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Health Care Utilization After Medical and Surgical Therapy for Gastroesophageal Reflux Disease
A Population-Based Study, 1996 to 2000
Leena Khaitan, MD, MPH;
Wayne A. Ray, PhD;
Michael D. Holzman, MD, MPH;
Walter E. Smalley, MD, MPH
Arch Surg. 2003;138:1356-1361.
ABSTRACT
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Hypothesis Patients who undergo surgical treatment for gastroesophageal reflux disease (GERD) will use fewer health care resources than those who continue to be treated medically during the same follow-up period.
Design Matched cohort study of patients with a diagnosis of GERD receiving surgical therapy or medical therapy.
Setting Tennessee Medicaid (TennCare) program from 1996 through 2000.
Patients Population-based sample of 7635 TennCare enrollees with a diagnosis of GERD served as the underlying population. Of these, 111 surgical patients who underwent fundoplication in 1996 met inclusion criteria. The 200 patients in the medically treated cohort were randomly matched to patients in the surgical cohort by demographic characteristics and previous use of acid-suppressing drugs.
Interventions The surgical group all underwent fundoplication in 1996. The medical group was treated without fundoplication.
Main Outcome Measures Health care utilization (medication use, outpatient visits, hospitalizations, and diagnostic studies) for each cohort through December 2000.
Results In the 4-year follow-up period, the surgical group had fewer GERD-related outpatient physician visits (5.5 ± 6.9 visits vs 6.7 ± 6.1 visits; P = .10). Utilization of other types of outpatient and inpatient care was similar. During each year of follow-up, the proportion of persons using GERD medication was lower in the surgical group. (0.67 vs 0.93 in year 1, 0.67 vs 0.91 in year 2, 0.72 vs 0.85 in year 3, and 0.74 vs 0.90 in year 4).
Conclusion The utilization of health care resources in patients treated surgically for GERD is associated with a modest decrease in the use of GERD-related medications and GERD-related visits.
INTRODUCTION
GASTROESOPHAGEAL reflux disease (GERD) is defined as abnormal acid exposure in the distal esophagus leading to symptoms such as heartburn and regurgitation. It is estimated that 15% to 44% of Americans experience heartburn monthly and 7% experience it daily.1 In 1985, heartburn was the primary or secondary reason for more than 2.5 million office visits in the United States.2 For many patients, reflux disease is a chronic disorder requiring lifelong therapy, resulting in an impaired quality of life3-4 and increased risk of other serious esophageal disease.5 This translates into a high utilization of health care resources, which is estimated to exceed $1 billion for persons with esophagitis.2
Conservative therapy for GERD, including lifestyle changes, diet modification, and over-the-counter agents, is successful in only 20% of patients with documented GERD-related esophagitis.6-7 Pharmacotherapy typically consists of medications such as histamine2 receptor antagonists and proton pump inhibitors (PPIs). The PPIs are the most effective medical therapy, resulting in symptomatic relief and healing of esophagitis in about 80% of cases.8-10 An estimated 35% to 50% of patients diagnosed as having GERD will require lifelong therapy.11
Fundoplication, a surgical approach to therapy, has traditionally been reserved for patients with complications of GERD or those in whom pharmacologic therapy is insufficient. However, surgical therapy is being considered for a wider array of patients since the development of laparoscopic approaches to fundoplication. The laparoscopic approach has been shown to provide long-term symptomatic relief in the majority of patients.12-13 Surgery, however, has potential for complications in 7% to 50% of patients12 and a reported failure rate of 1% per year.13
Few studies have compared medical and surgical therapy in a controlled, randomized fashion. A large Veterans Affairs Cooperative Study performed before the availability of PPIs and the availability of the laparoscopic approach to therapy concluded that surgery is more effective than medical treatment for complicated GERD for up to 2 years.14 However, during extended follow-up many of the surgical patients resumed use of antireflux medication.15-17 Other comparative studies of the outcomes of medical vs surgical therapy are not available, and there is a consensus that further studies are needed to determine the ideal treatment for GERD.18-20
Surgery has been suggested to be more cost-effective in the long term,21-23 because it has the potential to eliminate the need for costly antireflux medications. However, there are some data indicating that by 10 years, many of the surgical patients resumed antireflux medication use.15-17 Thus, direct evaluation of the actual utilization of health care after the 2 treatments is needed to better understand the costs and health care resources associated with the treatments. A previous study by our group described utilization of health care resources in medically and surgically treated cohorts followed up for 1 year.24 The purpose of the present study is to extend this follow-up to 4 years.
