Constipation-predominant Irritable Bowel Syndrome Research Articles

Is There Enough Evidence for the Association of GNβ3 C825T Polymorphism With Functional Dyspepsia and Irritable Bowel Syndrome?

TO THE EDITOR: I read with great interest the paper from the Kim et al1 on the G-protein beta3 subunit (GNβ3) C825T polymorphism with overlap syndrome of functional dyspepsia (FD) and irritable bowel syndrome (IBS) which demonstrated that no apparent association of the GNβ3 C825T polymorphism with FD, IBS or the overlap of FD and IBS existed. However, a recent study on Korean children showed the CC genotype of GNβ3 C825T may be associated with FD and diarrhea predominant IBS and the TT genotype might be associated with constipation predominant IBS.2 Since the first study3 from Germany which indicated homozygous GNβ3 825CC genotype was associated with unexplained predominantly upper abdominal symptoms, many studies4-13 around the world showed inconsistent results on the association between the GNβ3 C825T polymorphism and functional gastrointestinal disorders (FGIDs). Many factors including heterogeneity of the disease, sample size, sample selection or racial difference may have contributed to these conflicting results. Still, we need to perform further large-scaled well-controlled studies to clarify this unresolved issue. The GNβ3 C825T polymorphism may change gastrointestinal motor and sensory functions through intracellular signal transduction and biological activity. Camilleri et al14 showed that GNβ3 T allele was associated with lower fasting gastric volume, which was one of the factors that predicted a portion of the variance in the symptoms of patients with dyspepsia.15 Further physiologic studies that deal with the effect of the GNβ3 C825T polymorphism on gastrointestinal motor and sensory functions are necessary to clarify the pathophysiologic mechanism in which genetic variations contribute to gastrointestinal symptoms. Can the GNβ3 C825T polymorphism influence response to therapy in FGIDs? Camilleri et al16 recently showed that GNβ3 TC/TT genotype might be associated with lower sensations of gas and urgency in response to rectal distention after clonidine treatment in humans. These findings could lead us to select FGIDs patients potentially treatable with clonidine and other drugs, based on genetic variation. Further pharamcogenetic studies could open a new horizon on treating patients with FGIDs in the future.

Psychiatric, Somatic and Other Functional Gastrointestinal Disorders in Patients With Irritable Bowel Syndrome at a Tertiary Care Center

Background/AimsTo study the prevalence of somatic and psychiatric co-morbidities in the patients of irritable bowel syndrome (IBS) and to assess the quality of life (QOL) of these patients.MethodsOne hundred and eighty-four IBS patients and 198 controls were included. Diagnosis of IBS, its sub-classification and assessment of other functional gastrointestinal disorders (FGIDs) was made on basis of Rome III criteria. Severity of IBS was assessed using IBS severity scoring system. Psychiatric evaluation was done using Patient Heath Questionnaire. QOL was evaluated using WHO QOL-BREF.ResultsOne hundred and forty-seven (79.9%) and 158 (85.9%) patients with IBS had at least one other FGID or at least one somatic co-morbidity, respectively. Higher number of patients had at least one psychiatric co-morbidity compared to controls (79.9% vs 34.3%; P < 0.001). Major depressive syndrome (47.3% vs 5.1%; P < 0.001), somatoform disorder (50% vs 14.6%; P < 0.001) and panic syndrome (44% vs 11.6%; P < 0.001) were more common in IBS than controls. Only 14 (7.6%) patients were receiving drug treatment for their psychiatric illness. Severe IBS symptoms were present in significantly higher number of patients with constipation predominant IBS than diarrhea predominant IBS. Those with severe disease had higher prevalence of psychiatric (95.1%) and somatic (96.7%) co-morbidities compared with mild disease. QOL of IBS patients was significantly lower in all four domains compared to controls. Presence of at least one other FGID was significantly associated with presence of one or more psychiatric co-morbidity (P < 0.001).ConclusionsMajority of IBS patients presenting to a tertiary care center had associated psychiatric, somatic co-morbidities and reduced QOL. Very few of them received specific psychiatric treatment.

