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PubMed2006

The effect of image size on screen-positive rates for nuchal translucency screening.

It has been shown previously that the absolute measurement of nuchal translucency (NT) thickness, one of the most effective screening tests for fetal Down syndrome, significantly decreases with increasing image size. We undertook a prospective study to assess whether this effect materially alters the NT-derived risk estimation for fetal Down syndrome. In 350 women, NT was measured at both 100 and 200% image sizes. The median NT measurement at 200% was 8% smaller than at 100%. The screen-positive rates at 100 and 200% image sizes were 5.1% (18/350) and 2.3% (8/350), respectively (P= 0.048). Altering the image magnification settings is likely to decrease the sensitivity of NT-derived Down syndrome risk estimation. Further study is required to test the effect of our finding on the sensitivity of NT screening and to assess whether adjustments in gain settings mitigate the effect.

Adult↗

PubMed1977

Comparison between the automated reagin test and reagin screen test methods of VDRL screening tests for syphilis in use in a routine laboratory.

A comparison is made between the automated reagin test (ART) using Technicon AutoAnalyzer equipment and the reagin screen test (RST) introduced by Lederle using a new antigen formulation. Treponemal haemagglutination tests (TPHA) were done simultaneously as second screen tests. The absorbed fluorescent treponemal antibody test (FTA-ABS) was used in all seropositive cases. Altogether 1154 sera were tested; 1028 were negative with all tests, 66 were positive with all tests, 42 were positive with TPHA and negative with ART and RST, and 16 were positive with TPHA and RST and negative with ART. It was concluded that the use of the RST and TPHA together would be the more sensitive screen test.

Antibodies, Bacterial↗

PubMed2006

Single reading with computer-aided detection and double reading of screening mammograms in the United Kingdom National Breast Screening Program.

PURPOSE: To retrospectively determine if the use of a computer-aided detection (CAD) system can improve the performance of single reading of screening mammograms to match that of double reading in the United Kingdom. MATERIALS AND METHODS: Local research ethics committee approval was obtained; informed consent was not required. This study included a sample of 10 267 mammograms obtained in women aged 50 years or older who underwent routine screening at one of two breast screening centers in 1996. Mammograms that were double read in 1996 were randomly allocated to be re-read by eight different radiologists using CAD. The cancer detection and recall rates from double reading and single reading with CAD were compared. Statistical significance and confidence intervals were calculated with the McNemar test to account for the matched nature of the data. RESULTS: Single reading with CAD led to a cancer detection rate that was significantly (P = .02) higher than that achieved with double reading: 6.5% more cancers were detected by means of single reading with CAD than by means of double reading. However, the recall rate was higher for single reading with CAD than for double reading (8.6% vs 6.5%, respectively; P < .001). This was equivalent to relative increases of 15% and 32% in the cancer detection and recall rates, respectively. CONCLUSION: Single reading with CAD leads to an improved cancer detection rate and an increased recall rate.

Breast Neoplasms↗

PubMed1981

Radiographic screening for breast carcinoma. III. Appearance of carcinoma and number of projections to be used at screening.

The films of 117 patients with mammary carcinoma detected at population screening were reviewed. Sixteen per cent (19) of the women proved to have non-invasive and 43 per cent (50) small invasive carcinomas (diameter less than or equal to 10 mm). Calcifications were the dominating abnormality in 95 per cent of the non-invasive carcinomas, while a tumour mass was the most frequent abnormality in small invasive carcinomas. It was found that the appearance of small tumours may vary considerably from one projection to another and also on films in one and the same projection. Thus, approximately 20 per cent of small invasive carcinomas were either not visible or equivocal in one of the two projections used at screening. The corresponding figure for larger invasive carcinomas (diameter greater than 10 mm) was approximately 7 per cent. It is concluded that films in two projections, preferably the craniocaudal and oblique, should be obtained at screening.

Aged↗

PubMed2002

Comparison of high throughput screening technologies for luminescence cell-based reporter screens.

As higher density formats become more and more common in HTS labs, the expectations for maintaining faster, lower cost screens puts great pressure on traditional 96-well screens. In some cases higher density formats are not compatible with the assay. This seems especially true in cell-based assays. In our case, the nature of the cells' response forced us to remain in 96-well plates. In this paper, we describe the development of a luminescence reporter assay and its performance in two detection modes, flash and glow. The advantages in cost and throughput for each technique are explored, along with automation considerations. An additional new technology, the use of pins for low-volume transfers, is also briefly described because of its dramatic effect on our screen's throughput. However, it will be more thoroughly presented in a future publication. Comparing the technologies available for HTS aids in designing automated systems that meet the unique needs of each assay.

Anti-HIV Agents↗

PubMed2004

Multiplexing fluorescence polarization assays to increase information content per screen: applications for screening steroid hormone receptors.

As the push to reduce cost per well in high-throughput screening reaches the practical limitations of liquid handling, future cost savings will likely arise from an increase in information content per well. One strategy to increase information content is to perform discreet assays against multiple targets in a single well. In such assays, reagent usage and liquid handling steps do not scale-up in direct proportion to the increase in information content, providing for a simple method to increase data points per screen without further reductions in assay volume. The authors have used tracers incorporating the spectrally distinct fluorophores fluorescein and TAMRA to develop a high-throughput assay to identify selective estrogen receptor alpha or progesterone receptor ligands. Selectivity is assessed immediately in this assay, with no requirement for separate follow-up screening to determine selectivity. This methodology is easily adaptable to other target classes.

