Reflux Disease Patients Research Articles

Should we bravo?

Should we bravo?

Cost-effectiveness of different diagnostic strategies to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough in Italy

Background Chronic persistent cough is a common and disabling disorder and gastro-oesophageal reflux disease is considered to be the third leading cause, after asthma and postnasal drip. Therefore, patients with unexplained chronic persistent cough usually undergo a stepwise evaluation to establish the existence of a reflux disease. Aim To identify the most cost-effective diagnostic approach to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough. Methods Direct and indirect costs associated with six diagnostic strategies using 24-h oesophageal pH-metry, oesophago-gastroduodenoscopy and the proton pump inhibitors test in different sequences, were evaluated using a decision tree model. If the first test was positive, the diagnostic work-up was stopped, if negative the patient proceeded to the second test, and so on. Clinical data from an observational prospective trial conducted in 51 patients with unexplained chronic persistent cough were used in the economic model. Results All six strategies had the same clinical effectiveness (78.4%). The diagnostic work-up with the lowest cost was the proton pump inhibitors test followed by pH-metry and then oesophago-gastroduodenoscopy with a total cost of €211.08 (direct €142.93, indirect €68.15). Conclusions This study shows that the lowest cost is the strategy where proton pump inhibitors test is performed as first investigation. Implementation of this diagnostic work-up may lead to cost savings in the management of patients with chronic persistent cough.

Outcome research in gastroenterology: the case of gastroesophageal reflux disease (GERD)

AbstractGastroesophageal reflux disease (GERD) is a common, chronic disorder. The main symptom of GERD is heartburn, although a diverse range of symptoms can be associated with the disease including acid regurgitation and epigastric pain. GERD is also a risk factor for Barrett's oesophagus and esophageal adenocarcinoma. The impact of GERD symptoms on patients' lives can be profound and is unrelated to the presence or absence of esophagitis. The impact of GERD can be measured by assessing the patient perspective using Patient Reported Outcomes (PROs). A number of studies have demonstrated that health‐related quality of life (HRQoL) in reflux disease patients is significantly impaired in comparison to the general population, regardless of the endoscopic findings. Furthermore, this impairment is comparable to or greater than that observed in other chronic conditions, such as diabetes, arthritis, or congestive heart failure. Impaired HRQoL in GERD patients is a result of features such as disturbed sleep, reduced vitality, generalized body pain, an impaired sex life, and anxiety about the underlying cause of the symptoms. The burden of illness imposed by reflux disease on HRQoL also has an impact on productivity, both at and outside work. The impact of reflux disease on productivity is significant and comparable to that caused by headache or back pain. Effective treatment is available for reflux disease, and there is evidence that this can quickly restore HRQoL to levels observed in the general population. Drug Dev. Res. 67:251–259, 2006. © 2006 Wiley‐Liss, Inc.

Five-year results of laparoscopic Toupet fundoplication as the primary surgical repair in GERD patients: Is it durable?

Most surgeons operate on gastroesophageal reflux disease (GERD) patients using the concept of "tailored approach," which depends on esophageal motility. We have abandoned this concept and performed laparoscopic Toupet fundoplication in all patients suffering from GERD, independent of their esophageal motility. In a prospective trial we have assessed and evaluated our 5-year results of the first 100 consecutive patients treated with laparoscopic Toupet fundoplication. All patients were evaluated preoperatively by endoscopy and 24-h pH manometry. The patients were followed up clinically 1, 2, 6, 12 and 60 months postoperatively. The course of clinical DeMeester score, appearance and treatment of wrap-related side-effects as well as long-term outcome and patient satisfaction were evaluated. The 5-year follow-up rate was 87%. Laparoscopic Toupet fundoplication achieved a 5-year healing rate of GERD in 85%. Of all operated patients, 3.5% had to be reinstalled on a regular PPI treatment because of postoperative GERD reappearance. The median clinical DeMeester score decreased from 4.27 +/- 1.5 points preoperatively to 0.47 +/- 0.9 points 5 years postoperatively (p < 0.0005). Because of persistent postoperative dysphagia, 5% of the patients required endoscopic dilatation therapy. Persistent postoperative gas-bloat syndrome occurred in 1.1%. Wrap dislocation was identified in 3.4% of patients. Reoperation rate was 5%. Total morbidity rate was 19.5% and operative related mortality rate was 0%. Overall, 96.6% of patients were pleased with their outcome at late follow-up, and 95.4% of patients stated they would consider undergoing laparoscopic fundoplication again if necessary. Our long-term results showing a low recurrence and morbidity rate of laparoscopic Toupet fundoplication encourage us to continue to perform this procedure as the primary surgical repair in all GERD patients, independent of their esophageal motility. Laparoscopic Toupet fundoplication has proven to be a safe and successful therapeutic option in GERD patients.