Sensory neuro-immune interactions differ between Irritable Bowel Syndrome subtypes

ObjectiveThe gut is a major site of contact between immune and sensory systems and evidence suggests that patients with irritable bowel syndrome (IBS) have immune dysfunction. Here we show how...

Diet in subjects with irritable bowel syndrome: A cross-sectional study in the general population

BackgroundPatients with irritable bowel syndrome (IBS) often relate symptoms to the intake of certain foods. This study assesses differences in diet in subjects with and without IBS.MethodsThe cross-sectional, population-based study was conducted in Norway in 2001. Out of 11078 invited subjects, 4621 completed a survey about abdominal complaints and intake of common food items. IBS and IBS subgroups were classified according to Rome II criteria.ResultsIBS was diagnosed in 388 subjects (8.4%) and, of these, 26.5% had constipation-predominant IBS (C-IBS), 44.8% alternating IBS (A-IBS), and 28.6% diarrhoea-predominant IBS (D-IBS). Low intake of dairy products (portions/day) (Odds Ratio 0.85 [CI 0.78 to 0.93], p = 0.001) and high intake of water (100 ml/day) (1.08 [1.02 to 1.15], p = 0.002), tea (1.05 [1.01 to 1.10], p = 0.019) and carbonated beverages (1.07 [1.01 to 1.14], p = 0.023) were associated with IBS. A lower intake of dairy products and a higher intake of alcohol and carbonated beverages were associated with D-IBS and a higher intake of water and tea was associated with A-IBS. In subjects with IBS the severity of symptoms was associated with a higher intake of vegetables and potatoes in subjects with C-IBS, with a higher intake of vegetables in subjects with A-IBS, and with a higher intake of fruits and berries, carbonated beverages and alcohol in subjects with D-IBS.ConclusionsIn this study, the diet differed in subjects with and without IBS and between IBS subgroups and was associated with the severity of symptoms.

A Prospective Randomized Trial of Mosapride vs. Placebo in Constipation-Predominant Irritable Bowel Syndrome

To the Editor: Irritable bowel syndrome (IBS) is a common disorder affecting ~5% of adults and comprising 28% of gastroenterology practice (1,2). Treatment of IBS remains a challenge because of its poorly defined pathophysiology, high placebo response, and variable symptomatology (3). Mosapride citrate, a selective partial 5–HT4 receptor agonist, which enhances gastrointestinal motility after accelerating the release of acetylcholine from nerves in the gastrointestinal tract (4), has been shown to accelerate colonic motility in animals (5). A small Japanese study (6) involving 11 patients with constipation-predominant IBS (C-IBS) showed that mosapride reduced abdominal pain and distention, decreased flatus, shortened bowel transit time, and produced looser stools, suggesting that mosapride may be useful in C-IBS.

Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome

The glucagon-like peptide 1 (GLP-1) analog ROSE-010 reduced pain during acute exacerbations of irritable bowel syndrome (IBS). Our objective was to assess effects of ROSE-010 on several gastrointestinal (GI) motor and bowel functions in constipation-predominant IBS (IBS-C). In a single-center, randomized, parallel-group, double-blind, placebo-controlled, dose-response study, we evaluated safety, pharmacodynamics, and pharmacokinetics in female patients with IBS-C. ROSE-010 (30, 100, or 300 μg sc) or matching placebo was administered once daily for 3 consecutive days and on 1 day 2-10 days later. We measured GI and colonic transit by validated scintigraphy and gastric volumes by single-photon emission computed tomography. The primary end points were half time of gastric emptying of solids, colonic transit geometric center at 24 h, and gastric accommodation volume. Analysis included intent-to-treat principle, analysis of covariance (with body mass index as covariate), and Dunnett-Hsu test for multiple comparisons. Exposure to ROSE-010 was approximately dose-proportional across the dose range tested. Demographic data in four treatment groups of female IBS-C patients (total 46) were not different. Gastric emptying was significantly retarded by 100 and 300 μg of ROSE-010. There were no significant effects of ROSE-010 on gastric volumes, small bowel or colonic transit at 24 h, or bowel functions. The 30- and 100-μg doses accelerated colonic transit at 48 h. Adverse effects were nausea (P < 0.001 vs. placebo) and vomiting (P = 0.008 vs. placebo). Laboratory safety results were not clinically significant. In IBS-C, ROSE-010 delayed gastric emptying of solids but did not retard colonic transit or alter gastric accommodation; the accelerated colonic transit at 48 h with 30 and 100 μg of ROSE-010 suggests potential for relief of constipation in IBS-C.

