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Hershcovici T.,Neuroenteric Clinical Research Group | Hershcovici T.,University of Arizona | Jha L.K.,Neuroenteric Clinical Research Group | Jha L.K.,University of Arizona | And 7 more authors.
Journal of Clinical Gastroenterology | Year: 2012

Background: There is limited information regarding the contribution of diabetes mellitus (DM) to proton pump inhibitor (PPI) failure in gastroesophageal reflux disease (GERD) patients. Aim: To determine whether type 2 DM is a risk factor for PPI failure and the potential predictive factors for PPI failure among type 2 DM patients with GERD. DESIGN:: A case-control study was performed using hospital medical records of GERD patients treated with a PPI. The prevalence of type 2 DM and other risk factors (established >1 y before study enrollment) was determined in the PPI failure (treatment with more than once daily PPI) as compared with PPI responders. Results: A total of 732 GERD patients receiving PPI therapy, including 285 who failed PPI treatment, were included. The overall prevalence of PPI failure was significantly higher in diabetic versus nondiabetic patients. The relationship between PPI failure and type 2 DM depended on body mass index. Only in obese patients the odds ratio of PPI failure was significantly higher in type 2 DM as compared with non-DM patients. In the subgroup of GERD patients with type 2 DM (n=349), PPI failure was significantly associated with female sex, the presence of general comorbidities, and adequate DM control. Duration of DM, type of antidiabetic medication prescribed, and DM-associated complications were not associated with PPI failure. Conclusions:: PPI failure was significantly associated with type 2 DM in obese patients. Among GERD patients with type 2 DM, failure of PPI treatment was significantly associated with female sex and the presence of general comorbidities. Copyright © 2012 by Lippincott Williams & Wilkins.


Allen L.,Neuroenteric Clinical Research Group | Poh C.H.,Neuroenteric Clinical Research Group | Gasiorowska A.,Neuroenteric Clinical Research Group | Malagon I.,Neuroenteric Clinical Research Group | And 10 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2010

Background A significant increase in oesophageal acid exposure during early recumbent period has been demonstrated. Aim To determine if acid reflux during the early recumbent period occurs in the recumbent-asleep or recumbent-awake period using a novel integrative actigraphy and pH programme. Method Thirty-nine subjects with heartburn at least three times a week were included. Subjects underwent pH testing concomitantly with actigraphy. Simultaneously recorded actigraphy and pH data were incorporated using a novel integrative technique to determine sleep and awake periods. Characteristics of acid reflux were compared between the recumbent-awake and recumbent-asleep periods. Results Seventeen (44.7%) subjects had acid reflux events during recumbent-awake period as compared to seven (18.4%) in the corresponding recumbent-asleep period (P = 0.046). The mean number of acid reflux events in recumbent-awake period was significantly higher than in the corresponding recumbent-asleep period (8.1 ± 4.4 vs. 3.2 ± 1.5, P < 0.001). In the recumbent-awake period, 38.4% of acid reflux events were associated with GERD-related symptoms as compared with 3.7% of acid reflux events during the corresponding recumbent-asleep period (P = 0.01). Conclusion Increased acid reflux in the early recumbent period occurs primarily during the recumbent-awake and not during the recumbent-asleep period. © 2010 Blackwell Publishing Ltd.


Hershcovici T.,Neuroenteric Clinical Research Group | Fass R.,University of Arizona
Drugs | Year: 2011

Gastro-oesophageal reflux disease (GORD or GERD) is a very common disorder, and advancement in drug development over the years has markedly improved disease management. Proton pump inhibitors (PPIs) remain the mainstay of treatment for GERD due to their profound and consistent inhibitory effect on acid secretion. However, PPIs do not reduce the number of reflux events and do not provide long-term cure for GERD. In addition, although the safety profile of PPIs is excellent, recent population-based studies have suggested that long-term PPI use may be associated with a variety of adverse events. They include osteoporosis-related hip and spine fractures, community-acquired and nosocomial pneumonia, various enteric and non-enteric infections, fundic gland polyps and many others. Consequently, there is growing interest by patients and physicians alike in current, as well as future, non-PPI-related therapeutic strategies for GERD. This includes repositioning histamine H 2 receptor antagonists and prokinetics in our current GERD therapeutic algorithms and a resurgence of non-medical therapeutic modalities for GERD, such as anti-reflux surgery, endoscopic treatment, alternative and complementary medicine and psychological interventions. Furthermore, there will be renewed efforts in further developing new medical and non-medical therapeutic modalities for GERD. © 2011 Adis Data Information BV. All rights reserved.


