1. Anual assignment: Class 9 Regent: Prof. Doutor Altamiro da Costa Pereira Orientator: Drª Cristina Santos 15/12/2005

2. What is the sensitivity and specificity of amniotic fluid lamellar body count in detection of respiratory distress syndrome?

3. Introduction What is amniocentesis? What is the use of this method? What is a respiratory distress syndrome? What is a test's sensitivity and specificity? Why is this systematic review important? What is the aim of this study?

4. What is amniocentesis? Amniocentesis: is a percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. Pubmed research:”amniocentesis” [MeSH terms] GRAÇA, Luis Mendes da et al; Medicina materno-fetal; 3 rd edition; Lidel Lisboa

5. What is the use of this method? Amniocentesis is used to evaluate the lung maturity of the fetus; Throughout the lamellar body count in the amniotic fluid, it is possible to detect the respiratory distress syndrome. Pubmed research:”amniocentesis” [MeSH terms] GRAÇA, Luis Mendes da et al; Medicina materno-fetal; 3rd edition; Lidel Lisboa

6. What is a respiratory distress syndrome? Respiratory distress syndrome: Frequent in premature infants, children of diabetic mothers and infants delivered by cesarean section; Syndrome of respiratory difficulty caused by a deficiency of lung surfactant; Symptoms: dyspnea with cyanosis dilatation of the alae nasi expiratory grunt etc.

7. Possible treatments : extra oxygen(21%) CPAP (Continuous Positive Airway Pressure) surfactant In last case the baby is intubated Pubmed research:”respiratory distress syndrome” [MeSH terms] CUNNINGHAM, F.Gary et al ;William’s Obstetrics;22nd edition; Mc Graw-Hill; Medical Publishing Division; New York www.pedriatics.wisc.edu

8. What is a test's sensitivity and specificity? Sensitivity and specificity are parameters that express something about the tests’ performance; Sensitivity is the test ability to detect a disease when it is effectively present – true positives. If the babies suffer from respiratory distress syndrome, amniocentesis result is positive. Specificity is the test ability to detect true negatives. If the babies are healthy, amniocentesis result is negative. JECKEL, J et al; Epidemiology Biostatistics and preventive Medicine; W.R. Samders Text Company, 1996 TIMMCREEK, T. ; An Introduction to Epidemiology; Jones and Bontlett Publishers,1994 Wikipedia

9. Why is this systematic review important? Problem: There is some doubt about the sensitivity and specificity of amniocentesis in determination of respiratory distress syndrome So... This systematic review allows the analysis of all articles about this topic on Pubmed till October 2005. This systematic review can provides to all health personnel reliable information about amniocentesis sensitivity and specificity.

10. What is the aim of this study? The aim of our study is systematic review of all articles that evaluate the specificity and sensitivity of amniotic fluid lamellar body count in detection of respiratory distress syndrome.

11. Study Design Systematic review with possible metanalysis Steps of article: 1. Search for literature 2. Use predifined Inclusion/Exclusion Criteria to select the article 3. Evaluate quality of articles 4. Extract data 5. Statistical analysis of data

12. Research methods Database: Medline Limits: publications until 2005/10; Humans The search and methods aimed at finding all the evidence which could be useful in estimating the sensitivity and specificity of lamellar body count from the amniotic fluid in detection of respiratory distress syndrome in Newborn

13. Search Plan Objective:find articles related to diagnostic studies referring to the respiratory distress syndrome. 1.Find articles of all diagnostic studies 2.Find articles of all diagnostic studies referring to amniotic fluid 3.Find articles of all diagnostic studies referring respiratory distress syndrome, Newborn 4.Find articles of all diagnostic studies related to lamellar body count 5.Gather all data

