Gastroesophageal reflux symptoms among Italian university students: epidemiology and dietary correlates using automatically recorded transactions.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders worldwide, with relevant impact on the quality of life and health care costs.The aim of our study is to assess the prevalence of GERD based on self-reported symptoms among university students in central Italy. The secondary aim is to evaluate lifestyle correlates, particularly eating habits, in GERD students using automatically recorded transactions through cashiers at university canteen. METHODS: A web-survey was created and launched through an app, ad-hoc developed for an interactive exchange of information with students, including anthropometric data and lifestyle habits. Moreover, the web-survey allowed users a self-diagnosis of GERD through a simple questionnaire. As regard eating habits, detailed collection of meals consumed, including number and type of dishes, were automatically recorded through cashiers at the university canteen equipped with an automatic registration system. RESULTS: We collected 3012 questionnaires. A total of 792 students (26.2% of the respondents) reported typical GERD symptoms occurring at least weekly. Female sex was more prevalent than male sex. In the set of students with GERD, the percentage of smokers was higher, and our results showed that when BMI tends to higher values the percentage of students with GERD tends to increase. When evaluating correlates with diet, we found, among all users, a lower frequency of legumes choice in GERD students and, among frequent users, a lower frequency of choice of pasta and rice in GERD students. DISCUSSION: The results of our study are in line with the values reported in the literature. Nowadays, GERD is a common problem in our communities, and can potentially lead to serious medical complications; the economic burden involved in the diagnostic and therapeutic management of the disease has a relevant impact on healthcare costs. CONCLUSIONS: To our knowledge, this is the first study evaluating the prevalence of typical GERD-related symptoms in a young population of University students in Italy. Considering the young age of enrolled subjects, our prevalence rate, relatively high compared to the usual estimates, could represent a further negative factor for the future economic sustainability of the healthcare system.

Analyses of the Post-reflux Swallow-induced Peristaltic Wave Index and Nocturnal Baseline Impedance Parameters Increase the Diagnostic Yield of Impedance-pH Monitoring of Patients With Reflux Disease.

BACKGROUND & AIMS: Analyses of impedance parameters such as the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI) have been proposed to increase the accuracy of diagnosis of reflux disease. We assessed whether these improve the diagnostic yield of impedance pH monitoring of reflux disease. METHODS: We performed a prospective study of consecutive patients with proton pump inhibitor-responsive heartburn who underwent 24-hour impedance pH monitoring at hospitals in Italy from January 2011 through December 2013. Reviewers blindly analyzed off-therapy impedance pH tracings from 289 patients with proton pump inhibitor-responsive heartburn, 68 with erosive reflux disease and 221 with non-erosive reflux disease (NERD), along with 50 healthy individuals (controls). The PSPW index, the MNBI, the esophageal acid exposure time, the number of total refluxes, and the bolus exposure were calculated, as well as the symptom association probability (SAP) and the symptom index (SI). RESULTS: In receiver operating characteristic analysis, the area under curve of the PSPW index (0.977; 95% confidence interval, 0.961-0.993) was significantly greater than that of the other impedance pH parameters in identifying patients with reflux disease (P < .001). The PSPW index and the MNBI identified patients with erosive reflux disease with the highest level of sensitivity (100% and 91%, respectively), as well as the 118 pH-positive (99% and 86%) and 103 pH-negative (77% and 56%) cases of NERD. The PSPW index and the MNBI identified pH-negative NERD with the highest level of sensitivity; values were 82% and 52% for the 65 SAP-positive and/or SI-positive cases and 68% and 63% for the 38 SAP-negative and SI-negative cases. Diagnoses of NERD were confirmed by pH-only criteria, including those that were positive on the basis of the SAP or SI, for 165 of 221 cases (75%) and by impedance pH criteria for 216 of 221 cases (98%) (P = .001). CONCLUSIONS: The PSPW index and the MNBI increase the diagnostic yield of impedance pH monitoring of patients with reflux disease. Analysis of impedance pH data by calculating the PSPW index and the MNBI can increase the accuracy of diagnosis of patients with reflux disease, compared with pH-only data.

Functional Heartburn Overlaps With Irritable Bowel Syndrome More Often than GERD.

OBJECTIVES: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn. METHODS: Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH. RESULTS: Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (P<0.001). At multivariate analysis, IBS and anxiety were independent risk factors for FH in comparison with reflux-related heartburn (GERD+HE). CONCLUSIONS: IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.

Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

BACKGROUND & AIMS: Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). METHODS: In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. RESULTS: FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. CONCLUSIONS: Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements.

Understanding eating choices among university students: A study using data from cafeteria cashiers' transactions.

OBJECTIVE: To illustrate the use of automatically collected data from cashier transactions to understand eating habits among university students using cafeteria and to identify individual characteristics associated with the diverse behaviors. METHODS: The study was carried out at a large university located in Pisa, central Italy, using data about meals automatically recorded from cashier transaction meals during the academic year 2015-16 as well as data from the administrative archive of the university. A model-based clustering relying on multivariate beta distribution was used to cluster eating choices while multivariate multinomial logistic regressions were applied to identify variables associated to diverse clusters identified. RESULTS: Considering 4643 students and about 200,000 meals consumed, results suggest that healthy eaters represented a minority (11.2 %) of the study population while the large part of students composed their meals combining grains with processed food or proteins (32.7 %) and limiting the choice of fruit (42.9 %). Male gender and younger age were associated with eating behavior not in line with recommendations for a healthy diet. CONCLUSIONS: Eating choice resulted to be "compromised" in most of students and specific characteristics associated with unhealthy choice were also identified that can help inform and target specific policy. The use of routinely collected data gives the opportunity to both cafeterias and university to take an active role in policy development.

Critical appraisal of Rome IV criteria: hypersensitive esophagus does belong to gastroesophageal reflux disease spectrum.

The Rome IV Committee introduced a major change in the classification of functional gastrointestinal disorders, proposing a more restrictive definition of gastroesophageal reflux disease (GERD). It was suggested that hypersensitive esophagus (HE) may sit more firmly within the functional realm. It was suggested that GERD diagnosis should be based upon abnormal acid exposure time (AET) only, implying no advantage of impedance-pH over pH monitoring. Symptom association probability (SAP), symptom index (SI) and heartburn relief with proton pump inhibitor (PPI) therapy were regarded as unreliable, whereas a lack of response to PPI was considered as evidence of functional heartburn. These assumptions are contradicted by numerous studies showing the clinical relevance of weakly acidic refluxes and the diagnostic utility of SAP, SI and new impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI). The PSPW index and MNBI provide significant diagnostic advantage, particularly in patients with normal AET who can be classified as HE when both parameters are abnormal, even though SAP and SI are negative. Visceral pain modulators are recommended by the Rome IV Committee despite scanty evidence of efficacy, but a positive outcome with medical or surgical anti-reflux treatment has been reported by several studies of HE patients. Therefore, we believe that patients with endoscopy-negative heartburn should be investigated by means of impedance-pH monitoring with analysis of PSPW index and MNBI: such an approach provides accurate identification of HE cases, who remain, in our opinion, within the realm of GERD and should be treated accordingly.

Gastroesophageal reflux disease, functional dyspepsia and irritable bowel syndrome: common overlapping gastrointestinal disorders.

Several studies have indicated an overlap between gastroesophageal reflux disease (GERD) and various functional gastrointestinal disorders (FGIDs). The overlapping conditions reported have mainly been functional dyspepsia (FD) and irritable bowel syndrome (IBS). The available literature is frequently based on symptomatic questionnaires or endoscopic procedures to diagnose GERD. Rarely, among patients with heartburn, pathophysiological evaluations have been considered to differentiate those with proven GERD from those without. Moreover, both GERD and IBS or FD showed enormous heterogeneity in terms of the criteria and diagnostic procedures used. The GERD-IBS overlap ranges from 3-79% in questionnaire-based studies and from 10-74% when GERD has been diagnosed endoscopically. The prevalence of functional dyspepsia (after normal upper endoscopy) is 12-15% and an overlap with GERD has been reported frequently. Only a few studies have considered a potential overlap between functional heartburn (FH) and IBS using a 24-h pH-metry or impedance-pH evaluation. Similar data has been reported for an overlap between FH and FD. Recently, a revision of the Rome criteria for esophageal FGIDs identified both FH and hypersensitive esophagus (HE) as potential functional esophageal disorders. This might increase the potential overlap between different FGIDs, with FH and HE rather than with GERD. The aim of the present review article was to appraise and discuss the current evidence supporting the possible concomitance of GERD with IBS and FD in the same patients and to evaluate how various GERD treatments could impact on the quality of life of these patients.

Vegetal and Animal Food Proteins Have a Different Impact in the First Postprandial Hour of Impedance-pH Analysis in Patients with Heartburn.

