Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Are Depression and Anxiety Underdiagnosed in Socially Vulnerable Patients With Inflammatory Bowel Disease?

INTRODUCTION: Depression and anxiety are highly prevalent among individuals with inflammatory bowel disease (IBD); however, little is understood about how social determinants of health (SDOH) may impact mental health diagnoses in this population. The social vulnerability index (SVI) is a publicly available tool that can be used to study SDOH in IBD patients. METHODS: Home addresses from a retrospective cohort of IBD patients at a single center were used to geocode patients to their individual census tract and corresponding SVI. We used multivariable logistic regression to examine the relationship between SVI and comorbid mental health diagnoses in patients with IBD. Secondarily, data from standardized health questionnaires were then used to determine if patients were adequately screened for depression and anxiety. RESULTS: In all, 9644 patients were included; 18% had a diagnosis of depression, 21% anxiety, and 32% had a composite of "any mental health diagnosis." Depression (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.02-1.56) but not anxiety (OR, 0.87; 95% CI, 0.71-1.06) nor "any mental health diagnosis" (OR, 1.09; 95% CI, 0.92-1.30) was associated with higher levels of social vulnerability. However, overall rates of screening for depression and anxiety were low (15% and 8%, respectively), with the lowest screening rates among the most socially vulnerable (depression 8.2%, anxiety 6.3%). CONCLUSIONS: Disparities in the diagnoses of depression and anxiety for socially vulnerable patients with IBD exist. Awareness of these inequities is the first step toward developing interventions to improve mental health screening, eliminate barriers and bias, and promote referrals for appropriate mental health management.

Socially vulnerable patients with inflammatory bowel disease are more likely to be diagnosed with depression but not anxiety. However, overall rates of screening for depression and anxiety are low, particularly among more socially vulnerable patients.

Self-Efficacy and the Impact of Inflammatory Bowel Disease on Patients' Daily Lives.

INTRODUCTION: Self-efficacy, i.e., the confidence in one's capacity to perform a behavior, is crucial to the development of inflammatory bowel disease (IBD) self-management skills. We aimed to measure IBD self-efficacy and the relationship between self-efficacy and the patient-reported impact of IBD on daily life. METHODS: We surveyed patients with IBD from a single academic center using the IBD Self-Efficacy Scale (IBD-SES) and patient-reported outcome (PRO) measures. The IBD-SES assesses 4 IBD domains: patients' confidence in managing stress and emotions, symptoms and disease, medical care, and remission. IBD PROs evaluate daily life impact, coping strategies, emotional impact, and systemic symptoms. We examined the association between IBD-SES domains with the lowest scores and IBD daily life impact. RESULTS: A total of 160 patients completed the survey. Domain scores on the IBD-SES were lowest for managing stress and emotions (mean 6.76, SD 1.86) and symptoms and disease (mean 6.71, SD 2.12) on a 1-10 scale. Controlling for age, sex, IBD type, disease activity, moderate-to-severe disease, depression and anxiety, a higher confidence in managing stress and emotions (ß -0.12, 95% confidence interval -0.20 to -0.05, P = 0.001), and managing symptoms and disease (ß -0.28, 95% confidence interval -0.35 to -0.20, P < 0.001) were each associated with lower IBD daily life impact. DISCUSSION: Patients with IBD report low confidence in managing stress and emotion and managing symptoms and disease. Higher self-efficacy in these domains was associated with lower IBD daily life impact. Self-management tools that promote self-efficacy in managing these domains have the potential to reduce IBD's daily life impact.

Social Network Diversity and the Daily Burden of Inflammatory Bowel Disease.

INTRODUCTION: To examine the association between social network, daily inflammatory bowel disease (IBD) burden, and related cognitive factors such as loneliness and psychological well-being. METHODS: Using survey data, we compared the relationship between social network diversity and daily IBD burden with multivariable linear regression. RESULTS: Patients with IBD with higher social network diversity reported a lower daily IBD burden. This association was more common among those who reported a higher degree of loneliness than those with a low degree of loneliness. DISCUSSION: We should consider diverse social connections as an indicator of risk for higher IBD burden, especially among lonely patients.

Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature.

BACKGROUND: Dual targeted therapy (DTT) has emerged as an attractive therapeutic option for select patients with active inflammatory bowel disease (IBD) who are unable to achieve remission with biologic or small molecule monotherapy. We conducted a systematic review of specific DTT combinations in patients with IBD. METHODS: We conducted a systematic search of MEDLINE, EMBASE, Scopus, CINAHL Complete, Web of Science Core Collection, and Cochrane Library to identify articles related to the use of DTT for the treatment of Crohn Disease (CD) or ulcerative colitis (UC) published before February 2021. RESULTS: Twenty-nine studies were identified comprising 288 patients started on DTT for partially or non-responsive IBD. We identified 14 studies with 113 patients receiving anti-tumor necrosis factor (TNF) and anti-integrin therapies (i.e., vedolizumab and natalizumab), 12 studies with 55 patients receiving vedolizumab and ustekinumab, nine studies with 68 patients receiving vedolizumab and tofacitinib, five studies with 24 patients receiving anti-TNF therapy and tofacitinib, six studies with 18 patients receiving anti-TNF therapy and ustekinumab, and three studies with 13 patients receiving ustekinumab and tofacitinib. CONCLUSION: DTT is a promising approach to improve IBD treatment for patients with incomplete responses to targeted monotherapy. Larger prospective clinical studies are needed to confirm these findings as is additional predictive modeling to identify the patient subgroups most likely to require and benefit from this approach.

The Relationship Between Opioid Use and Healthcare Utilization in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pain is commonly experienced by patients with inflammatory bowel disease (IBD). Unfortunately, pain management is a challenge in IBD care, as currently available analgesics are associated with adverse events. Our understanding of the impact of opioid use on healthcare utilization among IBD patients remains limited. METHODS: A systematic search was completed using PubMed, Embase, the Cochrane Library, and Scopus through May of 2020. The exposure of interest was any opioid medication prescribed by a healthcare provider. Outcomes included readmissions rate, hospitalization, hospital length of stay, healthcare costs, emergency department visits, outpatient visits, IBD-related surgeries, and IBD-related medication utilization. Meta-analysis was conducted on study outcomes reported in at least 4 studies using random-effects models to estimate pooled relative risk (RR) and 95% confidence interval (CI). RESULTS: We identified 1969 articles, of which 30 met inclusion criteria. Meta-analysis showed an association between opioid use and longer length of stay (mean difference, 2.25 days; 95% CI, 1.29-3.22), higher likelihood of prior IBD-related surgery (RR, 1.72; 95% CI, 1.32-2.25), and higher rates of biologic use (RR, 1.38; 95% CI, 1.13-1.68) but no difference in 30-day readmissions (RR, 1.17; 95% CI, 0.86-1.61), immunomodulator use (RR, 1.13; 95% CI, 0.89-1.44), or corticosteroid use (RR, 1.36; 95% CI, 0.88-2.10) in patients with IBD. On systematic review, opioid use was associated with increased hospitalizations, healthcare costs, emergency department visits, outpatient visits, and polypharmacy. DISCUSSION: Opioids use among patients with IBD is associated with increased healthcare utilization. Nonopioid alternatives are needed to reduce burden on the healthcare system and improve patient outcomes.

Pain control in inflammatory bowel disease presents a challenge due to the potential for adverse effects of opioids in this population. This systematic review and meta-analysis demonstrates that opioid use in inflammatory bowel disease is associated with increased healthcare utilization.

Efficacy of Ustekinumab in Crohn's Disease With and Without Concurrent Autoimmune Skin Disease.

