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Diagnostic Accuracy of Tests in Pediatric GastroesophagealReux Disease

Rachel J. van der Pol, MD1,*, Marije J. Smits, MSc1,*, Leonie Venmans, PhD3, Nicole Boluyt, MD, PhD2,

Marc A. Benninga, MD, PhD1, and Merit M. Tabbers, MD, PhD1

Objective To systematically review the literature evaluating the diagnostic accuracy of commonly used diagnostictests over conventional history taking and physical examination in children #18 months and >18 months suspectedof gastroesophageal reflux disease (GERD).Study designWe searched Medline, Embase, and the Cochrane database for studies assessing the diagnosticaccuracy of pH-metry, pH-impedance, esophagogastroscopy, barium contrast study, scintigraphy, and empiricaltreatment as diagnostic tools. Quality was assessed according to Quality Assessment of Studies of Diagnostic Ac-curacy Included in Systematic Reviews criteria.Results Of the 2178 studies found, 6 studies were included, containing 408 participants (age 1 month-13.6 years)and 145 controls (age 1 month-16.9 years). Studies included children with GERD symptoms; 1 included an atypicalpresentation. In all the studies, the diagnostic accuracy of pH-metry was investigated, and in 2 studies esophago-gastroscopy was investigated as well. Sensitivity and specificity were calculated in 3 studies. The range of reported

sensitivity and specificity was broad and unreliable because of poor methodological quality according to Quality As-sessment of Studies of Diagnostic Accuracy Included in Systematic Reviews criteria and inadequate study design.ConclusionDiagnostic accuracy of tests in children suspected of GERD remains unclear and implications forpractice are hard to give. There is an urgent need of well-designed randomized controlled trials where the effectof treatment according to specific signs and symptoms will be compared with the effect of treatment based onthe results of additional diagnostic tests, for patient relevant outcomes. (J Pediatr 2013;162:983-7).

Gastroesophageal reflux (GER) is a physiologic process. Regurgitation occurs in over 70% of infants multiple timesa day, but it tends to disappear by the age of 12-14 months. 1,2 Gastroesophageal reflux disease (GERD) is definedand diagnosed when GER leads to troublesome symptoms and/or complications.3 In 2009, GERD prevalence was es-

timated to be 12.3% in North American infants and 1% in older children. 4 Troublesome symptoms in infants may include

excessive crying, back arching, regurgitation, and irritation around feedings; these could be regarded as nonspecific. In childrenand mainly in adolescents, heartburn is the more specific symptom occurring in GERD. Though complaints are often mild, theyare troublesome and may have a significant impact on the wellbeing of the child and family life. Moreover, complications asesophagitisand hematemesis, failure to thrive, or apparent life threatening events (ALTE) have to be prevented wheneverpossible.3,5,6

Diagnosing GERD in pediatric patients is difficult because no gold standard exists, and not one combination of symptoms isconclusive. Currently, the diagnosis of GERD is based on history and physical examination. This approach might be considered

as the gold standard. However, there is a need to quantify GERD in a more objective way because the GERD diagnosis issubject to free interpretation and is probably overdiagnosed.7 It may mimic disorders such as cows milk allergy and eosino-philic esophagitis.8,9

Tests for GERD can be divided into 2 categories: tests with the ability to measure reflux events (pH-metry, pH-impedance,

barium contrast studies, and scintigraphy) and tests to detect the consequences of reflux events (esophagogastroscopy).

Themost widespread test used to quantify GERD is 24-hour pH-metry. A pH < 4 in the esophagus is generallyconsidered as anacid reflux episode.3 Acid exposure is expressedas the reflux index (RI, % of time a pH < 4 was measured), forwhich currently noevidence based pediatric normal values exist. The European Society for Pediatric Gastroenterology, Hepatology, and Nutritionand North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines consider a RI >7%as abnormal, a RI


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In infants, however, frequency of feeds and bufferingcapacities of milk may confound outcomes of pH-metry stud-ies.10 In addition to 24-hour pH-metry, 24-hour

pH-impedance measurement (pH-impedance) was devel-oped.11 Equipped with a pH sensor and multiple electrodepairs, it measures the conductivity of liquid, gas, or mixedcontents in the esophagus and is able to detect non-acidand alkaline reflux besides acid reflux.12,13

