Spirulina Platensis Attenuates Rebound Dyspeptic Symptoms After Proton Pump Inhibitors' Discontinuation: Phase 2 Placebo-controlled Trial.

Context: Rebound acid hypersecretion after cessation of proton pump inhibitors (PPIs) can provoke dyspeptic symptoms. The search for alternatives to minimize the dyspeptic rebound symptoms after PPI discontinuation is warranted. Spirulina platensis, a dietary supplement made from blue-green algae, might be an alternative. Objective: The study intended to assess whether Spirulina platensis, through its anti-inflammatory and analgesic properties, can minimize rebound symptoms after PPI withdrawal. Design: The research team performed a randomized, phase 2, double-blinded, placebo-controlled clinical trial. Setting: The study took place at São Vicente de Paulo Hospital (trial registry number NCT04988347) in Passo Fundo, Brazil. Participants: Participants were 45 Brazilian patients in the clinical practice of two of the research team's member between November 2010 and February 2012, who were using PPIs regularly. Interventions: Participants underwent clinical and endoscopic evaluations after a 28-day run-in phase of 40 mg/day of pantoprazole. In the absence of a large hiatal hernia, peptic ulcer, or severe reflux esophagitis, participants stopped using PPIs, and the research team randomly assigned them to receive either 1.6g/day of spirulina or of a placebo for two months, followed by clinical and endoscopic reevaluations. Outcome measures: Using an intention-to-treat analysis, the primary outcomes postintervention were dyspepsia and typical reflux symptoms, either the appearance or maintenance of symptoms of >50% from baseline. Results: The median time of continuous PPI use was 32 months. The research team excluded two participants due to large hiatal hernias. Among the remaining 43 participants, 18 received spirulina (42%), and 25 used a placebo (58%). Two months later, 12 participants who had received spirulina (67%) and 18 who had received the placebo (72%) completed the study (P = .968). Rebound dyspepsia occurred in 10 out of 18 patients treated with spirulina (55.56%) and in 22 out of 25 patients treated with placebo (88%), with relative risk=0.63, CI95% (0.41-0.98), and P = .039. Reflux symptoms postintervention occurred in 72% and 76%, with the relative risk=0.95, CI95% (0.66-1.36), and P > .05, respectively. No significant side effects occurred in either group. The findings from endoscopy and gastric histology didn't differ between groups. Conclusions: A two-month course of Spirulina platensis was able to attenuate rebound dyspepsia but not reflux symptoms after PPI discontinuation. Considering its good safety profile, spirulina might be useful to relieve dyspeptic symptoms after PPI discontinuation.

Efficacy of Helicobacter pylori eradication therapy for treatment of functional dyspepsia: A protocol for systematic review and meta-analysis.

OBJECTIVE: The effect of Helicobacter pylori (H pylori) eradication therapy in functional dyspepsia (FD) patients was inconsistent in previously published randomized controlled trials. Therefore, we performed a comprehensive protocol for systematic review and meta-analysis in order to assess whether H pylori eradication therapy benefits patients with FD. METHODS: In this systematic review and meta-analysis, we will search Web of Science, Embase, PubMed, Wanfang Data, Medline, Science Direct, Cochrane Library through April, 2021. The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Data extraction was performed independently and only randomized clinical trials were included in this study. The risk of bias assessment was performed using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions. All calculations were carried out with Stata 11.0 (The Cochrane Collaboration, Oxford, United Kingdom). RESULTS: We hypothesized that H pylori eradication therapy compared to no eradication therapy has a statistically significant benefit for symptom relief and can also reduce the development of peptic ulcer disease. CONCLUSION: This study expects to provide credible and scientific evidence for the efficacy of H pylori eradication therapy for patients with FD. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/4EHRB.

Carbohydrate Hydrogel Products Do Not Improve Performance or Gastrointestinal Distress During Moderate-Intensity Endurance Exercise.

