Arthur Barrie

Association Between Telephone Activity and Features of Patients With Inflammatory Bowel Disease

BACKGROUND & AIMS Telephone communication is common between healthcare providers and patients with inflammatory bowel disease (IBD). We analyzed telephone activity at an IBD care center to identify disease and patient characteristics associated with high levels of telephone activity and determine if call volume could identify individuals at risk for future visits to the emergency department (ED) or hospitalization. METHODS We performed a prospective observational study in which we categorized telephone calls received by nursing staff over 2 years at a tertiary care IBD clinic (2475 patients in 2009 and 3118 in 2010). We analyzed data on 21,979 ingoing and outgoing calls in 2009 and 32,667 calls in 2010 and assessed associations between clinical factors and logged telephone encounters, and between patterns of telephone encounters and future visits to the ED or hospitalization. RESULTS Telephone encounters occurred twice as frequently as office visits; 15% of the patients generated >10 telephone encounters per year and were responsible for half of all telephone encounters. A higher percentage of these high telephone encounter (HTE) patients were female, had Crohns disease, received steroid treatment, had increased levels of C-reactive protein and rates of erythrocyte sedimentation, had psychiatric comorbidities, and had chronic abdominal pain than patients with lower telephone encounters. The HTE patients were also more frequently seen in the ED or hospitalized over the same time period and in subsequent years. Forty-two percent of patients with >8 telephone encounters within 30 days were seen in the ED or hospitalized within the subsequent 12 months. CONCLUSIONS Based on an analysis of telephone records at an IBD clinic, 15% of patients account for half of all calls. These HTE patients are a heterogeneous group with refractory disease who are likely to visit the ED or be hospitalized.

Association of Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Longitudinal Study.

OBJECTIVES:Emerging data suggest that vitamin D has a significant role in inflammatory bowel disease (IBD). Prospective data evaluating the association of vitamin D serum status and disease course are lacking. We sought to determine the relationship between vitamin D status and clinical course of IBD over a multiyear time period.METHODS:IBD patients with up to 5-year follow-up from a longitudinal IBD natural history registry were included. Patients were categorized according to their mean serum 25-OH vitamin D level. IBD clinical status was approximated with patterns of medication use, health-care utilization, biochemical markers of inflammation (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), pain and clinical disease activity scores, and health-related quality of life.RESULTS:A total of 965 IBD patients (61.9% Crohn’s disease, 38.1% ulcerative colitis) formed the study population (mean age 44 years, 52.3% female). Among them, 29.9% had low mean vitamin D levels. Over the 5-year study period, subjects with low mean vitamin D required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions, and surgery compared with subjects with normal mean vitamin D levels (P<0.05). Moreover, subjects with low vitamin D levels had worse pain, disease activity scores, and quality of life (P<0.05). Finally, subjects who received vitamin D supplements had a significant reduction in their health-care utilization.CONCLUSIONS:Low vitamin D levels are common in IBD patients and are associated with higher morbidity and disease severity, signifying the potential importance of vitamin D monitoring and treatment.

Impact of Obesity on the Management and Clinical Course of Patients with Inflammatory Bowel Disease.

Background:Obesity has been linked with a proinflammatory state and the development of inflammatory diseases. Data on the clinical course and treatment of obese patients with inflammatory bowel disease (IBD) are limited. We used an institutional IBD registry to investigate the impact of obesity on IBD severity and treatment. Methods:This was a retrospective analysis of prospectively collected data for 3 years (2009–2011). Patients with IBD were categorized by body mass index (BMI). IBD-related quality of life, biochemical markers of inflammation, comorbidities, health care utilization, and treatment were characterized. Obesity was defined as a BMI ≥30 (type I: 30–34.9, type II: 35–39.9, and type III ≥40). Results:Among 1494 patients with IBD, 71.9% were above their ideal BMI and 31.5% were obese. Obesity was more common in ulcerative colitis compared with patients with Crohns disease (P = 0.04). Obese class II and class III patients were predominantly female. Obesity in IBD was associated with female gender (P < 0.0001), diabetes mellitus (P < 0.001), hypertension (P < 0.001), hyperlipidemia (P < 0.001), poor quality of life (P < 0.0001), and increased rates of C-reactive protein elevation (P = 0.008). In logistic regression analysis, quality of life and C-reactive protein elevation were not independently correlated with obesity. There was no association between increasing BMI and annual prednisone use, emergency department visits, hospitalization, and surgery. Obesity was associated with lower milligrams per kilogram doses of purine analogs and biologics. Conclusions:Obesity in IBD is not associated with increased health care utilization and IBD-related surgeries. Optimal regimens for drug dosing in obese patients with IBD have yet to be defined.

