0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

Efficacy of Noninvasive Tests in the Diagnosis of Helicobacter pylori Infection in Pediatric Patients FREE

Tamara Sabbi, MD; Paola De Angelis, MD; Franco Colistro, MD; Luigi Dall’Oglio, MD; Giovanni Federici di Abriola, MD; Massimo Castro, MD
[+] Author Affiliations

Author Affiliations: Pediatric Unit, “Belcolle” Hospital, Viterbo, Italy (Dr Sabbi); Digestive Surgery and Endoscopic Unit (Drs De Angelis, Dall’Oglio, and di Abriola), Central Laboratory (Dr Colistro), and Gastroenterology Unit (Dr Castro), “Bambino Gesù” Pediatric Hospital, Rome, Italy.


Arch Pediatr Adolesc Med. 2005;159(3):238-241. doi:10.1001/archpedi.159.3.238.
Text Size: A A A
Published online

Background  Helicobacter pylori infection is likely acquired in childhood. Helicobacter pylori is recognized as a cause of gastritis and peptic ulcer.

Objective  To investigate some noninvasive tests, particularly H pylori fecal antigen, for the diagnosis of H pylori infection in comparison with the gold-standard invasive test, esophagogastroduodenoscopy with biopsy.

Methods  We studied 250 patients (102 male; age range, 3-18 years) who underwent esophagogastroduodenoscopy with biopsy (histologic examination and rapid urease test) for a suspicious upper gastrointestinal disease; in all of them, fecal H pylori antigen, serum H pylori immunoglobulin G, and cytotoxin-associated gene product A immunoglobulin G were measured. Sensitivity and specificity of noninvasive tests were compared with those of the gold-standard esophagogastroduodenoscopy with biopsy.

Results  Ninety-three patients (37%) had positive histopathologic (Giemsa staining) and rapid urease test results. The H pylori fecal antigen revealed a sensitivity of 97%, a specificity of 98%, a positive predictive value of 97%, and a negative predictive value of 98%; serum H pylori immunoglobulin G had a sensitivity of 86%, a specificity of 80%, a positive predictive value of 72%, and a negative predictive value of 90%; and serum cytotoxin-associated gene product A immunoglobulin G had a sensitivity of 83%, a specificity of 80%, a positive predictive value of 71%, and a negative predictive value of 89%.

Conclusions  Our study demonstrates that among noninvasive and easily applicable tests, particularly in small children, H pylori fecal test is simple, suitable, and has high accuracy for the screening of H pylori–positive patients.

Helicobacter pylori infection is common, even in pediatric patients. In European children, serum positivity of immunoglobulin G (IgG) antibodies is almost 5% to 15%. The infection is likely acquired early in childhood; in developing countries, the incidence of the infection in infancy may be up to 50%.1,2

Helicobacter pylori is now recognized as related to gastritis and peptic ulcer disease. Furthermore, H pylori infection is involved in the pathogenesis of gastric adenocarcinoma and lymphoma in adulthood.3,4 However, the H pylori role in dyspepsia and extradigestive diseases (vascular, immunological, and skin pathologic features; sideropenic anemia; and delayed statural growth)511 is quite controversial.

Children present an ideal population for studying the interaction between H pylori and gastric mucosa because pediatric age is free from common causes of secondary gastrointestinal diseases (drugs, tobacco, and alcohol).12 Also, the natural history of diseases related to H pylori is conditioned by the early acquiring of the bacterium.13

The gold-standard diagnostic test remains endoscopy with biopsy analyses (histologic analysis and urease rapid test or culture of gastric biopsy specimens).14,15 Invasive tests are not always suitable for the pediatric population; there is an increased interest in noninvasive tests for children. Serum (IgG and cytotoxin-associated gene product A [CagA] IgG) and salivary (IgG) antibodies are used for screening in epidemiological studies of large populations.1619 The detection of H pylori antigen in feces is considered useful for diagnosis and to confirm eradication.20

The aim of this prospective study has been to validate the accuracy of some noninvasive diagnostic methods, particularly H pylori fecal antigen, in comparison with the invasive gold standard (endoscopy with biopsy analyses).

