- Email: [email protected]
A validated symptom questionnaire (Chinese-GERDQ) for the diagnosis of gastroesophageal reflux disease in Chinese population
T1648
symptomatic only 20 (53%) had pathological reflux. Mean (sd)total time pH < 4 was no dill
Lifestyle and Dietary Modification as the Primary Therapy for Laryngopharyngeal Reflux John M. Wo, Steve Goudy, Welby Winstead, Zarina Mohiuddin Proton pump inhibitors are frequently used as first-line therapy m laryngopharymgealreflux (LPR). Benefit of non-pharmacologic therapy may be overlooked. Aim: To determine the efficacy of lifestyle and dietary- modification as primary therapy in newly diagnosed LPR+ Methods: Informed consents were obtained from subjects with suspected LPR. Subjects previously treated for LPR or GERD were excluded. Data w'ere obtained on alcohol use, smoking, second-hand smoke, caffeine and chocolate consumption, eating late at night and voice abuse behaviors. Esophageal manometry and pH test were obtained. A positive pH test was required for inclusion. Laryngeal exam score was obtained with larymgoscopy+ Each subject received counseling from physician and study coordinator and instructed to follow specific behavioral and dietary modifications for 6 wks. Follow-up phone-calls were made to maximize compliance Weekly diary was kept with visual analog scales (0-20) for globus, cough, sore throat, hoarseness, throat clearing and throat mucous. Total laryngeal symptom score (0-120) was defined as sum of symptoms above. Acid suppressing medications were prohibited. Laryngoscopy was repeated at 6-wk, Results: 17 subjects (6M/llF, mean age 53 yrs) were enrolled and completed study. Heartburn was present in only 35% of subjects Mean (SE) % time pH<4 in the hypopharynx, prommal and distal esophagus were 1.1% (0.6), 49% (1.4) and 10.7% (20), respectively. Weekly mean total laryngeal symptom scores are shown in figure. 6 subjects (35%) had >50% ~'mptom improvement, and 6 subjects (35%) had improvement but < 5 0 % No changes w'ere noted tbr gldbus and sore throat There were no improvement in laryngeal exam scores. Conclusion: With proper lifestyle and dietary" counseling, man)," LPR patients can obtain symptomatic imprm'ement without pharmacotherapy
Conclumons The symptomatic response of patients to either PPIs or antireflux surgery- is a poor indicator of successful treatment in terms of reduced lower oesophageal acid exposure. Cliniciarts should be aware that in those patients symptomatically improved on PPIs over 40% of patients may still have pathological levels of acid reflux Conversely, following antirefiux surgery the majority of patients who complain of residual reflux symptoms will have no evidence of significant reflux on pH merry.
T1646
Evaluation of Syruptoms Is an Unreliable Predictor of Relapse of Erosive Esophagitis in Palients Receiving Maintenance PPI Therapy David A. JoMsola,Karsten Lauritsen Ola Junghard, Douglas Levine Background: Following healing of erosive esophagins (EE), maintenance treatment with a proton pump inhibitor (PPI) is generally required to prevent relapse. In clinical trials, esomeprazole 20 mg once daily has been shown to be more efti:ctive than lansoprazole 15 mg fur the maintenance of bealing and rebel of symptoms in patients with EE. Among patients receiving n:aintenance therapy, recurrence of heartburn may signal a possible need for EGD GmverseIy, asymptomatic relapse represents a difficult clinical situation that has been documented in up to 9% of patients with recurrent EE. (Aliment Pharrr~acol Dter [997;11:473+82) The aim of this retrospective analysis was to determine the reliability of heartburn as a clinical marker of relapse of EE and to identify ~ the rote of asymptomatic rdapse in patmnts receiving maintenance PPI therapy. Methods: Foflomng 4 or 8 weeks of therapy with esomeprazole 40 mg once daily*for healing of EE, 1224 patients were randomized to nmintenance treatment with either esomepmzole 20 mg or lansoprazole 15 mg once daily lur up to 6 months in a muIticenter clinical trial Durmg maintenance therapy, all patients underwent routine EGD at months 3 and 6 EGD was ago performed tbr patients reporting moderate or severe heartburn and/or acid regurgitation persisting > 3 conseo.ltive days. Only patients with complete data for heartburn symptoms as recorded by the investigator and tired EGD were included in this analysis (n = 520 tor esomeprazole, n = 480 for lansoprazole) Resuhs: Recurrent heartburn was experienced by 9.7% of patients overall (8.3% with esomeprazole and 113% ot patients with lansoprazole) after up to 6 months of treatment Among patients with recurrent heartburn, relapse of EE was documented by EGD in 474% of patients (372% w~th esomeprazole and 556% witli lansoprazola) Asymptomatic relapse occurred in 67% of patients without heartburn. Conclusions: The presence of heartburn is not a reliable predictor of relapse of EE in patients receiving maintenance PPI therapy More" than one half of patients with recurrem heartburn had no erosions by EGD Relapse ot erosive esophagitis occurred in almost 7% of patients despite the absence of hearttmrn Treatment with (he most eft~'ctive acid suppressive therapy prmAdes the highest probability that l~mission wiI/be maintained
