perez Jaime , Moses Jonathan 
Published: January 2022

Abstract

BACKGROUND
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system. Approximately 20% of new diagnoses are pediatric patients. Treatment for pediatric IBD has changed in recent years, focusing on decreased steroid use, and shifting to early initiation of biologics, especially in those at risk for complicated disease. Infliximab (IFX) is used for induction and maintenance. Clinical trials have shown that IFX improves clinical remission rates, and decreases hospitalizations and surgery rates. However, there is conflicting long-term data on whether infliximab has changed the natural course of IBD and decreased surgical risk.

OBJECTIVE
The objective of our study was to evaluate factors associated with increased risk of surgery in pediatric CD and UC patients using a large national health claims network database.

METHODS
We used TriNetX database and identified patients up to age 18 years, with a diagnosis of CD or UC (using ICD 9 and 10 codes) and treated with infliximab from January 1, 2006 to October 1, 2020. For each patient, we collected data on demographics profile, medication use, IBD related surgeries, and complications. Patients were then categorized into “early treatment” and “late treatment” groups, with early treatment being those who initiated infliximab therapy within 90 days of IBD diagnosis. The primary outcome was the need for surgery (partial or total colectomy, small intestinal resection and stricturoplasty). Secondary outcome was any IBD related complications (intraabdominal abscess, fistula formation, perianal abscess, fistuloectomy and fistulotomy).

RESULTS
A total of 7,954 IBD patients met inclusion criteria, of which 5,756 patients had CD, and 2,198 patients had UC. There were 2366 patients who were started on infliximab therapy within 90 days of initial diagnosis and the remaining 5,558 patients were in the late treatment group. A total of 169 (2.1%) patients underwent a major surgery and 560 (7%) patients experienced an IBD-related complication. Multivariate regression analysis did not reveal any significant association between timing of initiation of infliximab therapy and risk of surgery for both CD (OR: 1.12; 95% CI: 0.72 to 1.69, P=0.60) and UC (OR:1.57 ;95% CI: 0.91, 2.67, P=0.09). However, among CD patients, TPN use (OR: 5.45; 95% CI: 1.15 to 18.76, P = 0.014), fistulizing CD (OR: 4.59; 95% CI: 2.73 to 7.49; P &lt;0.0001) and malnutrition (OR: 1.62; 95% CI: 1.02 to 2.47, P = 0.03), were more likely to develop IBD-related complications. There were no significant risk factors associated with greater odds of surgery or IBD-related complications in UC patients.

CONCLUSION
Late initiation of infliximab therapy was not associated with increased risk of surgery or IBD-related complication compared to early therapy. Prospective studies are needed to further evaluate these findings.
UHPLC-MS/MS-BASED PLASMA LIPIDOMICS REVEAL ALTERATIONS ASSOCIATED WITH EXCLUSIVE ENTERAL NUTRITION TREATMENT IN ADULT PATIENTS WITH ACTIVE CROHN’S DISEASE
Authors: Yang Qingfan , Huang ZiCheng , Liu Hailing , Chao Kang , Gao Xiang 
Published: January 2022

Abstract

BACKGROUND
Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn’s disease (CD), although the mechanisms is unclear. Lipid metabolism and signaling have been suggested to play an important role in the pathophysiology of the disease, but their relationship with EEN therapy has not been reported. Hence, we assessed plasma lipid profiles of adult patients with active CD before and after EEN and compared them to those of healthy controls.

METHODS
Adult patients with active CD (n=11) who received EEN with an amino acid-based enteral nutrition formula for 12 weeks and age- and sex-matched healthy controls (n=17) were recruited. Plasma lipid profiles of 869 lipid species were measured before and after EEN in both groups using ultrahigh performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The CD activity index (CDAI), high-sensitivity C-reactive protein (hs-CRP) level, and nutrition-associated indices were evaluated. CDAI &lt;150 and a Simple Endoscopic Score for CD (SES-CD) ≤2 indicated clinical remission and mucosal healing (MH), respectively.

