Pharmacodynamic studies on PPIs: look carefully at the country of origin.
Explore the source record for details and available documents.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Biomedical subjects
V Savarino
Publications and source records attributed to V Savarino.
Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease. Spectrum disease or distinct phenotypic presentations?
BACKGROUND: The traditional approach to gastro-oesophageal reflux disease as a spectrum disease has recently been criticised and the distinct phenotypic presentations model has been proposed. AIM: To evaluate the main pathophysiological characteristics of various gastro-oesophageal reflux disease presentations. METHODS: Oesophageal manometry and 24-h pH-monitoring were performed in a gastro-oesophageal reflux disease series collected in a 7-year period. RESULTS: Four hundred and twenty-one subjects were studied. Mean total percentage acid reflux time was significantly higher in long-segment Barrett's oesophagus and in ulcerative oesophagitis than in all the other gastro-oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus results were quite similar to those found in non-erosive reflux disease and in erosive reflux disease. Patients with ulcerative oesophagitis and long-segment Barrett's oesophagus were older than all the other gastro-oesophageal reflux disease groups. The mean lower oesophageal sphincter pressure was significantly reduced in non-erosive reflux disease, erosive reflux disease, ulcerative oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's oesophagus as compared with functional heartburn and hypersensitive oesophagus and with controls. CONCLUSIONS: In keeping with the spectrum model of gastro-oesophageal reflux disease, severity of acid reflux increases from non-erosive reflux disease through erosive reflux disease up to ulcerative oesophagitis and long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment Barrett's oesophagus could represent an advanced step in the natural history of gastro-oesophageal reflux disease. Our results do not confirm the distinct phenotypic presentations hypothesis.
Adult↗
Normal values of 24-h ambulatory intraluminal impedance combined with pH-metry in subjects eating a Mediterranean diet.
BACKGROUND AND AIMS: Multichannel intraluminal impedance combined with pH-metry is a novel technique for studying gastro-oesophageal reflux. As refluxes are particularly frequent after meals, we carried out this study in order to assess the impact of a Mediterranean diet on normal values of impedancemetry. METHODS: Twenty-five Italian healthy subjects (13 men, median age 29 years, range 22-67 years) without reflux symptoms were recruited for this study. They underwent oesophageal 24-h impedance + pH-metry. A Mediterranean diet was given to all subjects on the day of examination and its total energy intake was 9668.5 kJ (2300 kcal). RESULTS: A total of 1518 refluxes were recorded during 24 h with more upright than recumbent episodes (median 15 versus 0; p<0.01). The median total acid exposure time was 0.5% (range 0-4.2%). Acid and weakly acidic refluxes were equally reported (49% versus 51%). Weakly acidic episodes were more frequent than acid ones during 1-h postprandial periods (68% versus 32%; p<0.0001). Liquid-only and mixed refluxes reached the proximal oesophagus (15 cm above lower oesophageal sphincter) in 42.6% of cases. Median acid clearing time was longer than median bolus clearing time (28 s versus 12 s; p<0.01). CONCLUSIONS: This study provides normal values of pH-impedancemetry in Italian people eating a Mediterranean diet and are suitable for comparative pathophysiological investigations on reflux patients who have dietary habits similar to those of our country.
Adult↗
A study of 4- and 7-day triple therapy with rabeprazole, high-dose levofloxacin and tinidazole rescue treatment for Helicobacter pylori eradication.
BACKGROUND: Helicobacter pylori treatment failure is becoming an emergent problem in clinical practice. Shorter treatment duration should improve compliance to therapy and keep an acceptable H. pylori eradication rate. AIMS: To evaluate the efficacy of two rabeprazole, high-dose levofloxacin and tinidazole-based regimens as 'rescue' treatment for H. pylori eradication in an open-label, randomized, pilot study carried out in a clinical practice setting. METHODS: Eighty-five consecutive patients who have previously failed at least one H. pylori eradication attempt were randomized to receive rabeprazole (20 mg, b.d.), levofloxacin (500 mg, b.d.) and tinidazole (500 mg, b.d.) either for 4 (4-day RLT, n = 42) or 7 days (7-day RLT, n = 43). Cure of H. pylori infection was assessed by means of 13C-urea breath test. RESULTS: The 7-day RLT achieved 84% (95% CI: 69-93%) and 86% (95% CI: 72-95%) eradication rates in intention-to-treat and per-protocol analyses respectively. The shorter treatment obtained an 83% (95% CI: 69-93%) eradication rate in both intention-to-treat and per-protocol analysis. Both regimens were well tolerated, although patients who received the 4-day RLT reported fewer side-effects. CONCLUSIONS: In patients who have previously failed at least one H. pylori eradication attempt, both 4- and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens are effective in curing the infection in more than 80% of patients.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole.
