Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting.

BACKGROUND: Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. AIMS: We hypothesized that upadacitinib may be effective in treating acute severe colitis. METHODS: A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. RESULTS: Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores. CONCLUSION: Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.

Inflammatory Bowel Disease-Associated Arthritis Is Associated with Concomitant Autoimmune and Inflammatory Disorders.

BACKGROUND: Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA. METHODS: Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data. RESULTS: The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs. CONCLUSION: This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA.

Covasim: An agent-based model of COVID-19 dynamics and interventions.

The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility. Covasim also supports an extensive set of interventions, including non-pharmaceutical interventions, such as physical distancing and protective equipment; pharmaceutical interventions, including vaccination; and testing interventions, such as symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine. These interventions can incorporate the effects of delays, loss-to-follow-up, micro-targeting, and other factors. Implemented in pure Python, Covasim has been designed with equal emphasis on performance, ease of use, and flexibility: realistic and highly customized scenarios can be run on a standard laptop in under a minute. In collaboration with local health agencies and policymakers, Covasim has already been applied to examine epidemic dynamics and inform policy decisions in more than a dozen countries in Africa, Asia-Pacific, Europe, and North America.

Integration of telemedicine into clinical practice for inflammatory bowel disease.

PURPOSE OF REVIEW: In the context of the rising incidence and complexity of inflammatory bowel disease (IBD), telehealth offers new ways to support remote and efficient delivery of healthcare services. The aim of this review is to assess the current status of telehealth services in the management of IBD and challenges to adopting telehealth in clinical practice. RECENT FINDINGS: Different modalities of telehealth such as virtual clinics and remote patient monitoring have been studied in many IBD centers. They are found to be associated with high patient acceptance, decreased healthcare costs, improved quality of life, treatment adherence, and disease knowledge among patients. The major challenges encountered in the integration of telemedicine into clinical practice include risks to patient privacy and confidentiality, requirement for informed consent, lack of uniform reimbursement policies, operational difficulties, provider acceptance, and licensing. SUMMARY: Telehealth is an effective, efficient, and low-cost intervention that can address increasingly complex care of patients with IBD. However, for telemedicine to be adopted widely, new policies and reforms need to reduce the burden of physician licensing in multiple states, allow for receipt of all telehealth services in the patient's home or office, and require reimbursement for services on par with an office visit.

Remote Monitoring and Telemedicine in IBD: Are We There Yet?

PURPOSE OF REVIEW: Telehealth is the delivery of health care using the most recent technological advances. With the growing complexity of inflammatory bowel disease (IBD) care, telehealth allows for delivery of specialty services to an extended population. We reviewed the most recent literature on telehealth modalities, including patient-reported and disease outcomes associated with use of telehealth. RECENT FINDINGS: Current methods of telemedicine include telehealth, remote patient monitoring, and the use of mobile applications. Remote patient monitoring via web applications has been studied with improvement in patient-reported quality of life, medication adherence, and decreased heath care costs. Mobile applications can be used for symptom reporting and alert the medical team if a patient is reporting increased symptoms. These web and mobile applications allow for treatment decisions to occur without the delay of an office visit. There remain limitations to telehealth including technological concerns, physician acceptance, and licensing and reimbursement inequities. Telemedicine is a safe, effective, and accepted method of meeting the growing demand for complex IBD care throughout the world. The use of telehealth video conference and remote patient monitoring with web-based applications and text messaging has been shown to ease financial burdens of chronic disease, improve patient quality of life, and lead to improved clinical outcomes.

Psoriasiform Skin Lesions Are Caused by Anti-TNF Agents Used for the Treatment of Inflammatory Bowel Disease.

