bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATTERNS OF STEROID USE AMONG A REAL-WORLD NATIONAL COHORT OF VETERANS WITH INFLAMMATORY BOWEL DISEASE
Authors: Pham Codey , Xu Anthony , Sansgiry Shubhada , Waljee Akbar , Hou Jason 
Published: January 2023

Abstract

BACKGROUND
Corticosteroids are effective in the acute improvement of symptoms in inflammatory bowel disease (IBD) but are not recommended as maintenance therapy due to lack of long-term efficacy and significant adverse effects. Long term goals for medical management in IBD include achieving steroid-free remission. Biologics such as the anti-tumor necrosis factor alpha Infliximab (IFX) are used to achieve clinical remission, however patterns of continued steroid use among patients on maintenance IFX have not been fully studied. The aim of this study is to evaluate patterns of concomitant steroid use in individuals with IBD on maintenance IFX.

METHODS
We performed a retrospective cohort study using the national Veteran’s Health Administration dataset. Patients with IBD were identified using a previously validated algorithm of ICD9/10 codes and confirmed by manual chart review. Dispensed medications and demographic data were obtained from VA Corporate Data Warehouse. Patients were eligible for inclusion if they had a confirmed diagnosis of IBD and on maintenance IFX. Maintenance IFX- index date was defined as the first dose of IFX in 2017 with receipt of IFX 7 to 9 weeks before and after IFX-index date. The study period for steroid use was six months prior to and following the IFX-index date. Continued steroid use was defined as two or more filled prescription of oral steroids during the study period.

RESULTS
There were 642 individuals included who met the criteria outlined above. The majority (594, 92.5%) were male. The racial breakdown was as follows: 516 (80.3%) White, 85 (13.3%) Black, 18 (2.8%) other races, and 23 (3.6%) with unknown race. A total of 402 individuals (62.6%) had ulcerative colitis, 240 individuals (37.4%) had Crohn’s disease. The average age at the IFX-index date was 46.8 (±15.8) years. The average time from initial date of IFX exposure to the Maintenance IFX-index date was 3.6 years. During the study period, 198 (30.9%) patients filled at least one prescription for steroids. 145 of the 198 (73.2%) individuals prescribed had continued steroid use with two or more filled steroid prescriptions, with an average of 3.9 filled prescriptions of steroids during the study period.

CONCLUSION
While IFX has been shown to be effective in the induction and maintenance of remission in IBD, we observe high rates of continued steroid use in a national cohort of patients with IBD on maintenance IFX. Continued steroid use in patients on IFX maintenance implies inadequate IBD control despite IFX. Further study is required to understand reasons for continued steroid use in order to improve rates of steroid-free remission in IBD.
REAL-WORLD EXPERIENCE WITH TOFACITINIB DOSE DE-ESCALATION IN PATIENTS WITH MODERATE AND SEVERE ULCERATIVE COLITIS
Authors: Yu Amy , Shi Bingyan , Ha Nghiem , Beck Kendall 
Published: January 2023

Abstract

BACKGROUND
Tofacitinib is associated with sustained steroid-free remission and improved quality of life in patients with ulcerative colitis (UC), with the lowest effective dose recommended for maintenance therapy. However, there is limited real-world data to guide decision on optimal maintenance dose. We aimed to evaluate treatment outcomes of tofacitinib dose de-escalation in patients with UC in a real-world cohort.

METHODS
Included were adults with moderate-severe UC treated with tofacitinib between 1/2012-1/2022. Duration of treatment induction with 10 mg twice daily was 8, 16, or &gt;16 weeks. Dose de-escalation was defined as decrease to 5 mg twice daily. Primary outcome was UC flare, defined as UC-related hospitalization/surgery, reinduction with tofacitinib dose increase, corticosteroid, or change of therapy class. Predictors of UC flare were explored using univariable and multivariable Cox regression.