Hershcovici T.,Neuroenteric Clinical Research Group | Hershcovici T.,University of Arizona | Fass R.,Neuroenteric Clinical Research Group | Fass R.,University of Arizona
Best Practice and Research: Clinical Gastroenterology | Year: 2010

Patients with gastro-esophageal reflux disease (GERD) who are not responding to proton pump inhibitors (PPIs) given once daily are very common. These therapy-resistant patients have become the new face of GERD in clinical practice in the last decade. Upper endoscopy appears to have a limited diagnostic value. In contrast, esophageal impedance with pH testing on therapy appears to provide the most insightful information about the subsequent management of these patients. Commonly, doubling the PPI dose or switching to another PPI will be offered to patients who failed PPI once daily. Failure of such therapeutic strategies is commonly followed by assessment for weakly or residual acidic reflux. There is growing information about the potential value of compounds that can reduce transient lower esophageal sphincter relaxation rate. Esophageal pain modulators are commonly offered to patients with functional heartburn although supportive clinical studies are still missing.


Hershcovici T.,Neuroenteric Clinical Research Group | Jha L.K.,University of Arizona | Fass R.,Neuroenteric Clinical Research Group | Fass R.,University of Arizona
Annals of Medicine | Year: 2011

Dexlansoprazole MR is the R-enantiomer of lansoprazole that is delivered by a novel system, the dual delayed release formulation. The drug has been shown to be efficacious in healing erosive esophagitis as compared with lansoprazole. When compared to placebo, dexlansoprazole provided significantly higher maintenance rates for healed esophageal mucosa in patients with erosive esophagitis and symptom control in patients with non-erosive reflux disease. Dexlansoprazole could be taken without regard to food. Overall, dexlansoprazole is well tolerated and has a comparable side-effect profile to lansoprazole. © 2011 Informa UK, Ltd.


Poh C.H.,Neuroenteric Clinical Research Group | Allen L.,Neuroenteric Clinical Research Group | Gasiorowska A.,Neuroenteric Clinical Research Group | Navarro-Rodriguez T.,Neuroenteric Clinical Research Group | And 7 more authors.
Clinical Gastroenterology and Hepatology | Year: 2010

Background & Aims: More than half of patients with gastroesophageal reflux disease (GERD) report heartburn that awakens them from sleep. We aimed to determine the frequency of conscious awakenings associated with acid reflux events during sleep and their relationship with symptoms in patients with GERD compared with normal subjects. Methods: The study included 39 patients with heartburn and/or regurgitation at least 3 times each week and 9 healthy individuals as controls. Subjects underwent pH testing concomitantly with actigraphy. Novel software simultaneously integrated raw actigraphy and pH data matched by time to determine patients' conscious awakenings during sleep and their temporal relationship with acid reflux events and GERD-related symptoms. Results: A total of 104 and 11 conscious awakenings were recorded in 89.7% of patients and 77.8% of normal controls, respectively. The mean number of conscious awakenings was significantly higher in the group with GERD compared with(3.0 plusminus 0.3 vs 1.8 plusminus 0.4, P < .05). Of the conscious awakenings, 51.9% (51/104) were associated with an acid reflux event in GERD patients and 0 in controls (P < .01). Only 16.3% of total conscious awakenings were symptomatic. In most of the conscious awakenings that were associated with an acid reflux event (85.6%), the awakening preceded the reflux event. Conclusions: Acid reflux events occur primarily after an awakening episode. Conscious awakenings from sleep are common among patients with GERD and are frequently associated with acid reflux events. However, conscious awakenings associated with reflux events are seldom symptomatic. © 2010 AGA Institute.


Hershcovici T.,Neuroenteric Clinical Research Group | Jha L.K.,Neuroenteric Clinical Research Group | Johnson T.,Neuroenteric Clinical Research Group | Gerson L.,Stanford University | And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2011

Background A potential relationship has been suggested between gastro-oesophageal reflux disease (GERD) and interstitial lung diseases (ILDs). Aim To evaluate whether there is a causal relationship between GERD and different ILDs. Methods We conducted a systematic search of literature published between 1980 and 2010. After a review by two independent authors, each study was assigned an evidence-based rating according to a standard scoring system. Results We identified 319 publications and 22 of them met the entry criteria. Of those, the relationship between GERD and idiopathic pulmonary fibrosis (IPF) was investigated in 14 articles, pulmonary involvement in systemic sclerosis (SSc) in six articles and pulmonary involvement in mixed connective tissue disease (MCTD) in two articles. We found the prevalence of GERD and/or oesophageal dysmotility to be higher in patients with different types of ILD as compared with those without ILD [Evidence B]. Among patients with IPF, 67-76% demonstrated abnormal oesophageal acid exposure off PPI treatment. No relationship was demonstrated between severity of GERD and severity of IPF [Evidence B]. Data are scant on outcomes of antireflux treatment in patients with IPF. There is a correlation between the severity of ILD and the degree of oesophageal motor impairment in patients with SSc and MCTD [Evidence B]. Conclusions Based on the currently available data, a causal relationship between GERD and idiopathic pulmonary fibrosis cannot be established. There is scant evidence about antireflux therapy in idiopathic pulmonary fibrosis patients. There may be an association between lung and oesophageal involvement in systemic sclerosis and mixed connective tissue disease, but a causal relationship cannot be established. © 2011 Blackwell Publishing Ltd.


