Abdominal Pain Scores Research Articles

Application of carbon dioxide to the conventional colonoscopy

Objective To explore the application of CO2 as an insufflation agent in patients undergoing colonoscopy by comparing carbon dioxide(CO2) and air. Methods Consecutive 681 patients who underwent conventional colonoscopy from January to May in 2014 at endoscopy center of our hospital were included. The patients were randomly divided into the air group and CO2 group. The gas flow, capacity, operation time, PaCO2 and abdominal pain during and 20 min, 40 min, 1 h, 2 h, 12 h, 24 h after colonoscopy were recorded. The safety and advantages of CO2 in the colonoscopy were analyzed. Results The intubation time of CO2 group was significantly shorter than that of air group (P 0.05). There was also no difference in air flow and the total volume between the two groups (P>0.05). PaCO2 of two groups were within the normal range. PaCO2 during examination was significantly higher than that before and 20 minutes after examination (P 0.05). The abdominal pain scores during and 20 min, 40 min, 1 h, 2 h after the examination of air group were significantly higher than those of CO2 group (P 0.05). Conclusion CO2 is safe and could reduce abdominal discomfort after colonoscopy, which is suitable for clinical application. Key words: Carbon dioxide; Air; Colonoscopes; Comparative study

Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial

Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. In this multicenter, randomized, double-blind, placebo-controlled study, we assessed larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. The primary end point was met with the 0.5-mg dose of larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days (P = .017), a 31% increase in improved symptom days (P = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment (P = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness (P = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov: NCT01396213.

Pinaverium Reduces Symptoms of Irritable Bowel Syndrome in a Multicenter, Randomized, Controlled Trial

Pinaverium bromide (pinaverium) is an antispasmodic commonly used to treat irritable bowel syndrome (IBS), but there has been no convincing evidence for its effectiveness and safety. We evaluated these in a prospective, double-blind, placebo-controlled trial. Patients with IBS, based on Rome III criteria, were assigned randomly to groups given pinaverium (50 mg, 3 times/day; n = 218) or placebo (3 times/day; n = 209) at 4 hospitals in China, from August 2012 through December 2013. The primary end points were reductions in abdominal pain and Bristol stool score. Secondary end points were reductions in pain and stool frequencies and abdominal discomfort and its frequency. We also evaluated changes in IBS global symptom scores and the number of adverse effects. Based on an intention-to-treat analysis, a significantly larger proportion of patients receiving pinaverium met either of the primary end points (50.0% met an end point at week 2, and 77.5% met an end point at week 4), compared with placebo (P < .001). Pinaverium reduced at least 1 secondary end point in significantly more patients receiving pinaverium (76.1% had a reduction at week 2, and 91.7% had a reduction at week 4) than placebo (P < .001). Based on symptom scores, significantly higher percentages of patients receiving pinaverium believed that their IBS symptoms improved (60%) than in the placebo group (34%; P < .001); 29% of patients in the pinaverium group believed that their IBS symptoms stayed the same (29%) and 11% said they worsened. Pinaverium was not associated with severe adverse effects; common side effects included nausea (3.7%), dizziness (3.2%), increased blood pressure (2.3%), and abdominal discomfort (2.3%). Based on a controlled trial, pinaverium reduces symptoms of IBS. It can be considered a first-line treatment for IBS. NCT01641224 (www.ClinicalTrials.gov).

Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis.