The study involved 250 consecutive patients (102 male; mean age, 11 years; range, 3-18 years) with a suspicion of upper gastrointestinal disease (symptoms including recurrent abdominal pain, diurnal or nocturnal abdominal pain, nausea, vomiting, or iron deficiency) who were referred, in the last 2 years, to undergo esophagogastroduodenoscopy with biopsy. The recurrent abdominal pains were of such intensity that they prevented the normal activity of the child and were recurrent at least once a month during 3 months with asymptomatic intercritical periods.

In all the patients, noninvasive tests such as immunoassay for serological antibodies (IgG and CagA) against H pylori and detection of H pylori antigen in feces were measured. In 123 patients, salivary (IgG) antibody was also evaluated.

After signed informed consent was obtained, all patients received an upper gastrointestinal endoscopy with gastric biopsy, which is the gold standard for H pylori diagnosis. The biopsies were utilized for histologic examination and urease rapid test. The patients were considered H pylori positive if the histologic examination and urease rapid test indicated they had the bacterium.

Endoscopy was performed using Olympus videoscope XQ140 or GF100 (Olympus, Tokyo, Japan). Several biopsy specimens from 2 sites, the gastric body and the antrum, were obtained for histologic examination and urease rapid test. Section specimens were stained with hematoxylin-eosin and with Giemsa.

A rapid urease test result was obtained by adding a biopsy specimen to a urea broth (NaCl, KH2PO4, and NaOH); the result of the test was considered positive if there was a change of urea broth color from yellow-gold to pink-red due to an increase in pH induced by H pylori.21

An enzyme immunoassay (Premier Platinum HpSA; Meridian Diagnostics Inc, Cincinnati, Ohio) was used to detect H pylori in the frozen stool, utilizing polyclonal anti–H pylori antibody. A diluted feces sample and a peroxidase conjugated to polyclonal antibody were added to the wells and incubated for 1 hour at room temperature. A wash was performed to remove unbound material. The substrate was added and incubated for 10 minutes at room temperature. Color developed in the presence of bound enzyme. Stop solution was added and the results were interpreted visually or spectrophotometrically.

For the assay of salivary (IgG) and serum (IgG and CagA) antibodies, we used an enzyme immunoassay method still validated in children (EIA WELL-EUROSPITAL; Radim Spa, Pomezia, Italy), in which horseradish peroxidase was used as an enzyme tracer.22,23

For the serum antibodies, values between 0 and 22 (absorbance unit) UA/mL were considered normal; for the CagA, values greater than 7.5 UA/mL were considered positive. The cut off value for salivary antibodies was 20 UA/mL.

The accuracy of noninvasive tests was evaluated through sensitivity, specificity, and positive and negative predictive value (Table 1). Statistical analyses were performed with the χ2 test. The result was considered significant with P value <.05.

Table Graphic Jump LocationTable 1. Sensitivity, Specificity, and Positive and Negative Predictive Values of Noninvasive Tests*

The study was approved by the Scientific Secretariat, “Bambino Gesù” Pediatric Hospital, Rome, Italy.

In our case series, 93 (37%) of 250 patients tested H pylori positive by histologic examination and urease rapid test. Clinical features of the patients examined are reported in Table 2. There were no significant differences in symptoms between infected and noninfected patients (P>.05). Twenty-six infected children (28%) and 36 noninfected ones (23%) had parents affected by gastritis and duodenal ulcer. The domestic socioeconomic, hygiene, and living conditions were good.

Table Graphic Jump LocationTable 2. Clinical Features of 250 Patients Who Underwent Esophagogastroduodenoscopy for a Suspicion of Upper Gastrointestinal Tract Disease*

The H pylori fecal antigen revealed a sensitivity of 97%, a specificity of 98%, a positive predictive value of 97%, and a negative predictive value of 98%; serum H pylori IgG had a sensitivity of 86%, a specificity of 80%, a positive predictive value of 72%, and a negative predictive value of 90%; and serum CagA IgG had a sensitivity of 83%, a specificity of 80%, a positive predictive value of 71%, and a negative predictive value of 89%.

