Combined Screening Test Research Articles

P06.02: Introduction of ultrasound for nuchal translucency (NT) as part of combined screening test (CST): impact on local practice

This study is to find out the impact of changes in our clinical practice after the introduction of antenatal combined screening test (CST) with nuchal translucency (NT) in a local district general hospital in the United Kingdom. The data was collected retrospectively from the local and regional antenatal screening team. The data was analysed with SPSS.17 and the results presented. There were 1905 women booked with pregnancy from June 2010 to January 2011. 1496 (78%) women had the combined screening test. Those who had missed the opportunity for combined screening test were given option for triple test 370 (19%). 70 High risk pregnancies were detected. All were offered invasive testing, 52 (74%) accepted invasive testing. 63% had amniocentesis and 36% had chorionic villous sampling. Women with isolated raised NT of above 3.5 mm were also offered invasive test without serum screening and a further second trimester fetal echocardiogram. Prior to June 2010 for a year there were 2467 pregnancy booked of which 1675 (67%) had triple test and 194 (7%) had CST. There were 73 high risk cases diagnosed and 62 had invasive testing of which around 90% was by amniocentesis. All women (100%) during the study period diagnosed with trisomy 21 through the screening programme choose for termination of pregnancy. The introduction of CST is offering women an opportunity for early interpretation of the test results to identify the risk for fetal anomaly (Down syndrome). This study shows that 96% women were having fetal anomaly screening after the introduction of CST as compared to 75% women screened prior to the introduction of CST. The NT scan is combined with the dating scan done on the same visit; this seems to encourage women to have scans with majority of women booked at an earlier gestation. All the women with diagnosed chromosomal abnormality are opting for termination of pregnancy. The combined screening test provides an opportunity for earlier provision of these services without the need for feticide.

Screening in the presence of a vanished twin: Nuchal translucency or combined screening test?

Screening in the presence of a vanished twin: Nuchal translucency or combined screening test?

Credibility of the combined test in prenatal diagnostics

Congenital anomalies are the cause of perinatal death in 20-25% of the cases, while 3% of children are born with malformation of varying size. The objective of this study was to examine the predictive value and define the credibility ratio of the combined test results. Of 317 examined pregnant women, we had sixteen (5.05%) with the result of pathological karyotype after amniocentesis including: nine (2.84%) with fetal numerical aberrations and seven (2.21%) with fetal structural aberrations. While determining the ultrasonographic parameters of the combined test we used the standards of the Fetal Medicine Foundation. We carried out the quantitative settings of free ?-HCG and PAPP-A from vein blood of patients by applying commercial tests of firm DPC-USA. Tests were based on the analytical immunochemiluminescence assay and were realized by using the automated analyzer IMMULITE 2000. Manufacturer of the analyzer is also the firm DPC-USA. Sensitivity of the test is 94%, and specificity is 99%. Positive likelihood ratio [likelihood ratio test (LR+)] is 94.00, a negative likelihood ratio is [likelihood ratio test (LR-)] 12:06. Pretest probability that pregnant women carries fetus with chromosomal abnormality is 1:250 or 0004. Posttest odds after the combined test to discover this abnormality is 0.3760, and probability of the same case is 0.2732 if it happens that the test result is positive. The result of our study confirms the justification of combined test usage in routine clinical practice, since the posttest odds rate in the case of a positive screening increases several times over (almost 90 times), the probability of detecting a chromosomal abnormality was about 70 times. Combined screening test if used methodologically correct, has a high predictive value in detecting fetal congenital anomalies.

Intracardiac Echogenic Focus and Trisomy 21 in a Population Previously Evaluated by First-trimester Combined Screening