To investigate the efficacy of probiotics in irritable bowel syndrome (IBS) patients. PubMed, Cochrane library, Scopus, Google Scholar, and Clinicaltrial.gov databases were searched for literature published between September 2007 and December 2013. The applied Mesh terms were "probiotics," "irritable bowel syndrome," and "irritable bowel syndrome treatment." The collected data contained24 clinical trials, of which 15 were eligible for meta-analysis and nine were reviewed systematically. All studies were randomized placebo-controlled trials in patients with IBS that investigated the efficacy of probiotics in IBS improvement. The Jadad score was used to assess the methodological quality of trials. The quality scale ranges from 0 to 5 points, with a score ≤ 2 indicating a low quality report, and a score of ≥ 3 indicating a high quality report. Relative risk (RR), standardized effect size, and 95%CI were calculated using the DerSimonian-Laird method. The Cochran Q test was used to test heterogeneity with P < 0.05. Funnel plots were constructed and Egger's and Begg-Mazumdar tests were performed to assess publication bias. A total of 1793 patients were included in the meta-analysis. The RR of responders to therapies based on abdominal pain score in IBS patients for two included trials comparing probiotics to placebo was 1.96 (95%CI: 1.14-3.36; P = 0.01). RR of responders to therapies based on a global symptom score in IBS patients for two included trials comparing probiotics with placebo was 2.43 (95%CI: 1.13-5.21; P = 0.02). For adequate improvement of general symptoms in IBS patients, the RR of seven included trials (six studies) comparing probiotics with placebo was 2.14 (95%CI: 1.08-4.26; P = 0.03). Distension, bloating, and flatulence were evaluated using an IBS severity scoring system in three trials (two studies) to compare the effect of probiotic therapy in IBS patients with placebo, the standardized effect size of mean differences for probiotics therapy was -2.57 (95%CI: -13.05--7.92). Probiotics reduce pain and symptom severity scores. The results demonstrate the beneficial effects of probiotics in IBS patients in comparison with placebo.

Pancreatic duct stent preventing post endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients

Objective To evaluate the preventive effect of pancreatic duct stent against post endoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP)and hyperamylasemia in high-risk patients.Methods A total of 160 patients with high-risk PEP underwent ERCP therapy between Jan.2013 and Dec.2014 and were retrospectively analyzed.The patients were divided into pancreatic duct stent group(n=82)and control group(n=78)according to whether receiving pancreatic duct stent or not.Abdominal pain was evaluated after ERCP.The levels of serum amylase were detected at 3hand24 hafter ERCP.The incidences of PEP and hyperamylasemia were compared between the two groups.Results The serum amylase levels at 3hand 24 hafter ERCP in pancreatic duct stent group were significantly lower than those in control group([184.89±257.33]U/L vs [305.35±371.81]U/L,P0.05;[268.07±344.73]U/L vs [465.86±639.94]U/L,P0.05).The incidences of PEP and hyperamylasemia in pancreatic duct stent group were also significantly lower than those in control group(2.4% [2/82]vs 11.5% [9/78],P0.05;17.1% [14/82]vs 30.8% [24/78],P0.05).The incidence of abdominal pain and abdominal pain score were(19.5%[16/82],[1.24±0.58])in pancreatic duct stent group,which were significantly lower than those in control group(43.6% [34/78],[1.68±0.97])(P=0.001).Conclusion Pancreatic duct stent can effectively prevent PEP and hyperamylasemia in high-risk patients following ERCP.

Effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy.

To systematically evaluate the effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy (LC). We searched MEDLINE, EMBASE, and the Cochrane Library. Randomized controlled trials in English that compared the effect of intraperitoneal administration of local anesthetics on pain with that of placebo or nothing after elective LC under general anesthesia were included. The primary outcome variables analyzed were the combined scores of abdominal, visceral, parietal, and shoulder pain after LC at multiple time points. We also extracted pain scores at resting and dynamic states. We included 39 studies of 3045 patients in total. The administration of intraperitoneal local anesthetic reduced pain intensity in a resting state after laparoscopic cholecystectomy: abdominal [standardized mean difference (SMD) = -0.741; 95%CI: -1.001 to -0.48, P < 0.001]; visceral (SMD = -0.249; 95%CI: -0.493 to -0.006, P = 0.774); and shoulder (SMD = -0.273; 95%CI: -0.464 to -0.082, P = 0.097). Application of intraperitoneal local anesthetic significantly reduced the incidence of shoulder pain (RR = 0.437; 95%CI: 0.299 to 0.639, P < 0.001). There was no favorable effect on resting parietal or dynamic abdominal pain. Intraperitoneal local anesthetic as an analgesic adjuvant in patients undergoing laparoscopic cholecystectomy exhibited beneficial effects on postoperative abdominal, visceral, and shoulder pain in a resting state.

The Role of Low FODMAP Diet in the Management of Irritable Bowel Syndrome

The Role of Low FODMAP Diet in the Management of Irritable Bowel Syndrome

Continuous consumption of fermented milk containing Bifidobacterium bifidum YIT 10347 improves gastrointestinal and psychological symptoms in patients with functional gastrointestinal disorders.