METHODS
STUDY DESIGN AND DATA
We conducted a retrospective matched cohort study of patients with a history of GERD who underwent medical or surgical therapy. The study population was drawn from patients enrolled in the Tennessee expanded Medicaid program, TennCare, which includes persons meeting federal criteria for Medicaid as well as other persons with low to moderate income who are uninsured or uninsurable.25 TennCare maintains an extensive system of data, including a registry of all enrollees, records of patient-provider encounters, hospital and outpatient encounters, and prescriptions filled at the pharmacy.26 These administrative data and computerized health care records were used to identify the cohort of patients with treated GERD and to track their subsequent health care utilization. The study was approved by both the Vanderbilt University Institutional Review Board and the Tennessee Department of Health Institutional Review Board.
STUDY COHORTS
Identification of the surgical and medical cohorts was described in detail previously.24 Briefly, patients were eligible for the original surgical cohort if they underwent a fundoplication in 1996 and met additional criteria on the date of the fundoplication surgery. These criteria were age of 18 years or greater, at least 365 days of enrollment in the year preceding the surgery (the baseline year) as well as in the following year, and at least 2 GERD-related medical care episodes (outpatient visit or inpatient admission with a diagnosis consistent with GERD separated by at least 30 days), as well as 90 or more days of antireflux medication use in the baseline year. For the present study, we also required that patients remain enrolled in TennCare during the entire 4 years of follow-up. The original cohort included 133 patients; of these, 111 qualified for the present study (14 lost TennCare eligibility and 8 died before completing 4 years of follow-up).
The medical cohort was identified from patients comparable to those undergoing fundoplication who did not themselves have fundoplication during the study. There were 7502 qualifying medical patients identified, from whom 2 were matched with each surgical patient, with matching on age, sex, race, quartile of days of antireflux therapy in the baseline year, and TennCare managed care organization. A total of 248 patients thus composed the original medical cohort. Of these, 200 were enrolled throughout the 4 years of follow-up and were free of fundoplication (16 lost TennCare eligibility, 21 died, and 11 had fundoplication), and thus were included in the present study.
STUDY OUTCOMES
We studied the utilization of medical care during the 4 years after fundoplication surgery. Episodes of utilization were used instead of costs because the payments made to providers in TennCare for medical services reflect stringent managed care cost containment and may not be widely applicable.
PRESCRIPTION MEDICATIONS
Antireflux therapy, as determined from the computerized pharmacy files, included histamine2 receptor antagonists, PPIs, and prokinetic agents. The days of supply included in each prescription for these drugs was converted into standardized days of antireflux therapy as follows. First, a standard daily dose was defined by using the manufacturer's recommended daily dose for the treatment of GERD as noted in the Physicians' Desk Reference.27 These were cimetidine hydrochloride (1600 mg), ra-nitidine hydrochloride (300 mg), famotidine (40 mg), nizatidine (300 mg), omeprazole (20 mg), lansoprazole (30 mg), metoclopramide hydrochloride (40 mg), and cisapride monohydrate (40 mg). The total milligrams in each prescription was then divided by the standard daily dose to yield total days of acid suppression therapy.
The use of other prescription medication in the baseline year was assessed as an indicator of patient comorbidity. These included analgesics, antibiotics, cardiovascular medications, antidiabetic agents, antineoplastics, pulmonary medications, and psychotropic drugs.
GERD-RELATED DIAGNOSTIC AND THERAPEUTIC PROCEDURES
Diagnostic tests during the study period were identified from physician visit encounters. These studies included upper gastrointestinal tract endoscopy, esophageal manometry, pH testing, radiologic barium swallow studies, and abdominal radiology. Therapeutic procedures included esophageal dilations, surgery, and other endoscopic antireflux procedures.
OUTPATIENT VISITS
Other outpatient visits (both physician and emergency department) were classified as related to GERD, other gastrointestinal disease, or other condition on the basis of the primary diagnosis. Only a single visit was counted when multiple services (eg, laboratory, radiology, or office visit) were provided on a single day. The visit was classified hierarchically as related to GERD, other gastrointestinal disease, or other condition.
