BAGACAY, Julius

BASTINEN, Manice
BETANSOS, Kristine Mae
CO, Catherine
SAN JUAN, Chrizarah
SAN PEDRO, Mary Grace

CRITICAL APPRAISAL - DIAGNOSTICS

Case Scenario

Cc: Prenatal check up

HPI:

O.M.G., 25 year old G1P0 tested positive for pregnancy came in for follow up pre-natal check
up. Her LMP was November 5, 2013. She usually feels morning sickness symptoms upon awakening but
was relieved by food intake. There were no uterine contractions, no vaginal bleeding and abdominal pain.
Her past medical history was unremarkable except for VSD. She does not recall completion of
immunization except for TT1. Her younger sister has a history of Tetralogy of Fallot. She worries
because she has been exposed to her housemaid who has been diagnosed with measles. She would like to
know if this could affect her baby so she wanted to have her baby checked by ultrasound for any heart
anomalies because she read in the internet that an exposure to measles virus could result to congenital
heart defects. Being the doctor in charge, you would like to know what particular diagnostic test is
appropriate for her case. You searched the PUBMED and found an article entitled:

J. M. MARTI´NEZ, O. GO´ MEZ, M. BENNASAR, A. OLIVELLA, F. CRISPI, B. PUERTO

and E. GRATACO´ S The ‘question mark’ sign as a new ultrasound marker of tetralogy of Fallot in
the fetus. Ultrasound Obstet Gynecol 2010; 36: 556–560

You have not actually read the article yet so you have some refreshments served for O.M.G while
you read the article and decide if it provides a direct answer to the clinical question you ask, appraise
validity using the validity guides, appraise the results of the study, assess its applicability to your specific
patient, and calculate patient-specific results. How will you present the information to O.M.G?

ANSWER KEY:

Clinical question:
Among fetuses with tetralogy of fallot, is there an ultrasound finding that is diagnostic of TOF prenatally?

P Fetuses with congenital cardiovascular anomalies such as TOF, VSD, Valvular problems
I Ultrasound screening – presence of question mark sign prenatally
C Post-natal evaluation or autopsy
O Accuracy in detecting TOF
M Prospective study

Journal Appraisal
Title: The ‘question mark’ sign as a new ultrasound marker of tetralogy of Fallot in the fetus
Author: J. M. MARTI´NEZ, O. GO´ MEZ, M. BENNASAR, A. OLIVELLA, F. CRISPI, B. PUERTO
and E. GRATACO´ S

Type of study: Prospective study

Duration: 5 year study (January, 2004 – January, 2009)
Sample population: 3998 fetuses

Data Results:
Diagnosed with TOF = 42
 Classical TOF (with pulmonary stenosis) = 29
o (+) question mark = 16/29
 TOF with pulmonary atresia = 9
o (+) question mark = 8/9
 TOF with absent pulmonary valve syndrome = 4
o (+) question mark = 0/4
Terminated pregnancy as requested by the mother = 24/42

What is the question mark sign?

The question-mark sign was defined, in a fetus in cephalic position with posterior spine, as a typical
sonographic shape of the ascending aorta and aortic arch in axial planes, almost at the level of the three
vessels and trachea view, showing a very enlarged and dilated aorta, with a striking shape resembling a
question mark.

The ‘question-mark’ sign in a case of classical Figure 2 The ‘question-mark’ sign in a case of
tetralogy of Fallot. The aorta is significantly larger tetralogy of Fallot with pulmonary atresia
than the pulmonary trunk, and resembles a
question mark in shape. A, aorta; P, pulmonary
artery.

1. Was the diagnostic test evaluated in a representative spectrum of patients (like those in whom it
would be used in the practice?)
Yes. The subjects included are fetuses who showed presence of risk factors for CHD, from 12 weeks,
fetal age that is already visible in ultrasound, to 40 weeks AOG on the day of examination. Diagnosis
 of TOF was done via echocardiography and Color Doppler assessment by an experienced
obstetrician. The mothers were in the age range of 16-40 y/o.

2. Was the reference standard applied regardless of the index test result?
Yes. It was stated in the study that all patients were evaluated post-natally by a pediatric cardiologists
or by an autopsy in case of termination of pregnancy or perinatal death.

3. Was there an independent, blind comparison between the index test and an appropriate
reference (‘gold’) standard of diagnosis?
Yes. Experienced obstetricians and pediatric cardiologists were assigned to do the screening and
evaluation of the presence of congenital cardiovascular anomaly that may result to CHD. In each
diagnosis of TOF, 3 experienced examiners will reach a consensus on the presence or absence of
TOF. As have been mentioned, post-natal evaluation by a pediatric cardiologist or by autopsy as the
reference standard of diagnosis was applied in all patients in the study.