On-Demand Therapy with Pantoprazole 20 mg as Effective Long-Term Management of Reflux Disease in Patients with Mild GERD: The ORION Trial

Aims: To compare safety and efficacy of on-demand pantoprazole 20 mg/40 mg versus placebo in the long-term management of patients with mild gastroesophageal reflux disease (GERD) after heartburn relief. Methods: A total of 634 patients with endoscopically confirmed GERD grade 0/I and heartburn were included. During the acute phase, patients were treated with pantoprazole 20 mg once daily for 4 weeks. Those patients relieved from heartburn entered the long-term phase, and were randomly assigned to either treatment group pantoprazole 20 mg, 40 mg or placebo. Over 6 months, patients took study medication on demand (antacids as rescue medication) and discontinued the drug once symptoms abated. Results: After 4 weeks a total of 87.1%/90.0% of patients were free of heartburn (ITT/PP), and entered the subsequent long-term phase. The perceived average daily symptom load (placebo: 3.93, pantoprazole 20 mg: 2.91, pantoprazole 40 mg: 2.71, ITT) and the number of antacid tablets taken (average number, placebo: 0.68, pantoprazole 20 mg: 0.45, pantoprazole 40 mg: 0.33, ITT) were significantly higher in the placebo than in both pantoprazole groups (p < 0.0001), with no statistically significant difference between the two pantoprazole groups. The discontinuation rate due to insufficient control of heartburn was significantly lower in both pantoprazole groups compared to placebo (placebo: 10.9, pantoprazole 20 mg: 2.8, pantoprazole 40 mg: 0.9, ITT). Conclusions: Our findings favor on-demand treatment with pantoprazole 20 mg for the long-term management of heartburn in patients with uncomplicated GERD (grade 0/I) with superiority to placebo.

Unresolved Upper Gastrointestinal (UGI) and Extraesophageal (EE) Symptoms in Gastroesophageal Reflux Disease (GERD) Patients Despite Chronic Proton Pump Inhibitor (PPI) Therapy

Unresolved Upper Gastrointestinal (UGI) and Extraesophageal (EE) Symptoms in Gastroesophageal Reflux Disease (GERD) Patients Despite Chronic Proton Pump Inhibitor (PPI) Therapy

Acid Challenge to the Human Esophageal Mucosa: Effects on Epithelial Architecture in Health and Disease

The histological changes that occur in the squamous epithelium in response to acute acid challenge was examined in healthy controls and proton pump inhibitor-treated gastroesophageal reflux disease (GERD) patients and related to the state of untreated erosive GERD in a saline-controlled, randomized perfusion study. In the basal state a stepwise significant increase in the thickness of the basal cell layer, papillary length, and dilatation of intercellular spaces (DIS) was seen when the three groups were compared. Acid perfusion induced a slight increase in the height of the basal cell layer mainly in healthy volunteers; this layer appears to be reactive to acute acid challenge as well as to acid suppressive therapy. DIS increases promptly in response to acute acid exposure in the healthy epithelium but no changes were seen in the lengths of the papillae or regarding DIS in the GERD patients. A protective effect of luminal nitric oxide on DIS development is suggested.