The benefits of ingesting exogenous carbohydrate (CHO) during prolonged exercise performance are well established. A recent food technology innovation has seen sodium alginate and pectin included in solutions of multiple transportable CHO, to encapsulate them at pH levels found in the stomach. Marketing claims include enhanced gastric emptying and delivery of CHO to the muscle with less gastrointestinal distress, leading to better sports performance. Emerging literature around such claims was identified by searching electronic databases; inclusion criteria were randomized controlled trials investigating metabolic and/or exercise performance parameters during endurance exercise >1 hr, with CHO hydrogels versus traditional CHO fluids and/or noncaloric hydrogels. Limitations associated with the heterogeneity of exercise protocols and control comparisons are noted. To date, improvements in exercise performance/capacity have not been clearly demonstrated with ingestion of CHO hydrogels above traditional CHO fluids. Studies utilizing isotopic tracers demonstrate similar rates of exogenous CHO oxidation, and subjective ratings of gastrointestinal distress do not appear to be different. Overall, data do not support any metabolic or performance advantages to exogenous CHO delivery in hydrogel form over traditional CHO preparations; although, one study demonstrates a possible glycogen sparing effect. The authors note that the current literature has largely failed to investigate the conditions under which maximal CHO availability is needed; high-performance athletes undertaking prolonged events at high relative and absolute exercise intensities. Although investigations are needed to better target the testimonials provided about CHO hydrogels, current evidence suggests that they are similar in outcome and a benefit to traditional CHO sources.

Functional dyspepsia is associated with lower exercise levels: A population-based study.

BACKGROUND: Exercise improves symptoms of irritable bowel syndrome, but few data are available about functional dyspepsia. We compared the prevalence and frequency of different types of exercise between individuals with functional dyspepsia and general population controls. METHODS: A mailed survey was returned by 3160 people randomly obtained from the Australian electoral register. The survey included questions to identify the Rome III diagnosis for functional dyspepsia. Exercise was classified by the presence (yes or no) and the frequency (number of times) spent walking, and engaging in moderate and vigorous exercise, over the last 2 weeks based on the National Health Survey. Controls did not meet criteria for functional dyspepsia. Potential confounders included the presence of irritable bowel syndrome, smoking, body mass index, age and gender. RESULTS: A total of 14.8% (95% confidence interval (CI) 13.6%, 16.1%) subjects had functional dyspepsia. They reported significantly less walking (57% versus 63%, P = 0.04) and lower frequency of exercising, in terms of walking (P = 0.008) and engaging in moderate (P = 0.03) and vigorous activity (P = 0.02), compared with controls. The association remained significant for moderate exercise, independent of age, gender, body mass index and smoking, and excluding overlap with irritable bowel syndrome (odds ratio (OR) = 0.94 (95% CI 0.88, 0.99), P = 0.02). Postprandial distress syndrome was associated with less-vigorous exercise adjusting for confounders (OR = 0.65 (95% CI 0.42, 1.0), P = 0.05), but not epigastric pain syndrome. CONCLUSION: Functional dyspepsia is associated with lower exercise levels, but the causality still needs to be determined.

Characteristics and Predictive Factor of Helicobacter pylori-Associated Functional Dyspepsia in Japanese Patients.

BACKGROUND/AIM: Helicobacter pylori (HP) eradication therapy was first recommended as pharmacotherapy for functional dyspepsia (FD). However, the mechanism and effect of eradication on FD symptom improvement have not been fully investigated. This study aimed to investigate the pathology of patients with HP-associated FD, and predictive factors for HP-associated FD. METHODS: Ninety-seven patients with chronic gastritis caused by HP infection were divided into the group with FD symptoms and the group -without FD symptoms. Patient backgrounds, QOL, gastric mucosal atrophy severity, and serum pepsinogen (PG) value were compared between the 2 groups. Twelve months after eradication, those factors were evaluated between HP-associated FD and HP-non-associated FD, and predictive factors of HP-associated FD were analyzed. RESULTS: The FD-positive group existed in 45 (46.3%) out of 97 patients. Twelve months after eradication, there were 34 patients (75.6%) in the HP-associated FD. The mean PG I value in the HP-associated FD was significantly lower than that in the HP-non-associated FD, while the PG II values in the HP-associated FD tended to be lower than those in the HP-non-associated FD. QOL in the HP-associated FD significantly improved after HP eradication. On multivariate logistic regression analysis, it was found that PG II value was a significant predictive factor for FD symptom improvement in the HP-associated FD. CONCLUSION: HP eradication is an effective initial therapy for FD. PG II value is considered a predictive factor for FD symptom improvement through HP eradication.

Cost-effectiveness analysis of screen-and-treat strategy in asymptomatic Chinese for preventing Helicobacter pylori-associated diseases.