BACKGROUND: Approximately 33% of Crohn's disease (CD) patients have associated autoimmune skin disease. The pathophysiology of the latter frequently involves interleukin-12/interleukin-23 signaling pathways that may also impact gut inflammation. Ustekinumab is an anti-IL-12/23 FDA-approved biologic for psoriasis and inflammatory bowel disease. However, its relative efficacy has never been studied in CD with autoimmune skin disease (CD-ASD) vs CD without autoimmune skin disease (CD-none). METHODS: This is a retrospective, single-center, case-control study comparing markers of disease activity between CD-ASD and CD-none. Biomarkers (fecal calprotectin [FCP], C-reactive protein [CRP]) prior to drug initiation and after at least 5 months of standard IBD dose ustekinumab therapy were extracted from the medical record. In addition, 2 blinded observers performed 5-point Likert scoring before and after endoscopic, pathologic, and imaging reports. RESULTS: In all, 395 CD patients received ustekinumab therapy (79 CD-ASD, 316 CD-none). Patients were similar in age; gender; ethnicity; CD severity, phenotype, and duration; tobacco, immunomodulator, and steroid use. Ustekinumab had greater efficacy in CD-ASD when evaluated by FCP (P = .0337) and CRP (P = .078). The CD-ASD group also showed better outcomes in Likert scores of endoscopy (P = .016), histopathology (P = .074), and imaging (P = .094). In all Likert parameters, CD-ASD had more patients with complete resolution of moderate/severe disease (P < .05). Additional subanalyses for surgeries, ulcers, abscesses, fistulas, and colitis were conducted, with colitis reaching statistical significance (P = .0011). CONCLUSIONS: Concurrent autoimmune skin disease in CD is associated with greater ustekinumab effectiveness in controlling intestinal inflammation.

Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study.

BACKGROUND & AIMS: Despite rescue therapy, more than 30% of patients with acute severe ulcerative colitis (ASUC) require colectomy. Tofacitinib is a rapidly acting Janus kinase inhibitor with proven efficacy in ulcerative colitis. Tofacitinib may provide additional means for preventing colectomy in patients with ASUC. METHODS: A retrospective case-control study was performed evaluating the efficacy of tofacitinib induction in biologic-experienced patients admitted with ASUC requiring intravenous corticosteroids. Tofacitinib patients were matched 1:3 to controls according to gender and date of admission. Using Cox regression adjusted for disease severity, we estimated the 90-day risk of colectomy. Rates of complications and steroid dependence were examined as secondary outcomes. RESULTS: Forty patients who received tofacitinib were matched 1:3 to controls (n = 113). Tofacitinib was protective against colectomy at 90 days compared with matched controls (hazard ratio [HR], 0.28, 95% confidence interval [CI], 0.10-0.81; P = .018). When stratifying according to treatment dose, 10 mg three times daily (HR, 0.11; 95% CI, 0.02-0.56; P = .008) was protective, whereas 10 mg twice daily was not significantly protective (HR, 0.66; 95% CI, 0.21-2.09; P = .5). Rate of complications and steroid dependence were similar between tofacitinib and controls. CONCLUSIONS: Tofacitinib with concomitant intravenous corticosteroids may be an effective induction strategy in biologic-experienced patients hospitalized with ASUC. Prospective trials are needed to identify the safety, optimal dose, frequency, and duration of tofacitinib for ASUC.

Creatinine generation is reduced in patients requiring continuous venovenous hemodialysis and independently predicts mortality.

BACKGROUND: Existing systems for grading severity of acute kidney injury (AKI) rely on a change of serum creatinine concentration over a defined time interval. The rate of change in serum creatinine increases by degree of reduction in glomerular filtration rate, but is mitigated by low creatinine generation rate (CGR). Failure to appreciate variation in CGR may lead to erroneous conclusions regarding severity of AKI and distorted predictions regarding patient outcomes based on AKI severity. METHODS: Cohort study of 103 patients who received continuous venovenous hemodialysis (CVVHD) over a 2-year period in a tertiary care hospital setting. Study participants entered the cohort when they were anuric, receiving a stable and uninterrupted dose of CVVHD with serum creatinine in steady state. They were followed until hospital discharge. CGR was measured based on dialyzate effluent volume and effluent creatinine concentration (prospective cohort) and via effluent volume and serum creatinine concentration (retrospective cohort). RESULTS: CGR (mean 10.5, range 1.7-22.4 mg/kg/day) was substantially lower in this patient population than what would be predicted from existing equations. Correlates of CGR in multivariable analysis included the length of hospitalization prior to measurement and presence of an oncologic diagnosis. Lower CGR was independently associated with in-hospital mortality in unadjusted analysis and after multivariable adjustment for measures of severity of illness. CONCLUSIONS: Grading systems for severity of AKI fail to account for variation in CGR, limiting their ability to predict relevant outcomes. Calculation of CGR is superior to other risk metrics in predicting hospital mortality in this population.

