Yelena Zadvornova

Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life.

BACKGROUND Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aim of the study was to determine the prevalence and predictors of vitamin D deficiency in an IBD cohort. It was hypothesized that vitamin D deficiency is associated with increased disease activity and lower health-related quality of life (HRQOL). METHODS This was a retrospective cohort study. Harvey-Bradshaw index and ulcerative colitis disease activity index were used to assess disease activity. Short Inflammatory Bowel Disease Questionnaire scores were used to assess HRQOL. Multivariate logistic regression was used to identify independent predictors of vitamin D deficiency and its association with disease activity and HRQOL. RESULTS The study included 504 IBD patients (403 Crohns disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with older age (P = .004) and older age at diagnosis (P = .03). Vitamin D deficiency was associated with lower HRQOL (regression coefficient -2.21, 95% confidence interval [CI], -4.10 to -0.33) in CD but not UC (regression coefficient 0.41, 95% CI, -2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). CONCLUSIONS Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.

Association of Proton Pump Inhibitor Therapy With Spontaneous Bacterial Peritonitis in Cirrhotic Patients With Ascites

OBJECTIVES:Spontaneous bacterial peritonitis (SBP) is a frequent complication of cirrhosis. Bacterial contamination of ascites fluid leading to SBP is caused by bacterial translocation with subsequent bacteremia. Proton pump inhibitors (PPIs) suppress gastric acid secretion, allowing bacterial colonization of the upper gastrointestinal tract, and may predispose to bacterial overgrowth and translocation. The aim of this study was to determine whether PPI use in cirrhotics with ascites is associated with SBP.METHODS:A retrospective case–control study was performed. Seventy cirrhotics admitted with paracentesis-proven SBP between 2002 and 2007 were matched 1:1 (for age and Childs class) with comparable cirrhotics with ascites who were admitted for conditions other than SBP. We excluded patients on chronic antibiotic prophylaxis or with antecedent gastrointestinal bleeding. Outpatient PPI use at the time of admission was compared between groups, and the effect of covariates was analyzed.RESULTS:Patients with SBP had a significantly higher rate of prehospital PPI use (69%) compared with ascitic cirrhotics hospitalized without SBP (31%, P=0.0001). There was no significant difference in demographics, diabetes, etiology, or survival between groups. On multivariate analysis, PPI use was independently associated with SBP (odds ratio (OR) 4.31, confidence interval (CI) 1.34–11.7), and ascitic fluid protein was protective (OR 0.1, CI 0.03–0.25). In total, 47% of cirrhotic patients receiving PPI in this study had no documented indication for PPI treatment.CONCLUSIONS:PPI therapy is associated with SBP in patients with advanced cirrhosis. Prospective studies are needed to determine whether PPI avoidance can reduce the incidence of SBP and improve outcomes.

Clostridium difficile Is Associated With Poor Outcomes in Patients With Cirrhosis: A National and Tertiary Center Perspective

OBJECTIVES:Clostridium difficile–associated disease (CDAD) is associated with antibiotic use, acid suppression, and hospitalization, all of which occur frequently in cirrhosis. The aim was to define the effect of CDAD on outcomes and identify risk factors for its development in cirrhosis.METHODS:Case–control studies using the de-identified national (Nationwide Inpatient Sample, NIS) and an identified liver transplant center database of hospitalized cirrhotics with and without CDAD were performed. The NIS 2005 was queried for mortality, charges, and length of stay (LOS) in cirrhotics with/without CDAD. Outcomes of cirrhosis and infections were also analyzed. In the transplant center database, risk factors for CDAD were defined in hospitalized cirrhotics with/without CDAD who were age matched in a 1:2 ratio.RESULTS:The NIS 2005 included 1,165 cirrhotics with and 82,065 without CDAD. Cirrhotics with CDAD had a significantly higher mortality (13.8% vs. 8.2%, P<0.001), LOS (14.4 days vs. 6.7 days, P<0.001), and charges (

QuantiFERON TB gold testing for tuberculosis screening in an inflammatory bowel disease cohort in the United States.

79,351 vs.

The Effect of Fatigue on Driving Skills in Patients With Hepatic Encephalopathy

35,686, P<0.001) compared with those without CDAD. On multivariate analysis, CDAD was associated with higher mortality (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.29–1.85), charges, and LOS despite controlling for cirrhosis complications and infections. In the transplant center database, 54 cirrhotics with and 108 cirrhotics without CDAD were included. Outpatient spontaneous bacterial peritonitis prophylaxis (35% vs. 13%, P=0.01), inpatient antibiotic (63% vs. 35%, P=0.0001), and proton pump inhibitor (PPI) use (74% vs. 31%, P=0.0001) were significantly higher in those with CDAD.CONCLUSIONS:Cirrhotics with CDAD have a higher mortality, LOS, and charges on the NIS 2005 compared with those without CDAD. Antibiotic and PPI use are risk factors for CDAD development in hospitalized cirrhotics.

Impact of Autonomic Dysfunction on Inflammatory Bowel Disease

Background: Reactivation of latent Mycobacterium tuberculosis (TB) is a rare, yet devastating infectious complication associated with anti‐tumor necrosis factor alpha (TNF‐&agr;) therapy. We evaluated the performance of the QuantiFERON TB Gold test (QFT‐G) for TB screening in a cohort of inflammatory bowel disease (IBD) patients in the United States. Methods: We performed a retrospective, observational study of patients initiated and/or maintained on an anti‐TNF‐&agr; agent in a single IBD referral center and recorded the frequency and the test results of QFT‐G testing and the rate of TB reactivation. Results: 512 QFT‐G tests were done in 340 patients. Five patients (1.5%) had a positive, nine (2.7%) indeterminate, and 326 patients (95.8%) had a negative QFT‐G. After a mean follow‐up of 17 months there was one case of TB reactivation (0.3%). The use of immunosuppressive therapy or anti‐TNF therapy at the time of testing did not affect the results of the QFT‐G testing. Test–retest had substantial concordance (&kgr; = 0.72). 25% of patients (n = 85) had TST testing. Concordance between the TST and QFT‐G was found to be moderate (&kgr; = 0.4152, P = 0.0041). Conclusions: Most patients with negative QFT‐G tolerated anti‐TNF therapy with no evidence of TB reactivation. Concomitant use of immunosuppressive therapy or anti‐TNF did not seem to affect QFT‐G results. One patient had an indeterminate QFT‐G while on infliximab and later developed miliary TB. Concordance with TST is moderate. (Inflamm Bowel Dis 2011;)

Durability of Infliximab in Crohn's Disease: A Single-Center Experience

OBJECTIVES:Hepatic encephalopathy, both overt (OHE) and minimal (MHE), is associated with poor quality of life and fatigue. The aim of this study was to define the effect of fatigue on driving skills in MHE and OHE patients.METHODS:Cirrhotics and age/education-matched controls were administered a psychometric battery of tests to diagnose MHE. Cirrhotics with recent OHE on lactulose were also included. All subjects underwent a driving simulation; to assess fatigue, the second half performance was compared with the first half of the simulation. The outcomes were collisions, speeding, road excursions, and center crossings. Actual driving-associated fatigue was assessed by the American Medical Association (AMA) driver survey.RESULTS:A total of 100 cirrhotics (51 MHE, 27 no MHE, and 22 OHE) and 67 controls were included. A significantly higher proportion of OHE and MHE patients admitted to fatigue after actual driving on the AMA survey compared with no MHE patients (P=0.02). All patients who admitted to fatigue and none who denied fatigue on the AMA survey had simulator collisions. Psychometric and simulator performance in treated OHE patients was similarly impaired to MHE patients despite therapy. Within groups, a significant increase in collisions, speeding, and center crossings in the second half (P=0.01) was seen only in MHE patients.CONCLUSIONS:Psychometric and simulator performance in patients with recent OHE on treatment is similarly impaired as that of untreated MHE patients. Simulator performance in MHE worsens over time with fatigue. OHE and MHE patients had a higher rate of actual driving-associated fatigue on the AMA survey, which was significantly predictive of simulator collisions.

Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease

Functional symptoms are common in patients with inflammatory bowel disease (IBD). The autonomic nervous system has been proposed to be involved in the pathogenesis of IBD. Autonomic dysfunction (AD) is associated with systemic manifestations and altered gut motility that may contributed to functional symptoms. Aim To examine the impact of clinically manifest AD on patients with IBD. Methods This was a retrospective case-control study from a single tertiary referral IBD center. The cases comprised 43 IBD patients with AD diagnosed using a standardized battery of tests. Three disease-matched controls were selected for each case. We performed multivariate regression to compare health-related quality of life (SIBDQ), disease activity scores, and healthcare utilization. Results Female sex (83.7% vs. 53.5%, P<0.001) and psychiatric comorbidity (41.9% vs. 10.9%, P<0.001) were more common among IBD patients with AD than IBD controls. Small bowel transit times were significantly longer in cases (92.7 min) compared with controls (62.9 min, P=0.02). On multivariate analysis, AD was associated with a 7-point lower adjusted SIBDQ score compared with IBD controls [odds ratio (OR)−7.50; 95% confidence interval (CI), −12.0-−3.03]. AD was also significantly associated with having more than 3 annual gastroenterology office visits (OR 2.84; 95% CI, 1.09-7.35), and 1 or more IBD-related medical hospitalizations (OR 2.49; 95% CI, 1.09-5.71). Conclusions Clinically manifest AD is associated with lower quality of life and higher healthcare utilization in IBD patients. They may represent a cohort at risk for worse outcomes.

Impact of prior irregular infliximab dosing on performance of long-term infliximab maintenance therapy in Crohn's disease†

Background: Infliximab is effective maintenance for moderate to severe Crohns disease (CD); however, problems with immunogenicity and decreased efficacy often complicate long‐term use. Durability of infliximab maintenance therapy over multiple years has not been defined. Methods: This was a retrospective, observational study of CD patients who received maintenance infliximab for ≥1 year with the intention of ongoing maintenance. Patients were categorized into those who either discontinued treatment or continued maintenance therapy. We examined the impact of demographic, clinical characteristics, and prior episodic exposure on long‐term durability of infliximab therapy and also examined the reasons for discontinuation of therapy. Results: A total of 153 CD patients received maintenance infliximab treatment beyond 1 year and 42 (27%) ultimately discontinued treatment. The mean duration of maintenance treatment at the time of discontinuation was 42.4 ± 19.1 months compared to a follow‐up period of 49.4 ± 19.8 months in the cohort continuing therapy (P = 0.049). The main reasons for discontinuation were allergy/adverse reaction (44.2%) and decreased efficacy (38.2%). Use of concomitant immunosuppression was similar between the 2 groups (78.6% versus 83.8%, P = NS). However, the discontinued group had a higher rate of prior episodic dosing compared to CD patients who continued maintenance (28.8% versus 11.7%, P = 0.025), while there was no difference in the rate of intensified dosing (57.2% versus 50.5%, P = NS). Conclusions: One‐quarter of CD patients on long‐term infliximab maintenance discontinued treatment. A history of prior episodic dosing was significantly associated with infliximab discontinuation, despite concomitant immunosuppression. These data emphasize the need for optimization of infliximab for successful long‐term management. Inflamm Bowel Dis 2009

Initial Vancomycin Monotherapy is Associated With Higher Rates of Subsequent Clostridium difficile Infection in Inflammatory Bowel Disease Population

Background: Impairment of health‐related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohns disease [CD]). Between 2%–10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease‐specific HRQoL in this population compared to non‐PSC IBD controls. Methods: This was a retrospective, case–control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease‐specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey–Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. Results: There was no significant difference in the age, gender distribution, or disease duration between PSC‐IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC‐IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (−1.33, 95% confidence interval [CI] 95% CI −1.85 to −0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD‐related HRQoL. There was a higher proportion of permanent work disability in PSC‐IBD (7.7%) compared to controls (0%). Conclusions: PSC does not seem to influence disease‐specific HRQoL in our patients with IBD but is associated with a higher rate of work disability. (Inflamm Bowel Dis 2010)