A finding of intracardiac echogenic focus (IEF) within a region of the fetal ventricular papillary muscle is relatively common and considered to be a benign anatomic variant that resolves spontaneously during late gestation or early infancy. Most investigators believe that a single isolated IEF does not increase the risk of aneuploidy. A previous study, however, demonstrated an association between isolated IEF and trisomies 13 and 21. This association was confirmed for high risk but not low risk pregnancies. This prospective study was designed to investigate the possible association between IEF and trisomy 21 in a population of fetuses previously examined by first trimester combined screening, and to determine whether a finding of IEF during a routine fetal anatomy scan increases the risk of fetal Down syndrome. Four types of pregnancies were examined for prevalence of trisomy 21: (1) those with isolated IEF; (2) those with IEF and positive first trimester combined screening; (3) those with IEF and other ultrasound markers; and (4) those with IEF, positive first trimester combined screening and other ultrasound markers. Between 2004 and 2007, 7118 pregnant women underwent first trimester combined screening and a detailed mid-trimester fetal anatomical scan. Fetal karyotyping by amniocentesis was offered to women who had a positive first trimester combined screening test result, and to those with an IEF or other soft ultrasound markers of fetal aneuploidy detected by a mid-trimester targeted ultrasound exam. The prevalence of trisomy 21 in each group was the primary outcome measure. Twenty-five cases of trisomy 21 were diagnosed prenatally; this represents a prevalence rate of 0.35% (25/7118). Among fetuses with a positive first trimester combined screening test result, the likelihood ratio of trisomy 21 was significantly increased in those with IEF compared with those without IEF (3.5 vs. 0.8, P = 0.012). In contrast, among fetuses with a negative first trimester combined screening test result, the likelihood ratio of trisomy 21 was not significantly different for fetuses with and without IEF (P = 0.064). These findings demonstrate that fetal karyotyping is not indicated for pregnancies with isolated IEF, negative first trimester combined screening test results, and no additional anomalies detected by ultrasonographic examination.

Is ultrasound alone enough for prenatal screening of trisomy 18? A single centre experience in 69 cases over 10 years

To evaluate ultrasound scan and other prenatal screening tests for trisomy 18 in a regional obstetric unit and to review the management approach for women with positive trisomy 18 screening results. Prenatal diagnosis databases were accessed to identify fetuses that had confirmed trisomy 18 karyotypes or were at high risk for trisomy 18 on second-trimester biochemical screening or first-trimester combined screening tests over a period of 10 years from 1 September 1997 to 30 September 2007. Sixty-nine women were confirmed to have trisomy 18 fetuses by karyotyping either prenatally (n = 61) or postnatally/post-miscarriage (n = 8) during the study period. The detection rate of ultrasound scan ≤ 14 weeks and 18 to 21 weeks to detect trisomy 18 was 92.7 and 100%, respectively. A total of 80 and 87% of fetuses had two or more ultrasound abnormalities detected in the ≤ 14 weeks and 18 to 21 weeks anomaly scans, respectively. Forty-eight women screened positive for trisomy 18 by second-trimester biochemical screening with human chorionic gonadotrophin (hCG) and alpha fetoprotein (AFP). Only one was true positive (positive predictive value = 1/48 or 2%). Eleven women screened positive for trisomy 18 by first-trimester combined screening with nuchal translucency scan and maternal serum for pregnancy-associated plasma protein A (PAPP-A) and hCG between 11 and 13 + 6 weeks. Three were true positive (positive predictive value = 3/11 or 27%). All four cases with positive screening had ultrasound abnormalities. Ultrasound scan for fetal anomalies is the most effective screening test for trisomy 18. A policy of conservative management for women with positive second-trimester biochemical screening or first-trimester combined screening for trisomy 18 is reasonable in the absence of ultrasound fetal abnormalities. Unnecessary invasive tests can be avoided.

Evaluación de la eficacia del cribado prenatal del primer trimestre de embarazo en la Región de Murcia

Introduction First trimester combined screening test for chromosomal anomalies, with its high sensitivity and specificity, can help predict the risk of carrying a foetus with a chromosomal anomaly. Those pregnant women with a high risk can, after genetic advice, then decide to have an invasive diagnostic test. The aim of this article was to determine the sensitivity, negative predictive value and false positive rate of the first trimester combined screening test in our laboratory. Material and methods First trimester combined screening test was performed on 4494 pregnant women. The test consists of determining PAPP-A, free β-HCG and nuchal translucency. Karyotype was found in all pregnant women who had a high risk for Down's Syndrome (DS), Edward's Syndrome (ES) or both. Karyotype of the newborn was used for pregnant women who decided not to have the invasive diagnostic test. Risk was calculated with Prisca Software v.4.0.15.9 ® (DPC Dipesa ®), considering >1/270 as high risk. Results Out of the total of pregnant women, 260 first trimester screenings had a risk >1/270; 201 for DS, 39 for ES and 20 for both. The data obtained for DS and ES, respectively, were: true positives (TP): 5 and 5; false positives (FP): 216 and 54; true negatives (TN): 4273 and 4435; false negatives (FN): 0 and 0; Sensitivity: 100% for both; Specificity: 95% and 99%. Positive predictive value (PPV): 2% and 8%; negative predictive value (NPV): 100% for both. False positive rate was 4.83% for DS and 1.20% for ES. Conclusion The first trimester combined screening test is an efficient tool that reduces the number of invasive diagnostic tests, due to its high sensitivity, specificity and negative predictive value.

