Background/Aims: The Chicago Classification for diagnosis of esophageal motility disorders by high-resolution manometry (HRM) is based on single water swallows (SWS).Emerging data suggest that a "Rapid Drink Challenge" (RDC) increases sensitivity for motility disorders. This study establishes normal values and diagnostic thresholds for RDC in clinical practice. Methods Results:Normal values were determined in healthy (n=95; age 37.8 ± 12) and patient controls (n=44; age 46.4 ± 15). Development and validation sets included 178 (54 ± 17 years) and 226 (53 ± 16 years) patients, respectively. Integrated relaxation pressure during RDC was higher for SWS than RDC in all groups (overall P<.001), except achalasia. Rapid Drink Challenge suppressed contractility, except in achalasia type III, spasm, and hypercontractile motility disorders (P<.001). An effective aftercontraction was present more often in health than disease (P<.001). Optimal diagnostic thresholds identified in the development set (IRP-RDC ≥12 mmHg achalasia, IRP-RDC ≥ 8mmHg "all cause" EGJ dysfunction), were confirmed in the validation set (both, sensitivity ~85%, specificity >95%). Conclusions:Rapid Drink Challenge contributes clinically relevant information to routine HRM studies, especially in patients with EGJ dysfunction. K E Y W O R D Sdiagnostic classification, esophageal motility disorders, high-resolution manometry, multiple water swallows, prospective cohort study, Rapid Drink Challenge

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Motilin-induced gastric phase III is a hunger signal from GIT in man.

MATERIALS AND METHODS Identification of relevant studiesTo identify relevant studies, both computerised (Medline) and manual searches were performed, using the cited references of the retrieved articles. MeSH and freetext terms for FD therapies were combined with the terms dyspepsia, clinical trials, symptom assessment, questionnaires, patient reported measures and randomised for searches conducted for the time period between January 1979 and December 2008. FD therapeutic trials were retrieved and studied, with emphasis on the method used for evaluating outcome measures. Article reference lists were examined for relevant articles. Analysis of both full articles and abstracts was conducted, with particular emphasis on outcome measures. The literature search was performed independently by two of the authors, and their retrievals were merged. Inclusion criteriaThe following criteria were used to select trials for analysis: (i) randomised double blind controlled trials (RCT), (ii) parallel or single cross-over trial designs, (iii) adult patients with FD, (iv) baseline gastroscopy to exclude structural pathology; (v) comparison of therapy vs. active or placebo control; (vi) clear description of the method of assessing outcome measures for FD symptoms and (vii) articles in English. Outcome measuresOne of the main difficulties encountered with therapeutic trials in FGIDs, and FD in particular where efficacy has not been established for any treatment, is the lack of objectively measurable outcome measures. [11][12][13][14] In FD, symptom patterns do not correlate well with putative pathophysiological mechanisms such as gastric accommodation, sensitivity to distension and gastric emptying rates. 15 In the absence of quantifiable surrogate markers for symptom improvement, evaluation of treatment response has to rely on patient's reporting of symptom intensities. Several types of outcome measures have been used in FD clinical trials. These can be broadly classified into global outcomes, generic instruments and disease specific instruments.16 Global outcomes are measured either by a dichotomous binary type response (e.g. yes ⁄ no to symptom improvement) or a scoring method which can either be a Likert scale (categorical) or a visual analogue scale (VAS). Likert scales allow easier interpretation for the physician compared with the VAS, with 5-point or 7-point scales providing greater sensitivity than 4-point scales. 17 The VAS and 7-point Likert scales exhibit comparable responsiveness, although the ease of administration and interpretation of the 7-point scale recommend its use in clinical trials. 18 The Likert scale is often incorporated into global scales, such as the overall treatment effect (OTE), 19 generic instruments and disease specific R Re ev vi ie ew w: : d dy ys sp pe ep ps si ia a e en nd dp po oi in nt ts s f fo or r u us se e i in n d dr ru ug g t th he er ra ap py y t tr ri ia al ls s

Summary Background Standard high‐resolution manometry (HRM) protocols are based on 10 single water swallows acquired in the supine position. Aims To assess the impact of position, rapid drink challenge and solid test meal on the diagnosis of oesophageal motility disorders. Methods Seventy‐two healthy volunteers (20‐76 years) and 366 consecutive patients (18‐90 years) completed HRM with 10 single water swallows in the supine and upright positions. Rapid drink challenge was performed twice, before and after the solid test meal. Diagnosis based on single water swallows in the supine position (Chicago Classification v3.0) was compared with results in the upright position and with provocative tests. Results Overall, diagnostic agreement in the supine and upright positions was present in 296/438 (67.6%) subjects. This increased to 90.0% when ineffective oesophageal motility was considered with normal motility. Integrated relaxation pressure was 4 mm Hg higher in the supine position. There was a higher prevalence of inconsistent, likely false positive, diagnoses of outlet obstruction in the supine compared to the upright position (16/20 vs 1/4 patients, P = 0.0007). Similarly, the difference in concordance for the diagnosis of oesophago‐gastric junction obstruction or achalasia between single water swallows in the supine and upright positions with solid test meal was significant (12/29 (41.4%) vs 12/14 (85.7%), P = 0.0087). Conclusion Diagnostic agreement for oesophageal motility disorders based on single water swallows in the upright and supine positions was moderate, with frequent discordant findings for ineffective motility and outlet obstruction. HRM studies can be performed in either position, using appropriate reference values. Rapid drink challenge or solid test meal can resolve diagnostic discrepancies.

The management of patients with refractory GERD (rGERD) is a major clinical challenge for gastroenterologists. In up to 30% of patients with typical GERD symptoms (heartburn and/or regurgitation), acid-suppressive therapy does not provide clinical benefit. In this Review, we discuss the current management algorithm for GERD and the features and management of patients who do not respond to treatment (such as those individuals with an incorrect diagnosis of GERD, inadequate PPI intake, persisting acid reflux and persisting weakly acidic reflux). Symptom response to existing surgical techniques, novel antireflux procedures, and the value of add-on medical therapies (including prokinetics and reflux inhibitors) for rGERD symptoms are discussed. Pharmaceutical agents targeting oesophageal sensitivity, a condition that can contribute to symptom generation in rGERD, are also discussed. Finally, on the basis of available published data and our expert opinion, we present an outline of a current, usable algorithm for management of patients with rGERD that considers the timing and diagnostic use of pH-impedance monitoring on or off PPI, additional diagnostic tests, the clinical use of baclofen and the use of add-on neuromodulators (tricyclic agents and selective serotonin reuptake inhibitors)

NBI increased the detection rate of IM compared with HD-WLE.