Reduced Stool Frequency Research Articles

1041 Efficacy of Rifaximin for IBS Without Constipation in Men and Women

Background: Radiation proctitis (RAP) is defined as damage to the rectal mucosa resulting from radiotherapy to adjacent pelvic organs. More than 50 % of patients undergoing radiotherapy for prostate cancer (PC) will encounter symptoms such as diarrhea, blood and mucus in stool and tenesms that might alter qualitiy of life and might be dose limiting. The symptoms of radiation proctitis can be quantified by the acute EORTC/RTOG lower GI toxicity or the RAP score . Material and Methods: Patients undergoing radiotherapy (XRT) for PC were randomised to rectal budesonide (BUD) or placebo (PLB) treatment over 8 weeks. EORTC/RTOG lower GI toxicity score, RAP score and quality of life scores were taken at baseline and after 2, 4, 8 and 14 weeks as well as after 1 year. Flexible rectoscopy and assessment of the Vienna rectoscopy score (VRS) was done at baseline, after 8 weeks, 14 weeks and 1 year. 17 patients were included (n=8 budesonide, n=9 placebo) into the study. Results: 6/8 BUD patients and 6/9 PLB patients developed clinical signs of acute radiation proctitis, i.e. acute EORT/RTOG lower GI toxicity ≥ 1 for at least 2 consecutive days, during 8 weeks of treatment (p=0.8167). However, BUD ameliorated the severity of RAP by significantly reducing stool frequency at week 14 and after 1 year and numerically the number of tenesms at week 8. The endoscopic score for late radiation proctitis was diminished in the budesonide group compared to placebo. Conclusions: Rectal treatment with budesonide did not significantly prevent acute radiation proctitis in this pilot study. However, clinical symptoms of proctitis could be significantly reduced and the appearance of late radiation proctitis was diminished. Therefore BUD deserves further evaluation in the context of high dose XRT with curative intent to prevent or to ameliorate side effects that might be dose limiting.

Octreotide for the treatment of diarrhoea in patients with ileal pouch anal anastomosis: a placebo-controlled crossover study

Diarrhoea with urgency is a debilitating long-term complication of ileal pouch anal anastomosis (IPAA) after a proctocolectomy. Somatostatin analogues are used to control diarrhoea and high-output ostomies. Hence, we designed a prospective, double-blind, crossover trial to explore the efficacy and tolerability of octreotide to reduce diarrhoea in adult patients with IPAA. Patients were randomized to octreotide subcutaneously (SC), 500 μg three times daily (t.i.d.), or matching placebo SC for 7 days. Responders (a reduction in stool frequency of three or more stools per 24-h period and with a reduction in stool frequency of at least 30% after 7 days of treatment compared with baseline; the primary end-point) remained in the same group and nonresponders could cross over to the alternative treatment for 7 days. Open-label octeotide LAR 30 mg was offered to all responders on day 14. Flexible pouchoscopy with biopsies was performed at baseline in all patients and was repeated on days 7 and 14 in patients with pouchitis. Fifteen patients (11 men, median age 52 years), all with ulcerative colitis, were randomized. Three patients were withdrawn for side effects during the blinded phase. Response was achieved by two of 12 and two of 11 patients treated with octreotide or placebo, respectively (including crossover, P = 0.9). The median stool frequency remained stable in both groups [Δoctreotide: 0 (IQR, -4 to 0), Δplacebo: -1 (IQR, -1 to 1), P = 0.45]. Octreotide had no effect on the modified pouch disease activity index (mPDAI), and pouchitis persisted in five of six subjects with pouchitis at onset. One subject received open-label octreotide LAR. Octreotide has no clear beneficial effect on the stool pattern or on pouchitis severity in patients with high stool frequency after IPAA.

Double-blind, Randomized Evaluation of Clinical Efficacy and Tolerability of an Apple Pectin-Chamomile Extract in Children with Unspecific Diarrhea

