Efficacy and safety of omeprazole in Japanese patients with nonerosive reflux disease

BACKGROUND: There is increasing awareness of nonerosive reflux disease (NERD) as a disease requiring treatment in Japan. This randomized, double-blind, placebo-controlled, parallel-group study was conducted to investigate the efficacy and safety of omeprazole 10 mg and 20 mg once daily in Japanese patients with NERD. METHODS: Patients with heartburn for at least 2 days a week during the month before entry into the study and no endoscopic signs of a mucosal break (grade M or N according to Hoshihara's modification of the Los Angeles classification) were randomly assigned to one of three groups (omeprazole 10 mg or 20 mg, or placebo) once daily for 4 weeks. RESULTS: Overall, 355 patients were enrolled, of whom 284 were randomly assigned to one of the three groups (omeprazole 10 mg, n = 96; omeprazole 20 mg, n = 93; placebo, n = 95). The rate of complete resolution of heartburn in week 4 was significantly higher in patients treated with omeprazole 10 mg [32.3%, 95% confidence interval (CI), 22.9%-41.6%] or 20 mg (25.8%, 95% CI, 16.9%-34.7%) than in the placebo group (12.0%, 95% CI, 5.3%-18.6%). No significant difference between the two omeprazole groups was observed. The rate of complete resolution of heartburn by omeprazole was similar between patients with grade M and those with grade N esophagus. Omeprazole also increased the rate of sufficient relief from heartburn. Omeprazole was well tolerated. CONCLUSIONS: Omeprazole 10 mg or 20 mg once daily is effective and well tolerated in patients with NERD regardless of their endoscopic classification.     

Predicting the efficacy of proton pump inhibitors in patients with non-erosive reflux disease before therapy using dual-channel 24-h esophageal pH monitoring

Background and Aim: We aimed to determine whether reflux‐ and symptom‐related parameters can predict the efficacy of proton pump inhibitors (PPI) in non‐erosive reflux disease (NERD). Methods: Twenty‐seven NERD patients who had experienced heartburn more than once a week within the previous month were enrolled. Intraesophageal pH before therapy was measured simultaneously at 5 and 15 cm above the esophagogastric junction (EGJ) for 24 h. The PPI rabeprazole was administered at a dose of 10 mg once daily for 4 weeks. In the event that heartburn was not relieved, the dose was increased to 10 mg twice daily for an additional 2 weeks, and again to 20 mg twice daily for another 2 weeks. Results: Univariate analysis demonstrated no significant associations between any reflux‐ or symptom‐related parameters at either site and complete heartburn relief after 4 weeks, or cumulative complete heartburn relief after 8 weeks. However, post‐hoc analysis demonstrated more satisfactory heartburn relief after 4 weeks in patients with a high symptom index compared with those with a low symptom index, at 5 cm above the EGJ (P = 0.009). Cumulative satisfactory heartburn relief after 8 weeks was also greater in patients with a high total number of acid reflux episodes compared with those with a low total number of episodes, at 15 cm above the EGJ (P = 0.037). Conclusions: Pre‐therapeutic pH monitoring in the lower and mid‐esophagus is useful for predicting the efficacy of PPI in NERD patients.     

The pharmacodynamic effect of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease in Japan

Background To evaluate the pharmacodynamic effect, efficacy, and safety of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease (NERD) in Japan. Methods A total of 37 patients were randomized to omeprazole 10 mg or omeprazole 20 mg once daily for 4 weeks. Eligible patients had a history of moderate-to-severe heartburn for 2 days or more per week during the last 1 month or longer prior to the study screening, grade M or grade N on Hoshihara's modification of the Los Angeles classification (i.e., no sign of mucosal break on esophagogastroduodenoscopy), and heartburn episodes for 2 days or more per week during the last week of the observation period while taking antacids. Ambulatory 24-h intraesophageal pH was monitored on the day before treatment and on the last day of treatment. The occurrence of a heartburn episode was recorded during pH monitoring. The primary endpoint was the change in the percentage of time with intraesophageal pH < 4 during the 24-h period before and after omeprazole treatment. Results Both omeprazole 10 mg and omeprazole 20 mg once daily reduced the percentage of time with intraesophageal pH < 4. The percentage reduction in time with intraesophageal pH < 4 after treatment with omeprazole was associated with a reduced number of heartburn episodes. Patients with grade M or grade N esophagus had similar pH profiles and NERD characteristics (e.g., pH holding time, symptom index) and comparable responses to omeprazole. No serious, drug-related adverse events were reported. Conclusions Omeprazole 10 mg or 20 mg reduces the percentage of time with intraesophageal pH < 4, is efficacious, and is well tolerated in patients with NERD in Japan, regardless of the patient's endoscopic classification.     