Abnormal Ductus Venosus Flow and Tricuspid Regurgitation at 11–14 Weeks' Gestation have High Positive Predictive Values for Increased Risk in First-Trimester Combined Screening Test: Results of a Pilot Study

To investigate the relationship between two novel first-trimester ultrasound markers (abnormal fetal ductus venosus [DV] flow and presence of tricuspid regurgitation [TR]) and the results of the first-trimester combined screening test in pregnancies with a normal karyotype. The screening test involves nuchal translucency measurement by ultrasound, and measurement of serum free beta-chorionic gonadotropin and pregnancyassociated plasma protein A. The study included 58 pregnancies with amniocentesis-proven normal karyotypes and ultrasound-proven normal fetal anatomy. DV flow and TR were initially evaluated by ultrasound at 11-14 weeks' gestation. Sensitivity, specificity, and positive and negative predictive values of abnormal DV flow and TR for determining increased test risk (> 1 in 300) were calculated. Abnormal DV flow and TR were detected in seven (12%) and six (10%) women, respectively. The sensitivities of abnormal DV flow, TR, and dual abnormalities (abnormal DV flow plus TR) for predicting increased risk in the combined screening test were low (33.3%, 27.7%, and 26.3%, respectively). However, their corresponding specificities (97.5%, 97.5%, and 100%) and positive predictive values (85.7%, 83.3%, and 100%) were reasonably high, with particularly low false-positive rates (2.5%, 2.5%, and 0%). When abnormal DV flow and TR were both positive, the combined test risk was consistently above 1 in 300. Determination of DV flow and TR as initial markers in unselected pregnancies merits further investigation, as the combination of these parameters might reliably predict an increased risk in combined screening test result, with low false positivity.

Value of the Combined Test in Prenatal Diagnostics

Value of the Combined Test in Prenatal DiagnosticsCongenital anomalies are the cause of 20.0-25.0% of cases of perinatal death, while 3.0% of children are born with malformations of varying size. We examined the predictive values and defined the credibility ratio of the combined test results. Of 317 examined pregnant women, 16 (5.05%) gave a pathological karyotype after amniocentesis: of these, nine (2.84%) had chromosomal number aberrations and seven (2.21%) had chromosomal structure aberrations. We determined the ultrasonographic parameters using the standards of the Fetal Medicine Foundation (location please). We measured free β-subunit of choriogronadotropin (β-HCG) and pregnancy associated plasma protein A (PAPP-A) in venous blood from pregnant women using a combined commercial assay. Sensitivity of the test is 94.0%, and specificity is 99.0%. The positive likelihood ratio [likelihood ratio test (LR+)] is 94.00, a negative likelihood ratio is [likelihood ratio test (LR-)] 0.06. The pretest probability that pregnant women carry a fetus with chromosomal abnormality is 1:250. Posttest odds after the combined test to discover this abnormality is 0.3760, and probability of the same case is 0.2732 if it happens that the test result is positive. The result of our study confirms the justification of combined test usage in routine clinical practice, since the posttest odds rate in the case of a positive screening increases several times over (almost 90 times); the probability of detecting a chromosomal abnormality was about 70 times. The combined screening test, if used methodologically correctly, has a high predictive value in detecting fetal congenital anomalies.

Cord factor detection and macroscopic evaluation of mycobacterial colonies: an efficient combined screening test for the presumptive identification of Mycobacterium tuberculosis complex on solid media