Acute diarrhea is one of the most common childhood diseases. The main aim of therapy is oral rehydration, mostly using a glucose-electrolyte solution. Results from a previous study (DIALOG I) investigating adjuvant treatment with a medicinal preparation containing an apple pectin-chamomile extract (Diarrhoesan) indicated a significantly reduced duration of diarrhea in children. The objective of the present clinical placebo-controlled, double-blind study (DIALOG II) was to assess the clinical efficacy and tolerability of the apple pectin-chamomile extract on a larger number of patients. The investigation was designed as a multicenter, randomized, double-blind, placebo-controlled parallel study enrolling 255 patients presenting with acute diarrhea. Patients were aged between 6 months and 6 years and treated on an outpatient basis with either an apple pectin-chamomile preparation or placebo. As a basic medication, each child received a glucose-electrolyte solution on the first day of treatment. The primary outcome (primary efficacy parameter) included a combined analysis of stool frequency, stool The statistical analysis revealed a superior efficacy of the tested preparation over placebo with a significantly reduced stool frequency in the treatment group compared to the control group. The results were corroborated by efficacy assessment performed by investigators and patients. Treatment was well tolerated, with an incidence of adverse effects similar to placebo. These findings support the concept of a beneficial influence of the investigated vegetable extract in shortening the course of the disease and relieving associated symptoms.

Cochrane Review: Probiotics for treating acute infectious diarrhoea

AbstractBackgroundProbiotics may offer a safe intervention in acute infectious diarrhoea to reduce the duration and severity of the illness.ObjectivesTo assess the effects of probiotics in proven or presumed acute infectious diarrhoea.Search strategyWe searched the Cochrane Infectious Diseases Group's trials register (July 2010), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2010), MEDLINE (1966 to July 2010), EMBASE (1988 to July 2010), and reference lists from studies and reviews. We also contacted organizations and individuals working in the field, and pharmaceutical companies manufacturing probiotic agents.Selection criteriaRandomized and quasi‐randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent.Data collection and analysisTwo reviewers independently assessed the methodological quality of the trial and extracted data. Primary outcomes were the mean duration of diarrhoea, stool frequency on day 2 after intervention and ongoing diarrhoea on day 4. A random‐effects model was used.Main resultsSixty‐three studies met the inclusion criteria with a total of 8014 participants. Of these, 56 trials recruited infants and young children. The trials varied in the definition used for acute diarrhoea and the end of the diarrhoeal illness, as well as in the risk of bias. The trials were undertaken in a wide range of different settings and also varied greatly in organisms tested, dosage, and participants' characteristics. No adverse events were attributed to the probiotic intervention.Probiotics reduced the duration of diarrhoea, although the size of the effect varied considerably between studies.The average of the effect was significant for mean duration of diarrhoea (mean difference 24.76 hours; 95% confidence interval 15.9 to 33.6 hours; n=4555, trials=35) diarrhoea lasting ≥4 days (risk ratio 0.41; 0.32 to 0.53; n=2853, trials=29) and stool frequency on day 2 (mean difference 0.80; 0.45 to 1.14; n=2751, trials=20).The differences in effect size between studies was not explained by study quality, probiotic strain, the number of different strains, the viability of the organisms, dosage of organisms, the causes of diarrhoea, or the severity of the diarrhoea, or whether the studies were done in developed or developing countries.Authors' conclusionsUsed alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea. However, more research is needed to guide the use of particular probiotic regimens in specific patient groups.Plain Language SummaryProbiotics for treating acute infectious diarrhoeaEpisodes of acute infectious diarrhoea remain a major disease burden throughout the world, especially in developing countries. They are due to infection by many different organisms. Most episodes are self‐limiting and usually investigations are not done to identify the infectious agent. The main risk to health is dehydration and management aims to improve and maintain hydration status. However, rehydration fluids do not reduce the stool volume or shorten the episode of diarrhoea. Probiotics are "friendly" bacteria that improve health and are not harmful in themselves. A number of randomized controlled trials have been done to see whether probiotics are beneficial in acute infectious diarrhoea. We have searched for as many of these trials as possible and collected together the data in a systematic way to try to discover whether or not probiotics are beneficial in acute diarrhoea. We identified 63 trials, which included a total of 8014 people ‐ mainly infants and children. Probiotics were not associated with any adverse effects. Nearly all studies reported a shortened duration of diarrhoea and reduced stool frequency in people who received probiotics compared to the controls. Overall, probiotics reduced the duration of diarrhoea by around 25 hours, the risk of diarrhoea lasting four or more days by 59% and resulted in about one fewer diarrhoeal stool on day 2 after the intervention. However, there was very marked variability in the study findings and so these estimates are approximate. We concluded that these results were very encouraging but more research is needed to identify exactly which probiotics should be used for which groups of people, and also to assess the cost effectiveness of this treatment.

