Diagnosis of gastro-oesophageal reflux disease is enhanced by adding oesophageal histology and excluding epigastric pain.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) in clinical practice is limited by the sensitivity and specificity of symptoms and diagnostic testing. AIM: To determine if adding histology as a criterion and excluding patients with epigastric pain enhances the diagnosis for GERD. METHODS: Patients with frequent upper gastrointestinal symptoms who had not taken a proton pump inhibitor in the previous 2 months and who had evaluable distal oesophageal biopsies were included (Diamond study: NCT00291746). Epithelial hyperplasia was identified when total epithelial thickness was at least 430 µm. Investigation-based GERD criteria were: presence of erosive oesophagitis, pathological oesophageal acid exposure and/or positive symptom-acid association probability. Symptoms were assessed using the Reflux Disease Questionnaire and a pre-specified checklist. RESULTS: Overall, 127 (55%) of the 231 included patients met investigation-based GERD criteria and 195 (84%) met symptom-based criteria. Epithelial hyperplasia was present in 89 individuals, of whom 61 (69%) met investigation-based criteria and 83 (93%) met symptom-based criteria. Adding epithelial hyperplasia as a criterion increased the number of patients diagnosed with GERD on investigation by 28 [12%; number needed to diagnose (NND): 8], to 155 (67%). The proportion of patients with a symptom-based GERD diagnosis who met investigation-based criteria including epithelial hyperplasia was significantly greater when concomitant epigastric pain was absent than when it was present (P < 0.05; NND: 8). CONCLUSIONS: Histology increases diagnosis of GERD and should be performed when clinical suspicion is high and endoscopy is negative. Excluding patients with epigastric pain enhances sensitivity for the diagnosis of GERD.

Sleep disturbance due to heartburn and regurgitation is common in patients with functional dyspepsia.

BACKGROUND: Reflux symptoms (heartburn and regurgitation) are common in patients with functional dyspepsia who do not have gastroesophageal reflux disease (GERD). OBJECTIVE: The purpose of this study was to assess the relationship of reflux symptoms with sleep disturbances in patients with functional dyspepsia without GERD and in those with GERD. METHODS: This post-hoc analysis of data from the Diamond study (NCT00291746) included patients with frequent upper gastrointestinal symptoms, of whom 137 had functional dyspepsia and 193 had GERD (diagnosed by endoscopy and pH monitoring). Patients completed symptom questionnaires and were interviewed by physicians. RESULTS: During the seven nights before study entry, 46.0% of patients with functional dyspepsia and 64.8% of those with GERD reported sleep disturbances (any frequency) related to reflux symptoms. Frequent (often/every night) sleep disturbances were experienced by 12.4% of patients with functional dyspepsia and 24.9% of those with GERD (p = 0.005). Among patients with functional dyspepsia, the prevalence of sleep disturbances was highest in those whose heartburn and/or regurgitation were moderate to severe (vs mild/very mild) and frequent (4-7 vs 1-3 days/week). CONCLUSIONS: Sleep disturbances due to reflux symptoms are common in patients with functional dyspepsia who do not have GERD, and become more frequent with increasing reflux symptom severity and frequency.

Gender differences in symptoms in partial responders to proton pump inhibitors for gastro-oesophageal reflux disease.

BACKGROUND: Gender differences may exist in the symptom experience of patients with gastro-oesophageal reflux disease (GERD) who have a partial response to proton pump inhibitors (PPIs). OBJECTIVE: The purpose of this study was to analyse gender differences in partial responders to PPIs. METHODS: Patients with GERD who responded partially to PPIs (n = 580; NCT00703534) completed the Reflux Symptom Questionnaire 7-day recall (RESQ-7) and the Gastrointestinal Symptom Rating Scale (GSRS). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. RESULTS: Women had significantly higher RESQ-7 domain scores than men for Heartburn (frequency: 4.3 vs 3.9; intensity: 3.1 vs 2.8), Burping (frequency: 4.9 vs 4.4; intensity: 3.1 vs 2.8) and Hoarseness, cough and difficulty swallowing (frequency: 2.6 vs 2.2; intensity: 1.8 vs 1.5), and had higher GSRS domain discomfort scores than men for Abdominal pain (3.51 vs 3.23), Indigestion (3.80 vs 3.45) and Constipation (2.69 vs 2.17) (all p < 0.05). Anxiety and depression were significantly more prevalent in women than in men. CONCLUSION: In this population of partial responders, women had more frequent/intense heartburn and extra-oesophageal symptoms and more discomfort from abdominal pain, indigestion and constipation than men. Comorbid anxiety and depression may contribute to the increased symptom burden in women.

Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy.

BACKGROUND: A substantial proportion of patients with gastro-oesophageal reflux disease (GERD) have only a partial response to proton pump inhibitor (PPI) therapy. Prokinetic drugs may improve reflux symptoms by enhancing oesophageal motility and gastric emptying. AIM: To evaluate the effect of revexepride, a novel prokinetic 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist, compared with placebo, in patients with GERD who have a partial response to PPIs. METHODS: A phase 2b, double-blind, parallel-group study was conducted, in which patients were randomised to one of three revexepride treatment groups (0.1, 0.5 and 2.0 mg three times daily) or placebo (1:1:1:1 ratio). Daily e-diary data captured patients' symptoms over an 8-week treatment period. The primary efficacy outcome was the weekly percentage of regurgitation-free days in the second half of the study (weeks 5-8). RESULTS: In total, 480 patients were randomised and 477 received treatment (mean age 47.9 years; 61% women). The mean percentage of regurgitation-free days increased from baseline (range, 15.0-18.8%) to week 8 (62.3-70.5%) in all four study arms; however, there were no statistically significant differences in this change between placebo and the three treatment arms. No dose-dependent relationship in treatment effect was observed for any of the study endpoints. The incidence of treatment-emergent adverse events (TEAEs) was revexepride dose-dependent. Only one serious TEAE occurred and none resulted in death. CONCLUSIONS: Revexepride was no more effective than placebo in controlling regurgitation in patients with GERD symptoms partially responsive to PPIs. Revexepride was well tolerated. ClinicalTrials.gov Identifier: NCT01472939.

Randomised clinical trial: arbaclofen placarbil in gastro-oesophageal reflux disease--insights into study design for transient lower sphincter relaxation inhibitors.

BACKGROUND: Arbaclofen placarbil is a pro-drug of the gamma-aminobutyric acid-B agonist R-baclofen that has been shown to reduce reflux episodes in patients with gastro-oesophageal reflux disease (GERD). AIM: To evaluate the efficacy and safety of arbaclofen placarbil vs. placebo as adjunctive therapy in subjects with troublesome GERD symptoms despite therapy with once-daily doses of a proton pump inhibitor (PPI) and to identify the characteristics of patients who were responders. METHODS: Patients (n = 460) with symptomatic GERD experiencing troublesome symptoms on once-daily PPI therapy were enrolled in this phase II, randomised, multicentre, double-blind, placebo-controlled, dose-ranging study. Patients were randomised to receive placebo or arbaclofen placarbil (20 or 40 mg once daily, 20 or 30 mg twice daily) with their current PPI for 6 weeks. Patients recorded heartburn and other GERD symptoms in a daily diary and rated severity of each event. The primary endpoint was percent change from baseline in heartburn events per week. RESULTS: In the primary analysis, there was no significant difference between arbaclofen placarbil and placebo. Post hoc analyses removing mild and very mild heartburn events resulted in greater percent reductions for all arbaclofen placarbil doses with nominal P values <0.05 for each dose compared with placebo. There was a dose-related increase for the most common adverse events. CONCLUSIONS: Arbaclofen placarbil was not superior to placebo in the primary analysis. Post hoc analyses suggest that subjects with more clinically relevant moderate or severe symptoms are more likely to respond to arbaclofen placarbil (clinicaltrials.gov NCT00978016).

Funding source and conflict of interest disclosures by authors and editors in gastroenterology specialty journals revisited.