The salivary antibodies (IgG) were evaluated in 123 patients. Fifty of them had H pylori–positive histologic and urease rapid test results; the urease rapid test results were positive in 33 (66%) of the infected children and in 7 (9%) of the noninfected ones.

The fecal antigen detection results were positive in 90 (97%) of the infected children and in 3 (2%) of the noninfected ones.

All the statistical differences between the noninvasive tests were significant (P<.05).

At endoscopic examination of the 93 affected children, hyperemia and friability of the gastric antrum were observed in 27 patients (29%), micronodular appearance in 48 patients (52%), and a normal picture in 18 patients (19%). The histologic examination results of all infected patients showed active microerosive gastritis (neutrophilic infiltration) and chronic gastritis (lymphoplasmacytic infiltration).

The CagA-positive children had an endoscopic finding of more intense hyperemia of the gastric antrum associated with an important lymphoplasmacellular infiltrate and degenerative and vacuolar lesions of the gastric epithelium.

All the 157 noninfected patients had a normal gastric finding except the 25 H pylori–negative patients (18%) with epigastric nocturnal pain who had cardial hyperemia and distal esophageal erosions. In noninfected children, there were no histologic signs of inflammation.

The high prevalence of H pylori disease (37%) could be explained by the selected population in a specialized center. Several invasive and noninvasive methods are available at present for detecting H pylori infection. Esophagogastroduodenoscopy with biopsy is the gold standard for diagnosing the pathologic features related to H pylori rather than the H pylori infection.

Among the noninvasive tests, the urea breath test (13C urea breath test) is certainly the best, but it is more expensive, not always available (poor feasibility limit), and difficult to apply to the noncompliant child. In addition, its cut off value in pediatric patients remains unsettled. Regarding noninvasive tests, serum antibodies have the advantages of simplicity, low cost, and utility for epidemiological studies and screening programs.14 Saliva testing has a role in epidemiological studies and in screening dyspeptic patients in general practice, especially in children in whom blood sampling is more difficult.

In 1998, enzyme-linked immunoassay (Premier Platinum H pylori stool antigen; Meridian Diagnostics Inc) in stool was approved by the Food and Drug Administration for both diagnosis in adult symptomatic patients and monitoring the response to treatment.24,25Helicobacter pylori detection from stool with polymerase chain reaction is limited by the presence of inhibitors of H pylori DNA amplification in feces.14 Also, H pylori is difficult to culture from stool. The direct research of fecal antigen is simple, rapid, and inexpensive; in fact, only 1 stool specimen is required, the method does not need a technician or expensive equipment, and easy procedures are used for storing and transporting the stools, avoiding the need for freezing the stool sample.

Helicobacter pylori fecal antigen is a highly reliable diagnostic method for H pylori infection. Before extending its use in the general healthy population, many studies have compared the accuracy of this test with that of an invasive test in symptomatic patients.21 It could be used in epidemiological studies to determine the prevalence of H pylori infections in asymptomatic subjects.21 In general, H pylori prevalence is universally related to socioeconomic, hygiene, and living conditions.

Recently, a multicenter Italian study on the accuracy of the H pylori stool antigen test has reported the utility of fecal antigen in the diagnosis and follow-up of H pylori infection.25,26 Our study confirms the high sensitivity and specificity of the H pylori stool antigen test (in relation to diagnoses based on invasive examinations) already found by other investigators either in adults or in children.

Fecal antigen must be considered useful for screening and monitoring the overall pediatric population. The position that fecal antigen testing is a highly reliable method for the diagnosis of H pylori infection in children is contentious and not substantiated by the currently available biomedical literature. The current study, however, helps to add support for this point of view.

In conclusion, our study demonstrates that among noninvasive and more applicable tests, especially in small children, H pylori fecal antigen has shown high sensitivity, specificity, and positive and negative predictive value and that this test is the most useful for the screening of H pylori–positive patients. There is no characteristic clinical feature that could help in the diagnosis of H pylori infection.