RESULTS
Among 162 patients, 54% were male and 71% were white with a median age of 38 years, with 41% and 51% having moderate and severe UC, respectively. Eighty-three (52%) patients continued induction dose while 79 (48%) underwent dose de-escalation. There was no significant difference in number of prior biologic use or baseline endoscopic Mayo score, however, patients who underwent de-escalation were less likely to be steroid dependent during induction (50% vs 70%,p=0.01). After a median follow-up of 12 months, cumulative incidence rates of UC flare at 12 months were similar in patients with and without dose de-escalation (56% vs 58%,p=0.81), though patients without dose de-escalation had higher rates of UC-related hospitalization (27% vs 14%,p=0.04) and change of therapy class (39% vs 12%,p&lt;0.01) compared to those who de-escalated. Among patients with dose de-escalation, cumulative rates of UC flare at 12 months were higher in patients with ongoing severe disease (Mayo 3) at 6 months of tofacitinib (Figure 1). In univariable Cox regression, prolonged duration of induction course with 10 mg twice daily &gt;16 weeks was protective of UC flare (HR 0.37,95% CI 0.16-0.85) while ongoing severe disease (Mayo 3) was associated with UC flare (HR 6.41,95% CI 2.23-18.44), which remained significant after adjusting for age, sex, duration of induction course, and use of corticosteroid at dose de-escalation (HR 6.05, CI 2.00-18.35) (Table 1). Twenty-seven (29%) patients with UC flare had dose re-escalated to 10 mg twice daily with 63% recapturing clinical response at 12 months.

CONCLUSIONS
In this real-world cohort of UC patients with tofacitinib de-escalation, we observed a 56% cumulative incidence of UC flare at 12 months. Observed factors associated with UC flare after dose de-escalation included shorter induction course &lt;16 weeks and active disease at 6 months of tofacitinib. The majority were able to recapture clinical response after dose re-escalation.
USE OF UPADACITINIB IN 11 TOFACITINIB-REFRACTORY ULCERATIVE COLITIS PATIENTS AT A SINGLE TERTIARY CARE CENTER
Authors: Levine Jake , McKibbin Jey , Ham Rebecca , Higgins Peter , Bishu Shrinivas , Berinstein Jeffrey 
Published: January 2023

Abstract

INTRODUCTION
Ulcerative colitis (UC) is a chronic inflammatory condition characterized by diarrhea, abdominal pain, rectal bleeding, and weight loss. Upadacitinib is an oral, selective, small molecule Janus Kinase (JAK) inhibitor that was recently approved in the United States for moderate to severe UC. Clinical trials evaluating the efficacy of upadacitinib excluded patients with a previous exposure to tofacitinib, a nonselective JAK inhibitor; therefore, the efficacy of upadacitinib in patients with previous exposure to tofacitinib remains largely unknown.

METHODS
We present a small retrospective case series of all patients with a diagnosis of ulcerative colitis seen at our institution between with a prior exposure to tofacitinib who were initiated on upadacitinib between May and August of 2022. Demographic data was collected as well as outcome data on clinical improvement, steroid-free remission, biochemical improvement, colectomy status, and adverse events.

RESULTS
Eleven tofacitinib-refractory patients with ulcerative colitis were initiated on upadacitinib. Mean age was 38.1 years, five (45.5%) patients were female, nine (81.8%) patients were white, seven (63.6%) patients had pancolitis, and mean duration of UC was 7.4 years (Table 1). In this group, there were high rates of prior targeted therapy failures. These patients were followed for a mean of 121 days. The clinical course of each patient is presented in Table 2. Of the 11 patients included in our study, nine (81.8%) patients reported symptomatic improvement, six (54.5%) patients were able to successfully taper corticosteroids, and two (18.2%) patients underwent colectomy, one of which was elective and planned prior to initiating upadacitinib. The mean fecal calprotectin improvement was 1430mg/kg of patients with both baseline and follow-up testing. Three (27.3%) patients experienced an adverse event; two (18.2%) patients with mild COVID-19 not requiring hospitalization and one (9.1%) patient with Enteropathogenic E. Coli.

DISCUSSION
This real-world single-center case series of 11 patients, suggests that upadacitinib may be an effective option for patients with a previous tofacitinib exposure. Larger prospective studies are needed to confirm these findings.
VEDOLIZUMAB, USTEKINUMAB AND TOFACITINIB AS TRIPLE THERAPY FOR ULCERATIVE COLITIS
Authors: Thurston Theresa , Moskow Joshua , Glassner Kerri , Abraham Bincy 
Published: January 2023

Abstract

BACKGROUND
Therapies for ulcerative colitis include mesalamine, immunomodulators, biologics, and small molecules. Unfortunately, patient response is not universal, and efficacy can diminish with time, postulated to be from increased drug clearance, anti-drug antibodies with biologics, and immune mediated pathogenesis changes. Biologic combinations have been investigated for producing synergistic drug effects and extending targeted therapy in patients lacking monotherapy response, with promise shown in two drug combinations (1), but not investigated using three.