BACKGROUND: A survey of journals published in the field of Gastroenterology conducted 5 years ago showed marked variability in reporting of conflicts of interest or funding sources in these journals. AIM: To re-examine reporting of conflicts of interest and funding sources for original articles and editorials in Gastroenterology and Hepatology journals. METHODS: We evaluated all original articles and editorials in 15 leading journals (determined by impact factor-Thomson Reuter Science Citation Index) devoted to Gastroenterology and Hepatology for disclosures of conflicts and for editor's self disclosures. We examined each journal's editorial policy by contacting the journal directly if the information was not revealed on the Web site or print versions of the journal. RESULTS: Of the 1574 articles evaluated, a total of 1207 (77%) reported the presence or absence of a potential conflict of interest and 1047 (67%) reported the presence or absence of funding sources. A total of 3 of the 15 (20%) journals (American Journal of Gastroenterology, Gastroenterology, and Alimentary Pharmacology and Therapeutics reported the presence or absence of funding sources in all their published original articles. Only 5 of 15 (33%) journals (Gut, Gastrointestinal Endoscopy, American Journal of Gastroenterology, Neurogastroenterology & Motility and Alimentary Pharmacology and Therapeutics) publicly disclosed the conflicts of interest of the editors. CONCLUSIONS: (i) Funding sources and conflicts of interest are still reported variably in the GI literature. (ii) Editorials and review articles are influential, but have poor reporting of conflicts of interest. (iii) Editors of many journals still do not report their conflicts of interest.

Randomised clinical trial: the burden of illness of uninvestigated dyspepsia before and after treatment with esomeprazole--results from the STARS II study.

BACKGROUND: Patients with dyspepsia often experience troublesome symptoms. AIM: To assess the burden of uninvestigated dyspepsia (symptoms, health-related quality of life [HRQL] and work productivity) before and after 8 weeks' esomeprazole treatment. METHODS: Patients (n=1250) with uninvestigated dyspepsia (no endoscopy within 6 months and ≤ 2 endoscopies within 10 years) underwent a 1-week esomeprazole acid-suppression test before randomisation to 7 weeks' esomeprazole or placebo. The Reflux Disease Questionnaire (RDQ), Quality of Life in Reflux and Dyspepsia (QOLRAD) and Work Productivity and Activity Impairment (WPAI) questionnaires were completed at baseline (1-week off-treatment) and 8 weeks. WPAI results were further analysed among patients who responded to the acid-suppression test. RESULTS: The highest baseline symptom score was for the RDQ dyspepsia domain, and the highest disease burden was for QOLRAD vitality and food/drink problems. After 8 weeks, significant improvements vs. placebo were observed for all RDQ and QOLRAD domains. The sub-population of acid-suppression test responders, but not the total WPAI population, had a significant work productivity improvement vs. placebo. CONCLUSIONS: Uninvestigated dyspepsia is associated with high symptom load and impacts on HRQL and work productivity. Esomeprazole improves HRQL among such patients, and improves work productivity among 1-week acid-suppression trial responders. ClinicalTrials.gov identifier: NCT00251992.

Allograft entrapment after lung transplantation: a simple solution using a pleurocutaneous catheter.

BACKGROUND: Chronic pleural effusion following lung transplantation (LTx) is often responsible for respiratory insufficiency and can lead to lung entrapment. Decortication carries considerable morbidity, and extended use of tube thoracostomy is not practical. We have utilized an indwelling pleurocutaneous catheter in the setting of intractable post-transplant effusion and have reviewed our experience to determine whether this strategy: 1) facilitates resolution of effusion, and 2) adequately palliates lung entrapment. METHODS: Twelve PleurX (Denver Biomedical, Golden, CO, USA) catheters were placed in 9 LTx patients (6 unilateral, 3 bilateral) for refractory pleural effusions after standard tube thoracostomy drainage failed (12/12). Two-thirds of the patients (8/12) also had concomitant lung entrapment. RESULTS: There was no operative mortality. Median time from LTx to catheter placement was 79 days (range 21-769). Catheter use achieved the desired outcome in 11/12 placements. Catheters remained in place for a median of 86 days (range 35-190). Direct catheter-related complications included hemothorax (1) and empyema (1). CONCLUSION: Use of an indwelling pleurocutaneous catheter effectively achieves its intended goals of pleurodesis and management of entrapped lungs after LTx.