BACKGROUND: Tumor necrosis factor (TNF) antagonists used for the treatment of inflammatory bowel disease (IBD) have been associated with the development of psoriasiform skin lesions. We assessed the demographic and clinical characteristics associated with and outcomes of patients with anti-TNF-induced psoriasiform lesions. METHODS: Patients with Crohn's disease (CD) and ulcerative colitis (UC) receiving treatment with anti-TNF therapy (infliximab, adalimumab, or certolizumab pegol) at a tertiary referral center were identified using an IRB-approved clinical data repository. Patients that developed psoriasiform skin lesions after initiation of anti-TNF therapy were included as cases. A group of anti-TNF-treated patients without drug-related psoriasiform lesions were identified as controls. The association between demographic and clinical variables and psoriasiform lesions was assessed using Chi-square analyses and multivariable logistic regression. RESULTS: Five hundred twenty-one patients with IBD undergoing treatment with anti-TNF therapy were identified; of these, 18 (3.5%) had psoriasiform lesions (16 CD and 2 UC). Seventy-two patients were identified as controls. Lesions developed a mean of 58 weeks (range 4-240 weeks) after starting anti-TNF therapy. The majority of patients were female and Caucasian (63 and 78%, respectively). Thirty-nine percent of patients had upper tract disease location. Forty-five patients (50%) were current or former smokers. Location of psoriasiform lesions included palmo-plantar (53%), trunk (47%), and scalp (53%), with 88% reporting involvement of ≥2 locations. Treatment of psoriasiform lesions was instituted with topical therapy in eight patients and systemic therapy (± phototherapy) in five patients. Discontinuation of anti-TNF therapy was recommended in nine patients (50%); of those, three were retreated with a second anti-TNF agent and all had recurrence of psoriasiform lesions. When adjusted for multiple variables, upper GI tract disease was significantly associated with psoriasiform lesions. CONCLUSIONS: Anti-TNF-induced psoriasiform lesions developed in 3.5% of patients with IBD at a tertiary referral center. Similar to prior published studies, most patients were female, had involvement of the palmo-plantar and scalp regions, and did not have severe IBD activity. The presence of upper tract disease was associated with the development of psoriasiform lesions. Skin lesions led to discontinuation of anti-TNF therapy in 50% of patients. Based upon these results, IBD providers should educate patients about this adverse effect, refer to dermatology for treatment, and discuss alternative IBD therapeutic options early if a severe psoriasiform rash develops.

ExpLOring the role of the intestinal MiCrobiome in InflammATory bowel disease-AssocIated SpONdylarthritis (LOCATION-IBD).

Background: Inflammatory Bowel Disease (IBD)-associated arthritis is a frequent and potentially debilitating complication of IBD, that can affect those with or without active intestinal disease, and is often difficult to treat. The microbiome is known to play a role in IBD development and has been shown to be associated with inflammatory arthritis without concomitant IBD, but its role in IBD-associated arthritis is still unexplored. Further, disease localization is associated with development of IBD-associated arthritis, and stool compositional profiles are predictive of disease localization, yet mucosal location-specific microbiomes have not been well characterized. To address this gap in understanding, we designed a study (LOCATION-IBD) to characterize the mucosa-associated intestinal microbiome and metabolome in IBD-associated arthritis. Methods: Adults with an established diagnosis of IBD undergoing clinical colonoscopy between May of 2021 and February of 2023 were invited to participate in this study; those interested in participation who met inclusion criteria were enrolled. Prior to enrollment, participants were stratified into those with or without IBD-associated arthritis. All participants were interviewed and had clinical and demographic data collected, and 97.8% completed clinical colonoscopy with biopsy collection. Results and conclusion: A total of 182 participants, 53 with confirmed IBD-associated arthritis, were enrolled in this study, resulting in 1151 biopsies obtained for microbiome and metabolome analysis (median 6, mean 6.3 per participant). Clinical and demographic data obtained from the study population will be analyzed with microbiome and metabolome data obtained from biopsies, with the goal of better understanding the mechanisms underpinning the host-microbiome relationship associated the development of IBD-associated arthritis.