HOSPITAL DAYS
All hospitalizations during the study period were included. Hospital days included the date of admission through the date of discharge. The hospital days were categorized as GERD, other gastrointestinal disease, or other condition according to the primary discharge diagnosis in a hierarchical fashion similar to that for outpatient visits.24
ANALYSIS
For categorical variables, the proportions with the variable present in the surgical and medical groups were calculated and compared by the Fisher exact test or Pearson  2 where appropriate for categorical variables. For continuous variables, means and SDs were calculated and means were compared with the unpaired, 2-tailed t test. For skewed data, alternative analyses were conducted by means of the nonparametric Mann-Whitney test, which provided results essentially identical to those presented. All analyses were performed with Stata software (Stata Corp, College Station, Tex).
RESULTS
BASELINE CHARACTERISTICS OF MEDICAL AND SURGICAL GROUPS
The mean age of study patients was 46 years. Nearly two thirds were female, and 84% were white (Table 1). The matching ensured that these demographic characteristics were very similar for both the medical and surgical groups.
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Table 1. Characteristics of Medical and Surgical Patients at Baseline
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Medical and surgical patients did not differ significantly with regard to total days of antireflux therapy received in the baseline year (Table 1). The former received a mean of 326 days vs 345 days for the latter (P = .46). However, the use of individual agents differed, with PPI use being more common in the surgical group (medical group, 92 days; surgical group, 134 days; P = .02).
As expected, nearly all surgical patients had visits in the baseline year for diagnostic and therapeutic studies used to identify good candidates for fundoplication, whereas fewer medically treated patients had such studies (Table 1; 98% vs 72%; P<.001). Surgical patients also had more physician visits for either GERD or non–GERD-related gastrointestinal diagnoses, which may represent preoperative care.
However, medical and surgical patients had similar baseline utilization of other medical care (Table 1). This included inpatient hospital stays (for both GERD and non–GERD-related diagnoses), physician visits for nongastrointestinal diagnoses, and use of nongastrointestinal medications.
MEDICAL CARE DURING 4 YEARS OF FOLLOW-UP
As expected, the surgical group had greater use of inpatient and outpatient care during the 90-day perioperative period (Table 2). Forty-eight percent of surgical patients had a perioperative diagnostic or therapeutic procedure related to GERD, whereas only 19% of medical patients had such a procedure during a comparable period (P<.001). The difference was most pronounced for abdominal radiology (35% of the surgical group and 4% of the medical group; P<.001). Surgical patients had no increase in outpatient visits unrelated to GERD, but did have an elevation in mean hospital days (5.8 vs 1.6; P<.001).
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Table 2. Inpatient and Outpatient Encounters in the Perioperative Period (Date of Surgery and Subsequent 89 Days)
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Surgical patients continued to have greater use of selected diagnostic and therapeutic procedures during the remainder of postoperative follow-up (Table 3). The excess was most pronounced for fluoroscopic or upper gastrointestinal studies (17% of the surgical group and 9% of the medical group; P = .02) and abdominal radiology (31% vs 17%; P = .005). However, there were no differences during follow-up in other outpatient encounters. There was a trend toward greater mean inpatient days in the medical group (10 days in the surgical group vs 18 days in the medical group), but this was not statistically significant (P = .08).
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Table 3. Inpatient and Outpatient Encounters After the Perioperative Period (90 Days After Date of Surgery Through 4 Years)
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Surgical patients had substantially lower use of antireflux medications in the first postoperative year (Table 4 and Figure 1). Use declined from a mean 345 days in the year before surgery to 135 days. This use in the first follow-up year was 233 days less than that for medical patients (P<.001). The change was most pronounced for PPIs, where, in the baseline year, surgical patients had a mean of 42 days more use than medical patients, whereas postoperatively the surgical group had a mean of 109 days less use (P<.001). However, use of antireflux therapy increased among surgical patients for each of the remaining follow-up years. By year 4, this group had a mean of 224 days of use. Despite this increase, use in the surgical group remained a mean of 180 days lower than that for the medical patients (P<.001).
