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Biomedical subjects

Jan Tack

Publications and source records attributed to Jan Tack.

14 recordsLinked to original sources

Clinical and Psychosocial Characteristics of Adult Primary Care IBS Patients: A Post hoc Analysis of the DOMINO Study.

BACKGROUND: The majority of irritable bowel syndrome (IBS) patients are diagnosed and managed in primary care, but this setting is underinvestigated to date. OBJECTIVE: The present study aimed to improve our understanding of IBS in primary care by evaluating the clinical and psychosocial characteristics of affected patients. METHODS: We performed a cross-sectional post hoc analysis of the DOMINO study, which enrolled 483 adult IBS patients newly diagnosed by primary care physicians. We investigated baseline demographics and questionnaires assessing Rome IV criteria and stool pattern subtype, symptom severity (IBS-SSS), quality of life (IBS-QoL), somatic symptom disorder (PHQ-12), depression (PHQ-9) and anxiety (GAD-7). RESULTS: 70% of the primary care diagnosed IBS patients fulfilled the Rome IV criteria (Rome+). The stool pattern subtype distribution according to the Rome IV diagnostic questionnaire was: 20% constipation (IBS-C), 33% diarrhea (IBS-D), 31% mixed (IBS-M) and 16% unclassified (IBS-U). Mean IBS-SSS was 268 ± 98, with 46% and 36% of cases reporting moderate and severe IBS-SSS, respectively. Rome + patients had, compared to Rome-, a significantly higher IBS-SSS, lower quality of life and higher psychosocial comorbidity. IBS-M, IBS-D and IBS-C participants scored significantly higher on IBS-SSS and IBS-QoL than IBS-U. Furthermore, IBS-M had significantly higher somatic symptom disorder and depression and anxiety levels compared with IBS-U. CONCLUSION: The majority of primary care IBS patients fulfilled the Rome IV criteria, were subtyped as IBS-D or IBS-M and were characterised by moderate or severe IBS-SSS. Rome+ and IBS-M participants had higher symptom severity, lower quality of life and higher psychosocial comorbidity. CLINICALTRIALS: gov, Number NCT04270487.

Adult↗

Putting Globus Into Context: Prevalence, Characteristics, and Overlap With Other Disorders of Gut-Brain Interaction.

OBJECTIVE: Globus is characterized by the sensation of a lump in the throat without dysphagia or underlying structural abnormality or major motility disorder. Reported prevalences vary considerably across studies. Globus has been linked to both heartburn and affective disorders. This study aims to determine the global prevalence of globus, its association with heartburn, overlap with disorders of gut-brain interaction (DGBI) and psychosocial disorders, and its impact on health-related quality of life (HRQOL). METHODS: Internet surveys from the Rome Foundation Global Epidemiology study were used (N = 54,127). Rome IV criteria were used to identify globus and concurrent DGBI. Heartburn was defined as symptoms ≥ 2-3 days/week. Psychosocial co-morbidity and somatic symptom severity were assessed with PHQ-4 and PHQ-15, and HRQOL by PROMIS-10. RESULTS: The global prevalence of globus according to Rome IV criteria was 0.75%, representing 12.8% of esophageal DGBI and 1.86% of all DGBI. Prevalence was highest in Western Europe (0.94%) and Asia (0.90%), and lowest in the Middle East (0.31%). Globus was slightly more common in females (55.4%), and most affected individuals were aged between 40 and 64 years (46.6%). Coexisting heartburn was reported in 17.4% of cases, esophageal DGBI in 9.1%, and non-esophageal DGBI in 49.0%. Anxiety and/or depression was present in 60.5%. CONCLUSION: Global prevalence of globus is 0.75%, with a slight female predominance, and is most prevalent below 65 years. Overlap with non-esophageal DGBI was greater than with heartburn symptoms or esophageal DGBI, and most patients had anxiety and/or depressive symptoms.

Humans↗

Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans.

