Gastroesophageal reflux disease is a diversity disease that affects life quality of people in the world. Due to the complicated pathogenesis and variations in clinical manifestations, there is still no true gold standard for GERD diagnosis, and it is still difficult to diagnose this disease in some patients. The proton pump inhibitor’s diagnostic test (the PPI test) is noninvasive, of low cost, tied to treatment, and widely accepted. Our aim is to evaluate the diagnostic significance of coapplying a rabeprazole test with the SF-36 for GERD in this study. Our study shows that the SF-36 in combination with the rabeprazole test can screen GERD patients and increase the sensitivity and specificity of GERD diagnosis through reference to the change in SF-36 score before and after the treatment (65 in the trial).
Excessive gastroesophageal reflux can cause damage to the esophageal, throat, and even tracheal mucosa. Patients with gastroesophageal reflux disease (GERD) present with symptoms of heartburn, sour regurgitation, vomiting, onset retrosternal pain, and dysphagia. Bodily pain may influence mental status and is negatively associated with the patients’ work, study, and social intercourse. GERD has become a critical digestive system disease that strongly influences the quality of life [
GERD diagnoses are primarily based on reflux symptoms, 24-hour esophageal pH monitoring, and endoscopy. However, these tests have limitations. NERD (nonerosive reflux disease) patients account for 60% to 70% of GERD patients [
The proton pump inhibitor’s diagnostic test (the PPI test) is noninvasive, of low cost, tied to treatment, and widely accepted [
The reflux questionnaire is convenient and economical within a certain range of sensitivity and specificity [
The 36-item short-form health survey (SF-36) is the most common method in the standardized measurement of the quality of life and has been widely used in a series of studies because of its excellent reliability, validity, sensitivity, and feasibility. Recently, the quality of life for GERD patients has been studied more and more [
In this study, we utilized a combination of the PPI test and the SF-36 to offer an important basis for GERD diagnosis, particularly for NERD patients. This approach increases the diagnostic efficiency and the cost-efficacy ratio of GERD diagnoses.
A total of 90 patients were enrolled from September 2008 to December 2009. The inclusion criteria were as follows: (1) the patient visited due to epigastric discomfort, including sour regurgitation, vomiting, heart burn, and retrosternal pain, and was suspected to have GERD; (2) the patient was male or female, aged 18 to 70 years; (3) the patient was educated at least as far as elementary school and could read and fill out the questionnaire independently; (4) the patient had not been treated with nonsteroidal antiinflammatory drugs, PPI, H2-receptor antagonists, anticholinergic agents, antibiotics, or prokinetics in the four weeks prior to visiting; (5) the patient provided written informed consent; (6) an RDQ score ≥ 6 was taken as a basic criterion.
Exclusion criteria were as follows: (1) the patient could not tolerate endoscopy or 24-hour esophageal pH monitoring; (2) the patient had other digestive tract diseases and systemic diseases that could induce digestive discomfort, such as diabetes mellitus, systemic sclerosis, or nervous system diseases; (3) the patient had a history of gastroesophageal surgeries, esophageal stenosis, digestive ulcers, and esophageal or gastric tumors; (4) the patient was pregnant, nursing, or suffered from severe cardiac, hepatic, or renal insufficiency.
All the enrolled patients filled out the SF-36 questionnaire under the direction of trained gastroenterologists. They received endoscopy and 24-hour esophageal pH monitoring. Patients with esophageal erosion in the endoscopy were graded according to the Los Angeles (LA) classification. Patients with a positive result on one of the two measures (endoscopy or 24-hour esophageal pH monitoring) were considered to have GERD; otherwise, they were classified as non-GERD.
Ninety patients were randomly and double-blindly divided into Group A (
All the agents were delivered one week before the treatment. The SF-36 and RDQ measurement scales were administered before therapy, one week after therapy, and two weeks after therapy.
The ninety included patients (mean age
Characteristics of three groups.
Age (years) | LESP (mmHg) | UESP (mmHg) | SI (%) | |
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A group |
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B group |
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C group |
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0.109 | 0.496 | 0.385 | 0.687 |
There were no significant differences among three groups in the pretreatment, one week and two weeks after treatment (
Comparisons of SF-36 scores before and one and two weeks after the treatment.