Timing of lower extremity frontal plane motion differs between female and male athletes during a landing task.

BACKGROUND: Female athletes are at a greater risk for noncontact anterior cruciate ligament injuries than male athletes. Gender differences in frontal plane kinematics (hip adduction, knee valgus, and ankle eversion) and temporal relationships that make up the components of dynamic knee valgus may explain this discrepancy. HYPOTHESIS: The authors hypothesized that women would reach peak frontal plane kinematic values earlier during landing compared with their male counterparts. STUDY DESIGN: Controlled laboratory study. METHODS: Hip, knee, and ankle 3-dimensional kinematics were measured using high-speed motion capture in 10 National Collegiate Athletic Association Division I female athletes and 10 male practice squad athletes during a drop-jump landing. Independent t tests were used to analyze each dependent variable to identify differences between genders. RESULTS: Maximum hip adduction, knee valgus, and ankle eversion occurred earlier in women than in men (mean differences 33.7% of stance [95% CI, 20.2%-47.2%], 41.7% [95% CI, 31.5%-51.6%], 16.5% of stance [95% CI, 7.3%-25.6%], respectively). Maximum hip adduction and knee valgus occurred before maximum knee flexion in women and after in men (mean differences 0.11 seconds [95% CI, 0.05-0.18 seconds], 0.19 seconds [95% CI, 0.13-0.25 seconds], respectively). Maximum ankle eversion occurred earlier in women than in men (mean difference 0.06 seconds [95% CI, 0.01-0.11 seconds]). There was a significant difference between genders for angular velocity of knee valgus (mean difference = 25.53 deg/sec [95% CI, 8.30-42.77 deg/sec]). CONCLUSION: Frontal plane kinematic temporal relationships at the hip, knee, and ankle differ between genders. The components of dynamic knee valgus peak during the deceleration phase in women and during the acceleration phase in men during a drop-jump landing. These data suggest that men and women employ a completely different kinematic landing/jumping strategy and that women land and collapse very rapidly into valgus compared with their male counterparts. CLINICAL RELEVANCE: The differences in timing of the components of dynamic knee valgus between women and men may contribute to the increased risk of noncontact anterior cruciate ligament injuries in female athletes. There may be implications for neuromuscular reeducation training in those at risk for anterior cruciate ligament injury so the components of dynamic valgus occur later in the landing phase of jumping.

A 5° medial wedge reduces frontal but not saggital plane motion during jump landing in highly trained women athletes.

Lower extremity mechanics during landing have been linked to traumatic and nontraumatic knee injuries, particularly in women's athletics. The effects of efforts to mitigate these risks have not been fully elucidated. We previously reported that a 5° medial wedge reduced ankle eversion and knee valgus. In the present report we further investigated the effect of a 5° medial wedge inserted in the shoes of female athletes on frontal plane hip motion, as well as ankle, knee, hip, and trunk saggital plane motion during a jump landing task. Kinematic data were obtained from 10 intercollegiate female athletes during jump landings from a 31 cm platform with and without a 5° medial wedge. Hip adduction was reduced 1.98° (95% CI 0.97-2.99°) by the medial wedge but saggital plane motions were unaffected. A 5° medial wedge reduces frontal plane motion and takes the knee away from a position associated with anterior cruciate ligament injury and patellofemoral pain syndrome. Although frontal plane motion was not captured it is unlikely to have increased in a bilateral landing task. Thus, it is likely that greater muscle forces were generated in these highly trained athletes to dissipate ground reaction forces when a medial wedge was in place. Additional investigation in younger and lesser trained athletes is warranted to assess the impact of orthotic devices on knee joint mechanics.