80 compared to week 0
0
0')
E C3
60
E m
40
r r
r
T1647
m m
S)~nptom Response at One Week to Predict Outcome at Four Weeks with Esomeprazole (E) in Heartburn+Dominant Uninvnstigated Dyspepsia (HBDUD) Patients: The Confirmatory Acid Suppression Test (CAST) Study David Armstrong, Sander J Vau 7~anten, Alan Barkun, Lisa Tanser, Bijan Chakraboty, Krista Nevin
F-
0
0
Backgrmmd: The diaguosis ot gastroesophageal rdlux disease in primary care practice (PCP) is hampered by the lack ot a validated non-invasive test to confirm acid+related heartburn (ARH) Aims: To compare the sensitivW and specificity' of 1+week acid suppression tests for diagnosing ARH using E 40 mg bid or E 40 mg od by ret~'rence to symptom response alter 3 flarther weeks of E 40 mg od Methods: 388 subjects (215M: 173F; no ASA or NSA1Ds; no alm'm symptoms) with tIBDUD symptoms (>1 month) were recruited from PCP and randmmzed (double-blind) to receive E 40 mg od (N = 194) or E 40 mg bid (N = 194) tbr I week; all then received E 40 mg od for 3 weeks. Symptom response (1 and 4 wks) was ddined as a ~vduc ion of > 2 points on the Global Overall Synptoms (GOS) score U-point IJkert scale). Results: There were no sigmflcant differences between E 40 mg od and E 40 mg bid (Table) with respect to sensitivW (p = 0.70) or specificity (p = 1 0 0 ) Positive predictive values (PPV) were 961% and 988% am] negative predictive values (NIW) 28.3% and 475% (od and bid respectively) Both treatments were safe and well tolerated. Conclusions: The 1+week esomeprazole acid suppressiml test has a high PPV {br acid-related symptoms but a low NPV Despite high symptom response rates at 1 and 4 weeks, a l-week test may tail to identify" 21 2 4 % of patients +*~ith true ARH due to the time-related increase in response.
0
+w+_~
4w++
69,1% 70,6%
82.5% 84,5%
AGA
Abstracts
763% (68+9%,82,6%) 78,7% (71,6%, 84,7%}
2
3
4
5
6
T1649 A validated symptom questionnaire (Chinese-GERDQ) for the diagnosis of gastroesophageal reflux disease in Chinese population Wai-Man Wong, Shiu+Kum Lam, Kwok-Fai Lam, Wai-Mo Hui, Kam-Chuen 1.at, Wayne kIc Hu, Cindy Lk Lam, Nma Yh Wong, Harry Hx Xia, Annie On Chan, Benjamin Cy Wong Background and Aims: To develop a validated gastmesophageal disease (GERD) synrptom questionnaire for Chinese population. Methods: 95 Chinese patients with GERD and 101 healthy Chinese controls were presented with a 20+item GERD questionnaire in Chinese language (Chinese+GERDQ) based on previous published validated western questionnaire. Quality of life in GERD patients was assessed by SF-36. Standard dose of proton pump inhibitors (PP1) for 4 weeks was prescribed to 35 patients with newly- diagnosed GERD. The Chinese-GERDQ was performed before, 4 weeks and 8 weeks after treatment. Concept, content, construct, discrimmant validity and reliability" of the questionnaire were assessed Results: All items were considered comprehensible by more than 90% of subjects. Relevance of individual symptoms to GERD ranged from 60% to 100%. Seven items were selected by logistic regression to account tot most of the differences between control and GERD patients Test-retest reproducibility and internal consistency were good with the intradass correlation coefficient of 0.75 and Cmnbach's alpha coefficient of 0.9. A cut-off score of equal or greater than 12 was determined to discriminate between controls and GERD patients with an AUC of 0.91, a sensitivity, of 80% and a specificity of 83% by ROC analysis. The Chinese-GERDQ correlated negatively with 5 domains of the 8F+36 and &scrimmated between GERD patients
Es'dmate of ~fmptom response, sensitivity and specificity od bid
1
75+0%(50~9%,91+3%)
78,2% (5Z8%, 91,8%)
A-540
who reported a subjective symptomatic improvement during PPI treatment and symptoms deterioration dining withdrawal of PPI treatment. Conclusions: Chinese-GERDQ was easytomndersrand, internally consistent and reproducible. It predicted global symptom change, and the symptom seventy scores correlated negatively with quality of life. It could be used m epidemiologieal studies to assess the t~ceqnancyand severity of GERD in patient populations and in interventional studies of GERD.
Seven items selected by I o ~
Table 1. Ratios of geometric means with 90% Cls for Cm~, AUCx, and h~ (n = 32),
Eso combination/Ezo alone (n.--'al)
N cond)Jnation/Nalone (n:30),, Cl=confldence interval
regression and their relative weighting
Symptom assessed Freqeeoc~ of heEe~rn Severity of hudbum Frequency of ~ g of acidity in stomach Severity of feeling of acidity in stomach Frequency of acid regurgitation Sevet~ of acid r e g u ~ o n Frequency of use of antacids
Weighting by pdncipal,,componentmethod 0.3o9 0.290 0,390 0.372 0.441 0.403 0.416
Results of 24 h pH-meUy in 42 obese patients Nbof reflox/24h Nb of reflux > 5 mln Longer reflux (rain) % of time with pl.l~4
C ~ ratio (90% Cl) Eso r
(.,,~)
.