Polymorphisms of the Serotonin Transporter Gene and G-Protein β3 Subunit Gene in Korean Children with Irritable Bowel Syndrome and Functional Dyspepsia

Background/AimsMany candidate gene studies have revealed that polymorphisms of the 5'-flanking controlled SERT gene linked polymorphic region (5HTT-LPR) gene and G-protein β3 C825T gene might be associated with functional dyspepsia (FD) and irritable bowel syndrome (IBS). This study was performed to investigate polymorphisms of the 5HTT-LPR gene and G-protein β3 C825T gene in FD and IBS in Korean children.MethodsIn total, 102 patients with FD, 72 patients with IBS based on the Rome III criteria and 148 healthy controls without gastrointestinal symptoms were included in the study to analyze 5HTT-LPR and G-protein β3 C825T polymorphisms.Results5HTT-LPR genotype analysis revealed no signifi cant differences in FD and IBS patients compared with controls. The GNβ3 C825T genotype distribution for CC, CT, and TT was 23.6%, 53.4%, and 23.0% in controls, 36.3%, 38.2%, and 25.5% in FD and 37.5%, 38.9%, and 23.6% in IBS, respectively. The CC genotype was more common in FD and IBS patients than controls (p<0.05). When the IBS patients were grouped according to IBS subtypes, CC genotype GNβ3 C825T was common in diarrhea-dominant IBS, and the TT genotype was common in constipation-dominant IBS (p<0.05).ConclusionsThe CC genotype of G-protein β3 C825T may be associated with FD and diarrhea-predominant IBS. The TT genotype may be associated with constipation-predominant IBS.

Subtypes of irritable bowel syndrome on Rome III criteria: A multicenter study

The aim of this study was to explore the distribution and clinical characteristics of four subtypes of irritable bowel syndrome (IBS) based on Rome III criteria in Chinese. A total of 754 consecutive IBS outpatients from three tertiary hospitals in China were included. Diagnostic criteria were based on Rome II or Rome III. Among 754 outpatients, 510 (67.6%) patients met the Rome II criteria, 735 (97.5%) patients met the Rome III criteria and 492 (65.3%) patients met both sets of criteria. Among 735 patients who met the Rome III criteria, 66.3% had IBS with diarrhea (IBS-D), 14.7% had IBS with constipation (IBS-C), 4.2% had mixed IBS (IBS-M) and 14.8% had unsubtyped IBS (IBS-U). Most of the IBS-D, IBS-C and IBS-M patients based on the Rome III criteria matched the diarrhea-predominant IBS, constipation-predominant IBS and alternating IBS based on the Rome II criteria, respectively. Among IBS-U patients, 57.0%, 33.3% and 9.7% had constipation-predominant IBS, diarrhea-predominant IBS and alternating IBS, respectively. For IBS-M, the frequencies of bowel movements were stable in 48.4% patients and variable in 51.6% patients. Defecation urgency and straining were most frequent in IBS-M and least frequent in IBS-U patients than other subtypes. About 77.2% of IBS-U patients had abnormal stool frequency (< 3 times/week or > 3 times/day). The Rome III criteria are more sensitive and practical in diagnosing IBS. IBS-D is the most frequent subtype, which is followed by IBS-U, IBS-C and IBS-M. IBS-U is a new subtype, which warrants further studies.

