Expectations of IBS patients concerning disease and healthcare providers: Results of a prospective survey among members of a French patients' association.

BACKGROUND AND AIMS: IBS patients have an impaired quality of life (QoL) and feel dissatisfaction with medical care. We aim to describe the expectations of members of the French Association of IBS patients (APSSII) concerning health care providers (HCPs) and a patients' organization. PATIENTS AND METHODS: From January to June 2013, APSSII members were asked to answer questionnaires on their expectations and experiences concerning IBS and HCP. RESULTS: 222/330 (67%) responded (women: 68.5%, 46.5±17.7 years, disease duration: 8.8±0.7 years, IBS-D 33.6%, IBS-C 26.7%, IBS-M 38.2%. IBS-SSS>300 in 53% and HAD score>19 in 45%). QoL impairment was correlated with disease severity and HAD score (r=-0.707 and r=-0.484, P<0.001 respectively), but not with IBS subtype. Expectations for IBS were "improved health", "better information on causes and treatments" (94%) and "better disease recognition" (86%). A significant gap was observed between expectations and experiences with HCPs. Better information, less isolation, recognition of the disease and a decrease in medical expenses were the main expectations for joining a patients' organization. CONCLUSIONS: French IBS patients have a severe disease with a significant psychological impact and impaired QoL in half of the patients, certain unsatisfied expectations concerning HCP and high expectations in joining a patients' organization.

The diagnostic value of the functional lumen imaging probe versus high-resolution anorectal manometry in patients with fecal incontinence.

BACKGROUND: The functional lumen imaging probe (EndoFLIP® ) is a new technology that measures the distensibility of the anal canal represented by the anal distensibility index. The aims of this study were (i) to compare the anal distensibility index to anal pressure in a cohort of patients with fecal incontinence (FI) and (ii) to compare the diagnostic value of the EndoFLIP® to that of high-resolution anorectal manometry (HRAM) in the same cohort of patients. METHODS: Eighty-three consecutive patients with FI who underwent EndoFLIP® and HRAM assessments were enrolled. The diagnostic value of the EndoFLIP® was compared to that of HRAM and agreement between EndoFLIP® and HRAM data was assessed. KEY RESULTS: More than 70% of the patients diagnosed with anal deficiency at rest and/or during voluntary contractions by HRAM had the same diagnosis using the EndoFLIP® . Two patients with higher distensibility indexes at rest had normal anal resting pressures. Sixteen patients with a normal EndoFLIP® index (ie, normal distensibility index at rest and during voluntary contractions) had an abnormal HRAM result. Seven of these 16 patients (44%) had no sphincter lesion or neuropathic disorder that could explain an abnormal anal sphincter function. CONCLUSIONS & INFERENCES: We demonstrated that the anal distensibility index and HRAM results are largely in agreement. We did, however, identify several discrepancies between the two techniques, indicating that they may be complementary.

Are characteristics of abdominal pain helpful to identify patients with visceral hypersensitivity in irritable bowel syndrome? Results of a prospective study.

BACKGROUND: Some consider that patients with visceral hypersensitivity may represent a separate entity within the IBS population not only from a pathophysiological but also from a clinical perspective. The aim of this prospective exploratory study was to assess whether characteristics of abdominal pain in IBS patients could be suggestive of hypersensitivity. METHODS: This prospective study included consecutive IBS patients selected by Rome III criteria. Validated scores (IBS-SSS, Bristol stool scale, HADS) were used to phenotype patients who were also asked to describe the main location of their abdominal pain on a simple image (abdomen divided into 6 zones). Progressive isobaric rectal distensions were performed to demonstrate, with the ascending method of limits, allodynia (pain threshold lower than 24 mmHg). KEY RESULTS: Fifty patients (women: 72%), 42.6 ± 15.7 years old, were included. Sub-types were IBS-D, IBS-C and IBS-M in 58%, 22% and 20% of cases, respectively. Allodynia was present in 18% of cases. Neither IBS-SSS nor intensity of pain was predictive of hypersensitivity. In hypersensitive patients, pain was more often located in one of the two iliac fossa (P = 0.02) and located outside these areas in only 11% of cases. The sensitivity and the specificity of this pain location to differentiate hyper from normosensitive patients were 0.89 and 0.59, respectively. CONCLUSIONS & INFERENCES: The location of pain is different between hyper and normosensitive IBS patients. Pain located outside one of the two iliac fossa suggests that the patient is normosensitive.

