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What Are The Most Clinically Useful Cutoffs For The Alvarado AndPediatric Appendicitis Scores A Systematic Review
What Are The Most Clinically Useful Cutoffs For The Alvarado AndPediatric Appendicitis Scores A Systematic Review
What Are The Most Clinically Useful Cutoffs For The Alvarado AndPediatric Appendicitis Scores A Systematic Review
What Are the Most Clinically Useful Cutoffs for the Alvarado
and Pediatric Appendicitis Scores? A Systematic Review
Mark H. Ebell, MD, MS*; JoAnna Shinholser, BSHP
*Corresponding Author. E-mail: ebell@uga.edu, Twitter: @markebell.
Study objective: The objective of this study is to systematically review the accuracy of the Alvarado score and Pediatric
Appendicitis Score and to identify optimal cutoffs for low- and high-risk populations.
Methods: We performed a systematic review of the literature and identified 26 studies of the accuracy of the Alvarado
score and Pediatric Appendicitis Score. Data were abstracted in parallel, and only prospective, cohort studies that
avoided verification bias were included. We calculated summary likelihood ratios for low-, moderate-, and high-risk
groups, using all possible cutoffs based on available data, even if not reported in the original study.
Results: The pretest probability of appendicitis was approximately 33% in studies of children and approximately 66% in
studies of adults. Likelihood ratios at different cutoffs for the Alvarado score in adults were as follows: 0.03
(<4 points), 0.42 (4 to 6 points), and 3.4 (7 points); and 0.01 (<5 points), 0.98 (5 to 8 points), and 6.7 (9 points).
Likelihood ratios for the Alvarado score in children were as follows: 0.02 (<4 points), 0.27 (4 to 6 points), and
4.2 (7 points); and 0.04 (<5 points), 1.2 (5 to 8 points), and 8.5 (9 points). For the Pediatric Appendicitis
Score, likelihood ratios were 0.13 (<4 points), 0.70 (4 to 7 points), and 8.1 (8 points).
Conclusion: For children with a pretest probability of acute appendicitis of 60% or less, an Alvarado score below
4 rules out the diagnosis; this is also true for a score less than 5 if the pretest probability is up to approximately 40%. In
adults with a pretest probability greater than or equal to 60%, an Alvarado score of 8 or higher rules in the diagnosis,
whereas one of 9 or higher rules in the diagnosis at pretest probabilities greater than or equal to 40%. The Pediatric
Appendicitis Score did not identify clinically useful low- or high-risk groups at typical pretest probabilities. [Ann Emerg
Med. 2014;64:365-372.]
Please see page 366 for the Editor’s Capsule Summary of this article.
A feedback survey is available with each research article published on the Web at www.annemergmed.com.
A podcast for this article is available at www.annemergmed.com.
0196-0644/$-see front matter
Copyright © 2014 by the American College of Emergency Physicians.
http://dx.doi.org/10.1016/j.annemergmed.2014.02.025
SEE EDITORIAL, P. 373. clinical examination results, patients with acute abdominal pain
and a probability of appendicitis that is below the test threshold
may be discharged home without additional diagnostic tests,
INTRODUCTION whereas those with a high probability of disease that is above the
Background treatment threshold may be treated with immediate
Clinical decision rules integrate several findings from the appendectomy. Patients who have an intermediate risk of
medical history, physical examination, and simple laboratory tests appendicitis that is between the test and treatment thresholds
to predict the likelihood of a disease. Several clinical decision rules might undergo imaging or observation for further data gathering.
have been developed and prospectively evaluated for their accuracy A truly useful clinical decision rule would classify patients into
in diagnosis of appendicitis in both adults and children. Among low-, moderate-, and high-risk groups that correspond to the
the most widely studied are the Alvarado score and the Pediatric zones below the test threshold, between the test and treatment
Appendicitis Score.1,2 The Alvarado score can be used in adults thresholds, and above the treatment threshold, respectively.4 On
and children, whereas the Pediatric Appendicitis Score is used only the other hand, if a clinical decision rule for appendicitis creates
in children and adolescents. The scores are summarized in Table 1. low- and high-risk groups, but the low-risk group is not low risk
Pauker and Kassirer3 proposed the threshold model of enough to rule out appendicitis and the high-risk group is not
diagnosis, which identifies test and treatment thresholds for high risk enough to rule it in, then the clinical decision rule does
clinical decisionmaking. For example, according to the initial not have good clinical relevance.