Chest Pain From Gastroesophageal Reflux Disease in Patients With Coronary Artery Disease

Management of patients with coronary artery disease is a major challenge for physicians, patients, and the healthcare system. Chest pain experienced by patients with coronary disease can be of noncardiac origin, and symptoms frequently related to gastroesophageal etiologies. The distal esophagus and the heart share a common afferent nerve supply, suggesting that location and radiation of perceived pain may be identical. In addition, there is substantial overlap between the prevalence of coronary disease and gastroesophageal reflux disease. Many physicians, including cardiologists, prescribe acid-reducing therapy to coronary patients. However, no prospective, randomized studies to date have evaluated the potential benefit of such treatments to prevent chest pain symptoms for these patients. We review the studies on noncardiac chest pain demonstrating reflux in patients with and without coronary disease. Also, the association of reflux with exertional chest pain and cardiac syndrome X is discussed. A rationale is presented for prevention of noncardiac chest pain in coronary patients, and the potential role of acid-suppressive therapy in managing these patients is discussed.

Value of extended recording time with wireless pH monitoring in evaluating gastroesophageal reflux disease

Extending an ambulatory pH study by using a wireless capsule system could improve diagnosis of gastroesophageal reflux disease in patients with symptoms potentially related to acid reflux events. We determined the relative value of a 2-day versus a 1-day study in detection of abnormal esophageal acid exposure and reflux symptom associations. Subjects who had undergone pH monitoring with the wireless system for symptom evaluation and who had at least 1 typical or atypical symptom during monitoring were studied (n = 157). Acid exposure time, symptom index, and a measure of reflux-associated symptom probability were calculated after 1 day of recording and compared to final results from analysis of 2 days of data. Extending recording time increased the number of subjects recording symptoms by 6.8% and doubled the number of symptoms available for association with acid reflux events. Other advantages were greater in subjects off antireflux therapy, wherein lengthening recording time increased the proportion of subjects with abnormal acid exposure time by 12.4% and significantly increased the likelihood of a positive reflux symptom relationship in subjects with atypical symptoms. Accuracy of a 1-day study ranged from 0.87-0.88 for acid exposure time to as low as 0.72-0.87 for the probability test, the most sensitive of the symptom association tests. Extending recording time to 2 days with the wireless pH monitoring system increases the likelihood of detecting reflux disease in patients undergoing symptom evaluation. Benefits are most evident for subjects with atypical symptoms and for establishing reflux symptom associations by probability testing.

Long‐term treatment of gastro‐oesophageal reflux disease patients with frequent symptomatic relapses using rabeprazole: on‐demand treatment compared with continuous treatment

On-demand treatment may be an alternative in the long-term treatment of non-severe gastro-oesophageal reflux disease in patients with frequent symptomatic relapses. To compare the efficacy of on-demand treatment with rabeprazole 10 mg versus continuous treatment in the long-term treatment of patients with frequent symptomatic relapses of mild to moderate gastro-oesophageal reflux disease. This randomized, open-label study enrolled patients diagnosed with non-erosive reflux disease or oesophagitis grade 1 or 2 (Savary-Miller classification) reporting frequent symptomatic relapses (requiring > or =2 courses of antisecretory therapy during the previous year), whose intensity is rated at least moderate (>2 on a 5-point Likert scale). After a 4-week selection phase with rabeprazole 10 mg once daily, patients reporting symptom relief (Likert score < or =2) were randomized to receive either rabeprazole 10 mg continuous treatment or on-demand treatment for 6 months. The main evaluation criterion was the rate of symptom relief (scored on the Likert scale) after 6 months. One hundred and seventy-six patients were enrolled in the 4-week selection phase (men, 53%; mean age, 49 years; non-erosive reflux disease, 36.4%; gastro-oesophageal reflux disease 1, 53.4%; gastro-oesophageal reflux disease 2, 10.2%). Rabeprazole relieved symptoms in 88.6% of patients. Of this group, 152 were randomized to the comparative phase to receive rabeprazole 10 mg continuous treatment (once daily) or on-demand treatment (continuous treatment, n = 81; on-demand treatment, n = 71). At month 6 (end point), the symptom relief rate was slightly higher for patients in the continuous treatment group compared with those in the on-demand treatment group: 86.4% versus 74.6%, respectively. This difference was not statistically significant (P = 0.065). For the overall quality of life score, there was no difference between the continuous treatment and on-demand treatment groups (86.25 and 84.94). Mean daily consumption of rabeprazole was significantly lower in the on-demand treatment group versus the continuous treatment group (0.31 tablets versus 0.96 tablets; P < 0.0001). On-demand therapy with rabeprazole 10 mg provides an alternative to continuous therapy in patients with mild to moderate gastro-oesophageal reflux disease suffering from frequent symptomatic relapses.