RESULTS
After 12 weeks of EEN, 81.8% (9 of 11) patients achieved remission with a significant decrease in the CDAI (P&lt;0.001) and hs-CRP levels (P&lt;0.001). Ten patients had a SES-CD score of &gt;2 before EEN, which declined after EEN (P=0.009), with four patients achieving MH. Before EEN initiation, 80 lipid species/17 lipid classes were significantly different between patients with CD and healthy controls. After EEN initiation, 103 lipid species/11 lipid classes were significantly different between patients with CD and healthy controls. Thirty-eight significantly different lipid species from eight lipid classes—cholesterolester (n=1), lysophosphatidylcholine (n=3), monogalactosyldiacylglycerol (n=1), phosphatidylcholine (n=18), phosphatidylethanolamine (n=3), phosphatidylinositol (n=4), phosphatidylserine (n=1), and phosphatidylglycerol (n=7)—were identified in patients with CD before and after EEN. Among these lipid classes, the levels of monogalactosyldiacylglycerol, phosphatidylinositol, and phosphatidylcholine decrased significantly and that of phosphatidylglycerol increased significantly before EEN in patients with CD compared to those in healthy controls (P&lt;0.05). These lipids returned to similar levels of healthy controls after EEN (P&gt;0.05). Lipid classes and species were significantly associated with clinical indices of CDAI, hs-CRP, and MH. Pathway analysis suggested that arachidonic acid, glycerophospholipid, linoleate, and phosphatidylinositol phosphate metabolisms were related to the mechanism of EEN treatment.

CONCLUSION
EEN leads to the alterations in multiple lipid classes and species, in keeping with improvement in clinical response. However, further studies are needed to confirm their precise roles.
CONCORDANCE BETWEEN REMISSION DEFINED BY PATIENTS VS PATIENT-REPORTED OUTCOME MEASURES IN INFLAMMATORY BOWEL DISEASE
Authors: Kamp Kendra , Tse Chung Sang , Hawes Steven , Oberai Ridhima , Weaver Alandra , Singh Siddharth , Melmed Gil , Siegel Corey , van Deen Welmoed 
Published: January 2022

Abstract

BACKGROUND
Although validated patient-reported outcome measurements (PRO) can categorize patients with inflammatory bowel disease (IBD) into remission or active disease, patients may have different definitions of remission. Patients may assume a new normal with altered bowel habits/abdominal pain after diagnosis or consider themselves to have active disease even though disease activity measures show remission. We aim to examine concordance between patient-defined remission and remission based on PRO-2 (ulcerative colitis; UC) or PRO-3 (Crohn’s disease; CD), and associations with demographic and disease-related factors.

METHODS
We retrospectively analyzed 3257 de-identified surveys from 2004 unique patients (806 UC; 1198 CD) who consented to participate in the Crohn’s and Colitis Foundation’s IBD Qorus Learning Health System. Surveys were collected at IBD clinic visits between September 2019 and February 2021. We used logistic regression models with generalized estimating equations to analyze the sensitivity, specificity, concordance, and discordance between patient-defined remission (yes/no) and PRO-defined remission (PRO-2: stool frequency, rectal bleeding; PRO-3: stool frequency, abdominal pain, wellbeing). We also examined steroid-free PRO remission (PRO-defined remission plus absence of steroids).

RESULTS
In CD, 63.3% of patients with inactive disease based on PRO-3 considered themselves in remission (adjusted sens=0.62). Discordance was more common among patients with &lt;5 years disease duration (OR 1.6), and those who used prednisone (OR 4.2) or opioids (OR 5.3). Among patients with active disease based on PRO-3, 20.8% considered themselves in remission (adjusted spec=0.79) and discordance was more common with long disease duration (&gt;15 years; OR 2.6) and those who did not use prednisone (OR 3.0) and opioids (OR 5.4).
In UC, 77% of patients with inactive disease based on PRO-2 considered themselves in remission (adjusted sens=0.77). Discordance was more common among patients with disease duration of &lt;5 years compared to those &gt;15 years (OR 2.3). Among patients with active disease based on PRO-2, 19.2% considered themselves in remission (adjusted spec=0.79) and discordance was more common in patients who did not use prednisone (OR: 2.2).
Age and gender were not associated with discordance. Results were similar with steroid-free PRO defined remission (Table 2).

CONCLUSION
Discordance between how patients and PRO measures define remission is common. Patients with shorter disease duration were more likely to report active disease when they were in remission while patients with longer disease duration were more likely to report remission while they still experienced symptoms. 1 in 3 (32%) assessments of disease remission were discordance among patients with CD, and 1 in 4 (22%) in patients with UC.
FECAL CALPROTECTIN TESTING: AN INVESTIGATION OF PATIENT COMPLIANCE AND PERCEPTIONS
Authors: Perry Courtney , Hashim Mahmoud , Elmoursi Ahmed , Elkheshen Ahmed , Dugan Adam , Flomenhoft Deborah , Stuffelbeam Amy , Barrett Terrence 
Published: January 2022