Investigation of pretreatment prediction of proton pump inhibitor (PPI)-resistant patients with gastroesophageal reflux disease and the dose escalation challenge of PPIs��TORNADO study: a multicenter prospective study by the Acid-Related Symptom Research Group in Japan

Backgrounds

Some non-erosive reflux disease (NERD) and reflux esophagitis (RE) patients are unresponsive to a proton pump inhibitor (PPI) at standard dose. We investigated the predictive marker of the efficacy of PPI for GERD patients including NERD and RE treated with standard and increased doses of a PPI.

Methods

Patients with symptomatic gastroesophageal reflux disease (GERD) (NERD and RE) were treated with rabeprazole (RPZ) 10?mg once daily for 4?weeks. The RPZ dosage was increased to 10?mg twice daily for an additional 2?weeks and again to 20?mg twice daily for another 2?weeks if heartburn was not relieved. Baseline characteristics and efficacy of RPZ were assessed on the basis of a heartburn diary and frequency scale for symptoms of GERD (FSSG).

Results

Complete heartburn relief rates after 4?weeks were 42.5% (31/73) and 67.9% (19/28) in NERD and RE groups, respectively, which rose to 68.9 and 91.7% after dose escalation. Multivariate analysis revealed that parameters associated with resistance to RPZ 10?mg once daily were female, non-smoking, frequent heartburn, low score for question 4 (Q4) of the FSSG (subconsciously rubbing the chest), and high scores for Q3 (heavy stomach after meal) and Q7 (unusual sensation in the throat). Frequent heartburn and a high score for Q7 were associated with resistance to RPZ 20?mg twice daily. FSSG scores of patients resistant to RPZ were significantly higher in comparison with responders before and during treatment.

Conclusions

FSSG could predict response to a PPI for symptomatic GERD. Increase of RPZ dose is useful for treatment of GERD refractory to the standard dose of RPZ.     

A multicenter, randomized, comparative study to determine the appropriate dose of lansoprazole for use in the diagnostic test for gastroesophageal reflux disease

Background/Aims

The diagnostic proton pump inhibitor test (PPI test) is a method used in diagnosing gastroesophageal reflux disease (GERD). This study aimed to determine the appropriate dose of lansoprazole for use in the diagnostic test for GERD.

Methods

This study was a randomized, controlled, multicenter trial in the Daegu-Gyeongbuk area. Patients with typical reflux symptoms such as regurgitation and heartburn for at least three months were enrolled in this study. Patients were divided into two groups, the erosive reflux disease (ERD) group and the non-erosive reflux disease (NERD) group, and randomized to 14 days of treatment with lansoprazole at a dose of 15 mg, 30 mg or 60 mg once daily. The PPI test was considered positive if the patient''s symptoms improved by more than 50%.

Results

A total of 218 patients were enrolled, and analysis was performed on the 188 patients who completed the study. The PPI test was positive in 93.2% of the ERD group and 87.2% of the NERD group. A positive PPI test was observed in 91.7%, 89.4%, and 87.2% of the 15 mg, 30 mg, and 60 mg groups, respectively. Significant symptom score changes were observed starting on day 8 for the 15 mg, 30 mg, and 60 mg groups.

Conclusions

In this multicenter, randomized study of Korean patients, the standard dose of lansoprazole was as effective as a high dose of lansoprazole in relieving the symptoms of GERD, regardless of the presence of ERD, by day 14 of treatment.     