Cochrane Review: Lactulose versus Polyethylene Glycol for Chronic Constipation

AbstractBackgroundConstipation is a common clinical problem. Lactulose and Polyethylene Glycol (PEG) are both commonly used osmotic laxatives that have been shown to be effective and safe treatments for chronic constipation. However, there is no definitive data as to which provides the best treatment.ObjectivesTo identify and review all relevant data in order to determine whether Lactulose or Polyethylene Glycol is more effective at treating chronic constipation and faecal impaction.Search strategyWe searched the MEDLINE, EMBASE and CINAHL databases, and the Cochrane Central Register of Controlled Trials for all randomised controlled trials (RCTs) comparing the use of lactulose and polyethylene glycol in the management of faecal impaction and chronic constipation.Selection criteriaStudies were included if they were randomised controlled trials which compared lactulose with polyethylene glycol in the management of chronic constipation.Data collection and analysisData on study methods, participants, interventions used and outcomes measured was extracted from each study. Data was entered into the Cochrane Review Manager software (RevMan 5.0) and analysed using Cochrane MetaView.Main resultsIn the present meta‐analysis, we considered for the first time all ten randomised controlled trials so far performed. The ten trials enrolled a total of 868 participants and were conducted between 1997 and 2007. The trials were conducted in six different countries. Participant age ranged from 3 months to 70 years. Adults only were recruited for 4 studies. Five trials reported stool frequency per week. Singularly taken, all showed that PEG resulted in a higher stool frequency per week when compared with Lactulose. Two trials reported form of stool on the Bristol Stool Scale, both studies reported a higher Bristol Stool Score when using PEG compared with lactulose (softer stool). Three trials reported relief of abdominal pain. Two favoured PEG in this outcome; one found Lactulose and PEG to be comparable in this outcome. Three trials reported on use of additional products, all favoured PEG as requiring less use of additional products.Authors' conclusionsThe findings of our work indicate that Polyethylene glycol is better than lactulose in outcomes of stool frequency per week, form of stool, relief of abdominal pain and the need for additional products. On subgroup analysis, this is seen in both adults and children, except for relief of abdominal pain. Polyethylene Glycol should be used in preference to Lactulose in the treatment of Chronic Constipation.Plain Language SummaryPolyethylene Glycol should be used in preference to Lactulose in the treatment of Chronic Constipation.Constipation is a common clinical problem, encompassing much more than reduced stool frequency. In this review we compared two commonly used osmotic laxatives, Lactulose and Polyethylene Glycol (PEG). The findings of our work indicate that PEG is better than lactulose in outcomes of stool frequency per week, form of stool, relief of abdominal pain and the need for additional products. This is seen in both adults and children. Only exception is for relief of abdominal pain, where PEG is better than lactulose in children, but not in adults (no difference is seen). We conclude that Polyethylene Glycol should be used in preference to Lactulose in the treatment of Chronic Constipation.

A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery

Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). To assess the long-term safety and efficacy of pancrelipase (pancreatin) delayed-release capsules (Creon) in this population. This was a 6-month, open-label extension of a 7-day, double-blind, placebo-controlled study enrolling patients ≥18 years old with confirmed EPI due to CP or PS who were previously receiving PERT. Patients received individualised pancrelipase doses as directed by investigators (administered as Creon 24 000-lipase unit capsules). Overall, 48 of 51 patients completed the open-label phase; one withdrew due to the unrelated treatment-emergent adverse event (TEAE) of cutaneous burns and two were lost to follow-up. The mean age was 50.9 years, 70.6% of patients were male, 76.5% had CP and 23.5% had undergone PS. The mean±s.d. pancrelipase dose was 186960±74640 lipase units/day. TEAEs were reported by 22 patients (43.1%) overall. Only four patients (7.8%) had TEAEs that were considered treatment related. From double-blind phase baseline to end of the open-label period, subjects achieved a mean±s.d. body weight increase of 2.7±3.4 kg (P<0.0001) and change in daily stool frequency of -1.0±1.3 (P<0.001). Improvements in abdominal pain, flatulence and stool consistency were observed. Pancrelipase was well tolerated over 6 months and resulted in statistically significant weight gain and reduced stool frequency in patients with EPI due to CP or PS previously managed with standard PERT.

