Ulcerative Colitis: Nguyen GC

Nguyen GC, Harris ML, Dassopoulos T. · Division of Gastroenterology, The Johns Hopkins Hospital, 600 North Wolfe Street/Blalock 461, Baltimore, MD 21287, USA. · Curr Gastroenterol Rep. · Pubmed #17105689 No free full text.

Abstract: Immunomodulators are a class of drugs that attenuate the underlying inflammatory processes of Crohn's disease (CD) and ulcerative colitis (UC), the two major inflammatory bowel diseases (IBD). These agents play a prominent role in the management of refractory and steroid-dependent IBD. The immunomodulatory drugs in the IBD arsenal include azathioprine, 6-mercaptopurine, methotrexate, cyclosporine, and tacrolimus. Azathioprine and 6-mercaptopurine are considered first-line immunosuppressants due to their proven efficacy in both CD and UC and their safety profile, whereas cyclosporine occupies a niche as a surgery-sparing agent in the acute management of severe, steroid-refractory UC. Immunomodulators also appear to have a role as adjunctive therapy when used with infliximab or other biologic agents to reduce immunogenicity. Although data have been limited to observational studies, azathioprine and 6-mercaptopurine may be used during pregnancy.

Nguyen GC, Frick KD, Dassopoulos T. · Mount Sinai Hospital IBD Centre, University of Toronto, Toronto, Ontario, Canada. · Gastrointest Endosc. · Pubmed #19249771 No free full text.

Abstract: BACKGROUND: Management of unifocal, flat, low-grade dysplasia (LGD) in ulcerative colitis (UC) remains controversial. OBJECTIVE: To compare the relative costs and effectiveness of immediate colectomy and enhanced colonoscopic surveillance for the management of LGD. DESIGN AND SETTING: Medical decision analysis by using state-transition Markov models. Transition probabilities and health utilities were derived from the literature, and costs were derived from national hospital data sets and Medicare and/or Medicaid reimbursement schedules. PATIENTS: Two simulated cohorts of 10,000 patients with longstanding UC who were newly diagnosed with unifocal, flat LGD on initial surveillance colonoscopy. INTERVENTIONS: Immediate colectomy or enhanced surveillance (repeated colonoscopy at 3, 6, and 12 months, and then annually). MAIN OUTCOME MEASUREMENTS: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS: Immediate colectomy dominated over enhanced surveillance and yielded higher QALYs (20.1 vs 19.9 years) and lower costs ($75,900 vs $83,900). These findings were robust to variations in model parameters, with immediate colectomy remaining dominant in 90% of simulations in sensitivity analysis. Varying postcolectomy health utility outside the range in the probabilistic sensitivity analysis rendered enhanced surveillance cost effective. When the health utility was below 0.77, the incremental cost-effectiveness ratio was $50,000 per QALY. LIMITATIONS: Data based on observational studies and analyses rely on model assumptions. CONCLUSIONS: Our analysis showed that immediate colectomy was preferable to enhanced surveillance. Health preference toward the postcolectomy state is, however, an influential factor. This decision analysis model provides a conceptual framework for physicians and patients to understand the relative benefits and costs of both interventions.

Nguyen GC, Boudreau H, Harris ML, Maxwell CV. · Mount Sinai IBD Centre, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. · Clin Gastroenterol Hepatol. · Pubmed #19027089 No free full text.

Abstract: BACKGROUND & AIMS: Pregnant women with Crohn's disease (CD) or ulcerative colitis (UC) are at increased risk of adverse outcomes compared with pregnant women without these disorders. We estimated the occurrence of pregnancies in women with CD and UC in the United States and compared outcomes between these patients and the non-inflammatory bowel disease (IBD) obstetric population. METHODS: By using the 2005 Nationwide Inpatient Sample, we estimated the number of obstetric hospitalizations, deliveries, and Cesarean deliveries in women with CD, UC, and those without IBD. Outcomes included prevalences of Cesarean delivery, venous thromboembolism (VTE), blood transfusion, and malnutrition. RESULTS: Of an estimated 4.21 million deliveries, 2372 and 1368 occurred in women with CD and UC, respectively. Compared with the non-IBD population, adjusted odds of Cesarean delivery were higher in women with CD (adjusted odds ratio [aOR], 1.72; 95% confidence interval [CI], 1.44-2.04) and UC (aOR, 1.29; 95% CI, 1.01-1.66). The risk of VTE was substantially higher in women with CD (aOR, 6.12; 95% CI, 2.91-12.9) and UC (aOR, 8.44; 95% CI, 3.71-19.2) vs the non-IBD population. Blood transfusions occurred more frequently in women with CD (aOR, 2.82; 95% CI, 1.51-5.26), whereas protein-calorie malnutrition occurred more frequently in women with CD (aOR, 20.0; 95% CI, 8.8-45.4) or UC (aOR, 60.8; 95% CI, 28.2-131.0). CONCLUSIONS: Adverse pregnancy and maternal outcomes occur more frequently in women with IBD. Measures should be undertaken to reduce maternal complications such as VTE and malnutrition in women with these disorders.

