Contingent screening for down syndrome is an efficient alternative to non-disclosure sequential screening

Objective To present a first and second trimester Down syndrome screening strategy, whereby second-trimester marker determination is contingent on the first-trimester results. Unlike non-disclosure sequential screening (the Integrated test), which requires all women to have markers in both trimesters, this allows a large proportion of the women to complete screening in the first trimester. Methods Two first-trimester risk cut-offs defined three types of results: positive and referred for early diagnosis; negative with screening complete; and intermediate, needing second-trimester markers. Multivariate Gaussian modelling with Monte Carlo simulation was used to estimate the false-positive rate for a fixed 85% detection rate. The false-positive rate was evaluated for various early detection rates and early test completion rates. Model parameters were taken from the SURUSS trial. Results Completion of screening in the first trimester for 75% of women resulted in a 30% early detection rate and a 55% second trimester detected rate (net 85%) with a false-positive rate only 0.1% above that achievable by the Integrated test. The screen-positive rate was 0.1% in the first trimester and 4.7% for those continuing to be tested in the second trimester. If the early detection rate were to be increased to 45% or the early completion rate were to be increased to 80%, there would be a further 0.1% increase in the false-positive rate. Conclusion Contingent screening can achieve results comparable with the Integrated test but with earlier completion of screening for most women. Both strategies need to be evaluated in large-scale prospective studies particularly in relation to psychological impact and practicability.

Three-stage contingent screening for down syndrome

Objective To demonstrate the potential value of three-stage sequential screening for Down syndrome. Methods Protocols were considered in which maternal serum pregnancy associated plasma protein-A (PAPP-A) and free -human chorionic gonadotropin (hCG) measurements were taken on all women in the first trimester. Those women with very low Down syndrome risks were screened negative at that stage and nuchal translucency (NT) was measured on the remainder and the risk reassessed. Those with very low risk were then screened negative and those with very high risk were offered early diagnostic testing. Those with intermediate risks received second-trimester maternal serum -fetoprotein, free -hCG, unconjugated estriol and inhibin-A. Risk was then reassessed and those with high risk were offered diagnosis. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling using Monte-Carlo simulation. Results The modelling suggests that, with full adherence to a three-stage policy, overall detection rates of nearly 90% and false-positive rates below 2.0% can be achieved. Approximately two-thirds of pregnancies are screened on the basis of first-trimester biochemistry alone, five out of six women complete their screening in the first trimester, and the first-trimester detection rate is over 60%. Conclusion Three-stage contingent sequential screening is potentially highly effective for Down syndrome screening. The acceptability of this protocol and its performance in practice, should be tested in prospective studies. Copyright © 2006 John Wiley & Sons, Ltd.

Wide Variation in Adenoma Detection Rates at Screening Flexible Sigmoidoscopy

Background & Aims: Wide between-center variation in adenoma detection rates (ADRs) was observed in the U.K. Flexible Sigmoidoscopy Screening Trial (overall, 12.1%; range, 8.6%-15.9%; P <0.0001). The aim of this study was to determine whether the observed differences could be attributed to varying performance by endoscopists, to examine the effect of experience on performance, and to identify an attainable, standard ADR to which endoscopists could aspire. 

Methods: Thirteen medical endoscopists, one per trial center, each performed about 3000 examinations (200 per month) using the same equipment and protocol. Overall and monthly ADRs were compared using multivariable logistic regression. 

Results: Differences in ADRs were not explained by patient characteristics, incidence of colorectal cancer in the local population, or the endoscopists' medical specialty or previous experience. Average ADRs increased significantly with screening experience (up to 400 examinations). Endoscopists were classified as higher, intermediate, or lower adenoma detectors, and performance levels were maintained over time. Higher detectors had ADRs of 15% overall (men, 20%; women, 10%) and also detected more adenomas per case (higher/lower detectors, 21.7/10.4 adenomas per :100 examinations). 

Conclusions: The differences in ADRs were due to variation in performance of the endoscopists. Long-term follow-up will determine whether this variation is clinically important. We suggest that the standards in higher detecting centers should be achievable by all endoscopists screening unscreened populations aged older than 55 years. Endoscopists should aim to stay above the lower 95% confidence interval band for 200 examinations (10% overall; 5% in women, 15% in men).

Cloning from tissue surrogates: antimicrobial peptide (esculentin) cDNAs from the defensive skin secretions of Chinese ranid frogs

The defensive skin secretions of amphibians are a rich source of bioactive peptides. Here we describe a rapid technique for skin granular gland transcriptome cloning from a surrogate tissue-the secretion itself. cDNA libraries were constructed from lyophilized skin secretion from each of the Chinese frogs (Rana schmackeri, Rana versabilis, and Rana plancyi fukienensis) using magnetic oligo(dT) bead-captured polyadenylated mRNA as templates. Specific esculentin cDNAs were amplified by 3'-RACE using a degenerate primer designed for a consensus nucleotide sequence in the 5' untranslated region of previously characterized ranid frog peptide cDNAs. The cloned cDNAs were found to encode the antimicrobial peptides esculentins 1 and 2 from each of the species examined. The presence of predicted peptide structures in skin secretions was confirmed by MALDI-TOF mass spectrometry and automated Edman degradation. This experimental approach can thus rapidly expedite parallel transcriptome and peptidome analysis of amphibian granular gland secretions without harming or sacrificing donor animals.