14. Search process 1st step: Sensitity and Specificity Using a recommended search strategy* (sensitiv*[Title/Abstract] OR sensitivity and specificity[MeSH Terms] OR diagnos*[Title/Abstract] OR diagnosis[MeSH:noexp] OR diagnostic * [MeSH:noexp]) MeSH (Medical Headin Subject): sensitivity and specificity[MeSH Terms] ; diagnosis[MeSH:noexp ; diagnostic * [MeSH:noexp] Search 1: N=1962714 articles Haynes RB, Wilczynski NC for the Hedges Team. Optimal search strategies for retrieving scientifically strong studies of diagnosis from MEDLINE: analytical survey. BMJ. 2004 May 1;328(7447):1040

15. 2nd Step: Amniotic fluid Search: all diagnosis studies related to amniotic fluid. MeSH terms: “Amniotic Fluid” Search query: (search1) AND ("amniotic fluid "[Mesh]) N=12536 articles 3rd Step: MeSH term: respiratory distress syndrome, Newborn [MeSH] Query:(search1) AND ("respiratory distress syndrome, Newborn" [MeSH] OR "lung maturity" OR "respiratory distress syndrome" OR "FLM" OR “surfactant” OR “hyaline membrane”) N= 26438 articles

16. 4th step Search: obtain diagnosis studies related to the given intervention, lamellar body count, Query: (search1) AND ("lamellar body count" OR "lamellar bodies" ) N=454 articles

17. Final step: Finally all previous searches were crossed in order to obtain the final number of articles Query: (sensitiv*[Title/Abstract] OR sensitivity and specificity[MeSH Terms] OR diagnos*[Title/Abstract] OR diagnosis[MeSH:noexp] OR diagnostic * [MeSH:noexp] OR diagnosis,differential[MeSH:noexp] OR diagnosis[Subheading:noexp]) AND ("amniotic fluid" [MeSH]) AND ("respiratory distress syndrome, Newborn" [MeSH] OR "lung maturity" OR "respiratory distress syndrome" OR “surfactant” OR “hyaline membrane”) AND ("lamellar body count" OR "lamellar bodies" ) N=24 articles

18. Critics on research methods It was only used Medline database, not having used other data source such as Cochrane central or manual research Final search query may have been very specific Pai M, McCullock M, Gorman JD, Pai N, Enanoria W, Kennedy G, Tharyan P, Colford JM Jr. Systematic reviews and meta-analyses: Na illustrated, step-by-step guide. The National Medical Journal of India 2004; 17(2): 86-95

19. 3 independent reviewers will read the titles and abstract selecting the articles according to the inclusion/exclusion criteria. Title and abstract review

20. Criteria of Inclusion The articles must refer to:  Sensitivity and specificity  Diagnostic method of amniotic fluid lamellar body count  Amniocentesis in the detection of Respiratory Distress Syndrome  Provides the desired outcome data (True Positives, true Negatives, false positives, false negatives)

21. Criteria of exclusion  Studies which make reference to animals  All the articles that not obey to inclusion criteria

22. Accuracy and quality evaluation of the Articles To evaluate the accuracy and quality of the articles according to the criteria of inclusion/exclusion, independent reviewers will use the “Standards for Reporting of Diagnostic Accuracy” (STARD) checklist. Bossuyt, Patrick et all The STARD Initiative Towards Complete and Accurate Reporting of Studies of Diagnostic Accuracy Radiology 2003; 226:24–28

23. Flowchart

24. Data extraction True Positives, True Negatives; False positives; False negatives Values of: Sensitivity Specificity Sample Size / Number of articles Cut-off points Outcome Variable Confidence Interval (95%) Software used for input and analysis: metadisc

25. Data analysis 1. Presentation of the results of individual studies 2. Searching for the presence of heterogeneity 3. Testing of the presence of an (implicit) cut-point effect 4. Dealing with heterogeneity 5. Deciding which model should be used if statistical pooling is appropriate 6. Statistical pooling Devillé, Walter et all - Conducting systematic reviews of diagnostic studies - Didactic guidelines; BMC Medical Research Methodology 2002, 2:9

26. Gantt chart