BACKGROUND: Acid suppression is the mainstay of therapy in gastro-oesophageal reflux disease. Esomeprazole 40 mg is more effective than lansoprazole 30 mg in healing mucosal lesions in severe erosive reflux oesophagitis. However, data comparing esomeprazole with lansoprazole in patients with complications of gastro-oesophageal reflux disease, such as ulcerative reflux oesophagitis and Barrett's oesophagus, are lacking. AIM: To compare the efficacy of esomeprazole and lansoprazole at their standard dosages in suppressing oesophageal acid exposure in complicated gastro-oesophageal reflux disease. METHODS: Thirty patients with complicated gastro-oesophageal reflux disease (7 with ulcerative reflux oesophagitis and 23 with Barrett's oesophagus), randomly assigned to receive 40 mg esomeprazole (n=16) or 30 mg lansoprazole (n=14) once daily, underwent oesophageal 24-h pH monitoring while on therapy. Total, upright diurnal and supine nocturnal percentage acid reflux time were assessed. RESULTS: Esomeprazole was significantly more effective than lansoprazole in decreasing oesophageal acid exposure. Normalisation of both total and supine nocturnal percentage acid reflux time was obtained in 12 of 16 (75%) patients treated with esomeprazole but only in 4 of 14 (28%) cases treated with lansoprazole (p=0.026). CONCLUSIONS: Normalisation of oesophageal acid exposure can be achieved in the majority of complicated gastro-oesophageal reflux disease cases with esomeprazole 40 mg once daily.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Quality of life in acute and maintenance treatment of non-erosive and mild erosive gastro-oesophageal reflux disease.
BACKGROUND: Quality of life has been assessed in a large, multicentre randomized, open label study. AIM: To evaluate the economic and clinical consequences of two different maintenance treatment modalities, administered to 6017 gastro-oesophageal reflux disease patients at 451 gastroenterological centres in Italy. METHODS: Adult gastro-oesophageal reflux disease patients received, at enrolment, an acute treatment of esomeprazole 40 mg/day for 4 weeks and, if successfully treated, were randomized into two maintenance treatment strategies: esomeprazole 20 mg/day or esomeprazole on demand for 6 months. A baseline endoscopy allowed the exclusion of grade II-IV oesophagitis according to Savary-Miller's classification. Burden of gastro-oesophageal reflux disease was measured at baseline by the generic questionnaire Short-Form 36 and by a disease specific instrument, quality of life in reflux and dyspepsia (QOLRAD), also administered at start and conclusion of maintenance period. Investigators were required to collect patient judgement about the degree of satisfaction with treatment effect on heartburn, with a 7-point scale. RESULTS: A comparison between Short-Form 36 scores and the normative source of the Italian general population suggested that symptomatic gastro-oesophageal reflux disease patients experience a worse quality of life than the general population. At the end of the 4-week treatment with esomeprazole 40 mg all (QOLRAD) dimensions showed a statistically significant (P < 0.0001) and clinically meaningful improvement. Satisfaction level towards treatment was reported high in the total enrolled population after acute treatment with esomeprazole 40 mg/day (96.2% satisfied and 64.4% very satisfied). A statistically significant difference in (QOLRAD) scores was registered at the end of maintenance phase in favour of the continuous regimen, nevertheless the size of this difference was very small in all dimensions; similarly, the proportion of patients very satisfied was slightly higher in the continuous treatment arm (64.5%) than in the on-demand arm (59.7%). CONCLUSIONS: Gastro-oesophageal reflux disease can significantly impair health-related quality of life and esomeprazole therapy allows immediate relief in the acute phase of the disease. Quality of life improvement was maintained during the 6-month follow-up with a slight difference in term of quality of life in reflux and dyspepsia scores and patients' satisfaction in favour of the continuous treatment strategy.
Acute Disease↗
Helicobacter pylori and tolerance to H2-blockers.
Explore the source record for details and available documents.
Drug Resistance, Microbial↗
An evaluation of the antireflux properties of sodium alginate by means of combined multichannel intraluminal impedance and pH-metry.
