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.

Efficacy and tolerability of hydralazine, in conventional and slow-release preparations, during long-term treatment of primary hypertension.

In 23 patients with primary hypertension, the efficacy and tolerability of slow-release hydralazine administered once daily were compared with those of conventional hydralazine given two to four times a day. All patients were treated concomitantly with beta-blockers, diuretics, or both. Blood pressure control achieved with multiple doses of conventional hydralazine was maintained with slow-release hydralazine, with no discrepancy between once- and twice-daily administration, when the same daily dose of hydralazine was given. A differentiated method of assessing tolerability demonstrated no differences between the hydralazine formulations and dose regimens in the incidence of side effects. This finding indicates that larger single doses than are normally given with hydralazine can be given with slow-release hydralazine without increased risk of side effects.

Predictors of either rapid healing or refractory reflux oesophagitis during treatment with potent acid suppression.

BACKGROUND: Little is known regarding patient characteristics that influence the speed of reflux oesophagitis (RO) healing. AIM: To investigate patient characteristics that may influence RO healing rates. METHODS: A post hoc analysis of clinical trial data for potent acid suppression treatment of RO (esomeprazole or AZD0865) was conducted. Group A underwent endoscopy at baseline, week 2 and 4, and group B at baseline, week 4 and 8. Group A patients were sub-grouped as 'rapid' (healed at 2 weeks) or unhealed at 2 weeks. Group B patients were sub-grouped as 'slow' (healed at 8 weeks, not at 4 weeks) or 'refractory' (not healed at 8 weeks). Logistic regression analysis was performed only for comparisons within group A. RESULTS: At 2, 4 and 8 weeks, RO had healed in 68%, 65% and 61% of patients unhealed at previous endoscopy, respectively. Low-grade [vs. high-grade (C or D)] RO was the only independent predictor of rapid healing in group A after logistic regression analysis. Significantly more rapid healers had low grade RO (A or B) at baseline than patients with refractory RO (84% vs. 49%; P < 0.001), and significantly more refractory patients had frequent regurgitation at baseline than slow healers (80% vs. 63%; P = 0.039). CONCLUSIONS: Low- (vs. high-) grade RO determines the most rapid benefit from acid suppression. Roughly two-thirds of patients healed with each time increment of potent acid suppression therapy. This suggests that some unhealed patients may still heal with continued therapy and that truly refractory RO is rare. (ClinicalTrials.gov: NCT00206245).

Validation of the GerdQ questionnaire for the diagnosis of gastro-oesophageal reflux disease.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) remains a challenge as both invasive methods and symptom-based strategies have limitations. The symptom-based management of GERD in primary care may be further optimised with the use of a questionnaire. AIM: To assess the diagnostic validity of the GerdQ questionnaire in patients with symptoms suggestive of GERD. METHODS: Patients with symptoms suggestive of GERD without alarm features, underwent upper endoscopy, and if normal, pH-metry. Patients were followed for 4 weeks and GerdQ was completed blinded to the investigator at both visits. Reflux oesophagitis or pathological acid exposure was used as diagnostic references for GERD. The diagnostic accuracy for GERD on symptom response to proton pump inhibitor (PPI) was assessed. RESULTS: Among the 169 patients, a GerdQ cutoff ≥9 gave the best balance with regard to sensitivity, 66% (95% CI: 58-74), and specificity, 64% (95% CI: 41-83), for GERD. The high prevalence of reflux oesophagitis (81%) resulted in a high proportion of true positives, but at the same time a high proportion of false-negatives. Consequently, GerdQ had a high positive predictive value, 92% (95% CI: 86-97), but a low negative predictive value, 22% (95% CI: 13-34), for GERD. Symptom resolution on PPI therapy had high sensitivity, 76% (95% CI: 66-84), but low specificity, 33% (95% CI: 17-53), for GERD. CONCLUSIONS: GerdQ is a useful complementary tool for the diagnosis of gastro-oesophageal reflux disease in primary care. The implementation of GerdQ could reduce the need for upper endoscopy and improve resource utilisation. Symptom resolution on proton pump inhibitor did not predict gastro-oesophageal reflux disease.

