Double-dose Proton Pump Inhibitor Therapy Research Articles

Post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance predict PPI response in GERD patients with extra esophageal symptoms

BackgroundMean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index are able to increase the diagnostic yield of impedance-pH and are associated to proton pump inhibitor (PPI) response. Few data concerning these variables in patients with extra-esophageal symptoms (EES) are available. AimsTo evaluate, in EES patients, the role of the conventional and new impedance-pH variables in diagnosing GERD and the predictive value of impedance-pH variables for PPI response. MethodsConsecutive patients presenting suspected GERD-related EES underwent impedance-pH. Patients treated in the last six months with double dose PPI therapy were enrolled. The presence of concomitant typical symptoms was assessed. Results239 EES patients were studied; 102 responders and 137 non-responders. Eighty-one (34%) were affected by non-erosive reflux disease (NERD), 61 (26%) presented reflux hypersensitivity (RH) and 97 (40%) were non-GERD. In NERD and RH groups, a significantly higher proportion of patients with pathological PSPW index or MNBI values compared to non-GERD group was observed. 24 (25%) non-GERD patients presented a pathological PSPW index and/or MNBI. Pathological PSPW index, MNBI and presence of typical symptoms were associated to PPI response. ConclusionsMNBI and PSPW index measurement increases the diagnostic yield of impedance-pH; abnormal values are associated with a satisfactory response to acid-suppressive therapy in EES patients.

Management options for patients with GERD and persistent symptoms on proton pump inhibitors: recommendations from an expert panel.

The aim of this study was to assess expert gastroenterologists' opinion on treatment for distinct gastroesophageal reflux disease (GERD) profiles characterized by proton pump inhibitor (PPI) unresponsive symptoms. Fourteen esophagologists applied the RAND/UCLA Appropriateness Method to hypothetical scenarios with previously demonstrated GERD (positive pH-metry or endoscopy) and persistent symptoms despite double-dose PPI therapy undergoing pH-impedance monitoring on therapy. A priori thresholds included: esophageal acid exposure (EAE) time >6.0%; symptom-reflux association: symptom index >50% and symptom association probability >95%; >80 reflux events; large hiatal hernia: >3 cm. Primary outcomes were appropriateness of four invasive procedures (laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, radiofrequency energy delivery) and preference for pharmacologic/behavioral therapy. Laparoscopic fundoplication was deemed appropriate for elevated EAE, and moderately appropriate for positive symptom-reflux association for regurgitation and a large hiatal hernia with normal EAE. Magnetic sphincter augmentation was deemed moderately appropriate for elevated EAE without a large hiatal hernia. Transoral incisionless fundoplication and radiofrequency energy delivery were not judged appropriate in any scenario. Preference for non-invasive options was as follows: H2RA for elevated EAE, transient lower esophageal sphincter relaxation inhibitors for elevated reflux episodes, and neuromodulation/behavioral therapy for positive symptom-reflux association. For treatment of PPI unresponsive symptoms in proven GERD, expert esophagologists recommend invasive therapy only in the presence of abnormal reflux burden, with or without hiatal hernia, or regurgitation with positive symptom-reflux association and a large hiatus hernia. Non-invasive pharmacologic or behavioral therapies are preferred for all other scenarios.

Optimization strategies aimed to increase the efficacy of H.pylori eradication therapies.

As with any other infectious disease, we should aim for treatments offering ≥90% Helicobacter pylori eradication rates in clinical practice. To summarize optimization strategies aimed to increase the efficacy of H.pylori eradication therapies. A systematic bibliographic search (in PubMed up to August 2016) was designed to identify studies investigating optimization strategies aimed to increase the efficacy of H.pylori eradication therapies. The most direct way to optimize a treatment is using higher doses of drugs unless it has been shown that lower doses are equally effective. Similarly, prescriptions should use 14-day duration unless a shorter scheme has been shown locally to be equally effective. Double-dose proton-pump inhibitor therapy is recommended for triple therapy and may probably increase the efficacy of nonbismuth concomitant regimen as well. The efficacy of triple therapies in the presence of resistance can be significantly improved by the addition of bismuth salts, which offer an additive effect in combination with antibiotics. Overall, probiotics seem to reduce antibiotic side effects, but the increase in eradication rates is not so evident; therefore, they cannot be generally recommended for clinical practice yet. Using potent acid inhibition and/or higher antibiotic doses-especially by increasing the number of daily intakes-and lengthening treatments up to 14days improves efficacy in most regimens and should be generally recommended. Triple therapies can be efficiently improved by the addition of bismuth salts, turning them into quadruple therapies. Finally, some treatments will require a combination of optimization strategies to significantly improve results.

Editorial: Healing Erosive Esophagitis With a Proton Pump Inhibitor: The More the Merrier?

