Do we have an alternative for the Rome III gastroduodenal symptom-based subgroups in functional gastroduodenal disorders? A cluster analysis approach

BACKGROUND: Functional dyspepsia (FD) is a heterogeneous biopsychosocial disorder. The Rome III consensus proposed a subdivision into epigastric pain syndrome and postprandial distress syndrome, based on gastroduodenal symptom pattern only; nausea/vomiting- and belching disorders were classified as separate functional gastroduodenal disorders (FGD). We aimed to investigate an alternative subdivision of FGD, taking into account gastric sensorimotor function, anxiety & depression and 'somatization', besides gastroduodenal symptoms. METHODS: Gastroduodenal symptom data were available for 857 consecutive FGD patients (Rome II criteria). In a subsample (n = 259), additional data were obtained on gastric sensitivity, anxiety, depression and 'somatization'. Two separate cluster analyses were performed. In analysis 1, clustering was based on individual gastroduodenal symptom scores. In analysis 2, gastric sensitivity, anxiety & depression and 'somatization', besides total gastroduodenal symptoms score, were used for clustering. KEY RESULTS: Analysis 1 identified four clusters, largely supporting the Rome III classification, with early satiation, pain and nausea/vomiting clusters, besides a limited severity cluster (R-2 = 0.32). Analysis 2 suggested a five-cluster solution (R-2 = 0.48). Anxiety, depression and 'somatization' were the most important variables separating the clusters. 'Primary somatization' (with low psychiatric symptom levels) as well as 'secondary somatization' (with high anxiety & depression scores) subgroups were identified, besides three other subgroups characterized by psychiatric/gastroduodenal symptoms, mild anxiety symptoms and limited overall severity, respectively. CONCLUSIONS & INFERENCES: We propose an alternative to the current subgrouping in FGD that is exclusively based on gastroduodenal symptoms. This may have consequences for future classification of FGD, as well as broader relevance towards the debate on subgrouping 'functional somatic syndromes'.status: publishe

Factors associated with co-morbid irritable bowel syndrome and chronic fatigue-like symptoms in functional dyspepsia

BACKGROUND: It is unclear which factors explain the high co-morbidity between functional dyspepsia (FD) and other functional somatic syndromes. The aim of this study is to investigate the association between gastric sensorimotor function, psychosocial factors and 'somatization' on the one hand, and co-morbid irritable bowel syndrome (IBS) and chronic fatigue (CF)-like symptoms on the other, in FD. METHODS: In 259 tertiary care FD patients, we studied gastric sensorimotor function with barostat (sensitivity, accommodation). We measured psychosocial factors (abuse history, alexithymia, trait anxiety, depression, panic disorder) and 'somatization' using self-report questionnaires, and presence of IBS and CF-like symptoms. Hierarchical multiple logistic regression was used to determine which of these factors were independently associated with co-morbid IBS and CF-like symptoms, including testing of potential mediator effects. Key RESULTS: Co-morbid IBS or CF-like symptoms respectively were found in 142 (56.8%) and 102 (39.4%) patients; both co-morbidities were not significantly associated (P = 0.27). Gastric accommodation (beta = 0.003, P = 0.04) and 'somatization' (beta = 0.17, P = 0.0003) were independent risk factors for IBS (c = 0.74, P < 0.0001); the effect of adult abuse (beta = 0.72, P = 0.20) was mediated by 'somatization'. Depression (beta = 0.16, P = 0.008) and 'somatization' (beta = 0.18, P = 0.004) were overlapping risk factors for CF-like symptoms (c = 0.83, P < 0.0001); the effects of alexithymia and lifetime abuse were mediated by depression and 'somatization', respectively. CONCLUSIONS & INFERENCES: 'Somatization' is a common risk factor for co-morbid IBS and CF-like symptoms in FD and mediates the effect of abuse. Gastric sensorimotor function and depression are specific risk factors for co-morbid IBS and CF-like symptoms, respectively.status: publishe

The effect of rikkunshito on gastrointestinal symptoms and gastric motor function: The first study in a Belgian functional dyspepsia population

