Efficacy and Safety of STW 5-II for Functional Dyspepsia Treatment: A Patient Data-Based Meta-Analysis.

INTRODUCTION: Functional dyspepsia (FD) is a chronic relapsing gastroduodenal disorder with limited treatment options. Herbal products, like the six-herb combination STW 5-II, can target multiple FD gastrointestinal symptoms. In this meta-analysis, we evaluated the efficacy and safety of STW 5-II for overall FD, and key symptoms, based on Rome IV criteria. METHODS: We systematically screened the literature for randomized controlled clinical studies testing STW 5-II in FD. Meta-analysis was performed using data from individual patients with at least one key FD symptom (fullness, early satiety, or epigastric pain) of at least moderate severity at baseline. ANCOVA-based meta-analyses were performed on improvements in the total symptom sum score, and single symptoms, after 4 and 8 weeks. Safety data were analyzed by calculating odds ratios for all adverse events. RESULTS: Four randomized controlled trials, including 613 patients, were identified, and two were eligible for efficacy analysis. STW 5-II significantly improved the FD symptom sum score (mean difference of 1.74 after 4 weeks and 2.07 after 8 weeks) and key FD symptoms of fullness (0.28 and 0.29), early satiety (0.25 and 0.26), and epigastric/upper abdominal pain (0.26 and 0.3). Treatment-related or severe adverse events did not differ between STW 5-II and placebo. CONCLUSION: The results support that STW 5-II significantly improves FD symptoms after 4 and 8 weeks of treatment with no difference in relation to safety signals compared to placebo. Thus, STW 5-II can be considered an effective and safe treatment option for FD.

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.

Functional Abdominal Cramping Pain: Expert Practical Guidance.

Functional abdominal cramping pain (FACP) is a common complaint, which may present either on its own or in association with a functional gastrointestinal disorder. It is likely caused by a variety of, probably partly unknown, etiologies. Effective management of FACP can be challenging owing to the lack of usable diagnostic tools and the availability of a diverse range of treatment approaches. Practical guidance for their selection and use is limited. The objective of this article is to present a working definition of FACP based on expert consensus, and to propose practical strategies for the diagnosis and management of this condition for physicians, pharmacists, and patients. A panel of experts on functional gastrointestinal disorders was convened to participate in workshop activities aimed at defining FACP and agreeing upon a recommended sequence of diagnostic criteria and management recommendations. The key principles forming the foundation of the definition of FACP and suggested management algorithms include the primacy of cramping pain as the distinguishing symptom; the importance of recognizing and acting upon alarm signals of potential structural disease; the recognition of known causes that might be addressed through lifestyle adjustment; and the central role of antispasmodics in the treatment of FACP. The proposed algorithm is intended to assist physicians in reaching a meaningful diagnostic endpoint based on patient-reported symptoms of FACP. We also discuss how this algorithm may be adapted for use by pharmacists and patients.

[Psychosocial Support for People with Ulcerative Colitis and Irritable Bowel Syndrome: A Feasibility Study on Need, Focus and Viability]. / Psychosoziale Unterstützung von Menschen mit Colitis ulcerosa und Reizdarmsyndrom: eine Machbarkeitsstudie zu Bedarf, Fokus und Durchführbarkeit.

OBJECTIVES: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are associated with high somatic symptom burden, reduced quality of life, and increased psychological distress. The subjective burden, the wish of many patients, and the involvement of psychological processes in symptom perception justify the development of psychosocial support services. We aimed to evaluate need, content and feasibility of such an offer. We included patients with both UC and RDS in order to identify disease-specific and trans-diagnostic aspects for psychosocial interventions. METHODS: We conducted telephone interviews with adult patients with UC or IBS using a standardized interview guide. We used numerical rating scales and open-ended questions to assess burden of and coping with the disease, disease-related expectations and anxiety, satisfaction with care, support and information needs, and preferences regarding support programs. We calculated descriptive metrics for quantitative variables as well as diagnosis-specific group comparisons. The answers to the open questions were summarised and counted in close accordance with the participants' statements. RESULTS: N=35 patients (UC: n = 15; IBS: n=20) participated (age: M=40.80, SD=14.56; 71% female). In both groups, patients showed a medium level of disease burden, with higher rates for IBS. Both groups reported disease-related anxiety, with higher levels in patients with IBS. Disease-related expectations did not differ between groups. Patients with IBS showed low satisfaction with care and felt less informed about their disease than patients with UC. Both groups indicated a high motivation of participating in a psychological support program and named illness-related expectations and illness anxiety as important components of such. DISCUSSION: The results confirm an increased need for psychosocial support and the relevance of disease-related expectations and anxiety for both diseases. Differences in symptom perception and care satisfaction indicate the importance of disease-specific elements in psychosocial therapy programs. CONCLUSION: The results demonstrate the high need for psychosocial support of patients with UC and IBS and indicate the feasibility of a psychosocial therapy program.