Differences in internalizing symptoms between those with and without Cannabis Use Disorder among HBCU undergraduate students.

OBJECTIVE: To determine the differences in internalizing symptoms between those who met criteria for Cannabis Use Disorder (CUD) and those who did not in young adults attending a Historically Black College or University (HBCU). PARTICIPANTS: The sample included 619 undergraduate students, with 110 (18%) who met criteria for CUD. METHODS: Participants completed an online survey, which included demographic, anxious and depressive symptomatology, and substance use assessment. RESULTS: Those who met CUD criteria reported more depressive symptoms (M = 22.83 ± 10.74) and anxiety symptoms (M = 45.70 ± 12.82) than their non-CUD counterparts (M = 19.17 ± 10.58; M = 40.57 ± 14.11, respectively). CONCLUSION: Differences between those who met criteria for CUD and those who did not are consistent with previous literature and may aid in characterizing internalizing behaviors in HBCU students with CUD. Future research should examine the subgroups that may cycle through withdrawal symptoms, despite not having severe CUD. This subgroup may be at higher risk for psychopathology than their severe counterparts.

Six-year trends and intersectional correlates of meeting 24-Hour Movement Guidelines among South Korean adolescents: Korea Youth Risk Behavior Surveys, 2013-2018.

BACKGROUND: Grounded in intersectionality theory, this study examined the 6-year prevalence trend and correlates in meeting Canada's 24-Hour Movement Guidelines (Guidelines hereafter) in a nationally representative adolescent samples of South Korea (officially the Republic of Korea). METHODS: Self-reported, annually repeated cross-sectional data collected between 2013 and 2018 were used (n = 372,433, 12-17 years old, 47.9% females). Adolescents were categorized as meeting or not meeting different sets of physical activity, screen time (ST), and sleep recommendations within the Guidelines, separately for weekdays and weekend days. Intersectional correlates included sex and social class (i.e., family economic status, parental education level, and academic performance). Multiple logistic regression analyses were performed. RESULTS: Overall, the proportion of adolescents meeting physical activity, ST, and sleep recommendations were 5.3%, 60.3%, and 10.2% on weekdays and 5.3%, 28.2%, and 46.4% on weekend days, respectively. Between 2013 and 2018, no substantial changes were observed for meeting the physical activity or sleep recommendation, while meeting the ST recommendation was markedly lower in 2018. The proportion of meeting all 3 recommendations were 0.5% for weekdays and 0.8% for weekend days. Overall, compared to female adolescents, male adolescents were consistently associated with more favorable patterns of meeting different sets of recommendations, regardless of social class. Among females only, social class appeared to be not important or even detrimental in meeting different sets of recommendations. Being male, compounded with social class, was associated with meeting the ST recommendation. CONCLUSION: Less than 1% of Korean adolescents met the overall Guidelines. Intersectionality-based analysis and intervention may be important in promoting healthy active lifestyles among South Korean adolescents.

Histologic Inflammation can Predict Future Clinical Relapse in Ulcerative Colitis Patients in Endoscopic Remission.

Background: In ulcerative colitis (UC), endoscopic improvement, defined as a Mayo Endoscopic Score (MES) of 0 or 1, is a target of treatment. The aim of our study was to evaluate the risk of clinical relapse between patients with an MES of 0 or 1 and determine if histologic activity using the Robarts Histopathologic Index (RHI) was predictive of clinical relapse. Methods: UC patients with an MES score of 0 or 1, no prior colectomy, and at least 1 year of outpatient follow-up after colonoscopy were included. Demographic, clinical characteristics, and clinical relapse were retrospectively collected. Biopsy specimens were read by a gastrointestinal pathologist. Primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and/or colectomy. Results: Four hundred and forty-five UC patients were identified. Ninety-five percent of patients with MES 0 were in histologic remission by the RHI whereas only 35% of patients with MES 1 were in histologic remission. Twenty-six percent of patients experienced a clinical relapse; patients with MES 1 or RHI > 3 were significantly more likely to relapse (P < .01) compared to patients with MES 0 or RHI ≤ 3. When patients were stratified into 4 groups (MES 0, RHI ≤ 3; MES 0, RHI > 3; MES 1, RHI ≤ 3; MES 1, RHI > 3) and adjusted for age and sex, RHI > 3 was predictive of relapse (P = .008). Conclusions: UC patients with endoscopic improvement have a high rate of clinical relapse over time. Histologic activity is a predictor of clinical relapse.