The aim of this study was to investigate whether consumption of probiotic fermented milk containing Bifidobacterium bifidum YIT 10347 improves symptoms in patients with functional gastrointestinal disorders (FGID). Thirty-seven FGID patients (18 male, 19 female) aged 12–80 years (mean ± SD, 52.6 ± 17.5 years) whose condition had not improved despite being seen at several medical institutions consumed 100 mL/day of B. bifidum YIT 10347 fermented milk for 4 weeks. Symptoms were evaluated after the enrollment period (BL: baseline), sample consumption period (CP) and 4 weeks after the CP (FP: follow-up period). Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) and the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG); psychological symptoms were evaluated using the Profile of Mood States (POMS) short form. Concentrations of salivary stress markers and the oxidative stress marker urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) were measured. GSRS subscale scores for abdominal pain, diarrhea, and constipation significantly improved relative to BL after consumption of the fermented milk, as did FSSG subscale scores for symptoms of acid-related dyspepsia. Some subjective psychological symptoms improved. POMS scores significantly improved, and “Anger-Hostility” subscale scores significantly decreased after the consumption period, while “Vigor” subscale scores marginally increased during the consumption period. The concentrations of urinary 8-OHdG and the stress marker salivary cortisol were significantly lower at CP but returned to baseline levels at FP. Continuous consumption of B. bifidum YIT 10347 fermented milk is expected to improve gastrointestinal symptoms and reduce psychological stress in FGID patients.

Effectiveness Of Probiotics In Irritable Bowel Syndrome: A Systematic Review With Meta-Analysis.

AIM: To investigate the efficacy of probiotics in irritable bowel syndrome (IBS) patients. METHODS: PubMed, Cochrane library, Scopus, Google Scholar, and Clinicaltrial.gov databases were searched for literature published between September 2007 and December 2013. The applied Mesh terms were “probiotics,” “irritable bowel syndrome,” and “irritable bowel syndrome treatment.” The collected data contained24 clinical trials, of which 15 were eligible for meta-analysis and nine were reviewed systematically. All studies were randomized placebo-controlled trials in patients with IBS that investigated the efficacy of probiotics in IBS improvement. The Jadad score was used to assess the methodological quality of trials. The quality scale ranges from 0 to 5 points, with a score ≤ 2 indicating a low quality report, and a score of ≥ 3 indicating a high quality report. Relative risk (RR), standardized effect size, and 95%CI were calculated using the DerSimonian-Laird method. The Cochran Q test was used to test heterogeneity with P < 0.05. Funnel plots were constructed and Egger’s and BeggMazumdar tests were performed to assess publication bias. RESULTS: A total of 1793 patients were included in the meta-analysis. The RR of responders to therapies based on abdominal pain score in IBS patients for two included trials comparing probiotics to placebo was 1.96 (95%CI: 1.14-3.36; P = 0.01). RR of responders to therapies based on a global symptom score in IBS patients for two included trials comparing probiotics with placebo was 2.43 (95%CI: 1.13-5.21; P = 0.02). For adequate improvement of general symptoms in IBS patients, the RR of seven included trials (six studies) comparing probiotics with placebo was 2.14 (95%CI: 1.08-4.26; P = 0.03). Distension, bloating, and flatulence were evaluated using an IBS severity scoring system in three trials (two studies) to compare the effect of probiotic therapy in IBS patients with placebo, the standardized effect size of mean differences for probiotics therapy was -2.57 (95%CI: -13.05--7.92). CONCLUSION: Probiotics reduce pain and symptom severity scores. The results demonstrate the beneficial effects of probiotics in IBS patients in comparison with META-ANALYSIS Submit a Manuscript: http://www.wjgnet.com/esps/ Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx DOI: 10.3748/wjg.v21.i10.3072 World J Gastroenterol 2015 March 14; 21(10): 3072-3084 ISSN 1007-9327 (print) ISSN 2219-2840 (online) © 2015 Baishideng Publishing Group Inc. All rights reserved. 3072 March 14, 2015|Volume 21|Issue 10| WJG|www.wjgnet.com inhibitors, tricyclic antidepressants, and 5-hydroxytryptamine type-3 antagonists such as ramosetron and alosetron, and lubiprostone and linaclotide. However, due to lack of favorable efficacy and associated adverse events with pharmacologic treatments, some IBS patients look for alternative treatments such as herbal medications and Chinese acupuncture. Probiotics are live microorganisms which have been demonstrated to exhibit potential effects on human health. Probiotics may influence the IBS symptoms including abdominal pain, bloating, distension, flatulence, altered bowel movements, and gut microbiota. The nature of probiotics explains their beneficial role in intestinal function as they can protect against pathogenic bacteria via their antimicrobial properties. Probiotics also amplify the intestinal tight junctions and stabilize the permeability. Moreover, probiotics stimulate goblet cells to produce mucus to enhance the intestinal barrier function, normalize bowel movements, and reduce visceral hypersensitivity in pediatric and adult patients. Several probiotic strains showed beneficial outcomes in IBS patients. The present study was performed to update the previous meta-analysis with consideration of further clinical trials. A systematic review has been also conducted to assess the efficacy of probiotics in IBS patients in clinical trials that were not eligible for inclusion in the meta-analysis. MATERIALS AND METHODS Data sources PubMed, Cochrane library, Scopus, Google Scholar, and Clinicaltrial.gov databases were searched for articles published between September 2007 and December 2013. The applied Mesh terms were “probiotics,” “irritable bowel syndrome,” and “irritable bowel syndrome treatment.” Study selection Three reviewers inspected the topic and abstracts of all articles to eliminate identical studies, review articles, systematic reviews, and meta-analysis investigations. All relevant characteristics of included trials, such as IBS type, probiotic strain, dose of probiotics, trial and follow-up duration, and patient characteristics and outcomes, were collected and summarized. All randomized controlled trials that considered IBS symptom improvement as outcome of interest were included. The reference lists of searched articles were reviewed to identify any additional eligible articles. Assessment of trial quality The Jadad score, which indicates the quality of studies based on their description of randomization, blinding, and dropouts (withdrawals), was used to assess the methodological quality of trials. The quality Didari T et al . Effectiveness of probiotics in IBS 3073 March 14, 2015|Volume 21|Issue 10| WJG|www.wjgnet.com placebo.