Physician assessment of ulcerative colitis activity correlates poorly with endoscopic disease activity

Background: Subjective physician assessment is the cornerstone of routine ulcerative colitis (UC) management. Endoscopic and histologic assessment of UC provides objective measures of inflammatory disease activity. The level of agreement between physician impression of UC activity and endoscopic disease activity has not been evaluated. The aim was to assess the level of agreement between physicians clinical impression of UC disease activity and endoscopic and histologic findings of inflammation. Methods: Using the Medical Archival Retrieval System at the University of Pittsburgh Medical Center, we reviewed clinical information on all UC patients between 1995 and 2008 who had clinic visits recorded prior to colonoscopy. Clinical UC disease activity was defined by the physicians clinical impression and the endoscopic and histologic activity by colonoscopy with biopsy. The level of agreement between colonoscopy assessment of UC with histologic and clinical assessment was determined by sensitivity, specificity, positive and negative predictive values, and the kappa coefficient. Results: There were 369 UC patients who had a clinic visit proximate to a colonoscopy. The mean age of patients was 46 ± 16 years (50% female). The performance of clinical impression in recognizing disease activity, as determined by endoscopy, was relatively poor: sensitivity = 56.0%, predictive value negative = 56.8%, kappa coefficient = 0.35. In contrast, the performance of histological evaluation in recognizing disease activity was markedly better: sensitivity = 93.5%, predictive value negative = 89.1%, kappa coefficient = 0.70. Conclusions: The physicians clinical impression of UC activity shows poor agreement with endoscopy and histology, with over one‐third of patients with chronic inflammation underrecognized by clinical impression. The consequences of underestimated UC activity by clinical assessment may include undertreatment of active disease and uncontrolled chronic inflammation. (Inflamm Bowel Dis 2011;)

Tumor necrosis factor α antagonist-associated psoriasis in inflammatory diseases: an analysis of the FDA adverse event reporting system.

Background:Crohn’s disease (CD) is a chronic inflammatory, relapsing, and progressive condition that leads to bowel damage and subsequent stricturing or penetrating complications. Tumor necrosis factor (TNF) &agr; antagonists (e.g., infliximab) can achieve sustained remission in CD. However, a paradox exists as to whether use of these medications, which effectively treat psoriasis, also confer risk of developing psoriasiform lesions. Methods:Data from the Food and Drug Administration Adverse Event Reporting System (2004–2011) were analyzed. Adverse event reports for the TNF-&agr; antagonists infliximab, adalimumab, and certolizumab were reviewed. Primary “control” drugs examined included the non–CD drugs propranolol and lithium because of their recognized association with risk of psoriasis and the nonbiological CD drug mesalamine. Proportional reporting ratios for psoriasis adverse events were calculated for TNF-&agr; antagonists versus control drugs. Results:From more than 13 million reports in Adverse Event Reporting System, the biological group included 5432 reports with psoriasis listed (infliximab = 1789; adalimumab = 3475; and certolizumab = 168) compared with just 88 psoriasis reports for the control group (propranolol = 24; mesalamine = 24; and lithium = 40). Compared with control drugs, the psoriasis proportional reporting ratios for TNF-&agr; antagonists were as follows: infliximab (6.61), adalimumab (12.13), and certolizumab (5.43) (P < 0.0001). The aggregate “class” proportional reporting ratio for all TNF-&agr; antagonists versus control drugs was 9.24 (P < 0.0001). Similar results were observed when psoriasis reports were compared between TNF-&agr; antagonists and other drugs used to treat CD, including azathioprine, 6-mercaptopurine, methotrexate, corticosteroids, ciprofloxacin, and the antimalarial drug, hydroxychloroquine. Conclusions:Data from the Food and Drug Administration Adverse Event Reporting System suggest that TNF-&agr; antagonists used in the treatment of CD confer an increased risk of psoriasiform adverse events.