BACKGROUND: Alginate-based preparations act as mechanical antireflux barrier, which can reduce both acid and non-acid reflux events and limit the proximal migration of oesophageal refluxate. AIM: To evaluate all the above features with a novel technique, multichannel electrical impedance and pH-metry. METHODS: Ten reflux patients underwent stationary impedancemetry and pH-metry after eating a refluxogenic meal. They were studied 1 h in basal conditions and 1 h after taking 10 mL of Gaviscon Advance. In both sessions, measurements were obtained in right lateral and supine decubitus. RESULTS: Alginate preparation was able to decrease significantly (P < 0.05) the number of acid reflux events and the percentage time pH < 4.0 compared with baseline. There was no effect of the drug on non-acid refluxes. Gaviscon Advance was also significantly effective (P < 0.05) in reducing the height of proximal migration of reflux events compared with baseline in both decubitus positions. CONCLUSIONS: Our findings explain how Gaviscon Advance controls acid reflux episodes, limits the proximal migration of refluxed material and thereby decreases symptoms in clinical practice.
Adult↗
Air swallowing can be responsible for non-response of heartburn to high-dose proton pump inhibitor.
Intraluminal electrical impedance is a novel technique, which is able for the first time to provide a qualitative assessment of refluxed material moving from the stomach to the oesophagus. In other words, the presence of air can be differentiated from that of liquid, because the former is characterised by high and the latter by low impedance compared with baseline. Moreover, the combined measurement of electrical impedance and pH-metry permits to distinguish acid from non-acid liquid reflux. One of the most important clinical applications of this method is to assess the reasons for poor response of GORD patients to high-dose proton pump inhibitors. This case report describes the results of impedance in the evaluation of a young woman, who did not respond to twice-daily doses of rabeprazole. She continued to complain of heartburn as major symptom and impedance allowed us to clarify that it was not related to acid or non-acid reflux, but to air swallowing. Therefore, this technique identified aerophagia to be responsible for persistent heartburn despite high-dose proton pump inhibitor and prevented the adoption of more aggressive, but probably unuseful therapies, such as the surgical one.
2-Pyridinylmethylsulfinylbenzimidazoles↗
5-ASA and colorectal cancer chemoprevention in inflammatory bowel disease: can we afford to wait for 'best evidence'?
Patients with inflammatory bowel disease have a higher risk of developing colorectal cancer. The main risk factors for colorectal cancer are not suitable targets for therapeutic intervention, and primary chemoprevention is an intriguing therapeutic option. The analogies between acetyl-salicylic acid and 5-amino-salicylic acid, and the results obtained by using acetyl-salicylic acid as a chemopreventive agent in patients with sporadic colorectal cancer have prompted the study of potential chemopreventive effects of 5-amino-salicylic acid in inflammatory bowel disease. The results of both epidemiological and experimental studies have shown that long-term 5-amino-salicylic acid treatments appear to have a chemopreventive effect. The evidence for this effect is provided by retrospective and case-control studies whose results, however, do not reach the highest grades for evidence-based recommendations. Nevertheless, these results are supported by a series of experimental studies demonstrating the multiplicity of actions of 5-amino-salicylic acid. Although data regarding the chemopreventive effect of 5-amino-salicylic acid may not be rigorous enough to meet the criteria for the highest evidence-based medicine recommendations, we feel that the argument to wait until we have Grade A evidence is not necessarily rational in this case, because discontinuation of 5-amino-salicylic acid treatment to perform a randomised controlled trial would be unethical secondary to their proven efficacy for maintenance treatment.
Anti-Inflammatory Agents, Non-Steroidal↗
Application of the platelet count/spleen diameter ratio to rule out the presence of oesophageal varices in patients with cirrhosis: a validation study based on follow-up.