Need for Prokinetic Medications After Gastric Electrical Stimulation in Patients With Medically Refractory Gastroparesis

Introduction: Gastric electrical stimulation (GES) is an FDA-approved therapy for patients with medically refractory gastroparesis. Patients are invariably on prokinetic medications prior to GES. It is unclear how many patients require prokinetic medications after GES implantation. The objective was to evaluate symptom improvement, weight gain, hospitalization frequency, and need for enteral nutrition in patients on and off prokinetic medicines 1 year after GES therapy. Methods: Thirty-one patients (mean age 40 years; 77% female; 71% white) with GES implantation between 2007 and 2013 were evaluated. Eighteen were diabetic, 10 idiopathic and 3 post-surgical. Clinical improvement was assessed by a modified GCSI score on a Likert scale from 0-4 that inquired about vomiting, nausea, early satiety, bloating, and postprandial fullness. Abdominal pain and epigastric burning were also assessed. All patients were on 1 or more prokinetics prior to GES (metoclopramide, domperidone [under FDA-approved IND], and erythromycin). Some patients discontinued medication at 1 year due to subjective improvement. Patients on prokinetics were compared to those off prokinetics, after 1 year of GES therapy. Results: The mean GCSI score improved significantly more in patients on prokinetics compared to patients off prokinetics (1.35 vs. 2.20, p=0.02). Nausea, bloating, and abdominal pain reduced significantly in the prokinetic group (2.18 vs. 2.94; p=0.05, 0.86 vs. 2.29; p=0.003, and 1.00 vs. 2.18; p=0.02), respectively (Table 1). After 1 year, fewer patients on prokinetics required enteral nutrition and had a greater weight gain compared to patients off prokinetics (n=5 vs. n=7; p=0.55). There was no significant difference in the number of patients requiring hospitalization (n=7 vs. n=9, p=0.37) between the 2 groups.Table 1: Modified GCSI Score and Symptom Subscore in Gastroparesis Patients On and Off Prokinetics at 1 Uear Post-GES TherapyConclusion: Patients on prokinetics have significantly improved GCSI, nausea, bloating, and abdominal pain scores, a greater weight gain, and decreased use of enteral nutrition when compared to patients who discontinued prokinetic medications after 1 year of GES. GES and prokinetic medications appear to work in synergy to improve symptoms of severe gastroparesis.

