Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: A meta-analysis.

BACKGROUND AND AIM: Fenofibrate is a potential novel therapy for primary biliary cirrhosis (PBC). We performed a systematic review and a meta-analysis of studies of fenofibrate in PBC. METHODS: Electronic database search was performed for relevant studies. A search of abstracts presented in the main scientific meetings in the field and articles in press was also performed. Random effect model was used to pool the effect size across studies for changes in alkaline phosphatase, GGT, bilirubin and IgM levels before and after treatment and the overall rate of complete response to fenofibrate therapy. RESULTS: Six studies with 102 patients met the inclusion criteria. All studies were case series and in all, patients who had no or incomplete response to UDCA had fenofibrate added at a dose of 100-200mg daily. Treatment duration ranged from 8-100weeks. Treatment with fenofibrate was associated with a significant decrease in alkaline phosphatase (-114IU/L, 95% CI: -152 to -76, P<0.0001); a significant decrease in GGT level (-92IU/L, 95% CI: -149 to -43; P=0.0004); significant decrease in total bilirubin (-0.11mg/dL, 95% CI: -0.18 to -0.08; P=0.0008); and a significant decrease in IgM level (-88mg/dL, 95% CI: -119 to -58; P<0.0001). The complete response rate was 69% (95% CI: 53-82%) with an odds ratio of 82.8 (95% CI: 21.6-317.2; P=0.024) while on fenofibrate. CONCLUSIONS: Fenofibrate at doses of 100-200mg daily appears to be effective adjunctive therapy in PBC patients who had no or incomplete response to UDCA. There is a critical need for larger scale randomized trials to determine its effect on liver-related morbidity and mortality (or progression towards end-stage disease).

Racial Differences in the Prevalence of Celiac Disease in the US Population: National Health and Nutrition Examination Survey (NHANES) 2009-2012.

AIM: To provide an estimate of the prevalence of celiac disease by race/ethnic origin in large sample of US population. METHODS: Data from the 2009-2010 and 2011-2012 NHANES were combined and analyzed. The NHANES is a nationally representative survey with oversampling of certain minorities. Sample-based frequencies were reported and weighted frequencies were used to estimate prevalence. RESULTS: A total of 14,701 participants were checked for tissue transglutaminase (tTG) and endomysial (EMA) IgA antibodies. Seventy-four participants had positive tTG and/or EMA corresponding to prevalence of 0.79 % (95 % CI 0.54-1.04 %). Non-Hispanic white were more likely to be positive for both compared with other races (72.0 vs 31.7 %; p = 0.010) and less likely to be weakly positive for tTG but positive for EMA (3.6 vs 26.4 %; p = 0.03). The prevalence of positive serology according to race was as follows: 1.08 % (95 % CI 0.70-1.45 %) in non-Hispanic white, 0.23 % (95 % CI 0.03-0.43 %) in Mexican, 0.22 % (95 % CI 0.01-0.44 %) in non-Hispanic black, 0.38 % (95 % CI 0.00-0.89 %) in "other Hispanic," and 0.15 % (95 % CI 0.00-0.34 %) in other races including multiracial and undeterminable in non-Hispanic Asian due to the presence of only one positive EMA test. 0.9 % of the NHANES sample participants followed gluten-free diet. Of this group of participants, 85 % were never diagnosed with celiac disease and 99 % of them had negative celiac disease serology. CONCLUSIONS: Potentially 0.79 % of the general US population demonstrate serologic evidence of celiac disease autoimmunity. The prevalence is 4-8 times higher among non-Hispanic white compared with other races. Close to 1 % of the population is electively following gluten-free diet despite having little evidence of the disease.

Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active ulcerative colitis: a meta-analysis.