Patients with erosive esophagitis (EE) account for 30% of patients with gastroesophageal reflux disease; only a minority of these patients fail to achieve healing on treatment with a proton pump inhibitor (PPI), once-daily, for 8 weeks. For those patients with EE who have failed to heal on a PPI, given once-daily, current practice is to double the PPI dose although there is little published evidence to support this. In this issue of the American Journal of Gastroenterology, authors from Japan have demonstrated that double-dose PPI produced higher healing rates when given as a split, twice-daily dose than as a once-daily dose for patients with EE who had failed initial therapy with rabeprazole 10 mg once-daily. Quadruple-dose PPI, given as a split dose, did not increase the healing rates but did produce better symptom control, albeit limited, compared with double-dose PPI, given twice-daily. Because subjects, initially, received a lower PPI dose than that generally indicated for EE (rabeprazole 20 mg daily), this study does not provide the eagerly awaited justification for double-dose PPI therapy in patients with EE who have failed standard-dose PPI once-daily. However, it does demonstrate the clinical advantage of a split-dose regimen (AM and PM), compared with a once-daily regimen, when doubling the dose of a PPI for patients with residual EE after initial therapy.

Randomised clinical trial: twice daily esomeprazole 40 mg vs. pantoprazole 40 mg in Barrett’s oesophagus for 1 year

Barrett's oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett's oesophagus. To evaluate the expression of Ki67, cyclooxygenase-2 (COX-2) and apoptosis in Barrett's oesophagus after 12 months of double-dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared. Seventy-seven nondysplastic Barrett's oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow-up endoscopy was performed at the end of treatment. Sixty-five of 77 patients agreed to undergo oesophageal manometry and 24-h pH-metry. Barrett's oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX-2 expression; apoptosis was evaluated using TUNEL. In the esomeprazole group, a significant decrease in Ki67 and COX-2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX-2 and apoptosis did not vary significantly from baseline. By 24-h oesophageal pH-monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05). Treatment of Barrett's oesophagus patients with high-dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole.

Characteristics of Symptomatic Reflux Episodes in Patients with Non-Erosive Reflux Disease Who Have a Positive Symptom Index on Proton Pump Inhibitor Therapy

Background and Aim: The reason that some reflux episodes evoke symptoms is poorly understood, therefore the aim of this study is to assess the determinants of reflux perception in patients with non-erosive reflux disease (NERD) on proton pump inhibitor (PPI) therapy. Methods: Ten NERD patients with persistent symptoms, despite double-dose PPI therapy, were included in this study. All patients had a positive symptom index (SI), which was determined by ambulatory 24-hour combined impedance-pH monitoring. Reflux episodes were identified and classified as acid, weakly acidic or weakly alkaline reflux and were considered symptomatic if patients recorded a symptom within 5 min after a reflux episode. Results: A total of 954 liquid reflux episodes were detected, including 135 (14.2%) acid, 782 (82.0%) weakly acidic, and 37 (3.9%) weakly alkaline. Overall, 59 (6.2%) reflux episodes were symptomatic and the majority (88.1%) of symptomatic reflux episodes were weakly acidic reflux. When reflux episodes were confined to the distal esophagus, there were very few reflux symptoms. Proximal reflux is significantly more likely to be associated with reflux symptoms, irrespective of the acidity of the refluxate or the duration of proximal reflux episodes. Conclusions: In NERD patients who have a positive SI on double-dose PPI therapy, the high proximal extent of refluxate is a major factor associated with reflux perception.

When does testing for GERD become cost effective in an integrated health network?

Gastroesophageal reflux (GERD) is the most common gastrointestinal disorder, affecting as many as 14% of the US population. Rising rates of esophageal adenocarcinoma are seen in this population, and chronic proton pump inhibitor (PPI) use does not normalize cancer risk. It has also been demonstrated that up to one-third of patients on PPI therapy did not actually have GERD and could be taken off the medication. These facts form the basis for a quality-assurance study of care provided to patients in an integrated health care network who were on high-dose, long-term PPI therapy. A cost-benefit analysis of patients who were on double-dose PPI therapy for more than 6 months was performed. Pharmacy, facility, physician reimbursement, and radiologic data from a cohort who were both primary-care patients and insured in our system were utilized. Two hundred and twenty-four patients were prescribed a double dose of this medication for over 6 months. Utilizing a 4.5% discount rate, our break-even analysis showed that Bravo testing [with esophagogastroduodenoscopy (EGD)] needed to identify those patients who could be taken off PPI therapy paid for itself in 33 months. Bravo + EGD + manometry testing needed to screen for other possible pathologies paid for itself in 38 months. Bravo + barium swallow + EGD testing to screen patients for possible esophageal adenocarcinoma paid for itself in 42 months. Bravo + barium swallow + manometry + EGD testing paid for itself in 47 months. Significant savings can be realized through early use of upper endoscopy, Bravo testing, barium swallow, and manometry to identify patients that are taking double-dose PPIs unnecessarily based on presumptive diagnosis of GERD. This early testing also has the potential to diagnose a variety of other clinically important pathologic conditions more readily.