BACKGROUND: Rikkunshito, a traditional Kampo medicine, has shown efficacy to treat functional dyspepsia (FD) in controlled trials in Japan. Its putative benefit for European patients and mechanism of action has not been established. METHODS: This study examined the effect of rikkunshito on gastric motility and GI symptom perception in FD-PDS patients in a randomized, placebo-controlled, cross-over study. After a 2-week run-in period, patients received rikkunshito or matching placebo (2.5 g t.i.d.) for 4 weeks, separated by a 4-week washout period. Symptoms were assessed by the Leuven Postprandial Distress Scale (LPDS) diary throughout the study. At baseline and after both treatment arms, intragastric pressure (IGP) was measured to evaluate gastric accommodation and gastric motility. Simultaneously, GI symptoms were scored on a 100 mm visual analogue scale. Validated symptom questionnaires (PAGI-SYM, VSI, DSS, and PHQ) were completed each study visit. KEY RESULTS: Twenty-three patients completed the study (33 ± 14 years, 22.7 ± 3.22 kg/m2 ). Intragastric pressure was numerically, but not significantly, lower after rikkunshito compared with baseline and placebo (P = .14). No differences were found in gastric accommodation, nutrient volume tolerance, and symptoms assessed during IGP measurements. Early satiation and postprandial fullness (daily diary) decreased after rikkunshito compared with baseline (P < .041 for both). Placebo also improved most other symptoms assessed. No significant changes in VSI scores occurred. No adverse reactions occurred. CONCLUSIONS: Rikkunshito did not alter gastric motility. Treatment with rikkunshito improved upper GI symptoms in FD patients but similarly high placebo effects were observed using the LPDS diary, PAGI-SYM, SF-NDI, and DSS scores. Rikkunshito was safe and well-tolerated.status: publishe

Efficacy and safety of lanreotide in postoperative dumping syndrome: A Phase II randomised and placebo-controlled study

Background: Data on the efficacy and safety of the long-acting somatostatin analogue lanreotide (LAN) for postoperative dumping syndrome are lacking. Objective: We performed a double-blind, randomised and placebo-controlled crossover study of LAN Autogel® 90 mg in postoperative dumping. Methods: Adults with a positive prolonged oral glucose tolerance test or spontaneous hypoglycaemia and total dumping score (DS) ≥ 10 despite dietary measures were treated with three monthly injections of LAN or placebo in a randomised crossover fashion with an eight-week wash-out period. Primary outcome was the effect of LAN on total DS versus placebo. Secondary outcomes were the effect on early and late DS, treatment assessment, quality of life and safety. Results: Of 24 included patients (66.7% female; age 49.1 ± 2.1 years), 12 were randomised to LAN first. Pooled DS after three injections were lower compared to baseline after LAN (median=14 (interquartile range (IQR) 11.5-23) vs. median = 22 (IQR 16-27); p = 0.03) but not placebo (median = 20 (IQR 15-27) vs. median = 23 (IQR 13-29); p = 0.15). Improvement of early (median = 7.5 (IQR 4.5-13) vs. median = 12 (IQR 9-16); p = 0.03) but not late (median = 7 (IQR 6-10.3) vs. median = 9 (IQR 6-13); p = 0.26) DS was seen. Overall treatment assessment correlated with change in DS (r = -0.69, p = 0.004). Symptom improvement was not associated with changes in quality of life. Of the 81 reported adverse events, 44 occurred on LAN compared to 37 on placebo (p > 0.05), with seven serious adverse events on LAN. Conclusions: LAN is effective for treating early postoperative dumping symptoms, although side effects are common and quality of life is not significantly affected.status: publishe

A multidimensional model of psychobiological interactions in functional dyspepsia: A structural equation modeling approach

OBJECTIVE: Gastric sensorimotor function, abuse history, 'trait' and 'state' psychological factors and 'somatisation' all play a role in functional dyspepsia (FD) and its associated impaired quality of life (QoL), but their interplay remains poorly understood. We aimed to test a comprehensive, a priori hypothesised model of interactions between these dimensions in FD. DESIGN: In 259 FD patients, we studied gastric sensitivity with a barostat. We measured abuse history (sexual/physical, childhood/adulthood), 'trait' (alexithymia, trait anxiety) and 'state' (positive/negative affect, depression, panic disorder) psychological factors, somatic symptom reporting (somatic symptom count, dyspepsia, irritable bowel syndrome and fatigue symptoms) and QoL (physical, mental) using validated questionnaires. Confirmatory factor analysis (CFA) was used to assess whether four a priori hypothesised latent variables ('abuse', 'trait affectivity', 'state affect' and 'somatic symptom reporting') were adequately supported by the data. Structural equation modelling (SEM) was used to test the a priori hypothesised relationships between these latent variables and the observed variables gastric sensitivity and QoL. RESULTS: Both the CFA and SEM models fitted the data adequately. Abuse exerted its effect directly on 'somatic symptom reporting', rather than indirectly through psychological factors. A reciprocal relationship between 'somatic symptom reporting' and 'state affect' was found. Gastric sensitivity influences 'somatic symptom reporting' but not vice versa. 'Somatic symptom reporting' and 'trait affectivity' are the main determinants of physical and mental QoL, respectively. CONCLUSIONS: We present the first comprehensive model elucidating the complex interactions between multiple dimensions (gastric sensitivity, abuse history, 'state' and 'trait' psychological factors, somatic symptom reporting and QoL) in FD.status: publishe