BACKGROUND: VSL#3 is a probiotic mix preparation reported to be effective in the treatment of mild to moderately active ulcerative colitis. We aimed to perform a systematic review of the literature and a meta-analysis of studies on its efficacy. METHODS: The searched databases included PubMed, Scopus, and ScienceDirect. The Mantel-Haenszel method was used to pool the effect- ize across studies, and the odds ratios (ORs) and 95% confidence intervals (CIs) of experiencing a specific outcome were calculated. RESULTS: Five studies with 441 patients were identified. The pooled remission rate was 49.4% (95% CI, 42.7-56.1). Only 3 low risk of bias studies with 319 patients met the inclusion criteria for further analysis. A total of 162 patients received 3.6 × 10 CFU/d VSL#3, and 157 patients received placebo. A total of 95% of patients received concomitant therapies with 5-ASA and/or immunomodulators. The Ulcerative Colitis Disease Activity Index was used to define response and remission. A >50% decrease in the Ulcerative Colitis Disease Activity Index was achieved in 44.6% of the VSL#3-treated patients versus 25.1% of the patients given placebo (P = 0008; OR, 2.793; 95% CI, 1.375-5.676; number needed to treat = 4-5). The response rate was 53.4% in VSL#3-treated patients versus 29.3% in patients given placebo (P < 0001; OR, 3.03; 95% CI, 1.89-4.83; number needed to treat = 3-4). The remission rate was 43.8% in VSL#3-treated patients versus 24.8% in patients given placebo (P = 0007; OR, 2.4; 95% CI, 1.48-3.88; number needed to treat = 4-5). No serious side effects were reported. CONCLUSIONS: VSL#3, when added to conventional therapy at a daily dose of 3.6 × 10 CFU/d, is safe and more effective than conventional therapy alone in achieving higher response and remission rates in mild to moderately active ulcerative colitis.

Teduglutide in intestinal adaptation and repair: light at the end of the tunnel.

BACKGROUND: Malabsorption of nutrients, fluids and electrolytes is a key finding in patients with short bowel syndrome. If not compensated for by increased intake, it leads to diminished body stores and subclinical, and eventually clinical, deficiencies. Until recently, management options were limited to interventions aimed at provision of adequate macro- and micronutrients and fluids to prevent malnutrition, nutrient deficiencies and dehydration, treatment of associated infections and correction and prevention of acid-base disturbances. Identification of novel gut hormones, combined with the growing understanding of their pivotal role in intestinal adaptation, has provoked interest in developing more specific therapies. AIM: To provide an update on the recent advances on the use of teduglutide in patients with short bowel syndrome. METHODS: A comprehensive Medline search using the terms teduglutide, ALX-0600, dipeptidyl peptidase IV (DPP-IV) and glucagon like peptide-2 (GLP-2). RESULTS: Teduglutide (GATTEX, ALX-0600; NPS Allelix Corp) is a synthetic DPP-IV-resistant recombinant human GLP-2 analog that differs from GLP-2 only by an N-terminus substitution of glycine for alanine in position 2 of the peptide that renders the component resistant to enzymatic degradation. Based on the results of the few Phase II studies and the preliminary results of a Phase III trial, teduglutide at doses of 0.05 or 0.10 mg/kg/day may improve many clinical, laboratory and histologic abnormalities in short bowel syndrome patients. It appears to be safe and well tolerated. CONCLUSION: Teduglutide is a first-in-class therapy with the potential to create a new standard of care for patients suffering from short bowel syndrome. Future studies to address the appropriate initial and maintenance dosage and optimal duration of treatment are needed.

Wireless capsule endoscopy indication as a predictor of study quality.

PURPOSE: The aim of the study was to assess whether specific indications are associated with poor visualization during wireless capsule endoscopy (WCE) studies . Four hundred consecutive WCE studies performed at our institute were analyzed retrospectively. RESULTS: Data was available on cases involving 176 males and 224 females. About 23 capsules failed to exit the stomach (excluded from the study). Poor visualization was reported in 66 (17%) WCE studies. The most common indications were gastrointestinal (GI) blood loss (271 cases; 72%), abdominal pain and/or diarrhea (73 cases; 19%), and suspected inflammatory bowel disease (46 cases; 12%). Of the 271 patients suffering GI bleeding, visualization was reported to be poor in 53 (19%) patients; among those showing other indications, visualization was poor in 13 (11%) patients (P = 0.02). After controlling for secondary indications and age, GI bleeding was associated with a higher rate of poor visualization compared to all other indications (odds ratio 2.6; 95% confidence interval 1.4-6.8). CONCLUSIONS: Gastrointestinal bleeding as study indication for WCE is associated with a higher rate of poor visualization.