Decreased acid clearance and increased exposure to acid of the duodenum have been reported in a subset of functional dyspepsia patients. However, the mechanism by which increased duodenal acid exposure may affect symptoms is unclear. The aim of the present study was to investigate the effects of duodenal acidification on proximal gastric tone and mechanosensitivity in humans. An infusion tube with a pH electrode attached was positioned in the second part of the duodenum, and a barostat bag was located in the gastric fundus. In 12 healthy subjects, fundic tone and sensitivity to distensions were assessed before and during duodenal infusion of 0.1 N hydrochloric acid or saline in a randomized, double-blind design. In 10 healthy subjects, meal-induced accommodation was measured during duodenal infusion of acid or saline. Acid infusion in the duodenum significantly increased fundic compliance and decreased fasting fundic tone. This was accompanied by a significant decrease in the pressures and the corresponding wall tensions at the thresholds for discomfort. During infusion of acid, significantly higher perception and symptom scores were obtained for the same distending pressures. The meal-induced fundic relaxation was significantly smaller during acid infusion compared with saline infusion. In conclusion, duodenal acidification induces proximal gastric relaxation, increases sensitivity to gastric distension, and inhibits gastric accommodation to a meal. Through these mechanisms, increased duodenal acid exposure may be involved in the pathogenesis of dyspeptic symptoms.

Acids↗

Acid infusion enhances duodenal mechanosensitivity in healthy subjects.

Duodenal acid has been suggested to be of importance for dyspeptic symptoms. We investigated the effects of acid on duodenal mechanosensitivity and antroduodenal motility in 10 healthy subjects before and during duodenal infusion of acid (0.1 N HCl) or water by using a combined barostat-manometry assembly. During acid infusion, increased sensitivity to balloon distension was seen, with reduced perception (P = 0.04) and discomfort thresholds (P = 0.06) and higher intensity of discomfort (P = 0.02) compared with water. Higher balloon volumes were seen during acid infusion, indicating decreased tone (P = 0.05). Large volume waves were more prevalent during acid than water infusion (P = 0.009). The acid infusion suppressed antral contractions (P = 0.04) and increased the number of contractions in the proximal duodenum (P = 0.02) compared with before the infusion. In conclusion, duodenal acid enhances mechanical sensitivity in the duodenum, affects gastroduodenal motor function, and might be of importance for dyspeptic symptoms.

Adult↗

Functional dyspepsia: evaluation and treatment.

Functional dyspepsia is one of the most common disorders seen in general practice and by gastroenterologists. New concepts regarding the pathophysiology and its role for the symptom pattern have emerged during the last few years. This is of importance for development of new treatment alternatives in the near future. At the moment, however, empirical treatment with acid-suppressive agents and prokinetics is the recommended therapeutic approach in the management of these patients, despite limited efficacy. Identification and treatment of H pylori infection has been recommended for uninvestigated dyspepsia, because it may cure underlying peptic ulcer disease, but is unlikely to provide symptomatic benefit to patients with functional dyspepsia. Refractory patients may respond to antidepressants or to psychologic treatments, but proof of efficacy is limited. New and more effective approaches are badly needed for functional dyspepsia.

Abdominal Pain↗

P-glycoprotein attenuating effect of human intestinal fluid.

PURPOSE: To evaluate the effect of human intestinal fluid (HIF) on P-glycoprotein (P-gp)-mediated efflux. METHODS: HIF was obtained from eight healthy volunteers by duodenal aspiration. HIF was applied at different concentrations (0-75%) to the apical compartment of the Caco-2 system. Cyclosporin A (CsA) was used as a model compound for P-gp mediated efflux. RESULTS: When the bidirectional transport of CsA across Caco-2 monolayers was assessed, a significant polarity in transport could be observed, the absorptive transport being much lower than the secretory transport. Inclusion of HIF resulted in a moderate increase of the absorptive transport, as well as a significant concentration dependent decrease of the secretory transport, without compromising the integrity of the monolayer. Interestingly, a possible gender difference could be detected as inclusion of HIF obtained from female subjects resulted in a decreased absorptive transport of CsA, whereas inclusion of HIF obtained from male subjects resulted in an increased absorptive transport. The P-gp modulating effect of HIF is not caused by a lack of glucose as an energy source for the efflux mechanism when high concentrations of HIF were present in the buffer used. CONCLUSIONS: The results of this study indicate that the contribution of P-gp efflux carriers may be overestimated when using salt buffer solutions as transport media. Additionally, it can be concluded that (presently unidentified) components of HIF may attenuate the P-gp mediated intestinal efflux. The clinical significance of this modulating effect remains to be investigated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Dietary restrictions during ambulatory monitoring of duodenogastroesophageal reflux.