BACKGROUND AND AIMS: By means of 24 h impedance-pH monitoring, we aimed to evaluate the effect of two different meals with a bromatological balanced composition: one with a prevailing component of animal proteins and the other with vegetable proteins. PATIENTS AND METHODS: We enrolled 165 patients with heartburn and negative endoscopy, who underwent impedance-pH monitoring off therapy. Patients were allocated to receive a Mediterranean diet with a total caloric intake of about 1694 kcal, divided into two meals: one with a prevailing component of animal proteins and the other with vegetable proteins. We evaluated the total reflux number, acid exposure time (AET), and symptom-reflux association with impedance-pH analysis. Moreover, during the first postprandial hour (at lunch and dinner), we evaluated the total reflux number, number of acid and weakly acidic refluxes, AET, and presence of symptoms. RESULTS: The male/female ratio was 80/85. Mean age was 51.9 ± 12.1 years. Impedance-pH analysis showed that 55/165 patients had pathological AET or a number of refluxes (nonerosive reflux disease (NERD)), 49/165 had normal AET and a number of refluxes but positive symptom-reflux association (hypersensitive esophagus (HE)), and 61/165 had normal AET and a number of refluxes with negative symptom-reflux association (functional heartburn (FH)). The overall first postprandial hour analysis showed a higher total reflux number, acid reflux number, and AET after the animal protein meal than after the vegetable protein meal. Moreover, more symptoms were reported after the animal protein meal. Similar results have been observed in the three different subcategories of patients (NERD, HE, and FH). CONCLUSIONS: Vegetable proteins are associated with a lower number of refluxes, particularly acid refluxes, and with a reduced number of symptoms during the first postprandial hour. This is a pilot study and future investigations are warranted to confirm these results.

Extra-esophageal presentation of gastroesophageal reflux disease: new understanding in a new era.

Associations of gastroesophageal reflux disease (GERD) with extraesophageal manifestations, such as chronic cough, asthma, and laryngitis, are reported frequently, and there is a strong evidence of biological plausibility in support of this relationship. On the other hand, extraesophageal reflux disease (EERD) is usually multifactorial in nature with reflux being just one of the several potential contributing cofactors. Moreover, the accuracy of currently available diagnostic tests for EERD is suboptimal, and therefore the causal relationship between GERD and EERD remains far from being conclusively proven. In addition, there is a general paucity of data supporting a beneficial effect of anti-reflux treatments on symptoms of patients with suspected EERD. Therefore, diagnostic as well as therapeutic management of EERD remains largely empirical. Current guidelines suggest an initial empiric trial of proton pump inhibitors in patients without alarm features, who present also typical GERD symptoms. For those patients who improve with PPIs, GERD is presumed to be the etiology. In patients with refractory reflux, combined impedance/pH monitoring might provide the single best strategy for evaluating reflux symptoms. In this context, as symptoms ascribable to GERD may depend on other causes, investigations that excludes GERD can help to redirect the diagnostic and treatment efforts to other pathological conditions. The present review intends to discuss the current state of knowledge regarding the challenging diagnostic and therapeutic management of patients with suspected EERD, emphasizing the points of strengths and limitations of currently available diagnostic options, and to provide an update on major diagnostic innovations in this area.

Vonoprazan fumarate for the management of acid-related diseases.

INTRODUCTION: Proton pump inhibitors (PPIs) display a number of limitations and unmet clinical needs that have prompted the development of novel drugs to improve the outcomes of acid-related diseases, including the eradication of H. pylori. In this context, a new synthesized potassium-competitive acid blocker (P-CAB), vonoprazan, showed higher suppression of gastric acid secretion. Areas covered: This review discusses the current knowledge regarding the efficacy of vonoprazan in the treatment of acid-related diseases, with a particular focus on its use in Helicobacter pylori eradication. Expert opinion: Vonoprazan showed some advantages over PPIs in terms of the pharmacokinetic and pharmacodynamic profile: fast onset of action without requiring acid activation and specific administration timing, more potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability. Recent evidence suggests that vonoprazan can be preferred to PPIs as maintenance therapy for reflux esophagitis and eradication of Helicobacter pylori owing to its stronger antisecretory effect. Moreover, vonoprazan displays favorable safety and tolerability profiles, even though long-term studies on the effects of vonoprazan are required.

A review of pharmacotherapy for treating gastroesophageal reflux disease (GERD).