Abstract

INTRODUCTION
Inflammatory Bowel Disease (IBD) is a lifelong illness requiring close management. Prompt disease recognition and tight control of disease activity reduces disease morbidity and improves outcomes1. Endoscopy with histologic examination is the gold standard for assessing “deep remission2.” However, frequent endoscopic evaluation is not always feasible or cost effective. Fecal Calprotectin (FC), a paradigm shifting biomarker, is both sensitive and specific for histologic inflammation in IBD2. However, the efficacy of this test rests on patient’s willingness to handle and submit stool samples. Studies investigating FC non-compliance are scarce, and all have been performed outside the US. Thus, we elected to survey our patients to assess barriers to FC compliance.

METHODS
We recruited 104 participants with Crohn’s disease (CD) or Ulcerative Colitis (UC) from our IBD clinic to participate in a prospective cross-sectional study. We administered an author-designed mixed-method questionnaire consisting of 23 questions with multiple choice, yes/no, rank order, and open-ended questions. The primary outcomes of interest were risk factors for non-compliance. Patient compliance over a two year period (1/2018 through 1/2020) was self-reported and verified retrospectively by the authors. Responses to questions were grouped according to level of FC compliance (&lt;50% compliance, 50-99% compliance, 100% compliant). Categorical variables were analyzed using chi2 and Fishers exact test. Continuous variables were analyzed using Mann-Whitney and Kruskal-Wallis tests.

RESULTS
Among the 104 participants surveyed, 56 were always compliant with FC testing (53.8%).The remaining 48 participants fell on a spectrum of compliance, with most participants completing between 50-75% of fecal calprotectin tests over the study period (n=29, 60.4%). Only 8 participants were “never” compliant. Physician determined compliance was significantly associated with participant completion (p=0.001). Number of “no-show” clinic visits was associated with FC compliance (p=0.013). Participants who reported FC testing embarrassing were significantly less likely to be compliant (p=0.037), and were less likely to report that they found stool testing important (p=0.020). In the qualitative portion of the survey, recurring frustrations included inconvenience of testing, embarrassment associated with stool submission, and lack of streamlined sample submission.

CONCLUSION
Fecal calprotectin is a valuable tool for IBD monitoring, but testing can be cumbersome and usefulness is limited by compliance. Embarrassment was a significant compliance barrier, suggesting that improved education and protocols for laboratory discretion would improve FC submission and patient experience.
STIGMA PERCEPTIONS IN NON-WHITE IBD PATIENTS AND RELATIONSHIPS WITH PATIENT OUTCOMES
Authors: Veracruz Nicolette , Taft Tiffany 
Published: January 2022

Abstract

INTRODUCTION
Disease-related stigmatization is present in IBD, with a substantial proportion of patients reporting that they perceive discriminatory attitudes or behaviors from others because of their IBD status. These perceptions are associated with poor outcomes. However, stigma perceptions are not well studied in patients from underrepresented racial and ethnic minority (URM) groups. As such, we aim to assess stigma perceptions in URM IBD patients and their relationship to Health Related Quality of Life (HRQoL).

METHODS
Adult patients 18+ recruited via social media and researchmatch.org website completed an anonymous online survey: demographics, disease information, Harvey Bradshaw Index (HBI) or simple clinical colitis activity index (SCCAI) with &gt;4 = active IBD, NIH-PROMIS QoL module (anxiety, depression, fatigue, sleep disturbance, pain interreference, social function), and the Perceived Stigma Scale for IBS (“IBS” replaced with “IBD”). Elevated stigma was identified via median split (Median=28). Independent samples t-Test, Pearson’s correlation, and hierarchical linear regression statistics were used.

RESULTS
90 participants: 50% UC, 79% female, 66% South/Southeast Asian, 10% Hispanic, Age (Mean±SD))=34.8±9.8 years. 52% had active IBD (5.77±4.22) with “biologic” medications most used (38.9%). 59% reported high levels of perceived stigma (Mean IBD-PSS score: 30.57±16.3); no differences by IBD type, age, gender, race, or ethnicity. Patients with active IBD reported significantly more stigma experiences (36.0±2.7 vs. 23.3±10.9, p&lt;.001). Stigma perception was significantly correlated with all HRQoL domains: anxiety r=0.414, depresison r=0.471, fatigue r=0.424, sleep disturbance r=0.293, pain interference r=0.474, social function r= -0.439 (all p&lt;.01). When controlling for HBI/SCCAI, stigma was a larger predictor of anxiety (β=.365, p=.002), depression (β=.386, p&lt;.001), social function (β= -.341, p=.003) than symptom severity, and smaller but significant predictor of fatigue (β=.254, p=.014) and pain interference (β=.290, p=.003). Stigma perceptions did not predict sleep disturbance (p=.087).