BACKGROUND: The high prevalence of Helicobacter pylori (H pylori) infection in China results in a substantial public health burden. Medical experts have not agreed on the best solution of population intervention for this problem. We presented a health economic evaluation of a population-based H pylori screen-and-treat strategy for preventing gastric cancer, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). MATERIALS AND METHODS: Decision trees and Markov models were developed to evaluate the cost-effectiveness of H pylori screening followed by eradication treatment in asymptomatic Chinese. The modeled screen-and-treat strategy reduced the risk of gastric cancer, PUD, and NUD. The main outcomes were the costs, effectiveness, and the incremental cost-effectiveness ratio. Uncertainty was explored by one-way and probabilistic sensitivity analyses. RESULTS: For preventing gastric cancer, PUD, and NUD together in a cohort of 10 million asymptomatic Chinese at the age of 20 years, the H pylori screen-and-treat strategy saved 288.1 million dollars, 28 989 life years, and 111 663 quality-adjusted life years, and prevented 11 611 gastric cancers, 5422 deaths from gastric cancer, and 1854 deaths from PUD during life expectancy. Uncertainty of screening age from 20 to 60 did not affect the superiority of the screen-and-treat strategy over the no-screen strategy. The one-way and probabilistic sensitivity analyses confirmed the robustness of our study's results. CONCLUSIONS: Compared with the no-screen strategy, population-based screen-and-treat strategy for H pylori infection proved cheaper and more effective for preventing gastric cancer, PUD, and NUD in Chinese asymptomatic general population.

Dyspepsia in non-steroidal anti-inflammatory drug users and the effect of preventive measures.

OBJECTIVE: To evaluate regular non-steroidal anti-inflammatory drug (NSAID) users for dyspepsia, as well as to assess the effect of preventive measures, and the reasons for non-adherence to gastroprotective agents (GPA) from a real-world perspective. METHODS: A prospective longitudinal study was conducted among outpatients with regular NSAID usage. The presence of dyspepsia was assessed by locally validated versions of the Leeds dyspepsia questionnaire (LDQ), GPA and the participants' adherence to the drugs were assessed at recruitment and 2 weeks later. GPA was defined as the use of antisecretory medications or cyclooxygenase-2 inhibitors. RESULTS: Initially, 409 participants (mean age 52.3 ± 14.6 years, 60.6% females, 48.4% treated for musculoskeletal pain) were recruited. At recruitment, 50.9% of the participants had at least one upper gastrointestinal symptom. Complete data for follow-up analysis were collected from 158 participants who were naive NSAID users, had no prior gastrointestinal medication and who could be contacted. At 2-week follow-up there was no significant difference in the LDQ score change between NSAID users treated with GPA and those did not. However, there was a greater reduction in abdominal pain/discomfort (8.8% vs 5.0%, P < 0.001) and burping (8.8% vs 4.0%, P < 0.001) among participants using GPA compared with those who were not. Adherence to GPA was poor, with study participants citing the absence of gastrointestinal symptoms as their main reason for non-adherence. CONCLUSIONS: The use of GPA in patients on regular NSAIDs does not improve their overall dyspepsia, but it reduces abdominal pain and burping. Poor adherence to GPA may be a contributing factor.

The effects of helicobacter pylori eradication on modification of metabolic syndrome parameters in patients with functional dyspepsia.

BACKGROUND: Helicobactor pylori (H. pylori) have the potential role in the pathogenesis of various extra-gastric disorders such as metabolic disorders. But, it is now questioned about whether H. pylori eradication reduces or induces the risk for metabolic disorders especially in patients with dyspepsia. Hence, the present study aimed to assess the effects of H. pylori eradication on criteria of metabolic syndrome. METHODS: H. pylori infected patients with dyspepsia were included. The patients were treated with omeprazole (20mg, q12h), amoxicillin (1g, q12h), and clarithromycin (500mg, q12h) for two weeks, then H. pylori eradication was evaluated by C14 Breathing test (UBT) 6 weeks after the end of the treatment. Demographic data, clinical manifestation and metabolic parameters were recorded before and three months after completing treatment regimen. The data was analyzed by SPSS version 16.0. RESULTS: Of 110 patients were initially enrolled, 91 patients completed the study. Overall eradication rate was 61.5%. Significant differences in the serum level of total cholesterol(180.7±34 vs. 172.1±28, p=0.001), LDL(107.0±25 vs. 100.8±20, p<0.001), HDL(46.2±8.7 vs. 48.9±8.6, p<0.001), fasting blood sugar (93.7±12 vs. 90.9±10, p=0.001), hemoglobin A1c(5.37±0.52 vs 5.25±0.53, p=0.006), and as well as for waist circumference(92.2±14 vs. 91.4±13.9, p=0.03) was found after treatment. Data for body weight, systolic and diastolic blood pressure and triglyceride level remained without any significant changes. CONCLUSION: H. pylori eradication could relatively reduce the risk of metabolic syndrome criteria such as fasting blood sugar, hemoglobin A1c, lipid profile and waist circumference.