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Most Clinically Useful Cutoffs for Appendicitis Scores Ebell & Shinholser
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Volume 64, no. 4 : October 2014
With With
Reference Mean Age (SD), Appendicitis Appendicitis
Study Population Standard n Range, Years Male (%) (0%-100%) (0%-100%) Country
Adults
Al Qahtani, 200411 Consecutive patients with suspected Surgeryþclinical f/u by telephone 2–3 211 32, 13–72 59.2 56.9 87.7 Saudi Arabia
appendicitis days after d/c
Baidya, 200712 Clinically suspected appendicitis Surgeryþclinical f/u at hospital d/c 231 26.3, 16–72 61 51.5 93.7 India
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Kim, 200813 Clinically suspected appendicitis Surgeryþclinical f/u at 3 mo 157 37.1 (16.5), 15–84 40.1 57.3 96.8 Korea
Limpawattanasiri, 201114 Clinically suspected appendicitis Surgeryþinpatient f/u at 24þ h 1,000 NR, 15–72 40.7 71.5 85.3 Thailand
Pouget-Baudry, 201015 RLQ abdominal pain Surgeryþfollow-up clinical f/u at 1 wk 233 31.5, 15–88 48.1 73.4 98.3 France
Pruekprasert, 200416 Clinically suspected appendicitis Surgeryþfinal f/u at hospital d/c 231 27, 14–75 58 80.5 92.5 Thailand
Sanabria, 200717 Patients >14 y with pain in the right Surgeryþfollow-up telephone 374 29.5 (10.8), 15–71 47.6 55.2 76.60 Columbia
lower quadrant call at 30 days
Memon, 200918 Clinically suspected appendicitis Surgical findings 100 24.8 (9), 13–55 65 91 91 Pakistan
undergoing surgery
Inci, 201119 Clinically suspected appendicitis Surgical findings 66 26.5 (11.3), 14–72 52.9 86.4 86.4 Turkey
undergoing surgery
Canavosso, 200820 Clinically suspected appendicitis Surgical findings 207 26.6, 13–82 52.2 91.3 91.3 Argentina
undergoing surgery
Denizbasi, 200321 Clinically suspected appendicitis Surgical findings 221 26.6, 14þ 53.6 79.2 79.2 Turkey
undergoing surgery
Kang, 198940 Clinically suspected appendicitis Surgeryþclinical follow-up 62 45.8, 18–78 66.1 67.7 85.7 China
Sigdel, 201022 Clinically suspected appendicitis Surgical findings 100 27.5 (9.8), 15–68 72 94 94 Nepal
undergoing surgery
Children
Shreef, 201023 Suspected acute appendicitis Surgeryþ24-h f/u or telephone call 350 9.3, 8–14 56.1 37.7 72.5 Egypt,
Saudi Arabia
Schneider, 200728 Clinically suspected appendicitis Surgeryþf/u telephone call 2 wk later 588 11.9, 3–21 NR 33.5 91.7 USA
Bhatt, 200929 Abdominal pain <3 days and Surgeryþf/u telephone call 1 mo later 246 10.9 (3.4), 4–18 59.8 33.7 87.4 Canada
appendicitis suspected
Goldman, 200830 Abdominal pain <7 days Surgeryþtelephone call 5–7 days later 849 NR, 1–17 NR 14.5 NR Canada
Zuniga, 201231 Clinically suspected Surgeryþclinical f/u 7 days later 101 9.5 (2.8) 54.5 27.7 93.3 Spain
appendicitis <7 days
Wu, 201238 Clinically suspected appendicitis Surgeryþtelephone call 2 wk after 1,395 11.1 (4.2), 3–18 46.2 63.2 NR Taiwan
discharge from ED
Wu, 201239 Clinically suspected appendicitis Surgeryþtelephone call 2 wk after 594 11.1 (4.2), 4–18 60.3 51.5 74.8 Taiwan
discharge from ED
f/u, follow-up; d/c, discharge; h, hours; wk, week; mo, month.