Persistent acid reflux and symptoms in patients with Barrett's oesophagus on proton-pump inhibitor therapy

OBJECTIVES: To assess both acid gastro-oesophageal reflux (GOR) suppression in patients with Barrett's oesophagus on proton-pump inhibitors (PPI) and the predictive value of symptoms.DESIGN A prospective study of patients with Barrett's epithelium (> 3 cm, containing specialized intestinal metaplasia).PATIENTS AND METHODS: Forty-five patients with Barrett's epithelium were recruited. Therapy was adjusted to omeprazole 20 mg twice daily. Oesophageal manometry and 24 h pH studies were performed on treatment. Heartburn score was calculated before and after PPI dose adjustment. In patients with persisting acid reflux, omeprazole dose was increased to 20 mg three times daily and pH studies repeated. Adequacy of GOR suppression, assessed by pH monitoring, was related to heartburn score (0-3). RESULTS: Twenty of the 45 patients were symptomatic (mean score 1.9) on pre-study treatment (mainly omeprazole < 20 mg once daily); on omeprazole 20 mg twice daily, only six patients remained symptomatic (mean score 1.6). Ten patients (22%) had persisting GOR on omeprazole 20 mg twice daily (median % total time with pH < 4 was 8%). Abnormal nocturnal reflux was found in nine and abnormal daytime reflux in only four patients. Heartburn persisted in three of these 10 patients (30%). Those remaining symptomatic had more daytime acid reflux than the asymptomatic patients with persistent reflux (median percentage daytime at pH < 4 was 13.6% vs 0.6%, respectively; P < 0.01). By increasing the omeprazole dose to 20 mg three times daily, only three of the 10 had persistent acid reflux. CONCLUSIONS: Persistent acid reflux on PPI therapy is common in patients with Barrett's oesophagus. Although nocturnal acid reflux is the most common finding, symptoms tended to occur in those with abnormal daytime reflux. Symptom resolution does not guarantee acid reflux control.     

Efficacy of omeprazole for the treatment of symptomatic acid reflux disease without esophagitis

BACKGROUND: Up to three quarters of patients with gastroesophageal reflux disease (GERD) have symptoms, such as heartburn, but no macroscopic evidence of erosive esophagitis, making symptomatic GERD a common clinical problem in the primary care setting. OBJECTIVE: To compare the efficacy and safety of omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; and placebo in the treatment of symptomatic GERD without erosive esophagitis. METHODS: Patients with a history of heartburn (> or =12 months) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week, randomized, double-blind, placebo-controlled trial. The absence of erosive esophagitis was established through endoscopy. Eligible patients were randomized to 1 of 3 treatment groups: omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; or placebo. Patients were assessed at weeks 2 and 4. The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data: daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment. The efficacy of omeprazole for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea was also assessed. RESULTS: Of 359 randomized patients, 355 were included in the statistical analysis (intention-to-treat population). Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group (62%, day 7; 74%, day 27) than in the 10-mg omeprazole group (41%, day 7; 49%, day 27) or the placebo group (14%, day 7; 23%; day 27). Complete resolution of heartburn every day during the last treatment week was significantly (P< or =.002) higher in the 20-mg omeprazole group (48%) than in the 10-mg omeprazole (27%) or placebo (5%) group. Omeprazole was significantly (P< or =.003) more effective than placebo for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea. CONCLUSIONS: Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief. Omeprazole, 20 mg once daily, was superior to omeprazole, 10 mg once daily, and to placebo in providing early and sustained resolution of heartburn, as well as treatment of other troublesome GERD symptoms.     

Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux

AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed. RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%,P<0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one. CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.     

Heartburn and regurgitation have different impacts on life quality of patients with gastroesophageal reflux disease

AIM: To investigate the impact of heartburn and regurgitation on the quality of life among patients with gastroesophageal reflux disease (GERD).METHODS: Data from patients with GERD, who were diagnosed according to the Montreal definition, were collected between January 2009 and July 2010. The enrolled patients were assigned to a heartburn or a regurgitation group, and further assigned to an erosive esophagitis (EE) or a non-erosive reflux disease (NERD) subgroup, depending on the predominant symptoms and endoscopic findings, respectively. The general demographic data, the scores of the modified Chinese version of the GERDQ and the Short-form 36 (SF-36) questionnaire scores of these groups of patients were compared.RESULTS: About 108 patients were classified in the heartburn group and 124 in the regurgitation group. The basic characteristics of the two groups were similar, except for male predominance in the regurgitation group. Patients in the heartburn group had more sleep interruptions (22.3% daily vs 4.8% daily, P = 0.021), more eating or drinking problems (27.8% daily vs 9.7% daily, P = 0.008), more work interferences (11.2% daily vs none, P = 0.011), and lower SF-36 scores (57.68 vs 64.69, P = 0.042), than patients in the regurgitation group did. Individuals with NERD in the regurgitation group had more impaired daily activities than those with EE did.CONCLUSION: GERD patients with heartburn or regurgitation predominant had similar demographics, but those with heartburn predominant had more severely impaired daily activities and lower general health scores. The NERD cases had more severely impaired daily activity and lower scores than the EE ones did.     