Acute Pancreatitis as Initial Presentation of Crohn’s Disease: Report of a Rare Case

Introduction: Acute pancreatitis related to Crohn’s disease (CD) has rarely been reported, but whether a causal association exist remains unclear. Forgut CD occurs in 0.5-4% of patients with ileocolonic CD. The pathogenesis of pancreatitis in CD seems to be multifactorial. We sought to describe a case of acute pancreatitis before the establishment of CD. Methods: A 19-year-old African American male with history of hypertension was admitted to our hospital for sharp epigastric abdominal pain of 10 days duration and 10 Ibs of weight loss. He presented 1 year previously with similar pain and was diagnosed with peptic ulcer disease, confirmed with an upper endoscopy. Omeprazole was prescribed, which he has been taking since then. He denied smoking, drinking alcohol, and using NSAID or recreational drugs. No drugs known to be involved in the causation of pancreatitis were taken by the patient. He was found to have lipase of 3,000 but normal liver chemistry, triglyceride, calcium, IgG4, and anti-neutrophilic antibody. Abdominal ultrasound ruled out gallstone or any biliary dilation, whereas abdominal CT revealed mild dilation of stomach, narrowing of second part of the duodenum, and changes consistent with acute pancreatitis, though no pseudocyst and mass were noted. Classical treatment strategies including food restriction, fluid, and electrolyte restoration were sought. Further investigation with an upper esophagogastroduodenoscopy was performed to determine the cause of the duodenal narrowing, which revealed moderate ulceration in duodenal bulb with mild post-bulbar stenosis. Biopsies showed fibrinopurulent exudate consistent with ulcer, with no evidence of Helicobacter pylori infection. Results: He responded to conservative therapy. Given his young age, concern regarding duodenal CD was raised. He subsequently underwent MR enterography, which showed a moderate degree of thickness and narrowing of terminal ileum. Colonoscopy was performed, which showed aphthous-like ulcers in the ileocecal valve, a moderate degree of erythema, and edema scattered throughout the colon. Histology was consistent with inflammatory infiltration of lamina propria and granulomas. Treatment with certolizumab pegol was initiated. He had total resolution of his abdominal pain and Harvey Bradshaw score of zero in 3-month clinic follow-up. Discussion: Patients with inflammatory bowel disease are prone to develop acute pancreatitis with numerous possible etiologies. In the present case, duodenal involvement was likely the predisposing factor. Search for etiological factors should focus attention on serious side effects of medical treatment, morphological abnormalities in the upper GI tract, gallstone, sclerosing cholangitis, and extra intestinal manifestation. Disclosure - Dr. Sarah Glover - Advisory Committee: Abbvie, Grant/Research Support: Biogen, Bristol Myers Squibb, Celgene, Elan, Janssen, Pfizer and UCB.

Evaluation of Alosetron Using the New FDA Composite Endpoint Demonstrates Strong Treatment Effect in Females With Severe Irritable Bowel Syndrome With Diarrhea