Johnson T.,Neuroenteric Clinical Research Group | Gerson L.,Stanford University | Hershcovici T.,Neuroenteric Clinical Research Group | Stave C.,Stanford University | Fass R.,Neuroenteric Clinical Research Group
Alimentary Pharmacology and Therapeutics | Year: 2010

Aliment Pharmacol Ther 31, 607-614 SummaryBackground Carbonated beverages have unique properties that may potentially exacerbate gastro-oesophageal reflux disease (GERD), such as high acidity and carbonation. Cessation of carbonated beverage consumption is commonly recommended as part of lifestyle modifications for patients with GERD. Aims To evaluate the relationship of carbonated beverages with oesophageal pH, oesophageal motility, oesophageal damage, GERD symptoms and GERD complications. Methods A systematic review. Results Carbonated beverage consumption results in a very short decline in intra-oesophageal pH. In addition, carbonated beverages may lead to a transient reduction in lower oesophageal sphincter basal pressure. There is no evidence that carbonated beverages directly cause oesophageal damage. Carbonated beverages have not been consistently shown to cause GERD-related symptoms. Furthermore, there is no evidence that these popular drinks lead to GERD complications or oesophageal cancer. Conclusions Based on the currently available literature, it appears that there is no direct evidence that carbonated beverages promote or exacerbate GERD. © 2010 Blackwell Publishing Ltd.


Hershcovici T.,Neuroenteric Clinical Research Group | Achem S.R.,Mayo Medical School | Jha L.K.,Neuroenteric Clinical Research Group | Fass R.,Neuroenteric Clinical Research Group
Alimentary Pharmacology and Therapeutics | Year: 2012

Background Treatment of noncardiac chest pain (NCCP) remains a challenge. This is in part due to the heterogenous nature of this disorder. Several conditions are associated with NCCP including gastro-oesophageal reflux disease (GERD), oesophageal dysmotility, oesophageal hypersensitivity as well as others. Aim To determine the currently available therapeutic modalities for NCCP. Methods We performed a systematic review of the literature that was published between January, 1980 and March, 2011. We identified 734 studies; 68 of them met entry criteria. Results Patients with GERD-related NCCP should receive proton pump inhibitors (PPI) twice daily for at least 8 weeks. Smooth muscle relaxants are only recommended for temporary relief of NCCP with motility disorders. Botulinum toxin injection of the distal oesophagus may be effective in the treatment of NCCP and spastic oesophageal motility disorders. Studies assessing the value of tricyclic antidepressants, trazodone and selective serotonine reuptake inhibitors in NCCP are relatively small, but suggest an oesophageal analgesic effect in NCCP patients that is limited by their side effects profile. The usage of theophylline to treat patients with non-GERD-related NCCP should be weighed against its potential toxicity. Use of complementary medicine has been scarcely studied in NCCP. Patients with coexisting psychological morbidity or those not responding to any medical therapy should be considered for psychological intervention. Cognitive behavioural therapy and hypnotherapy may be useful in the treatment of NCCP. Conclusions Patients with GERD-related noncardiac chest pain should be treated with at least double dose PPI. The primary treatment for non-GERD-related noncardiac chest pain, regardless if oesophageal dysmotility is present, is pain modulators. © 2011 Blackwell Publishing Ltd.


PubMed | Neuroenteric Clinical Research Group
Type: Journal Article | Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | Year: 2010

More than half of patients with gastroesophageal reflux disease (GERD) report heartburn that awakens them from sleep. We aimed to determine the frequency of conscious awakenings associated with acid reflux events during sleep and their relationship with symptoms in patients with GERD compared with normal subjects.The study included 39 patients with heartburn and/or regurgitation at least 3 times each week and 9 healthy individuals as controls. Subjects underwent pH testing concomitantly with actigraphy. Novel software simultaneously integrated raw actigraphy and pH data matched by time to determine patients conscious awakenings during sleep and their temporal relationship with acid reflux events and GERD-related symptoms.A total of 104 and 11 conscious awakenings were recorded in 89.7% of patients and 77.8% of normal controls, respectively. The mean number of conscious awakenings was significantly higher in the group with GERD compared with controls (3.0 0.3 vs 1.8 0.4, P < .05). Of the conscious awakenings, 51.9% (51/104) were associated with an acid reflux event in GERD patients and 0 in controls (P < .01). Only 16.3% of total conscious awakenings were symptomatic. In most of the conscious awakenings that were associated with an acid reflux event (85.6%), the awakening preceded the reflux event.Acid reflux events occur primarily after an awakening episode. Conscious awakenings from sleep are common among patients with GERD and are frequently associated with acid reflux events. However, conscious awakenings associated with reflux events are seldom symptomatic.

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