Multicenter Study of Nonadherence to Self-Injectable Biologic Therapy in Patients With Inflammatory Bowel Disease: Risk Factors and Outcomes.

Background and Aims: This study aimed to evaluate adherence to subcutaneous biologic therapy and impact of nonadherence including risk factors and outcomes in academic centers with integrated specialty pharmacies for patients with inflammatory bowel disease (IBD). Methods: This was a multicenter, retrospective cohort analysis of patients aged ≥18 years receiving care in 3 tertiary care outpatient IBD clinics with integrated specialty pharmacies. Subjects were prescribed injectable anti-TNF therapy (adalimumab, certolizumab, golimumab) or anti-IL 12/23 therapy (ustekinumab) with at least 3 consecutive prescription claims. The primary outcomes were medication possession ratio (MPR), percent achieving optimal adherence (MPR > 0.86); in addition, we sought to verify a prior risk factor model including smoking status, narcotic use, psychiatric history, and prior biologic use. Secondary outcomes included emergency department visits (ED) and IBD-related hospitalizations. Statistical analysis was performed using Wilcox rank sum test, Pearson's Chi-squared test, and logistic regression model as an unordered, factor variable to flexibly estimate the probabilities of adherence. Results: Six hundred eight subjects were included. Overall median MPR was 0.95 (interquartile range 0.47, 1) and adherence was 68%-70%. When the number of risk factors for nonadherence increased, the likelihood of nonadherence increased (P < .05). In unadjusted and adjusted analysis, nonadherence increased the likelihood of ED visits [rate ratio 1.45 (95% confidence interval 1.05, 1.97)] and hospitalizations [rate ratio 1.60 (95% confidence interval 1.16, 2.10)]. Conclusion: Academic centers with integrated pharmacies had high adherence. Prior risk factors for nonadherence remained significant in this multicenter model. Nonadherence was associated with higher likelihood of hospitalizations and ED visits.

Cannabis use disorder severity and sleep quality among undergraduates attending a Historically Black University.

Nearly one third of Americans experience poor sleep, which is associated with numerous deleterious health outcomes. Poor sleep may be exacerbated when an individual attends college, as they experience drastic shifts in lifestyle and sleep patterns. Previous research suggests cannabis has therapeutic potential for sleep disorders but may also impair sleep quality long-term. However, no study has examined the differences in sleep quality within individuals who meet criteria for Cannabis Use Disorder (CUD). The purpose of the current study was to determine differences in sleep quality among undergraduate students who met criteria for mild CUD (n = 18), moderate CUD (n = 22), severe CUD (n = 16) and students who did not meet criteria for CUD (n = 244). Participants included 300 predominantly Black/African American undergraduate students (79% female), aged between 18 and 25 years. Each participant completed an online survey that included measures assessing sleep quality and CUD criteria. Employing analysis of covariance, the moderate CUD subgroup (M = 9.00, SD = 3.32) reported poorer sleep quality than individuals who did not meet criteria for CUD (M = 6.93, SD = 3.03). Interestingly, the severe CUD subgroup (M = 6.75, SD = 2.52) reported similar sleep quality to individuals who did not meet criteria for CUD (M = 6.93, SD = 3.03). Individuals meeting criteria for mild and moderate CUD reported the poorest sleep quality among the groups, suggesting a differentiation within CUD severity. Future research should assess withdrawal and cannabis use frequency among individuals who meet criteria for CUD to further elucidate disturbances in sleep quality among those with CUD.