Introduction: Prior to 2010, most clinical trials of drug treatments for irritable bowel syndrome (IBS) evaluated drug effect by a global measure of overall IBS condition (i.e., adequate relief) and grading of specific relevant symptoms (i.e., abdominal pain, bowel urgency, stool form). The new FDA recommended assessment uses composite or co-primary endpoints which quantify the sum of scores for abdominal pain (AP) and stool consistency (SC) for IBS with diarrhea (IBS-D). To determine if previously approved drugs are also effective by the new FDA standard, we evaluated data from two pivotal Phase III alosetron (ALO) trials [S3BA3001 and 3002 selecting only severe IBS-D patients (mean SC ≥3.5; mean AP ≥2.0; bowel urgency on ≥50% days and, if available, IBS-impaired activity on ≥25% days)] plus one post marketing (PM) double blind placebo controlled study (S3B30040) conducted in female patients who met appropriate Rome IBS criteria. The PM study entered only female patients with severe IBS-D. Methods: In all 3 trials, patients met baseline criteria for eligibility and were randomized to 12 weeks treatment with ALO 1.0 mg bid or placebo (PBO). Symptoms were self assessed daily and registered using a telephone reporting system to rate AP [1=none; 5=severe] and SC [1=very hard; 5=watery]. Data from the 3 trials were mined to select for analysis only patients having baseline criteria for severe IBS-D. A monthly responder showed advantage for ALO over PBO in the composite endpoint for ≥2 of 4 weeks. Comparison of responder results is based on Fisher’s exact test. Results: The table shows differences in responder rates (ALO minus PBO) for the new composite endpoint in both treatment groups in the 3 studies (**p≤0.005; *p≤0.05). Conclusion: Re-analysis of similar, high quality alosetron clinical trials using the FDA recommended composite endpoint demonstrated a robust positive treatment effect for alosetron, as was also shown (p≤0.05) in the same patients for the adequate relief endpoint. Both endpoints gave similar results and support a significant treatment effect with alosetron. Results are among the first to compare treatment effect between the older global and newer composite score endpoints. Disclosure - Dr. Camilleri - no relevant disclosures. Dr. Krause - no relevant disclosures. Dr. Deveze - Employee of Prometheus Laboratories Inc. Dr. Rao - Employee of Prometheus Laboratories Inc. Dr. Earnest - Consultant for Prometheus Laboratories Inc. This research was supported by an industry grant from The study was conducted by financial support from Prometheus Laboratories Inc.Table 1

Evaluation of an Interim Crohn’s Disease Outcome Measure (PRO−2) Based on 2 Patient-Reported Components (Stool Frequency, Abdominal Pain) of the Crohn’s Disease Activity Index (CDAI) in the Ustekinumab CERTIFI Study

Introduction: The CDAI has been the standard outcome measure in CD trials for ˜40 years, but its complexity, high placebo response, and inconsistency with FDA guidance on patient-reported outcome (PRO) measures are disadvantages. This has generated interest in exploring a PRO based on the stool frequency (SF) and abdominal pain (AP) components of the CDAI, known as PRO-2. A potential PRO-2 definition for remission (mean daily score of AP≤1 AND [also] SF≤1.5) was proposed based on data from 2 CD populations, one with mild-moderate disease and one with steroid-dependent disease. Whether this PRO-2 definition is optimal in patients with moderate-to-severe disease, and/or refractory to tumor necrosis factor (TNF)-α antagonists is unknown. Methods: Using the previously reported 8 week induction data from the ustekinumab (UST) Phase 2 CERTIFI study (in patients previously failing and/or intolerant to TNF-antagonists; mean baseline CDAI=324), the contributions of SF/AP to baseline CDAI and subsequent improvements post-treatment were assessed. Sensitivity(SENS)/specificity(SPEC) analyses that defined optimal cutoffs for detecting remission (CDAI<150) at week 8 were used to generate remission definitions based on unweighted mean daily scores for AP alone, SF alone, or both: Either requiring maximums for each (e.g. AP≤1 AND SF≤1.5) or, applying maximum thresholds to the sum of AP+SF, using standard CDAI weightings. The treatment effects of UST in CERTIFI were then evaluated and compared using the selected definitions. Results: The unweighted mean daily score cutoffs of AP ≤1/SF ≤3/combined AP≤1 AND SF≤3, respectively, provided better balance of SENS (87.1%; 84.7%; 72.9%) and SPEC (77.1%; 73.9%; 94.1%) compared with the previously proposed cutoff of combined AP≤1 AND SF≤1.5 (55.3% SENS;96.8% SPEC) in the detection of remission at week 8. A weighted total AP+SF score cutoff of <75 best optimized SENS ( 91.8%) and SPEC (85.3%) compared with the unweighted mean daily AP/SF cutoffs. Candidate remission definitions all demonstrated significant treatment effects (UST vs. PBO): total AP+SF <75 (29.4% vs.16.7%; p=0.004), combined AP≤1 AND SF≤3 (19.3% vs.9.1%; p=0.007), combined AP≤1 AND SF≤1.5 (13.7% vs.5.3%; p=0.009). Conclusion: Definitions of PRO-2 remission based on SF&AP CDAI components are sensitive and specific in an anti-TNF refractory/intolerant population with high CD activity. In this population, the PRO-2 definition of AP≤1 AND SF≤3 better reflects clinical remission than the previously proposed AP≤1 AND SF≤1.5 threshold, identified in the mild-to-moderate patient populations. A weighted total AP+SF score <75 may be a good PRO-2 definition of remission, because it provides the best overall balance of SENS/SPEC and facilitates comparisons with studies utilizing the full CDAI. Disclosure - C Gasink-employee Janssen R&D, LLC; J Friedman-employee Janssen R&D, LLC; LL Gaoemployee Janssen R&D, LLC; D Chan- employee Janssen R&D, LLC; W Sandborn-Grant/Research support Janssen R&D, LLC; B Feagan-Grant/Research support Janssen R&D, LLC