Barium contrast studies consist of a series of radiographs

of the esophagus and stomach using a barium emulsion totrack swallows and possible reflux, which sometimes revealstructural anatomic causes underlying GERD.14 In gastro-esophageal scintigraphy, patients consume a 99technetium la-beled meal prior to start of the scans, and postprandial reflux

becomes visible when labeled stomach contents move up-wards in the esophagus.3

Reflux esophagitis, one of the complications of GERD, canbe measured by esophagogastroscopy. This enables both mac-roscopic and microscopic grading of the esophageal wall. Todate, there are insufficient data to support the use of histology

in diagnosing GERD. Currently, themain reason fortaking bi-opsies is to exclude other diseases causing esophagitis such aseosinophilic esophagitis, Crohns disease, and infections.3,15

Finally, a trial with an antireflux agent may be used to di-agnose GERD. A proton pump inhibitor (PPI) is often theagent of choice and an empiric trial of 2-4 weeks is common. 3

Data on sensitivity and specificity is scarce, both in adults andchildren, amplified by the fact that GERD symptoms may im-prove spontaneously or respond by a placebo effect.3

The accuracy of the above-mentioned tests is unclear, and,

therefore, it is questionable if these more invasive and expen-sive tools should be used. We carried out a systematic review

to evaluate the accuracy of pH-metry, pH-impedance ofesophagogastroscopy, barium contrast study, scintigraphy,and diagnostic treatment compared with conventionalhistory and physical examination when diagnosing GERD.

Methods

A clinical librarian searched Medline, Embase, and theCochrane Database of systematic reviews (SR) electronic da-tabase for SRs, and clinical studies from inception to May2012. The key words used to describe the study population

were esophagogastroscopy, pH-metry, pH-impedance,

gastric emptying scintigraphy, barium radiography,GER, GERD, heartburn, extraesophageal symptoms,reflux esophagitis, infant, child, and adolescent(medical subject headings and all fields). No language restric-tion was applied. Reference lists of reviews and included

studies were searched for additional studies. The full searchstrategy is available from the authors.

Two reviewers independently selected the abstracts of iden-tified studies for suitability. Inclusion criteria were: (1) the

study was an SR or clinical study; (2) children were aged 0-18 years presenting with signs and symptoms (through historyor clinical examination) suggestive of GERD; (3) the aim of the

study was to evaluate the diagnostic accuracy of esophagogas-

troscopy, pH-metry, pH-impedance (symptom index, symp-

tom sensitivity index, and symptom association probabilityhad to be given), scintigraphy, barium swallow/radiograph ofesophagus/stomach, or diagnostic treatment (at least 1 weekof treatment compared with history and physical examina-

tion); and (4) the study had to use a control group. Exclusioncriteria were: (1) no definition of GERD; (2) patients who hada disease frequently related to GERD (eosinophilic esophagitis,malformation of the esophagus, [congenital] hernia diaphrag-matica, achalasia, cystic fibrosis, gastric paresis, systemic scle-rosis, children with neurologic impairment, cows milk

allergy, and rumination syndrome); (3) patients who hadundergone surgical therapy; and (4) children who were treatedfor GERD during history and physical examination or prior tothe investigated diagnostic test or vice versa (and the GERDtherapy was not the investigated diagnostic tool).

All potentially relevant studies and the studies for which

the abstracts did not provide sufficient information for in-or exclusion were retrieved as full articles.

Two reviewers assessed methodological quality of all iden-

tified studies by the Quality Assessment of Studies of Diagnos-tic Accuracy Included in Systematic Reviews (QUADAS)checklist.16 Because the revised QUADAS checklist was pub-lished after the quality assessment process took place, wewere not able to incorporate this newer checklist.17 The re-vised QUADAS checklist offers additional and improved fea-

tures and has improved in distinguishing between bias andapplicability and is capable of rating risk of bias. From theoriginal standardized list, we choose 11 items (scored yes,no, or unclear) that could optimally differentiate for meth-

odological quality (Table I; available at www.jpeds.com).Calculations on summary scores are not provided because

they ignore the importance of individual items and becausecut-off values on what is a good or bad score will bearbitrarily determined; these results may be misleading.16 Ingeneral, the more items answered with yes, the highermethodological quality is presumed.