BACKGROUND: Screening for oesophageal varices represents an important part of the diagnostic work-up of cirrhotic patients. We have previously shown that the platelet count/spleen diameter ratio is a parameter that can rule out the presence of oesophageal varices safely and in a cost-effective fashion. AIM: To evaluate the prognostic and diagnostic accuracy of the platelet count/spleen diameter ratio for ruling out the presence of oesophageal varices in the follow-up of a cohort of cirrhotic patients without oesophageal varices at inclusion. METHODS: After initial endoscopy, the 106 cirrhotic patients without oesophageal varices who participated in our previous study were followed-up with annual or biannual surveillance endoscopy. Patients were censored at the time of diagnosis of oesophageal varices or at their last visit, and at that time platelet count and spleen diameter were recorded. Sixty-eight patients made up the study cohort after excluding patients who were lost to follow-up or died before undergoing control endoscopy. RESULTS: During the follow-up, 27 patients (40%) developed oesophageal varices. Patients with higher baseline platelet count/spleen diameter ratios (p<0.0001) as well as a ratio above 909 were less likely to develop oesophageal varices (p<0.0005). At follow-up, a platelet count/spleen diameter ratio < or = 909 had 100% negative predictive value and 84% efficiency in identifying the presence of oesophageal varices. CONCLUSIONS: The use of the platelet count/spleen diameter ratio proved to be an effective means for ruling out the presence of oesophageal varices even in the longitudinal follow-up of patients.
Aged↗
[Inflammatory and metaplasia lesions in the esophagogastric junction].
Explore the source record for details and available documents.
Esophagitis↗
Pathophysiological characteristics of patients with non-erosive reflux disease differ from those of patients with functional heartburn.
BACKGROUND: Patients with endoscopy-negative heartburn can be subdivided into non-erosive reflux disease and functional heartburn on the basis of abnormal and normal, respectively, oesophageal acid exposure. Different pathophysiological characteristics could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn. AIM: To assess if non-erosive reflux disease and functional heartburn are pathophysiologically distinguishable. METHODS: Oesophageal manometry and pH-monitoring were performed in 145 patients with endoscopy-negative heartburn, in 72 patients with erosive reflux disease, in 58 patients with complicated reflux disease, and in 60 controls. RESULTS: Patients with non-erosive reflux disease (84 cases) and functional heartburn (61 cases) differed with regard to the prevalence of hiatal hernia (49% vs. 31%, P = 0.008), the mean lower oesophageal sphincter tone (18.5 vs. 28.4 mmHg, P < 0.05), and the number of upright diurnal acid refluxes lasting more than 5 min (3.6 vs. 0.37, P < 0.05). The results were very close in thenon-erosive reflux disease, erosive reflux disease and complicated reflux disease groups, whilst patients with functional heartburn were indistinguishable from controls. CONCLUSIONS: Pathophysiological characteristics typical of gastro-oesophageal reflux disease are found in patients with non-erosive reflux disease but not in patients with functional heartburn. This could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn and suggests considering different management strategies.
Adult↗
Carditis in patients with gastro-oesophageal reflux disease: results of a controlled study based on both endoscopy and 24-h oesophageal pH monitoring.
BACKGROUND: There are conflicting reports on the role of gastro-oesophageal reflux disease (GERD) and Helicobacter pylori infection in the aetiology of carditis. AIM: The role of reflux and H. pylori infection in causing carditis was assessed in 113 consecutive patients with GERD and in 25 controls. METHODS: All subjects underwent endoscopy and pH test and carditis was diagnosed on biopsies taken across the squamocolumnar junction. Helicobacter pylori was assessed by histology and rapid urease test. GERD was diagnosed by endoscopic oesophagitis or abnormal pH test. RESULTS: Carditis was detected in 53 of 71 GERD patients and in 15 of 20 controls. Among patients, 18 showed absent, 39 mild and 14 marked cardia inflammation and their H. pylori infection rates were 17, 23 and 57%, respectively (P < 0.025). Most patients with carditis (68%) lacked H. pylori infection. pH-metry was abnormal in 15 of 18 patients with normal cardia, 33 of 39 with mild carditis and 12 of 14 with marked inflammation. CONCLUSIONS: Carditis is a frequent finding in GERD and controls. Mild, non-active carditis is frequent in GERD patients. Marked inflammation is associated with both H. pylori and abnormal pH testing. Thus, both GERD and H. pylori infection may play a role in inducing carditis.
Adult↗
Combined multichannel intraluminal impedance and pH-metry: a novel technique to improve detection of gastro-oesophageal reflux literature review.
