A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a very common condition affecting more than 10% of the population. While there is no cure, a few drugs have been found to be effective for the relief of symptoms, although most are only effective in a subgroup of patients. We assess and compare the efficacy of a fixed peppermint/caraway-oil-combination (Menthacarin) on symptoms and quality of life (QoL) in patients with FD symptoms consistent with epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). METHODS: In a prospective, double-blind, multicenter trial, 114 outpatients with chronic or recurrent FD were randomized and treated for 4 weeks with the proprietary peppermint- and caraway-oil-preparation Menthacarin or placebo (2×1 capsule/day). Improvement of abdominal pain and discomfort were used as co-primary efficacy measures (scores measured with the validated Nepean Dyspepsia Index). KEY RESULTS: After 2 and 4 weeks, active treatment was superior to placebo in alleviating symptoms consistent with PDS and EPS (P all <.001). After 4 weeks of treatment, pain and discomfort scores improved by 7.6±4.8 and 3.6±2.5 points (full analysis set; mean±SD) for Menthacarin and by 3.4±4.3 and 1.3±2.1 points for placebo, respectively. All secondary efficacy measures showed advantages for Menthacarin. CONCLUSIONS & INFERENCES: Menthacarin is an effective therapy for the relief of pain and discomfort and improvement of disease-specific QoL in patients with FD and significantly improves symptoms consistent with EPS and PDS.

The Validity of a New Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS) for Evaluating Symptoms in the Clinical Setting.

BACKGROUND: The clinical assessments of patients with gastrointestinal symptoms can be time-consuming, and the symptoms captured during the consultation may be influenced by a variety of patient and non-patient factors. To facilitate standardized symptom assessment in the routine clinical setting, we developed the Structured Assessment of Gastrointestinal Symptom (SAGIS) instrument to precisely characterize symptoms in a routine clinical setting. AIMS: We aimed to validate SAGIS including its reliability, construct and discriminant validity, and utility in the clinical setting. METHODS: Development of the SAGIS consisted of initial interviews with patients referred for the diagnostic work-up of digestive symptoms and relevant complaints identified. The final instrument consisted of 22 items as well as questions on extra intestinal symptoms and was given to 1120 consecutive patients attending a gastroenterology clinic randomly split into derivation (n = 596) and validation datasets (n = 551). Discriminant validity along with test-retest reliability was assessed. The time taken to perform a clinical assessment with and without the SAGIS was recorded along with doctor satisfaction with this tool. RESULTS: Exploratory factor analysis conducted on the derivation sample suggested five symptom constructs labeled as abdominal pain/discomfort (seven items), gastroesophageal reflux disease/regurgitation symptoms (four items), nausea/vomiting (three items), diarrhea/incontinence (five items), and difficult defecation and constipation (2 items). Confirmatory factor analysis conducted on the validation sample supported the initially developed five-factor measurement model ([Formula: see text], p < 0.0001, χ 2/df = 4.6, CFI = 0.90, TLI = 0.88, RMSEA = 0.08). All symptom groups demonstrated differentiation between disease groups. The SAGIS was shown to be reliable over time and resulted in a 38% reduction of the time required for clinical assessment. CONCLUSIONS: The SAGIS instrument has excellent psychometric properties and supports the clinical assessment of and symptom-based categorization of patients with a wide spectrum of gastrointestinal symptoms.

Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study.