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Table 4. Use of GERD Therapy Prescription Medications During Baseline and Years 1 Through 4 of Follow-up, for 200 Medical and 111 Surgical Patients
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Use of prescription therapy for gastroesophageal reflux disease through year 4.
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During each year of the follow-up period, the proportion of surgical patients receiving GERD therapy was lower than the proportion of medical patients who received GERD therapy (Table 5). During the final year of follow-up, 74% of surgical patients were receiving GERD therapy, while 90% of medical patients were receiving it.
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Table 5. Proportion of Patients Receiving Various Types of GERD Therapy, by Year for 200 Medical and 111 Surgical Patients
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COMMENT
At present, there is a vigorous controversy over the optimal therapy for GERD, with surprisingly few data to guide the choice between medical and surgical therapy. The only randomized clinical trial of this question, conducted by the Department of Veterans Affairs Cooperative Studies Program,14 reported initially that surgical therapy led to improved symptom control. However, the recent report with up to 10 years of follow-up15 challenged both this initial finding and the assumption that surgery improved clinical outcomes. Furthermore, by the end of follow-up, 62% of surgical patients were receiving antireflux therapy. In addition, the findings of this trial are limited by the restriction to a veteran population, the nonrandomized nature of the long-term follow-up, and subsequent changes in both surgical technique and antireflux medications.
One of the assumed benefits of surgical therapy has been the potential to make lifelong treatment with medications unnecessary. This in turn reduces the likelihood of adverse medication effects or drug-drug interactions, patient inconvenience, and costs, both for patients and for the health care system. However, our findings reinforce the conclusion of the Veterans Affairs Cooperative Study that surgical patients are likely to continue material use of antireflux medications.15
In the current study as well as the Veterans Affairs Cooperative Study, the reason for the resumption of antireflux medications is not known. There is no objective information noted in either study regarding pH studies to assess for the recurrence of GERD in any of these patients. In this study, none of the surgical patients had pH studies during the follow-up period, even though antireflux medications were prescribed to many. Some of the use of antisecretory medications in the postoperative patients might have been for symptoms other than GERD. In clinical trials where gastroesophageal reflux has been objectively studied after fundoplication procedures with 24-hour pH studies, only 16% of patients were actually found to have abnormal Johnson-DeMeester scores28 and only up to 23% had abnormal acid exposure time.29 Another study of more than 1000 patients who had an antireflux procedure reported that only 16% of patients were reported to be taking antireflux medications and 97% of patients were satisfied with their procedure.11 Administrative data of the type used in this study cannot adequately measure effectiveness of therapy or quality of life. In some cases, surgical patients might have an improved quality of life or control of symptoms by using medications that had been less effective before fundoplication.
Outcomes in clinical practice such as those seen in this population-based study may differ from the results seen in clinical trials. Less stringent patient selection and variability in technical expertise may lead to an observed difference in "real-world" effectiveness compared with the clinical trial efficacy demonstrated in a well-controlled setting.30
There was a trend toward increasing use of antireflux therapy in the medical group during the follow-up period, although not as pronounced as that for the surgical patients. This finding suggests that some of the increase among the latter may be due to use of the very popular antisecretory drugs for other reasons. Despite this trend in the medical group, the gap between surgical and medical patients narrowed during each of the 4 years of follow-up.
The present study had several limitations. The study cohort consisted of TennCare enrollees, which may limit generalizability. Nevertheless, this cohort does include large numbers of women, who were virtually absent from the Veterans Affairs Cooperative Study. The TennCare cost-containment measures during the study period, which included prior authorization for PPIs, may have limited use of antireflux therapy. However, this restriction is used by private insurers and, unlike with many private insurers, patients had little or no copayment. Although the study could not detect use of over-the-counter medications, patients had strong economic incentives to obtain antisecretory drugs by prescription.
Because the study outcome was health care utilization, we could not assess differences in medical and surgical patients with regard to symptom control. Furthermore, the small sample size and limited duration of follow-up precluded assessment of clinical outcomes. However, understanding of the health care utilization is essential to economic evaluation of the medical and surgical therapeutic modalities. Indeed, our findings call into question several of the published cost-effectiveness analyses that assume surgery results in virtually no subsequent use of antireflux therapy.21-23 The study cohorts were identified in 1996, and subsequent changes in surgical technique and selection of operative candidates may limit applicability of our findings.