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

Efficacy and tolerability of linaclotide in the treatment of irritable bowel syndrome with constipation in a real­world setting - results from a German noninterventional study.

BACKGROUND: Linaclotide is a minimally absorbed peptide guanylate cyclase-C agonist approved for the treatment of irritable bowel syndrome with constipation (IBS-C). This study assessed the efficacy and tolerability of linaclotide in IBS-C in routine clinical practice in Germany. METHODS: This was a 52-week, noninterventional study of linaclotide in patients aged ≥ 18 years with moderate to severe IBS-C. Severity of abdominal pain and bloating and frequency of bowel movements were assessed over 5 study visits. Treatment-related adverse events were recorded. RESULTS: The study enrolled 375 patients; the mean observation duration was 4.4 months. Linaclotide marketing was halted during the study period for economic reasons, accounting for low patient numbers and short observation duration. Linaclotide significantly reduced mean (standard deviation [SD]) scores between treatment start (visit 1) and study end (visit 5) for abdominal pain intensity (visit 1: 4.87 [2.63] vs. visit 5: 2.40 [2.20], p < 0.0001), mean [SD] bloating intensity (visit 1: 5.30 [2.70] vs. visit 5: 2.86 [2.34], p < 0.0001), and increased mean [SD] bowel movement frequency (visit 1: 2.71 [1.80] vs. 4.38 [1.86], p < 0.0001). Diarrhea, occurring in 5.1 % of patients, was the most common adverse event. CONCLUSION: Linaclotide is effective in improving the major symptoms of IBS-C and demonstrates a favorable safety profile in the real-world environment of routine clinical practice. DRKS (www.drks.de/): DRKS00005088.

Pharmacological, Pharmacokinetic, and Pharmacogenomic Aspects of Functional Gastrointestinal Disorders.

This article reviews medications commonly used for the treatment of patients with functional gastrointestinal disorders. Specifically, we review the animal models that have been validated for the study of drug effects on sensation and motility; the preclinical pharmacology, pharmacokinetics, and toxicology usually required for introduction of new drugs; the biomarkers that are validated for studies of sensation and motility endpoints with experimental medications in humans; the pharmacogenomics applied to these medications and their relevance to the FGIDs; and the pharmacology of agents that are applied or have potential for the treatment of FGIDs, including psychopharmacologic drugs.

Efficacy of three-in-one capsule bismuth quadruple therapy for Helicobacter pylori eradication in clinical practice in a multinational patient population.

BACKGROUND: Bismuth quadruple therapy (BQT) has been proven superior to standard triple therapy for Helicobacter pylori eradication in randomized clinical trials; however, little is known about the efficacy of BQT in daily routine practice. METHODS: In a single-center cohort study, we analyzed consecutive H. pylori-positive patients in whom three-in-one capsule BQT (Pylera® + omeprazole) has been prescribed. All patients were instructed in a standardized fashion, and a prospective follow-up was planned. PCR on gastric biospies for clarithromycin and levofloxacin resistance was performed before treatment in a subgroup of patients. Treatment outcome was assessed by 13C urea breath test or by histology not earlier than 4 weeks after end of treatment. RESULTS: Three-in-one capsule BQT has been prescribed in 322 patients. Approximately 70.2% of patients had a migrational background. PCR results were available in 163 patients and identified resistance to clarithromycin and levofloxacin in 29 (17.8%) and 20 (12.3%) of cases, respectively. BQT was prescribed as first-line, second-line, and salvage treatments in 74%, 17%, and 9% of cases, respectively. Five patients discontinued treatment due to side effects (1.8%). By modified intention-to-treat and per-protocol analyzes, the overall H. pylori eradication rates were 95.0% (95% CI 94.92%-95.08%) and 96.7% (95% CI 94.6%-98.8%), respectively. The low number of treatment failures (n = 9) did not allow to identify risk factors for failure. CONCLUSION: Three-in-one capsule bismuth quadruple therapy is effective and safe for treatment of H. pylori infection in routine practice, irrespective of the patient's migrational background or the number of previous treatment failures.