Treatment of Perianal Fistula and Abscess: Crohn's and Non-Crohn's.

The management of perianal abscesses and fistulas is relatively straightforward in most cases and based on a sound knowledge of the anatomy of the anorectum and adherence to established medical and surgical principles. Asymptomatic fistulas should not be treated, whereas abscesses require surgical drainage under general anesthesia. Fistula treatment includes drainage of any associated sepsis and eradication of the fistula track to prevent recurrence while preserving sphincter integrity. A small percentage of anal abscesses and fistulas are complex and very challenging to manage, particularly in conditions such as rectovaginal fistulas and abscesses and/or fistulas complicating Crohn's disease. Treatment strategies in these situations rely on an accurate clinical assessment of the degree of rectal inflammation and perianal pathology. Treatment should combine aggressive medical therapy (antibiotics, immunomodulators, and anti-tumor necrosis factor antibody treatment) and minimal surgical interventions. Patients with proctitis have a significantly lower healing rate and a significantly higher complication rate with aggressive surgical interventions.

Development of an instrument to assess and predict satisfaction and poor tolerance among patients undergoing endoscopic procedures.

We aimed to test the reliability of a developed questionnaire that measures and predict aversive endoscopic experience. Two questionnaires (pre- and postprocedure) were given to patients presenting for routine endoscopy. The first questionnaire elicited demographics, prior endoscopic experience, history of drug or alcohol use, patient expectations, and levels of anxiety and nervousness before procedure. After endoscopy, tolerance and willingness to repeat the examination were determined. The primary outcome of "adverse endoscopic experience" (AEE) was defined as a score of > or =5 on the postprocedure overall level of satisfaction or unwillingness to repeat endoscopy. Thirteen of 148 subjects reported an AEE. Items measuring the primary outcome were internally validated by reliability analysis which significantly correlated with measures of aversive experience like pain, nervousness, and suffering during the procedure. Preprocedure factors that were associated with AEE in the univariate analysis and multivariate analysis were nervousness (P = 0.02) and chronic use of psychotropic drugs or alcohol (P = 0.03). In conclusion, we have developed a questionnaire that reliably measures aversive endoscopic experience. Nervousness before procedure and chronic use of psychotropic drugs are reliable predictors of such experience.

Gastroduodenal Crohn's disease is associated with NOD2/CARD15 gene polymorphisms, particularly L1007P homozygosity.

Limited data exist on the specific association between gastroduodenal Crohn's disease (GDCD) and NOD2/CARD15 gene polymorphisms. The aim of this study was to assess the association between NOD2 polymorphisms and GDCD, and to assess the specific association between each of the 3 major allelic variants G908R, L1007P, and R702W and the clinical features of Crohn's disease. We retrospectively reviewed the records of 202 patients with confirmed Crohn's disease and complete data was performed. Seventy-one patients (35%) had at least 1 allelic variant: 55 had 1 variant, 4 were homozygous for L1007fs, 2 homozygous for R702W, and 10 were compound heterozygous. Eighteen patients with confirmed GDCD were identified; 10 (56%) had wild type, 4 (22%) had 1 variant, and 4 (22%) had 2 allelic variants (2 were L1007P homozygous and 2 compound heterozygous). Compared to patients without gastroduodenal involvement, those with GDCD were more likely to have 2 allelic variants (22% vs. 6%; odds ratio [OR] 2.7; 95% confidence interval [CI] 1.6-7.3) and to be homozygous for L1007P (11% vs. 1%; OR 5.2; 95% CI 2.5-9.4). G908R heterozygosity was associated with ileal involvement (OR 1.4; 95% CI 1.1-2.9) and smoking habits (OR 2.4; 95% CI 1.2-3.8), whereas L1007P homozygosity was associated with GDCD (OR 5.8; 95% CI 2.6-10.8). L1007P variation was associated with younger age at diagnosis as well. There was no specific association between R702W homo- or heterozygosity and any of the characteristics examined. In conclusion, GDCD is associated with double dose of the NOD2/CARD15 gene variants, particularly L1007P homozygosity. There is evidence of specific variant-phenotype associations. G908R heterozygosity is associated with ileal involvement and smoking, whereas L1007P homozygosity is strongly associated with GDCD and younger age at diagnosis.