CASE
A 20-year-old Caucasian male with UC presented in August 2015 following 1 month hospitalization for Clostridium difficile infection. He had 2 infusions of infliximab 10 mg/kg continued post-discharge, and started mesalamine 4.8gm qd, 6-mercaptopurpine (6MP) 100mg qd, and prednisone taper. By November 2015, colonoscopy showed severe Mayo 3 pancolitis. Due to insufficient response 6MP and infliximab were discontinued and he started vedolizumab. August 2016 colonoscopy had chronic colitis with Mayo 2 inflammation of the ascending, transverse, descending and rectosigmoid colon so prednisone 40mg was initiated and vedolizumab increased to vedolizumab q4 weeks. He responded well clinically and was tapered off prednisone by October 2016. November 2016 colonoscopy had right sided colitis resolution with residual proctosigmoiditis (Mayo 2); May 2017 colonoscopy still had rectosigmoid inflammation (Mayo 2) with chronic active colitis, so ustekinumab q8 weeks was added. December 2017 colonoscopy was unimproved so ustekinumab increased to q4 weeks, prednisone was increased, and he requested addition of budesonide and mesalamine. With clinical improvement, prednisone was tapered by February 2020.
However, December 2020 colonoscopy showed severe (Mayo 3) recto-sigmoiditis with mild colitis in the descending to transverse colon, so tofacitinib XR 22 mg qd was added. He improved clinically, so budesonide was discontinued in February 2021. November 2021 colonoscopy showed complete endoscopic remission (Mayo 0) so he initiated de-escalation with initially discontinuing mesalamine and increasing ustekinumab initially to q8 week intervals and later vedolizumab to q8 weeks with maintenance of clinical remission. Given marginal effect, ustekinumab was discontinued initially and later, tofacitinib was discontinued. He remains in remission on vedolizumab q8 weeks monotherapy.

CONCLUSION
Combination therapies may be considered for suitable patients experiencing severe, refractory disease. Although patients with multiple comorbidities, frailty, immunosuppression or certain contraindications may not be well suited, this patient presents as an ideal candidate with no comorbidities and few other therapeutic options.

REFERENCES
(1) Privitera G et al. Combination therapy in IBD. Autoimmunity Reviews. 2021 Jun 1;20(6):102832.
EFFICACY OF UPADACITINIB IN PATIENTS PREVIOUSLY TREATED WITH TOFACITINIB FOR THE MANAGEMENT OF ULCERATIVE COLITIS
Authors: Radcliffe Marlana , Long Millie , Barnes Edward , Herfarth Hans , Hansen Jonathan , Jain Animesh 
Published: January 2023

Abstract

BACKGROUND
Tofactinib is a JAK inhibitor that targets mainly JAK 1 and JAK3 approved to treat Ulcerative Colitis (UC) in 2018. The JAK inhibitor Upadacitinib (upa) was recently approved to treat UC in March 2022 and has increased selectivity for JAK1. The relative efficacy and safety of these two JAK inhibitors is not presently clear. An important clinical question is whether patients who have not responded or lost response to tofacitinib will have a reasonable likelihood of response with upadacitinib.

AIM
To determine whether patients previously exposed to tofacitinib would benefit from treatment with upa.

METHODS
We identified adult patients at our center with active UC who had previously been treated with tofacitinib who were started on upa in the spring of 2022. Pre- and post- upa characteristics were recorded including demographic information, prior treatments, hemoglobin (hgb), albumin (alb), C-reactive protein (CRP), and partial Mayo score (pMS). Primary end points evaluated were clinical response (decrease in pMS &gt;2), and clinical remission (pMS &lt; 2). Secondary endpoints included serious adverse events, steroid use at time of follow up, and normalization of CRP, hgb and alb. IRB approval was obtained for the study.

RESULTS
A total of 3 patients were identified. All patients were given upa 45 mg daily for 8 weeks followed by 30 mg daily for maintenance. Median follow up time was 10 weeks (range 10-11 weeks). All three patients achieved the primary endpoints of clinical response and remission with pMS values of 0 at time of follow up. Patients 1 and 2 were concurrently started on a prednisone taper when initiating upa and were no longer on prednisone at time of follow up. Patients 1 and 2 had normalization of their CRP values, patient 3 only had a pre-upa CRP value available and that was 0. See table 1 for data on hgb and alb levels. Patient 1 had a pre-upa endoscopic mayo score of 3, while patients 2 and 3 had pre-upa endoscopic mayo scores of 2. No patient had post-upa endoscopic evaluation at time of follow up. No patient had any serious adverse events.