Prevalence and clinical features of opioid-induced constipation in the general population: A French study of 15,000 individuals.

BACKGROUND: Constipation is common during opioid therapy and can compromise analgesia. AIM: The aim of this article is to determine the prevalence and clinical characteristics of opioid-induced constipation (OIC) in France. METHODS: A questionnaire study was conducted in a representative sample of the French general population. Participants completed a 31-item questionnaire covering opioid use during the previous six months, and the occurrence of constipation (defined as <3 bowel movements per week, straining during defaecation, or both) during opioid treatment. RESULTS: Data were obtained from 15,213 participants, of whom 4753 (31.2%) reported opioid use. Most analgesics (96.5%) were classified as World Health Organization step II analgesics, and the remainder were step III. The most common indications for opioids were bone or joint pain, and soft tissue pain. Overall, 414/4753 (8.7%) opioid users reported OIC while the prevalence of OIC reached 21% in case of regular or prolonged (>1 month) opioid use. Other characteristics associated with OIC included female gender, age ≥50 years and use of step III opioids. Only 177/414 (42.8%) participants with OIC had used medications (most commonly osmotic laxatives) to treat constipation, and satisfaction with constipation medication was moderate (mean (SD) score 7.2 (1.3) on a scale of 0-10). CONCLUSIONS: Approximately one-third of a representative French population had used opioids within the previous six months, and 9% of users had experienced OIC, which is more frequent in case of regular use. OIC appears to be under-treated, and participants' satisfaction with their constipation medications was only moderate, suggesting that significant unmet need remains in OIC management.

Tolerance and Long-Term Efficacy of Polyethylene Glycol 4000 (Forlax®) Compared to Lactulose in Elderly Patients with Chronic Constipation.

OBJECTIVES: To assess the tolerance and potential nutritional consequences of long-term repeated doses of PEG 4000 (10 to 30 g/day) in elderly patients with chronic constipation as compared to lactulose (10-30 g/day). DESIGN: Single blind, randomised, multicentre, parallel group comparative study. SETTING: Community-dwelling patients and nursing homes residents aged 70 years and older with a history of chronic constipation. Treatment intervention: PEG 4000 (10-30 g/day) or lactulose (10-30 g/day) for six months. ASSESSMENTS: Clinical nutritional status (Mini Nutritional Assessment), blood and stool samples were taken at baseline and after three and six months for assay of nutritional and absorption parameters. A patient diary documented digestive symptoms and adverse events were recorded. Information on efficacy (stool frequency and consistency) was collected as a secondary outcome measure. RESULTS: Of the 316 patients screened, 245 eligible patients constituted the ITT population (PEG 4000: N = 118; lactulose group: N = 127). The proportion of patients receiving PEG 4000 with abnormal levels of electrolytes, nutritional markers or vitamins did not significantly change in the six months after initiating laxative treatment and do not differ between the two groups. After a D-xylose challenge test, the proportion of patients with abnormally low xylosaemia (suggesting malabsorption) varied from 24.6% at baseline to 35.8% after six months in the PEG 4000 group and from 29.1% to 42.4% in the lactulose group, with no significant between-group or within-group differences. The proportion of patients with poor nutritional status (MNA score <17) varied from 8.5% at baseline to 9.8% after 6 months in the PEG 4000 group and from 3.9% to 5.0% in the lactulose group. No changes in stool fat or total or soluble stool nitrogen were observed in the minority of patients for whom stool analysis was performed. A significantly higher stool frequency (p <0.05) and improved stool consistency (p <0.05) was observed in the PEG 4000 group compared to the lactulose group at each monthly evaluation period. CONCLUSIONS: After six months of treatment with PEG 4000, no clinically relevant changes in biochemical and nutritional parameters and no unanticipated treatment-related adverse events were detected, demonstrating the good clinical tolerance of PEG 4000 in this population of elderly constipated patients. This tolerance was associated with a better clinical efficacy of PEG 4000 compared to lactulose.

