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Short-Term Treatment with Proton-Pump Inhibitors as a Test for Gastroesophageal Reflux Disease: A Meta-Analysis of Diagnostic Test Characteristics

Mattijs E. Numans, MD, PhD; Joseph Lau, MD; Niek J. de Wit, MD, PhD; and Peter A. Bonis, MD
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From University Medical Center Utrecht, Utrecht, the Netherlands, and Tufts-New England Medical Center, Boston, Massachusetts.

Acknowledgment: This work is part of the GERD-guidelines project of the European Society of Primary Care Gastroenterology (ESPCG).

Grant Support: Mattijs Numans, MD, PhD, was financially supported for this study in the United States by the Netherlands Organization for Scientific Research, the University Medical Centre, Utrecht, the Netherlands (Foundation Girard de Mielet van Coehoorn), and by unrestricted grants from the Dutch divisions of Altana Pharma, Jansen Cilag, and AstraZeneca. Joseph Lau, MD, is supported in part by a grant (R01 HS013328) from the Agency for Healthcare Research and Quality.

Potential Financial Conflicts of Interest:Stock ownership or options (other than mutual funds): J. Lau (Merck, Pfizer); Expert testimony: N.J. de Wit (Janssen Cilag); Grants received: M.E. Numans (AstraZeneca, Altana Pharma, Janssen Cilag), N.J. de Wit (Altana Pharma, Novartis, Janssen Cilag).

Requests for Single Reprints: Mattijs E. Numans, MD, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, the Netherlands; e-mail, m.e.numans@med.uu.nl.

Current Author Addresses: Drs. Numans and de Wit: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, the Netherlands.

Drs. Lau and Bonis: Center for Clinical Evidence Synthesis, Tufts-New England Medical Center, Kneeland Drive, Boston MA 02111.

Author Contributions: Conception and design: M.E. Numans, J. Lau, N.J. de Wit, P.A. Bonis.

Analysis and interpretation of the data: M.E. Numans, J. Lau, P.A. Bonis.

Drafting of the article: M.E. Numans, P.A. Bonis.

Critical revision of the article for important intellectual content: M.E. Numans, J. Lau, N.J. de Wit, P.A. Bonis.

Final approval of the article: M.E. Numans, J. Lau, P.A. Bonis.

Provision of study materials or patients: M.E. Numans.

Statistical expertise: M.E. Numans, J. Lau, P.A. Bonis.

Obtaining of funding: M.E. Numans, N.J. de Wit.

Administrative, technical, or logistic support: J. Lau.

Collection and assembly of data: M.E. Numans, P.A. Bonis.

Ann Intern Med. 2004;140(7):518-527. doi:10.7326/0003-4819-140-7-200404060-00011
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Although 38% to 90% of the patients suspected of having uncomplicated GERD responded to an empirical trial of treatment with a PPI, our findings suggest that a favorable response does not confidently establish the diagnosis of GERD when GERD is defined according to traditional objective criteria (45). In addition to signaling the presence of GERD, the observed clinical benefit may also indicate the presence of another acid-related condition, a placebo effect, or enhanced esophageal sensitivity to acid exposure (46). On the other hand, 20% to 40% of the patients who have GERD on the basis of objective testing may not exhibit a response to a short course of treatment with a PPI, possibly because they need a higher dose or longer duration of treatment.

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Grahic Jump Location
Figure 2.
Summary receiver-operating characteristic curve analysis of the proton-pump inhibitor test with relevant esophagitis found on esophagogastroduodenoscopy as the reference standard (n= 978).
Grahic Jump Location
Grahic Jump Location
Figure 1.
Summary receiver-operating characteristic curve analysis of the proton-pump inhibitor test with abnormal 24-hour pH monitoring as the reference standard (n= 232).
Grahic Jump Location




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Is diagnosis all we need?
Posted on July 20, 2004
Agostino Colli
Department of Internal Medicine
Conflict of Interest: None Declared

The systematic review of Numans ME et al. shows that a positive proton pump inhibitors (PPI) test does not support and a negative one does not exclude the diagnosis of GERD as defined according to traditional objective criteria ( that are: upper endoscopy or pH monitorig or symptoms scores). However the authors suggest that a PPI trial might be reasonable in clinical practice. This apparent contradiction raises from regarding PPI test as a diagnostic one. It is not obvious to label a patient in whom PPI relieve symptoms but does not reach a diagnostic symptoms score as a False Positive. Short-term treatment with PPI can be useful for symptomatic patients no matter if they satisfy any formal diagnostic criteria. On the contrary a negative PPI test suggest the need of further investigation. Thus PPI test seems to really assess efficacy of an intervention. Clearly a positive result does not exclude between a placebo effect nor alternative diagnosis ( sensitive to PPI treatment). But in every day practice it seems not so essential to have a precise diagnosis: alternative diagnoses are similar for both prognostic and therapeutic point of view, PPI are relatively safe and inexpensive drugs. In conclusion why should we worry to have a precise diagnosis if patients have no more symptoms? It seems worth while to order further investigations only if alternative diagnoses show quite different prognosis or therapeutic approach : for instance in case of chest pain and nitroglycerin test[1]

REFERENCES 1.. Henrikson C A, Howell E E, Bush D E, Shawn Miles J,. Meininger G R, Friedlander T, Bushnell AC, and Chandra-Strobos N Chest Pain Relief by Nitroglycerin Does Not Predict Active Coronary Artery Disease Ann Intern Med 2003; 139: 979 - 986.

Conflict of Interest:

None declared

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Summary for Patients

Does Symptom Response Diagnose Gastroesophageal Reflux Disease?

The summary below is from the full report titled “Short-Term Treatment with Proton-Pump Inhibitors as a Test for Gastroesophageal Reflux Disease. A Meta-Analysis of Diagnostic Test Characteristics.” It is in the 6 April 2004 issue of Annals of Internal Medicine (volume 140, pages 518-527). The authors are M.E. Numans, J. Lau, N.J. de Wit, and P.A. Bonis.


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