A prospective multicenter clinical and endoscopic follow-up study of patients with gastroesophageal reflux disease

BACKGROUND: Despite its high prevalence, data on the course of gastroesophageal reflux disease (GERD) are still sparse. There is also an ongoing debate on the natural history of its various manifestations, i.e., non-erosive reflux disease (NERD) vs. erosive reflux disease (ERD) vs. Barrett's esophagus (BE). PATIENTS AND METHODS: This study was conducted within the framework of a prospective multicenter study on the course and prevalence of intestinal metaplasia at the gastroesophageal junction. 1014 dyspeptic patients were screened by the means of upper GI endoscopy. Clinical data were recorded by the use of a questionnaire. At least 15 months after the initial examination, all patients were invited for follow-up (FU) examination. Patients were analyzed separately with respect to their clinical and endoscopic findings. For the latter, only patients without any treatment with proton-pump-inhibitors (PPI) prior to initial and follow-up examinations were included. Patients were categorized as GERD positive if typical symptoms were present and/or proton pump inhibitors were used. RESULTS: Sufficient clinical and/or endoscopic data were available in 590 GERD patients with heartburn at least once a week. Follow-up data could be obtained in 320 patients (clinical FU: n = 304; endoscopic FU: n = 52) after a mean follow-up period of 35 months (18-48 months). 96 of 144 previously asymptomatic patients (67%) remained asymptomatic at follow-up, the rest (n = 48) were symptomatic. 143 of 304 previously symptomatic patients (47%) were symptom-free at follow-up, and only 161 patients (53%) remained symptomatic or had concomitant therapy with proton-pump-inhibitors (PPI). For follow-up endoscopy in patients off PPI (n = 52), ERD was no longer confirmed in 7/12 ERD patients (58%), whereas progress to ERD was found in 3/34 patients (9%) in the NERD group. BE was newly diagnosed in two NERD patients but could no longer be detected in 2 of 6 patients with an initial diagnosis of BE. CONCLUSIONS: With respect to its clinical as well as its endoscopic manifestations, gastroesophageal reflux disease does not appear to be very stable over time. However, in most cases this is due to regression rather than progression of the disease.     

Rabeprazole is equivalent to omeprazole in the treatment of erosive gastro-oesophageal reflux disease: A randomised, double-blind, comparative study of rabeprazole and omeprazole 20 mg in acute treatment of reflux oesophagitis, followed by a maintenance open-label, low-dose therapy with rabeprazole

BACKGROUND: Previous studies have shown similar effects of rabeprazole and omeprazole, when used at the same dose in the treatment of reflux oesophagitis. However, such studies have been conducted as superiority studies but interpreted as equivalence ones. AIM: To properly assess the comparative efficacy of rabeprazole and omeprazole in inducing complete endoscopic healing and symptom relief in patients with reflux oesophagitis. METHODS: Patients (n=560) with Savary-Miller grade I-III reflux oesophagitis were randomised in a double-blind, double-dummy fashion to rabeprazole or omeprazole 20 mg once daily for 4-8 weeks. Then, patients endoscopically healed and symptomatically relieved were openly maintained with rabeprazole 10 mg or 2x10 mg once daily (in the event of clinical and/or endoscopic relapse) for a maximum of 48 weeks. RESULTS: After 4-8 weeks of treatment, healing (primary end-point) was observed in 228/233 (97.9%) patients in the rabeprazole group and in 231/237 (97.5%) in the omeprazole one (equivalence effect demonstrated by p<0.0001 at Blackwelder test and an upper confidence limit at 97.5% of 0.023). However, rabeprazole was faster in inducing heartburn relief than omeprazole (2.8+/-0.2 versus 4.7+/-0.5 days of therapy to reach the first day with satisfactory heartburn relief, p=0.0045 at log-rank test). In the maintenance phase, 15.2% of patients had an endoscopic and/or clinical relapse. CONCLUSION: Rabeprazole is equivalent to omeprazole in healing reflux oesophagitis, but shows a faster activity on reflux symptoms in the early treatment phase.     

Effectiveness of proton pump inhibitors in nonerosive reflux disease.