Quality of life and impact of bile reflux after retro colic retro gastric gastrojejunostomy in Whipple surgery.

BACKGROUND: Delayed gastric emptying and bile reflux are common concerns in long-term survivors after Whipple surgery. The study was designed to assess modified retro colic retro gastric gastrojejunostomy in reducing macro and microscopic bile reflux and impact on dyspepsia related quality of life in long-term survivors. METHODS: Out of 43 patients operated, 23 long-term survivors were included. All underwent gastroscopy and bile reflux was grouped as normal, yellowish bile lakes and presence of greenish bile lakes. Six standard gastric biopsies were taken. Microscopic bile reflux index (BRI) was calculated and a score more than 14 was considered significant. Validated Nepean dyspepsia index-short form (NDI-SF) was used to assess the severity of dyspepsia-related quality of life and compared with age and gender-matched control. RESULTS: The median age was 48 (21-70) years. Median survival of the group was 37 months (6-40). Endoscopically, 20/23 (87%) had macroscopic bile reflux (74% yellowish bile lakes, 13% greenish bile lakes). None had stomal ulcers or macroscopic inflammation. Mean bile reflux index score was 9.7 (range 1.77-34). Mean NDI-SF score of Whipple group was 23.1 (SD 8.88). In controls, mean score was 19.9 (SD 8.23), showing no significant difference (p = 0.245). CONCLUSIONS: Though there was macroscopic bile reflux, clinical symptoms and microscopic changes were minimal. The modified technique had good long-term results.

Tablet and oral liquid L-thyroxine formulation in the treatment of naïve hypothyroid patients with Helicobacter pylori infection.

To compare the clinical efficacy of tablet and oral liquid L-thyroxine (LT4) formulation in naïve hypothyroid subjects with Helicobacter pylori infection. Forty-seven adult naïve hypothyroid subjects with dyspeptic symptoms were investigated with upper endoscopy and divided into: 28 patients with Helicobacter pylori infection (Group A); 15 patients without gastric alterations (group B); 4 patients with autoimmune gastritis were excluded from the study. Subjects were randomly treated with a same dose of LT4 tablet (TAB) or oral liquid formulation (SOL), for 9 months on group A and 6 months on group B. Helicobacter pylori infection was eradicated after 3 months of LT4 treatment. On group A, after 3 months (before Helicobacter pylori eradication), subjects treated with SOL showed a greater thyroid-stimulating hormone reduction (ΔTSH3-0: TAB = -4.1 ± 4.6 mU/L; SOL = -7.7 ± 2.5 mU/L; p = 0.029) and a greater homogeneity in the thyroid-stimulating hormone values (TSH3mo: TAB = 5.7 ± 4.9 mU/L; SOL = 4.1 ± 2.0 mU/L; p = 0.025), compared to LT4 tablet. At 9 months (after 6 months of Helicobacter pylori eradication) mean thyroid-stimulating hormone values were lower in subjects treated with LT4 tablet (TSH9mo: TAB = 1.8 ± 1.2 mU/L; SOL = 3.2 ± 1.7 mU/L; p = 0.006). On group B no difference were observed, at each time point, in the mean thyroid-stimulating hormone values and thyroid-stimulating hormone variations between two LT4 formulations. LT4 liquid formulation may produce a better clinical response compared to the tablet formulation in hypothyroid subjects with Helicobacter pylori infection.

Randomised trial of the effect of a gastrin/CCK2 receptor antagonist on esomeprazole-induced hypergastrinaemia: evidence against rebound hyperacidity.