BACKGROUND: Traditionally, functional gastrointestinal disorders (FGIDs) are conceptualised as originating in the brain via stress pathways (brain-to-gut). It is uncertain how many with irritable bowel syndrome (IBS) and functional dyspepsia (FD) have a gut origin of symptoms (gut-to-brain pathway). AIMS: To determine if there is a distinct brain-to-gut FGID (where psychological symptoms begin first) and separately a distinct gut-to-brain FGID (where gut symptoms start first). METHODS: A prospective random population sample from Newcastle, Australia who responded to a validated survey in 2012 and completed a 1-year follow-up survey (n = 1900). The surveys contained questions on Rome III IBS and FD and the Hospital Anxiety and Depression Scale. RESULTS: We found that higher levels of anxiety and depression at baseline were significant predictors of developing IBS (OR = 1.31; 95% CI 1.06-1.61, P = 0.01; OR = 1.54; 95% CI 1.29-1.83, P < 0.001) and FD (OR = 1.28; 95% CI 1.05-1.55, P = 0.01; OR = 1.55, 95% CI 1.32-1.83, P < 0.001), respectively, at the 1-year follow-up. Among those people who did not have elevated levels of anxiety and depression at baseline, subjects at baseline with documented IBS (mean difference 0.34; 95% CI 0.13-0.55, P = 0.002; 0.81; 95% CI 0.47-1.15, P < 0.001) and FD (0.38; 95% CI 0.14-0.63, P = 0.002; 0.92; 95% CI 0.57-1.27, P < 0.001), reported significantly higher levels of anxiety and depression at the 1-year follow-up. We calculated in one-third of individuals a mood disorder precedes FGID but in two-thirds an FGID precedes the mood disorder. CONCLUSION: While brain-gut pathways are bidirectional, a major subset begin with gut symptoms first and only then psychological distress develops, implicating primary gut mechanisms as drivers of the gut and extra-intestinal features in many cases.

Identification of early environmental risk factors for irritable bowel syndrome and dyspepsia.

BACKGROUND: The role of childhood environment including exposure to infection via siblings and pets in irritable bowel syndrome (IBS) and dyspepsia is relatively unknown. We assessed proxy measures of microbial exposure in early childhood to assess if these are associated with IBS and functional dyspepsia in later life. METHODS: Participants (n = 767, response rate = 53%) were a random population sample from Sydney, Australia who previously responded to a validated survey. IBS and functional dyspepsia were defined using Rome III criteria. Early environmental risk factors assessed included type of birth delivery, premature birth, breastfeeding, bedroom sharing, and pet exposure (the latter two then combined as early hygiene factors) up to 5 years of age. Post infectious IBS (PI-IBS) was assessed by development of IBS following gastroenteritis. KEY RESULTS: In this sample, in adult life 17% developed IBS (of which 20% had PI-IBS) and 12% functional dyspepsia. Development of IBS was associated with childhood factors-a shorter duration of breastfeeding (odds ratios [OR] = 0.87, 95% CI: 0.78-0.97, p = 0.01), sharing a bedroom (OR = 1.89, 95% CI: 1.73-3.08, p = 0.01), exposure to a herbivore pet (OR = 1.65 (1.10, 2.48), p = 0.02), and hygiene factors (OR = 4.39; 95% CI: 1.89-10.21, p = 0.001). The sole factor associated with functional dyspepsia was exposure to a herbivore pet (1.79; 95% CI: 1.19-2.87, p = 0.02). CONCLUSIONS & INFERENCES: Childhood environment factors, particularly bedroom sharing and pet exposure, combined with subsequent risk of microbial exposure are a risk factor for IBS in later life. These associations however need confirmation to rule out any risk of a type I error.

Differentiation of functional constipation and constipation predominant irritable bowel syndrome based on Rome III criteria: a population-based study.