.
.
.
alone
R comblnati~lR alone (n=30) Cl=conf~ence interval
.
.
.
AUCTra6o (90% c~) ....
N~onrm~ (n = 17)
N o m J { n = 25)
78,3 +/- 27.9 6.3 ,q- 2.2 18,2 +t- 13.7 8.8-4- 3.5
32.5 .4-11.6 1.1-4-1.1 4,7 +/- 1,8 Z3.4-1.1
T1653
Table L Ratios of geometric means with 90% CIs for C.~, AUCT, and h~ (n = 32) .
0.96 (0.93-0.98)..
Obesity is considered as a predisposing factor to gastroesophageal reflux disease (GERD) but the characteristics of GERD in patients with morbid obesity remains poorly studied. Moreover, in patients with morbid obesity- selected for bariatric surgeD,, symptomatic GERD might influence the surgical technique i.e. ring gastroplasty or gastric by-pass. Aims: to determine prospectively in obese patients selected for bariatric surgeD' the prevalence of GERD and to study the relationships between obesity, and GERD. Methods: every obese patients (BM1 > 40 kg/m2 or > 35 kg/m2 in association with comorbidity) selected for bariatric surgery were prospectively studied with a careful evaluation of GERD symptoms recorded by a standardized questionnaire, upper GI endoscopy and 24 h pH-metry, Results (mean +A SD): 42 patients (38 women) have been included. Mean age was 37.5 +A 11.6 years, and BMI was 40.4 +A 9.9 kg/m2. Heartburn, regurgitations and epigastric pain were present in 29 (69%), 21 (50%) and 15 (36%) patients, respectively. Considering extra digestive symptoms, 9 (21%) patients had chronic pharyngitis and 11 (26%) were asthmatic. Endoscopy evidenced a hiatal hernia in 21 (60%) patients and esophagitis (grade 1 to 3) in 5 (14%). The pH-metry (De Mester score) was pathologic in 17 patients (40%) (table). 17 patients had more than 50 reflUx episodes by 24 h, 16 had GERD symptoms at least 3 times a week. There was a significant relationship between the number of reflux > 5 rain and BMI (r = 0.373, p < 0.05). However no significant relationship between BMI and the total number of reflux or the % of time with pH < 4 have been evidenced, Conclusion: GERD is frequent in patients with morbid obesity requiring bariatric surgeD,. In obese patients with reflux the main pathophysiologic mechanism could be abnormal oesophageal clearance. Testing for GERD could be helpful before bariatric surgery as a ring gastroplasty could favour the apparition of GERD or increase the intensity of pre-existing GERD.
Introduction: Cox-2 selective non-steroidal anti-inflammatories (NSAIDs), such as rofecoxib, are increasingly being used for treatment of arthritis, particularly in patients at risk for developing NSAID-associated ulcers. The degree of gasmc damage caused by NSAIDs is highly dependent on intragastric pH, Esomeprazole, the s-isomer of omeprazole, provides more time with intragasmc pH>4 than other proton pump inhibitors and is expected to decrease the risk tbr gastric and duodenal ukeratinn in Cox-2 selective NSAID users. The potential for drng~drug interactions between esomeprazole and rofecoxib was investigated. Methods: In an open randomized, three-way cross-over study, 32 healthy subjects (15 males and 17 females) with a mean age of 26),ears and a mean weight of 69 kg received esomeprazole (Eso) 40 mg once daily (qd), rofecoxib (R) 12.5 mg qd, or Eso+R in combination for 7 days. The three study periods were separated by a washout period of two weeks. Blood samples tbr determination of Eso and R were collected 24 bouts post-dose on day' 7 and were analysed using normal-phase liquid chromatography" with UV-detection. Pharmacokinetm parameters of Esa9and R were estimated by non-compartmental analysis and were calculated using analysis of variance (ANOVA), Results: The pharntacokinetie parameters following the combination of esomeprazde and rofecoxib were similar to those following monotherapy except for a slight increase in Cm~, Of mfecoxib during combination therapy (Table 1). The 90% confidence intervals of the geometric means Show equivalence within the range of 0 8 to 1.25. There was no evidence of any increase of adverse events when the two drugs were combined. In general, esomeprazole was well tolerated both alone and in combination with rofecoxib. Conclusion: No drug-drug interactions between esomeprazole and rofecoxib were observed. Thus, rotecoxib can be administered together with esomeprazole witbout dosage alteration.
.
..0.98/0.95-1.01 )
Prevalence of Gastro Esophageal Reflux Disease in Patients with Morbid Obesity Selected for Bariatric Surgery, A Prospective Study in 42 Patients Mohamed Merrouche, Simon Msika, Florence Hamois, Jean Marc Sabate, Benoit Coffin
Lack of Drug-Drug Interaction between Esomeprazole and Rofecoxib in Healthy Subjects Mohammed Hassan-Alin, Catharina Nilssou-Pieschl, Jorgen Naesdal, Goran Langstrom, Marie Lundgren, Lars Nyman
.
