The near future, applications and activities G. Magazzù and L. Greco.
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Transcript of The near future, applications and activities G. Magazzù and L. Greco.
![Page 1: The near future, applications and activities G. Magazzù and L. Greco.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649d475503460f94a22a69/html5/thumbnails/1.jpg)
The near future, applications and activities
G. Magazzù and L. Greco
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OUTLINE• Relevance and limits of the retrospective
study• Importance of prospective studies which
could also represent an opportunity “unique” for critically revising ESPGHAN criteria
• Is useful to preliminarily perform the Point-of-care study in a setting with the same characteristics of the setting foreseen by the study but where it is easier to monitor all variables?
• Is useful to perform studies of comparison between case finding vs screening for increasing CD diagnosis in order to detect the most cost/effective strategy for different countries and settings?
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OUTLINE• Relevance and limits of the retrospective
study• Importance of prospective studies which
could also represent an opportunity “unique” for critically revising ESPGHAN criteria
• Is useful to preliminarily perform the Point-of-care study in a setting with the same characteristics of the setting foreseen by the study but where it is easier to monitor all variables?
• Is useful to perform studies of comparison between case finding vs screening for increasing CD diagnosis in order to detect the most cost/effective strategy for different countries and settings?
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Retrospective study relevance
• Diagnosis without biopsy in 370/661 (49.7%)
• HLA can contribute to diagnosis if always and everywhere performed
• SAGE allows the diagnosis even without serology and in absence of villus atrophy
• most cases are symptomatic and the majority still show classical symptoms and therefore they have a high pre-test probability
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Retrospective study limits• Diagnosis without biopsy in
370/661 (49.7%)• HLA can contribute to diagnosis if
always and everywhere performed• SAGE allows the diagnosis even
without serology and in absence of villus atrophy
• most cases are symptomatic and the majority still show classical symptoms and therefore they have a high pre-test probability
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744
83 SAGE < 4T0-T2 61
661 SAGE ≥4
291 with histology370 without
histologyT0-T2 40
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Out of the patients who continued a gluten containing diet 15% developed villus atrophy and 15% normalized serology in a two-year follow-up (Clin Gastroenterol Hepatol 2011;9:320-5)
Natural history of potential celiac disease in children
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Retrospective study limits• Diagnosis without biopsy in
370/661 (49.7%)• HLA can contribute to diagnosis if
always and everywhere performed• SAGE allows the diagnosis even
without serology and in absence of villus atrophy
• most cases are symptomatic and the majority still show classical symptoms and therefore they have a high pre-test probability
![Page 9: The near future, applications and activities G. Magazzù and L. Greco.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649d475503460f94a22a69/html5/thumbnails/9.jpg)
3 cases diagnosed by SAGE score
Case S A G E Total
I 2 2 n.d. n.d. 4
II 2 n.d. 1 1 4
III 2 1 1 0 4
Are you sure that all are celiac?
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Retrospective study limits• Diagnosis without biopsy in
370/661 (49.7%)• HLA can contribute to diagnosis if
always and everywhere performed• SAGE allows the diagnosis even
without serology and in absence of villus atrophy
• most cases are symptomatic and the majority still show classical symptoms and therefore they have a high pre-test probability
![Page 11: The near future, applications and activities G. Magazzù and L. Greco.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649d475503460f94a22a69/html5/thumbnails/11.jpg)
How to calculate the post-test probability
• Let’s calculate the Likelihood ratio (LR) positive (when the test is positive) and negative (when the test results negative)
• Let’s apply LR to the pre-test probability of the subject
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Let’s define the Likelihood ratio
• The likelihood that a given test result would be expected in a patient with the target disorder compared with the likelihood that the same result would be expected in a patient without the target disorder.
• LRpos = sensitivity / (1 - specificity) • LRneg = (1 - sensitivity) / specificity
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Let’s apply LR to the pre-test probability of the subject
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A patient wth a classic picture of CD
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A first degree relative
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In the general population
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Let’s define the Likelihood ratio
• The likelihood that a given test result would be expected in a patient with the target disorder compared with the likelihood that the same result would be expected in a patient without the target disorder.