Tough‐to‐treat gastro‐oesophageal reflux disease patients: who are they and how to treat?

Tough‐to‐treat gastro‐oesophageal reflux disease patients: who are they and how to treat?

Systematic review: the effect of Helicobacter pylori and its eradication on gastro-oesophageal reflux disease in patients with duodenal ulcers or reflux oesophagitis.

The effect of Helicobacter pylori in provoking or protecting against gastro-oesophageal reflux disease is unclear and studies have given conflicting results. Recent guidelines recommend H. pylori eradication in patients on long-term proton pump inhibitors. To ascertain the effect of H. pylori eradication on gastro-oesophageal reflux disease outcomes (reflux oesophagitis and heartburn) in patients with duodenal ulcer disease, and to ascertain the effect of H. pylori infection on reflux oesophagitis concerning heartburn, pH, severity, healing and relapse rates. A systematic review of electronic databases was undertaken to September 2003. Experts in the field, pharmaceutical companies and journals were contacted about unpublished trials. Studies were reviewed according to predefined eligibility and quality criteria. Twenty-seven studies/trials were included in the systematic review. Study variation rather than therapy-influenced results in relation to the presence or absence of oesophagitis in patients with duodenal ulcer who underwent H. pylori eradication at 6-48 months follow-up. In patients with reflux oesophagitis no obvious differences were discovered in heartburn scores, 24-h pH values, healing and relapse rates between H. pylori-positive and -negative cases. There is no evidence to indicate that H. pylori eradication in duodenal ulcer disease provokes reflux oesophagitis or worsens heartburn; (ii) there are insufficient data to draw firm conclusions about the impact of H. pylori in patients with reflux oesophagitis.

Increased gastro-oesophageal reflux disease in patients with severe COPD.

The prevalence and clinical consequences of gastro-oesophageal reflux disease (GERD) in chronic obstructive pulmonary disease (COPD) are not well characterised. The present study prospectively studied 42 males with COPD (forced expiratory volume in one second % predicted: 35%, range 20-49) and 16 healthy volunteers of similar age without respiratory or gastro-oesophageal symptoms. The diagnosis of GERD was confirmed using oesophageal 24 h pH monitoring. In the current study group, reflux symptoms were measured using the Vigneri score, cough and dyspnoea with the modified Medical Research Council questionnaire, and pulmonary function with bronchodilator response and health status using St George's Respiratory Questionnaire. Pathological reflux was documented in 26 out of 42 patients (62%) and in three volunteers (19%). In patients with GERD, 15 patients (58%) did not report any reflux symptoms. There were no differences in symptoms, health status, bronchodilator treatment and pulmonary function test between patients with and without GERD. Oxygen desaturation coincided with episodes of increased oesophageal acidity in 40% of patients with GERD. Patients with severe chronic obstructive pulmonary disease have a high prevalence of asymptomatic gastro-oesophageal reflux. The association between this reflux and oxygen desaturation deserves further attention.

Personal view: to treat or not to treat? Helicobacter pylori and gastro-oesophageal reflux disease - an alternative hypothesis.

Helicobacter pylori causes acute on chronic gastritis and is responsible for most peptic ulcers and gastric cancer. However, recent papers have suggested that it may protect against gastro-oesophageal reflux, Barrett's oesophagus and oesophageal cancer. Furthermore, the rapid increase in gastro-oesophageal reflux disease, Barrett's oesophagus and adenocarcinoma of the oesophagus in the developed world has been attributed by some to the falling prevalence of H. pylori. These considerations have led to the suggestion that H. pylori infection should not necessarily be treated, especially in patients with gastro-oesophageal reflux disease. Conversely, data from prospective randomized studies have shown that H. pylori eradication does not cause gastro-oesophageal reflux disease in patients with duodenal ulcer or in the normal population, nor does it worsen the outcome of pre-existing gastro-oesophageal reflux disease. Therefore, although H. pylori is negatively associated with gastro-oesophageal reflux disease, its eradication does not induce the disease. A hypothesis is presented suggesting that the increased prevalence of gastro-oesophageal reflux disease is a result of rising acid secretion in the general population, which, in turn, is a consequence of the increased linear height (a predictor of acid secretion). The greater acid secretion could also explain the decline in the prevalence of H. pylori and perhaps account for the inverse relationship between H. pylori and gastro-oesophageal reflux disease. These considerations are explored in discussing whether H. pylori infection should be treated in infected patients presenting with gastro-oesophageal reflux disease.