Pediatric functional constipation treatment withBifidobacterium-containing yogurt: A crossover, double-blind, controlled trial

To evaluate the treatment of pediatric functional chronic intestinal constipation (FCIC) with a probiotic goat yogurt. A crossover double-blind formula-controlled trial was carried out on 59 students (age range: 5-15 years) of a public school in Belo Horizonte, MG, Brazil, presenting a FCIC diagnostic, according to Roma III criteria. The students were randomized in two groups to receive a goat yogurt supplemented with 10(9) colony forming unit/mL Bifidobacterium longum (B. longum) (probiotic) daily or only the yogurt for a period of 5 wk (formula). Afterwards, the groups were intercrossed for another 5 wk. Defecation frequency, stool consistency and abdominal and defecation pain were assessed. Both treatment groups demonstrated improvement in defecation frequency compared to baseline. However, the group treated with probiotic showed most significant improvement in the first phase of the study. An inversion was observed after crossing over, resulting in a reduction in stool frequency when this group was treated by formula. Probiotic and formula improved stool consistency in the first phase of treatment, but the improvement obtained with probiotic was significantly higher (P = 0.03). In the second phase of treatment, the group initially treated with probiotic showed worsening stool consistency when using formula. However, the difference was not significant. A significant improvement in abdominal pain and defecation pain was observed with both probiotic and formula in the first phase of treatment, but again the improvement was more significant for the group treated with B. longum during phase I (P < 0.05). When all data of the crossover study were analyzed, significant differences were observed between probiotic yogurt and yogurt only for defecation frequency (P = 0.012), defecation pain (P = 0.046) and abdominal pain (P = 0.015). An improvement in defecation frequency and abdominal pain was observed using both supplemented and non-supplemented yogurt, but an additional improvement with B. longum supplementation was obtained.

Probiotics for treating acute infectious diarrhoea.

Probiotics may offer a safe intervention in acute infectious diarrhoea to reduce the duration and severity of the illness. To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. We searched the Cochrane Infectious Diseases Group's trials register (July 2010), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2010), MEDLINE (1966 to July 2010), EMBASE (1988 to July 2010), and reference lists from studies and reviews. We also contacted organizations and individuals working in the field, and pharmaceutical companies manufacturing probiotic agents. Randomized and quasi-randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. Two reviewers independently assessed the methodological quality of the trial and extracted data. Primary outcomes were the mean duration of diarrhoea, stool frequency on day 2 after intervention and ongoing diarrhoea on day 4. A random-effects model was used. Sixty-three studies met the inclusion criteria with a total of 8014 participants. Of these, 56 trials recruited infants and young children. The trials varied in the definition used for acute diarrhoea and the end of the diarrhoeal illness, as well as in the risk of bias. The trials were undertaken in a wide range of different settings and also varied greatly in organisms tested, dosage, and participants' characteristics. No adverse events were attributed to the probiotic intervention.Probiotics reduced the duration of diarrhoea, although the size of the effect varied considerably between studies.The average of the effect was significant for mean duration of diarrhoea (mean difference 24.76 hours; 95% confidence interval 15.9 to 33.6 hours; n=4555, trials=35) diarrhoea lasting ≥4 days (risk ratio 0.41; 0.32 to 0.53; n=2853, trials=29) and stool frequency on day 2 (mean difference 0.80; 0.45 to 1.14; n=2751, trials=20).The differences in effect size between studies was not explained by study quality, probiotic strain, the number of different strains, the viability of the organisms, dosage of organisms, the causes of diarrhoea, or the severity of the diarrhoea, or whether the studies were done in developed or developing countries. Used alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea. However, more research is needed to guide the use of particular probiotic regimens in specific patient groups.

The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health

The short-term effects of methylnaltrexone (MNTX), a peripherally acting mu-opioid receptor antagonist, on gastrointestinal and colonic transit remain unclear. To compare the effects of placebo, codeine, subcutaneous (s.c.) MNTX and codeine with s.c. MNTX on gastrointestinal and colonic transit of solids in healthy humans. In a randomized, parallel-group, double-blind, placebo-controlled trial of 48 healthy volunteers, effects of 6 consecutive days of placebo [s.c. and p.o. (orally), n = 8], codeine (p.o. 30 mg q.d.s., n = 8), MNTX (s.c. 0.30 mg/kg, n = 16) and combined MNTX and codeine (same doses and routes, n = 16) on gastrointestinal and colonic transit were assessed. A validated scintigraphic method was used to measure transit during the last 48 h of treatment. Bowel function was estimated during treatment as well as 1 week preceding treatment using standard diaries. Analysis of covariance was used to assess treatment effects. Codeine delayed colonic transit [geometric centre at 24 h (P = 0.04) and ascending colon t(1/2) (P = 0.02)] and reduced stool frequency (P = 0.002), but had no effect on stool form. MNTX did not affect transit, stool frequency or stool form, either alone or with codeine (P > 0.3). No drug interaction effects were detected (P > 0.15). Methylnaltrexone does not alter gastrointestinal or colonic transit and does not reverse acute codeine-associated delayed gut transit in health.

