Bias associated with delayed verification in test accuracy studies: accuracy of tests for endometrial hyperplasia may be much higher than we think!

BACKGROUND: To empirically evaluate bias in estimation of accuracy associated with delay in verification of diagnosis among studies evaluating tests for predicting endometrial hyperplasia. METHODS: Systematic reviews of all published research on accuracy of miniature endometrial biopsy and endometr ial ultrasonography for diagnosing endometrial hyperplasia identified 27 test accuracy studies (2,982 subjects). Of these, 16 had immediate histological verification of diagnosis while 11 had verification delayed > 24 hrs after testing. The effect of delay in verification of diagnosis on estimates of accuracy was evaluated using meta-regression with diagnostic odds ratio (dOR) as the accuracy measure. This analysis was adjusted for study quality and type of test (miniature endometrial biopsy or endometrial ultrasound). RESULTS: Compared to studies with immediate verification of diagnosis (dOR 67.2, 95% CI 21.7–208.8), those with delayed verification (dOR 16.2, 95% CI 8.6–30.5) underestimated the diagnostic accuracy by 74% (95% CI 7%–99%; P value = 0.048). CONCLUSION: Among studies of miniature endometrial biopsy and endometrial ultrasound, diagnostic accuracy is considerably underestimated if there is a delay in histological verification of diagnosis

Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and/or small for gestational age.</p> <p>Methods</p> <p>The data sources included Medline, Embase, Cochrane library, Medion (inception to February 2007), hand searching of relevant journals, reference list checking of included articles, contact with experts. Two reviewers independently selected the articles in which the accuracy of an analyte used in Downs's serum screening before the 25^thgestational week was associated with the occurrence of pre-eclampsia and/or small for gestational age without language restrictions. Two authors independently extracted data on study characteristics, quality and results.</p> <p>Results</p> <p>Five serum screening markers were evaluated. 44 studies, testing 169,637 pregnant women (4376 pre-eclampsia cases) and 86 studies, testing 382,005 women (20,339 fetal growth restriction cases) met the selection criteria. The results showed low predictive accuracy overall. For pre-eclampsia the best predictor was inhibin A>2.79MoM positive likelihood ratio 19.52 (8.33,45.79) and negative likelihood ratio 0.30 (0.13,0.68) (single study). For small for gestational age it was AFP>2.0MoM to predict birth weight < 10^thcentile with birth < 37 weeks positive likelihood ratio 27.96 (8.02,97.48) and negative likelihood ratio 0.78 (0.55,1.11) (single study). A potential clinical application using aspirin as a treatment is given as an example.</p> <p>There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals.</p> <p>Conclusion</p> <p>Down's serum screening analytes have low predictive accuracy for pre-eclampsia and small for gestational age. They may be a useful means of risk assessment or of use in prediction when combined with other tests.</p

Miocene transgression in the central and eastern parts of the Sivas Basin (Central Anatolia, Turkey) and the Cenozoic palaeogeographical evolution

International audienceWe present here a reappraisal of the tectonic setting, stratigraphy and palaeogeography of the central part of the Sivas Basin from Palaeocene to late Miocene. The Sivas Basin is located in the collision zone between the Pontides (southern Eurasia) and Anatolia (a continental block rifted from Gondwana). The basin overlies ophiolites that were obducted onto Anatolia from Tethys to the north. The Central Anatolian Crystalline Complex (CACC) experienced similar ophiolite obduction during Campanian time, followed by exhumation and thrusting onto previously emplaced units during Maastrichtian time. To the east, crustal extension related to exhumation of the CACC created grabens during the early Tertiary, including the Sivas Basin. The Sivas Basin underwent several tectonic events during Paleogene–Neogene. The basin fill varies, with several sub-basins, each being characterised by a distinctive sequence, especially during Oligocene and Miocene. Evaporite deposition in the central part of the basin during early Oligocene was followed by mid-late Oligocene fluvio-lacustrine deposition. The weight of overlying fluvial sediments triggered salt tectonics and salt diapir formation. Lacustrine layers that are interbedded within the fluviatile sediments have locally yielded charophytes of late Oligocene age. Emergent areas including the pre-existing Sivas Basin and neighbouring areas were then flooded from the east by a shallow sea, giving rise to a range of open-marine sub-basins, coralgal reef barriers and subsiding, restricted-marine sub-basins. Utilising new data from foraminifera, molluscs, corals and nannoplankton, the age of the marine transgression is reassessed as Aquitanian. Specifically, age-diagnostic nannoplankton assemblages of classical type occur at the base of the transgressive sequence. However, classical stratigraphic markers have not been found within the planktic foraminiferal assemblages, even in the open-marine settings. In the restricted-marine sediments, there are rich planktic foraminiferal assemblages of classical type but these are of little use in stratigraphy. In contrast, the gastropod fauna indicate a Burdigalian age. Sediment reworking in the restricted-marine environments precludes stratigraphic determination. In such environments, micro- and nano-organisms experienced atypical developmental conditions. The small benthic foraminifera and associated ostracod assemblages are good indicators of salinity which varied considerably within the restricted-marine sub-basins. Some of the corals within the coralgal reefs barriers are also dated as Aquitanian. A combination of the salt tectonics and the late Miocene north-westward-verging thrusting created the present basin complexity