Most Clinically Useful Cutoffs for Appendicitis Scores Ebell & Shinholser
categories. Many studies reported the number of patients with Excluding studies that enrolled only patients who underwent
and without a final diagnosis of appendicitis for each value of the surgery, the pooled percentage of patients with appendicitis was
Alvarado score or Pediatric Appendicitis Score. Even if the 66.0% in the adult studies (range 51.5% to 80.5%), 38.8% in
original study reported only the accuracy for a single the mixed-population studies (range 35.0% to 58.3%), and
dichotomous cutoff or pair of cutoffs, this information allowed us 33.4% in the studies of children (range 14.5% to 71.1%). The
to abstract data for a series of dichotomous cutoffs and for mean age ranged from 25 to 37 years in studies of adults, 23 to
commonly reported pairs of cutoffs such as less than 4, 4 to 6, 30 years in studies with a mixed population, and 9.3 to
and greater than or equal to 7 points, and less than 5, 5 to 8, and 11.9 years in studies of children.
greater than or equal to 8 points for the Alvarado score. Because we used methodologically rigorous inclusion criteria,
Data were recorded in parallel in a Google Docs spreadsheet. all included studies were prospective cohort studies of unselected
After discrepancies were reconciled as described above, the final patients with abdominal pain or suspected appendicitis, had
data set was imported into Stata (version 12.1; StataCorp, adequate follow-up, and reported sufficient data to calculate
College Station, TX) for analysis. Alvarado or Pediatric Appendicitis Score scores. None of the
studies blinded outcome assessors, and both scores were always
Primary Data Analysis
calculated before surgery or on admission. Five studies enrolled
We used the MIDAS library (Ben Dwamena, 2007. MIDAS:
only patients undergoing surgery,18-22 whereas the remainder
A program for Meta-analytical Integration of Diagnostic
were all judged to have adequate clinical follow-up in
Accuracy Studies in Stata. Division of Nuclear Medicine,
nonoperated patients to avoid verification bias. Most studies
Department of Radiology, University of Michigan Medical
specified that the decision to perform surgery was independent of
School, Ann Arbor, Michigan) to calculate summary likelihood
the clinical decision rule(s). In 3 studies, the decision to operate
ratios for the final diagnosis of appendicitis for patients who
was guided by the score result,12,14,20 and for 5 studies it was not
scored above and below each cutoff. MIDAS uses a bivariate
clear whether the surgery decision was independent.11,19,24,30,31
mixed-effects regression model5,6 that has been modified for
A summary of the quality assessment is shown in Figure 1.
meta-analysis of diagnostic accuracy studies.7
The accuracy of the Alvarado score in adults for the most
We took the approach of Ohle et al6 to calculate likelihood
commonly used sets of decision thresholds is summarized in
ratios for low-, moderate-, and high-risk groups. For example, if
Table 3. The likelihood ratio for the low-risk groups in adults
low-, moderate-, and high-risk groups were defined as less than
ranged from 0.01 to 0.38 and was less than 0.05 for 6 of 10 study
4, 4 to 6, and greater than or equal to 7 points, respectively, we
populations. Two studies had significantly higher likelihood
calculated the likelihood ratios for less than 4 versus greater than
ratios for the low-risk group.13,15 One of these 2 studies found
or equal to 4, less than 7 versus greater than or equal to 7, and 4
appendicitis in 23 of 55 patients with a score less than 4 points,
to 6 versus all other scores. In some cases, studies contributed
but the score was calculated by an intern on call, so lack of
data for the upper or lower cutoff, but not both. We also report
clinical experience may have contributed to a failure to detect
95% confidence intervals (CIs) for each summary likelihood
clinical signs and symptoms of appendicitis.15 The other was a
ratio. Bivariate summary receiver operating characteristic curves
Korean study that found appendicitis in 11 of 34 patients with a
were created for the key lower and upper clinical cutoff points
score less than 4 points; however, we could find no explanation
with the MIDAS procedure where possible. Because they use a
for the higher rate of appendicitis compared with that in other
bivariate random-effects regression model, they can be used to
studies.13 In regard to the high-risk groups in adults, the
provide a valid estimate of the summary likelihood ratios.
likelihood ratio ranged from 1.76 to 13.7. The summary
likelihood ratio was 3.4 (95% CI 2.5 to 4.6) for a cutoff of
RESULTS greater than or equal to 7 points and 6.7 (95% CI 3.5 to 12.7)
Our initial PubMed search yielded 526 studies, and a search for a cutoff of greater than or equal to 9 points. Bivariate
for “‘pediatric appendicitis score’[tiab]” yielded 14 studies. The summary receiver operating characteristic curves for cutoffs of
reference lists for previously published systematic reviews8-10 less than 4, greater than or equal to 7, and greater than or equal
were reviewed and identified 10 additional studies not found by to 9 in adults are shown in Figure E1A through C (available
the initial PubMed searches. The final total was 544 unique online at http://www.annemergmed.com); receiver operating
original research studies, of which a total of 29 met our inclusion characteristic curves for cutoffs of less than 4, less than 5, greater
criteria. The remaining studies generally did not study accuracy than or equal to 7, and greater than or equal to 9 in children are
or did not report sufficient data to calculate accuracy, were shown in Figure E2A through D (available online at http://www.
retrospective, or used a case-control design. annemergmed.com).