BACKGROUND & AIMS: Little information is available about the efficacy of proton pump inhibitors (PPIs) in patients with nonerosive reflux disease (NERD). We aimed to synthesize available data and determine the effectiveness of PPIs on symptom resolution in patients with NERD. METHODS: A systematic review of the literature identified studies reporting the effects of PPIs in patients with NERD. Heartburn resolution data were pooled across studies. The effectiveness of PPI therapy in inducing complete heartburn resolution was compared in patients with NERD vs. erosive esophagitis (EE). RESULTS: Seven trials evaluating heartburn resolution in NERD were identified. Higher proportions of patients reported achieving sufficient heartburn resolution compared with complete heartburn resolution. The effect of PPIs on sufficient heartburn resolution was observed sooner than was complete heartburn resolution. Therapeutic gain of PPI therapy over placebo ranged from 30% to 35% for sufficient heartburn control and from 25% to 30% for complete heartburn control. Pooled response rates at 4 weeks were significantly higher for patients with EE compared with NERD (56% vs. 37%, P < 0.0001). CONCLUSIONS: PPIs provide a more modest therapeutic gain in patients with NERD as compared with those with EE. A trend in increased therapeutic gain for NERD patients was shown throughout the 4 weeks, suggesting that 4 weeks of follow-up evaluation may be insufficient to show full therapeutic gain in this patient population.     

Symptom relief in patients with reflux esophagitis: comparative study of omeprazole, lansoprazole, and rabeprazole

BACKGROUND AND AIM: Rabeprazole has a faster onset of antisecretory activity than omeprazole and lansoprazole. The aim of the present study was to clarify whether there is any difference in the speed of symptom relief in patients with reflux esophagitis following the administration of these three proton pump inhibitors (PPI). METHODS: Eighty-five patients with erosive reflux esophagitis were randomized to receive 8 weeks of 20 mg of omeprazole (n = 30), 30 mg of lansoprazole (n = 25), or 20 mg of rabeprazole (n = 30) once a morning. Daily changes in heartburn and acid reflux symptoms in the first 7 days of administration were assessed using a six-point scale (0: none, 1: mild, 2: mild-moderate, 3: moderate, 4: moderate-severe, 5: severe). RESULTS: The mean heartburn score in patients administered rabeprazole decreased more rapidly than those given the other PPI. Complete heartburn remission also occurred more rapidly in patients administered rabeprazole (compared with omeprazole: P = 0.035, compared with lansoprazole: P = 0.038 by log-rank test). No differences were seen in the rate of endoscopic healing of reflux esophagitis at 8 weeks between the three treatment regimens. CONCLUSION: Rabeprazole may be more effective than omeprazole and lansoprazole for the rapid relief of heartburn symptoms in patients with reflux esophagitis.     

Comparing lansoprazole and omeprazole in onset of heartburn relief: results of a randomized, controlled trial in erosive esophagitis patients

OBJECTIVE: This randomized, double-blind, multicenter study was conducted to confirm a previous finding that lansoprazole relieves heartburn faster than omeprazole in patients with erosive esophagitis. METHODS: A total of 3510 patients with erosive esophagitis and at least one episode of moderate to very severe daytime and/or nighttime heartburn during the 3 days immediately before the screening visit were randomized to lansoprazole 30 mg once daily or omeprazole 20 mg once daily for 8 wk. Patients recorded the presence and severity of daytime and nighttime heartburn in daily diaries. On treatment days 1-4, patients were telephoned to confirm the completion of their daily diary. The primary efficacy parameters were the percentage of heartburn-free days and heartburn-free nights, as well as the average severity of daytime and nighttime heartburn. RESULTS: During treatment day I and all evaluation time points including the entire 8-wk treatment period, significantly (p < 0.05) higher percentages of patients treated with lansoprazole than those treated with omeprazole did not experience a single episode of heartburn. Onset of heartburn relief was more rapid in lansoprazole-treated versus omeprazole-treated patients: on day 1, 33% versus 25% of lansoprazole- versus omeprazole-treated patients were heartburn-free. The percentages of heartburn-free days and heartburn-free nights were also significantly (p < 0.01) greater for patients treated with lansoprazole at all evaluation time points. Heartburn severity was significantly less among those treated with lansoprazole compared with omeprazole. Both treatments were safe and well tolerated. CONCLUSIONS: Over 8 wk, lansoprazole 30 mg once daily relieved heartburn symptoms faster and more effectively than omeprazole 20 mg once daily in patients with erosive esophagitis.     