INTRODUCTION: Medical therapy of gastroesophageal reflux disease (GERD) is based on the use of proton pump inhibitors (PPIs) as first choice treatment. Despite their effectiveness, about 20-30% of patients report an inadequate response and alternative drugs are required. Areas covered: This review provides an overview of current pharmacotherapy for treating GERD by showing the results of PPIs, reflux inhibitors, antidepressants and mucosa protective medications. Expert opinion: Medical therapy of GERD does not definitely cure the disease, because even PPIs are not able to change the key factors responsible for it. However, they remain the mainstay of medical treatment, allowing us to alleviate symptoms, heal esophagitis and prevent complications in the majority of cases. Nevertheless, many patients do not respond, because acid does not play any pathogenetic role. Prokinetics and reflux inhibitors have the potential to control motor abnormalities, but the results of clinical trials are inconsistent. Antidepressant drugs are effective in specific subgroups of NERD patients with visceral hypersensitivity, but larger, controlled clinical studies are necessary. Protective drugs or medical devices have been recently adopted to reinforce mucosal resistance and preliminary trials have confirmed their efficacy either combined with or as add-on medication to PPIs in refractory patients.

Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn.

BACKGROUND: Hypersensitive esophagus (HE) is defined by endoscopy-negative heartburn with a normal acid exposure time but positive symptom association probability (SAP) and/or symptom index (SI) on impedance-pH monitoring, and proton pump inhibitor (PPI) responsiveness. Functional heartburn (FH) is distinguished by negative SAP/SI and PPI refractoriness. The clinical value of SAP and SI has been questioned. We aimed to investigate whether impairment of chemical clearance and of mucosal integrity, expressed by the postreflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), characterize HE independently of SAP and SI. METHODS: Impedance-pH tracings from PPI-responsive endoscopy-negative patients, 125 with nonerosive reflux disease and 108 with HE, distinguished by an abnormal and a normal acid exposure time, and from 70 patients with FH were retrospectively selected and blindly reviewed. RESULTS: The mean PSPW index and MNBI were significantly lower in nonerosive reflux disease (30 %, 1378 Ω) than in HE (51 %; 2274 Ω) and in both of them as compared with FH (76 %; 3445 Ω) (P = 0.0001). Both the PSPW index (adjusted odds ratio 0.863, P = 0.001) and the MNBI (adjusted odds ratio 0.998, P = 0.001) were independent predictors of HE; with their combined assessment, the area under the curve on receiver operating characteristic analysis was 0.957. SAP and/or SI was positive in 67 of the 108 HE patients (62 %), whereas the PSPW index and/or MNBI was abnormal in 99 of the 108 HE patients (92 %; P < 0.0001). CONCLUSIONS: HE is characterized by impairment of chemical clearance and mucosal integrity, which explains the increased reflux perception. When SAP and SI afford uncertain results, the PSPW index and MNBI should be analyzed.

Ilaprazole for the treatment of gastro-esophageal reflux.

INTRODUCTION: Despite the undoubted benefit of proton pump inhibitors (PPIs), they have several shortcomings, such as a slow onset of action and a remarkable inter-individual variability, that limit the complete success of these drugs. Recently, a new PPI, ilaprazole, has been developed and used in GERD patients. AREAS COVERED: The present review provides an update on the following points: current knowledge of GERD mechanisms; limitations of actual therapies; pharmacokinetic profile and metabolism of ilaprazole; initial studies on the therapeutic efficacy of ilaprazole in GERD. EXPERT OPINION: Compared with all other approved PPIs, ilaprazole has shown an extended plasma half-life, a metabolism not significantly influenced by CYP2C19 genetic polymorphism and similar safety. This characteristics account for a low inter-individual variability, particularly in Asian populations, a higher suppression of gastric acid secretion, a more rapid acid control and consequent quicker symptom relief and a better effect on nocturnal acidity. However, clinical investigations assessing the efficacy of ilaprazole in the management of GERD are lacking and therefore the potential improvements achievable with ilaprazole in the current standard of care for acid-suppressing treatment must be confirmed in large and randomly controlled clinical trials enrolling patients with both erosive and non-erosive reflux disease.

Vonoprazan for treatment of gastroesophageal reflux: pharmacodynamic and pharmacokinetic considerations.