To avoid food impaction artifacts during ambulatory bile reflux monitoring (Bilitec), some groups have allowed only a liquid diet, while others omitted the meal and postprandial periods from the analysis. Our aim was to study whether Bilitec monitoring requires the use of a liquid diet. In 40 healthy subjects and 211 consecutive patients evaluated for suspected gastroesophageal reflux disease, we performed ambulatory 24-hr esophageal pH and Bilitec monitoring. The subjects were randomized to either solid or liquid meals during the procedure. All patients underwent an upper gastrointestinal endoscopy. In healthy subjects, liquid and solid diets were followed by similar acid exposure of the distal esophagus. During bile reflux monitoring, major meal artifacts occurred in 19% of the patients using solid meals, but in none of the patients using liquid meals. With liquid meals, but not with solid meals, a progressive increase in duodenoesophageal reflux occurred with increasing severity of endoscopic lesions. With liquid meals, but not with solid meals, the prevalence of pathological exposure to duodenoesophageal reflux increased with increasing severity of endoscopic lesions. With liquid meals, the results of pH monitoring and bile reflux monitoring correlated better than with solid meals. Thus, ambulatory Bilitec monitoring requires the use of liquid meals, as the use of solid meals is associated with too many meal artifacts and a poorer correlation with acid reflux and severity of endoscopic lesions.

Adolescent↗

Heterogeneity of symptom pattern, psychosocial factors, and pathophysiological mechanisms in severe functional dyspepsia.

BACKGROUND & AIMS: Categorization of functional dyspepsia into subgroups is based on expert opinion according to (dominant) symptoms or on underlying pathophysiological mechanisms. We used an evidence-based approach to the determination of subtypes of functional dyspepsia. METHODS: Consecutive functional dyspepsia patients were recruited from a tertiary referral center. The following were performed: (1) exploratory (EFA) and confirmatory factor analysis (CFA) of symptom patterns in a large group of patients with functional dyspepsia; (2) external validation of these factors by the determination of their association pattern with physio- and psychopathological mechanisms, and with health-related quality of life and sickness behavior; and (3) cluster analysis of their distribution in this population. RESULTS: Both EFA and CFA do not support the existence of functional dyspepsia as a homogeneous (unidimensional) condition. A 4-factor model is found to be valid, with differential distribution within the patient population according to cluster analysis. Factor 1 is characterized by nausea, vomiting, early satiety, and weight loss and factor 2 by postprandial fullness and bloating. Both factor 1 and 2 are associated with delayed emptying, but only factor 1 is associated with younger age, female sex, and sickness behavior. Factor 3 is characterized by pain symptoms and associated with gastric hypersensitivity and several psychosocial dimensions including medically unexplained symptoms and health-related quality of life dimensions. Factor 4, characterized by belching, is also associated with hypersensitivity, but is unrelated to psychosocial dimensions. CONCLUSIONS: In a tertiary care population, functional dyspepsia is a heterogeneous condition characterized by 4 major dimensions differentially associated with psychopathological and physiopathological mechanisms.

Abdominal Pain↗

Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia.

OBJECTIVE: The relationship between functional dyspepsia and delayed gastric emptying of solids or liquids is still unclear. The aim of the present study was to investigate in dyspeptic patients the prevalence of delayed gastric emptying for solids or for liquids and to investigate the relationship to the dyspepsia symptom pattern. METHODS: In 392 and 330 patients with functional dyspepsia, the solid and liquid gastric emptying, respectively, was measured using breath tests, and the severity of eight dyspeptic symptoms was scored. RESULTS: Gastric emptying of solids and liquids were delayed in 23% and 35% of the patients. Multivariate analysis showed that the presence of vomiting and postprandial fullness was associated with delayed solid emptying (OR 2.65, 95% CI = 1.62-4.35 and OR 3.08, 95% CI = 1.28-9.16, respectively). Postprandial fullness was also associated with the risk of delayed liquid emptying when symptom was present (OR 3.5, 95% CI = 1.57-8.68), relevant or severe (OR 2.504, 95% CI = 1.41-4.65), and severe (OR 2.214, 95% CI = 1.34-3.67). Severe early satiety was associated with the risk of delayed liquid emptying (OR 1.902, 95% CI = 1.90-3.30). CONCLUSIONS: A subset of dyspeptic patients has delayed gastric emptying of solids or of liquids. Delayed gastric emptying of solids was constantly associated with postprandial fullness and with vomiting. Delayed emptying for liquids was also associated with postprandial fullness and with severe early satiety.