Correspondence: Tamara Sabbi, MD, Endoscopic Digestive Unit, “Bambino Gesù” Pediatric Hospital, P.zza S. Onofrio, 4, 00165 Rome, Italy (sabbi.t@libero.it).

Accepted for Publication: October 13, 2004.

Camorlinga-Ponce  MTorres  JPerez-Perez  G  et al.  Validation of a serologic test for the diagnosis of Helicobacter pylori infection and the immune response to urease and CagA in children. Am J Gastroenterol 1998;931264- 1270
PubMed Link to Article
Ernst  PBGold  BD Helicobacter pylori in childhood: new insights into the immunopathogenesis of gastric disease and implication for managing infection in children. J Pediatr Gastroenterol Nutr 1999;28462- 473
PubMed Link to Article
Smith  WBoyle  T Helicobacter pylori. Walker  WADurie  PRHamilton  RJWalker-Smith  JAWatkins  JBeds.Pediatric Gastrointestinal Disease 2nd ed. Philadelphia, Pa BC Decker Inc1991;512- 520
Rosenstock  SKay  LRosenstock  CAndersen  LPBonnevie  OJorgensen  T Relation between Helicobacter pylori infection and gastrointestinal symptoms and syndromes. Gut 1997;41169- 176
PubMed Link to Article
Gasbarrini  AFranceschi  FArmuzzi  A  et al.  Extradigestive manifestations of Helicobacter pylori gastric infection. Gut 1999;45 ((suppl 1)) I9- I12
PubMed Link to Article
Dufour  CBrisigotti  MFaretti  G  et al.  Helicobacter pylori gastric infection and sideropenic refractory anemia. J Pediatr Gastroenterol Nutr 1993;17225- 227
PubMed Link to Article
Perri  FPastore  MLeandro  G  et al.  Helicobacter pylori infection and growth delay in older children. Arch Dis Child 1997;7746- 49
PubMed Link to Article
Dale  AThomas  JEDarboe  MK  et al.  Helicobacter pylori infection, gastric acid secretion, and infant growth. J Pediatr Gastroenterol Nutr 1998;26393- 397
PubMed Link to Article
Patel  PMendall  MAKhulusi  S  et al.  Helicobacter pylori infection in childhood: risk factors and effect on growth. BMJ 1994;3091119- 1123
PubMed Link to Article
Carnicer  JBadia  RArgemì  J Helicobacter pylori gastritis and sideropenic refractory anemia. J Pediatr Gastroenterol Nutr 1997;25441
PubMed Link to Article
Vaira  DMenegatti  MSalardi  S  et al.  Helicobacter pylori and diminished growth in children: is it simply a marker of deprivation? Ital J Gastroenterol Hepatol 1998;30129- 133
PubMed
Queiroz  DMRocha  GAMendes  EN  et al.  Differences in distribution and severity of Helicobacter pylori gastritis in children and adults with duodenal ulcer disease. J Pediatr Gastroenterol Nutr 1991;12178- 181
PubMed Link to Article
Cave  DR How is Helicobacter pylori transmitted? Gastroenterology 1997;113S9- S14
PubMed Link to Article