Cognitive Factors Affect Treatment Response to Medical and Psychological Treatments in Functional Bowel Disorders

For clinical trials in functional bowel disorders (FBD), the definition of a responder, one who meets the predefined criteria for a clinical response, is needed. Factors that determine clinical response aside from treatment itself are unknown. The aim of this study was to determine what baseline and post-treatment factors affect treatment response. Females (n=397) with FBD entering a 12-week, four-arm, randomized NIH treatment trial (desipramine (DES), CBT, pill placebo, and education) were studied at baseline and after treatment. Demographic, clinical, psychosocial, and physiological variables were considered in the analysis. A responder was defined as a patient obtaining a score>3.5 on an averaged eight-item, five-point satisfaction-with-treatment questionnaire. Baseline and post-treatment logistic regressions were performed for each treatment condition to predict the responder outcome variable. Similar cognitive features predisposed participants to treatment response across the treatment conditions: sense of control over the condition, positive relationship with therapist or study coordinator, confidence in treatment, improvement in maladaptive cognitions, and quality of life during treatment. Demographic and clinical variables studied were not predictive. Some treatment-specific effects predicting responder status were noted, including a reduction in stool frequency with DES treatment and lack of abuse history in the placebo group. For medication, psychological, and placebo treatment in FBD, satisfaction with treatment depends on cognitive factors of confidence in treatments, perceived control over illness and symptoms, and reduction in negative cognitions related to symptom experience. Addressing these issues among patients with FBD may enhance treatment response to a variety of treatments.

Efficacy and Safety of a New Formulation of Pancrelipase (Ultrase MT20) in the Treatment of Malabsorption in Exocrine Pancreatic Insufficiency in Cystic Fibrosis

Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (PI). Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in patients with CF and PI. Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs), and overall signs and symptoms. Methods. Patients (n = 31) were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared. Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp., P < .0001 for both), reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE. Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.

Do Stool Form and Frequency Correlate With Whole-Gut and Colonic Transit? Results From a Multicenter Study in Constipated Individuals and Healthy Controls

Despite a lack of supportive data, stool form and stool frequency are often used as clinical surrogates for gut transit in constipated patients. The aim of this study was to assess the correlation between stool characteristics (form and frequency) and gut transit in constipated and healthy adults. A post hoc analysis was performed on 110 subjects (46 chronic constipation) from nine US sites recording stool form (Bristol Stool Scale) and frequency during simultaneous assessment of whole-gut and colonic transit by wireless motility capsule (WMC) and radio-opaque marker (ROM) tests. Stool form and frequency were correlated with transit times using Spearman's rank correlation. Accuracy of stool form in predicting delayed transit was assessed by receiver operating characteristic analysis. In the constipated adults (42 females, 4 males), moderate correlations were found between stool form and whole-gut transit measured by WMC (r=-0.61, P<0.0001) or ROM (-0.45, P=0.0016), as well as colonic transit measured by WMC (-0.62, P<0.0001). A Bristol stool form value <3 predicted delayed whole-gut transit with a sensitivity of 85% and specificity of 82% and delayed colonic transit with a sensitivity of 82% and specificity of 83%. No correlation between stool form and measured transit was found in healthy adults, regardless of gender. No correlation was found between stool frequency and measured transit in constipated or healthy adults. The correlation between stool frequency and measured transit remained poor in constipated adults with <3 bowel movements per week. Stool form predicts delayed vs. normal transit in adults. However, only a moderate correlation exists between stool form and measured whole-gut or colonic transit time in constipated adults. In contrast, stool frequency is a poor surrogate for transit, even in those with reduced stool frequency.