Nguyen GC, Sam J. · Mount Sinai Hospital IBD Centre, University of Toronto School of Medicine, Toronto, Ontario, Canada. · Am J Gastroenterol. · Pubmed #18684186 No free full text.

Abstract: BACKGROUND: We sought to determine nationwide, population-based trends in rates of venous thromboembolism (VTE) among hospitalized inflammatory bowel disease (IBD) patients in the United States and to determine its mortality and economic impact. METHODS: We analyzed discharges from the Nationwide Inpatient Sample and used ICD-9-CM codes to identify Crohn's disease (CD) and ulcerative colitis (UC) between 1998 and 2004. Rates of VTE were compared between those with and without IBD. The impact of VTE on in-hospital mortality and resource utilization was quantified using regression analysis. RESULTS: After multivariate adjustment, both UC (OR 1.85, 95% CI 1.70-2.01) and CD discharges (OR 1.48, 95% CI 1.35-1.62) had higher rates of VTE compared to non-IBD discharges. Prevalence of VTE was greater among UC compared to CD discharges (OR 1.32, 95% CI 1.17-1.48). Among CD patients, active fistulizing disease was independently associated with greater VTE (OR 1.39, 95% CI 1.13-1.70). There was an annual 17% rise in odds of VTE among IBD admissions over 7 yr. VTE was associated with greater mortality among IBD patients (adjusted OR 2.50, 95% CI 1.83-3.43). This age- and comorbidity-adjusted excess mortality from VTE was 2.1-fold higher for IBD than for non-IBD patients (P < 0.0001). IBD patients with VTE had longer length of stay (11.7 vs 6.1 days, P < 0.0001) and incurred higher hospital charges ($47,515 vs $21,499; P < 0.0001). CONCLUSIONS: VTE is increasingly prevalent among hospitalized IBD patients and has substantial mortality and economic impact. These findings drive the need for widespread prophylaxis against and early detection of VTE among IBD inpatients.

Nguyen GC, Steinhart AH. · Mount Sinai Hospital IBD Centre, University of Toronto Faculty of Medicine, Toronto, Ontario, Canada. · Inflamm Bowel Dis. · Pubmed #18623172 No free full text.

Abstract: BACKGROUND: We sought to determine patterns of hospitalizations for inflammatory bowel disease (IBD) to centers that regularly admit high volumes of IBD patients and whether they impacted health outcomes. METHODS: We queried US hospital discharges in the Nationwide Inpatient Sample to identify admissions with a primary diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) between 1998 and 2004. We determined patterns and predictors of hospitalization at high IBD volume admission centers (HIVACs) (>or=145 IBD admissions annually) and assessed their impact on mortality. RESULTS: Over 7 years the proportion of patients admitted to HIVACs increased from 2.3% to 14.8%. IBD patients were less likely to be admitted to an HIVAC if they were insured by Medicare (odds ratio [OR] 0.74; 95% confidence interval [CI]: 0.65-0.83) or Medicaid (OR 0.71; 95% CI: 0.60-0.84), or were uninsured (OR 0.42; 95% CI: 0.30-0.58) compared with those privately insured. Neighborhood income above the national median favored admission to an HIVAC (OR 1.99; 95% CI: 1.46-2.71). In-hospital mortality was lower among HIVACs compared to non-HIVACs (3.5/1000 versus 7.2/1000, P < 0.0001) and was persistent after adjustment for surgery status, age, comorbidity, and health insurance (OR 0.65; 95% CI: 0.49-0.87). When stratified by diagnosis, mortality was reduced at HIVACs among CD (OR 0.58; 95% CI: 0.37-0.90) but not UC admissions. CONCLUSIONS: There is a rising trend in hospitalizations for IBD at HIVACs, which confers mortality benefit for those with CD. Prospective studies are warranted to further explore the impact of these high-volume centers on IBD health outcomes.