CONCLUSIONS
In this small case-series, use of upadacitinib in patients previously treated with tofacitinib was safe and effective in achieving clinical remission.
Histologic Predictors of Clinical Outcomes and Healthcare Utilization in Patients With Ileal Pouch-Anal Anastomosis
Authors: Chang Shannon , Hong Simon , Hudesman David , Remzi Feza , Sun Katherine , Cao Wenqing , Kani H Tarik , Axelrad Jordan , Sarkar Suparna A 
Published: January 2023

Abstract

Background
The prognostic significance of histology in ileal pouch-anal anastomosis (IPAA) remains unclear. The aim of this study was to evaluate if histologic variables are predictive of IPAA clinical outcomes and healthcare utilization.

Methods
This was a retrospective cohort study of patients with IPAA undergoing surveillance pouchoscopy at a tertiary care institution. Pouch body biopsies were reviewed by gastrointestinal pathologists, who were blinded to clinical outcomes, for histologic features of acute or chronic inflammation. Charts were reviewed for clinical outcomes including development of acute pouchitis, chronic pouchitis, biologic or small molecule initiation, hospitalizations, and surgery. Predictors of outcomes were analyzed using univariable and multivariable logistic and Cox regression.

Results
A total of 167 patients undergoing surveillance pouchoscopy were included. Polymorphonuclear leukocytes (odds ratio [OR], 1.67), ulceration and erosion (OR, 2.44), chronic inflammation (OR, 1.97), and crypt distortion (OR, 1.89) were associated with future biologic or small molecule initiation for chronic pouchitis. Loss of goblet cells was associated with development of chronic pouchitis (OR, 4.65). Pyloric gland metaplasia was associated with hospitalizations (OR, 5.24). No histologic variables were predictive of development of acute pouchitis or surgery. In an exploratory subgroup analysis of new IPAA (&lt;1 year), loss of goblet cells was associated with acute pouchitis (OR, 14.86) and chronic pouchitis (OR, 12.56). Pyloric gland metaplasia was again associated with hospitalizations (OR, 13.99).

Conclusions
Histologic findings may be predictive of IPAA outcomes. Pathologists should incorporate key histologic variables into pouchoscopy pathology reports. Clinicians may need to more closely monitor IPAA patients with significant histologic findings.
Association of Culturable-Virus Detection and Household Transmission of SARS-CoV-2, California and Tennessee, 2020–2022
Authors: Deyoe Jessica E , Kelly J Daniel , Grijalva Carlos G , Bonenfant Gaston , Lu Scott , Anglin Khamal , Garcia-Knight Miguel , Pineda-Ramirez Jesus , Hagen Melissa Briggs , Saydah Sharon , Abedi Glen R , Goldberg Sarah A , Tassetto Michel , Zhang Amethyst , Donohue Kevin C , Davidson Michelle C , Sanchez Ruth Diaz , Djomaleu Manuella , Mathur Sujata , Shak Joshua R , Deeks Steven G , Peluso Michael J , Chiu Charles Y , Zhu Yuwei , Halasa Natasha B , Chappell James D , Mellis Alexandra , Reed Carrie , Andino Raul , Martin Jeffrey N , Zhou Bin , Talbot H Keipp , Midgley Claire M , Rolfes Melissa A 
Published: January 2023

Abstract
From 2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission studies (enrolling April 2020 to January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable virus detected after onset. Regardless of duration of culturable virus, most secondary infections (70%, 28/40) had serial intervals &lt;6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection, and highlight the potential for prolonged infectiousness (≥6 days) in many individuals.
Introduction
Authors: Goforth Anisa N. , Pham Andy V. 
Published: January 2023

Abstract
This chapter provides an introduction to the purpose and outline of this volume. The authors focus on the foundations of culturally responsive practice, culturally responsive assessment, and promoting resilience through counseling, interventions, and evaluation of programs. Culturally responsive practice and engaging in cultural humility are the foundation of this book, and the authors share their process of critical reflexivity in writing it. Further, a rationale is provided for using certain terms and language throughout the book. This book is a much-needed resource for a broad range of practitioners in schools and can be useful for general educators, special educators, and administrators who are interested in understanding how to provide culturally responsive services to culturally and linguistically diverse students.
Evaluating School-Based Programs for Diverse Students
Authors: Goforth Anisa N. , Pham Andy V. 
Published: January 2023