Chang  MCWu  MSWang  HH  et al.  Helicobacter pylori stool antigen (HpSA) test: a simple, accurate and non-invasive test for detection of Helicobacter pylori infection. Hepatogastroenterology 1999;46299- 302
PubMed
Vaira  DMalfertheiner  PMegraud  F  et al. HpSA European study group, Diagnosis of Helicobacter pylori infection with a new non-invasive antigen based assay. Lancet 1999;35430- 33
PubMed Link to Article
Luzza  FOderda  GMaletta  M  et al.  Salivary immunoglobulin G assay to diagnose Helicobacter pylori infection in children. J Clin Microbiol 1997;353358- 3360
PubMed
De Pascalis  RDel Pezzo  MTardone  G  et al.  Performance characteristics of an enzyme-linked immunosorbent assay for determining salivary immunoglobulin G response to Helicobacter pylori. J Clin Microbiol 1999;37430- 432
PubMed
Gosciniak  G IgG and IgA antibodies in Helicobacter pylori infections. Zentralbl Bakteriol 1997;286494- 502
PubMed Link to Article
Atherton  JC CagA: a role at last. Gut 2000;47330- 331
PubMed Link to Article
Vakil  NAshorn  M Cost-effectiveness on noninvasive testing and treatment strategies for Helicobacter pylori infection in children with dyspepsia. Am J Gastroenterol 1998;93562- 568
PubMed Link to Article
Trevisani  LSantori  SGalvani  F  et al.  Evaluation of a new enzyme immunoassay for detecting Helicobacter pylori in feces: a prospective pilot study. Am J Gastroenterol 1999;941830- 1833
PubMed Link to Article
Nichols  LSughayer  MDegirolami  PC  et al.  Evaluation of diagnostic methods for Helicobacter pylori gastritis. Am J Clin Pathol 1991;95769- 773
PubMed
Shepherd  AJWilliams  CLDoherty  CP  et al.  Comparison of an enzyme immunoassay for the detection of Helicobacter pylori antigens in the feces with the urea breath test. Arch Dis Child 2000;83268- 270
PubMed Link to Article
Vincent  P Transmission and acquisition of Helicobacter pylori infection: evidences and hypothesis. Biomed Pharmacother 1995;4911- 18
PubMed Link to Article
Oderda  GRapa  ARonchi  B  et al.  Detection of Helicobacter pylori in stool specimens by non-invasive antigen enzyme immunoassay in children: multicentre Italian study. BMJ 2000;320347- 348
PubMed Link to Article
Braden  BPosselt  HGAhrens  P  et al.  New immunoassay in stool provides an accurate noninvasive diagnostic method for Helicobacter pylori screening in children. Pediatrics 2000;106115- 117
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Sensitivity, Specificity, and Positive and Negative Predictive Values of Noninvasive Tests*
Table Graphic Jump LocationTable 2. Clinical Features of 250 Patients Who Underwent Esophagogastroduodenoscopy for a Suspicion of Upper Gastrointestinal Tract Disease*