Commentary: long-term lubiprostone for constipation predominant IBS

Commentary: long-term lubiprostone for constipation predominant IBS

Coeliac disease in irritable bowel syndrome (Rome III) in Southeast Iran

Background and study aimsIrritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder and coeliac disease (CD) is an auto-immune enteropathy that can mimic almost any functional GI disorder. Both IBS and coeliac disease share common symptoms. The aim of the present study was to estimate the prevalence of CD in patients with IBS and its sub-types. Patients and methodsIn this cross-sectional study (2008–2010), all consecutive patients with IBS who fulfilled the Rome III criteria attending the GI units in Zahedan (Southeast Iran) were included. Patients based on the sub-type of IBS were classified as diarrhoea-predominant irritable bowel syndrome (D-IBS), constipation-predominant irritable bowel syndrome (C-IBS) and alternating symptoms (mixed type). Immunoglobulin A (IgA) tissue transglutaminase (anti-tTG) was used to screen patients for CD. In the case of positive serologic test, duodenal biopsies were taken to confirm the diagnosis. ResultsA total of 364 (221 females and 143 males) patients with IBS were included. The mean±standard deviation (SD) age of patients was 37.4±12.4years. Twenty (5.5%) patients were found to have positive IgA anti-tTG. Main symptoms of patients were diarrhoea (11/20), bloating (10/20) and abdominal distension (6/20). Thirteen (10.5%) patients were found to have positive IgA anti-tTG among the D-IBS, two (1.6%) in the C-IBS and five (4.2%) in M-IBS groups. ConclusionThe prevalence of CD in IBS is high. IBS subjects whose main complaint is diarrhoea, bloating or even abdominal distension should be evaluated for CD.

Acute Tryptophan Depletion and Functional Brain Imaging in Irritable Bowel Syndrome (Gut 2011;60:1196-1203)

Serotonin (5-hydroxytryptamine; 5-HT) is an important signaling molecule in the brain-gut axis, and abnormalities of 5-HT signaling system in the gastrointestinal (GI) tract have been investigated in irritable bowel syndrome (IBS).1 However, there are few studies on of acute tryptophan depletion (ATD)-induced 5-HT modulation at the brain level in IBS. The current study by Labus et al2 is worth examining because it provides novel information on brain network and the augmented activity that may play an important role in pathophysiology of irritable bowel syndrome. This study was aimed at testing 2 hypotheses. The first was that ATD in healthy women increases the engagement of an emotional arousal circuit during rectal distension. The second was that these changes in the brain are consistent with those changes in female patients with constipation predominant IBS (IBS-C). These 2 hypotheses were tested by ATD and functional magnetic resonance image (fMRI) during visceral stimuli. The subjects were 12 healthy women and 14 female patients with IBS-C. ATD was used as a technique for lowering brain 5-HT. Functional MRI was used as a non-invasive tool to measure brain responses to visceral stimuli. Balloon inflation was used for rectal distension with 2 levels of pressure, including non-painful distension pressure and maximum tolerable pressure. Effective connectivity analysis was used as a mean to test hypotheses regarding neural circuits and network functioning. In healthy women, balloon inflation in the rectum showed changes in brain activity, and ATD enhanced these changes in brain activity. Brain regions activated with ATD and balloon inflation were the homeostatic afferent network and the emotional arousal network. The amygdala, a key brain region in the emotional arousal network, and the thalamus showed a transient high activation during ATD, while other regions showed sustained activity. Effective connectivity analyses revealed that ATD made a stronger engagement of the emotional arousal circuitry compared to placebo in healthy women during balloon inflation. In other words, ATD resulted in reduced feedback inhibition of the amygdala during an aversive visceral stimulus in healthy women. A similar pattern of effective connectivity within the emotional arousal network was observed in IBS-C patients during rectal distension even without ATD.