M1209 Reduced Stool Frequency Does Not Predict Colonic and Whole Gut Transit in Constipated Patients

Introduction: The Rome III consensus proposed to subdivide functional dyspepsia (FD) into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), based on the symptom pattern (Tack et al, Gastroenterology 2006). The same consensus proposed to consider separate diagnostic categories for nausea/vomiting and for belching disorders. Aim: To empirically investigate the validity of this symptom-based subgrouping. Methods: In 705 consecutive tertiary care patients, clinically diagnosed with FD according to Rome II criteria, the severity of 8 FD symptoms (pain, fullness, bloating, early satiation, nausea, vomiting, belching & epigastric burning) was scored on a Likert scale [range: 0-3 (absent, mild, moderate, severe)]. First, hierarchical cluster analysis with Ward's clustering method was used to determine the most appropriate number of clusters for subsequent non-hierarchical cluster analysis. Second, non-hierarchical cluster analysis with full seed replacement was performed to determine the optimal cluster solution. Results: The median (IQR) score was 2 (0-2) for pain & early satiation, 2 (1-3) for fullness, 2 (1-2) for bloating, 1 (0-2) for nausea, belching & epigastric burning and 0 (0-1) for vomiting. Hierarchical cluster analysis suggested a 4 cluster solution, based on the R2 method. Non-hierarchical cluster analysis with 4 clusters on all 8 variables showed very low R2 values for the variable belching, indicating that it may no be sufficiently appropriate for forming clusters. Therefore, this variable was removed from the final analysis. Non-hierarchical cluster analysis with 4 clusters on the 7 remaining variables resulted in an overall R2 of 0.37, indicating considerable overlap between the clusters. Vomiting, pain and early satiation were found to be the most important variables separating the clusters, with R2 values of 0.67, 0.54 and 0.52, respectively. The first cluster was characterized by high early satiety, fullness & bloating and moderate pain (‘postprandial distress cluster'). The second cluster was characterized by high vomiting, nausea and fullness (‘nausea-vomiting cluster'). The third cluster was characterized by high pain (‘epigastric pain cluster'). The fourth cluster was characterized by low scores on all symptoms (‘limited severity cluster'). Conclusion: The symptom-based subgroups from the Rome III criteria are supported by the present data which confirmed the existence of EPS and PDS subgroups and a nausea/vomiting cluster. On the other hand, another ‘low severity” subgroup was also identiefied and overlap between subgroups is considerable.

P178 - A pilot study of elemental diet for chronic pouchitis

P178 - A pilot study of elemental diet for chronic pouchitis

Effect of Zinc Supplementation in Children with Acute Diarrhea: Randomized Double Blind Controlled Trial.

BackgroundTo test the hypothesis that daily supplementation of zinc has any effect on clinical course of acute diarrhea, i.e. frequency of stool, on stool amount and duration of acute diarrhea.MethodsIn a randomized double blind placebo controlled trial, 117 children aged 6 months to 59 months in a medical college hospital, with acute diarrhea of less than 14 days were assigned by permuted block design 1:1 to receive intervention of zinc supplemented syrup (n = 60) or placebo syrup (n = 57).ResultsBaseline characteristics were similar in both the groups. Mean age in zinc supplemented group was 22.14 ± 16.68 months and in placebo group 25.66 ± 17.02 months. Reduction in stool frequency per day was found 62% in zinc supplemented group and 26% reduction was found in placebo supplemented group with obvious difference of 36% between these two groups from day 1 to day 3 and day 5, which was found statistically highly significant. Similarly, significant difference was observed for reduction in amount of stool per day from day 1 to day 3 and day 5 with obvious difference of 45% between the study groups.ConclusionsOral zinc administration in acute diarrhea reduces the frequency of diarrhea and output of stool by changing the natural course of acute diarrheal disease, causes early normalization of stool consistency, early recovery and decreases total duration of hospital stay. Zinc supplementation is simple, acceptable and affordable strategy which should be considered in management of acute diarrhea.