CONCLUSION
Approximately half of URM IBD patients reported high levels of stigma experiences. These perceptions were associated with negative outcomes across all HRQoL domains with the exception of sleep disturbance. Our results show stigma perceptions are an important consideration when evaluationg these outcomes in IBD, rather than disease activity alone. Further research on a larger scale and with more diverse population is needed in order to better understand the effects of disease stigmatization in URM IBD patients.
REAL-WORLD VEDOLIZUMAB PHARMACOKINETIC STUDY IN CHILDREN IDENTIFIES TWO NOVEL BIOMARKERS OF DRUG CLEARANCE
Authors: Colman Ruben , Mizuno Tomoyuki , Hyams Jeffrey , Noe Joshua , Boyle Brendan , Denson Lee , Vinks Alexander , Minar Phillip 
Published: January 2022

Abstract

INTRODUCTION
Use of vedolizumab in pediatric inflammatory bowel disease (IBD) often requires an interval intensification from standard dosing due to distinct pharmacokinetics (PK) in children. Adult population PK models found inclusion of albumin, weight, anti-TNF naivety and antibodies-to-vedolizumab (ATV) as covariates of drug clearance (CL) improved model accuracy. We aimed to build a population-PK model for children and identify novel covariates of drug CL to better account for pediatric-specific variability in vedolizumab PK.

METHODS
This was a prospective multicenter cohort study for pediatric IBD patients starting vedolizumab. Vedolizumab dosing regimens were managed by the treating clinician. Stool, serum and plasma were collected at standardized intervals for robust PK sampling and biomarker analysis. Population PK analysis were conducted with nonlinear mixed effects modeling (NONMEM 7.5). A 1-compartment model with proportional error model was created based on the PK data. In the final model, novel covariates were identified using a stepwise approach. A decrease in the objective function value (OFV) &gt;3.84 was considered significant (P&lt;0.05).

RESULTS
Twenty-one patients had a total of 277 infusions with 274 measured vedolizumab peak and trough concentrations. Among these, 57% were male, 76% had Crohn’s disease, and 81% had prior anti-TNF exposure. The median (IQR) age was 16 years (13-18), and median weight was 52kg (41-71). Baseline biomarkers are described in Table 1.
Baseline CL was inversely correlated with albumin (R=-0.54, P= 0.012), hemoglobin (R=-0.45, P= 0.048), and platelets (R=-0.5, P= 0.026). There was a positive correlation of CL with CRP (R=0.8, P&lt; 0.001), neutrophil CD64 (nCD64, R=0.68, P= 0.001), fecal calprotectin (FCP, R=0.63, P= 0.009), and BSA (R=0.59, P= 0.007).
The final model estimated CL as 0.168 L/d (relative standard error (RSE), 13%) and volume (V) distribution as 3.97L (8%). The interindividual variability (IIV) of the final model was 62.2% (25%) of CL and 37% (8%) of V. Covariates that significantly decreased the OFV were incorporated into the final model including weight for V and albumin, ESR, and nCD64 for CL. Prior anti-TNF, immunomodulators (MTX, n=3) or ATV (n=1) did not impact CL.
Baseline CL &lt;0.161 L/d predicted an end of induction FCP remission (&lt;250μg/g) with an area under the curve (AUC) 0.7 (sensitivity 0.8, specificity 0.75) with the final model. A cut-off of 37 μg/mL at infusion-3 and 20 μg/mL at infusion-4 predicted end of induction clinical remission (Figure 1).

CONCLUSIONS
We describe a novel pediatric PK model for vedolizumab that identified novel covariates, including ESR and nCD64, that may guide model-informed precision dosing. Larger cohorts should establish whether additional compartments and pediatric-specific covariates can further decrease the remaining unexplained variability.
Testing behaviour may bias observational studies of vaccine effectiveness
Authors: Glasziou Paul , McCaffery Kirsten , Cvejic Erin , Batcup Carys , Ayre Julie , Pickles Kristen , Bonner Carissa 
Published: January 2022