Structured data extraction was performed by 2 reviewersindependently. Data derived from included articles con-tained items such as author and year of enrollment, diagnos-tic method, study setting, methods, patient characteristics,number of participants and controls, index test and execu-

tion, sensitivity, and specificity. Because symptom presenta-tion and pathophysiology is different in infants (#18

months) and children, we choose to extract data, if possible,for infants and children separately. If disagreement between

the 2 reviewers existed, consensus was formed, or a third re-viewer (M.T.) made the final judgment.

Results

The search generated 2178 studies, of which 106 met ourinclusion criteria (Figure; available atwww.jpeds.com). Novalid SR was encountered. After retrieving the full-text

articles, 100 articles were excluded because of the lack ofa control group, comparison between 2 diagnostic tests,

and, therefore, no comparison with history and physical

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examination, use of antireflux medication during the study,and/or 1 of the other inclusion and/or exclusion criteria(Figure).

The 6 studies included were all conducted in tertiary cen-ters from Europe (Italy, Spain, and Belgium). Data from 408participants (age 1 month-13.6 years) and 145 controls (age 1month-13.6 years) were included. Because of the heterogene-ity, especially for symptom presentation of GERD betweenthe included studies with regard to all participants, diagnos-

tic, and outcome measures, a meta-analysis was not possible,and all studies are, therefore, discussed separately. Studycharacteristics are presented inTable II (available atwww.

jpeds.com).

Five studies included children referred for symptoms andsigns of GERD that could be regarded as troublesome (eg, re-gurgitation, vomiting, hematemesis, weight failure, and re-current pneumonia),18-22 and 1 study included childrenwith ALTE.23 The latter study was included because ALTEwas regarded as a possible presentation of GERD. This studyfound no relationship between pH drops and the onset of ap-

neas, the latter being the possible cause of ALTE.All 6 included studies assessed the diagnostic valueofpH-

metry (5 by glass electrode and 1 antimone electrode),22 and2 studies assessed the diagnostic value of esophagogastro-scopy (macroscopy and histology) as well.21,22 Cut-off valuesfor pH-metry were defined differently as 1or 2 SDs of the

mean of the control groupin 4 studies.18-21 In 1 study, nocut-off values were defined.23 In the last study, cut-off valueswere defined without further reference to literature or expla-nation.22 In 2 studies assessing esophagogastroscopy, macro-

scopic criteria were defined differently. Histology was gradedin both studies equally as described in Table II.

In 3 studies, it was possible to calculate sensitivity for pH-metryof the extracted data (Table III; available at www.jpeds.com).19,20,22 Sensitivity ranged from 41%-81%. Of the 2studies performing esophagogastroscopy, sensitivity wascalculated for macroscopy from the extracted data.21,22

Both sensitivity and specificity could be calculated forhistology.21,22 Hence, no studies were retrieved fulfillingour inclusion criteria assessing impedance, scintigraphy,barium swallow/radiograph of esophagus/stomach, and/ora diagnostic treatment.

Results of the methodological quality are presented in

Table I. In all included studies, the patient groups were

representative for those patients who would receivea diagnostic test in clinical practice. Furthermore, selectioncriteria were clearly described, and execution of the indextest was described in sufficient detail to permit replication.Because GERD signs and symptoms are not distinctive and,

therefore, difficult to diagnose, it was unclear if the referencestandard (signs and symptoms) used in the 6 includedstudies, was correctly classifying the target condition.However, in all studies, except 1,18 signs and symptomswere clearly described. Only in the study assessing ALTE and

GER, the time period between presentation of the signs and/or symptoms (ALTE) and time of measurement was

reported, which was 24-48 hours.

23

In the 2 studies assessing

histology, assessors were blinded, but blinding procedure formacroscopy was unclear.21,22 For pH-metry, outcomeassessors were blinded for the clinical profile of the

included patients in 3 studies. Also, outcome assessors wereuninformed about the pH-metry results when interpretingthe results of history taking and physical examination.20,21,23

In 2 studies results were assessed unblinded,18,19 and in 1study this was unclear.22 Neither uninterruptible norintermediate test results were reported; an explanation of

withdrawals was not reported. Surprisingly, withdrawalswere not described in any of the included studies.