Antimotility agents for chronic diarrhoea in people with HIV/AIDS

AIDS-related diarrhoea is a common cause of morbidity and mortality in HIV positive individuals, especially in the sub-Saharan Africa where 70% of deaths from HIV occur. It often compromises quality of life both in those receiving antiretroviral therapy (ART) and the ART naive. Empirical antidiarrhoeal treatment may be required in about 50% of cases which are non-pathogenic or idiopathic and in cases resulting from antiretroviral therapy. Antimotility agents (Loperamide, Diphenoxylate, Codeine) and adsorbents (Bismuth Subsalicylate, Kaolin/Pectin, Attapulgite) are readily available, and have been found to be useful in this condition and so, are often used. Antimotilitics are opioids, decreasing stool output by reducing bowel activity thereby increasing fecal transit time in the gut, promoting fluid and electrolyte retention while adsorbents act by binding to fluids, toxins and other substances to improve stool consistency and eliminate the toxins. Due to its potential impact on the management of chronic diarrhoea in persons with HIV/AIDS, we reviewed the effectiveness of antimotility agents in controlling chronic diarrhoea in immunocompromised states caused by HIV/AIDS. To assess the effectiveness of antimotility agents in controlling chronic diarrhoea in people with HIV/AIDS. We searched Medline, EMBASE, the Cochrane Controlled Trials Register, the Cochrane HIV/AIDS Register and AIDSearch databases in November 2006. We also contacted WHO, CDC, pharmaceutical companies and experts in the field for information on previous or on-going trials and checked reference list from retrieved studies, irrespective of language and publication status. Randomised controlled trials comparing an antimotility agent or an adsorbent with another antimotility agent, placebo, an adsorbent or no treatment in children and adults diagnosed with HIV and presenting with diarrhoea of three or more weeks duration. Two authors independently undertook study selection and examined full articles of potentially eligible studies. One trial was found assessing the use of an adsorbent (attapulgite) compared to a placebo for chronic diarrhoea in people with HIV/AIDS. It included 91 adults (Aged 18 to 60), diagnosed with AIDS and experiencing diarrhoea for at least 7 days. There was no evidence that attapulgite is superior to placebo in controlling diarrhoea by reducing stool frequency and normalising stool consistency on days 1 (0.34 (95% CI 0.01 - 8.15)), 3 (1.35 (95% CI 0.51 - 3.62)) and 5 (1.74 (95% CI 0.89 - 3.38)). This was a small trial and may not have had enough power to show evidence of effects. Five deaths were reported which was not classified according to the arms of the study.Studies assessing the use of antimotility agents were not found. This review highlights the absence of evidence for the use of antimotility agents and adsorbents in controlling diarrhoea in people with HIV/AIDS. While no trials assessing the use of Antimotilitics were found, the retrieved study showed that attapulgite was not better than placebo in controlling diarrhoea in HIV/AIDS patients . For optimum patient care, these agents can still be used, with greater emphasis placed on adjunct therapies like massive fluid replacement while evidence for practice is awaited from further studies and reviews.

Medical Prevention and Treatment of Acute and Chronic Radiation Induced Enteritis - Is there any Proven Therapy? A short Review.

Radiation enteritis is a severe problem in patients receiving irradiation of the abdomen or pelvis in the course of cancer treatment. Nevertheless, there is a lack of standardised strategies for medical prevention and therapy. A PubMed based literature search was performed to address the available data on the prevention of and therapy for acute and chronic radiation enteritis. Four double-blind and placebo-controlled studies used 5-aminosalycilates in the prevention of acute radiation enteritis. Only for sulphasalzine 2 g/d was a positive effect proven. Prophylactic administration of probiotics reduced the incidence of acute radiation enteritis in a large placebo-controlled trial. If acute radiation enteritis was present octreotide ameliorated radiation-induced diarrhoea in a randomised study. Two investigations, only one of them randomised, described the effectiveness of loperamide in the treatment of acute radiation enteritis. If diarrhoea was also the main symptom of chronic radiation enteritis, loperamide reduced stool frequency in a double-blind and placebo-controlled study. A retrospective analysis of severe cases of chronic radiation enteritis with obstruction and fistula indicated that parenteral nutrition at home was more effective than surgery. Reduction of radiation dose and field size are still the most important factors in the prevention of acute and chronic radiation enteritis. Valid data particularly on the treatment of chronic radiation enteritis are lacking. A better understanding of the pathopysiology especially in chronic radiation enteritis might offer new therapeutic perspectives. Inhibition of TGF-beta, for example, might be a new promising therapy approach.