An expert consensus definition of failure of a treatment to provide adequate relief (F-PAR) for chronic constipation - an international Delphi survey.

BACKGROUND: As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. AIM: To establish the definition of failure of a treatment to provide adequate relief (F-PAR) to support this management and referral process in patients with chronic constipation. METHODS: We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms. RESULTS: The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed). CONCLUSIONS: We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.

Lactose malabsorption in systemic sclerosis.

BACKGROUND: There are no studies on systemic sclerosis (SSc) assessing the relationship between food intake, especially lactose, and gastrointestinal dysfunction. AIM: To determine the prevalence of lactose malabsorption, using lactose breath test, in patients with SSc. To evaluate the correlation between lactose malabsorption and gastrointestinal involvement. To predict which SSc patients exhibit lactose malabsorption. METHODS: Seventy-seven consecutive Caucasian patients with SSc and 20 control subjects underwent lactose breath test. All patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. RESULTS: The prevalence of lactose malabsorption was higher in SSc patients than in controls (44.3% vs. 10%; P = 0.004). We observed a marked correlation between the presence of lactose malabsorption and: higher values of GSS (P < 0.0001); severe oesophageal (P = 0.018) and small intestinal (P = 0.04) motor disorders; and joint involvement (P = 0.019). Furthermore, in SSc patients with symptomatic lactose malabsorption, the median value of GSS of digestive symptoms was lower after initiation of lactose-free diet (P < 0.0001). CONCLUSIONS: Our study underscores the fact that lactose malabsorption often occurs in patients with systemic sclerosis. Furthermore, our findings highlight the fact that lactose breath test is a helpful, noninvasive method, by identifying the group of patients with systemic sclerosis with symptomatic lactose malabsorption that may benefit from a reduction in lactose intake.

Long term outcome of patients with low level of cryoglobulin (<0.05g/L).

OBJECTIVES: To date, no studies have yet assessed the characteristics of non-HCV patients with low level of cryoglobulin (≤0.05 g/L). The aims of the current study were thus to: 1) determine the prevalence of cryoglobulin ≤0.05 g/L in patients with non-HCV cryoglobulin; and 2) compare clinical features and long term outcome, including organ complications and mortality rate, between non-HCV patients with cryoglobulin level ≤0.05 g/L and those exhibiting cryoglobulin level >0.05 g/L. METHODS: Among 6379 cryoglobulin testing, cryoglobulin was detected in 618 patients (9.69% of cases); of these 618 patients, 453 non-HCV patients were included in the study. The medical records of these patients were reviewed. RESULTS: Of the 453 non-HCV cryoglobulin-positive patients, 265 (58.6%) exhibited cryoglobulin level ≤0.05 g/L. We showed that patients with cryoglobulin level ≤0.05 g/L had: 1) less commonly: palpable purpura (p<0.001), digital ulcers (p=0.006), peripheral neurologic involvement (p=0.03) and renal impairment (p=0.03); and 2) lower median values of ESR (p<0.001) and C-reactive protein (p=0.001). The patients with cryoglobulin level ≤0.05 g/L less often experienced infections (p=0.04) and hematological malignancies (p=0.01); both groups did not differ regarding prevalence of connective tissue diseases and solid tumors. Mortality rate was as high as 13.6% in patients with cryoglobulin level ≤0.05 g/L; death was mainly due to: solid tumors (16.6%), cardiovascular complications (13.8%), hematological malignancies (11.1%), infections (8.3%), pulmonary/renal complications of cryoglobulin (8.3%) and connective tissue diseases (8.3%). CONCLUSION: Our study shows a high prevalence of cryoglobulin level ≤0.05 g/L in clinical practice. Our findings further underscore that non-HCV cryoglobulin level ≤0.05 g/L may be responsible for severe renal and neurological complications, leading to high morbidity and mortality in these patients. Thus, our data suggest that both appropriate therapy and close follow-up may be required to improve such patients' outcome.

Do endoflip assessments of anal sphincter distensibility provide more information on patients with fecal incontinence than high-resolution anal manometry?