Nguyen GC, Kaplan GG, Harris ML, Brant SR. · Mount Sinai Hospital IBD Centre, University of Toronto School of Medicine, Toronto, Ontario, Canada. · Am J Gastroenterol. · Pubmed #18513271 No free full text.

Abstract: BACKGROUND: We sought to determine nationwide, population-based trends in rates of Clostridium difficile (C. difficile) infection among hospitalized inflammatory bowel disease (IBD) patients in the United States, and to determine its mortality and economic impact. METHODS: We analyzed discharge records from the Nationwide Inpatient Sample, and used the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes to identify Crohn's disease (CD) and ulcerative colitis (UC) cases, and cases of C. difficile infection between 1998 and 2004. Temporal patterns of C. difficile incidence in IBD patients were compared to non-IBD gastroenterology patients and all-hospitalized patients. The impact of C. difficile on in-hospital mortality and resource utilization was quantified using multiple regression analysis. RESULTS: The prevalence of C. difficile among UC patients (37.3 per 1,000, 95% confidence interval [CI] 34.0-40.7 per 1,000) was higher than that among CD patients (10.9 per 1,000, 95% CI 9.9-12.0 per 1,000), non-IBD gastrointestinal (GI) patients (4.8 per 1,000, 95% CI 4.6-5.0 per 1,000), and general medical patients (4.5 per 1,000, 95% CI 4.2-4.7 per 1,000). C. difficile incidence nearly doubled among UC patients (26.6 per 1,000 to 51.2 per 1,000) over 7 yr. After adjustment for confounders, C. difficile infection was associated with greater mortality among patients with UC (odds ratio [OR] 3.79, 95% CI 2.84-5.06), but not CD (OR 1.66, 95% CI 0.75-3.66). C. difficile was also associated with 65% and 46% longer lengths of stay, which correlated with 63% and 46% higher average hospital charges, for CD and UC patients, respectively. CONCLUSIONS: C. difficile infection is a growing public health issue among hospitalized IBD patients, especially those with UC, and is associated with higher mortality and resource utilization, prompting the need for better preventative measures and early detection.

Nguyen GC, Munsell M, Harris ML. · Mount Sinai Hospital IBD Centre, University of Toronto School of Medicine, Toronto, Ontario, Canada. · Inflamm Bowel Dis. · Pubmed #18302272 links to  free full text

Abstract: BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of protein-calorie malnutrition. We sought to determine the prevalence of clinically diagnosable malnutrition among those hospitalized for IBD throughout the United States and whether this malnutrition influenced health outcomes. METHODS: We queried the Nationwide Inpatient Sample between 1998 and 2004 to identify admissions for Crohn's disease (CD) or ulcerative colitis (UC) and a representative sample of non-IBD discharges. We assessed the prevalence and predictors of malnutrition and its association with in-hospital mortality and resource utilization. RESULTS: The prevalence of malnutrition was greater in CD and UC patients than in non-IBD patients (6.1% and 7.2% versus 1.8%, P < 0.0001). The adjusted odds ratio for malnutrition among IBD admissions compared with non-IBD admissions was 5.57 [95% confidence interval (CI): 5.29-5.86]. More IBD discharges than non-IBD discharges with malnutrition received parenteral nutrition (26% versus 6%, P < 0.0001). There was increased likelihood of malnutrition among those with fistulizing CD (OR 1.65; 95% CI: 1.50-1.82) and among those who had undergone bowel resection (OR 1.37; 95% CI: 1.27-1.48). Malnutrition was associated with increased in-hospital mortality 3.49 (95% CI: 2.89-4.23), length of stay (11.9 days versus 5.8 days, P < 0.00001), and total charges ($45,188 versus $20,295, P < 0.0001). CONCLUSIONS: Clinically apparent malnutrition is more frequent among IBD admissions than among non-IBD admissions. Its association with greater mortality and resource utilization may reflect more severe underlying disease that can lead to both malnutrition and worse outcomes. Nonetheless, diagnosable malnutrition may serve as a clinical marker of poor IBD prognosis in hospitalized patients.