The characteristics of included studies are summarized in The accuracy of the Alvarado score and Pediatric Appendicitis
Table 2. Of the 29 studies, 13 reported on use of the Alvarado Score in children is summarized in Table 4. The likelihood of
score in adults11-22,40 and 11 on use of the Alvarado score or appendicitis was significantly higher in the low-risk group for the
Pediatric Appendicitis Score in children.23-31,38,39 Five additional Pediatric Appendicitis Score (0.13; 95% CI 0.04 to 0.4) than for
studies reported data for a mixed population of adults and the Alvarado score (0.02 for a cutoff of <4 points; 0.04 for a
children32-36 and were excluded from the analysis. cutoff of <5 points). On the other hand, the high-risk group for
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Ebell & Shinholser Most Clinically Useful Cutoffs for Appendicitis Scores
Figure 1. Assessment of study quality. Green indicates low risk of bias, yellow unclear risk of bias, and red high risk of bias for each
aspect of study quality.
the Pediatric Appendicitis Score had a higher likelihood ratio et al30 enrolled all children with abdominal pain, not just
than for the Alvarado scores, but with considerable heterogeneity. children with right lower quadrant pain or suspected
Two studies were outliers, with higher likelihood ratios for the appendicitis. We could find no reason why the other study26
low-risk group than other studies.26,30 The study by Goldman might have been an outlier. Seven studies reported data sufficient
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Most Clinically Useful Cutoffs for Appendicitis Scores Ebell & Shinholser
Table 4. Performance of the Alvarado score and Pediatric Appendicitis Score in children.*
Likelihood Ratio (95% CI)
Study n Low Risk Moderate Risk High Risk
Alvarado score <4 4–6 7
Bond, 199024 189 0.01 (0–0.24) 0.24 (0.13–0.44) 3.12 (2.16–4.50)
Schneider, 200728 588 0.06 (0.02–0.18) 0.49 (0.38–0.63) 3.76 (3.01–4.69)
Shreef, 201023 350 0.03 (0–0.47) 0.19 (0.13–0.30) 5.09 (3.76–6.88)
Escriba, 201125 99 0.03 (0–0.53) 0.17 (0.06–0.44) 10.3 (4.44–24.0)
Wu, 201239 594 4.38 (3.33–5.76)
Mandeville, 201126 287 0.38 (0.21–0.70) 0.31 (0.21–0.46) 2.72 (2.04–3.62)
Summary 1,513 0.02 (0–0.36) 0.27 (0.19–0.40) 4.21 (3.33–5.32)
I2¼83 I2¼67 I2¼49
Alvarado score <5 5–8 9
Bond, 199024 189 0.01 (0–0.19) 1.03 (0.80–1.33) 6.17 (3.58–14.7)
Borges, 200327 76 0.12 (0.04–0.31)
Schneider, 200728 588 0.18 (0.11–0.29) 1.25 (1.09–1.43) 6.75 (3.89–11.7)
Shreef, 201023 350 0.01 (0–0.19) 1.15 (1.01–1.32) 10.6 (4.22–26.5)
Escriba, 201125 99 0.02 (0–0.33) 1.25 (0.84–1.87) 52.6 (3.27–847)
Mandeville, 201126 287 0.30 (0.19–0.48) 1.07 (0.87–1.32) 6.67 (2.95–15.1)
Summary 1,589 0.04 (0–0.36) 1.16 (1.06–1.27) 8.47 (5.61–12.8)
I2¼80 I2¼0 I2¼0
PAS <4 4–7 8
Schneider, 200728 588 0.16 (0.08–0.32) 0.71 (0.60–0.84) 5.04 (3.63–7.00)
Goldman, 200830 849 0.67 (0.58–0.77) 4.20 (3.05–5.80) 1.69 (0.35–8.02)
Bhatt, 200929 246 0.04 (0.01–0.26) 0.70 (0.53–0.92) 11.3 (5.59–22.8)
Escriba, 201125 99 0.03 (0–0.48) 0.50 (0.31–0.83) 79.6 (5.00–1266)
Mandeville, 201126 287 0.43 (0.21–0.88) 0.42 (0.31–0.55) 3.37 (2.35–4.85)
Zuniga, 201231 101 0.09 (0.01–1.43) 0.58 (0.37–0.91) 8.34 (3.38–20.6)
Summary 2,170 0.13 (0.04–0.40) 0.70 (0.45–1.11) 8.10 (4.13–15.9)
I2¼96 I2¼95 I2¼91
*All studies used surgeryþclinical follow-up as the reference standard.