Before treatment | One week after treatment | Two weeks after treatment |
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A group |
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<0.00 |
B group |
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<0.00 |
C group |
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<0.00 |
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0.058 | 0.302 | 0.064 |
The differences were significant in improving SF-36 scores between GERD and non-GERD patients in Groups A and B (
Comparison of improving SF-36 scores between GERD and non-GERD patients after one-week and two-week therapy.
One week after therapy | Two weeks after therapy | |||||
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GERD | Non-GERD | GERD | Non-GERD | |||
A group |
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<0.00 |
B group |
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0.038 |
C group |
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0.028 |
There were significant differences in improvement rates for SF-36 scores between GERD and non-GERD patients in Group A (
Comparison of improving SF-36 rate between GERD and non-GERD patients after one-week and two-week therapy.
One week after therapy (%) | Two weeks after therapy (%) | |||||
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GERD | Non-GERD | GERD | Non-GERD | |||
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A group |
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0.006 |
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0.037 |
B group |
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>0.05 |
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>0.05 |
C group |
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>0.05 |
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>0.05 |
A receiver operating characteristic (ROC) curve was plotted on the basis of pretreatment SF-36 scores. The area under the ROC (Az) was 0.27, indicating poor diagnostic value. Therefore, it was not suitable for diagnosing GERD (Figure
ROC of SF-36 scores prior to treatment.
The scores decreased in group A (40 mg/day) and group B (20 mg/day). However, the differences in sensitivity, specificity, and coincident rate were not significant from the perspective of diagnostic efficacy (
Comparison of rabeprazole tests of different doses and treatment courses.
Administration duration | Dose | Sensitivity | Specificity | Coincident rate |
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One week | 20 mg | 85.7% | 44.5% | 73% |
40 mg | 88.4% | 63.4% | 81% | |
Two weeks | 20 mg | 90.4% | 33.3% | 80% |
40 mg | 92.3% | 50.0% | 83% |
Comparison of coincident rates of rabeprazole tests of different doses and treatment courses.
Dose | Treatment course | ||
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One week | Two weeks |
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20 mg | 73% | 80% | 0.688 |
40 mg | 81% | 83% | 0.774 |
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0.095 | 0.117 | — |
The 95% confidence intervals (CI) of Az after one- and two-week treatment overlapped, illustrating that the diagnostic value after one week and two weeks did not differ significantly (Figure
ROC of changes of SF-36 scores after one-week or two-week treatment.
Changes of Youden’s index in GERD patients.
The area above the ROC was 0.884 (95% CI, 0.778–0.991,
ROC curve for coapplying rabeprazole test and SF-36 in diagnosing GERD.
At
Youden’s index for coapplying rabeprazole test and SF-36 in diagnosing GERD.
Based on the above results, rabeprazole 10 mg b.i.d. was applied in the PPI test. An increment of 65 score units from pretreatment to posttreatment was taken as the standard for a GERD diagnosis. Thus, of 71 patients with GERD, 67 were diagnosed with GERD and 4 were excluded from GERD; the false negative rate was 5.6%. Of 19 non-GERD patients, 4 were diagnosed with GERD and 15 were excluded from GERD; the false positive rate was 21.1% (Table
Sensitivity and specificity of the rabeprazole test combined with SF-36 in diagnosing GERD when
Screening results | GERD | Non-GERD | Total | |||
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Number of patients | 95% CI (%) | Number of patients | 95% CI (%) | Number of patients | 95% CI (%) | |
+ | 67 | 94.4 (89.1–99.7) |
4 | 21.1 (2.7–39.4) |
71 | 94.3 (88.9–99.7) |
− | 4 | 5.6 (0.2–10.9) |
15 | 78.9 (60.5–97.2) |
19 | 67.8 (60.6–97.2) |
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Total | 71 | 100 | 19 | 100 | 90 | 91.1 (85.2–96.9) |
A randomized, double-blind, and controlled design was adopted in this trial. The physicians who were responsible for endoscopy, 24-hour esophageal pH monitoring, and administering the questionnaire survey were relatively independent. After tests, another physician performed the statistical analysis in order to guarantee the objectivity and validity of tests.