Gastroesophageal reflux disease is a common and expensive chronic disorder that can seriously affect patient quality of life.3-4 Furthermore, there is considerable evidence that it predisposes to life-threatening illnesses.5 Despite this, there is a paucity of rigorous data that address some of the most basic questions regarding its management, including the relative merits, in terms of both efficacy and cost, of the medical vs surgical approaches to symptom management, and of the effect of treatment on long-term clinical outcomes. Thus, a high-quality randomized clinical trial that addresses these questions is urgently needed.
AUTHOR INFORMATION
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Corresponding author: Walter E. Smalley, MD, MPH, C-2104 MCN, Division of Gastroenterology, Vanderbilt University, 21st and Garland, Nashville, TN 37232. Reprints: Leena Khaitan, MD, MPH, Department of Surgery, Emory University, 1364 Clifton Rd NE, Suite H124, Atlanta, GA 30322.
Accepted for publication June 6, 2003.
This study was supported in part by a cooperative agreement (grant HS1-0384) from the Agency for Health Care Research and Quality, Center for Education and Research on Therapeutics, Vanderbilt University, Nashville, Tenn; grant HL 67964 from the Public Health Service, Rockville, Md; and a cooperative agreement (FD-U-001641) with the US Food and Drug Administration, Rockville.
None of the funding for this study was provided by any pharmaceutical company.
From the Departments of Surgery (Drs Khaitan, Holzman and Smalley), Preventive Medicine (Drs Ray and Smalley), and Medicine (Dr Smalley), Vanderbilt University School of Medicine, Vanderbilt University Center for Education and Research on Therapeutics, and the Geriatric Research, Education, and Clinical Center, Nashville Veterans Affairs Center (Drs Ray and Smalley), Nashville, Tenn. Dr Khaitan is now with the Department of Surgery, Emory University, Atlanta, Ga.
REFERENCES
1. Nebel OT, Fornes MT, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis. 1976;21:953-956.
FULL TEXT
|
ISI
| PUBMED
2. Digestive Diseases in the United States: Epidemiology and Impact. Bethesda, Md; US Dept of Health and Human Services; 1994.
3. Slim K, Bousquet J, Kwiatkowski F, Lescure G, Pezet D, Chipponi J. Quality of life before and after laparoscopic fundoplication. Am J Surg. 2000;180:41-45.
FULL TEXT
|
ISI
| PUBMED
4. McDougall NI, Johnson BT, Kee F, Collins JSA, McFarland RJ, Love AHG. Natural history of reflux oesophagitis: a 10 year follow up of its effect on patient symptomatology and quality of life. Gut. 1996;38:481-486.
FREE FULL TEXT
5. Shaheen N, Ransohoff DF. Gastroesophageal reflux, Barrett esophagus, and esophageal cancer. JAMA. 2002;287:1972-1981.
FREE FULL TEXT
6. Lieberman DA. Medical therapy for chronic reflux esophagitis: long-term follow-up. Arch Intern Med. 1987;147:1717-1720.
FREE FULL TEXT
7. Behar J, Sheahan DG, Biancani P, Spiro HM, Storer EH. Medical and surgical management of reflux esophagitis: a 38-month report of a prospective clinical trial. N Engl J Med. 1975;293:263-268.
ABSTRACT
8. Behar J, Brand DL, Brown FC, et al. Cimetidine in the treatment of symptomatic gastroesophageal reflux: a double blind controlled trial. Gastroenterology. 1978;74(2, pt 2):441-448.
ISI
| PUBMED
9. Sontag S, Robinson M, McCallum RW, Barwick KW, Nardi R. Ranitidine therapy for gastroesophageal reflux disease: results of a large double-blind trial. Arch Intern Med. 1987;147:1485-1491.
FREE FULL TEXT
10. Euler AR, Murdock RH Jr, Wilson TH, Silver MT, Parker SE, Powers L. Ranitidine is effective therapy for erosive esophagitis. Am J Gastroenterol. 1993;88:520-524.
ISI
| PUBMED
11. Terry M, Smith CD, Branum GD, Galloway K, Waring JP, Hunter JG. Outcomes of laparoscopic fundoplication for gastroesophageal reflux disease and paraesophageal hernia: experience with 1000 consecutive cases. Surg Endosc. 2001;15:691-699.