ZENTASE, A NOVEL PANCREATIC ENZYME PRODUCT (PEP), IS SAFE AND EFFECTIVE IN MILD, MODERATE, AND AGGRESSIVE EXOCRINE PANCREATIC INSUFFICIENCY (EPI)

Background: PEP therapy helps prevent maldigestion and malabsorption in patients with EPI. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of Zentase (EUR-1008), a novel, zero-overfill, highly-stable formulation of porcine-derived pancreatic enzymes, in cystic fibrosis (CF) patients with EPI. Methods: Patients had confirmed CF and EPI, age ≥7 years, fecal elastase < 100 ng/g good nutritional status and weight ≤ 70 kg. Patients with a coefficient of fat absorption (CFA) > 80% were included. No drugs affecting gastric pH or motility were allowed. After open-label dose titration, patients were randomized to one week of Zentase or placebo. Following another open-label normalization, patients were crossed over to the alternative treatment arm. The primary endpoint was change in CFA following oral administration of Zentase vs. placebo. Secondary endpoints included change in coefficient of nitrogen absorption (CNA), cholesterol, fat soluble vitamins, and malabsorption signs and symptoms. Safety was also evaluated. Results: Thirty-four patients were enrolled (mean age 15.4 years); 32 were evaluated. Zentase treatment was associated with significant increases in both CFA and CNA vs. placebo (P < 0.001), improved vitamin K status and improvement in malabsorption signs and symptoms, including a statistically significant reduction in stool frequency and fewer soft/watery stools. Zentase treatment improved signs and symptoms of malabsorption regardless of EPI severity, including in patients with CFA values > 80% on placebo treatment. A positive correlation was observed between Zentase dose and response, particularly in patients with abnormal stool at baseline. Zentase was safe and well-tolerated, with no unexpected or significant differences in the frequency or type of AEs between Zentase and placebo. Two serious AEs were considered unrelated to the study drug and both resolved. Conclusion: In this Phase III study, Zentase, a novel PEP, was safe, well tolerated and effective in the treatment of EPI, with clinically and statistically significant improvements in CFA, CNA, and malabsorption signs and symptoms in the absence of any concomitant treatment affecting gastrointestinal motility and pH. The therapeutic benefit of Zentase was seen in patients with mild EPI (CFA values >80% on placebo), as well as in patients with moderate and aggressive disease.

Pilot study on the effect of reducing dietary FODMAP intake on bowel function in patients without a colon

Poorly absorbed short-chain carbohydrates (FODMAPs) in the diet should, by virtue of their osmotic effects, increase fecal output following colectomy and ileal pouch formation or ileorectal anastomosis (IRA). The aim was to perform a proof-of-concept evaluation of this hypothesis. Fifteen patients (13 pouch, 2 IRA) had dietary and symptomatic evaluation before and during a low FODMAP diet. Carbohydrate malabsorption was evaluated by breath tests. Pouchitis was assessed clinically/endoscopically or by fecal lactoferrin. Of 8 patients with a breath hydrogen response to lactulose, 7 had fructose malabsorption, 3 with lactose malabsorption, and 1 had lactose malabsorption alone. Five of 7 studied retrospectively improved stool frequency (from median 8 to 4 per day; P = 0.02), this being sustained over 0.5-3 years of follow-up. Five of 8 patients completed a prospective arm of the study. One patient had sustained improvement in stool frequency and 1 had reduced wind production. Overall, none of 8 patients who had pouchitis improved. In contrast, median daily stool frequency fell from 8 to 4 (P = 0.001) in the 7 without pouchitis. The degree of change in FODMAP intake also predicted response. There was a tendency for pouchitis to be associated with low baseline FODMAP intake. There is a high prevalence of carbohydrate malabsorption in these patients. Reduction of the intake of FODMAPs may be efficacious in reducing stool frequency in patients without pouchitis, depending on dietary adherence and baseline diet.

Patterns of constipation in urogynecology: Clinical importance and pathophysiologic insights

We have analyzed the prevalence and patterns of constipation in women with urinary symptoms and/or genital prolapse. Seven hundred and eighty-six consecutive urogynecologic patients underwent a questionnaire and structured clinical assessment. Comparison between constipated and nonconstipated women was made. Fisher exact test, Wilcoxon rank sum test, and logistic regression were used for statistical analysis (P < .05 for significance). Thirty-two percent of women were constipated (172 difficult stool passage, 13 reduced stool frequency, 64 both). A genital prolapse > or = 2 degree Half Way System (HWS) was present in 44% of women. A posterior colpocele was more frequent in constipated women (35% vs 19%; P < .0001), resulting in a risk factor for constipation (OR 2.31; 95% CI 1.63-3.27). By contrast, higher degrees of anterior colpocele appeared to protect against constipation (OR 0.80; 95% CI 0.66-0.96). No differences in prevalence of constipation were observed for urinary symptoms or urodynamic diagnosis. Bowel dysfunction correlates exclusively with posterior aspects of the pelvic floor support.