Gender Role in Irritable Bowel Syndrome: A Comparison of Irritable Bowel Syndrome Module (ROME III) Between Male and Female Patients

Background/AimsIrritable bowel syndrome (IBS) is a widespread chronic health condition which is significantly more prevalent in women. We conducted a gender difference analysis by comparing findings of men and women to determine whether any significant differences exist or not.MethodsThis single-center study was conducted in Tehran, Iran during 2009-2010. IBS was diagnosed on the basis of Rome III criteria. A simple "10 point" objective questionnaire was used.ResultsA total number of 144 IBS patients including 44 (30.6%) males and 100 (69.4%) females with the mean age of 37.50 ± 11.50 years, were assessed. The only differently observed symptom was nausea which was significantly more prevalent in females (49% vs 18.2%, P < 0.001). The commonest subtype of IBS in male patients was diarrhea predominant IBS (38.6%); while, constipation predominant IBS was the most frequent type among females (38%). Moreover, the frequency of loose, mushy or watery stools within the last 3 months was significantly higher among males (2.11 ± 1.67 vs 1.37 ± 1.50, P = 0.009).ConclusionsWe report that gender is important in IBS. Although qualitative comparison of different subtypes of IBS between male and female failed to meet the statistically significant level, the answers to the corresponding questions of ROME III IBS module suggest the higher prevalence of bowel movements and looser stool in males. Moreover, nausea was reported more often by females.

Autonomic nervous system activity in constipation-predominant irritable bowel syndrome patients

SummaryBackgroundThe main mechanism underlying irritable bowel syndrome is currently believed to be a dysfunction of the brain-gut axis. Autonomic nervous system dysfunction can contribute to development of irritable bowel syndrome symptoms by disturbing visceral sensations.Material/MethodsThirty patients with a diagnosis of constipation-predominant irritable bowel syndrome and 30 healthy volunteers were included in the study. Resting and functional autonomic nervous system tests and percutaneous electrogastrography were performed. Plasma adrenalin, noradrenalin, insulin, ghrelin and cholecystokinin activity was analyzed.ResultsIncreased sympathetic activation with disturbed parasympathetic function was demonstrated. Patients had substantially higher plasma catecholamine concentration, which confirms sympathetic overbalance. Hyperinsulinemia may explain sympathetic predominance followed by gastric and intestinal motility deceleration. Abnormal, reduced ghrelin and cholecystokinin titre may disturb brain-gut axis functioning and may be responsible for gastric motility deceleration. In electrogastrography, distinctly lower values of fasting normogastria percentage and dominant power were observed. Patients had substantially lower slow wave coupling percentage both in fasting and postprandial periods, which negatively correlated with plasma catecholamines level. Gastric myoelectrical activity disturbances may result from lack of sympatho-parasympathetic equilibrium.ConclusionsCentral sympathetic influence within the brain-gut axis is most probably responsible for myoelectrical activity disturbances in irritable bowel syndrome patients.

Effect of composite yogurt enriched with acacia fiber andBifidobacterium lactis

To investigate whether composite yogurt with acacia dietary fiber and Bifidobacterium lactis (B. lactis) has additive effects in irritable bowel syndrome (IBS). A total of 130 patients were randomly allocated to consume, twice daily for 8 wk, either the composite yogurt or the control product. The composite yogurt contained acacia dietary fiber and high-dose B. lactis together with two classic yogurt starter cultures. Patients were evaluated using the visual analog scale via a structured questionnaire administered at baseline and after treatment. Improvements in bowel habit satisfaction and overall IBS symptoms from baseline were significantly higher in the test group than in the control group (27.16 vs 15.51, P = 0.010, 64.2 ± 17.0 vs 50.4 ± 20.5, P < 0.001; respectively). In constipation-predominant IBS, improvement in overall IBS symptoms was significantly higher in the test group than in the control group (72.4 ± 18.4 vs 50.0 ± 21.8, P < 0.001). In patients with diarrhea-predominant IBS, improvement in bowel habit satisfaction from baseline was significantly higher in the test group than in the control group (32.90 vs 7.81, P = 0.006). Our data suggest that composite yogurt enriched with acacia fiber and B. lactis has greater therapeutic effects in patients with IBS than standard yogurt.