Ambulatory pH monitoring is currently the best method for detection of gastro-oesophageal reflux. However, pH electrodes are able to measure only acid reflux, and therefore, non-acid reflux episodes, a potentially important cause of symptoms, are ignored by this technique. Multichannel intraluminal electrical impedance has recently been proposed as a novel method to overcome the above limitation of pH testing. Impedance (expressed in ohms) is a measure of the total opposition to current flow between adjacent electrodes. As refluxed contents are characterised by different conductivity, which is the inverse of impedance, for the first time a pH-independent accurate and practical qualitative analysis of refluxate is possible. For instance, the conductivity of air is almost zero and then impedance increases compared with baseline, whereas the conductivity of liquid is much higher and the impedance curve decreases remarkably. The combination of electrical impedance with traditional pH monitoring has the only aim of differentiating acid from non-acid liquid reflux. Moreover, the impedance catheter contains multiple pairs of ring electrodes along the oesophagus, so that an exact assessment of the proximal extent of refluxed material can be achieved. From a clinical point of view, electrical impedance + pH-metry could be useful for identifying the number and percent times of gas, acid and non-acid reflux episodes, to improve the yield of symptom index, to evaluate the reasons for poor response of reflux symptoms to proton pump inhibitors and to know the proximal extent of reflux events in patients with atypical symptoms. Thus, this technique has the potential to become a useful tool for improving our knowledge of gastro-oesophageal reflux disease and optimising the management of these patients.
Electric Impedance↗
Gastric emptying evaluation by 13C-octanoic acid breath test.
Explore the source record for details and available documents.
Autonomic Nervous System↗
Comparable Helicobacter pylori eradication rates obtained with 4- and 7-day rabeprazole-based triple therapy: a preliminary study.
BACKGROUND: Rabeprazole is a new proton pump inhibitor, which has been reported to induce a faster acid suppression than other drugs of the same category. This might be useful to reduce the duration of anti-Helicobacter therapies. AIMS: The aim of this study was to assess whether there is the possibility of shortening a rabeprazole-based triple therapy from 7 to 4 days without compromising its efficacy in the eradication of Helicobacter pylori infection. PATIENTS: A total of 128 consecutive dyspeptic patients with H. pylori infection were recruited for this controlled, randomized, open and parallel-group trial comparing the efficacy of two durations of the same rabeprazole-based triple therapy. METHODS: All patients were subdivided to receive a combination of rabeprazole 20 mg twice daily, clarithromycin 250 mg twice daily and metronidazole 500 mg twice daily (RCM) for 4 days (n = 63) and for 7 days (n = 65). At baseline, they underwent breath 13C-urea test and endoscopy with biopsies for rapid urease testing and histology to confirm infection with H. pylori. Eradication was determined by a negative 13C-urea breath test within 28-32 days after the end of therapy. RESULTS: Overall eradication rates were similar for patients treated with the 4- and the 7-day periods (intention-to-treat and per-protocol analyses showed a success rate of 81% versus 78% and 88% versus 85%, respectively; P = NS). Tolerance was similar in both groups. Most adverse events were mild to moderate, and only two patients were withdrawn because of them. CONCLUSIONS: The eradication rate of the 4-day regimen was equivalent to that of the same 7-day regimen based on rabeprazole plus clarithromycin and metronidazole. Therefore, the 4-day regimen of RCM seems to give us the possibility of adopting a shorter-than-usual duration of therapy against H. pylori.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Effective intra-oesophageal acid suppression in patients with gastro-oesophageal reflux disease: lansoprazole vs. pantoprazole.
BACKGROUND: : Effective intra-oesophageal acid suppression is an important therapeutic goal in complicated and atypical gastro-oesophageal reflux disease. AIM: : To compare the efficacy of lansoprazole and pantoprazole in normalizing oesophageal acid exposure. METHODS: : Fifty patients with complicated or atypical gastro-oesophageal reflux disease were randomly assigned to receive 30 mg lansoprazole (n = 26) or 40 mg pantoprazole (n = 24) once daily. Three to four weeks after the start of treatment, patients underwent 24-h oesophageal pH monitoring whilst on therapy. If the results were improved but still abnormal, the dosage was doubled and pH monitoring was repeated. If oesophageal acid exposure was not improved, the patient was shifted to the alternative drug regimen. RESULTS: : Oesophageal acid exposure was normalized in all 26 patients treated with lansoprazole (in 35% of cases with a double daily dosage), whereas in six of the 24 (25%) patients treated with pantoprazole it was neither normalized nor lowered (P = 0.008). Accordingly, the mean percentage acid reflux time was significantly lower for the lansoprazole group (2.1) than for the pantoprazole group (5.8) (P = 0.032). CONCLUSIONS: : Effective intra-oesophageal acid suppression can be accomplished more reliably with lansoprazole than with pantoprazole in patients with complicated and atypical gastro-oesophageal reflux disease.
2-Pyridinylmethylsulfinylbenzimidazoles↗