BACKGROUND: Anal manometry is the standard technique for evaluating anal sphincter function. However, the functional lumen imaging probe (EndoFLIP(®) ) can be used to measure sphincter distensibility during volume-controlled distensions. Our aims were (i) to assess anal distensibility in patients with fecal incontinence (FI) and in healthy subjects using the EndoFLIP(®) and (ii) to compare the results with anal pressures measured by 3D high-resolution manometry (3D-HRM) to determine whether the EndoFLIP(®) was more sensitive and specific for diagnosing FI than 3D-HRM. METHODS: EndoFLIP(®) and 3D-HRM assessments of 34 female FI patients and 40 healthy female subjects were performed. Anal distensibility was measured as the median cross-sectional area at the narrowest point divided by the corresponding intra-bag pressure at rest and during peak voluntary contraction and was expressed in mm(2) /mmHg. KEY RESULTS: A 40-mL anal distensibility index was selected for further comparisons as it provided the best discrimination between the FI patients and the healthy subjects. The index was significantly higher in the FI patients than in the healthy subjects at rest (p = 1.10(-4) ) and during voluntary contraction (p = 1.10(-4) ). The index at rest and during voluntary contraction appeared to be more appropriate than anal pressures for discriminating between FI patients and healthy subjects. CONCLUSIONS & INFERENCES: The present study confirmed that FI is associated with an abnormally high distensibility index at rest and during voluntary contraction. The ability of the distensibility index to discriminate between FI patients and healthy subjects was significantly better than anal pressure.

Acute sacral nerve stimulation reduces visceral mechanosensitivity in Rat through spinal opioid pathway.

BACKGROUND: Sacral nerve stimulation (SNS) is an alternative surgical treatment of refractory urge incontinence and/or fecal incontinence. Despite its clinical efficacy, the mechanisms of action of SNS remain poorly understood. The aim of this experimental study was to evaluate the effect of SNS on visceral mechanosensitivity in rats. METHODS: Anesthetized Sprague-Dawley rats were treated with SNS or sham stimulation. SNS was performed by implanting an electrode close to the sacral nerve root S1. Rats were administered either a non-selective opioid receptor antagonist (naloxone) or a nitric oxide synthase inhibitor (L-NAME). Colonic mechanosensitivity was evaluated using the variation of arterial blood pressure as a spino-bulbar reflex in response to graded isobaric colorectal distension (CRD). C-fos immunoreactive neurons were quantified in spinal and supraspinal sites. µ-opioid receptor (MOR) internalization was counted in the sacral spinal cord with sham or effective SNS in response to CRD. KEY RESULTS: SNS reduced visceral mechanosensitivity in response to CRD. This effect was reversed by intrathecal and intraveinous naloxone administration. In both models, CRD induced increased c-fos immunoreactivity in the dorsal horn neurons of the sacral spinal cord and supraspinal areas. This increase was prevented by SNS. MOR internalization was significantly higher in stimulated group. CONCLUSIONS & INFERENCES: SNS impacts on visceral mechanosensitivity by decreasing the spino-bulbar reflex in response to CRD. Spinal opioid receptors are likely involved in this effect.

Fecal calprotectin in systemic sclerosis and review of the literature.

Fecal calprotectin (FC) is a simple, non-invasive and reproducible test, which has been described to be highly elevated in patients with active inflammatory bowel diseases. Recently, few authors have reported increased levels of FC in SSc patients, although the relationship between FC levels and the degree of gastrointestinal involvement has not yet been determined in patients with SSc. Thus, this prospective study aimed to: 1) determine the prevalence of increased fecal calprotectin (FC) levels in unselected patients with systemic sclerosis (SSc); 2) make prediction about which SSc patients exhibit increased levels of FC; and 3) evaluate the correlation between increased levels of FC and digestive symptoms, and gastrointestinal involvement, including the presence of small intestinal bacterial overgrowth (SIBO) using glucose H2/CH4 breath test. 125 consecutive patients with SSc underwent FC levels and glucose H2/CH4 breath test. All of the patients with SSc also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. 93 (74.4%) patients had abnormal levels of FC (>50 µg/g); 68 patients (54.4%) exhibited highly elevated levels of FC (>200 µg/g). A marked correlation was found between abnormal FC levels and GSS score of digestive symptoms, esophageal involvement and delayed gastric emptying. Moreover, we found a strong association between abnormal levels of FC and the presence of SIBO on glucose H2/CH4 breath test, with the higher correlation between the presence of SIBO and the level of FC ≥275 µg/g with an area under the receiver operating characteristic curve of 0.97 ± 0.001 (CI: 0.93-0.99; p<10(-6)); the sensitivity of FC level ≥275 µg/g for predicting SIBO was as high as 0.93, while the specificity was 0.95. Finally, eradication of SIBO was obtained in 52.4% of the SSc patients with a significant improvement of intestinal symptoms. Finally, after 3 months of rotating courses of alternative antibiotic therapy, eradication of SIBO was associated with significant decrease of FC levels in SSc patients. The current study underscores that abnormal FC levels were correlated with gastrointestinal impairment, especially SIBO. Because FC levels ≥275 µg/g were markedly associated with the presence of SIBO, our findings suggest that FC may be a helpful test in identifying the group of SSc patients at high risk for SIBO requiring glucose breath test to detect SIBO. Finally, we also suggest that FC levels may be helpful in SSc patients to assess SIBO eradication, as long-term antibiotic therapy is costly and carries risks such as the onset of pseudo-membranous colitis and SIBO-related antibiotic resistance.