1.00{0.97-1.04}
T1652
T1650
.
C~ztio pa)% CI) AUCTratio (90% el) t,= ratio (8~% , cl) 0.92 {0.86-0,99) 0.96 (0.90-1.02) 1.02 (0.99-1.06)
t,~ ratio (90%
A Comparison of Patient and Clinician Ratings of Heartburn Ola Junghard, lngela K. Wiklund
cD
1,05 (0.96-1.16)
1.05 (0.97-1.13)
0.99 (0.92-1.07)
1:,!4 (1.04.1.26}
1.15 (1,08-1,23)
1.06 {0,99-1,14}
Background: Traditionally, ratings of heartburn severity* and frequency have been based on the clinician assessment at least in clinical trials. To what extent this assessment adequately mirrors the patients reporting of synlptoms has not been extensible explored. Since regulatory agencies nowadays tend to focus more on the patient perspective more information is needed on how these measures compare. Aim: The aim of this study was to compare patient and clinician ratings of heartburn and other gastrointestinal (GI) symptoms. Patients and methods: 1850 endoscopy negative patients included in clinical trials (male gender 46%, mean age 48.3 years, SD= 14,0) with mild to severe heartburn were included in this analysis. The patient reported data were collected using a standard symptom rating scale, the Gastrointestinal Symptom Rating Scale (GSRS), while the clinician reported symptoms were recorded in Case Report Forms (CRFs). Results: At baseline the agreement between patient and clinician ratings (heartburn: r=0.42, acid regurgitation r=0.51 and abdominal pain r=0.36) was moderate while after 2 weeks of treatment ,a4th Proton Pump Inhibitors (PPls) the concordance between patient and clinician ratings had increased (heartburn: r = 0.68, acid regurgitation r=0.61 and abdominal pain r=0.50). At baseline the patient ratings indicated that botbersomeness of heartburn, acid regurgitation and upper abdominal pain was perceived as being the same or slightly' worse compared to the clinician ratings of symptom severity. Effect sizes were higher when assessed by" the patient for acid regurgitation (1.12 vs. 0.77) and upper abdominal pain (0.76 vs. 0.54) while the effect size for heartburn was comparable (1.92 vs. 1.82). Conclusions: Patient ratings of treatment induced relief of acid regurgitation and upper abdominal pain were more responsive to change than the clinician rating. With regard to relief of heartburn patient and clinician rating were equally" responsive. At baseline patient ratings are similar to clinicians ratings of the impact of symptoms.
T1651
Lack of Drug-Drug Interaction between Esomeprazole and Naproxen in Healthy Subjects Mohammed Hassan*Min, Catharina Nilsson-Pieschl, Jorgen Naesdal, Goran Langstrom, Marie Lundgren, Lars Nyman Introduction: The degree of gastric damage caused by non-sternidal antMnflammatories (NSA1Ds) is highly" dependent on intragastrie pH. Esomeprazole, the s-isomer of omeprazole, provides more rune with intragastric p H > 4 than other proton pump inhibitors and is expected to be even more eftective than these for the prevention of NSAID-associated ulcers. The potential fbr interaction between esomeprazole and naproxen was evaluated, as esomeprazole is expected to provide GI protection in NS?dD users at risk for developing ulcers. Napmxen was chosen as a widely used representative of non-selective NSAIDs. Method: In an open randomized, three-way cross-over study, 32 healthy subjects (13 males and 19 tenkales) with a mean age of 24 years and mean weight of 69 kg received esomeprazole (E~) 40 mg once daily, napmxen (N) 250 mg twice daily or Eso+N in combinatinn for 7 day's. The three study periods were separated by a washout period of two weeks. Blood samples for determination of Eso and N were collected 24 hours post-dose on day 7 and were analysed using normal-phase liquid chromatography with UV-detectinn. Pharmacokinetic parameters of Eso and N were estimated by non-compartmental analysis and were calculated using analysis of waFLance(ANOVA). Results: No drng=dmg interactions were observed between esomeprazole and naproxen as shown by the 90% confidence intervals that are completely within the equivalence range of 0 8 to 125 (Table 1). There was no evidence of any increase of adverse events when the two drngs were combined. In general, esomeprazole was well tolerated both alone and in combination with naprnxen. Conclusion: No drug-drug interactions between esomeprazole and naproxen were observed. Thus, naproxen can be administered together with esomeprazole without dosage aheration,
T1654
Gastro-Esophageal Reflux Disease (GERD) in the Greek General Population George V. Papatheodoridis, Demetrios G. Karamanolis Background/Aims: The prevalence of GERD has been reported to range widely (5%-40%) among countries, but there are few well organised epidemiologic studies in unselected general population, In a random sample of the Greek general population, we studied a) the prevalence of GERD, b) the effect of GERD on patients' quality of life, and c) associations of GERD with patient characteristics. Methods: 700 individuals, older than 14 years, from the Athens greater area were included. The sample was selected by a 2-stage scheme based on official maps of the Hellenic Statistic Service. First, geographical areas were selected and then households were randomly sampled from the selected areas. Questionnaires with 70