Residual pneumoperitoneum volume and postlaparoscopic cholecystectomy pain.

Background:Gasretention in the peritoneal cavity plays an important role in inducing postoperative pain after laparoscopy, which is inevitably retained in the peritoneal cavity.Objectives:The aim of this study was to detect the relation between the volume of residual gas and severity of shoulder and abdominal pain.Patients and Methods:In this Prospective study 55 women who were referred for laparoscopic cholecystectomy, were evaluated for the effect of residual pneumoperitoneum on postlaparoscopic cholecystectomy pain intensity. The pneumoperitoneum was graded as absent, mild (1-5 mm), moderate (6-10 mm) and severe (> 11 mm). Patients were followed for postoperative abdominal and shoulder pain using visual analogue scale (VAS), postoperative analgesic requirements, presence of nausea and vomiting, time of unassisted ambulation, time of oral intake and time of return of bowel function in the recovery room and at 6, 12 and 24 hours after operation.Results:At the end of the study, 17 patients (30.9%) had no residual pneumoperitoneum after 24 hours; which 23 (41.81%) had mild residual pneumoperitoneum, eight (14.54%) had moderate pneumoperitoneum and seven (12.72%) had severe pneumoperitoneum. Patients with no or mild residual pneumoperitoneum had significantly lower abdominal and shoulder pain scores than whom with moderate to severe pneumoperitoneum (P = 0.00) and need less meperidine requirements (P = 0.00). Patients did not have any significant difference in time of oral intake, return of bowel function, nausea and vomiting percentages.Conclusions:We conclude that volume of residual pneumoperitoneum is a contributing factor in the etiology of postoperative pain after laparoscopic cholecystectomy.

Comparing the impact of intraperitoneal hydrocortisone with bupivacaine on postoperative pain after laparoscopic cholecystectomy.

Background:Postoperative pain is a major complaint following laparoscopic cholecystectomy.Objectives:The aim of this study was to compare the impact of intraperitoneal hydrocortisone with intraperitoneal bupivacaine on pain relief after laparoscopic cholecystectomyPatients and Methods:In a double blind clinical trial, 63 candidates for laparoscopic cholecystectomy were randomly allocated to receive intraperitoneal instillation of either 100 mg bupivacaine in 250 mL normal saline (n = 32) or 100 mg hydrocortisone in 250 mL normal saline (n = 31) before insufflation of CO2 into the peritoneum for postoperative pain relief. Patients were investigated regarding abdominal and shoulder pain using (visual analog scale) VAS in recovery room and at 6, 12 and 24 hours postoperatively. Patients were also followed regarding postoperative analgesic requirements, nausea and vomiting, and return of bowel function.Results:Sixty patients completed the study. Patients in the hydrocortisone group had no statistically significant abdominal and shoulder pain scores compared to the bupivacaine group. The patients were similar regarding postoperative analgesic requirements, return of bowel function, nausea and vomiting. No adverse effect was detected in either group.Conclusions:Intraperitoneal administration of hydrocortisone is as effective as bupivacaine to reduce pain and analgesic requirements after laparoscopic cholecystectomy.