Impaired fasting pyloric compliance in gastroparesis and the therapeutic response to pyloric dilatation.

BACKGROUND: Pyloric pressure and compliance have never been investigated in health nor gastroparesis. AIM: We hypothesised that pyloric pressure and/or compliance may be altered in gastroparesis. METHODS: Fasting pyloric pressure and compliance were investigated in 21 healthy volunteers (HV), 27 gastroparetic patients (GP) and 5 patients who had undergone oesophagectomy without pyloroplasty as positive controls. Under videofluoroscopic control, pyloric compliance and pressure were measured by the EndoFLIP technique. Gastric emptying half time (T1/2 ) using (13) C-octanoic acid breath test, as well as symptoms and quality of life (GIQLI score) were also monitored. RESULTS: Mean fasting pyloric compliance was measured at 25.2 ± 2.4 mm²/mmHg in HV, and was lower both in GP (16.9 ± 2.1 mm²/mmHg; P < 0.05) and patients with oesophagectomy (10.9 ± 2.9 mm²/mmHg; P < 0.05). By contrast, fasting pyloric pressure was not different among groups. Fasting pyloric compliance and pressure correlated with T1/2 in GP (R = -0.43; P = 0.04). Fasting pyloric compliance, but not pressure, correlated with symptoms and GIQLI score. Pyloric dilation in 10 GP with low fasting pyloric compliance (<10 mm²/mmHg) increased compliance from 7.4 ± 0.4 to 20.1 ± 4.9 mm²/mmHg (P < 0.01) and improved the GIQLI score from 72.5 ± 5.5 to 89.3 ± 6.1 (P = 0.04). CONCLUSION: This prospective study assessed pyloric compliance for the first time, and showed that fasting pyloric compliance is decreased in gastroparetic patients and is associated with T1/2 , symptoms and quality of life. This suggests that pyloric compliance may be a new relevant metric in gastroparetic patients, and may be useful to target patients for pyloric dilation or botulinum toxin injection.

Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis.

BACKGROUND: To date, there are no large studies on videocapsule endoscopy in systemic sclerosis (SSc). Consequently, the prevalence and features of gastrointestinal mucosal abnormalities in SSc have not been determined. AIMS: To determine both prevalence and characteristics of gastrointestinal mucosal abnormalities in unselected patients with SSc, using videocapsule endoscopy. To predict which SSc patients are at risk of developing potentially bleeding gastrointestinal vascular mucosal abnormalities. METHODS: Videocapsule endoscopy was performed on 50 patients with SSc. RESULTS: Prevalence of gastrointestinal mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were predominant, including: watermelon stomach (34.6%), gastric and/or small intestinal telangiectasia (26.9%) and gastric and/or small intestinal angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P = 0.02), lower levels of ferritin (P < 0.0001) and anti-centromere antibody. CONCLUSIONS: Our study identifies a high frequency of gastrointestinal mucosal abnormalities in SSc, with a marked predominance of vascular mucosal damage. Furthermore, our study shows a strong correlation between gastrointestinal vascular mucosal lesions and presence of severe extra-digestive vasculopathy (digital ulcers and higher nailfold videocapillaroscopy scores). This latter supports the theory that SSc-related diffuse vasculopathy is responsible for both cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold videocapillaroscopy may be a helpful test for managing SSc patients. In fact, nailfold videocapillaroscopy score should be calculated routinely, as it may result in identification of SSc patients at higher risk of developing potentially bleeding gastrointestinal vascular mucosal lesions.