Abstract
Culturally responsive evaluation (CRE) is essential for identifying whether a program works in its specific context and integrates community members, parents, and school personnel throughout the process. It is a decision-making process that involves both critical reflexivity and collaboration to assess the strengths and needs of students. CRE uses a strengths-based approach to promote social justice and shifts the conversation from problems to opportunities for meaningful growth. This chapter reviews the six steps within the school-based culturally responsive program evaluation model. It wraps up with a discussion of the ethical considerations in program evaluation with culturally and linguistically diverse communities.
Sessions 6 and 7: Defusion from Your Inner Experiences: You Are Not Your Urges to Pull
Authors: Woods Douglas W. , Twohig Michael P. 
Published: January 2023

Abstract
This chapter discusses that the urges, thoughts, and emotions around hair pulling do not necessarily need to be treated literally. Accepting urges and inner experiences involves learning to defuse from these feelings to what they really are. This ability to defuse from inner experiences allows thoughts to separate from the person. Defusion exercises are provided to help the patient see that thoughts, urges, and emotions do not need to influence action. “Being present” exercises are presented to help patients become more aware of their thinking process.
Introduction: Introductory Information for Therapists and Assessment
Authors: Lee Eric B. 
Published: January 2023

Abstract
This chapter provides background on trichotillomania (TTM), a disorder of secrecy and shame. Many with the problem do not know it has a name, and many who know what they have cannot find knowledgeable providers. Research on the etiology, maintenance, and treatment of TTM has grown dramatically since the program was first published. This chapter introduces Acceptance and Commitment Therapy (ACT) Enhanced Behavior Therapy for Trichotillomania (AEBT-T) as a treatment for adolescents and adults. The treatment blends the traditional behavior therapy elements of habit reversal training and trigger reduction strategies with the more contemporary behavioral elements of ACT. AEBT-T teaches clients to effectively manage their pulling and to actively increase their functioning.
Session 8: Practicing Acceptance and Commitment Therapy (ACT)
Authors: Woods Douglas W. , Twohig Michael P. 
Published: January 2023

Abstract
This chapter describes the eighth session of the Acceptance and Commitment Therapy (ACT) Enhanced Behavior Therapy for Trichotillomania (AEBT-T) treatment package. It emphasizes how the client should be aware that urges to pull and other inner experiences surrounding pulling are incredibly difficult to control. Learning to see urges for what they are and make room for the presence of these experiences, rather than trying to control them, might be a more functional way to address them. The chapter suggests procedures from exposure therapy, which can be done in a context where the client is encouraged to “make friends” with the urge to pull. Avoidance can generally be detected when a client refuses or avoids a feeling, thought, or inner experience; it can occur in an exercise when a client is unwilling to do a part of it or suggests doing something easier.
Session 9: Practicing Acceptance and Commitment Therapy (ACT) and Review of Treatment
Authors: Woods Douglas W. , Twohig Michael P. 
Published: January 2023

Abstract
This chapter describes the ninth session of the Acceptance and Commitment Therapy (ACT) Enhanced Behavior Therapy for Trichotillomania (AEBT-T) treatment package. It includes exercises to help clients create a new relationship with pulling-related inner experiences. It also illustrates how to move from a situation where pulling-related inner experiences are events that push the client to engage in actions that regulate experiences, to a situation where these inner experiences are just inner experiences the client notices and does not interact with. In one exercise, the client practices having the particular inner experience with which they most commonly struggle. It determines which processes of change the client should focus on while engaged in a behavioral exercise.
Modifications for Working with Adolescents
Authors: Petersen Julie M. 
Published: January 2023

Abstract
This chapter focuses on the implementation of Acceptance and Commitment Therapy (ACT) Enhanced Behavior Therapy for Trichotillomania (AEBT-T) in adolescent clients. It includes session-by-session alterations and suggestions for implementing AEBT-T with adolescents. The client’s developmental level and insight into trichotillomania are likely the best guides for determining where and how to modify the protocol. Adolescents might not have struggled against their pulling as long as most adults have and thus may have lower motivation to change and may not be as aware of their struggle with urges to pull. The chapter highlights new elements of treatment for adolescents, including the need to work on motivation issues with reinforcement programs.