BACKGROUND: While the Rome III classification recognises functional constipation (FC) and constipation predominant IBS (IBS-C) as distinct disorders, recent evidence has suggested that these disorders are difficult to separate in clinical practice. AIM: To identify whether clinical and lifestyle factors differentiate Rome III-defined IBS-C from FC based on gastrointestinal symptoms and lifestyle characteristics. METHOD: 3260 people randomly selected from the Australian population returned a postal survey. FC and IBS-C were defined according to Rome III. The first model used logistic regression to differentiate IBS-C from FC based on lifestyle, quality-of-life and psychological characteristics. The second approach was data-driven employing latent class analysis (LCA) to identify naturally occurring clusters in the data considering all symptoms involved in the Rome III criteria for IBS-C and FC. RESULTS: We found n = 206 (6.5%; 95% CI 5.7-7.4%) people met strict Rome III FC whereas n = 109 (3.5%; 95% CI 2.8-4.1%) met strict Rome III IBS-C. The case-control approach indicated that FC patients reported an older age at onset of constipation, were less likely to exercise, had higher mental QoL and less health care seeking than IBS-C. LCA yielded one latent class that was predominantly (75%) FC, while the other class was approximately half IBS-C and half FC. The FC-dominated latent class had clearly lower levels of symptoms used to classify IBS (pain-related symptoms) and was more likely to be male (P = 0.046) but was otherwise similar in distribution of lifestyle factors to the mixed class. CONCLUSION: The latent class analysis approach suggests a differentiation based more on symptom severity rather than the Rome III view.

Impact of persistent constipation on health-related quality of life and mortality in older community-dwelling women.

OBJECTIVES: Very little is known about whether the reported health-related impact of constipation is worse in people who experience constipation over a long period of time vs. those with more transient symptoms. We aimed to determine the impact of persistent vs. transient constipation on health-related quality of life (QOL), depression, and mortality. METHODS: We analyzed data from 5,107 women (aged 70-75 years in 1996) who answered "Have you had constipation in the past 12 months?" in all five surveys sent out every 3 years of the Australian Longitudinal Study on Women's Health. RESULTS: Of the 5,107 women, 20.9, 54.1, and 24.7% reported having persistent constipation on at least 4 out of 5 surveys, transient constipation reported on 1-3 surveys, or none reported over the 15-year time frame, respectively. Women who reported persistent constipation had significantly lower scores for all domains of QOL on the SF-36 except role-emotional, and had higher levels of self-reported depression, even after adjusting for number of chronic illnesses and fluid intake. Mortality rates were increased when comparing women with no reported constipation with persistently reported constipation (8.2% vs. 11%, odds ratio = 1.32, 95% confidence interval 1.0, 1.74, P = 0.05) controlling for specific chronic illnesses. CONCLUSIONS: Persistent constipation among older women is associated with poor health outcomes.

Psychological impact and risk factors associated with new onset fecal incontinence.

OBJECTIVES: We aim to evaluate the psychological impact and risk factors associated with new onset FI over 12 years in adults over 18 years for the first time in a population-based study. METHODS: Participants (n = 1775) were a random population sample from Penrith, Australia who responded to a survey in 1997 and completed a 12-year follow-up survey (response rate = 60%). FI was defined as having leakage of stool over the past 12 months. The original and follow-up surveys contained valid questions on demographic, gastrointestinal and psychological symptoms. RESULTS: 114 (11.4%) reported new onset FI at the 12 year follow-up. People who reported FI at the 12 year follow-up were significantly more anxious and depressed. In terms of baseline risk factors only bloating (OR = 1.3; 95%CI 1.0-1.6, P = 0.026) was an independent predictor of developing new onset FI. However, current bowel symptoms measured at follow-up including less likelihood of <3 bowel motions a week, increased urgency and mucus were independently associated with having FI at follow-up. CONCLUSION: FI is associated with anxiety and depression. Baseline GI symptoms do not appear to be as important as current bowel symptoms in determining who develops FI.

The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study.