Discussion

This systematic review clearly shows that, despite a largenumber of publications, there is a lack of high quality studies

of the diagnostic accuracy compared with the current defini-tion of GERD, which is based on history and physical exam-ination. Therefore, the accuracy of tests in children #18months and >18 months suspected of GERD remains un-

clear.Nearly all studies investigating theaccuracy of pH-metry

used glass electrode catheters, 18-21,23 but ion sensitive fieldeffect transistor catheters are preferred nowadays becauseof themost accurate in vivo measurements of acid exposuretime.24 In the study that included children with ALTE, the

absence of a relationship between apneas and pH dropsmight be due to the fact that pH-metry can only detectacid reflux.25 Apneas might not be triggered by acid GERbut could be due to nonacid reflux or reasons other than

GERD. Considering the low overall amount of detected pHdrops below 4 (116 in total in 18 children, measured during

1 night), the question arises whether this population sufferedfrom GERD at all. Furthermore, literatureisinconsistent re-garding the association of GER and ALTE,26 and pathologiccentral and obstructive apnea.27,28 Up until now, it is notconvincingly shown that these are related.29

Although pH-impedance is increasingly popular,30,31 oursearch did not retrieve any suitable articles on the accuracyof pH-impedance in children. The main reason is thatpH-impedance is frequently studied with other tests and,therefore, not compared with history and physical examina-tion, which is 1 of our inclusion criteria. pH-impedance is

currently the only tool assessing acid, weakly acid, and alka-

line reflux, proximal extent and nature of the reflux episodesbeing gas, liquid, or mixed. These types of GER are thoughtto play an important role in childhood GERD, and it ap-pears that using pH-impedance adds significant benefit incorrelating symptoms and GER in infants.32 The European

Society for Pediatric Gastroenterology, Hepatology, and Nu-trition and North American Society for Pediatric Gastroen-terology, Hepatology, and Nutrition guidelines recommend,partly based on expert opinion, to consider pH-impedance

in persisting irritability in infants, despite conservative mea-sures, in children older than 18 months with regurgitationand vomiting, or in childrenwith ALTE with possible symp-

toms and signs of GERD.

33

The European Medical Agency

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recommends to perform pH-impedance in therapeutic stud-ies totruly quantify and monitor symptom association re-sults.34 However, whether pH-impedance can be

considered as a diagnostic tool with a proven diagnostic ac-curacy over history and physical examination has never beenproperly investigated.

In studies investigating the value of esophagogastroscopyfor GERD, macroscopic criteria were defined differently,but histology was equally graded in both studies. Indeed, en-

doscopy can effectively pinpoint the existence of macroscopicesophagitis, which is a possible but rare complication ofGERD in younger children. It is still under debate, however,when to use this invasive technique in children because the

existence of esophagitis correlates poorly with symptoms, es-pecially in infants.21,22 For histology, both included studiesshowed a relative high sensitivity and specificity in diagnosing

GERD, and multiple studies showed inconsistent correlationbetween histology and GERD symptoms.35 No evidence existswhy these 2 poorly correlate; 1 of the many explanations isthe patchy distribution of lesions of reflux esophagitis.

It could be argued that questionnaires, developed to mea-sure pediatric GERD, could be a better diagnostic test toquantify GERD. However, the best-validated questionnaire,the Infant-GER Questionnaire Revised, has a high sensitivitybut through its low specificity, it is still advised to use addi-tional invasive testing.6 In this study, no attempt was made to

distinguish between symptomatic infants with and withoutGERD; therefore, it is difficult to implement this tool in clin-ical practice. In clinical practice, diagnosis of GERD is basedon the presence of bothersome symptoms and/or complica-

tions. However, because this is the only tool quantifyingsymptoms of infant GERD, it is a useful instrument to mea-

sure change in symptoms, for example, in research settings.Reported outcomes in the included studies cannot guide

clinical practice. Although many reports exist giving guid-ance on which test to perform in clinical practice,32,36-38

the evidence based value of diagnostic tools remains unclear,

and the question whether these more invasive and expensivetools should be used remains unanswered.