The rapid differentiation between Mycobacterium tuberculosis and nontuberculous mycobacteria is fundamental for patients co-infected with tuberculosis and HIV. To that end, we use two methods in our laboratory: detection of cord factor and PCR-restriction enzyme analysis (PRA). The objective of this study was to evaluate the accuracy of a screening test on solid medium as a rapid method for the presumptive identification of M. tuberculosis complex, considering costs and turnover time. A total of 152 strains were submitted to a combined screening test, consisting of the detection of cord factor under microscopy (Ziehl-Neelsen staining) and evaluation of the macroscopic aspect of colonies, as well as to PRA, which was used as the gold standard. Costs were estimated by calculating the price of all of the materials needed for each test. The overall accuracy of cord factor detection alone was 95.4% (95% CI: 90.7-98.1%), and that of the combined screening test was 99.3% (95% CI: 96.4-100%). Cord factor detection costs US$ 0.25, whereas the PRA costs US$ 7.00. Results from cord factor detection are ready in 2 days, whereas PRA requires 4 days to yield results. The presumptive identification of M. tuberculosis using the macroscopic evaluation of colonies combined with cord factor detection under microscopy is a simple, rapid and inexpensive test. We recommend the combined screening test to rapidly identify M. tuberculosis in resource-poor settings and in less well-equipped laboratories while awaiting a definite identification by molecular or biochemical methods.

Eigenerhebung der Leseleistung mit dem ACTO-Selbsttest bei AMD-Patienten nach intravitrealen Injektionen

Monthly controls are necessary after injections of vascular endothelial growth factor (VEGF) to enable timely recognition of a renewed decrease in vision. However, these monthly control intervals are not realistic for many older patients with age-related macular degeneration (AMD), and outpatient clinics often reach their logistical limits because of inadequate funding for the additional medical work. Against this background, we conceived the ACTO self-test as a novel screening method for patients to discover unnoticed visual changes outside the routinely scheduled ophthalmic examination. The paper version of the ACTO self-test consists of a reading chart gradated in decimal steps as well as six questions regarding the quality of the Amsler grid. The patient uses a self-screening test to examine each eye separately and then transfers the results to a table. Along with the self-examination, the Action Eyesight Service Center is available to the patient by phone to motivate the patient and schedule a new appointment if improved test results occur. If decreased values or suspected decreased visual function occur, these are verified immediately by the referring physician. There is a good correlation between the steps of the ACTO self-test and standard visual acuity at 4 m (r(2)=0.9). Altogether, 1,444 patients were followed by phone and 745 participated in repeated regular audits, for a total of 3,003 phone contacts. The treating physician was informed about decreased visual acuity or increased Amsler distortion in the ACTO test in 137 cases, and immediate verification was done. We had 699 dropouts; the reasons were decreased visual acuity below the limits of the ACTO test in 39%, additional monthly examinations by the local ophthalmologist in 29%, and a desire for no more telephone follow-up (despite initial written consent) in 32%. Decreased vision when reading or an increased score on the Amsler test within the ACTO screening test was observed in 18% of AMD patients during the maintenance phase. Monthly screening by the ACTO screening test in combination with phone audits offers a new way to test visual acuity, with the Amsler score helping to detect changes in visual function. For patients with visual changes, confirmation by the ophthalmic physician can be achieved in time. Self-assessment cannot replace qualified ophthalmologic examination, but monthly self-controls enhance safety, reduce the number of physician contacts, and improve the detection of visual changes, with the option of immediate ophthalmic retreatment.

OP02.05: Performance of first trimester combined screening test for trisomy 21 and trisomy 13/18 with the double test taken before or after 10 weeks in 44,537 singleton pregnancies

OP02.05: Performance of first trimester combined screening test for trisomy 21 and trisomy 13/18 with the double test taken before or after 10 weeks in 44,537 singleton pregnancies

Maternal plasma inhibin A at 11–13 weeks of gestation in hypertensive disorders of pregnancy

To investigate the potential value of maternal plasma inhibin A in first-trimester screening for preeclampsia (PE). The concentration of inhibin A at 11-13 weeks was measured in samples from 121 pregnancies that developed PE, 87 cases of gestational hypertension (GH) and 208 normal controls. The distributions of inhibin A multiple of median (MoM) in the control and hypertensive groups were compared. Logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders. The maternal plasma inhibin A MoM was significantly higher in the early and late PE groups (1.55 MoM and 1.24 MoM, respectively; p < 0.0083), compared to the controls (0.98 MoM), but not in GH. Significant contributions for the prediction of PE were provided by maternal factors, plasma inhibin A and uterine artery pulsatility index (PI) and with combined screening the detection rates for early and late PE were 88% and 42%, respectively, for a false positive rate of 10%. The proposed combined screening test could be used to identify women at high risk for PE and intensive monitoring in such patients would lead to earlier identification of the disease which could potentially improve pregnancy outcome.