OBJECTIVE: Psychological factors are known to be associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD). No prospective studies have evaluated whether it is the brain (eg, via anxiety) that drives gut symptoms, or whether gut dysfunction precipitates the central nervous system features such as anxiety. In a 12-year longitudinal, prospective, population-based study, we aimed to determine the directionality of the brain-gut mechanism in FGIDs. DESIGN: Participants (n=1775) were a random population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research; 1002 completed the 12-year follow-up survey (response rate =60%), with 217, 82 and 45 people meeting Rome II for new onset FGIDs, IBS and FD, respectively. Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up. RESULTS: Among people free of a FGID at baseline, higher levels of anxiety (OR 1.11; 95% CI 1.03 to 1.19, p=0.006) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later. Among people who did not have elevated levels of anxiety and depression at baseline, those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up (mean difference coefficient 0.76, p<0.001 and 0.30, p=0.01 for anxiety and depression, respectively). In IBS higher levels of anxiety and depression at baseline were predictive of IBS at follow-up, while only depression was predictive of FD at follow-up. CONCLUSIONS: The central nervous system and gut interact bidirectionally in FGIDs.

Epidemiology of the functional gastrointestinal disorders diagnosed according to Rome II criteria: an Australian population-based study.

BACKGROUND: Population-based studies of the prevalence of all functional gastrointestinal disorders (FGID) using the Rome II criteria are lacking. It is also not certain whether subjects who meet the Rome II criteria for an FGID are different in terms of demographic and psychological characteristics from those subjects meeting exclusively the more restrictive Rome I criteria. AIM: To determine whether using the more restrictive Rome I criteria would result in a more biologically determined group of FGID than when the Rome II is applied. METHODS: Subjects included individuals aged 18 years and older (n = 1,225) from the Penrith population who were initially surveyed with the Penrith District Health Survey in 1997. Subjects were sent a self-report questionnaire that contained items on gastrointestinal symptoms applying the Rome II criteria. Subjects were also assessed on psychological and personality factors and on physical and mental functioning. RESULTS: A total of 36.1% (n = 275) of respondents was diagnosed with an FGID according to Rome II criteria. The five most prevalent FGID were functional heartburn (10.4%), irritable bowel syndrome (8.9%), functional incontinence (7.6%), proctalgia fugax (6.5%) and functional chest pain (5.1%). Subjects meeting Rome II only criteria for FGID scored significantly higher on measures of psychological caseness and emotionality than Rome I only subjects, and these were independently associated with meeting Rome I only versus Rome II only criteria for FGID. CONCLUSION: The Rome II criteria FGID are common and do not appear to identify a vastly different group of FGID sufferers compared with the earlier Rome I criteria.

Predictors of conventional and alternative health care seeking for irritable bowel syndrome and functional dyspepsia.

BACKGROUND: The drivers of conventional and, especially, alternative health care use for irritable bowel syndrome and functional dyspepsia are not clear. AIM: To determine the predictors of conventional and alternative health care use for irritable bowel syndrome and functional dyspepsia. METHODS: Two hundred and seven subjects with irritable bowel syndrome or functional dyspepsia, identified from a previous population survey, were included in the study. Individuals with irritable bowel syndrome/functional dyspepsia were defined as consulters (n = 103) if they had visited their doctor for gastrointestinal symptoms more than once in the past year. Controls (n = 100) did not report having any abdominal pain. Subjects were given structured interviews to assess the Diagnostic and Statistical Manual - version IV (DSM-IV) and International Classification of Disorders - version 10 (ICD-10) psychiatric diagnosis for anxiety, depression, somatization or any psychiatric diagnosis, aspects of health care use and symptom factors. RESULTS: About one-half (n = 103, 49.8%) of community subjects with irritable bowel syndrome/functional dyspepsia had sought conventional care for gastrointestinal symptoms in the past 12 months. Lifetime rates for alternative health care use for gastrointestinal symptoms were 20.8% (n = 43). Independent predictors of conventional health care use were more frequent abdominal pain, greater interference of gastrointestinal symptoms with work and activities and a greater satisfaction with the physician-patient relationship. Being female independently predicted alternative health care use. CONCLUSIONS: Psychological morbidity did not predict conventional or alternative health care use for gastrointestinal symptoms. Other factors were more important.

Predictors of health care seeking for irritable bowel syndrome and nonulcer dyspepsia: a critical review of the literature on symptom and psychosocial factors.