INTRODUCTION: About 30-40% of GERD patients report an inadequate response to proton pump inhibitors (PPIs) due to their suboptimal pharmacological profiles. Recently, a new synthesized P-CABs, vonoprazan, showed higher suppression of gastric acid secretion as compared to lansoprazole. Areas covered: This review provides an update on the pharmacokinetic properties of vonoprazan and their correlates with pharmacodynamics; preliminary data on the therapeutic efficacy of vonoprazan as compared to lansoprazole in GERD patients Expert opinion: At variance from all available PPIs, vonoprazan acts directly on H+,K+-ATPase irrespectively of its activity, providing a fast onset of action without requiring acid activation and specific administration timing. Clinical and pharmacological investigations have confirmed a more rapid, potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability, as compared with PPIs. Preliminary data in patients with erosive esophagitis (EE) have shown the non-inferiority of vonoprazan to lansoprazole in terms of symptom relief and healing rate. Since these pharmacokinetic advantages, it is expected that it will have a significant favorable impact on GERD management. However, the clinical use of vonoprazan raises also some issues about its efficacy and safety in the long-term that deserve verification and careful investigation.

Barrett's esophagus in 2016: From pathophysiology to treatment.

Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett's esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.

Esophageal testing: What we have so far.

Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising.

Genetics and pharmacogenetics of aminergic transmitter pathways in functional gastrointestinal disorders.

Functional gastrointestinal disorders (FGIDs) are highly prevalent syndromes, without evident underlying organic causes. Their pathogenesis is multifactorial in nature, with a combination of environmental and genetic factors contributing to their clinical manifestations, for which most of current treatments are not satisfactory. It is acknowledged that amine mediators (noradrenaline, dopamine and serotonin) play pivotal regulatory actions on gut functions and visceral sensation. In addition, drugs of therapeutic interest for FGIDs act on these transmitter pathways. The present article reviews current knowledge on the impact of genetics and pharmacogenetics of aminergic pathways on FGID pathophysiology, clinical presentations, symptom severity and medical management, in an attempt of highlighting the most relevant evidence and point out issues that should be addressed in future investigations.

Optimal management of constipation associated with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common chronic functional disorder of the gastrointestinal tract, meanly characterized by recurrent abdominal pain or discomfort and altered bowel habit. It is a complex disorder involving biological, environmental, and psychosocial factors. The diagnosis is achieved according to the Rome III criteria provided that organic causes have been excluded. Although IBS does not constitute a life-threatening condition, it has a remarkable prevalence and profoundly reduces the quality of life with burdening socioeconomic costs. One of the principal concerns about IBS is the lack of effective therapeutic options. Up to 40% of patients are not satisfied with any available medications, especially those suffering from chronic constipation. A correct management of IBS with constipation should evolve through a global approach focused on the patient, starting with careful history taking in order to assess the presence of organic diseases that might trigger the disorder. Therefore, the second step is to examine lifestyle, dietary habits, and psychological status. On these bases, a step-up management of disease is recommended: from fiber and bulking agents, to osmotic laxative drugs, to new molecules like lubiprostone and linaclotide. Although new promising tools for relief of bowel-movement-related symptoms are being discovered, a dedicated doctor-patient relationship still seems to be the key for success.

Manually calculated oesophageal bolus clearance time increases in parallel with reflux severity at impedance-pH monitoring.

BACKGROUND: Oesophageal clearance has been scarcely studied. AIMS: Oesophageal clearance in endoscopy-negative heartburn was assessed to detect differences in bolus clearance time among patients sub-grouped according to impedance-pH findings. METHODS: In 118 consecutive endoscopy-negative heartburn patients impedance-pH monitoring was performed off-therapy. Acid exposure time, number of refluxes, baseline impedance, post-reflux swallow-induced peristaltic wave index and both automated and manual bolus clearance time were calculated. Patients were sub-grouped into pH/impedance positive (abnormal acid exposure and/or number of refluxes) and pH/impedance negative (normal acid exposure and number of refluxes), the former further subdivided on the basis of abnormal/normal acid exposure time (pH+/-) and abnormal/normal number of refluxes (impedance+/-). RESULTS: Poor correlation (r=0.35) between automated and manual bolus clearance time was found. Manual bolus clearance time progressively decreased from pH+/impedance+ (42.6s), pH+/impedance- (27.1s), pH-/impedance+ (17.8s) to pH-/impedance- (10.8s). There was an inverse correlation between manual bolus clearance time and both baseline impedance and post-reflux swallow-induced peristaltic wave index, and a direct correlation between manual bolus clearance and acid exposure time. A manual bolus clearance time value of 14.8s had an accuracy of 93% to differentiate pH/impedance positive from pH/impedance negative patients. CONCLUSIONS: When manually measured, bolus clearance time reflects reflux severity, confirming the pathophysiological relevance of oesophageal clearance in reflux disease.