Role of uterine artery Doppler in interpreting low PAPP‐A values in first‐trimester screening for Down syndrome in pregnancies at high risk of impaired placentation

Low maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) are associated with both increased risk of aneuploidies and impaired trophoblastic invasion, while high uterine artery (UtA) resistance is associated with impaired trophoblastic invasion but not with an increased risk of aneuploidies. The aim of this study was to determine whether high UtA resistance plays a role in explaining low PAPP-A levels in the absence of aneuploidies. This was a prospective study of 116 singleton pregnancies at high risk for impaired placentation (having at least one major risk factor: prior history of pre-eclampsia, pregestational diabetes mellitus, chronic hypertension, chronic kidney disease, body mass index >30, autoimmune disorder, thrombophilia or recurrent pregnancy loss), booked for routine assessment of risk for aneuploidies by means of the first-trimester combined screening test (nuchal translucency thickness (NT) + PAPP-A + beta-human chorionic gonadotropin (beta-hCG)). Measurement of NT and the mean UtA pulsatility index (PI) were carried out at the 11 to 13 + 6-week scan. All values were calculated in multiples of the median (MoM) adjusted for gestational age. A cut-off risk of 1/270 at time of sampling was adopted to differentiate high- from low-risk groups for trisomy 21. There were 108 patients deemed to be at low risk for trisomy 21 and eight at high risk. None had chromosomal defects, giving a false-positive rate for trisomy 21 of 6.9%. The greatest differences between patients at low risk and those at high risk for trisomy 21 were found in their PAPP-A (0.98 vs. 0.38 MoM, P < 0.01) and beta-hCG (1.09 vs. 1.77 MoM, P = 0.04) values. Greater NT thickness (1.02 vs. 0.90 MoM) and higher mean UtA-PI (1.05 vs. 0.96 MoM) were recorded in the high-risk group, although the differences did not reach statistical significance (P = 0.19 and 0.40, respectively). After log-transformation there were no significant correlations between mean UtA-PI and NT and between mean UtA-PI and beta-hCG. There was a significant negative linear correlation between mean UtA-PI and PAPP-A (r = -0.331; P < 0.01). After adjusting the PAPP-A values by UtA-PI, the false-positive rate for trisomy 21 decreased to 2.6%. Mean UtA-PI at the 11 to 13 + 6-week scan may be an effect-modifier variable for PAPP-A that should be taken into account in the first-trimester combined screening for aneuploidies, at least in pregnancies at high risk for impaired placentation.

Performance profile of FDG-PET and PET/CT for cancer screening on the basis of a Japanese Nationwide Survey

The aim of this study is to survey the situation of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening in Japan and to describe its performance profile. "FDG-PET for cancer screening" was defined as FDG-PET or positron emission tomography and computed tomography (PET/CT) scan with or without other tests performed for cancer screening of healthy subjects. We sent questionnaires regarding FDG-PET cancer screening to 99 facilities in which FDG-PET tests were performed during the fiscal year 2005. Replies were obtained from 68 of the 99 facilities, of which 46 facilities performed FDG-PET cancer screening. The total number of subjects who underwent FDG-PET cancer screening was 50 558. From 38 of 46 facilities, reliable results of thorough examinations were obtained for the subjects who were positive by FDG-PET and/or one or more of the combined screening tests was performed and were referred for further evaluation. The total number of subjects in these 38 facilities amounted to 43 996. A total of 50,558 healthy subjects underwent FDG-PET (including PET/CT) scanning with or without other tests for cancer screening in 46 PET centers during the fiscal year of 2005 in Japan. Thorough examination was indicated for 9.8% of the cases as a result of positive findings suggesting possible cancer. On analyzing 43 996 cases from 38 PET centers from which detailed information was obtained, 500 cases of cancers (1.14%) were found, of which 0.90% were PET positive and 0.24% were PET negative, resulting in the relative sensitivity of PET being 79.0%. Cancers of the thyroid, colon/rectum, lung, and breast were most frequently found (107, 102, 79, and 35 cases, respectively) with high PET sensitivity (88%, 90%, 80%, and 92%). PET showed an overall positive predictive value of 29.0%. PET/CT had a better detection rate, sensitivity, and positive predictive value than dedicated PET (P < 0.01). We were able to clarify the performance profile of "FDG-PET for cancer screening" on the basis of a Japanese nationwide survey. The number of facilities possessing PET is increasing steadily, highlighting the necessity of evaluating the usefulness of "FDG-PET cancer screening" as soon as possible by undertaking long-term investigations of large series of subjects.