Demographic and Clinical Predictors of High Healthcare Use in Patients with Inflammatory Bowel Disease.

Background:Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory condition requiring significant healthcare expenditure. Subgroups of individuals contribute disproportionately to spending. We aimed to determine demographic and clinical factors predictive of high healthcare expenditures for IBD patients followed over a multiyear period. Methods:This was a registry analysis using a prospective observational, consented, natural history registry from a tertiary IBD center and associated medical charges, not including pharmacy expenses. The 100 patients with the highest medical charges (top 5%) were compared with the median 300 patients. Logistic regression determined demographic and clinical factors associated with high charge patients. Results:IBD patients in the high charge group had significantly more unemployment (P < 0.0001), were of black race (P = 0.013), comorbid psychiatric illness (P = 0.002), hypertension (P = 0.01), diabetes (P = 0.004), opiate use (P < 0.0001), perianal involvement (P = 0.002), penetrating disease (P < 0.0001), and extensive colitis (P = 0.01). In multivariate analysis, unemployment (Crohns disease [CD]: odds ratio [OR], 3.04; 95% confidence interval [CI], 1.32–7.02; ulcerative colitis [UC]: OR, 2.68; 95% CI, 1.20–5.99), psychiatric illness (UC: OR, 2.08; 95% CI, 1.03–4.19), opiates (CD: OR, 5.61; 95% CI, 2.67–11.82; UC: OR, 5.14; 95% CI, 2.52–10.48), prior surgery (CD: OR, 3.29; 95% CI, 1.59–6.82; UC: OR, 2.72; 95% CI, 1.39–5.32), penetrating CD (OR, 3.29; 95% CI, 1.02–10.62), and corticosteroid requirement (CD: OR, 3.78; 95% CI, 1.86–7.65; UC: OR, 2.98; 95% CI, 1.51–5.90) remained independently associated with high charges. Conclusions:High expenditure IBD patients were affected by more severe disease. The high prevalence of depression, anxiety, and chronic pain in these patients suggests the need for focused treatment of these comorbidities ultimately to reduce financial burden.

Silent Crohn's Disease: Asymptomatic Patients with Elevated C-reactive Protein Are at Risk for Subsequent Hospitalization.

Background:Patient-reported Crohns disease (CD) symptoms and endoscopic evaluation have historically guided routine care, but the risk of complications in asymptomatic patients with elevated C-reactive protein (CRP) is unknown. Methods:We conducted a prospective observational cohort study of patients with CD from a tertiary care center. Subjects with short inflammatory bowel disease questionnaire scores ≥50, Harvey–Bradshaw CD scores ⩽4, and same-day CRP measurement were eligible for inclusion. The primary outcome was disease-related hospitalization up to 24 months after the qualifying clinic visit. We assessed the relationship between CRP elevation and subsequent hospitalization. Results:There were 351 asymptomatic patients with CD (median age 40 yr; 50.4% female) who met inclusion criteria, and CRP was elevated in 19.7% of these individuals (n = 69). At 24 months, 16.8% (n = 59) of the study population had been hospitalized for CD-related complications. Significantly, more patients with an elevated CRP were hospitalized (33.3% versus 12.8%, P < 0.0001) compared with those with a normal CRP and were hospitalized at increased rate (P < 0.001) on Kaplan–Meier analysis. CRP elevation was significantly and independently associated with increased risk of hospitalization (adjusted hazard ratio 2.12; 95% confidence interval, 1.13–3.98; P = 0.02) in multivariable survival analysis. Conclusions:Asymptomatic patients with CD with elevated CRP are at a nearly 2-fold higher risk for hospitalization over the subsequent 2 years compared with asymptomatic patients with CD without CRP elevation.

