A placebo-controlled trial of itopride in functional dyspepsia

Dyspepsia remains a common and costly problem in primary care and gastroenterology practice; in most patients who are examined, no structural lesions causing these symptoms are found.1 Dyspepsia in the absence of a clinically identifiable structural lesion is referred to as functional dyspepsia,2,3 in part because disturbed gastrointestinal function is believed to play a role in the development of symptoms.4 Pharmacologic treatments for patients with functional dyspepsia remain unsatisfactory.5 The results of controlled trials have generally been disappointing, and only small benefits relative to placebo have been found with histamine H 2 -receptor antagonists,6 proton-pump inhibitors,7 and Helicobacter pylori eradication.8 Although several randomized, controlled trials and metaanalyses have demonstrated the superiority of cisapride over placebo,9-11 the use of cisapride is now restricted in most countries because of cardiac side effects. In Japan, itopride, which is a dopamine D2 antagonist with acetylcholinesterase inhibitory actions, is often prescribed for patients with functional dyspepsia. Although this drug has been shown to stimulate gastric motility,12 large, properly designed, randomized, controlled trials in patients with functional dyspepsia are lacking. In Japan, administration of 50 mg three times daily is standard practice. However, little is known regarding the dose response in other populations. For this reason, we aimed to study the efficacy of itopride in patients with functional dyspepsia in terms of symptom improvement and to compare various doses of itopride in terms of efficacy and safety in a white population. Methods Study Design and Patient Population Patients Outpatients who were considered to have functional dyspepsia on the basis of the Rome II criteria3 were eligible for the trial. Functional dyspepsia was diagnosed if persistent or recurrent upper abdominal pain or discomfort was present. Discomfort was characterized by the presence of one or more symptoms that included early satiety, postprandial fullness, bloating, and nausea

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Non-AIDS-, non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.publishedVersio

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose: Thrombocytopenia (platelet count &lt; 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic

Genetic disorders in gastroenterology and hepatology - Susceptibility genes and functional gastrointestinal disorders

Article first published online: 12 OCT 2005T Liebregts, B Adam and G Holtman

Irritable bowel syndrome

© Georg Thieme Verlag Stuttgart · New YorkPatients with irritable bowel syndrome (IBS) are highly prevalent among subjects seeking medical attention at the general practitioner or specialist level. While IBS lacks any disease associated excess mortality, this disorders is relevant to the affected subjects due to the considerable burden with regard to the symptoms and an impaired quality of life. Furthermore, this disease has a substantial impact on society due to the economical consequences. In recent years substantial progress has been achieved regarding our pathophysiological understanding. However, as usual, there has been a substantial delay between the discovery of disease mechanisms and its translation into improved patient care. For diagnosing IBS standardized criteria have been established (i. e. Rome II- or the DGVS-criteria). Regarding treatment, life style advice such as avoidance of specific nutrients that precipitate or aggravate or the "little psychotherapy" (addressing patients concerns and anxiety regarding the symptoms) are considered essential. However, the overall response rate is disappointing. Evidence-based pharmacological interventions include herbal preparations, spasmolytics, low dose tricyclic antidepressants and 5-HT-3-receptor antagonists and 5-HT-4-receptor agonists. At present no cure for patients with IBS exists. Thus, all currently available treatments target palliation of symptoms. This, however, may change in the future.B. Adam, T. Liebregts, G. Holtman

Intestinal T lymphocyte homing is associated with gastric emptying and epithelial barrier function in critically ill: a prospective observational study

BACKGROUND: Impaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little is known about gut-directed immune activation, intestinal barrier function and its association with impaired gastric emptying in critically ill patients at ICU admission. METHODS: We conducted a prospective observational study at two tertiary care medical ICUs. Fifty consecutive patients needing invasive mechanical ventilation were recruited within 24 h of ICU admission, prior to any nutritional support. The acute physiology and chronic health evaluation (APACHE) II score, the sequential organ failure assessment (SOFA) score and the multiple organ dysfunction score (MODS) were used to assess illness severity and multiple organ dysfunction. Gastric emptying was assessed by paracetamol absorption test. Peripheral blood mononuclear cells were freshly isolated and cultured for 24 h, and TNF-α, IL-1β and IL-10 measured in cell culture supernatants and in serum by ELISA. The intestinal epithelial barrier was assessed, quantifying serum concentrations of intestinal fatty acid binding protein (I-FABP), ileal bile-acid binding protein (I-BABP) and zonulin-1 by ELISA. Small bowel homing T lymphocytes (CD4+ α4β7 + CCR9+) were analyzed by flow cytometry. The Mann-Whitney test and Spearman correlation were used in statistical evaluation. RESULTS: CD4 + α4β7 + CCR9+ T lymphocytes were inversely correlated with gastric emptying. Patients with delayed gastric emptying at ICU admission (n = 35) had significantly higher serum and PBMC-induced TNF-α and IL-1β and increased intestinal barrier disruption reflected by higher I-FABP, I-BABP and zonulin-1. Patients who died in the ICU had significantly impaired gastric empting at admission compared to ICU survivors. No differences were observed in APACHE II, SOFA or MODS in patients with delayed gastric emptying compared to patients with normal gastric emptying. CONCLUSIONS: Exaggerated CD4 + α4β7 + CCR9+ T lymphocyte homing with increased pro-inflammatory cytokine release and intestinal epithelial barrier disruption are associated with delayed gastric emptying. This is not simply due to differences in overall severity of illness at ICU admission and may represent a pathophysiological mechanism of gut-directed immune activation leading to impaired barrier function in the critically ill