PURPOSE: Hypergastrinaemia induced by proton pump inhibitor (PPI) therapy may cause ECL-cell and parietal-cell hyperplasia and rebound hyperacidity and dyspepsia after PPI withdrawal. The aim of the study was to assess the effect of different dosage-regimens of netazepide, a gastrin/CCK2 receptor antagonist, on PPI-induced hypergastrinaemia and elevated chromogranin A (CgA). METHODS: Six groups of eight healthy subjects participated in a randomised, double-blind study of esomeprazole 40 mg daily for 28 days, in combination with netazepide 1, 5 or 25 mg or placebo, daily, during the last 14 days of esomeprazole or during 14 days after treatment withdrawal. Fasting serum gastrin and plasma CgA were measured during treatment and after withdrawal, as biomarkers of acid suppression and ECL-cell activity, respectively. Dyspepsia was monitored throughout the study. RESULTS: Esomeprazole increased gastrin and CgA. Netazepide increased gastrin, but not CgA, and inhibited dose dependently the CgA response to esomeprazole. Gastrin and CgA returned to baseline within 2-3 days of esomeprazole withdrawal; netazepide did not shorten that time. There was no rebound dyspepsia after esomeprazole withdrawal. CONCLUSIONS: Esomeprazole and netazepide each increase gastrin, consistent with a secondary effect of gastric acid suppression, but by different mechanisms. Esomeprazole-induced hypergastrinaemia stimulates ECL cells and thereby increases CgA. Netazepide-induced hypergastrinaemia does not increase CgA, because netazepide blocks gastrin/CCK2 receptors on ECL cells. Co-administration of netazepide 5 mg abolishes the effect of esomeprazole-induced hypergastrinaemia on ECL cells. The quick return to baseline of gastrin and CgA and absence of dyspepsia after esomeprazole withdrawal do not support the concept of rebound hyperacidity.

Probiotic administration among free-living older adults: a double blinded, randomized, placebo-controlled clinical trial.

BACKGROUND: Diseases of the digestive system have been found to contribute to a higher symptom burden in older adults. Thus, therapeutic strategies able to treat gastrointestinal discomfort might impact the overall health status and help older adults to increase their overall health status and optimal functionality. OBJECTIVE: The aim of this double-blinded, randomized, placebo-controlled clinical trial was to evaluate the effect of the probiotic strain Lactobacillus reuteri on digestive health and wellbeing in older adults. METHODS: The study enrolled general older adults (>65 years). After eligibility screening qualified subjects (n = 290) participated in a 2-arm study design, with each arm consisting of 12 weeks of intervention of either active or placebo product. Primary outcome measure was set to changes in gastrointestinal symptoms and secondary outcome measures were changes in level of wellbeing, anxiety and stress. Follow up was performed at 8 and 12 weeks. RESULTS: No persistent significant effects were observed on the primary or secondary outcome parameters of the study. A modest effect was observed in the probiotic arm, were levels of stress decreased at week 8 and 12. Similarly, we found that subjects suffering from indigestion and abdominal pain, respectively, showed a significant decrease of anxiety at week 8 after probiotic treatment, but not at week 12. CONCLUSION: The RCT failed to show any improvement in digestive health after daily intake of a probiotic supplement containing L. reuteri. Neither was any significant improvement in wellbeing, stress or anxiety observed. Even though the RCT had a negative outcome, the study highlights issues important to take into consideration when designing trials among older adults. TRIAL REGISTRATION: Clinicaltrials.gov/ NCT01837940 .

Gastrointestinal Symptoms in Celiac Disease Patients on a Long-Term Gluten-Free Diet.

Experience suggests that many celiac patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD). We investigated the prevalence and severity of these symptoms in patients with variable duration of GFD. Altogether, 856 patients were classified into untreated (n = 128), short-term GFD (1-2 years, n = 93) and long-term GFD (≥3 years, n = 635) groups. Analyses were made of clinical and histological data and dietary adherence. Symptoms were evaluated by the validated GSRS questionnaire. One-hundred-sixty healthy subjects comprised the control group. Further, the severity of symptoms was compared with that in peptic ulcer, reflux disease, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Altogether, 93% of the short-term and 94% of the long-term treated patients had a strict GFD and recovered mucosa. Untreated patients had more diarrhea, indigestion and abdominal pain than those on GFD and controls. There were no differences in symptoms between the short- and long-term GFD groups, but both yielded poorer GSRS total score than controls (p = 0.03 and p = 0.05, respectively). Furthermore, patients treated 1-2 years had more diarrhea (p = 0.03) and those treated >10 years more reflux (p = 0.04) than controls. Long-term treated celiac patients showed relatively mild symptoms compared with other gastrointestinal diseases. Based on our results, good response to GFD sustained in long-term follow-up, but not all patients reach the level of healthy individuals.

Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.

BACKGROUND: The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. OBJECTIVES: The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. METHODS: Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. RESULTS: Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. CONCLUSIONS: Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921).

An Investigation of the Acute Effects of Oligofructose-Enriched Inulin on Subjective Wellbeing, Mood and Cognitive Performance.

Inulin is a natural food component found in many plants that are part of the human diet (e.g., leeks, onions, wheat, garlic, chicory and artichokes). It is added to many foods and is used to increase dietary fibre, replace fats or carbohydrates, and as a prebiotic (a stimulant of beneficial bacteria in the colon). Oligofructose, which is also present in these foods, produces similar effects and most research has used a combination of these products. A previous study (Smith, 2005) investigated the effects of regular consumption of oligofructose-enriched inulin on wellbeing, mood, and cognitive performance in humans. The results showed that oligofructose-enriched inulin had no negative effects but that it did not improve wellbeing, mood, or performance. The aim of the present study was to examine the acute effects of oligofructose-enriched inulin (5 g) over a 4 h period during which the participants remained in the laboratory. A double blind placebo (maltodextrin) controlled study (N = 47) was carried out with the order of conditions being counterbalanced and the two sessions a week apart. On each test day mood and cognitive performance were assessed at baseline (at 8:00) and then following inulin or placebo (at 11:00). Prior to the second test session (at 10:30) participants completed a questionnaire assessing their physical symptoms and mental health during the test morning. The inulin and placebo were provided in powder form in 5 g sachets. Volunteers consumed one sachet in decaffeinated tea or decaffeinated coffee with breakfast (9:00). Questionnaire results showed that on the day that the inulin was consumed, participants felt happier, had less indigestion and were less hungry than when they consumed the placebo. As for performance and mood tasks, the most consistent effects were on the episodic memory tasks where consumption of inulin was associated with greater accuracy on a recognition memory task, and improved recall performance (immediate and delayed). Further research is required to identify the mechanisms that underlie this effect with glucose metabolism being one candidate.

[Drug-induced dyspepsia]. / Medikamenten-induzierte Oberbauchbeschwerden.

Gastrointestinal symptoms are among the most common side effects of drugs. There is a broad spectrum of symptoms. Patients often report upper abdominal pain, an early sense of satiety, epigastric discomfort or pain in the upper abdomen or behind the breastbone, flatulence, diarrhoea or constipation. Some of these symptoms are attributed to the stomach or upper abdomen by the patient and/or the physician. "Stomach pain", pain in the epigastric region, occurs in most cases in combination with other symptoms such as a feeling of pressure in the upper abdomen or bloating, early satiety, nausea or vomiting--a combination called dyspepsia. Given the high frequency of these symptoms in the general population and the large number of medications many patients are taking, it can be very difficult in a given patient to differentiate between drug-induced side effects and spontaneously occurring symptoms.

Lipase Supplementation before a High-Fat Meal Reduces Perceptions of Fullness in Healthy Subjects.

BACKGROUND/AIMS: Postprandial symptoms of fullness and abdominal discomfort are common after fatty meals. Gastric lipases hydrolyze 10% to 20% of dietary triglycerides during the stomach trituration period of digestion. The aim of this study was to evaluate the effects of acid-resistant lipase on upper gastrointestinal symptoms, including fullness and bloating, as well as on gastric myoelectrical activity after healthy subjects ingested a high-fat, liquid meal. METHODS: This study utilized a double-blind, placebo-controlled, crossover design with 16 healthy volunteers who ingested either a capsule containing 280 mg of acid-resistant lipase or a placebo immediately before a fatty meal (355 calories, 55% fat). Participants rated their stomach fullness, bloating, and nausea before and at timed intervals for 60 minutes after the meal. Electrogastrograms were obtained to assess the gastric myoelectrical activity. RESULTS: Stomach fullness, bloating, and nausea increased significantly 10 minutes after ingestion of the fatty meal (p<0.01), whereas normal gastric myoelectrical activity decreased and tachygastria increased (p<0.05). With lipase, reports of stomach fullness were significantly lower compared with placebo (p<0.05), but no effect on gastric myoelectrical activity or other upper gastrointestinal symptoms was observed. CONCLUSIONS: The high-fat meal induced transient fullness, bloating, nausea, and tachygastria in healthy individuals, consistent with postprandial distress syndrome. Acid-resistant lipase supplementation significantly decreased stomach fullness.