A-541
AGA Abstracts
symptomatic only 20 (53%) had pathological reflux. Mean (sd)total time pH < 4 was no dill
Lifestyle and Dietary Modification as the Primary Therapy for Laryngopharyngeal Reflux John M. Wo, Steve Goudy, Welby Winstead, Zarina Mohiuddin Proton pump inhibitors are frequently used as first-line therapy m laryngopharymgealreflux (LPR). Benefit of non-pharmacologic therapy may be overlooked. Aim: To determine the efficacy of lifestyle and dietary- modification as primary therapy in newly diagnosed LPR+ Methods: Informed consents were obtained from subjects with suspected LPR. Subjects previously treated for LPR or GERD were excluded. Data w'ere obtained on alcohol use, smoking, second-hand smoke, caffeine and chocolate consumption, eating late at night and voice abuse behaviors. Esophageal manometry and pH test were obtained. A positive pH test was required for inclusion. Laryngeal exam score was obtained with larymgoscopy+ Each subject received counseling from physician and study coordinator and instructed to follow specific behavioral and dietary modifications for 6 wks. Follow-up phone-calls were made to maximize compliance Weekly diary was kept with visual analog scales (0-20) for globus, cough, sore throat, hoarseness, throat clearing and throat mucous. Total laryngeal symptom score (0-120) was defined as sum of symptoms above. Acid suppressing medications were prohibited. Laryngoscopy was repeated at 6-wk, Results: 17 subjects (6M/llF, mean age 53 yrs) were enrolled and completed study. Heartburn was present in only 35% of subjects Mean (SE) % time pH<4 in the hypopharynx, prommal and distal esophagus were 1.1% (0.6), 49% (1.4) and 10.7% (20), respectively. Weekly mean total laryngeal symptom scores are shown in figure. 6 subjects (35%) had >50% ~'mptom improvement, and 6 subjects (35%) had improvement but < 5 0 % No changes w'ere noted tbr gldbus and sore throat There were no improvement in laryngeal exam scores. Conclusion: With proper lifestyle and dietary" counseling, man)," LPR patients can obtain symptomatic imprm'ement without pharmacotherapy
Conclumons The symptomatic response of patients to either PPIs or antireflux surgery- is a poor indicator of successful treatment in terms of reduced lower oesophageal acid exposure. Cliniciarts should be aware that in those patients symptomatically improved on PPIs over 40% of patients may still have pathological levels of acid reflux Conversely, following antirefiux surgery the majority of patients who complain of residual reflux symptoms will have no evidence of significant reflux on pH merry.
T1646
Evaluation of Syruptoms Is an Unreliable Predictor of Relapse of Erosive Esophagitis in Palients Receiving Maintenance PPI Therapy David A. JoMsola,Karsten Lauritsen Ola Junghard, Douglas Levine Background: Following healing of erosive esophagins (EE), maintenance treatment with a proton pump inhibitor (PPI) is generally required to prevent relapse. In clinical trials, esomeprazole 20 mg once daily has been shown to be more efti:ctive than lansoprazole 15 mg fur the maintenance of bealing and rebel of symptoms in patients with EE. Among patients receiving n:aintenance therapy, recurrence of heartburn may signal a possible need for EGD GmverseIy, asymptomatic relapse represents a difficult clinical situation that has been documented in up to 9% of patients with recurrent EE. (Aliment Pharrr~acol Dter [997;11:473+82) The aim of this retrospective analysis was to determine the reliability of heartburn as a clinical marker of relapse of EE and to identify ~ the rote of asymptomatic rdapse in patmnts receiving maintenance PPI therapy. Methods: Foflomng 4 or 8 weeks of therapy with esomeprazole 40 mg once daily*for healing of EE, 1224 patients were randomized to nmintenance treatment with either esomepmzole 20 mg or lansoprazole 15 mg once daily lur up to 6 months in a muIticenter clinical trial Durmg maintenance therapy, all patients underwent routine EGD at months 3 and 6 EGD was ago performed tbr patients reporting moderate or severe heartburn and/or acid regurgitation persisting > 3 conseo.ltive days. Only patients with complete data for heartburn symptoms as recorded by the investigator and tired EGD were included in this analysis (n = 520 tor esomeprazole, n = 480 for lansoprazole) Resuhs: Recurrent heartburn was experienced by 9.7% of patients overall (8.3% with esomeprazole and 113% ot patients with lansoprazole) after up to 6 months of treatment Among patients with recurrent heartburn, relapse of EE was documented by EGD in 474% of patients (372% w~th esomeprazole and 556% witli lansoprazola) Asymptomatic relapse occurred in 67% of patients without heartburn. Conclusions: The presence of heartburn is not a reliable predictor of relapse of EE in patients receiving maintenance PPI therapy More" than one half of patients with recurrem heartburn had no erosions by EGD Relapse ot erosive esophagitis occurred in almost 7% of patients despite the absence of hearttmrn Treatment with (he most eft~'ctive acid suppressive therapy prmAdes the highest probability that l~mission wiI/be maintained