Omeprazole (40 mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagitis

The efficacy and safety of omeprazole, 40 mg once daily for four to eight weeks of treatment, were studied in 61 patients with ulcerative reflux esophagitis. A double-blind controlled study design was used, and the patients were randomly allocated to treatment with either omeprazole 40 mg once daily or ranitidine 150 mg twice daily. Endoscopy was performed prior to inclusion into the study, after four weeks and, if unhealed, again after eight weeks. Healing of esophagitis was defined as complete disappearance of all esophageal ulcerations. Symptoms were recorded before entry, after four weeks, and again after eight weeks in unhealed patients. Fifty-one patients were included in the per-protocol analysis at day 29, and 50 patients at day 57. The healing rate after four weeks of treatment was 22 of 26 patients (85%) treated with omeprazole and 10 of 25 patients (40%) treated with ranitidine (P<0.001). The corresponding figures after eight weeks were 24 of 25 (96%), and 13 of 25 (52%) (P<0.001). These results were confirmed in the intent-to-treat analysis. Patients treated with omeprazole showed a significantly faster and more profound relief in heartburn than patients treated with ranitidine: 85% had no heartburn after four weeks of treatment with omeprazole compared to 24% in patients treated with ranitidine (P=0.00007). The percentage of patients who were free of all reflux symptoms was significantly greater in the omeprazole-treated group as compared to the ranitidine-treated group (62% and 12% respectively, P=0.0001). There were no clinically significant changes in laboratory values in any of the treatment groups. Adverse events were few and mainly mild and transient.     

A Comparison Between Sodium Alginate and Magaldrate Anhydrous in the Treatment of Patients with Gastroesophageal Reflux Symptoms

The aims of the present study were to compare effects of sodium alginate and the antacid magaldrate anhydrous in adults with gastroesophageal reflux (GOR) symptoms.Patients with heartburn and/or acid regurgitation for at least 3 days in the week before the study started (n=203) were randomized to receive a single dose of sodium alginate or magaldrate anhydrous at the onset of symptoms during a 3-day run-in period. Patients with symptoms during the run-in (n=191) were rerandomized to receive a 14-day treatment with either drug given as four daily doses. A speed of action ≤30 min was significantly more frequent among patients in the alginate group (49.4% vs. 40.4%; P=0.0074). A trend toward a more prolonged duration of action (median: 16.5 vs. 12.7 hr) and a greater sum of the symptom intensity difference (median: 40.0 vs. 31.0) was observed in the sodium alginate group. Total disappearance of symptoms was reported in 81.6% and 73.9% of patients in the sodium alginate group and magaldrate group, respectively. We conclude that sodium alginate was faster than magaldrate in relieving GRO symptoms and showed a tendency toward a more prolonged duration of action and a higher level of efficacy.     

Functional heartburn patients demonstrate traits of functional bowel disorder but lack a uniform increase of chemoreceptor sensitivity to acid

BACKGROUND: Functional heartburn (FH) patients have a profound impact on the response to anti-reflux therapy of the nonerosive reflux disease (NERD) group as compared to the response of the erosive esophagitis group. Thus far, there is paucity of information about their physiological and clinical characteristics that may separate them from the other NERD patients. AIM: To compare physiological and clinical characteristics of patients with FH to their counterparts within the NERD group (NERD-positive [NERD+]). METHODS: Subjects with typical heartburn symptoms, at least twice a week, were evaluated by an upper endoscopy. Only those with normal esophageal mucosa were recruited into the study and underwent pH testing to assess esophageal acid exposure. The patients were divided into those with normal pH test (FH) and those with abnormal pH test (NERD+). The groups were compared for demographics, gastroesophageal reflux disease symptom characteristics, psychological profile, and reported quality of life. Additionally, the two patient groups were compared for stimulus response functions to acid, autonomic function response, and rate of Helicobacter pylori infection. RESULTS: Fifty-two patients included 30 with FH and the rest with NERD+. There was no statistical difference in demographics, frequency of hiatal hernia and H. pylori infection between the two groups. Patients with FH had a significantly longer history of heartburn and reported more episodes of chest pain than NERD+ patients (M--7.5 yr and M--once a week vs M--3.5 yr and M--once a month, respectively, p < 0.05). Patients with FH scored significantly higher in the somatization domain than patients with NERD+ (M--60 vs 52.5, p < 0.05), but had similar reported quality of life. Patients with NERD+ demonstrated a significantly shorter time to symptom perception and higher intensity rating (p < 0.05). Only patients with FH demonstrated a statistically significant increase in heart rate and skin conductance after acid perfusion, as compared to those with NERD+ (p < 0.05). CONCLUSION: Patients with FH demonstrate increased reports of chest pain and somatization, an alteration in autonomic function but lack a uniform increase in chemoreceptor sensitivity to acid as compared to those with NERD+. This suggests that while FH patients harbor clinical traits of a functional bowel disorder, hypersensitivity to acid is not a general phenomenon.     