Editorial Are probiotics effective in management of irritable bowel syndrome?

Irritable bowel syndrome (IBS) is a chronic disorder of the gut that is common in the world, causing a financial burden to health service and people. IBS is generally divided into several types including diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C), and mixed IBS (sometimes constipation, sometimes diarrhea). Despite the high prevalence of IBS, the exact pathophysiology of IBS is not clear but autonomous nervous system dysfunction seems the most important factor [1]. The management of IBS is often based on severity of disease, and the patient or practitioner preferences. Effective medications for treating symptoms in all IBS subtypes include tricyclic antidepressants (TCAs) [2], antispasmodics [3], selective serotonin reuptake inhibitors (SSRIs) [4], fiber supplements, loperamide, rifaximin, pregabalin, and complementary and alternative medicine therapies such as probiotics, herbal therapies [5] and acupuncture [6, 7]. According to evidence, until this time no complete effective curable drug is known for IBS and thus most of the drugs are still in evaluation. In recent years many drugs from synthetic or natural sources have been introduced. Most researchers in recent years have focused on phosphodiesterase inhibitors [8], melatonin [9], herbal products [5], and probiotics [10].

Drugs and Constipation in Elderly in Nursing Homes: What Is the Relation?

Introduction. Constipation is a common adverse drug reaction. Objective. Study associations between drugs and constipation in nursing home residents. Design. Cross-sectional study. Material and Methods. Nursing home residents above 60 years of age were included. Demographics, diet, physical activity, activity of daily living, nutritional status, use of drugs, and diseases were recorded. Constipation was defined as functional constipation or constipation-predominant IBS according to the Rome III criteria and/or regular use of laxatives. Drugs were classified according to the Anatomical-Therapeutic-Chemical Classification System (ATC), and anticholinergic effect was noted. Results. In all, 79 men and 188 women with a mean age of 85.4 (SD 7.1) years were included. The prevalence of constipation was 71.5%. Use of drugs in general, including polypharmacy, was not associated with constipation. Reduced activity of daily living (OR = 0.71, 95% CI : 0.60–0.84, P < 0.001), other antidepressants (N06AX) (OR 3.08, 95% CI : 1.09–8.68, P = 0.03), and benzodiazepine derivatives (N05BA) (OR = 2.80, 95% CI : 1.12–7.04, P = 0.03) were significantly associated with constipation; drugs with markedly anticholinergic effect (OR = 3.7, 95% CI : 0.78–17.53, P = 0.10), natural opium alkaloid (N02AA) (OR = 5.01, 95% CI : 0.95–25.94, P = 0.06), and propionic acid derivatives (M01AE) (OR = 7.00, 95% CI : 0.75–65.08, P = 0.09) showed a trend. Conclusion. In elderly with constipation, focus should be on specific groups of drugs and nonpharmacological factors, not on drugs in general.