80 compared to week 0
0
0')
E C3
60
E m
40
r r
r
T1647
m m
S)~nptom Response at One Week to Predict Outcome at Four Weeks with Esomeprazole (E) in Heartburn+Dominant Uninvnstigated Dyspepsia (HBDUD) Patients: The Confirmatory Acid Suppression Test (CAST) Study David Armstrong, Sander J Vau 7~anten, Alan Barkun, Lisa Tanser, Bijan Chakraboty, Krista Nevin
F-
0
0
Backgrmmd: The diaguosis ot gastroesophageal rdlux disease in primary care practice (PCP) is hampered by the lack ot a validated non-invasive test to confirm acid+related heartburn (ARH) Aims: To compare the sensitivW and specificity' of 1+week acid suppression tests for diagnosing ARH using E 40 mg bid or E 40 mg od by ret~'rence to symptom response alter 3 flarther weeks of E 40 mg od Methods: 388 subjects (215M: 173F; no ASA or NSA1Ds; no alm'm symptoms) with tIBDUD symptoms (>1 month) were recruited from PCP and randmmzed (double-blind) to receive E 40 mg od (N = 194) or E 40 mg bid (N = 194) tbr I week; all then received E 40 mg od for 3 weeks. Symptom response (1 and 4 wks) was ddined as a ~vduc ion of > 2 points on the Global Overall Synptoms (GOS) score U-point IJkert scale). Results: There were no sigmflcant differences between E 40 mg od and E 40 mg bid (Table) with respect to sensitivW (p = 0.70) or specificity (p = 1 0 0 ) Positive predictive values (PPV) were 961% and 988% am] negative predictive values (NIW) 28.3% and 475% (od and bid respectively) Both treatments were safe and well tolerated. Conclusions: The 1+week esomeprazole acid suppressiml test has a high PPV {br acid-related symptoms but a low NPV Despite high symptom response rates at 1 and 4 weeks, a l-week test may tail to identify" 21 2 4 % of patients +*~ith true ARH due to the time-related increase in response.
0
+w+_~
4w++
69,1% 70,6%
82.5% 84,5%
AGA
Abstracts
763% (68+9%,82,6%) 78,7% (71,6%, 84,7%}
2
3
4
5
6
T1649 A validated symptom questionnaire (Chinese-GERDQ) for the diagnosis of gastroesophageal reflux disease in Chinese population Wai-Man Wong, Shiu+Kum Lam, Kwok-Fai Lam, Wai-Mo Hui, Kam-Chuen 1.at, Wayne kIc Hu, Cindy Lk Lam, Nma Yh Wong, Harry Hx Xia, Annie On Chan, Benjamin Cy Wong Background and Aims: To develop a validated gastmesophageal disease (GERD) synrptom questionnaire for Chinese population. Methods: 95 Chinese patients with GERD and 101 healthy Chinese controls were presented with a 20+item GERD questionnaire in Chinese language (Chinese+GERDQ) based on previous published validated western questionnaire. Quality of life in GERD patients was assessed by SF-36. Standard dose of proton pump inhibitors (PP1) for 4 weeks was prescribed to 35 patients with newly- diagnosed GERD. The Chinese-GERDQ was performed before, 4 weeks and 8 weeks after treatment. Concept, content, construct, discrimmant validity and reliability" of the questionnaire were assessed Results: All items were considered comprehensible by more than 90% of subjects. Relevance of individual symptoms to GERD ranged from 60% to 100%. Seven items were selected by logistic regression to account tot most of the differences between control and GERD patients Test-retest reproducibility and internal consistency were good with the intradass correlation coefficient of 0.75 and Cmnbach's alpha coefficient of 0.9. A cut-off score of equal or greater than 12 was determined to discriminate between controls and GERD patients with an AUC of 0.91, a sensitivity, of 80% and a specificity of 83% by ROC analysis. The Chinese-GERDQ correlated negatively with 5 domains of the 8F+36 and &scrimmated between GERD patients
Es'dmate of ~fmptom response, sensitivity and specificity od bid
1
75+0%(50~9%,91+3%)
78,2% (5Z8%, 91,8%)
A-540
who reported a subjective symptomatic improvement during PPI treatment and symptoms deterioration dining withdrawal of PPI treatment. Conclusions: Chinese-GERDQ was easytomndersrand, internally consistent and reproducible. It predicted global symptom change, and the symptom seventy scores correlated negatively with quality of life. It could be used m epidemiologieal studies to assess the t~ceqnancyand severity of GERD in patient populations and in interventional studies of GERD.
Seven items selected by I o ~
Table 1. Ratios of geometric means with 90% Cls for Cm~, AUCx, and h~ (n = 32),
Eso combination/Ezo alone (n.--'al)
N cond)Jnation/Nalone (n:30),, Cl=confldence interval
regression and their relative weighting
Symptom assessed Freqeeoc~ of heEe~rn Severity of hudbum Frequency of ~ g of acidity in stomach Severity of feeling of acidity in stomach Frequency of acid regurgitation Sevet~ of acid r e g u ~ o n Frequency of use of antacids
Weighting by pdncipal,,componentmethod 0.3o9 0.290 0,390 0.372 0.441 0.403 0.416
Results of 24 h pH-meUy in 42 obese patients Nbof reflox/24h Nb of reflux > 5 mln Longer reflux (rain) % of time with pl.l~4
C ~ ratio (90% Cl) Eso r
(.,,~)
.