Adolescent↗

Functional Heartburn.

Functional heartburn is defined as the presence of a retrosternal burning sensation in the absence of pathologic gastroesophageal reflux. The underlying pathophysiology seems to be heterogeneous. In a subset of patients, esophageal hypersensitivity to physiologic esophageal acid exposure is involved, and this is likely to respond to intensive antireflux treatment. Antireflux surgery was not studied systematically in these patients and should be considered only in exceptional cases. In the remaining patients, non-acid reflux, esophageal mechanosensitivity, and psychological factors may be involved. Treatment options in these patients are limited owing to a lack of studies. Emerging therapies include selective serotonin reuptake inhibitors and relaxation therapy.

Journal Article↗

Clinical and pathophysiological characteristics of acute-onset functional dyspepsia.

BACKGROUND & AIMS: Functional bowel disorders may follow acute intestinal infection. In animals, postinflammatory dysmotility is associated with nitrergic dysfunction. The aim of this study was to identify and characterize patients with presumed postinfectious dyspepsia (PD) compared with unspecified-onset dyspepsia (UD). METHODS: A total of 400 consecutive dyspeptic patients filled out a questionnaire to assess whether their symptoms were of postinfectious origin. They underwent testing for Helicobacter pylori infection as well as gastric emptying and gastric barostat studies. Pharmacological studies of nitrergic gastric function were performed in controls, in patients with presumed PD, and in patients with UD using sumatriptan, an activator of nitrergic neurons, and amylnitrite, a nitric oxide donor. RESULTS: Presumed PD was present in 17% of the patients and associated with more prevalent early satiety, weight loss, nausea, and vomiting compared with UD. Both groups did not differ in H. pylori infection, gastric emptying, or gastric sensitivity. Impaired accommodation was significantly more prevalent in patients with presumed PD (67% vs. 30%; P < 0.05). Sumatriptan relaxed the stomach in controls and patients with UD but not in patients with presumed PD, whereas amyl nitrite relaxed the stomach in all subjects. CONCLUSIONS: A subset of dyspeptic patients has a history suggestive of postinfectious dyspepsia. These patients have a high prevalence of impaired accommodation attributable to a dysfunction at the level of gastric nitrergic neurons.

Adolescent↗

Prospective study on the incidence of chronic ear complaints related to gastroesophageal reflux and on the outcome of antireflux therapy.

Over a 2-year period (1997 to 1999), 5 consecutive adult patients with chronic refractory secretory otitis media (CSOM) and 16 with a chronic refractory feeling of pressure in the ear(s) (CRFP) thought to be related to concomitant eustachian tube dysfunction were prospectively studied for coexisting gastroesophageal reflux (GER). All patients underwent an extensive standardized otorhinolaryngological examination, ambulatory 24-hour dual-probe esophageal pH monitoring with a distal pH probe 5 cm and a proximal probe 20 cm above the lower esophageal sphincter, and upper gastrointestinal endoscopy. Most of them also underwent esophageal manometry. All patients with CSOM and 12 of the 16 patients with CRFP had evidence of GER. Only 5 patients experienced heartburn or regurgitation. All patients responded very well to antireflux therapy with omeprazole 20 mg twice per day (40 mg twice per day in 2 patients) accompanied by conservative antireflux measures, ie, complete cessation of their middle ear complaints. This study demonstrates the role of GER in the pathogenesis of refractory CSOM and CRFP and the effectiveness of sustained antireflux therapy.

Adult↗

Tegaserod: a new 5-HT(4) agonist in the treatment of irritable bowel syndrome.

Tegaserod is a selective partial agonist acting on serotonergic type 4 receptors (5-HT(4)). Pharmacodynamic studies indicate that tegaserod is able to stimulate gut propulsion and secretion with a net prokinetic effect. In contrast to other 5-HT(4) agonists endowed with a complex pharmacological profile, tegaserod has a reliable prokinetic activity in the colon. Clinical trials show that tegaserod is effective and safe in the treatment of patients with irritable bowel syndrome. In particular, tegaserod relieves symptoms of abdominal pain, discomfort, abdominal bloating and constipation.

Animals↗