Distinct microbial populations exist in the mucosa‐associated microbiota of sub‐groups of irritable bowel syndrome

There is increasing evidence to support a role for the gastrointestinal microbiota in the etiology of irritable bowel syndrome (IBS). Given the evidence of an inflammatory component to IBS, the mucosa-associated microbiota potentially play a key role in its pathogenesis. The objectives were to compare the mucosa-associated microbiota between patients with diarrhea predominant IBS (IBS-D), constipation predominant IBS (IBS-C) and controls using fluorescent in situ hybridization and to correlate specific bacteria groups with individual IBS symptoms. Forty-seven patients with IBS (27 IBS-D and 20 IBS-C) and 26 healthy controls were recruited to the study. Snap-frozen rectal biopsies were taken at colonoscopy and bacterial quantification performed by hybridizing frozen sections with bacterial-group specific oligonucleotide probes. Patients with IBS had significantly greater numbers of total mucosa-associated bacteria per mm of rectal epithelium than controls [median 218 (IQR - 209) vs 128 (121) P = 0.007], and this was chiefly comprised of bacteroides IBS [69 (67) vs 14 (41) P = 0.001] and Eubacterium rectale-Clostridium coccoides [52 (58) vs 25 (35) P = 0.03]. Analysis of IBS sub-groups demonstrated that bifidobacteria were lower in the IBS-D group than in the IBS-C group and controls [24 (32) vs 54 (88) vs 32 (35) P = 0.011]. Finally, amongst patients with IBS, the maximum number of stools per day negatively correlated with the number of mucosa-associated bifidobacteria (P < 0.001) and lactobacilli (P = 0.002). The mucosa-associated microbiota in patients with IBS is significantly different from healthy controls with increases in bacteroides and clostridia and a reduction in bifidobacteria in patients with IBS-D.

Prucalopride: safety, efficacy and potential applications.

Chronic constipation is a very common functional gastrointestinal disorder which can be associated with significant impairments in quality of life for some people with the condition. Its management has, traditionally, been based on dietary and lifestyle changes and the use of a variety of laxative agents. The evidence base for the efficacy of the latter is, in many cases, slim. Not surprisingly, many patients remain dissatisfied with laxatives thus leading to the development of more pharmacological approaches. Among these approaches is the use of prokinetic agents; while prior molecules have been troubled by lack of selectivity and cardiac side effects, the new agent, prucalopride, appears to be highly selective for the serotonin 5-HT4 receptor and is, therefore, a potent stimulator of gut motility. In three large pivotal randomized controlled trials, prucalopride has been effective in relieving the cardinal symptoms of chronic constipation; these effects have been sustained in open-label follow up for as long as 18 months. The safety profile has been encouraging and, especially so, the absence of arrhythmogenic potential. Studies in men, in constipation-predominant irritable bowel syndrome and in other motor disorders are eagerly awaited.

Tegaserod in the treatment of constipation-predominant irritable bowel syndrome. Do the risks outweigh the benefits?