Nguyen GC, Laveist TA, Brant SR. · Mount Sinai Hospital IBD Centre, University of Toronto School of Medicine, Toronto, ON, Canada. · Aliment Pharmacol Ther. · Pubmed #17931346 No free full text.

Abstract: BACKGROUND: Parenteral nutrition has a limited role in the in-patient management of inflammatory bowel disease. AIM: To determine nationwide patterns of in-patient parenteral nutrition utilization and its demographic determinants and impact on outcomes. METHODS: We identified inflammatory bowel disease discharges in the Nationwide Inpatient Sample between 1998 and 2003 and determined rates of parenteral nutrition utilization among US census regions, in-hospital mortality and hospital resource utilization. RESULTS: The parenteral nutrition utilization rate among hospitalized inflammatory bowel disease patients was 6%. Only 64% of Crohn's disease and 55% of ulcerative colitis discharges who received parenteral nutrition had malnutrition, fistulizing or obstructive Crohn's disease, or surgery as an indication. The adjusted odds ratio of receiving parenteral nutrition were 0.36 (95% CI: 0.26-0.51) for the mid-west, 0.47 (0.37-0.56) for the south and 0.70 (0.56-0.89) for the west, compared to the north-east. Use of parenteral nutrition was associated with higher in-hospital mortality (OR 2.5; 95% CI: 1.93-3.24), length of stay (13.7 vs. 5.7 days, P < 0.001) and hospital charges ($51,729 vs. $19,563, P < 0.001). CONCLUSIONS: In-patient utilization of parenteral nutrition for inflammatory bowel disease varies markedly by census region, expends significant resources, and leads to potentially significant adverse outcomes. These findings underscore the need for guidelines for judicious parenteral nutrition use in inflammatory bowel disease.

Nguyen GC, Tuskey A, Dassopoulos T, Harris ML, Brant SR. · Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Inflamm Bowel Dis. · Pubmed #17828784 links to  free full text

Abstract: BACKGROUND: Recent epidemiological studies suggest that the prevalences of Crohn's disease (CD) and ulcerative colitis (UC) are increasing in the United States. We sought to determine whether nationwide rates of inflammatory bowel disease (IBD) hospitalizations have increased in response to temporal trends in prevalence. METHODS: We identified all admissions with a primary diagnosis of CD or UC, or 1 of their complications in the Nationwide Inpatient Sample between 1998 and 2004. National estimates of hospitalization rates and rates of surgery were determined using the U.S. Census population as the denominator. RESULTS: There were an estimated 359,124 and 214,498 admissions for CD and UC, respectively. The overall hospitalization rate for CD was 18.0 per 100,000 and that for UC was 10.8 per 100,000. There was a 4.3% annual relative increase in hospitalization rate for CD (P < 0.0001) and a 3.0% annual increase for UC (P < 0.0001). Surgery rates were 3.4 bowel resections per 100,000 for CD and 1.2 colectomies per 100,000 for UC and remained stable. There were no temporal patterns for average length of stay for CD (5.8 days) or for UC (6.8 days). The national estimate of total inpatient charges attributable to CD increased from $762 million to $1,330 million between 1998 and 2004, and that for UC increased from $592 million to $945 million.CONCLUSIONS: Hospitalization rates for IBD, particularly CD, have increased within a 7-year period, incurring a substantial rise in inflation-adjusted economic burden. The findings reinforce the need for effective treatment strategies to reduce IBD complications.

Dassopoulos T, Nguyen GC, Bitton A, Bromfield GP, Schumm LP, Wu Y, Elkadri A, Regueiro M, Siemanowski B, Torres EA, Gregory FJ, Kane SV, Harrell LE, Franchimont D, Achkar JP, Griffiths A, Brant SR, Rioux JD, Taylor KD, Duerr RH, Silverberg MS, Cho JH, Steinhart AH. · Johns Hopkins University Meyerhoff Inflammatory Bowel Disease Center, Baltimore MD, USA. · Inflamm Bowel Dis. · Pubmed #17427244 links to  free full text