.
.
.
alone
R comblnati~lR alone (n=30) Cl=conf~ence interval
.
.
.
AUCTra6o (90% c~) ....
N~onrm~ (n = 17)
N o m J { n = 25)
78,3 +/- 27.9 6.3 ,q- 2.2 18,2 +t- 13.7 8.8-4- 3.5
32.5 .4-11.6 1.1-4-1.1 4,7 +/- 1,8 Z3.4-1.1
T1653
Table L Ratios of geometric means with 90% CIs for C.~, AUCT, and h~ (n = 32) .
0.96 (0.93-0.98)..
Obesity is considered as a predisposing factor to gastroesophageal reflux disease (GERD) but the characteristics of GERD in patients with morbid obesity remains poorly studied. Moreover, in patients with morbid obesity- selected for bariatric surgeD,, symptomatic GERD might influence the surgical technique i.e. ring gastroplasty or gastric by-pass. Aims: to determine prospectively in obese patients selected for bariatric surgeD' the prevalence of GERD and to study the relationships between obesity, and GERD. Methods: every obese patients (BM1 > 40 kg/m2 or > 35 kg/m2 in association with comorbidity) selected for bariatric surgery were prospectively studied with a careful evaluation of GERD symptoms recorded by a standardized questionnaire, upper GI endoscopy and 24 h pH-metry, Results (mean +A SD): 42 patients (38 women) have been included. Mean age was 37.5 +A 11.6 years, and BMI was 40.4 +A 9.9 kg/m2. Heartburn, regurgitations and epigastric pain were present in 29 (69%), 21 (50%) and 15 (36%) patients, respectively. Considering extra digestive symptoms, 9 (21%) patients had chronic pharyngitis and 11 (26%) were asthmatic. Endoscopy evidenced a hiatal hernia in 21 (60%) patients and esophagitis (grade 1 to 3) in 5 (14%). The pH-metry (De Mester score) was pathologic in 17 patients (40%) (table). 17 patients had more than 50 reflUx episodes by 24 h, 16 had GERD symptoms at least 3 times a week. There was a significant relationship between the number of reflux > 5 rain and BMI (r = 0.373, p < 0.05). However no significant relationship between BMI and the total number of reflux or the % of time with pH < 4 have been evidenced, Conclusion: GERD is frequent in patients with morbid obesity requiring bariatric surgeD,. In obese patients with reflux the main pathophysiologic mechanism could be abnormal oesophageal clearance. Testing for GERD could be helpful before bariatric surgery as a ring gastroplasty could favour the apparition of GERD or increase the intensity of pre-existing GERD.
Introduction: Cox-2 selective non-steroidal anti-inflammatories (NSAIDs), such as rofecoxib, are increasingly being used for treatment of arthritis, particularly in patients at risk for developing NSAID-associated ulcers. The degree of gasmc damage caused by NSAIDs is highly dependent on intragastric pH, Esomeprazole, the s-isomer of omeprazole, provides more time with intragasmc pH>4 than other proton pump inhibitors and is expected to decrease the risk tbr gastric and duodenal ukeratinn in Cox-2 selective NSAID users. The potential for drng~drug interactions between esomeprazole and rofecoxib was investigated. Methods: In an open randomized, three-way cross-over study, 32 healthy subjects (15 males and 17 females) with a mean age of 26),ears and a mean weight of 69 kg received esomeprazole (Eso) 40 mg once daily (qd), rofecoxib (R) 12.5 mg qd, or Eso+R in combination for 7 days. The three study periods were separated by a washout period of two weeks. Blood samples tbr determination of Eso and R were collected 24 bouts post-dose on day' 7 and were analysed using normal-phase liquid chromatography" with UV-detection. Pharmacokinetm parameters of Esa9and R were estimated by non-compartmental analysis and were calculated using analysis of variance (ANOVA), Results: The pharntacokinetie parameters following the combination of esomeprazde and rofecoxib were similar to those following monotherapy except for a slight increase in Cm~, Of mfecoxib during combination therapy (Table 1). The 90% confidence intervals of the geometric means Show equivalence within the range of 0 8 to 1.25. There was no evidence of any increase of adverse events when the two drugs were combined. In general, esomeprazole was well tolerated both alone and in combination with rofecoxib. Conclusion: No drug-drug interactions between esomeprazole and rofecoxib were observed. Thus, rotecoxib can be administered together with esomeprazole witbout dosage alteration.
.
..0.98/0.95-1.01 )
Prevalence of Gastro Esophageal Reflux Disease in Patients with Morbid Obesity Selected for Bariatric Surgery, A Prospective Study in 42 Patients Mohamed Merrouche, Simon Msika, Florence Hamois, Jean Marc Sabate, Benoit Coffin
Lack of Drug-Drug Interaction between Esomeprazole and Rofecoxib in Healthy Subjects Mohammed Hassan-Alin, Catharina Nilssou-Pieschl, Jorgen Naesdal, Goran Langstrom, Marie Lundgren, Lars Nyman
.