References

Camorlinga-Ponce  MTorres  JPerez-Perez  G  et al.  Validation of a serologic test for the diagnosis of Helicobacter pylori infection and the immune response to urease and CagA in children. Am J Gastroenterol 1998;931264- 1270
PubMed Link to Article
Ernst  PBGold  BD Helicobacter pylori in childhood: new insights into the immunopathogenesis of gastric disease and implication for managing infection in children. J Pediatr Gastroenterol Nutr 1999;28462- 473
PubMed Link to Article
Smith  WBoyle  T Helicobacter pylori. Walker  WADurie  PRHamilton  RJWalker-Smith  JAWatkins  JBeds.Pediatric Gastrointestinal Disease 2nd ed. Philadelphia, Pa BC Decker Inc1991;512- 520
Rosenstock  SKay  LRosenstock  CAndersen  LPBonnevie  OJorgensen  T Relation between Helicobacter pylori infection and gastrointestinal symptoms and syndromes. Gut 1997;41169- 176
PubMed Link to Article
Gasbarrini  AFranceschi  FArmuzzi  A  et al.  Extradigestive manifestations of Helicobacter pylori gastric infection. Gut 1999;45 ((suppl 1)) I9- I12
PubMed Link to Article
Dufour  CBrisigotti  MFaretti  G  et al.  Helicobacter pylori gastric infection and sideropenic refractory anemia. J Pediatr Gastroenterol Nutr 1993;17225- 227
PubMed Link to Article
Perri  FPastore  MLeandro  G  et al.  Helicobacter pylori infection and growth delay in older children. Arch Dis Child 1997;7746- 49
PubMed Link to Article
Dale  AThomas  JEDarboe  MK  et al.  Helicobacter pylori infection, gastric acid secretion, and infant growth. J Pediatr Gastroenterol Nutr 1998;26393- 397
PubMed Link to Article
Patel  PMendall  MAKhulusi  S  et al.  Helicobacter pylori infection in childhood: risk factors and effect on growth. BMJ 1994;3091119- 1123
PubMed Link to Article
Carnicer  JBadia  RArgemì  J Helicobacter pylori gastritis and sideropenic refractory anemia. J Pediatr Gastroenterol Nutr 1997;25441
PubMed Link to Article
Vaira  DMenegatti  MSalardi  S  et al.  Helicobacter pylori and diminished growth in children: is it simply a marker of deprivation? Ital J Gastroenterol Hepatol 1998;30129- 133
PubMed
Queiroz  DMRocha  GAMendes  EN  et al.  Differences in distribution and severity of Helicobacter pylori gastritis in children and adults with duodenal ulcer disease. J Pediatr Gastroenterol Nutr 1991;12178- 181
PubMed Link to Article
Cave  DR How is Helicobacter pylori transmitted? Gastroenterology 1997;113S9- S14
PubMed Link to Article
Chang  MCWu  MSWang  HH  et al.  Helicobacter pylori stool antigen (HpSA) test: a simple, accurate and non-invasive test for detection of Helicobacter pylori infection. Hepatogastroenterology 1999;46299- 302
PubMed
Vaira  DMalfertheiner  PMegraud  F  et al. HpSA European study group, Diagnosis of Helicobacter pylori infection with a new non-invasive antigen based assay. Lancet 1999;35430- 33
PubMed Link to Article
Luzza  FOderda  GMaletta  M  et al.  Salivary immunoglobulin G assay to diagnose Helicobacter pylori infection in children. J Clin Microbiol 1997;353358- 3360
PubMed
De Pascalis  RDel Pezzo  MTardone  G  et al.  Performance characteristics of an enzyme-linked immunosorbent assay for determining salivary immunoglobulin G response to Helicobacter pylori. J Clin Microbiol 1999;37430- 432
PubMed
Gosciniak  G IgG and IgA antibodies in Helicobacter pylori infections. Zentralbl Bakteriol 1997;286494- 502
PubMed Link to Article
Atherton  JC CagA: a role at last. Gut 2000;47330- 331
PubMed Link to Article
Vakil  NAshorn  M Cost-effectiveness on noninvasive testing and treatment strategies for Helicobacter pylori infection in children with dyspepsia. Am J Gastroenterol 1998;93562- 568
PubMed Link to Article
Trevisani  LSantori  SGalvani  F  et al.  Evaluation of a new enzyme immunoassay for detecting Helicobacter pylori in feces: a prospective pilot study. Am J Gastroenterol 1999;941830- 1833
PubMed Link to Article
Nichols  LSughayer  MDegirolami  PC  et al.  Evaluation of diagnostic methods for Helicobacter pylori gastritis. Am J Clin Pathol 1991;95769- 773
PubMed
Shepherd  AJWilliams  CLDoherty  CP  et al.  Comparison of an enzyme immunoassay for the detection of Helicobacter pylori antigens in the feces with the urea breath test. Arch Dis Child 2000;83268- 270
PubMed Link to Article
Vincent  P Transmission and acquisition of Helicobacter pylori infection: evidences and hypothesis. Biomed Pharmacother 1995;4911- 18
PubMed Link to Article
Oderda  GRapa  ARonchi  B  et al.  Detection of Helicobacter pylori in stool specimens by non-invasive antigen enzyme immunoassay in children: multicentre Italian study. BMJ 2000;320347- 348
PubMed Link to Article
Braden  BPosselt  HGAhrens  P  et al.  New immunoassay in stool provides an accurate noninvasive diagnostic method for Helicobacter pylori screening in children. Pediatrics 2000;106115- 117
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 19

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

Users' Guides to the Medical Literature
Clinical Scenario

The Rational Clinical Examination
Peptic ulcer disease and GERD most commonly cause organic upper gastrointestinal symptoms. Peptic...