• LRpos = sensitivity / (1 - specificity) • LRneg = (1 - sensitivity) / specificity
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Biopsy No. with TGAse level
TGAse < 10 X N
TGAse ≥ 10 X N
Total
M0-M2 49 40 89
M3 255 346 601
Total 304 386 690
Histology according to TGAse level 10 x N (all centers)
Sens. 58% Spec. 55% LR+ 1.28 LR- 0.77
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Why was “10xN” chosen as cut-off in SAGE?
• Barker CC, Mitton C, Jevon G, et al . Can tissue transglutaminase antibody titers replace small-bowel biopsy to diagnose celiac disease in select pediatric populations? Pediatrics 2005;115:1341-6.
• Donaldson MR, Firth SD, Wimpee H, et al. Correlation of duodenal histology with tissue transglutaminase and endomysial antibody levels in pediatric celiac disease. Clin Gastroenterol Hepatol 2007;5:567-73.
• Donaldson MR, Book LS, Leiferman KM, et al. Strongly positive tissue transglutaminase antibodies are associated with Marsh 3 histopathology in adult and pediatric celiac disease. J Clin Gastroenterol 2008;42:256-60.
• All these studies used a 100 AU cut-off
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Biopsy No. with TGAse level
TGAse < 100
UA
TGAse ≥ 100 UA
Total
M0-M2 18 0 18
M3 56 26 82
Total 74 26 100
Histology according to TGAse level 100 UA in 100 cases from Sicily
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Summing up
• We need to validate SAGE score before applying it in different settings, assigning a different weight to the four items
• Serology needs revision and standardization
• The positive predictive value of serology and HLA-typing combination should be defined
• Potential celiac disease is not negligible and should be taken into account revising the celiac disease diagnostic protocol
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OUTLINE• Relevance and limits of the retrospective
study• Importance of prospective studies which
could also represent an opportunity “unique” for critically revising ESPGHAN criteria
• Is useful to preliminarily perform the Point-of-care study in a setting with the same characteristics of the setting foreseen by the study but where it is easier to monitor all variables?
• Is useful to perform studies of comparison between case finding vs screening for increasing CD diagnosis in order to detect the most cost/effective strategy for different countries and settings?
![Page 23: The near future, applications and activities G. Magazzù and L. Greco.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649d475503460f94a22a69/html5/thumbnails/23.jpg)
Prospective study critical issues
• To define the diagnostic accuracy of non-invasive tests which can avoid in some cases intestinal biopsy
• Standardization of serology • To overcome selection and self-fulfilling
prophecy bias• Apply gold standard regardless of
serological tests in all cases with high pre-test probability
• Definition of cases by the web-database• To build a new diagnostic score and
protocol through a prospective study
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• POCT could be very useful in peripheral villages or town far from hospital and/or laboratories where EMA and TGA are available
• It should be validated likely (and together with) to conventional serology
Prospective study critical issues
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OUTLINE• Relevance and limits of the retrospective
study• Importance of prospective studies which
could also represent an opportunity “unique” for critically revising ESPGHAN criteria
• Is useful to preliminarily perform the Point-of-care study in a setting with the same characteristics of the setting foreseen by the study but where it is easier to monitor all variables?
• Is useful to perform studies of comparison between case finding vs screening for increasing CD diagnosis in order to detect the most cost/effective strategy for different countries and settings?
![Page 26: The near future, applications and activities G. Magazzù and L. Greco.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649d475503460f94a22a69/html5/thumbnails/26.jpg)
Average prevalence of Celiac Disease got by different strategies
• 0.6%-1.3% in blod donors• 0.3-1% in the general population• 0.12% in case finding studies
Case finding is precious for increasing awareness of health operators for CD but it could not bridge the diagnostic gap
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OUTLINE• Relevance and limits of the retrospective
study• Importance of prospective studies which
could also represent an opportunity “unique” for critically revising ESPGHAN criteria
• Is useful to preliminarily perform the Point-of-care study in a setting with the same characteristics of the setting foreseen by the study but where it is easier to monitor all variables?
• Is useful to perform studies of comparison between case finding vs screening for increasing CD diagnosis in order to detect the most cost/effective strategy for different countries and settings?
![Page 28: The near future, applications and activities G. Magazzù and L. Greco.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649d475503460f94a22a69/html5/thumbnails/28.jpg)
The role of Sicily in the MEDICEL project
• Available an already established regional network
• Involvement of Regional Government to facilitate project financing
• Involvement of an already established organization for cooperation in the Mediterranean area
• Involvement of patient Association (AIC – Sicilia onlus) for fund raising