FULL TEXT
|
ISI
| PUBMED
12. Bowrey DJ, Peters JH. Current state, techniques, and results of laparoscopic antireflux surgery. Semin Laparosc Surg. 1999;6:194-212.
PUBMED
13. Hinder RA. Surgical therapy for GERD: selection of procedures, short and long-term results. J Clin Gastroenterol. 2000;30(3, suppl):S48-S50.
FULL TEXT
|
ISI
| PUBMED
14. Spechler SJ, for the Department of Veterans Affairs Gastroesophageal Reflux Disease Study Group. Comparison of medical and surgical therapy for complicated gastroesophageal reflux disease in veterans. N Engl J Med. 1992;326:786-792.
ABSTRACT
15. Spechler SJ, Lee E, Ahnen D, et al. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. JAMA. 2001;285:2331-2338.
FREE FULL TEXT
16. Harary AM. Medical vs surgical treatment of gastroesophageal reflux [letter]. JAMA. 2001;286:1709.
FREE FULL TEXT
17. DeMeester SR. Medical vs surgical treatment of gastroesophageal reflux [letter]. JAMA. 2001;286:1709.
18. Lundell L, Dalenvack J. Omeprazole or antireflux surgery in the long term management of gastroesophageal reflux disease: results of a multicentre, randomized, clinical trial. Gastroenterology. 1998;114:A207. Abstract 0848.
ISI
19. Allgood PC, Bachmann M. Medical or surgical treatment for chronic gastro-oesophageal reflux? a systematic review of published evidence of effectiveness. Eur J Surg. 2000;166:713-721.
FULL TEXT
|
ISI
| PUBMED
20. Fennerty MB, Castell D, Fendrick AM, et al. The diagnosis and treatment of gastroesophageal reflux disease in a managed care environment: suggested disease management guidelines. Arch Intern Med. 1996;156:477-484.
FREE FULL TEXT
21. Heudebert GR, Marks R, Wilcox CM, Centor RM. Choice of long-term strategy for the management of patients with severe esophagitis: a cost-utility analysis. Gastroenterology. 1997;112:1078-1086.
FULL TEXT
|
ISI
| PUBMED
22. Viljakka M, Nevalainen J, Isolauri J. Lifetime costs of surgical versus medical treatment of severe gastro-oesophageal reflux disease in Finland. Scand J Gastroenterol. 1997;32:766-772.
ISI
| PUBMED
23. Van Den Boom G, Go PM, Hameeteman W, Dallemagne B, Ament AJ. Cost effectiveness of medical versus surgical treatment in patients with severe or refractory gastroesophageal reflux disease in the Netherlands. Scand J Gastroenterol. 1996;31:1-9.
PUBMED
24. Holzman MD, Mitchel EF, Ray WA, Smalley WE. Use of healthcare resources among medically and surgically treated patients with gastroesophageal reflux disease: a population-based study. J Am Coll Surg. 2001;192:17-24.
FULL TEXT
|
ISI
| PUBMED
25. Mirvis DM, Chang CF, Hall CJ, Zaar GT, Applegate WB. TennCare: health system reform for Tennessee. JAMA. 1995;274:1235-1241.
FREE FULL TEXT
26. Ray WA, Griffin MR. Use of Medicaid data for pharmacoepidemiology. Am J Epidemiol. 1989;129:837-849.
FREE FULL TEXT
27. Physicians' Desk Reference. 45th ed. Montvale, NJ: Thomson Healthcare; 1991.
28. Khajanchee YS, O'Rourke RW, Lockhart B, Patterson EJ, Hansen PD, Swanstrom LL. Postoperative symptoms and failure after antireflux surgery. Arch Surg. 2002;137:1008-1014.
FREE FULL TEXT
29. Lord RV, Kaminski A, Oberg S, et al. Absence of gastroesophageal reflux disease in a majority of patients taking acid suppression medications after Nissen fundoplication. J Gastrointest Surg. 2002;6:3-9.
FULL TEXT
|
ISI
| PUBMED
30. Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in Health and Medicine. New York, NY: Oxford University Press; 1996:142-146.
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