Impact of persistent, frequent regurgitation on quality of life in heartburn responders treated with acid suppression: a multinational primary care study.

BACKGROUND: In gastro-oesophageal reflux disease (GERD), heartburn responds well to acid suppression, but regurgitation is a common cause of incomplete treatment response. AIM: To assess the prevalence and burden of persistent, frequent regurgitation in primary care patients with GERD treated with acid suppression. METHODS: We analysed observational data from 134 sites across six European countries in patients diagnosed with GERD. Within 3 months of the index visit, symptoms were assessed using the Reflux Disease Questionnaire, and their impact on sleep and work productivity with the Quality of Life in Reflux and Dyspepsia questionnaire and the Work Productivity and Activity Impairment Questionnaire, respectively. Patients provided information on concomitant over-the-counter (OTC) GERD medication use. RESULTS: Persistent, frequent (3-7 days/week) regurgitation was reported by 13.2% (153/1156) of GERD patients with no heartburn on acid suppression; the prevalence was very similar for patients with up to 2 days/week of ongoing mild heartburn. Among patients without heartburn, sleep disturbance of any type was reported by 50.7-60.1% with persistent, frequent regurgitation, compared with 38.1-51.1% and 14.4-19.2% of those with less frequent or no regurgitation respectively. Persistent, frequent regurgitation was associated with increased use of OTC medication and more hours of work missed, whether mild, infrequent heartburn was present or not. CONCLUSIONS: Frequent regurgitation, which persisted in 12-13% of patients with no or infrequent, mild heartburn on acid suppression, negatively affected sleep and work productivity, and increased use of OTC medication. Persistent, frequent regurgitation is problematic for primary care patients with GERD.

Partial symptom-response to proton pump inhibitors in patients with non-erosive reflux disease or reflux oesophagitis - a post hoc analysis of 5796 patients.

BACKGROUND: Although most patients with gastro-oesophageal reflux disease (GERD) benefit from proton pump inhibitor (PPI) therapy, some experience only partial symptom relief. AIM: To determine the prevalence of partial heartburn response to PPIs and its impact on health-related quality of life. METHODS: Four randomised, double-blind studies in adults with reflux disease compared esomeprazole 40 mg/day or 20 mg/day with omeprazole 20 mg/day, or esomeprazole 40 mg/day with pantoprazole 40 mg/day. Patients with heartburn on ≥4 days during the 1-week recall period at baseline were included. Partial response was defined as heartburn on ≥3 days during the last treatment week and reduced heartburn frequency after 4 weeks of treatment compared with baseline. RESULTS: The analysis included 2645 patients with non-erosive reflux disease (mean age: 48.8 years; 54.4% women) and 3151 patients with reflux oesophagitis (mean age: 50.6 years; 37.1% women). At baseline, most patients reported heartburn on 5-7 days (non-erosive reflux disease: 82.2%; reflux oesophagitis: 86.8%). Partial heartburn response occurred in 19.9% of patients with non-erosive reflux disease and 14.0% with reflux oesophagitis. Defining partial response as heartburn on ≥2 days increased these rates to 26.2% and 19.3%, respectively; defining partial response as heartburn of moderate or severe intensity on ≥3 days decreased these rates to 6.4% and 5.3%, respectively. Nonresponse to PPIs was rare (non-erosive reflux disease: 2.4%; reflux oesophagitis: 1.4%). CONCLUSION: Using our conservative definition, partial heartburn response to proton pump inhibitor therapy occurred in 14-20% of gastro-oesophageal reflux disease patients, more commonly in non-erosive reflux disease than in reflux oesophagitis.

Dyspepsia and irritable bowel syndrome in China: a population-based endoscopy study of prevalence and impact.