Accuracy of a new ultrafast rapid urease test to diagnose Helicobacter pylori infection in 1000 consecutive dyspeptic patients.

BACKGROUND: Rapid diagnostic tools for Helicobacter pylori are important in endoscopy. AIMS: To assess the accuracy of a new 5 min rapid urease test (UFT300, ABS Srl, Cernusco sul Naviglio, Milan, Italy) and to compare it with the 1 h Pyloritek (Serim Laboratories, Elkhart, IN, USA) and the 24 h CLO test (Kimberly-Clark Ballard Medical Products, Roswell, GA, USA). METHOD: Consecutive dyspeptic patients referred to our unit for endoscopy were prospectively studied. All patients underwent a (13)C-urea-breath test, histology and the UFT300 (ABS Srl; Cernusco sul Naviglio, Milan, Italy). In a sub-set of patients (n = 375), two additional RUTs were performed. Patients were deemed infected if both (13)C-UBT and histology were positive. RUTs were read at 1, 5, and 60 min. RESULTS: Of 1000 enrolled patients 45.3% were infected with H. pylori. The sensitivity of the UFT 300 was 90.3%, 94.5% and 96.2% at 1, 5 and 60 min respectively (specificity 100%). The Pyloritek and the UFT were comparable, but the CLO test was not reliable at 5 and 60 min. CONCLUSION: The UFT 300 test is comparable to the Pyloritek test, but the CLO test is significantly less sensitive at early time points. Reading test results at 1 min may increase false negative results, thereby decreasing sensitivity.

Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care.

BACKGROUND: Accurate diagnosis and effective management of gastro-oesophageal reflux disease (GERD) can be challenging for clinicians and other health care professionals. AIM: To develop a patient-centred, self-assessment questionnaire to assist health care professionals in the diagnosis and effective management of patients with GERD. METHODS: Questions from patient-reported GERD instruments, previously documented in terms of content validity and psychometric properties (RDQ, GSRS and GIS) and data on the diagnosis of GERD in primary and secondary care were used in the formal development of a diagnostic and management tool, the GerdQ, involving psychometric validation and piloting in patient focus groups. RESULTS: Analyses of data from over 300 primary care patients, moderated by patient input from qualitative interviews, were used to select specific items from the existing instruments to create a new six-item diagnostic and management tool (GerdQ). ROC analysis indicated a sensitivity for GerdQ of 65% and a specificity of 71% for the diagnosis of GERD, similar to that achieved by gastroenterologists. CONCLUSION: The GerdQ is a potentially useful tool for family practitioners and other health care professionals in diagnosing and managing GERD without initial specialist referral or endoscopy.

Cluster analysis of risk factor genetic polymorphisms in Alzheimer's disease.

Multiple genetic variants may contribute to the risk of developing Alzheimer's disease. We have analyzed polymorphisms in 9 genes to determine whether particular combinations would contribute to this risk. The genes were APOE, LDLr, CST3, CTSD, TNF, BACE1, MAPT, STH, eNOS, and TFCP2. Three risk groups for the disease were identified. Risk group I was younger, was heterozygous for the CST3 (GA), CTSD2936 (AG), TNF -308 (AG) genetic variants. Risk group II was older, was homozygous for the -427 APOE promoter polymorphism (TT), and heterozygous for the MAPT deletion and for the STH variant (QR). Group III had both the youngest and oldest subjects, were heterozygous for the -863 (AC) and -1031 (CT) TNF promoter polymorphisms. All three groups carried the APOE 4 allele and were heterozygous for both BACE1 polymorphisms. The control groups were carriers of the APOE 3 allele and were homozygous for the BACE1 genetic variants.