Crohn's disease: a two-year prospective study of the association between psychological distress and disease activity.

Our objective was to explore the relationship between psychological distress and subsequent Crohn's disease (CD) activity. Eighteen CD patients were followed prospectively for 2 years at 8- to 12-week intervals. Disease activity was assessed using the Crohn's Disease Activity Index (CDAI). Psychological distress was assessed using the following self-administered questionnaires: Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Beck Hopelessness Scale (BHS), and multiple Holmes Recent Life Changes (RLC) Questionnaires. The effects of psychological distress on current and subsequent CDAI (approximately 8-12 weeks later) were assessed using generalized estimating equations (GEE). The mean CDAI score during follow-up was 138 +/- 86, with a median of 121 (range, 0 to 394). BDI scores (possible range of 0 to 63) were independently associated with CDAI scores simultaneously (beta = 5.64, P = 0.004) and 8-12 weeks later (beta = 6.08, P = 0.004). Higher levels of anxiety, hopelessness, and recent life changes were also suggestive of higher CDAI scores, however, their effects were generally of lesser magnitude and not independent of the influence of depressive symptoms. Levels of depressive symptoms are positively associated with future changes in CDAI. Routine psychological assessment may help to identify patients at higher risk for exacerbation.

Utility of measuring 6-methylmercaptopurine and 6-thioguanine nucleotide levels in managing inflammatory bowel disease patients treated with 6-mercaptopurine in a clinical practice setting.

BACKGROUND: Measuring levels of 6-mercaptopurine (6-MP) metabolites (6-thioguanine nucleotides [6-TGNs] and 6-methylmercaptopurine [6-MMP]) has been proposed as a method to adjust 6-MP dose to optimize therapeutic response while minimizing toxicity in patients with inflammatory bowel disease. A 6-TGN level of >230 pmol/8 x 108 red blood cells (RBCs) has been reported to be associated with a higher efficacy rate, and a level of >450 pmol/8 x 108 RBCs has been reported to be associated with myelotoxicity. A 6-MMP level of >5,700 pmol/8 x 108 RBCs has been reported to be associated with an increased frequency of abnormal results of liver function tests (LFTs). GOALS: To report our experience with 6-MMP and 6-TGN levels in a clinical practice setting. STUDY: Using outpatient clinic medical records, we identified 53 measurements. Indications for measurement, 6-MP dose, and subsequent adjustments were documented. RESULTS: Indications for measurements included the following: persistent symptoms, 31 cases (58.5%); abnormal LFT results, 7 (13.2%); steroid dependency, 6 (11.3%); anemia, 4 (7.5%); and leukopenia, 2 (3.8%). Of the 31 cases with persistent symptoms, 12 had "therapeutic" 6-TGN levels and other interventions were undertaken. 6-TGN levels were "subtherapeutic" in 19. The 6-MP dose was increased, and remission was achieved in 10 cases after a mean period of 3.6 weeks. Among the cases with abnormal LFT results, 6-MMP levels were high in five and low in two. Among the steroid dependency cases, 6-TGN levels were "subtherapeutic" in five. The dose was increased and steroids were weaned in three cases. The 6-TGN level was high in one of the leukopenia cases and the 6-MP dose was decreased. 6-TGN levels were not above the "target range" in any of the anemia cases. CONCLUSION: Measuring levels of 6-MP metabolites may have a role in customizing 6-MP dosing. This role is not completely clear and needs to be explored in larger well-controlled studies.