Acid and non-acid reflux in Japanese patients with non-erosive reflux disease with persistent reflux symptoms, despite taking a double-dose of proton pump inhibitor: a study using combined pH-impedance monitoring

Combined multi-channel intra-luminal impedance and pH (Mll-pH) monitoring can detect gastro-esophageal reflux and identify acid and non-acid reflux (NAR) events. It can be used for patients with persistent symptoms who are having proton pump inhibitor (PPI) therapy. The aim of this study is to determine the frequency of acid reflux and NAR and to establish their relationship with persistent reflux symptoms in Japanese patients with non-erosive reflux disease (NERD) who are on a double-dose of PPI therapy. Thirteen patients with NERD, with persistent reflux symptoms, despite taking PPI at least twice daily, were included in this study. Twenty-four-hour combined Mll-pH monitoring was carried out on all patients and reflux episodes were detected by impedance channels, located at 3, 5, 7, 9, 15 and 17 cm above the lower esophageal sphincter (LES) and classified into acid reflux and NAR, based on pH data from 5 cm above the LES. A positive symptom index (SI) was declared, if at least half of the symptoms were preceded by reflux episodes within 5 min. A total of 916 liquid reflux episodes were detected, and a total of 171 symptoms were recorded. Eight (4.7%) of 171 symptoms were related to acid reflux, and 68 (39.8%) were related to NAR. Seven (53.8%) patients had a positive SI and in these seven patients, a total of 79 symptoms were recorded. 5 (6.3%) of the 79 symptoms were related to acid reflux and 44 (55.7%) were related to NAR. Persistent reflux symptoms, in SI-positive patients with NERD on double-dose PPI therapy, are more likely to be associated with primarily non-acid reflux.

Pilot series of radiofrequency ablation of Barrett’s esophagus with or without neoplasia

Radiofrequency ablation is a rapidly evolving therapeutic modality for Barrett's esophagus. The aim of this ongoing 12-month trial is to assess Barrett's esophagus eradication after radiofrequency ablation using a balloon-based (HALO-360) and a plate-based (HALO-90) device. We report here our experience with the first 10 patients (out of 40) who have completed 12 months of follow-up. Following radiofrequency ablation using the HALO-360 device all patients were maintained on double-dose proton pump inhibitor therapy. Endoscopic evaluation was performed at 3 and 12 months postablation. Patients with residual Barrett's esophagus at 3 months underwent repeat ablation. Ten patients, seven with nondysplastic Barrett's esophagus, two with low-grade and one with high-grade dysplasia have completed the study to date. Complete Barrett's esophagus eradication was achieved in seven patients, and partial eradication was achieved in three. There were no major complications. One case of buried Barrett's metaplasia was encountered and successfully re-ablated, with complete Barrett's esophagus eradication achieved at 12 months. In this study, Barrett's eradication rates were comparable to previously published reports. One case of buried Barrett's metaplasia was identified out of 247 biopsies and was eradicated with repeat ablation.

Pharyngeal pH measurements in patients with respiratory symptoms before and during proton pump inhibitor therapy

Background: Pharyngeal pH monitoring is a diagnostic tool used to identify Gastroesophageal reflux disease (GERD) as an etiology of respiratory symptoms. We performed pharyngeal pH monitoring on 14 patients with respiratory symptoms thought to be induced by GERD. Methods: Symptoms and pH monitoring (esophageal and pharyngeal) were assessed prior to and 3 months after the initiation of double-dose proton pump inhibitor therapy. Results: Symptoms included cough, hoarseness, and throat clearing. Ten patients had at least one episode of pharyngeal reflux (PR+) and 4 patients had no pharyngeal reflux (PR−). Pharyngeal reflux episodes in PR+ patients decreased from 3.5 to 0.9 ( P <0.05) per day with 8 of 10 (80%) patients having elimination or reduction of such episodes. Eight of 9 PR+ patients (89%) with suppressed pharyngeal reflux on medical therapy had resolution of respiratory symptoms. Three of 4 PR− patients (75%) had persistent symptoms on medical therapy. Conclusions: Proton pump inhibitor therapy improves clinical symptoms and decreases pharyngeal reflux episodes in patients with respiratory symptoms related to GERD. Direct measurement of pharyngeal pH is helpful in the identification of patients likely to respond to antireflux therapy.