In adults, it is recommended to perform esophagogastro-scopy when troublesome dysphagia is present or when anempiric trial of PPIs failed to diminish complaints after 1or 2 months. When no esophagitis is present, pH-metry

and pH-impedance should be considered.39 This is especially

of value in patients with atypical GERD symptoms, otherthan the classic heartburn and regurgitation.31 For adults,normal values for pH-metry as well as for pH-impedanceare firmly established. Moreover, enhanced intercellularspace dilatation on histology can be an indication of noner-

osive (nonacidic) reflux disease and may, therefore, be usefulin diagnosing GERD refractory to PPI therapy in adults.39

However, even in adults, this is still fully under investigation,and future studies will elaborate if medical agents interferingwith dilated intracellular spaces need to be developed. Ex-

trapolating adult data toward children and infants mightconfound for multiple reasons, mainly because of the differ-

ence in GERD symptoms in younger children.

It could be hypothesized that if GERD symptoms are pres-ent in an infant or child, but no warning signals like hema-

temesis or failure to thrive exist, further diagnostic testingis unnecessary. A thorough work-up is warranted when dif-ferential diagnosis of signs and symptoms of GERD containsany cause other than GERD that requires further examina-

tion. The test to be used should depend on each specific sit-uation. For example, when food allergies or eosinophilic

esophagitis are suspected, these should be excluded before as-suming GERD is present. Especially with the latter, a condi-tion with an increasing incidence worldwide,9,40 symptompresentation is not distinguishable from classic GERD in in-fants.41 In older children, dysphagia is often present. How-ever, diagnosis can only be made through endoscopy.

Alternatively, the decision to perform further diagnosticwork-up and the choice of the diagnostic tool used couldalso be approached from a therapeutic perspective. Currenttherapy of GERD consists of conservative measures andacid reducing agents. In common practice, these agents are

frequently prescribed without a prior pH-metry. Therefore,

the therapeutic consequences of additional tests will, inmost cases, be very limited. Even if reflux esophagitis is foundduring esophagogastroscopy, GERD therapy will still focuson acid suppression. Only if signs and symptoms persist dur-ing acid suppression or, as previously mentioned, a diagnosis

other than GERD is considered, additional diagnostic testingcould be considered.

Research of high quality in this patient population is chal-lenging, amplified by the difficulties of recruiting proper re-

search groups and defining clear selection criteria. Apartfrom ethical dilemmas of putting children through possiblyunnecessary invasive procedures, parents are not likely to

give permission to subject their child to such research.42Most patients eligible forsuch studies areoften missedbecausemost of them take place in tertiary centers, whereas the major-ity of GERD related problems are seen in primary care. n

The authors would like to thank Arnold Leenders for all his effort inconducting the search strategy.

Submitted for publication Jun 25, 2012; last revision received Aug 23, 2012;

accepted Oct 16, 2012.

Reprint requests: Rachel J. van der Pol, MD, Department of Pediatric

Gastroenterology and Nutrition, Emma ChildrensHospital, AcademicMedical

Center, Meibergdreef 9, C2-312, 1105 AZ Amsterdam, The Netherlands. E-

mail:[email protected]

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2407-15.


Diagnostic Accuracy of Tests in Pediatric Gastroesophageal Reflux Disease 987
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500052741.pdfhttp://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500052741.pdfhttp://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500052741.pdfhttp://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500052741.pdf


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Table I. Summary of methodological quality of included studies according to the QUADAS checklist

Boix1980

Da Dalt1989

Cucchiara1990

Kahn1990

Cucchiara1993

Ravelli2006

Was the spectrum of patients representative of the patients who wouldreceive the test in practice?

1 1 1 1 1 1

Were selection criteria clearly described? 1 1 1 1 1 1Is the reference standard likely to correctly classify the target condition? 0 0 0 0 0 0Is the time period between reference standard and index test short enough

to be reasonably sure that the target condition did not change betweenthe 2 tests?

0 0 0 1 0 0

Was the execution of the index test described in sufficient detail to permitreplication of the test?

1 1 1 1 1 1

Was the execution of the reference standard described in sufficient detail topermit its replication?

2 1 1 1 1 1

Were the index test results interpreted without knowledge of the results ofthe reference standard?

2 2 1 1 0/0/1* 1/0/1*

Were the reference standard results interpreted without knowledge of the

results of the index test?

2 2 1 1 0/0/1* 1/0/1*

Were the same clinical data available when test results were interpreted aswould be available when the test is used in practice?

1 1 1 1 1 1

Were not interpretable/intermediate test results reported? 2 2 2 2 2 2Were withdrawals from the study explained? 2 2 2 2 2 2

1, yes; 2, no; 0, unclear.

*pH-metry/histology/macroscopy.