EditorialIrritable bowel syndrome (IBS) is a common disorderaffecting up to 20% of the population in the USA(Johanson 2004). IBS is considered a functional boweldisorder resulting in abdominal pain and bloating, consti-pation and/or diarrhoea. Women are affected twice asfrequently as men, generally in the 30–50 year age group.Costs to society either directly (medical and diagnostic) orindirectly(time off work)wereestimated tobeapproximatelyUS $4 billion per year for all functional bowel disorders in2004 (American Gastroenterological Association (2011)website). Hence, this is a significant medical problem and alarge therapeutic market.Medical therapies to date have been varied and oftensymptomatic. Antispasmodics, antidiarrhoeals, laxatives,dietary modification, antidepressants and simple analgesicshave all been utilised. None of these agents show whatwould be considered to be a good (level 1) evidence ofefficacy (Johanson 2004; Enck et al. 2010).The current concept of pathogenesis in IBD suggests adysregulation between central nervous (CNS) and entericnervous system (ENS) control.Intrinsic bowel functions suchasmotilityandsecretoryfunctionsaredeterminedbytheENSwithmodificationbytheCNS.Theneurotransmitterinvolvedin many of these sites is serotonin (5-hydroxytryptamine, 5-HT). Hence, manipulation of transmitter levels would beexpected to change symptomatology. 5-HT3 increases gutsecretion, motility and sensation. 5-HT4 receptor agonistshave been shown to increase peristaltic activity in animalmodels (Grider et al. 1998).These pre-clinical findings led to the development of twopotential treatments for IBS, alosetron (a 5-HT3 receptorantagonist)andtegaserod(aselective5-HT4receptoragonist).Tegaserod is in a novel class of drugs (aminoguanidineindoles) designed to be similar in structure to serotonin and toact selectively at 5-HT4 receptors in the GI tract. Tegaserodappears to be effective when assessed by a symptom score intwo large, randomised, placebo-controlled trials (Novick et al.2002;Muller-Lissneretal.2001).The adverse events most frequently recorded withTegaserod are diarrhoea and headache occurring at approx-imately 10% and 15% of patients treated respectively(Johanson 2004; Muller-Lissner et al. 2001; Novick et al.2002; Schoenfeld 2004). The severity of these events isusually mild.Long-term safety data (up to 12 months of treatment)suggest that diarrhoea (10.1%), headache (8.3%), abdominalpain (7.4%) and flatulence (5.5%) remain the most commonproblems (Tougas et al. 2002).ECG data from 2,516 patients with IBS treated with 4–12 mg of Tegaserod per day suggest that no significantelectrocardiographic changes occur (Morganroth et al. 2002).Tegaserod was approved in the USA in 2002 fortreatment of constipation-predominant IBS in women andextended in 2004 to include both men and women up to theage of 65 years. It was denied approval in the EU andsubsequently removed from the US market in March 2007(Food and Drug Administration 2011; http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/UCM051284)whenfindings (from 29 trials and reported to the FDA by the

Health-related quality of life, work productivity and health care resource use associated with constipation predominant irritable bowel syndrome

Objectives:Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Prevalence estimates of IBS vary widely, from 10 to 15%, in the U.S. However, few studies have examined constipation predominant IBS (IBS-C), a subtype of IBS. The aim of this study was to assess the effect of IBS-C on health-related quality of life (HRQOL), work productivity and activity impairment, and health care resource use.Methods:Using data from the 2007 U.S. National Health and Wellness Survey, IBS-C patients (n = 789) were compared to a propensity-score matched comparison group (n = 789). Differences between the groups were examined on HRQOL (SF-12v2), work productivity and activity impairment (WPAI questionnaire), and self-reported resource use in the last 6 months.Results:Patients with IBS-C reported significantly lower levels of HRQOL (physical component summary score: 41.55 [95% CI: 40.72–42.37] versus 44.49 [95% CI: 43.67–45.31]; mental component summary score: 40.58 [95% CI: 39.75–41.40] vs. 45.87 [95% CI: 45.04–46.70]) and significantly higher mean levels of presenteeism (31.72% [95% CI: 28.25%–35.61%] vs. 21.43% [95% CI: 19.03%–24.15%]), overall work impairment (35.54% [95% CI: 31.76%–39.76%] vs. 25.29% [95% CI: 22.59%–28.30%]), and activity impairment (45.78% [95% CI: 43.08%–48.66%] vs. 33.03% [95% CI: 31.08%–35.11%]) than matched comparators (all P values < 0.01). Patients with IBS-C reported significantly more provider visits (8.07 [95% CI: 7.38–8.82] vs. 5.55 [95% CI: 5.07–6.08]) and emergency room visits (0.57 [95% CI: 0.46–0.70] vs. 0.36 [95% CI: 0.29–0.45]) in the past 6 months (all Ps < 0.01). No statistically significant differences between the groups were observed in absenteeism or the number of the days hospitalized.Conclusions:IBS-C was associated with poorer HRQOL, greater work productivity loss and activity impairment, and greater healthcare resource use. Limitations include the study’s cross-sectional design and its self-reported nature. Nevertheless, improved management of IBS-C may reduce the humanistic and economic burden of the condition and benefit patients, employers, and the healthcare system.