Functional heartburn and non-erosive reflux disease

Gastroesophageal reflux disease (GERD) is a common disorder in Western countries. For many years our attention has been focused on patients with erosive esophagitis, but in recent times we have realized that endoscopy-negative reflux disease is the most common presentation of this illness, affecting up to 70% of these individuals. Patients with the non-erosive form (NERD) are a heterogeneous group including various subpopulations with different mechanisms for their main symptom of heartburn: reflux of acidic and non-acidic gastric contents, mucosal hypersensitivity, intraesophageal distension by gas, intraduodenal infusion of fat, muscle contractions and psychological abnormalities. As to esophageal acid exposure, patients with NERD can be subdivided into those with abnormal and normal pH testing. The latter group includes patients with a positive correlation between symptoms and reflux events, in whom heartburn can be controlled by proton pump inhibitor (PPI) therapy. According to the recent Rome III criteria, they are still in the realm of GERD. An additional group is called functional heartburn, because this typical symptom is associated neither with an abnormal pH test nor with a positive symptom index. Their response to PPIs is very disappointing. Therefore, there is an increasing consensus on the fact that they do not have GERD and should be treated with drugs other than PPIs.     

Nonerosive reflux disease

Until recently, the finding of erosive esophagitis in patients with chronic heartburn was thought to indicate more severe gastroesophageal reflux disease. However, recent data suggests that this is not necessarily true. Seventy-five percent of patient's chronic heartburn have moderate to severe symptoms, regardless of the presence or absence of esophagitis. Nonerosive reflux disease (NERD) is characterized by heartburn symptoms for at least 3 months with no evidence of esophagitis. Patients with NERD are similar to patients with esophagitis in symptom severity, quality of life scores, and response to anti-reflux therapy. There are probably 3 distinct groups of NERD patients, those with pathologic reflux, those with a heightened sensitivity to physiologic reflux and those with other medical problems mistaken for reflux. This article discusses the 3 clinical scenarios.     

Prospective follow-up data from the ProGERD study suggest that GERD is not a categorial disease

OBJECTIVES: There is a controversy as to whether gastroesophageal reflux disease (GERD) exists as a spectrum of disease severity or as a categorial disease in three distinct groups: nonerosive (NERD) and erosive reflux disease (ERD) and Barrett's esophagus (BE). Aim of the study was to assess progression or regression of GERD over 2 yr in a large cohort of patients (N = 3,894) under routine clinical care in Germany, Austria, and Switzerland (ProGERD study). METHOD: Patients with predominant heartburn, with or without esophagitis, were recruited and classified according to endoscopic status at baseline, i.e., NERD, erosive reflux disease-Los Angeles (ERD-LA) grade A/B and ERD-LA grade C/D, and BE. After an initial treatment with esomeprazole, they were followed, regardless of their response. Medical therapy or endoscopy was initiated at the discretion of their primary care physician, in line with routine care. At 2 yr, endoscopy with biopsy was performed according to the protocol. RESULTS: After 2 yr, 25% of patients who had NERD at baseline progressed to LA A/B and 0.6% to LA C/D; 1.6% of patients who had LA A/B progressed to LA C/D and 61% regressed to NERD; 42% of patients who had LA C/D regressed to LA A/B and 50% regressed to NERD (all figures exclude patients with confirmed BE at baseline). At 2 yr, 22% of patients had been off medication for at least 3 months. Patients with ERD-LA grade C/D were at greatest risk of developing BE: 5.8% compared with 1.4% for ERD-LA grade A/B and 0.5% for NERD. CONCLUSION: GERD does not seem to be a categorial disease. Progression and regression between grades was observed in this large cohort of patients under routine clinical care.