Options for Down Syndrome Screening: What Will Women Choose?

Down syndrome screening has been offered to pregnant women since the early 1980s. Protocols have changed as research confirmed improvements that result in higher detection rates and lower false-positive rates. Results from 2 clinical trials evaluating screening protocols that include ultrasound measurement of nuchal translucency and biochemical testing in the first and second trimester are now available. First-trimester screening is an option if there are adequate ultrasound, diagnostic, and counseling services available. Regional variation in the availability of these services may limit the implementation of first-trimester screening. Combining screening tests for Down syndrome from both trimesters as an integrated test offers the highest detection rate with the lowest false-positive rate. The possibility of avoiding a positive screen will make this an attractive option for some. Timing, detection rate, false-positive rates, and personal factors influence the decision women make regarding screening versus diagnostic testing. This article reviews the efficacy of current protocols for Down syndrome screening. Accurate information about available screening tests will facilitate informed decisions about screening and testing.

First-Trimester Combined Test Screening for Down Syndrome: Results of A Series with 5,036 Cases

Summary Objective To assess the sensitivity of a first-trimester combined screening test for fetal chromosomal abnormalities. Materials and Methods From April 1999 to December 2002, 5,036 unselected women with singleton pregnancies underwent a first-trimester combined test (nuchal translucency thickness, pregnancy-associated plasma protein-A, and free β-human chorionic gonadotropin) screening for Down syndrome. They included 298 (5.9%) women aged 35 years or older and 4,738 (94.1%) women aged below 35 years. A positive result was defined as an estimated Down syndrome risk of greater than 1/270. Results Twenty-five (0.50%) chromosomal abnormalities were identified, with a false-positive rate of 7.1% (333/4,717) in women younger than 35 years and a false-positive rate of 17.3% (51/294) in women of advanced maternal age. The 25 chromosomal abnormalities included trisomy 21 in six fetuses, trisomy 18 and Turner's syndrome in four fetuses each, Klinefelter's syndrome, a marker chromosome and pseudohermaphroditism in one fetus each, and structural rearrangements in eight, including four with balanced translocations. One fetus with trisomy 18 was not discovered at screening, but a fetal ventricular septal defect was found on ultrasound at 30 weeks' gestation. The detection rate for fetal chromosomal abnormalities was 95.2% (20/21). If a cutoff of 1 in 200 was used, the false-positive rate would be 5.6% with the same detection rate, whereas the test still yielded a detection rate of 90.5% (19/21) with a 5% false-positive rate. In 83.3% of cases with trisomy 21 and 5.7% of normal pregnancies, fetal nuchal translucency thickness measurement was above the 95 th percentile, whereas in 0.7% of the study population and in 24% of those with fetal chromosomal abnormalities, the fetal nuchal translucency thickness was at least 3 mm. Conclusion Our results indicate that the first-trimester combined test for Down syndrome is effective in identifying fetal chromosomal abnormalities. Moreover, the measurement of fetal nuchal translucency thickness at 10 to 13 weeks of gestation enables early detection of major fetal structural anomalies.

Cost-effectiveness of human papillomavirus DNA testing for cervical cancer screening in women aged 30 years or more.

To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing as a primary screening test in combination with cervical cytology in women aged 30 years or more. A state-transition mathematical model was used to simulate the natural history of HPV and cervical cancer in a cohort of U.S. women. Strategies included no screening and screening at different frequencies with conventional cytology, liquid-based cytology with HPV testing used for triage of equivocal results, and HPV DNA testing and cytology in combination after women had reached the age of 30. Outcomes measured included cancer incidence, life expectancy, lifetime costs, and incremental cost-effectiveness ratios. The estimated reduction in lifetime risk of cervical cancer varies from 81% to 93% depending on the screening frequency, type of cytology, and test strategy. Every 3-year screening with liquid-based cytology administered to women at all ages and every 3-year screening using HPV DNA testing and cytology in combination administered to women aged 30 years or more provide equivalent or greater benefits than those provided by annual conventional cytology and have incremental cost-effectiveness ratios of US dollars 95300 and US dollars 228700 per year of life gained, respectively. In comparison, annual screening with HPV DNA testing and cytology in combination provides only a few hours of additional life expectancy and has a cost-effectiveness ratio of more than Us dollars 2000000 per year of life gained. For women aged 30 years and more, every 2- or 3-year screening strategy that uses either HPV DNA testing in combination with cytology for primary screening or cytology with reflex HPV DNA testing for equivocal results will provide a greater reduction in cancer and be less costly than annual conventional cytology.