to calculate a simple dichotomous cutoff of 7 or more points for combined results from studies using different cutoffs.7 Two
the Pediatric Appendicitis Score.25,26,28-31,38 This yielded a previous systematic reviews included studies that gathered data
positive likelihood ratio of 5.2 (95% CI 3.1 to 8.6) and negative retrospectively or had incomplete follow-up of nonoperated
likelihood ratio of 0.38 (95% CI 0.20 to 0.74). patients, which might lead to partial verification bias.5,6 Finally,
we identified high-quality, primary studies that met our inclusion
criteria but were not identified by previous studies because of
LIMITATIONS
language exclusion criteria or publication date.5-7
A limitation of the current study is threats to validity in the
In the current study, we limited our analysis to studies that
included studies. There were also differences in the level of
avoided these important biases: they used prospective data
training of the physicians gathering the clinical data. However,
collection, performed follow-up to determine the outcome for
we limited our analysis to high-quality, prospective studies that
nonoperated patients, and did not use a case-control design. We
avoided verification bias. Another limitation is that pretest
also examined the accuracy for cutoffs not reported by the
probabilities are not well known to most physicians in their
original study to identify all high-quality studies that examined a
practice setting and that the test and treatment thresholds are
particular cutoff for the test or treatment threshold.
generally determined intuitively by each physician rather than by
We were interested in identifying optimal cutoffs for the test
a formal assessment of the benefits or harms of testing, treating,
and treatment thresholds because this reflects modern clinical
or neither. Finally, CIs were fairly large for some estimates,
decisionmaking about appendicitis. Patients with a high
notably, the high-risk group for a cutoff of 9 for the Alvarado
probability of appendicitis are generally taken directly to the
score in adults and most of the low-risk groups. The latter was
operating theater, those with a very low probability are either
due primarily to 2 studies that were outliers.26,30
observed or discharged, and those with an intermediate
probability generally undergo imaging. The lower decision
DISCUSSION threshold corresponds to the “test threshold,” whereas the upper
Previous systematic reviews on this topic have had limitations. cutoff corresponds to the “treatment threshold.”
For example, some analyzed results only for either a single Figure 2 summarizes the clinical implications of our study for
cutoff,5 a single pair of cutoffs (ie, <5, 5 to 6, or 7 points),6 or the Alvarado score. We used likelihood ratios for test and
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Ebell & Shinholser Most Clinically Useful Cutoffs for Appendicitis Scores
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Most Clinically Useful Cutoffs for Appendicitis Scores Ebell & Shinholser
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compared with the general surgery resident. Eur J Emerg Med. prediction rule to identify children at low risk for acute appendicitis.
2003;10:296-301. Arch Pediatr Adolesc Med. 2012;166:738-744.
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Ebell & Shinholser Most Clinically Useful Cutoffs for Appendicitis Scores
Figure E1. Bivariate receiver operating characteristic curves for different low and high cutoffs of the Alvarado score in adults.
A, A cutoff of less than 4 points. B, A cutoff of 7 or more points. C, A cutoff of 9 or more points. Because of the small number of
studies and events within studies, the MIDAS procedure in Stata was unable to create a receiver operating characteristic curve for
the cutoff of less than 5 points.
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Most Clinically Useful Cutoffs for Appendicitis Scores Ebell & Shinholser
Figure E2. Bivariate receiver operating characteristic curves for different low and high cutoffs of the Alvarado score in children.
A, A cutoff of less than 4 points. B, A cutoff of less than 5 points. C, A cutoff of 7 or more points. D, A cutoff of 9 or more points.
Downloaded for Mahasiswa 1 FK UNPAD (mhs.clinicalkey1@fk.unpad.ac.id) at Universitas Padjadjaran from ClinicalKey.com by Elsevier on October 04, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.