Assessing the validity of the Self-Report Webexec Questionnaire: Self-report vs performance neurocognitive inferences.

The Webexec is a self-reported neuropsychological measure, which previous research suggests is associated with personality and executive functions. Though the Webexec could be useful for brief neuropsychological assessment, there is limited literature examining its validity. The current study's purpose was to determine Webexec's validity and association with mood symptomatology in two Historically Black College or University (HBCU) undergraduate student samples. Study 1 employed a neurocognitive battery for convergent validity testing, while the second study utilized psychological measures to determine the Webexec's association with mood-based symptomatology. Study 1 included 149 participants, with a mean age of 20.08 (SD = 1.75) years. Participants completed a demographic questionnaire, the Webexec, and a neuropsychological battery. The neuropsychological battery measured verbal fluency, visual scanning, and working memory. The Webexec was positively associated with working memory (r = 0.18, p = 0.03), but no other neuropsychological measures. Study 2 utilized an online survey with 799 HBCU participants. Results suggest Webexec was associated with depressive symptomatology (r = 0.41, p = 0.01), anxiety symptomatology (r = 0.39, p = 0.01), and impulsivity (r = 0.21, p = 0.01). Taken together, results from both studies suggest the Webexec is not consistently associated with performance measures of executive function and maybe more consistent with self-reported psychological symptoms.

Controlling COVID-19 via test-trace-quarantine.

Initial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures. However, these interventions have had enormous societal and economic costs. Here, we demonstrate the feasibility of an alternative control strategy, test-trace-quarantine: routine testing of primarily symptomatic individuals, tracing and testing their known contacts, and placing their contacts in quarantine. We perform this analysis using Covasim, an open-source agent-based model, which has been calibrated to detailed demographic, mobility, and epidemiological data for the Seattle region from January through June 2020. With current levels of mask use and schools remaining closed, we find that high but achievable levels of testing and tracing are sufficient to maintain epidemic control even under a return to full workplace and community mobility and with low vaccine coverage. The easing of mobility restrictions in June 2020 and subsequent scale-up of testing and tracing programs through September provided real-world validation of our predictions. Although we show that test-trace-quarantine can control the epidemic in both theory and practice, its success is contingent on high testing and tracing rates, high quarantine compliance, relatively short testing and tracing delays, and moderate to high mask use. Thus, in order for test-trace-quarantine to control transmission with a return to high mobility, strong performance in all aspects of the program is required.

Treatment of Ulcerative Colitis with Steroids (in Whom, How Long, What Dose, What Form).

Corticosteroids are a nonspecific immune modulator used in the treatment of ulcerative colitis. Topical and systemic forms of corticosteroids have been shown to be effective in induction of clinical remission and remain first-line therapy for acute severe ulcerative colitis. A large proportion of patients experience adverse effects, however, including some serious adverse effects, including infection and increased mortality. Newer formulations of gut selective corticosteroids have reduced adverse effects associated with steroids.

An Unusual Presentation of Baker's Cyst Rupture in an Inflammatory Bowel Disease Patient.

When evaluating a patient with acute onset unilateral leg pain and concurrent inflammatory bowel disease (IBD), keeping a broad differential diagnosis will allow for prompt diagnosis and management. The patient described in this case report is a 32-year-old male with inflammatory ileocolonic Crohn's disease (CD) status after ileocecectomy with perianal involvement and known Type 1 arthropathy. He presented with a three-day history of unilateral leg swelling and tenderness. Initial evaluation focused on possible thrombosis given the development of erythema and systemic symptoms. Final diagnosis was ruptured Baker's (popliteal) cyst. This pathology is not well described in existing literature, but should be considered in IBD patients given their chronic inflammatory state and common associated intra-articular pathology.