Clinical and endoscopic evaluantion of gastroesophageal reflux disease in patients successfully treated with esomeprazole

Esomeprazole, an S-isomer of omeprazole, is the first proton pump inhibitor developed as an optical isomer, and it has shown high healing rates in erosive esophagitis. To evaluate the efficacy and tolerability of esomeprazole in subjects with erosive esophagitis, according to the Los Angeles classification study design: an open, multi-center clinical study. Two hundred and eighteen subjects with reflux esophagitis confirmed by endoscopy were included in an open, multi-center study in Brazil. All of them received esomeprazole 40 mg, once daily, for a 4-week period. Subjects who had unhealed esophagitis by week 4 continued the treatment for another 4 weeks. The primary efficacy endpoint was the healing rates by weeks 4 and 8. The secondary endpoints were the number of patients with symptom resolution by week 4, the number of days to sustained symptom resolution, number of symptom-free days and nights and safety and tolerability of the drug. Healing rates by weeks 4 and 8 were 82% (confidence interval: 77.4%-87.6%) and 96.1% (confidence interval: 93.5% - 98.8%), respectively. Ninety-nine (99%) of the patients had heartburn resolution by week 2. The most common adverse events were headache (4%), diarrhea (2.6%) and epigastric pain (2.2%). For the studied period, esomeprazole was shown to be a safe and well-tolerated drug, providing significant healing rates of mucosal breaks, regardless of LA classification, in patients with erosive esophagitis. Esomeprazole was also shown to be effective in quickly relieving symptoms.

Rabeprazole (RAB) provides fast symptom relief in gastroesophageal reflux disease (GERD) patients with low pretreatment health-related quality of life (HRQOL)

Rabeprazole (RAB) provides fast symptom relief in gastroesophageal reflux disease (GERD) patients with low pretreatment health-related quality of life (HRQOL)

Objective physiologic measurements of gastroesophageal reflux disease in patients with anxiety and depression disorders

Objective physiologic measurements of gastroesophageal reflux disease in patients with anxiety and depression disorders

Rapid relief of symptoms and sustained improvement in health related quality of life (HRQOL) in moderate-severe gastroesophageal reflux disease (GERD) patients treated with pantoprazole

Rapid relief of symptoms and sustained improvement in health related quality of life (HRQOL) in moderate-severe gastroesophageal reflux disease (GERD) patients treated with pantoprazole

Complete fundoplication has similar long-term results in patients with and without esophageal body dysmotility.

Partial fundoplication is advocated for the treatment of gastroesophageal reflux disease in patients with poor esophageal body function. We hypothesized that a complete floppy wrap may be just as safe in patients with poor esophageal motility. A retrospective, case-control study was performed on patients who underwent a complete fundoplication and had poor esophageal motility. Study patients were matched with controls with normal esophageal body pressures according to sex, age, and duration of reflux symptoms. Patients were followed up and interviewed using a modified symptom and life quality questionnaire. Twenty-two patients and 22 matched controls underwent a complete fundoplication. The mean esophageal body pressure was 42.1 and 87.5 mmHg in the study and control groups, respectively (p <0.05). Average time to resolution of dysphagia was 10.1 weeks in the study group and 12 weeks in the control group. All patients but 1 (control) graded their life quality improvement as good to excellent. Our data suggest that a 360 degrees fundoplication has similar long-term results regardless of esophageal body motility. We suggest that a partial fundoplication may be reserved for patients with severe esophageal body dysfunction. The role of manometry in the preoperative workup should be reassesed: it may be mandatory only in patients with preoperative dysphagia or when achalasia is suspected.

Ineffective esophageal motility (IEM) increases reflux in nonerosive reflux disease (NERD) patients?

Ineffective esophageal motility (IEM) increases reflux in nonerosive reflux disease (NERD) patients?