Can multichannel intraluminal pH-impedance monitoring be limited to 3 hours? Comparison between ambulatory 24-hour and post-prandial 3-hour recording.

Esophageal multichannel intraluminal pH-impedance recording (MII) is now a valid technique for determining the acidic, liquid, gas or mixed nature of gastroesophageal reflux episodes. However, some recordings may stop prematurely due to technical reasons or poor patient tolerance of the probe. Therefore, we questioned whether analysis of post-prandial 3-hour recording could predict the results obtained in ambulatory 24-hour recording. Fifty patients with symptoms of gastroesophageal reflux disease were investigated. For each patient, post-prandial 3-hour MII was recorded after a test meal, then followed by ambulatory 21-hour MII. Correlation between the total number of liquid reflux events in the 3-hour and 24-hour recordings was elevated (R=0.71; P<0.001), with better correlation for acid (R=0.80; P<0.001) and weak acid reflux (R=0.56; P<0.001) than non-acid reflux (R=0.44; P<0.01). Sensitivity and specificity of 3-hour recording in detecting elevated liquid reflux over 24 hours (id>75reflux/24 h) were 49% and 100%, respectively, for 8 or less liquid/mixed reflux events per 3 hours, and 78% and 88%, respectively for 15 or more liquid/mixed reflux events per 3 hours. The sensitivity and specificity of symptom association probability (SAP) calculated over 3 hours were 56% and 91%, respectively. In conclusion, we identified relevant indicators on the 3-hour post-prandial recording likely to give accurate prediction of absence or presence of gastroesophageal reflux disease from 24-hour MII recording.

Effect of transcranial magnetic stimulation on rectal sensitivity in irritable bowel syndrome: a randomized, placebo-controlled pilot study.

AIM: Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex can induce analgesic effects in patients with chronic pain syndromes through its effect on central pain-modulatory systems. Our aim was to evaluate the effect of rTMS on rectal sensitivity in irritable bowel syndrome (IBS) patients. METHOD: In this randomized, sham-controlled, proof-of concept trial, 21 IBS patients (11 women and 10 men; mean age 44.0 ± 12.6 years) were randomized, using a double-blind crossover protocol, to active or sham rTMS for 5 days of treatment. The primary outcome was the increase in the pressure pain threshold after rTMS. Secondary outcomes were the changes in maximum tolerated rectal volume, rectal compliance and average pain intensity between baseline and the end of the treatments. RESULTS: There were no statistically significant differences between active and sham rTMS in terms of an increase in the pressure pain threshold, maximum tolerated volume and rectal compliance at the end of the treatments compared with baseline. However, in the subgroup of patients with the most marked rectal hypersensitivity, the volume threshold was significantly improved by active, but not by sham, rTMS (P = 0.03). Patients experienced a significant improvement in pain regardless of the type of stimulation. CONCLUSION: This pilot study failed to demonstrate any benefit of rTMS on our primary end-point. However, the effect of rTMS on rectal tolerated volume in the most hypersensitive patients was encouraging enough to plan more powered studies.

On-demand treatment with alverine citrate/simeticone compared with standard treatments for irritable bowel syndrome: results of a randomised pragmatic study.