Measuring quality of Life among Colorectal Cancer Patients in Jordan

Quality of life among colorectal cancer (CRC) patients was evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and EORTC QLQ-CR29. We interviewed 74 CRC patients, and our results indicated lower anxiety functional scores and higher abdominal pain and embarrassment symptom scores among patients aged 55 and under. Patients with disease metastasis showed significantly lower global health scores and higher fatigue, loss of appetite, hair loss, and change in taste symptom scores. Scores for emotional functioning were significantly lower among patients with stage IV disease. Fatigue, nausea and vomiting, loss of appetite, abdominal pain, and change in taste symptom scores were significantly higher in patients treated with a combination of surgery and chemotherapy compared to surgery alone. Age, disease metastasis, late disease stage, and combined treatment modalities were associated with lower scores on health-related quality-of-life scales; patients likely to have low scores on these measures should receive special attention from healthcare providers and be targeted by supportive care strategies.

Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study.

Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms. The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychological and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels. Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 weeks. Subjects completed bowel and psychological questionnaires, underwent rectal sensitivity testing and saliva melatonin assays. Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores (r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated (r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits (r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life. VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin production, hence modulating IBS symptoms, in individuals with a normal circadian rhythm.

American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation.

Irritable bowel syndrome (IBS) and chronic idiopathic constipation ((CIC) also referred to as functional constipation) are two of the most common functional gastrointestinal disorders worldwide. IBS is a global problem, with anywhere from 5 to 15 % of the general population experiencing symptoms that would satisfy a defi nition of IBS ( 1,2 ). In a systematic review on the global prevalence of IBS, Lovell and Ford ( 1 ) documented a pooled prevalence of 11 % with all regions of the world suff ering from this disorder at similar rates. Given its prevalence, the frequency of symptoms, and their associated debility for many patients and the fact that IBS typically occurs in younger adulthood, an important period for furthering education, embarking on careers, and / or raising families, the socioeconomic impact of IBS is considerable. Th ese indirect medical costs are frequently compounded by the direct medical costs related to additional medical tests and the use of various medical and nonmedical remedies that may have limited impact. CIC is equally common; in another systematic review, Suares and Ford ( 3 ) reported a pooled prevalence of 14 % , and also noted that constipation was more common in females, in older subjects, and those of lower socioeconomic status ( 3 ). Chronic constipation has also been linked to impaired quality of life ( 4 ), most notably among the elderly ( 5 ). Neither IBS nor CIC are associated with abnormal radiologic or endoscopic abnormalities, nor are they associated with a reliable biomarker; diagnosis currently rests entirely, therefore, on clinical grounds. Although a number of clinical defi nitions of both IBS and CIC have been proposed, the criteria developed through the Rome process, currently in its third iteration, have been those most widely employed in clinical trials and, therefore, most relevant to any review of the literature on the management of these disorders. According to Rome III, IBS is defi ned on the basis of the presence of:

Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis.

Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI. The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70-0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week=1.49; 95% CI=1.02-1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy=0.78; 95% CI 0.67-0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn. Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain.

Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome.

The pharmacology, pharmaco-kinetics, and clinical efficacy and safety of linaclotide in the management of chronic constipation (CC) and constipation-predominant irritable bowel syndrome (IBS-C) are reviewed. Linaclotide (Linzess, Forest Pharmaceuticals) is a 14-amino acid peptide indicated for the treatment of adults with CC and IBS-C. Linaclotide acts on guanylate cyclase-C receptors on the luminal membrane to increase chloride and bicarbonate secretions into the intestine and inhibit the absorption of sodium ions, thus increasing the secretion of water into the lumen and improving defecation; the drug is minimally absorbed into the systemic circulation. Linaclotide is approved by the Food and Drug Administration (FDA) for oral once-daily administration at doses of 145 μg for CC and 290 μg for IBS-C. In placebo-controlled Phase III clinical trials, linaclotide significantly increased weekly spontaneous bowel movements and complete spontaneous bowel movements (CSBMs) while reducing abdominal pain in patients with CC. In patients with IBS-C, linaclotide was demonstrated to be effective in meeting FDA-recommended endpoints such as reductions of at least 30% from baseline in abdominal pain scores and CSBM frequency. The most common adverse effect of linaclotide is diarrhea, which was reported in 16-20% of clinical trial participants. Linaclotide is an important advance in the treatment of CC and IBS-C, with a novel mechanism of action resulting in accelerated intestinal transit. In clinical trials, linaclotide demonstrated efficacy relative to placebo for treatment of both CC and IBS-C. Linaclotide's adverse effects are generally mild and confined to the gastrointestinal tract.