Figure. Flowchart: result of search strategy.


987.e1 van der Pol et al


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Table II. Continued

Study Diagnostic method/setting

Number of subjects(mean/median,

age range) Index (test parameters)Method of execution

of index test Cases (refer

Ravelli200622

pH-metry (antimony)Endoscopy (macroscopy/histology)Pediatric gastroenterology

clinic

I: 48(3.95 y, 2 mo-11.9 y)C: 22

(5.85 y, 1-16.9 y)

Percentage of time pH < 4Number of refluxes pH < 4Number of refluxes >5 min

Duration of longest reflux episodePercentage of time pH < 4: mild

(5%-10%), moderate (10%-20%)and severe (>20%)

Aberrant macroscopy: erosivelesions

Aberrant histology: basal zone

hyperplasia, papillar elongation,mucosal erosions, dilatationof interpapillary vascular spaces;increased number of neutrophils,eosinophils and lymphocytes,erosions or ulcerations and

granulation tissue.

pH-metry positioned between9th and 10th dorsal vertebra

and fluoroscopyEsophagogastroduodenoscopy:

(under sedation). Standard

scopes were used, outerdiameter depending on sizeand age. Biopsies: n = 2-4,minimal 1.5 mm thickness,3-5 cm above the Z line.

History of: vomitin

epigastric pain,and/or dysphagbehavioral symfussiness, back

meals; n = 5; renocturnal coughrecurrent pneumn = 17.

C, control group; IBD, irritable bowel disease; IBS, irritable bowel syndrome; I, intervention group; LES, lower esophageal sphincter; NSAID, nonsteroidal anti-inflammatory drug.

987.e3

vanderPoletal


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Table III. Sensitivity and specificity

Study Method

Number of Patients withGERD/number of Patients

without GERD (based on signsand symptoms at presentation) Sens Spec

Boix-Ochoa 198018 pH-metry 44/20 Unable to calculate sens or spec.No Pvalues or cut-off values given. Final

score calculated out of different components

was highest in the disease group.Da Dalt 198919 pH-metry 111/14 positive pH-metry: n = 45

Sens = 45/111 = 41%Unable to calculate spec. Values of

controls used as normal values.Cucchiara 199020 pH-metry 114/63 RI parameter:

22 (14.6% GERD n = 45; 21.7% GERD +oesophagitis n = 69) normal RI.

Sens = 92/114 * 100 = 81%Duration >5 min reflux parameter:34 (29.17% GERD n = 45; 30.34% GERD +

oesophagitis n = 69) normal duration.

Sens = 80/114 *100 = 70%

Unable to calculate spec. Values ofcontrols used as normal values.Therefore, Spec will always be 100%.

Kahn 199023 pH-metry 10/10 Unable to calculate sens or spec. NoPvaluesor cut-off values given. ALTE versus controlgroup no statistical difference in numberreflux episodes, lowest pH value, durationof longest reflux episode and drops in pH.

Cucchiara 199321

pH-metryendoscopy

81/16 pH-metry:Unable to calculate sens for pH metry. No

cut-off values.Macroscopy:61.9% = 44 of patients with microscopic

esophagitis had normal macroscopicresult. Abnormal: 81-44 = 27

Sens = 27/81 *100 = 33%Histology:n = 10 patients had normal histologic result.

Abnormal = 81-10 = 71Sens = 71/81 *100 = 88%

pH-metry:Unable to calculate spec for pH metry.

No cut-off values.Macroscopy:Unable to calculate spec for macroscopy.

No data on controls given.Histology:

Abnormal histologic changes wereabsent in controls.

Spec = 16/16 * 100 = 100%

Ravelli 2006 pH-metry

endoscopy

48/22 pH-metry:

Percentage of time pH < 4: (15 of 29patients had a positive RI (5.7 < RI > 36).

Sens = 15/29 * 100 = 52%

Macroscopy:7 of 48 GERD patients had macroscopicesophagitis

Sens = 7/48 * 100 = 15%

Histology:40 of 48 patients had histologic esophagitisSens = 40/48 * 100 = 83%

pH-metry:

No controls underwent pH metryMacroscopy:Unable to calculate spec since results of

controls are not givenHistology:In all controls (n = 22), histology was

normal

Spec = 22/22 * 100 = 100%

Sens, sensitivity;Spec, specificity.


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