I. What were the results?

Are the test characteristics presented?
w/ TOF W/o TOF
(+) test with 24 1 25
question mark

(-) test with 18 3955 3973

question mark

42 3956 3998

Computations Results
Sensitivity = A/(A+C) * 100% 57%
= 24/42 = 0.57 x 100%
Specificity = D/(B+D) * 100% 99.97% or 100%
= 3955/3956 = 0.9997 x 100%
Accuracy rate = (A+D)/(A+B+C+D) * 100% 99.5%
= 3979/3998 = 0.995 x 100%
(+) predictive value (PPV) = A/(A+B) * 100% 96%
= 24/25 = 0.96 x 100%
(-) predictive value (NPV) = D/(C+D) * 100 99.5%
3955/3973 = 0.995 x 100%
Likelihood ratio (+) (LRP) = Sn/ (1- Sp) 1900
= 0.57/ (1 – 0.9997)
Likelihood ratio (-) (LRN) = (1-Sn)/Sp 0.43
(1-0.57)/0.9997 = 0.43
Prevalence rate = (A+C) / (A+B+C+D) 1%
42/3998 = 0.01 x 100%

Set values =
Diagnostic Threshold – 25%
Treatment Threshold – 75%
Pretest Probability = 50%
Post-test probability = 100% (based on Nomogram)

Hence, the presence of the question mark sign during a prenatal ultrasound screening highly suggests
presence of tetralogy of fallot. It can be used to improve the prenatal diagnosis of TOF. Moreover, based
on the findings of the study, it is particularly associated with TOF with pulmonary atresia and that it was
never observed in cases with right aortic arch, in which the aorta always follows a straight anteroposterior
trajectory due to its right disposition with respect to the trachea. It is also less likely to be found in TOF
with either pulmonary stenosis or absent pulmonary valve.

References
Congenital Heart Defects and Physical Activity. (Sep 15,2011). American Heart Association . Retrieved
from
http://www.heart.org/HEARTORG/Conditions/CongenitalHeartDefects/CareTreatmentforCongenitalHear
tDefects/Congenital-Heart-Defects-and-Physical-Activity_UCM_307738_Article.jsp
Nelson’s Textbook of Pediatrics 18th Edition
Preparing Children for Surgery. (Jan 24,2011). American Heart Association .
Schwartz Principles of Surgical Therapy 9th edition

PRECEPTORIAL GUIDE

1. The students are given with a case scenario and journal to be appraised. Ask students to discuss
information and salient features and to come up with differential diagnosis.

“Identify the salient features of the case?”

“What is your primary impression?” Differrentials?

2. Ask students to make a foreground question and clinical question of the case and the journal. Is the
objective of the study similar to clinical dilemma?

Clinical question:
Among fetuses with tetralogy of fallot, is there an ultrasound finding that is diagnostic of TOF prenatally?

P Fetuses with congenital cardiovascular anomalies such as TOF, VSD, Valvular problems
I Ultrasound screening – presence of question mark sign prenatally
C Post-natal evaluation or autopsy
O Accuracy in detecting TOF
 M Prospective study

3. Ask students of Pre-test probability, Diagnostic threshold and Therapeutic threshold. Ask students
what factors determine the diagnostic and therapeutic threshold.

Diagnostic Threshold – 25%

Treatment Threshold – 75%
Pretest Probability = 50%

Ask students of primary and secondary validity guides.

Was the diagnostic test evaluated in a representative spectrum of patients (like those in whom it
would be used in the practice?) Ask students about exlusion and inclusion criteria and
representativeness.

Yes. The subjects included are fetuses who showed presence of risk factors for CHD, from 12 weeks,
fetal age that is already visible in ultrasound, to 40 weeks AOG on the day of examination. Diagnosis
of TOF was done via echocardiography and Color Doppler assessment by an experienced
obstetrician. The mothers were in the age range of 16-40 y/o.

Was the reference standard applied regardless of the index test result?
Yes. It was stated in the study that all patients were evaluated post-natally by a pediatric cardiologists
or by an autopsy in case of termination of pregnancy or perinatal death.

Was there an independent, blind comparison between the index test and an appropriate
reference (‘gold’) standard of diagnosis?
Yes. Experienced obstetricians and pediatric cardiologists were assigned to do the screening and
evaluation of the presence of congenital cardiovascular anomaly that may result to CHD. In each
diagnosis of TOF, 3 experienced examiners will reach a consensus on the presence or absence of
TOF. As have been mentioned, post-natal evaluation by a pediatric cardiologist or by autopsy as the
reference standard of diagnosis was applied in all patients in the study.

Were the methods for performing the test described in sufficient detail to permit replication?

4. Ask the students to summarize the validity of the study.

5. Ask students to compute for sensitivity, specificity, positive predictive value, negative predictive
value, Likelihood ratio. Give the students 30 mins to compute for the needed values and draw them in
a 2 x 2 table.

6. Ask students the results of their computation and the plotted post test probability on a nomogram.

7. Ask students if the results can help them in caring for their patients.
 STUDENT’S EVALUATION FORM

Name of Preceptor: ______________________________________________________

______________________________________________________-

Score the following students based on the ff ratings:

5 = very good 4 = good 3 = satisfactory 2 = fair 1 = needs improvement 0 = no score

Name Attendance Cooperation Knowledge Application Total

1.

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5.

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10