Prenatal Diagnosis after ART Success: The Role of Early Combined Screening Tests in Counselling Pregnant Patients

First-trimester Down syndrome screening may cause a higher false positive rate in pregnant patients who have undergone ART (assisted reproductive technologies). The aim of this paper is to contribute to this analysis with the second largest series of combined biophysical and biochemical tests in the first trimester of pregnancy after ART. One hundred and forty-two singleton successful ART pregnancies were selected for this study: 50 pregnancies induced by using in-vitro fertilization (IVF), and 92 using intracytoplasmic sperm injection (ICSI). Each patient was matched with three naturally conceived pregnancies based on maternal age and gestational age. Free beta-HCG and PAPP-A were measured on dried blood spots and converted to MoMs. Nuchal translucency (NT) was measured by certified operators. Mean maternal age was 33±4. NT, free beta-HCG and PAPP-A values of the control cases were not significantly different from local standards evaluated on 3043 cases. NT between ART pregnancies and matched controls was not significantly different. PAPP-A was reduced but not significantly lower in ART pregnancies. Free beta-HCG was the only analyte that resulted in significantly higher values in ART pregnancies (1.12 MoM) versus controls (0.99 MoM). No significant differences were found for biochemical values observed between ICSI and IVF patients. The screen positive rates observed in ART and control pregnancies were 5.5 per cent and 4.6 per cent respectively NT measurements were not affected by ART pregnancies. Our results (non-significant lower values of PAPP-A and significantly higher free beta-HCG values) were consistent with other reported series. The increase in the screen positive rate determined by these biological variations was not greater than 0.9 per cent. This higher false positive rate has a negligible impact on counselling ART patients. The algorithm used to calculate the relative risk after the combined tests should not be changed until the detection rate of trisomies in ART pregnancies is not fully disclosed by larger series.

Potential value of Plasmodium falciparum-associated antigen and antibody detection for screening of blood donors to prevent transfusion-transmitted malaria.

Malaria antibody detection is a valuable tool in the prevention of transfusion-transmitted malaria in countries with a high proportion of donors with travel exposure to malaria. The immunofluorescent antibody test (IFAT) is still the reference method, but it is not suitable for screening of blood donors. ELISA would be an interesting alternative to the IFAT, but it lacks sensitivity. To evaluate the potential value of a combined screening strategy based on malaria antigen and antibody detection, plasma samples from 203 patients infected with Plasmodium falciparum were tested with an ELISA for the detection of malaria antibodies (Malaria IgG CELISA, Cellabs) and a P. falciparum histidine-rich protein-2 kit (Malaria P.f., ICT Diagnostics) for the detection of malaria antigens. Among patients with positive IFAT results, CELISA had a sensitivity of 71 percent, whereas the combined screening tests (CELISA and Malaria P.f.) had a sensitivity of 88 percent (p < 0.001). Sequential samples from 50 patients were tested. The combined screening tests shortened the detection of seroconversion from 11.4 +/- 1.6 to 5.3 +/- 1.1 days (p < 0.001). Combined malaria antigen and antibody detection, with methods compatible with mass screening, may constitute an attractive alternative to the IFAT for blood donor screening.

Essai de deux reactifs combinés dans le diagnostic biologique de l'infection par les virus de l'immunodéficience humaine type 1 et 2

In aim to reduce the serological window period, combined screening tests to anti-human immunoneficiency viruses types 1 and 2 (HIV 1 2 ) antibodies (Abs) with simultaneous detection of HIV1 p24 antigen, have been introduced in France. A comparative study of two combined screening tests and one classical Abs screening test shows that efficiency in term of fidelity, linearity and limit dilution of a multimarker run control, is similar. By use of HIV1 seroconverter panels, the classical test evaluated may be more sensitive than combined screening tests with, in one case, an earlier detection of seropositivity (up to eleven days). Lastly, the specificity of HIV 1 2 Abs combined screening tests remains lower (between 0.18 and 0.23% of false positive sample) than this of classical Abs screening tests which is minus or equal to 0.12%. Some progress are necessary in this field. Introduction of p24 antigen does not improve the efficiency of the test.