OBJECTIVES: Health care use is a costly outcome of the irritable bowel syndrome (IBS) and nonulcer dyspepsia (NUD), but the predictors of this behavior remain poorly defined. We aimed to systematically review the literature to determine which symptoms and psychosocial factors drive health care seeking in these disorders. METHODS: A broad based MEDLINE and Current Contents search between 1966 and 2000 identified 44 relevant publications. References from these articles were also reviewed. RESULTS: The literature suggests that symptom severity is an important factor, but only explains a small proportion of the health care seeking behavior associated with these disorders in population-based studies. Psychosocial factors including life event stress, psychological morbidity, personality, abuse and abnormal illness attitudes and beliefs have been found to characterize those that seek help versus those that do not. The role of other psychosocial factors such as social support, coping style and knowledge about illness are as yet undetermined. CONCLUSIONS: A model for health care seeking for IBS and NUD, with an emphasis on psychosocial factors is presented, but remains to be tested.

Irritable bowel syndrome according to varying diagnostic criteria: are the new Rome II criteria unnecessarily restrictive for research and practice?

OBJECTIVES: It has been suggested that the variation in the prevalence of irritable bowel syndrome (IBS) may be due to the application of different diagnostic criteria. New criteria for IBS have been proposed (Rome II). It is unknown whether persons meeting different criteria for IBS have similar psychological and symptom features. The aim of this study was to measure the prevalence of IBS according to Manning and Rome definitions of IBS and to evaluate the clinical and psychological differences between diagnostic categories. METHODS: A total of 4500 randomly selected subjects, with equal numbers of male and female subjects aged > or = 18 yr and representative of the Australian population, took part in this study. Subjects were mailed a questionnaire (response rate, 72%). Characteristics measured were gastrointestinal symptoms over the past 12 months, neuroticism and extroversion (Eysenck Personality Questionnaire), anxiety and depression (Delusions-Symptoms-States Inventory), mental and physical functioning (SF-12), and somatic distress (Sphere). RESULTS: The prevalence for IBS according to Manning, Rome I, and Rome II was 13.6% (95% confidence interval [CI] = 3.5-5.1%), 4.4% (CI 6.0-7.8%), and 6.9% (CI 12.3-14.8%), respectively [corrected]. Only 12 persons with Rome I did not also meet Rome II criteria; 196 persons with Manning criteria did not meet Rome II cut-offs. Having IBS regardless of which criteria were used was significantly associated with psychological morbidity, but psychological factors were not important in discriminating between diagnostic categories. However, pain and bowel habit severity independently discriminated between diagnostic groups. CONCLUSIONS: IBS is a relatively common disorder in the community. The new Rome II criteria may be unnecessarily restrictive in practice.

The impact of functional gastrointestinal disorders on quality of life.

OBJECTIVE: The impact of functional gastrointestinal disorders (FGIDs) on quality of life is unknown. We aimed to evaluate whether FGIDs impair quality of life in terms of mental and physical functioning in patients and nonpatients. METHODS: A random sample of 4500 subjects, representative of the Australian population, were mailed a questionnaire on gastrointestinal symptoms in the past 12 months. Quality of life was assessed using the valid SF-12, in which the lower the scores, the greater the impairment of quality of life. The response rate was 72%. RESULTS: Among those fulfilling Rome I criteria for a diagnosis of a FGID (n = 1006) versus those not having a FGID (n = 1904) (healthy controls), there was a significant association with impaired mental (43.9 vs. 48.1) and physical (47.7 vs. 51.6) functioning. Mental functioning (43.3 vs. 44.9) and physical functioning (46.0 vs. 50.5) was significantly more impaired in patients versus nonpatients with a FGID. Furthermore, nonpatients with a FGID had more impaired mental and physical functioning than healthy controls. CONCLUSION: FGIDs impair quality of life, particularly in those that consult for health care.