Results showed that the 90 patients consisted of 59 males and 31 females, with the male-to-female ratio approaching 2 : 1. This ratio is similar to previous reports and may be due to histories of smoking, and drinking. Reportedly [
Group A (40 mg/day for two weeks), Group B (20 mg/day for two weeks), and Group C (placebo for the 1st week and rabeprazole 20 mg/d for the 2nd week) were designed to investigate the effects of PPI in different doses and treatment duration on test results. Results indicate that SF-36 scores had no significant differences between pretreatment and after one or two weeks of treatment, which may be attributed to non-GERD patients mingling between all the groups. Therefore, GERD and non-GERD patients should be analyzed separately. When patients were grouped according to GERD and non-GERD diagnosis, differences in SF-36 scores were only noted between GERD and non-GERD groups after two weeks of treatment for Group A. The differences were not significant between GERD and non-GERD groups before and after one and two weeks of treatment in other groups. It is believed that SF-36 scores, the common disease scale, are affected not only by GERD itself but also the occupation, material status, family and social relationships, education, household income, and social class of patients. The Az was 0.27 in the SF-36 score ROC prior to the treatment, suggesting that SF-36 alone is a poor tool for diagnosing GERD in a primary care setting and is not sufficient to establish a GERD diagnosis. Further analysis showed that the differences were significant in improved SF-36 scores between GERD and non-GERD patients in Groups A and B (
In this trial, the diagnostic value of the rabeprazole test did not differ significantly according to duration; the diagnostic value can be considered approximately equivalent after one week of treatment and after two weeks of treatment. The diagnostic coincident rate is 73%, the sensitivity is 85.7%, and the specificity is 44.5% after a one-week administration of rabeprazole 10 mg twice per day. Significant differences in diagnostic sensitivity and specificity at the two-week mark are not noted compared to that at the one-week mark. Diagnostic efficacy is consistent and the expense increases significantly. Therefore, diagnostic administration for two weeks is unnecessary for judging results. There are no significant differences in the sensitivity and specificity of the 40 mg/day and 20 mg/day groups. Therefore, rabeprazole given as 10 mg b.i.d. for one week is optimum for the PPI test and has the added benefit of being less costly. Results of diagnostic tests with rabeprazole, as reported by Schenk et al. [
The SF-36 consists of 3 major parts: functional status, health satisfaction, and total evaluation. It includes eight fields: physical function, physical responsibility, body pain, activation, social function, and emotional responsibility. The eight fields are classified further into physical component scales and mental component scales. The SF-36, a common scale, not only measures its own items but also investigates several specific problems as affecting factors when determining the quality of life with GERD. It comprises more contents than the relatively limited RDQ. Some GERD patients present primarily with extraesophageal symptoms such as coughing and throat discomfort, which strongly influence the quality of life. After treatment, patients improved and their life quality increased. Therefore, rabeprazole in combination with the SF-36 can make a diagnosis through a comparison of pretreatment and posttreatment scores. A common scale may be more helpful than a GERD-specific scale to clarify the reason for decline in the quality of life.
The PPI test is a current diagnostic method for GERD. This study aims to determine the effectiveness of coapplying the PPI test and the SF-36 for GERD diagnosis. Rabeprazole is metabolized in nonenzymic fashion, with a longer half-life, more stable pharmacokinetics, and greater efficacy than the first generation of PPI. In clinical practice, administration of rabeprazole can improve reflux symptoms and the quality of life rapidly [
In conclusion, our study shows that the SF-36 in combination with the rabeprazole test can screen GERD patients and increase the sensitivity and specificity of GERD diagnosis through reference to the change in SF-36 score before and after the treatment (65 in the trial). This not only reduces the expense of clinical diagnosis but also reduces the pain that might be inflicted for gastroscopy and pH monitoring. With this method, diagnosis and treatment can be performed concurrently to shorten diagnosis duration.
Certainly, more exact diagnostic criteria require more large-sample, multicenter, randomized control, and double-blinded studies.
The authors declare that they have no conflict of interests.
This study was supported in part by Grants from The Science and Technology Commission of Shanghai Municipality (no. 054119544).