One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension.

OBJECTIVE: To evaluate the safety of the fixed combination of ibuprofen and famotidine compared with ibuprofen alone from two 24-week, multicenter, double-blind trials designed to evaluate the comparative incidence of endoscopically documented upper gastrointestinal ulcers and a 28-week double-blind extension study. RESEARCH DESIGN AND METHODS: Safety was analyzed by pooling data from the two double-blind trials and the follow-on study. Safety was assessed by monitoring the incidence, causality, and severity of adverse events (AEs). RESULTS: In the pivotal efficacy and safety trials, discontinuation rates due to any cause and dyspepsia were significantly lower for the ibuprofen/famotidine combination versus ibuprofen alone. Other than dyspepsia, gastrointestinal and cardiovascular AEs of special interest were similar. Events judged to be treatment related were significantly lower with the ibuprofen/famotidine combination (20.6% vs. 25%). In the safety extension population, there were no differences in the discontinuation rates and the reporting of AEs or serious AEs (SAEs) between the two groups. Gastrointestinal-related events were similar between the groups. Incidence of cardiovascular-related AEs of special interest were 11% (ibuprofen/famotidine) and 2% (ibuprofen) (p=0.06), possibly due to a higher number of rheumatoid arthritis patients in the combination group. Of these, 80% were reports of hypertension (8% ibuprofen/famotidine vs. 2% ibuprofen). Three cases of hypertension in the ibuprofen/famotidine group were considered treatment related. The probability of a cardiovascular event decreased during days 112-167 of treatment and remained low with continued treatment. CONCLUSIONS: One-year safety data from two pivotal trials and a long-term extension study indicate that the ibuprofen/famotidine combination demonstrates a favorable gastrointestinal safety profile and more patients continued on therapy compared to ibuprofen alone. No new safety signals have been identified. These data offer additional evidence supporting a new therapeutic option to improve gastrointestinal safety and adherence for patients who require long-term ibuprofen.

One-year open-label safety evaluation of the fixed combination of ibuprofen and famotidine with a prospective analysis of dyspepsia.

OBJECTIVE: To assess the long-term safety of the single-tablet combination of ibuprofen 800 mg and famotidine 26.6 mg. RESEARCH DESIGN AND METHODS: A phase 3b open-label study (NCT00984815) was conducted in 86 adults requiring daily non-steroidal anti-inflammatory drug (NSAID) administration for ≥12 months. The combination tablet of ibuprofen/famotidine was self-administered orally three times daily for up to 54 consecutive weeks. Adverse events (AEs) were collected beginning at the first dose and continued through completion (54 weeks). The Severity of Dyspepsia Assessment (SODA) questionnaire was completed by patients to assess tolerability. RESULTS: Most patients (65%) finished the trial, with 76% contributing data at 6 months, and 21% withdrew due to adverse effects. Overall and gastrointestinal AE discontinuation rates (21% and 13%, respectively) were lower than that previously reported with ibuprofen 2400 mg given alone. Each of the SODA subscale scores demonstrated improvement by week 6 and improved statistically significantly at week 24 and week 54. Of the cardiovascular AEs, hypertension was reported most frequently (9/86, 9.3%), with 3.5% determined to be drug related. Twelve serious AEs were reported by 9 of 86 (10%) patients; two were considered possibly related to the study medication (unstable angina and gastric ulcer). There were no reports of serious gastrointestinal or CV complications. Most AEs were mild or moderate in severity and not considered drug related. CONCLUSIONS: These data, together with previously reported findings of a significant decrease in upper gastrointestinal endoscopic ulcer rate at 6 months, support the overall safety, compliance, and tolerability of this single-tablet formulation.