BACKGROUND: In routine practice, irritable bowel syndrome (IBS) symptoms are often difficult to be relieved and impair significantly patients' quality of life (QoL). A randomised, double-blind, placebo-controlled study has shown the efficacy of alverine citrate/simeticone (ACS) combination for IBS symptom relief. AIM: As IBS symptoms are often intermittent, this pragmatic study was designed to compare the efficacy of an on-demand ACS treatment vs. that of usual treatments. METHODS: Rome III IBS patients were enrolled by 87 general practitioners who were randomly allocated to one of two therapeutic strategies: on-demand ACS or usual treatment chosen by the physician. The primary outcome measure was the improvement of the IBSQoL score between inclusion and month 6. RESULTS: A total of 436 patients (mean age: 54.4 years; women: 73.4%) were included, 222 in the ACS arm and 214 patients in the usual treatment arm, which was mainly antispasmodics. At 6 months, improvement of IBSQoL was greater with ACS than with the usual treatment group (13.8 vs. 8.4; p < 0.0008). The IBS-severity symptom score (IBS-SSS) was lower with ACS than in the usual treatment arm with a mean (SE) decrease of 170.0 (6.6) vs. 110.7 (6.7), respectively (p = 0.0001). An IBS-SSS < 75 was more frequent in the ACS group (37.7% vs. 16.0%; p < 0.0001). Improvement of both abdominal pain and bloating severity was also greater with the on-demand ACS treatment, which was associated with both lower direct and indirect costs. CONCLUSIONS: After 6 months, on-demand ACS treatment led to a greater improvement of QoL, reduced the burden of the disease and was more effective for IBS symptom relief than usual treatments.

Influence of gastric emptying on gastro-esophageal reflux: a combined pH-impedance study.

BACKGROUND: The involvement of delayed gastric emptying (GE) in the pathophysiology of gastro-esophageal reflux disease (GERD) remains debated and has been to date only assessed using esophageal pH-metry that only detects acidic reflux. We therefore investigated whether delay in GE could impact on liquid, mixed, and gas reflux detected using combined esophageal pH-impedance recording. PATIENTS AND METHODS: Thirty consecutive patients were explored with GE and esophageal pH-impedance measurement in the workup of typical symptoms of GERD. Gastric emptying was assessed using the (13) C-octanoic acid breath test and an ambulatory esophageal pH-impedance recording was performed off proton pump inhibitors (PPIs) for 24 h. KEY RESULTS: Gastric emptying was normal in 17 patients and delayed in 13 patients. Delay in GE increased the daily number of liquid/mixed reflux events detected by combined esophageal pH-impedance monitoring, but had no effect of esophageal acid exposure or gas reflux. This translated in increased number of postprandial reflux events, with a longer bolus clearance time and increased esophageal proximal extension. In patient with delayed GE, symptomatic reflux had a higher proximal extension and a longer bolus clearance time compared to symptomatic reflux events from patients with normal GE. CONCLUSIONS & INFERENCES: Delay in GE increases daily and postprandial liquid/mixed reflux events. Reflux characteristics differently trigger symptoms in patients with normal and delayed GE, and may impact on the therapeutic strategy.

Glucose-induced incretin hormone release and insulin sensitivity are impaired in patients with idiopathic gastroparesis: results from a pilot descriptive study.

BACKGROUND: Incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)] released by the gut modulate gastrointestinal motility and influence gastric emptying (GE). Abnormal secretion or sensitivity to these hormones could contribute to the pathogenesis of gastroparesis. The aim of this study was to investigate incretin hormone secretion during a prolonged oral glucose load in non-diabetic patients with documented idiopathic gastroparesis. METHODS: Fifteen patients referred for digestive postprandial discomfort with delayed GE demonstrated by a (13) C-labeled octanoate breath test were included and compared with 10 healthy controls. A 75 g oral glucose load was performed, with blood samplings every 30 min for 5 h, to determine glucose, insulin, GIP, and GLP-1 blood levels. KEY RESULTS: Fasting GIP concentration was significantly higher in the patient group (56.1 ± 5.8 pg mL(-1) vs 29.9 ± 7.7 pg mL(-1), P =0.012). Postglucose load GIP concentrations were also significantly elevated in patients with gastroparesis, whereas GLP-1 concentrations during fasting and postglucose load conditions were not different to those of healthy controls. Moreover, glucose tolerance during glucose load was abnormal in patients, combining hyperglycemic insulin resistance and hyperinsulinism patterns, while fasting values for glycemia, insulin sensitivity, and insulin concentrations were normal. CONCLUSIONS & INFERENCES: Patients with idiopathic gastroparesis exhibit abnormal GIP levels associated with impaired insulin sensitivity during oral glucose load. Further studies are needed to establish the involvement of these defects in the pathophysiology of gastroparesis.