1.00{0.97-1.04}
T1652
T1650
.
C~ztio pa)% CI) AUCTratio (90% el) t,= ratio (8~% , cl) 0.92 {0.86-0,99) 0.96 (0.90-1.02) 1.02 (0.99-1.06)
t,~ ratio (90%
A Comparison of Patient and Clinician Ratings of Heartburn Ola Junghard, lngela K. Wiklund
cD
1,05 (0.96-1.16)
1.05 (0.97-1.13)
0.99 (0.92-1.07)
1:,!4 (1.04.1.26}
1.15 (1,08-1,23)
1.06 {0,99-1,14}
Background: Traditionally, ratings of heartburn severity* and frequency have been based on the clinician assessment at least in clinical trials. To what extent this assessment adequately mirrors the patients reporting of synlptoms has not been extensible explored. Since regulatory agencies nowadays tend to focus more on the patient perspective more information is needed on how these measures compare. Aim: The aim of this study was to compare patient and clinician ratings of heartburn and other gastrointestinal (GI) symptoms. Patients and methods: 1850 endoscopy negative patients included in clinical trials (male gender 46%, mean age 48.3 years, SD= 14,0) with mild to severe heartburn were included in this analysis. The patient reported data were collected using a standard symptom rating scale, the Gastrointestinal Symptom Rating Scale (GSRS), while the clinician reported symptoms were recorded in Case Report Forms (CRFs). Results: At baseline the agreement between patient and clinician ratings (heartburn: r=0.42, acid regurgitation r=0.51 and abdominal pain r=0.36) was moderate while after 2 weeks of treatment ,a4th Proton Pump Inhibitors (PPls) the concordance between patient and clinician ratings had increased (heartburn: r = 0.68, acid regurgitation r=0.61 and abdominal pain r=0.50). At baseline the patient ratings indicated that botbersomeness of heartburn, acid regurgitation and upper abdominal pain was perceived as being the same or slightly' worse compared to the clinician ratings of symptom severity. Effect sizes were higher when assessed by" the patient for acid regurgitation (1.12 vs. 0.77) and upper abdominal pain (0.76 vs. 0.54) while the effect size for heartburn was comparable (1.92 vs. 1.82). Conclusions: Patient ratings of treatment induced relief of acid regurgitation and upper abdominal pain were more responsive to change than the clinician rating. With regard to relief of heartburn patient and clinician rating were equally" responsive. At baseline patient ratings are similar to clinicians ratings of the impact of symptoms.
T1651
Lack of Drug-Drug Interaction between Esomeprazole and Naproxen in Healthy Subjects Mohammed Hassan*Min, Catharina Nilsson-Pieschl, Jorgen Naesdal, Goran Langstrom, Marie Lundgren, Lars Nyman Introduction: The degree of gastric damage caused by non-sternidal antMnflammatories (NSA1Ds) is highly" dependent on intragastrie pH. Esomeprazole, the s-isomer of omeprazole, provides more rune with intragastric p H > 4 than other proton pump inhibitors and is expected to be even more eftective than these for the prevention of NSAID-associated ulcers. The potential fbr interaction between esomeprazole and naproxen was evaluated, as esomeprazole is expected to provide GI protection in NS?dD users at risk for developing ulcers. Napmxen was chosen as a widely used representative of non-selective NSAIDs. Method: In an open randomized, three-way cross-over study, 32 healthy subjects (13 males and 19 tenkales) with a mean age of 24 years and mean weight of 69 kg received esomeprazole (E~) 40 mg once daily, napmxen (N) 250 mg twice daily or Eso+N in combinatinn for 7 day's. The three study periods were separated by a washout period of two weeks. Blood samples for determination of Eso and N were collected 24 hours post-dose on day 7 and were analysed using normal-phase liquid chromatography with UV-detectinn. Pharmacokinetic parameters of Eso and N were estimated by non-compartmental analysis and were calculated using analysis of waFLance(ANOVA). Results: No drng=dmg interactions were observed between esomeprazole and naproxen as shown by the 90% confidence intervals that are completely within the equivalence range of 0 8 to 125 (Table 1). There was no evidence of any increase of adverse events when the two drngs were combined. In general, esomeprazole was well tolerated both alone and in combination with naprnxen. Conclusion: No drug-drug interactions between esomeprazole and naproxen were observed. Thus, naproxen can be administered together with esomeprazole without dosage aheration,
T1654
Gastro-Esophageal Reflux Disease (GERD) in the Greek General Population George V. Papatheodoridis, Demetrios G. Karamanolis Background/Aims: The prevalence of GERD has been reported to range widely (5%-40%) among countries, but there are few well organised epidemiologic studies in unselected general population, In a random sample of the Greek general population, we studied a) the prevalence of GERD, b) the effect of GERD on patients' quality of life, and c) associations of GERD with patient characteristics. Methods: 700 individuals, older than 14 years, from the Athens greater area were included. The sample was selected by a 2-stage scheme based on official maps of the Hellenic Statistic Service. First, geographical areas were selected and then households were randomly sampled from the selected areas. Questionnaires with 70
A-541
AGA Abstracts