AbstractBackgrounRecent observational studies have suggested that vaccines for the omicron variant of SARS-Cov2 may have little or no effect in preventing infection. However, the observed effects may be confounded by patient factors and preventive behaviours or vaccine-related differences in testing behaviour. To assess the potential degree of confounding, we aimed to estimate differences in testing behaviour between unvaccinated and vaccinated populations.MethodsWe recruited 1,526 Australian adults for an online randomised study about COVID testing between October and November 2021, and collected self-reported vaccination status and three measures of COVID-19 testing behaviour. We examined the association between testing intentions and vaccination status in the cross-sectional baseline data of this trial.ResultsOf the 1,526 participants (mean age 31 years): 22% had a COVID-19 test in the past month and 61% ever; 17% were unvaccinated, 11% were partially vaccinated (1 dose), 71% were fully vaccinated (2+ doses). Fully vaccinated participants were twice as likely (RR 2.2; 95% CI 1.8 to 2.8) to report positive COVID testing intentions than those who were unvaccinated (p<.001). Partially vaccinated participants had less positive intentions than those fully vaccinated (p<.001) but higher intentions than those who were unvaccinated (p=.002).DiscussionFor all three measures vaccination predicted greater COVID testing intentions. If the unvaccinated tested at half the rate of the vaccinated, a true vaccine effectiveness of 30% could appear to be a “negative” observed vaccine effectiveness of -40%. Assessing vaccine effectiveness should use methods to account for differential testing behaviours. Test negative designs are currently the preferred option, but its assumptions should be more thoroughly examined.
“Effectiveness of COVID-19 Vaccines in preventing Infectiousness, Hospitalization and Mortality: A Historical Cohort Study Using Iranian Registration Data During Vaccination program”
Authors: Mirahmadizadeh Alireza , Heiran Alireza , Lankarani Kamran Bagheri , Serati Mohammadreza , Habibi Mohammad , Eilami Owrang , Heiran Fatemeh , Moghadami Mohsen 
Published: January 2022

AbstractBackgroundThere are some concerns about the effectiveness of the inactivated and vector-based vaccines against SARS-CoV-2 in the real-world settings with the emergence of new mutations, especially variants of concern. Data derived from administrative repositories during mass-vaccination campaigns or programs are of interest to study vaccine effectiveness (VE).MethodsUsing 4-repository administrative data linkage, we conducted a historical cohort study on a target population of 3,628,857 inhabitants aged at least 18 years residing in Southern Iran.ResultsWe estimated 71.9% [95% CI: 70.7-73.1%], 81.5% [95% CI: 79.5-83.4%], 67.5% [95% CI: 59.5-75.6%], and 86.4% [95% CI: 84.1-88.8%] hospitalization reduction for those who received the full vaccination schedule of BIBP-CorV, ChAdOx1-S/nCoV-19, rAd26-rAd5, and BIV1-CovIran vaccines, respectively. A high reduction in mortality – at least 85% – was observed in all age subgroups of fully immunized population.ConclusionThe pragmatic implementation of a vaccination plan including all available vaccine options in the Iranian population was associated with a significant reduction in documented COVID-19 infection, hospitalization, and death associated with COVID-19.Key pointsThe mass vaccination program with implementing a group of vaccines, that even for some of them (rAd26-rAd5, and BIV1-CovIran vaccines) have been only regionally authorized for emergency use, has been associated with a dramatic reduction in documented COVID-19 infection, as well as in hospitalization and deaths related to the COVID-19 diagnosis.
Single-nuclei paired multiomic analysis of young, aged, and Parkinson’s disease human midbrain reveals age- and disease-associated glial changes and their contribution to Parkinson’s disease
Authors: Adams Levi , Song Min Kyung , Tanaka Yoshiaki , Kim Yoon-Seong 
Published: January 2022

AbstractAge is the primary risk factor for Parkinson’s disease (PD), but how aging changes the expression and regulatory landscape of the brain remains unclear. Here, we present a single-nuclei multiomic study profiling shared gene expression and chromatin accessibility of young, aged and PD post-mortem midbrain samples. Combined multiomic analysis along a pseudopathogenesis trajectory reveals all glial cell types are affected by age, but microglia and oligodendrocytes are further altered in PD. We present evidence for a novel disease-associated oligodendrocyte subtype and identify genes lost over the aging and disease process, including CARNS1, that may predispose healthy cells to develop a disease-associated phenotype. Peak-gene association analysis from paired data identifies 89 PD-associated SNP loci, including five in MAPT, that show differential association with gene expression in disease-associated oligodendrocytes. Our study suggests a previously undescribed role for oligodendrocytes in aging and PD pathogenesis.