Prostaglandin E2 and IL‐23 plus IL‐1β Differentially Regulate the Th1/Th17 Immune Response of Human CD161+CD4+ Memory T Cells

Prostaglandin E2 (PGE2), interleukin (IL)‐23, and IL‐1beta (β) propagate inflammatory bowel disease (IBD) by enhancing the development and function of IL‐17 producing CD4+ T helper (Th17) cells. CD4+ T cells that express the C‐type lectin‐like receptor CD161 have been proposed to be the physiologic pool of circulating Th17 cells implicated in IBD. We sought to understand how PGE2, alone and in combination with IL‐23 and IL‐1β, modulate human peripheral CD161+CD4+ memory T cells. We found that CD161+ cells comprise a significant proportion of human peripheral CD4+ memory T cells. PGE2 and IL‐23 plus IL‐1β synergistically induced early IL‐17A secretion from CD161+CD4+ memory T cells and the selective enrichment of IL‐17A+CD161+CD4+ memory T cells in culture. Conversely, IL‐23 plus IL‐1β partially opposed the PGE2‐mediated repression of early interferon gamma (IFN‐γ) secretion from CD161+ cells, as well as the PGE2‐mediated depletion of IFN‐γ+CD161+ cells. Our results suggest that PGE2 and IL‐23 plus IL‐1β induce the Th17 immune response preferentially in CD161+CD4+ memory T cells, while divergently regulating their ability to express IFN‐γ. We hypothesize that Th17‐mediated chronic inflammation in IBD depends on the net response of CD161+CD4+ memory T cells to both PGE2 and IL‐23 plus IL‐1β. Clin Trans Sci 2011; Volume 4: 268–273

The IL17A and IL17F loci have divergent histone modifications and are differentially regulated by prostaglandin E2 in Th17 cells

Prostaglandin E2 (PGE2), IL-23 and IL-1β are implicated in inflammatory bowel disease susceptibility, likely in part by modulating IL-17 producing CD4(+) T helper (Th17) cells. To better understand how these three mediators affect Th17 cell memory responses, we characterized the gene expression profiles of activated human peripheral CD4(+) effector memory T cells and sorted Th17 memory cells from healthy donors concurrent with IL17A mRNA induction mediated by PGE2 and/or IL-23 plus IL-1β. We discovered that PGE2 and IL-23 plus IL-1β differentially regulate Th17 cytokine expression and synergize to induce IL-17A, but not IL-17F. IL-23 plus IL-1β preferentially induce IL-17F expression. The addition of PGE2 to IL-23 plus IL-1β only enhances IL-17A expression as mediated by the PGE2 EP4 receptor, and promotes a switch from an IL-17F to an IL-17A predominant immune response. The human Th17 HuT-102 cell line was also found to constitutively express IL-17A, but not IL-17F. We went on to show that the IL17A and IL17F loci have divergent epigenetic architectures in unstimulated HuT-102 and primary Th17 cells and are poised for preferential expression of IL17A. We conclude that the chromatin for IL17A and IL17F are distinctly regulated, which may play an important role in mucosal health and disease.

The Influence of Anti-tumor Necrosis Factor Agents on Hemoglobin Levels of Patients with Inflammatory Bowel Disease.

Background:Anti–tumor necrosis factor (TNF) agents are an important component of inflammatory bowel disease (IBD) treatment, but data on their influence on anemia, a frequent complication of IBD, are limited. The aim of this study was to evaluate the effect of anti-TNF agents on hemoglobin (Hb) levels in a large IBD cohort. Methods:Prospectively collected demographic, clinical, laboratory, and treatment data from IBD patients who started anti-TNF treatment at a tertiary referral center during the years 2010 to 2012 were analyzed. Follow-up data including disease activity scores (Harvey–Bradshaw index or ulcerative colitis activity index), quality of life scores (short IBD questionnaire) completed at each visit, and laboratory data were analyzed. Data from the year of anti-TNF initiation (yr 0) to the following year (yr 1) were compared. Results:A total of 430 IBD patients (324 with Crohns disease, 51.6% females) started anti-TNF treatment. The prevalence of anemia and median Hb levels did not change between years 0 and 1. Median short IBD questionnaire was significantly improved at year 1 (P = 0.002). IBD patients with anemia had significantly higher median Hb levels at year 1 compared with year 0 (P = 0.0009). Hematopoietic response (increase of Hb ≥2 g/dL) was observed in only 33.6% of the 134 anemic IBD patients, despite iron replacement being administered in 126 anemic patients (oral, 77%). Improvement in Hb levels was independently significantly correlated with change of C-reactive protein levels (P = 0.04) and immunomodulator use (P = 0.03). Conclusions:Anemia remains a significant manifestation of IBD 1 year after treatment with anti-TNF agents.