Abstract: BACKGROUND: The NIDDK IBD Genetics Consortium (IBDGC) collects DNA and phenotypic data from inflammatory bowel disease (IBD) subjects to provide a resource for genetic studies. No previous studies have been performed on the reliability and validity of phenotypic determinations in either Crohn's disease (CD) or ulcerative colitis (UC) using primary records. Our aim was to determine the reliability and validity of these phenotypic assessments. METHODS: The de-identified records of 30 IBD patients were reviewed by 2 phenotypers per center using a standard protocol for phenotypic assessment. Each phenotyper evaluated 10 charts on 2 occasions 5 months apart. Reliability was expressed as the kappa (kappa) statistic. Performance characteristics were determined by comparison to a consensus-derived "gold standard" and by generation of receiver operating characteristic (ROC) curves. RESULTS: Agreement for diagnosis was excellent (kappa = 0.82; 95% confidence interval [CI]: 0.71-0.92). Agreement for CD location was good for jejunal, ileal, colorectal, and perianal disease with kappa between 0.60 and 0.74 but was fair for esophagogastroduodenal (kappa = 0.36). Agreement for UC extent (kappa = 0.67; 95% CI: 0.48-0.85), and CD behavior (kappa = 0.67; 95% CI: 0.49-0.83) were very good. Area under the ROC curves was greater than 0.84 for diagnosis, CD behavior, UC extent, and ileal and colonic CD location. CONCLUSIONS: IBD phenotype classification using a standard protocol exhibited very good to excellent inter- and intrarater agreement and validity. This study highlights the importance of standard protocols in generating reliable and valid phenotypic assessments. The data will facilitate estimates of phenotyping misclassification rates that should be considered when making inferences from IBD genotype-phenotype studies.

Nguyen GC, Laveist TA, Gearhart S, Bayless TM, Brant SR. · Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. · Clin Gastroenterol Hepatol. · Pubmed #17162242 No free full text.

Abstract: BACKGROUND & AIMS: Ulcerative colitis is a debilitating disease for which colectomy is curative. Racial disparities have been described for a wide spectrum of surgical procedures. The goal of this study was to characterize racial and geographic differences in colectomy rates among hospitalized ulcerative colitis (UC) patients. METHODS: We analyzed discharge records from the Nationwide Inpatient Sample, the largest representative sample of acute care hospitals throughout the United States. A total of 23,389 discharges with UC from 1998-2003 were included for analysis. Colectomy rates, in-hospital mortality, and length of stay were calculated for non-Hispanic whites, African Americans, and Hispanics. RESULTS: After adjustment for age, gender, health insurance, comorbidity, and hospital characteristics, the colectomy rate ratios for African Americans and Hispanics compared with whites were 0.46 (95% confidence interval, 0.35-0.60) and 0.74 (95% confidence interval, 0.59-0.93), respectively. African Americans experienced a longer interval between admission and colectomy than whites (8.8 vs 5.6 days, P=.02). There were also significant geographic variations in colectomy, with the West and Midwest regions yielding rates 3-fold higher than the Northeast. Although adjusted in-hospital mortality did not differ by race, Medicaid patients had 3.3-fold higher mortality than those with private insurance. Between 1998 and 2003, the colectomy rate decreased among whites but not African Americans and Hispanics. A temporal narrowing of geographic variation in colectomy was also observed. CONCLUSIONS: The rate of colectomy among hospitalized UC patients varies significantly by race and geographic location. Further studies are needed to elucidate the social and biologic underpinnings of these variations.

Nguyen GC, Torres EA, Regueiro M, Bromfield G, Bitton A, Stempak J, Dassopoulos T, Schumm P, Gregory FJ, Griffiths AM, Hanauer SB, Hanson J, Harris ML, Kane SV, Orkwis HK, Lahaie R, Oliva-Hemker M, Pare P, Wild GE, Rioux JD, Yang H, Duerr RH, Cho JH, Steinhart AH, Brant SR, Silverberg MS. · Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Am J Gastroenterol. · Pubmed #16696785 No free full text.

Abstract: OBJECTIVES: Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population. METHODS: Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions. RESULTS: African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4-5.5), colorectal disease (OR = 1.9; 95% CI: 1.1-3.4), perianal disease (OR = 1.7; 95% CI: 1.03-2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32-0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3-13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55-10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8-4.6) and erythema nodosum (3.3; 95% CI: 1.7-6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts. CONCLUSIONS: There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations.