39 results on '"Pardi, Darrell S."'
Search Results
2. Effectiveness and Safety Profile of Budesonide Maintenance in Microscopic Colitis: A Systematic Review and Meta-Analysis.
- Author
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Tome J, Tariq R, Hassett LC, Khanna S, and Pardi DS
- Subjects
- Humans, Maintenance Chemotherapy, Recurrence, Remission Induction, Treatment Outcome, Randomized Controlled Trials as Topic, Anti-Inflammatory Agents therapeutic use, Anti-Inflammatory Agents adverse effects, Budesonide therapeutic use, Budesonide adverse effects, Budesonide administration & dosage, Colitis, Microscopic drug therapy
- Abstract
Background: Microscopic colitis (MC) is a common cause of chronic diarrhea. Randomized controlled trials (RCTs) have demonstrated the efficacy of budesonide treatment for MC. However, relapse is frequent after discontinuation of budesonide, and data on maintenance therapy are limited. We performed a systematic review and meta-analysis evaluating these outcomes in clinical trials and real-world settings., Methods: A systematic search was performed on October 31, 2022, of Medline, Embase, Cochrane, and Scopus. Case series, case-control, cohort studies, and RCTs of adults with MC were included. Data were pooled using random effects models to calculate weighted pooled estimates and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic., Results: We included 35 studies (11 RCTs, 24 observational studies) with 1657 MC patients treated with budesonide induction and 146 for maintenance. The overall pooled clinical remission rate with budesonide treatment was similar between RCTs and observational studies. The pooled remission rate with budesonide maintenance therapy was 84% (95% CI, 0.60-1.00; I2 = 91%). After budesonide discontinuation, the pooled relapse rate was 53% (95% CI, 0.42-0.63; I2 = 76%). On maintenance therapy, no differences were noted in adverse events (eg, metabolic bone disease, hypertension, hyperglycemia, cataracts/glaucoma) in those on budesonide vs placebo or other noncorticosteroid medications for MC (P = .9)., Conclusions: Budesonide is an effective maintenance treatment for MC. There is a high risk of recurrence after budesonide discontinuation, but long-term use at the lowest effective dose appears to be relatively safe and have limited adverse effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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3. Clinical Course and Impact of Immune Checkpoint Inhibitor Colitis Resembling Microscopic Colitis.
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Fredrick TW, Ramos GP, Braga Neto MB, Kane S, Faubion WA, Loftus EV Jr, Pardi DS, Pasha SF, Farraye FA, Zhang L, and Raffals LE
- Abstract
Background: Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC., Methods: A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response., Results: Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment., Conclusions: MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)
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- 2022
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4. Durability of Response to Fecal Microbiota Transplantation After Exposure to Risk Factors for Recurrence in Patients With Clostridioides difficile Infection.
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Saha S, Mara K, Pardi DS, and Khanna S
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- Adult, Clostridioides, Fecal Microbiota Transplantation, Female, Humans, Male, Middle Aged, Recurrence, Retrospective Studies, Risk Factors, Treatment Outcome, Clostridioides difficile, Clostridium Infections therapy, Neoplasms
- Abstract
Background: Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI., Methods: We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure., Results: Overall, 460 patients were included (median age, 57 years [18-94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%-84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI, .15-.49; P < .001)., Conclusions: The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2021
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5. RBX7455, a Non-frozen, Orally Administered Investigational Live Biotherapeutic, Is Safe, Effective, and Shifts Patients' Microbiomes in a Phase 1 Study for Recurrent Clostridioides difficile Infections.
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Khanna S, Pardi DS, Jones C, Shannon WD, Gonzalez C, and Blount K
- Subjects
- Adult, Clostridioides, Fecal Microbiota Transplantation, Humans, Recurrence, Treatment Outcome, Clostridioides difficile, Clostridium Infections drug therapy, Microbiota
- Abstract
Background: Recurrent Clostridioides difficile infections (rCDI) are a global public health threat. To reduce rCDI, microbiota-restoring therapies are needed, particularly standardized, easy-to-administer formulations., Methods: This phase I open-label trial assessed the safety, efficacy in preventing rCDI recurrence, and intestinal microbiome effects of RBX7455, a room temperature-stable, orally administered investigational live biotherapeutic. Adult participants with 1 or more prior episodes of rCDI received: 4 RBX7455 capsules twice daily for 4 days (group 1); 4 RBX7455 capsules twice daily for 2 days (group 2); or 2 RBX7455 capsules twice daily for 2 days (group 3). For all groups, the first dose was administered in clinic, with remaining doses self-administered at home. Adverse events were monitored during and for 6 months after treatment. Treatment success was defined as rCDI prevention through 8 weeks after treatment. Participants' microbiome composition was assessed prior to and for 6 months after treatment., Results: Nine of 10 group 1 patients (90%), 8 of 10 group 2 patients (80%), and 10 of 10 group 3 patients (100%) were recurrence-free at the 8-week endpoint with durability to 6 months. Seventy-five treatment-emergent adverse events were observed in 27 participants with no serious investigational product-related events. Prior to treatment, participants' microbiomes were dissimilar from the RBX7455 composition with decreased Bacteroidia- and Clostridia-class bacteria, whereas after treatment, responders' microbiomes showed increased Bacteroidia and Clostridia., Conclusions: Three dosing regimens of RBX7455 were safe and effective at preventing rCDI. Responders' microbiomes converged toward the composition of RBX7455. These results support its continued clinical evaluation., Clinical Trials Registration: NCT02981316., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2021
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6. SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial.
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McGovern BH, Ford CB, Henn MR, Pardi DS, Khanna S, Hohmann EL, O'Brien EJ, Desjardins CA, Bernardo P, Wortman JR, Lombardo MJ, Litcofsky KD, Winkler JA, McChalicher CWJ, Li SS, Tomlinson AD, Nandakumar M, Cook DN, Pomerantz RJ, Auninš JG, and Trucksis M
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- Aged, Clostridioides, Drugs, Investigational, Female, Humans, Male, Recurrence, Clostridioides difficile, Clostridium Infections drug therapy, Clostridium Infections prevention & control, Microbiota
- Abstract
Background: Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs., Methods: In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile-positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed., Results: 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11-2.81), while the <65 group showed no benefit. Early engraftment of SER-109 was associated with nonrecurrence (P < .05) and increased secondary bile acid concentrations (P < .0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal. Adverse events were generally mild to moderate in severity., Conclusions: Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial., Clinical Trials Registration: NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw= 2&rank=4., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2021
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7. A 1-Year Cross-sectional Inflammatory Bowel Disease Surveillance Colonoscopy Cohort Comparing High-definition White Light Endoscopy and Chromoendoscopy.
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Coelho-Prabhu N, Bruining DH, Faubion WA, Kane SV, Kisiel JB, Papadakis KA, Pardi DS, Raffals LE, Schroeder KW, Tremaine WJ, Fruth K, Harmsen WS, and Loftus EV
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- Colonoscopy, Cross-Sectional Studies, Humans, Hyperplasia epidemiology, Cholangitis, Sclerosing epidemiology, Inflammatory Bowel Diseases diagnostic imaging, Inflammatory Bowel Diseases epidemiology
- Abstract
Background: We sought to compare the dysplasia detection rate of high-definition white light endoscopy (HDWLE) with that of chromoendoscopy in patients with long-standing inflammatory bowel disease (IBD)., Methods: This is a retrospective observational cohort of patients with IBD who underwent surveillance colonoscopy between October 1, 2016 and September 30, 2017. We assessed the association between dysplasia detection and multiple variables., Results: A total of 808 unique colonoscopies were performed, of which 150 (18.6%) included chromoendoscopy. Primary sclerosing cholangitis was a comorbid diagnosis in 24.5% of patients. The performing endoscopist was an IBD specialist with 37.1% of patients and had >10 years' experience with 64.9% of patients. Prior dysplasia had been seen in 245 (30.3%) patients: 102 (68.0%) and 143 (22.0%) among patients who had chromoendoscopy and HDWLE, respectively. Dysplasia in polyps was found in 129 procedures (15.1%). Among patients who had chromoendoscopy and HDWLE, polypoid dysplasia was identified in 50 (33.0%) and 79 (12.0%) patients, respectively, P < 0.01. Dysplasia in random biopsies was found in 39 patients (4.8%): 15 (10%) who had chromoendoscopy and 24 (3.6%) who had HDWLE (P < 0.001). On multivariate analysis, patient and disease characteristics significantly associated with an increased odds for polypoid dysplasia included older age at diagnosis (odds ratio [OR] = 1.3 per 10 years; 95% confidence interval [CI], 1.07-1.60), having an IBD physician endoscopist (OR = 1.6; 95% CI, 1.01-2.67), having an endoscopist with less than 10 years' experience (OR = 1.8; 95% CI (1.16-2.89), and prior random dysplasia (OR = 4.2; 95% CI (1.93-9.17). Concomitant primary sclerosing cholangitis was significantly associated with random dysplasia (OR = 2.3; 95% CI, 1.02-5.07). After multivariate analysis adjusting for these variables, chromoendoscopy was no more likely to identify dysplasia than was HDWLE., Conclusions: Chromoendoscopy and HDWLE had a similar diagnostic yield for dysplasia detection in patients with chronic IBD-colitis after adjusting for multiple known risk factors., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2021
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8. Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.
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Tariq R, Disbrow MB, Dibaise JK, Orenstein R, Saha S, Solanky D, Loftus EV, Pardi DS, and Khanna S
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- Adult, Clostridioides difficile, Colitis microbiology, Diarrhea microbiology, Diarrhea therapy, Enterocolitis, Pseudomembranous microbiology, Female, Humans, Male, Middle Aged, Recurrence, Retrospective Studies, Symptom Flare Up, Treatment Outcome, Colitis, Ulcerative microbiology, Crohn Disease microbiology, Enterocolitis, Pseudomembranous therapy, Fecal Microbiota Transplantation, Inflammatory Bowel Diseases microbiology
- Abstract
Background: Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients., Methods: We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results., Results: We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified., Conclusions: Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
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9. Reply to Lagier et al.
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Tariq R, Pardi DS, and Khanna S
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- Fecal Microbiota Transplantation, Humans, Clostridioides difficile
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- 2020
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10. In Search of the (Clostridium difficile) Holy Grail.
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Pardi DS and Khanna S
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- Biomarkers, Clostridioides, Diarrhea, Humans, Clostridioides difficile, Clostridium Infections diagnosis, Clostridium Infections epidemiology
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- 2020
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11. Reply to Khoruts and Sadowsky.
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Khanna S, Tariq R, and Pardi DS
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- Diagnostic Tests, Routine, Clostridioides difficile, Fecal Microbiota Transplantation
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- 2019
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12. Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis.
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Tariq R, Pardi DS, Bartlett MG, and Khanna S
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- Humans, Randomized Controlled Trials as Topic, Recurrence, Clostridium Infections therapy, Fecal Microbiota Transplantation
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Background: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridium difficile infection (CDI) in observational studies (>90%), but cure rates in clinical trials are lower. We performed a systematic review and meta-analysis to assess the efficacy of FMT for recurrent CDI in open-label studies and clinical trials ., Methods: A systematic search from January 1978 to March 2017 was performed to include clinical trials of FMT for CDI. We analyzed CDI resolution by calculating weighted pooled rates (WPRs)., Results: Thirteen trials were included, comprising 610 patients with CDI treated with single FMT. Overall, 439 patients had clinical cure (WPR, 76.1%; 95% confidence interval (CI), 66.4%-85.7%). There was significant heterogeneity among studies (I2 = 91.35%). Cure rates were lower in randomized trials (139/216 patients; WPR, 67.7%; 95% CI, 54.2%-81.3%) than in open-label studies (300/394 patients; WPR, 82.7%; 71.1%-94.3%) (P < .001). Subgroup analysis by FMT delivery modality showed lower cure rates with enema than colonoscopy (WPR, 66.3% vs 87.4%; P < .001) but no difference between colonoscopy and oral delivery (WPR, 87.4% vs 81.4%; P = .17). Lower rates were seen for studies including both recurrent and refractory CDI than for those including only recurrent CDI (WPR, 63.9% vs 79%; P < .001)., Conclusions: FMT was associated with lower cure rates in randomized trials than in open-label and in observational studies. Colonoscopy and oral route are more effective than enema for stool delivery. The efficacy also seems to be higher for recurrent than for refractory CDI., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
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13. Colon Surgery Risk With Corticosteroids Versus Immunomodulators or Biologics in Inflammatory Bowel Disease Patients With Clostridium difficile Infection.
- Author
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Solanky D, Pardi DS, Loftus EV, and Khanna S
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- Adult, Aged, Aged, 80 and over, Clostridium Infections epidemiology, Clostridium Infections microbiology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Minnesota epidemiology, Prognosis, Retrospective Studies, Risk Factors, Young Adult, Adrenal Cortex Hormones adverse effects, Biological Products adverse effects, Clostridioides difficile isolation & purification, Clostridium Infections therapy, Colectomy statistics & numerical data, Immunologic Factors adverse effects, Inflammatory Bowel Diseases complications
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Background: Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), and CDI often precipitates IBD exacerbation. Because CDI cannot be distinguished clinically from an IBD exacerbation, management is difficult. We aimed to assess factors associated with adverse outcomes in IBD with CDI, including the role of escalating or de-escalating IBD therapy and CDI treatment., Methods: Records for patients with IBD and CDI from 2008 to 2013 were abstracted for variables including IBD severity before CDI diagnosis, CDI management, subsequent IBD exacerbation, CDI recurrence, and colon surgery. Colon surgery was defined as resection of any colonic segment within 1 year after CDI diagnosis., Results: We included 137 IBD patients (median age, 46 years; 55% women): 70 with ulcerative colitis (51%), 63 with Crohn's disease (46%), and 4 with indeterminate colitis (3%). Overall, 70% of CDIs were mild-moderate, 14% were severe, and 15% were severe-complicated. Clostridium difficile infection treatment choice did not vary by infection severity (P = 0.27). Corticosteroid escalation (odds ratio [OR], 5.94; 95% confidence interval [CI], 2.03-17.44) was a positive predictor of colon surgery within 1 year after CDI; older age (OR, 0.09; 95% CI, 0.01-0.44) was a negative predictor. Modifying the corticosteroid regimen did not affect CDI recurrence or risk of future IBD exacerbation. Adverse outcomes did not differ with CDI antibiotic regimens or biologic or immunomodulator regimen modification., Conclusions: Corticosteroid escalation for IBD during CDI was associated with higher risk of colon surgery. Type of CDI treatment did not influence IBD outcomes. Prospective studies are needed to further elucidate optimal management in this high-risk population., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2019
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14. Clinical Benefit of Capsule Endoscopy in Crohn's Disease: Impact on Patient Management and Prevalence of Proximal Small Bowel Involvement.
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Hansel SL, McCurdy JD, Barlow JM, Fidler J, Fletcher JG, Becker B, Prabhu NC, Faubion WA, Hanson KA, Kane SV, Kisiel JB, Loftus EV Jr, Papadakis KA, Pardi DS, Raffals LE, Schoenoff S, Tremaine WJ, and Bruining DH
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- Adult, Aged, Female, Humans, Intestine, Small pathology, Magnetic Resonance Imaging, Male, Middle Aged, Patient Safety, Prospective Studies, Tomography, X-Ray Computed, Young Adult, Capsule Endoscopy, Crohn Disease diagnostic imaging, Intestine, Small diagnostic imaging
- Abstract
Background: Ileocolonoscopy and computed tomography (CT) or magnetic resonance (MR) enterography (CTE/MRE) are utilized to evaluate patients with small bowel (SB) Crohn's disease (CD). The purpose of our study was to estimate the impact of capsule endoscopy (CE) on patient management after clinical assessment, ileocolonoscopy, and CTE/MRE., Methods: We prospectively analyzed 50 adult CD patients without strictures at clinically indicated ileocolonoscopy and CTE/MRE exams. Providers completed pre- and post-CE clinical management questionnaires. Pre-CE questionnaire assessed likelihood of active SBCD and management plan using a 5-point level of confidence (LOC) scales. Post-CE questionnaire assessed alteration in management plans and contribution of CE findings to these changes. A change of ≥2 on LOC scale was considered clinically meaningful., Results: Of the 50 patients evaluated (60% females), median age was 38 years, median disease duration was 3 years, and median Crohn's Disease Activity Index (CDAI) score was 238 points. All CTE/MRE studies were negative for proximal disease. CE detected proximal disease in 14 patients (28%) with a median Lewis score of 215 points. CE findings altered management in 17 cases (34%). The most frequent provider-perceived benefits of CE were addition of new medication (29%) and exclusion of active SB mucosal disease (24%)., Conclusion: CE is a safe imaging modality that alters clinical management in patients with established SBCD by adding incremental information not available at ileocolonoscopy and cross-sectional enterography.
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- 2018
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15. Low Risk of Primary Clostridium difficile Infection With Tetracyclines: A Systematic Review and Metaanalysis.
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Tariq R, Cho J, Kapoor S, Orenstein R, Singh S, Pardi DS, and Khanna S
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- Case-Control Studies, Clostridioides difficile, Clostridium Infections prevention & control, Enterocolitis, Pseudomembranous epidemiology, Enterocolitis, Pseudomembranous prevention & control, Humans, Incidence, Observational Studies as Topic, Odds Ratio, Risk Factors, Anti-Bacterial Agents therapeutic use, Clostridium Infections epidemiology, Tetracyclines therapeutic use
- Abstract
Background: The choice of antibiotics for systemic infections in patients with a high risk of Clostridium difficile infection (CDI) remains a clinical practice dilemma. Although some studies suggest that tetracyclines may be associated with a lower risk of CDI than other antibiotics, other results are conflicting. We conducted a systematic review and metaanalysis of studies that assessed the risk of CDI with tetracyclines compared to other antibiotics., Methods: We conducted a systematic search of Medline, Embase, and Web of Science from January 1978 through December 2016 to include studies that assessed the association between tetracycline use and risk of CDI. Weighted summary estimates were calculated using generalized inverse variance with a random-effects model using RevMan 5.3. Study quality was assessed using the Newcastle-Ottawa scale., Results: Six studies (4 case control, 2 cohort) with patient recruitment between 1993 and 2012 were included. Metaanalysis using a random-effects model, demonstrated that tetracyclines were associated with a decreased risk of CDI (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.47-0.81; P < .001). There was significant heterogeneity, with an I2 of 53% with no publication bias. Subgroup analysis of studies that evaluated the risk of CDI with doxycycline alone also demonstrated a decreased risk of CDI (OR, 0.55; 95% CI, 0.40-0.75; P < .001)., Conclusions: Metaanalyses of existing studies suggest that tetracyclines may be associated with a decreased risk of CDI compared with other antimicrobials. It may be reasonable to use tetracyclines whenever appropriate to decrease CDI associated with antibiotic use., (© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2018
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16. Reply to Davido et al.
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Khanna S, Tariq R, Tosh PK, Walker RC, Razonable RR, and Pardi DS
- Subjects
- Fecal Microbiota Transplantation, Humans, Clostridium Infections, Urinary Tract Infections
- Published
- 2018
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17. Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection Reduces Recurrent Urinary Tract Infection Frequency.
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Tariq R, Pardi DS, Tosh PK, Walker RC, Razonable RR, and Khanna S
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- Aged, Aged, 80 and over, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Clostridioides difficile drug effects, Clostridium Infections complications, Clostridium Infections drug therapy, Female, Humans, Male, Microbial Sensitivity Tests, Recurrence, Retrospective Studies, Clostridium Infections epidemiology, Clostridium Infections therapy, Fecal Microbiota Transplantation, Urinary Tract Infections complications, Urinary Tract Infections epidemiology
- Abstract
Broad-spectrum antibiotics for recurrent multidrug-resistant urinary tract infections (UTIs) disrupt the gut microbiome and promote antibiotic resistance. Fecal microbiota transplantation led to resolution of recurrent Clostridium difficile, significantly decreased recurrent UTI frequency, and improved antibiotic susceptibility profile of UTI-causing organisms., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2017
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18. Extended-release Multimatrix Budesonide for Microscopic Colitis.
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Kamboj AK, Cotter TG, Hicks SB, Tremaine WJ, Loftus EV Jr, and Pardi DS
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- Adolescent, Adult, Aged, Aged, 80 and over, Delayed-Action Preparations, Drug Compounding, Female, Humans, Male, Middle Aged, Prognosis, Young Adult, Anti-Inflammatory Agents therapeutic use, Budesonide therapeutic use, Colitis, Microscopic drug therapy
- Published
- 2017
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19. A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection.
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Khanna S, Pardi DS, Kelly CR, Kraft CS, Dhere T, Henn MR, Lombardo MJ, Vulic M, Ohsumi T, Winkler J, Pindar C, McGovern BH, Pomerantz RJ, Aunins JG, Cook DN, and Hohmann EL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biological Therapy adverse effects, Diarrhea prevention & control, Female, Humans, Male, Middle Aged, Young Adult, Biological Therapy methods, Clostridioides difficile growth & development, Clostridium Infections prevention & control, Gastrointestinal Microbiome, Gastrointestinal Tract microbiology, Secondary Prevention methods
- Abstract
Background: Patients with recurrent Clostridium difficile infection (CDI) have a ≥60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI., Methods: Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 × 10(9) spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 × 10(8) spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed., Results: Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea., Conclusions: SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
- Published
- 2016
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20. Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study.
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Orenstein R, Dubberke E, Hardi R, Ray A, Mullane K, Pardi DS, and Ramesh MS
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- Adult, Aged, Aged, 80 and over, Diarrhea therapy, Enema, Female, Humans, Male, Middle Aged, Prospective Studies, Recurrence, Clostridioides difficile, Enterocolitis, Pseudomembranous therapy, Fecal Microbiota Transplantation adverse effects, Microbiota
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Background: Managing recurrent Clostridium difficile infection (CDI) presents a significant challenge for clinicians and patients. Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent CDI, yet availability of a standardized, safe, and effective product has been lacking. Our aim in this study was to assess the safety and effectiveness of RBX2660 (microbiota suspension), a commercially prepared FMT drug manufactured using standardized processes and available in a ready-to-use format., Methods: Patients with at least 2 recurrent CDI episodes or at least 2 severe episodes resulting in hospitalization were enrolled in a prospective, multicenter open-label study of RBX2660 administered via enema. Intensive surveillance for adverse events (AEs) was conducted daily for 7 days following treatment and then at 30 days, 60 days, 3 months, and 6 months. The primary objective was product-related AEs. A secondary objective was CDI-associated diarrhea resolution at 8 weeks., Results: Of the 40 patients enrolled at 11 centers in the United States between 15 August 2013 and 16 December 2013, 34 received at least 1 dose of RBX2660 and 31 completed 6-month follow-up. Overall efficacy was 87.1% (16 with 1 dose and 11 with 2 doses). Of 188 reported AEs, diarrhea, flatulence, abdominal pain/cramping, and constipation were most common. The frequency and severity of AEs decreased over time. Twenty serious AEs were reported in 7 patients; none were related to RBX2660 or its administration., Conclusions: Among patients with recurrent or severe CDI, administration of RBX2660 via enema appears to be safe and effective., Clinical Trials Registration: NCT01925417., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
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- 2016
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21. Comparative outcomes of younger and older hospitalized patients with inflammatory bowel disease treated with corticosteroids.
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Weber NK, Bruining DH, Loftus EV Jr, Tremaine WJ, Augustin JJ, Becker BD, Kammer PP, Harmsen WS, Zinsmeister AR, and Pardi DS
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- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Case-Control Studies, Child, Female, Follow-Up Studies, Humans, Male, Medical Records, Middle Aged, Prognosis, Young Adult, Adrenal Cortex Hormones therapeutic use, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Hospitalization statistics & numerical data
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Background: Data on the differences in inpatient treatment approaches and outcomes between younger and older patients with inflammatory bowel disease (IBD) are limited. Therefore, we used a parallel cohort study design to compare outcomes between younger and older patients with IBD., Methods: All anti-tumor necrosis factor (TNF)-naive patients aged 60 years and older hospitalized at our institution between 2003 and 2011 and treated with corticosteroids for an IBD flare were matched 1:1 to younger patients aged 18 to 50 years. Rates of corticosteroid response, colectomy, and initiation of anti-TNF therapy were compared., Results: Sixty-five patients were identified in each cohort. Median ages were 70 years (range, 60-94) and 30 years (range, 18-50) for the older and younger groups, respectively. Twenty-three percent of older patients were refractory to corticosteroids compared with 38% of the younger cohort (odds ratio, 0.5; 95% confidence intervals, 0.2-1.1). Older corticosteroid-refractory patients had surgery (80% versus 72%) and were started on anti-TNF therapy (20% versus 12%; P = 0.71), at a similar frequency as younger patients. Older steroid-responsive patients were less likely to start an anti-TNF agent during the first year of follow-up than younger patients (7% versus 31%, P = 0.006), but there was no difference in 1-year colectomy rates (27% versus 28%, P = 0.63)., Conclusions: Corticosteroid response was similar in older and younger patients hospitalized for IBD. Inpatient treatment for corticosteroid-refractory patients was similar between cohorts. Older corticosteroid-responsive patients were less likely to be treated with an anti-TNF than younger patients.
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- 2013
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22. Cytomegalovirus infection of the ileoanal pouch: clinical characteristics and outcomes.
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McCurdy JD, Loftus EV Jr, Tremaine WJ, Smyrk TC, Bruining DH, Pardi DS, Raffals LE, Kisiel JB, Coelho-Prabhu N, Kane SV, Faubion WA, and Papadakis KA
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- Adult, Anastomosis, Surgical, Antiviral Agents therapeutic use, Child, Colonic Pouches pathology, Cytomegalovirus pathogenicity, Cytomegalovirus Infections drug therapy, Cytomegalovirus Infections pathology, Female, Follow-Up Studies, Ganciclovir therapeutic use, Humans, Inflammatory Bowel Diseases surgery, Male, Middle Aged, Postoperative Complications, Pouchitis drug therapy, Pouchitis pathology, Proctocolectomy, Restorative, Prognosis, Recurrence, Young Adult, Colonic Pouches virology, Cytomegalovirus Infections virology, Pouchitis virology
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Background: Up to 30% of cases of pouchitis are felt to have a secondary cause. Cytomegalovirus (CMV) may represent a possible etiopathological agent. Here, we report our experience with CMV involvement of the pouch, including risk factors, clinical features, and pouch outcomes in patients with inflammatory bowel disease after proctocolectomy with ileal pouch-anal anastomosis., Methods: The pathology database at Mayo Clinic in Rochester was searched between January 1995 and October 2012 for patients with a tissue diagnosis of CMV of the pouch following ileal pouch-anal anastomosis., Results: Seven patients with CMV inclusions of the pouch were identified. The median age was 35 (range, 10-53) years, and the majority were female (71%). Five patients (71%) were on immunosuppressive medications including 4 who had undergone orthotopic liver transplantation for primary sclerosing cholangitis. The clinical presentation was similar among all patients: the majority had diarrhea (86%), fever (71%), and abdominal pain (57%). All had mucosal inflammation, with 71% having focal ulcerations in the pouch and 60% having inflammatory changes in the prepouch ileum. All patients improved with ganciclovir. None required pouch excision or had recurrent CMV infection. Three patients had recurrent nonspecific pouchitis., Conclusions: A high index of suspicion is needed to diagnose CMV of the pouch. An increase in stool frequency and fever in patients on immune suppression or in those who have failed empiric antibiotics should prompt assessment for CMV infection. Antiviral therapy seems to be effective, and postinfection pouch outcomes seem favorable, particularly in those presenting with their first episode of pouchitis.
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- 2013
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23. Management of the elderly patients with inflammatory bowel disease: practical considerations.
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Katz S, Surawicz C, and Pardi DS
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- Aged, Comorbidity, Disease Management, Humans, Prognosis, Aging, Inflammatory Bowel Diseases therapy
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The aging U.S. population will approach 20% of the total population by 2030. The number of older patients with inflammatory bowel disease is anticipated to increase accordingly bringing the burden of multiple comorbidities, polypharmacy with drug interactions, the aging immune system, and extended social and financial issues to overall management of an already challenging management of these patients. Each of these concerns is measured by the metric of distinguishing the "fit versus frail" elderly and will be discussed in this review with an emphasis on a practical guide to therapy.
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- 2013
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24. Effect of ursodeoxycholic acid use on the risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a systematic review and meta-analysis.
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Singh S, Khanna S, Pardi DS, Loftus EV Jr, and Talwalkar JA
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- Colorectal Neoplasms etiology, Humans, Meta-Analysis as Topic, Prognosis, Cholagogues and Choleretics therapeutic use, Cholangitis, Sclerosing complications, Colorectal Neoplasms prevention & control, Inflammatory Bowel Diseases complications, Ursodeoxycholic Acid therapeutic use
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Background: Ursodeoxycholic acid (UDCA) may modify the risk of inflammatory bowel disease (IBD)-associated colorectal cancer. We performed a systematic review and meta-analysis of studies evaluating the effect of UDCA on the risk of IBD-associated colorectal neoplasia (CRN) (defined as colorectal cancer and/or dysplasia) in patients with primary sclerosing cholangitis with concomitant IBD (PSC-IBD)., Methods: We conducted a systematic search of Medline, Embase, and Web of Science and manually reviewed the literature. Studies were included if they: (1) evaluated exposure to UDCA in patients with PSC-IBD, (2) reported IBD-associated CRN as outcome, and (3) reported relative risks or odds ratios (ORs) or provided data for their calculation. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random-effects model., Results: Eight studies (5 observational, 3 randomized controlled trials) reporting 177 cases of CRN in 763 patients with PSC-IBD were included in the analysis. Overall, meta-analysis showed no significant protective association between UDCA use and CRN (OR, 0.81; 95% CI, 0.41-1.61). However, there was a significant chemopreventive effect on the risk of advanced CRN (colorectal cancer and/or high-grade dysplasia) (OR, 0.35; 95% CI, 0.17-0.73). In a subgroup analysis, low-dose UDCA use (8-15 mg/kg/d) was associated with significant risk reduction of CRN (OR, 0.19; 95% CI, 0.08-0.49)., Conclusions: UDCA, particularly at low doses, may reduce the risk of advanced CRN in patients with PSC-IBD. However, results should be interpreted with caution, given limited reporting of cancer-related outcomes, primarily from tertiary care centers.
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- 2013
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25. Tacrolimus salvage in anti-tumor necrosis factor antibody treatment-refractory Crohn's disease.
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Gerich ME, Pardi DS, Bruining DH, Kammer PP, Becker BD, and Tremaine WT
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- Administration, Oral, Adult, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Female, Follow-Up Studies, Humans, Infliximab, Male, Middle Aged, Prognosis, Retrospective Studies, Young Adult, Antibodies, Monoclonal pharmacology, Crohn Disease drug therapy, Drug Resistance drug effects, Immunosuppressive Agents therapeutic use, Salvage Therapy, Tacrolimus therapeutic use, Tumor Necrosis Factor-alpha antagonists & inhibitors
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Background: Several small retrospective studies have reported encouraging response rates in patients with Crohn's disease (CD) treated with tacrolimus., Methods: We conducted a retrospective study of the use of oral tacrolimus for severe CD refractory to anti-tumor necrosis factor agents. Response was defined as a clinician's assessment of improvement after at least 7 days of treatment of one or more of the following: bowel movement frequency, fistula output, rectal bleeding, abdominal pain, extraintestinal manifestations, or well-being. Remission required all of the following: <3 stools per day, no bleeding, abdominal pain or extraintestinal manifestations, and increased well-being., Results: Twenty-four eligible patients were treated with tacrolimus for a median of 4 months. Approximately 37% were steroid dependent or steroid refractory. Response and steroid-free remission rates were 67% and 21%, respectively, and lasted for a median of 4 months. Approximately 42% of patients were able to stop steroids and 54% of patients ultimately required surgery within a median of 10 months after starting tacrolimus. Patients with mean tacrolimus trough levels of 10 to 15 ng/mL had the highest rates of response (86%) and remission (57%). Surgery seemed to be postponed in this group compared with others. An adverse event occurred in 75% of patients. Eight of these events (33%) required dose reduction and 6 (25%) led to treatment discontinuation. There were no irreversible side effects or deaths attributable to tacrolimus over a median follow-up of 56 months., Conclusions: Oral tacrolimus seems to be safe and effective in some patients with severe CD refractory to anti-tumor necrosis factor therapy, particularly at a mean trough level of 10 to 15 ng/mL.
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- 2013
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26. The epidemiology of Clostridium difficile infection in children: a population-based study.
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Khanna S, Baddour LM, Huskins WC, Kammer PP, Faubion WA, Zinsmeister AR, Harmsen WS, and Pardi DS
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- Adolescent, Child, Child, Preschool, Clostridium Infections diagnosis, Clostridium Infections microbiology, Cohort Studies, Community-Acquired Infections diagnosis, Community-Acquired Infections epidemiology, Community-Acquired Infections microbiology, Cross Infection diagnosis, Cross Infection epidemiology, Cross Infection microbiology, Female, Humans, Immunoenzyme Techniques, Infant, Male, Minnesota epidemiology, Polymerase Chain Reaction, Public Health Surveillance, Recurrence, Treatment Outcome, Clostridioides difficile isolation & purification, Clostridium Infections epidemiology
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Background: The incidence of Clostridium difficile infection (CDI) is increasing, even in populations previously thought to be at low risk, including children. Most incidence studies have included only hospitalized patients and are thus potentially influenced by referral or hospitalization biases., Methods: We performed a population-based study of CDI in pediatric residents (aged 0-18 years) of Olmsted County, Minnesota, from 1991 through 2009 to assess the incidence, severity, treatment response, and outcomes of CDI., Results: We identified 92 patients with CDI, with a median age of 2.3 years (range, 1 month-17.6 years). The majority of cases (75%) were community-acquired. The overall age- and sex-adjusted CDI incidence was 13.8 per 100 000 persons, which increased 12.5-fold, from 2.6 (1991-1997) to 32.6 per 100 000 (2004-2009), over the study period (P < .0001). The incidence of community-acquired CDI was 10.3 per 100 000 persons and increased 10.5-fold, from 2.2 (1991-1997) to 23.4 per 100 000 (2004-2009) (P < .0001). Severe, severe-complicated, and recurrent CDI occurred in 9%, 3%, and 20% of patients, respectively. The initial treatment in 82% of patients was metronidazole, and 18% experienced treatment failure. In contrast, the initial treatment in 8% of patients was vancomycin and none of them failed therapy., Conclusions: In this population-based cohort, CDI incidence in children increased significantly from 1991 through 2009. Given that the majority of cases were community-acquired, estimates of the incidence of CDI that include only hospitalized children may significantly underestimate the burden of disease in children.
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- 2013
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27. Symptomatic overlap between microscopic colitis and irritable bowel syndrome: a prospective study.
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Abboud R, Pardi DS, Tremaine WJ, Kammer PP, Sandborn WJ, and Loftus EV Jr
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- Abdominal Pain epidemiology, Abdominal Pain etiology, Adult, Aged, Aged, 80 and over, Cohort Studies, Colitis, Microscopic complications, Diagnosis, Differential, Diarrhea epidemiology, Diarrhea etiology, Female, Humans, Irritable Bowel Syndrome complications, Male, Middle Aged, Prevalence, Prospective Studies, Colitis, Microscopic diagnosis, Irritable Bowel Syndrome diagnosis
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Background: Microscopic colitis and irritable bowel syndrome (IBS) are the common causes of watery diarrhea, abdominal discomfort, and other gastrointestinal symptoms. Previous retrospective data and post hoc analysis of information from a randomized controlled trial have suggested that there is considerable overlap between the symptoms seen in patients with microscopic colitis and the symptom-based criteria for IBS. We sought to study this overlap in a prospective cohort., Methods: A random cohort of patients with biopsy-proven microscopic colitis seen at our institution were administered a symptom questionnaire. Based on their responses, the proportion of patients who met various definitions for IBS was determined. Clinical characteristics of those meeting IBS criteria were compared with those who did not., Results: In the 120 patients who were included, 38% to 58% met the diagnostic criteria for IBS. These patients tended to be younger and more likely female than those who did not meet IBS criteria., Conclusions: Patients with microscopic colitis frequently meet the diagnostic criteria for IBS. Therefore, these criteria are not specific enough to exclude the presence of microscopic colitis. In patients with watery diarrhea, colonoscopy with mucosal biopsies should be performed if symptoms are not controlled by antidiarrheal medications.
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- 2013
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28. "Community-acquired Clostridium difficile infection: an emerging entity".
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Khanna S and Pardi DS
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- Humans, Clostridioides difficile pathogenicity, Clostridium Infections epidemiology, Genes, Bacterial, Population Surveillance methods
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- 2012
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29. Benefit of computed tomography enterography in Crohn's disease: effects on patient management and physician level of confidence.
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Bruining DH, Siddiki HA, Fletcher JG, Sandborn WJ, Fidler JL, Huprich JE, Mandrekar JN, Harmsen WS, Evans PE, Faubion WA, Hanson KA, Ingle SB, Pardi DS, Schroeder KW, Tremaine WJ, and Loftus EV Jr
- Subjects
- Abscess diagnostic imaging, Adolescent, Adult, Aged, Constriction, Pathologic diagnostic imaging, Crohn Disease pathology, Crohn Disease therapy, Female, Humans, Intestine, Small diagnostic imaging, Male, Middle Aged, Prospective Studies, Sensitivity and Specificity, Surveys and Questionnaires, Young Adult, Crohn Disease diagnostic imaging, Tomography, X-Ray Computed methods
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Background: Computed tomographic enterography (CTE) has been shown to have a high sensitivity and specificity for active small bowel inflammation. There are only sparse data on the effect of CTE results on Crohn's disease (CD) patient care., Methods: We prospectively assessed 273 patients with established or suspected CD undergoing a clinically indicated CTE. Providers were asked to complete pre- and postimaging questionnaires regarding proposed clinical management plans and physician level of confidence (LOC) for the presence or absence of active small bowel disease, fistula(s), abscess(es), or stricturing disease. Correlative clinical, serologic, and histologic data were recorded. Following revelation of CTE results, providers were questioned if CTE altered their management plans, and whether LOC changes were due to CTE findings (on a 5-point scale)., Results: CTE altered management plans in 139 cases (51%). CTE changed management in 70 (48%) of those with established disease, prompting medication changes in 35 (24%). Management changes were made post-CTE in 69 (54%) of those with suspected CD, predominantly due to excluding CD (36%). CTE-perceived changes in management were independent of clinical, serologic, and histologic findings (P < 0.0001). Clinically meaningful LOC changes (2 or more points) were observed in 212 (78%)., Conclusions: CTE is a clinically useful examination, altering management plans in nearly half of patients with CD, while increasing physician LOC for the detection of small bowel inflammation and penetrating disease. These findings further support the use of CTE in CD management algorithms., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)
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- 2012
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30. Measurement of disease activity in ulcerative colitis: interobserver agreement and predictors of severity.
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Thia KT, Loftus EV Jr, Pardi DS, Kane SV, Faubion WA, Tremaine WJ, Schroeder KW, Harmsen SW, Zinsmeister AR, and Sandborn WJ
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- Adult, Aged, Colitis, Ulcerative pathology, Colon pathology, Colonoscopy standards, Female, Humans, Intestinal Mucosa pathology, Male, Middle Aged, Observer Variation, Prospective Studies, Severity of Illness Index, Video Recording, Young Adult, Colitis, Ulcerative diagnosis
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Background: Endoscopic evaluation plays a pivotal role in the assessment of treatment response in ulcerative colitis (UC). This study aimed to determine the interobserver agreement (IOA) for assessment of mucosal lesions, and to determine lesions predictive of global assessment of endoscopic severity (GAES)., Methods: Fifty-one UC patients had digital videorecording of their colonoscopic examinations, edited into videoclips representative of five colonic segments (rectum, sigmoid, descending, transverse, ascending/cecum). Seven gastroenterologists specializing in inflammatory bowel disease (IBD) independently and blindly rated individual lesions and endoscopic severity for each segment and globally. Edema, erythema, stricture, loss of haustral folds, rigidity, and pseudopolyps were scored as absent or present while vascular pattern, granularity, ulceration, and bleeding-friability were scored using a predefined severity scale. The GAES was based on a 4-point scale and a 10-cm visual analog scale (VAS). The IOA among raters was estimated using Lin's concordance correlation coefficient (CCC). Strength of agreement was categorized as excellent (0.81-1.00), good (0.61-0.80), moderate (0.41-0.60), and fair (0.21-0.40). Linear regression analysis was used to identify lesions predictive of overall endoscopic severity and develop a scoring system for clinical use., Results: Granularity, vascular pattern, ulceration, bleeding/friability, and pseudopolyps had good IOA in most segments. There was excellent agreement for VAS and good agreement for GAES and the VAS was significantly associated with GAES (P < 0.001). Granularity, vascular pattern, ulceration, and bleeding-friability were significant predictors of overall endoscopic severity., Conclusions: Granularity, vascular pattern, ulceration, and bleeding-friability demonstrated good reproducibility and were predictors of the GAES in UC patients., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)
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- 2011
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31. Adalimumab for Crohn's disease in clinical practice at Mayo clinic: the first 118 patients.
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Swoger JM, Loftus EV Jr, Tremaine WJ, Faubion WA, Pardi DS, Kane SV, Hanson KA, Harmsen WS, Zinsmeister AR, and Sandborn WJ
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- Adalimumab, Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Aged, Antibodies, Monoclonal, Humanized, Clinical Trials as Topic, Dose-Response Relationship, Drug, Female, Humans, Infliximab, Male, Middle Aged, Remission Induction, Retrospective Studies, Treatment Outcome, Young Adult, Anti-Inflammatory Agents therapeutic use, Antibodies, Monoclonal therapeutic use, Crohn Disease drug therapy
- Abstract
Background: We sought to assess the effectiveness and safety of adalimumab for the treatment of Crohn's disease (CD) in clinical practice., Methods: Demographic, clinical, and treatment data were abstracted from the medical record. The primary outcome was clinical response to induction therapy with adalimumab for CD (complete, partial, or nonresponse)., Results: In all, 118 patients were prescribed adalimumab for CD between January 2003 and June 2007. All but five subjects (96%) had received prior infliximab and 50 were on systemic corticosteroids at the time of initial adalimumab dose (44%). A complete response was achieved in 53 patients and 20 patients had no response. The cumulative probability of any response (complete or partial) was 81.3% at 1 year. Dose escalation was required in 59 patients (1-year cumulative probability, 54.0%). Among patients with complete response, 18 lost response during follow-up (1-year cumulative probability, 21.4%). Among 50 patients on corticosteroids at baseline the median daily dose was 20 mg, which decreased to a median of 0 mg during treatment. Sixty-four patients (54%) experienced a total of 117 adverse events. Thirteen patients (11%) experienced 15 serious adverse events. Sixteen patients (14%) discontinued adalimumab due to an adverse event., Conclusions: Adalimumab was both effective and well tolerated for the treatment of CD in this tertiary practice with a high prevalence of past infliximab exposure. This experience largely predates FDA approval of adalimumab for CD.
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- 2010
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32. Assessment of appropriateness of indications for CT enterography in younger patients.
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Guimarães LS, Fidler JL, Fletcher JG, Bruining DH, Huprich JE, Siddiki H, Sandborn WJ, Loftus EV Jr, Pardi DS, and McCollough CH
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- Adult, Age Factors, Crohn Disease diagnosis, Crohn Disease diagnostic imaging, Gastrointestinal Diseases diagnostic imaging, Humans, Magnetic Resonance Imaging, Practice Patterns, Physicians' standards, Retrospective Studies, Risk Assessment, Tomography, X-Ray Computed adverse effects, Gastrointestinal Diseases diagnosis, Tomography, X-Ray Computed statistics & numerical data
- Abstract
Background: The small potential risk of radiation-induced cancer is increased in younger patients undergoing serial imaging with computed tomography enterography (CTE). We sought to determine the appropriateness of CTEs based on clinical indication in patients < or =35 years old, and the potential impact of evolution of practice to alternative magnetic resonance enterography (MRE)., Methods: Over a 7-year period, the medical records of all patients < or =35 years old undergoing CTE were reviewed to determine the clinical indications for each CTE exam. An interdisciplinary consensus panel evaluated the appropriateness of all CTE exams based on American College of Radiology appropriateness criteria and peer-reviewed literature, classifying indications into "appropriate" or "inappropriate." For repeat CTEs, an "alternative MRE suggested" pathway was created. Criteria for evolution of practice to "alternative MRE" were suspicion of obstruction and evaluation of disease activity/therapeutic response in the absence of new symptoms., Results: In all, 2022 patients < or =35 years old underwent 2295 CTEs. Ninety-nine percent (2008/2022) of first-time CTE exams were "appropriate" by the defined criteria. A total of 197 patients (9.7%) underwent multiple exams, with 73% of these patients having Crohn's disease. Repeat exams occurred in 9% (18/197) with obstructive symptoms and evaluation of disease activity/therapeutic response in the absence of new symptoms in 41% (80/197)., Conclusions: A multidisciplinary expert panel concluded that the vast majority of young patients underwent clinically appropriate first-time CTE exams. However, a shift in clinical practice to MRE appears warranted for approximately half of young patients undergoing repeat CTE examinations.
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- 2010
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33. Clinical guidelines for the management of pouchitis.
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Pardi DS, D'Haens G, Shen B, Campbell S, and Gionchetti P
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- Colitis, Ulcerative surgery, Humans, Ileostomy adverse effects, Pouchitis diagnosis, Pouchitis etiology, Proctocolectomy, Restorative adverse effects, Risk Factors, Pouchitis therapy
- Abstract
When surgery is necessary in patients with ulcerative colitis, total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the procedure of choice. Several inflammatory and noninflammatory complications can occur after IPAA. Pouchitis is the most common, occurring in approximately 50% of patients. Whereas "acute" pouchitis can be treated rapidly and successfully in the majority of patients, "refractory" and "chronic pouchitis" remain therapeutic challenges to patients and physicians. This article reviews the literature and offers consensus guidelines on issues related to the epidemiology, diagnosis, pathogenesis, risk factors, and treatment of pouchitis.
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- 2009
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34. Open-label study of adalimumab in patients with ulcerative colitis including those with prior loss of response or intolerance to infliximab.
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Afif W, Leighton JA, Hanauer SB, Loftus EV Jr, Faubion WA, Pardi DS, Tremaine WJ, Kane SV, Bruining DH, Cohen RD, Rubin DT, Hanson KA, and Sandborn WJ
- Subjects
- Adalimumab, Adult, Aged, Antibodies, Monoclonal, Humanized, Female, Follow-Up Studies, Humans, Infliximab, Male, Middle Aged, Prognosis, Salvage Therapy, Treatment Outcome, Anti-Inflammatory Agents therapeutic use, Antibodies, Monoclonal therapeutic use, Colitis, Ulcerative drug therapy
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Background: The aim of this study was to assess the clinical benefit and tolerability of adalimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF), in patients with ulcerative colitis (UC)., Methods: Patients with active UC, including those who had lost response or developed intolerance to the chimeric anti-TNF antibody infliximab, were enrolled in a 24-week uncontrolled trial. Patients were treated with subcutaneous adalimumab 160 mg at week 0, 80 mg at week 2, and 40 mg every other week starting at week 4. After week 8 the dose could be escalated to 40 mg weekly for incomplete response. Outcome measures included clinical response and remission and mucosal healing., Results: Twenty patients were enrolled, of whom 13 had previously received infliximab. Seven patients had dose escalation of adalimumab between weeks 8 and 16, from 40 mg every other week to 40 mg weekly, due to incomplete response. The rates of clinical response were 25% at week 8 and 50% at week 24. The rates of clinical remission were 5% at week 8 and 20% at week 24. The rate of mucosal healing was 30% at week 8. The rates of clinical response and remission and mucosal healing were similar in infliximab-naïve and previously exposed patients. None of the patients experienced hypersensitivity reactions during treatment with adalimumab., Conclusions: Adalimumab is well tolerated and appears to be a clinically beneficial option for patients with UC, including those who have previously lost their response to or cannot tolerate infliximab.
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- 2009
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35. Observer variability in the histologic diagnosis of microscopic colitis.
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Limsui D, Pardi DS, Smyrk TC, Abraham SC, Lewis JT, Sanderson SO, Kammer PP, Dierkhising RA, and Zinsmeister AR
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- Biopsy, Colitis, Microscopic classification, Colitis, Microscopic epidemiology, Humans, Observer Variation, Colitis, Microscopic diagnosis, Pathology, Clinical standards
- Abstract
Background: Microscopic colitis is diagnosed based on histologic criteria. There has been no investigation of the reproducibility of the histologic diagnosis of microscopic colitis. Our aim was to evaluate interobserver and intraobserver variation in this diagnosis., Methods: Colonic biopsies from 90 subjects (20 lymphocytic colitis, 20 collagenous colitis, 20 inflammatory bowel disease, and 30 normal) were blindly and independently reviewed by 4 gastrointestinal pathologists. The biopsies were classified by each pathologist into 1 of 6 diagnostic categories: lymphocytic colitis, collagenous colitis, active chronic colitis, focal active colitis, normal, or other. The slides were then relabeled and blindly reinterpreted 3 months later. The degree of agreement was determined using kappa statistics (lambda)., Results: Interobserver agreement with the 6 diagnostic categories was 69% (kappa = 0.76, 95% CI 0.69, 0.83) and 70% (kappa = 0.71, 95% CI 0.61, 0.79) for the first and second observations, respectively. Interobserver agreement with final diagnostic categories of microscopic colitis versus nonmicroscopic colitis was 91% (kappa = 0.90, 95% CI 0.82, 0.96) and 88% (kappa = 0.83, 95% CI 0.73, 0.92), respectively. Mean intraobserver agreement with the 6 diagnostic categories was 83% (kappa = 0.77). Mean intraobserver agreement with the final diagnostic categories of microscopic colitis versus nonmicroscopic colitis was 95% (kappa = 0.89)., Conclusions: Both interobserver and intraobserver agreement were good in distinguishing among the 6 diagnostic categories, and excellent in distinguishing between microscopic colitis and nonmicroscopic colitis diagnoses. The histologic criteria for microscopic colitis provide for consistent and reproducible interindividual and intraindividual diagnoses in the evaluation of colonic biopsies.
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- 2009
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36. Symptomatic overlap between irritable bowel syndrome and microscopic colitis.
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Limsui D, Pardi DS, Camilleri M, Loftus EV Jr, Kammer PP, Tremaine WJ, and Sandborn WJ
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- Adult, Aged, Aged, 80 and over, Colitis pathology, Diagnosis, Differential, Female, Humans, Intestines pathology, Irritable Bowel Syndrome pathology, Male, Middle Aged, Colitis diagnosis, Irritable Bowel Syndrome diagnosis
- Abstract
Background: Microscopic colitis is diagnosed on the basis of histologic criteria, and irritable bowel syndrome (IBS) is diagnosed by symptom-based criteria. There has been little investigation into the symptomatic overlap between these conditions. Our aim was to assess the prevalence of symptoms of irritable bowel syndrome in a population-based cohort of patients with microscopic colitis., Methods: The Rochester Epidemiology Project (REP), a medical records linkage system providing all health care data for the defined population of Olmsted County, Minnesota, was used to identify all county residents with a diagnosis of microscopic colitis between 1985 and 2001. The medical records of these individuals were reviewed to ascertain symptoms consistent with Rome, Rome II, and Manning criteria for irritable bowel syndrome., Results: One hundred thirty-one cases of microscopic colitis were identified. Median age at diagnosis was 68 years (range, 24-95); 71% were women. Sixty-nine (53%) and 73 (56%) met Rome and Rome II criteria for irritable bowel syndrome, respectively. Fifty-four (41%) had three or more Manning criteria. Forty-three (33%) had previously been diagnosed with irritable bowel syndrome., Conclusions: In this population-based cohort of histologically confirmed microscopic colitis, approximately one-half met symptom-based criteria for the diagnosis of irritable bowel syndrome. The clinical symptom-based criteria for irritable bowel syndrome are not specific enough to rule out the diagnosis of microscopic colitis. Therefore, patients with suspected diarrhea-predominant irritable bowel syndrome should undergo biopsies of the colon to investigate for possible microscopic colitis if symptoms are not well controlled by antidiarrheal therapy.
- Published
- 2007
- Full Text
- View/download PDF
37. Microscopic colitis is not associated with cholecystectomy or appendectomy.
- Author
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Laing AW, Pardi DS, Loftus EV Jr, Smyrk TC, Kammer PP, Tremaine WJ, Schleck CD, Harmsen WS, Zinsmeister AR, Melton LJ 3rd, and Sandborn WJ
- Subjects
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Colitis, Microscopic pathology, Female, Humans, Male, Middle Aged, Postoperative Complications, Risk Factors, Appendectomy adverse effects, Cholecystectomy adverse effects, Colitis, Microscopic etiology
- Abstract
Background: Microscopic colitis is a common cause of chronic watery diarrhea of unknown origin. Some patients develop diarrhea after cholecystectomy, and some patients with microscopic colitis have evidence of bile acid malabsorption. However, the association between cholecystectomy and microscopic colitis has not been studied. A protective effect of appendectomy on the development of ulcerative colitis also has been reported, but its relationship with microscopic colitis has not been studied. The aim of this study was to assess cholecystectomy and appendectomy as potential risk factors for the development of microscopic colitis in a nested case-control study., Materials and Methods: Using the Rochester Epidemiology Project, we identified all Olmsted County (Minnesota) residents with an initial diagnosis of microscopic colitis between January 1, 1985, and December 31, 2001. Rates of antecedent cholecystectomy or appendectomy in patients with microscopic colitis were compared with age-, gender-, and calendar year-matched community controls through conditional logistic regression., Results: Microscopic colitis was identified in 130 cases. Cholecystectomy preceded the diagnosis of microscopic colitis in 12 cases (9%) compared with 17 (13%) in the control group (odds ratio [OR] 0.7; 95% CI 0.3-1.5). Appendectomy preceded the diagnosis of microscopic colitis in 39 subjects (30%) compared with 28 (22%) in the control group (OR 1.6; 95% CI 0.9-2.7). Similar results were obtained when the analysis was restricted to microscopic colitis subtype (lymphocytic colitis or collagenous colitis)., Conclusions: In this population-based nested case-control study, no significant association was seen between cholecystectomy or appendectomy and the development of microscopic colitis or its subtypes.
- Published
- 2006
- Full Text
- View/download PDF
38. Budesonide in the treatment of inflammatory bowel disease: the first year of experience in clinical practice.
- Author
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Chopra A, Pardi DS, Loftus EV Jr, Tremaine WJ, Egan LJ, Faubion WA, Hanson KA, Johnson TA, and Sandborn WJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Anti-Inflammatory Agents therapeutic use, Budesonide therapeutic use, Inflammatory Bowel Diseases drug therapy
- Abstract
Background: Delayed release budesonide was approved by the FDA for the treatment of mildly to moderately active Crohn's disease involving the ileum and ascending colon. Controlled trials have demonstrated that budesonide is effective in inducing remission and for maintenance of remission, with less frequent steroid side effects than conventional steroids. We sought to determine the benefit of this medication in clinical practice and to identify any non-FDA-approved uses that may warrant further study., Methods: Patients in whom oral budesonide was prescribed between November 1, 2001 and October 31, 2002, were identified and medical records were reviewed. Patients were categorized by indication for therapy: ileocolonic Crohn's disease (group 1), Crohn's disease elsewhere (group 2), and other conditions (group 3)., Results: A total of 225 patients were identified (108 in group 1, 62 in group 2, and 55 in group 3). Group 3 included patients with microscopic colitis (n = 28), pouchitis (n = 13), ulcerative colitis (n = 12), and celiac disease (n = 2). A favorable outcome occurred in 61% of group 1 patients but only 24% of patients in group 2. In group 3, only microscopic colitis patients and pouchitis patients experienced response rates >50% (77% and 60%, respectively)., Conclusion: Budesonide is effective in a majority of patients with ileocolonic Crohn's disease and microscopic colitis, which is consistent with results reported from clinical trials. A majority of patients with pouchitis also benefit from budesonide therapy, but prospective controlled trials are necessary to clarify the benefit in this group.
- Published
- 2006
- Full Text
- View/download PDF
39. Microscopic colitis: an update.
- Author
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Pardi DS
- Subjects
- Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Colitis drug therapy, Colitis pathology, Decision Trees, Humans, Colitis physiopathology
- Abstract
Microscopic colitis is an increasingly common cause of chronic diarrhea, and often causes abdominal pain and weight loss. The colonic mucosa appears normal or nearly normal endoscopically, and the diagnosis is made in the appropriate clinical setting when there is intraepithelial lymphocytosis and a mixed lamina propria inflammatory infiltrate. The 2 subtypes, collagenous and lymphocytic colitis, are similar clinically and histologically, and are distinguished by the presence or absence of a thickened subepithelial collagen band. Many potential pathophysiologic mechanisms have been proposed, but no convincing unifying mechanism has been identified. There are many anecdotal reports on treatment, but few controlled trials have been performed in these patients, although a systematic approach to therapy often leads to the satisfactory control of symptoms.
- Published
- 2004
- Full Text
- View/download PDF
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