BACKGROUND: Dyspepsia and irritable bowel syndrome (IBS) are common in Western populations. AIM: To determine the epidemiology of dyspepsia and IBS in China. METHODS: A representative sample of 18 000 adults from five regions of China were asked to complete the modified Rome II questionnaire; 20% were asked to complete the 36-item Short Form Health Survey (SF-36). Participants from Shanghai were invited to provide blood samples and undergo oesophago-gastroduodenoscopy. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using a multivariate logistic regression model. RESULTS: The survey was completed by 16 091 individuals (response rate: 89.4%). Overall, 387 participants (2.4%) had dyspepsia and 735 (4.6%) had IBS. All SF-36 dimension scores were at least five points lower in individuals with than without dyspepsia or IBS (P < or = 0.001). In Shanghai, 1030 (32.7%) of the 3153 respondents agreed to endoscopy; neither dyspepsia nor IBS was found to be associated with reflux oesophagitis, peptic ulcer disease or Helicobacter pylori infection. CONCLUSIONS: Prevalence estimates for dyspepsia and IBS in China are lower than in Western populations. In China, dyspepsia or IBS symptoms are generally not associated with underlying organic disease.

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.

Evaluation of once daily hydralazine in inadequately controlled hypertension.

Despite the short plasma half-life of hydralazine, once daily Slow Apresoline has been shown to maintain blood pressure control in well controlled hypertension. In the present investigation of 118 inadequately controlled hypertensives, we have shown that 50-150 mg Slow Apresoline once daily induces a significant blood pressure reduction and is well tolerated. Normotension, i.e. supine diastolic blood pressure less than 95 mmHg, was reached in 53% of the patients. Normotension or a supine diastolic blood pressure reduction of greater than or equal to 10 mmHg was achieved in 72% of the patients, the hydralazine responders. Sixteen patients discontinued treatment due to symptoms probably related to hydralazine. Acetylator phenotyping showed that slow acetylators predominated in the group of patients discontinuing hydralazine due to side-effects. In contrast, 90% of the phenotyped non-responders were rapid acetylators, which suggests a suboptimal use of hydralazine in some rapid acetylators.

Pharmacokinetics of oral hydralazine in chronic heart failure.

The influence of various disease states, other than hypertension, on the pharmacokinetic behaviour of hydralazine is not completely known. In the present study the pharmacokinetics of oral hydralazine has been evaluated in 7 patients with severe, chronic heart failure, using 8 compensated hypertensives as controls. The pharmacokinetics was evaluated by measuring the plasma concentrations of hydralazine ("apparent" and "real" hydralazine) and hydralazine pyruvate hydrazone, and by assessing acetylator phenotype after a small dose of dapsone. The AUC (area under the plasma concentration curve) following a single, oral 50 mg dose was significantly larger in patients with chronic heart failure NYHA Class III-IV than in patients with essential hypertension without cardiac decompensation. A decreased rate of hepatic elimination of hydralazine is suggested as a major contributory factor to this finding.

Clinical efficacy of hydralazine in chronic heart failure: one-year double-blind placebo-controlled study.

In a placebo-controlled trial 62 patients with chronic congestive heart failure (CHF) (New York Heart Association class III) had hydralazine (149 +/- 11 mg daily) or placebo added to conventional therapy. During 12 months' follow-up 27 patients dropped out, 15 of 32 in the hydralazine group and 12 of 30 among the control subjects. The 1-year mortality rate was 28% in the hydralazine group compared to 27% in the control group. Symptomatic improvement was noted in both groups; however, it was gradually more pronounced in the actively treated group with a statistically significant difference between the two groups at month 12 (p less than 0.05). The hydralazine patients increased their exercise capacity 25%, from 53 +/- 3 watts at month 0 to 67 +/- 4 watts at month 12 (p less than 0.01). No improvement in exercise capacity took place in the placebo group. A significant improvement in chest x-ray examination was found with hydralazine (p less than 0.01) in contrast to a significant deterioration among the control subjects (p less than 0.05). Thus, we conclude that hydralazine used in chronic CHF has beneficial clinical effects during long-term treatment.