Drug Evaluation, Preclinical↗

PubMed2005

A more aggressive breast cancer spheroid model coupled to an electronic capillary sensor system for a high-content screening of cytotoxic agents in cancer therapy: 3-dimensional in vitro tumor spheroids as a screening model.

One major problem in cancer therapy is the immortality of tumor cells showing an active telomerase, which is responsible for the elongation of the telomeres after each cellular division and the knocking down of apoptotic suppressors. A further phenomenon occurring during cancer therapies is the problem of multicellular resistance. To develop therapeutic anticancer approaches inducing cellular apoptosis, gene-modified biological in vitro systems were established and evaluated for drug screening in a capillary system for a real-time, impedimertic monitoring. Multicellular spheroids of the human breast cancer cell line T-47D clone 11 were transfected with 1) antisense caspase-3 cDNA expression vectors for knocking down the main cell death molecule and 2) sense Bcl-xl cDNA expression vectors for overexpressing the apoptotic suppressor, resulting in more aggressive tumor models. These gene-modified tumor spheroids less sensitive for apoptosis were developed for screening drugs such as methotrexate in tumor spheroid-based biosensor systems via impedance spectroscopy. In this report, it is demonstrated that this could successfully exhibit that this real-time monitoring system with tumor spheroids positioned in a capillary system with a 4-electrode configuration is the most efficient high-content screening module for impedimetric measurements of physiological alterations during gene modification and drug application.

Antineoplastic Agents↗

PubMed2006

Development and validation of a high-throughput screen for inhibitors of SARS CoV and its application in screening of a 100,000-compound library.

The authors have developed a high-throughput screen (HTS) that allows for the identification of potential inhibitors of the severe acute respiratory syndrome coronavirus (SARS CoV) from large compound libraries. The luminescent-based assay measures the inhibition of SARS CoV-induced cytopathic effect (CPE) in Vero E6 cells. The assay was validated in 96-well plates in a BSL3 containment facility. The assay is sensitive and robust, with Z values > 0.6, signal to background (S/B) > 16, and signal to noise (S/N) > 3. The assay was further validated with 2 different diversity sets of compounds against the SARS CoV. The "hit" rate for both libraries was approximately 0.01%. The validated HTS assay was then employed to screen a 100,000-compound library against SARS CoV. The hit rate for the library in a single-dose format was determined to be approximately 0.8%. Screening of the 3 libraries resulted in the identification of several novel compounds that effectively inhibited the CPE of SARS CoV in vitro-compounds which will serve as excellent lead candidates for further evaluation. At a 10-microM concentration, 3 compounds with selective indexes (SI50) of > 53 were discovered.

Animals↗

PubMed1999

A Screening Strategy Based on Differential Binding of Ligand to Receptor and to Binding Proteins: Screening for Compounds Interacting with Corticotrophin-Releasing Factor-Binding Protein.

The ligand-receptor interaction has been commonly used in development of high throughput screening assays for new drugs. In some cases, an endogenous ligand interacts not only with membrane receptors but also with soluble binding proteins. Corticotrophin-releasing factor (CRF) is an important stress neurotransmitter/hormone involved in both the central and peripheral nervous systems. CRF exerts its function by interacting with CRFR1 and CRFR2 receptors. In addition, CRF-binding protein (CRF-BP) binds CRF with high affinity. Accordingly, CRF-BP has been suggested to play an important role in modulating CRF function. Based on the potential involvement of CRF-BP in many neurological disorders, it is desirable to develop a screening assay to look for drugs that either mimic or interfere with CRF binding to CRF-BP. An assay was developed to monitor the interactions of radiolabeled CRF with human/rat CRF-BP and the mouse CRFR1 (mCRFR1) receptor. By carefully examining the binding characteristics of radiolabeled CRF to mCRFR1, the assay was able to identify compounds that bind to CRF-BP with high affinity and have little or no affinity for mCRFR1 receptors. Based on a mathematical model, we have verified the screening system with several well-characterized CRF ligands that all have different affinities for CRF receptors and CRF-BP.

Journal Article↗

PubMedDate not supplied

Evaluation of diagnostic accuracy of screening by fecal occult blood testing (FOBT). Comparison of FOB Gold and OC Sensor assays in a consecutive prospective screening series.

We evaluated a new immunological fecal occult blood testing assay (FOB Gold, Sentinel = SENT) compared to the assay currently employed in the Florence screening program (OC-Hemodia, Eiken = OC). A total of 4,133 subjects were screened with both tests and underwent colonoscopy if positive (100 ng/mL Hb cutoff) to either test: 190 (4.59%) were positive (OC =140 (3.4%); SENT = 131 (3.2%)). The relative sensitivity for 7 cancers was 100% with OC and 67.9% with SENT, and for 48 high-risk adenomas (HRAs) it was 77.0% with OC and 66.6% with SENT. The positive predictive value (PPV) for cancer+HRA was 31.4% for OC and 28.2% for SENT and the specificity was 97.7 for both. The differences were not statistically significant. Adding SENT to OC increased the positivity rate by 32% and the cancer+HRA detection rate by 25%, and decreased the PPV by 10%. Both tests were performed on the same tubes in 1,601 cases, and in 18 of 47 cases they differed on different tubes but not on the same tube, suggesting inhomogeneous Hb content or varying fecal matrix influence in different samples. SENT has practical advantages for screening [corrected] (fully automated, high output, requires no dedicated instrument), a comparable specificity and a lower sensitivity, though the latter difference may be partially ascribed to differences in sampling and not to the assay itself [corrected] Because of the statistical insignificance of the differences, further studies are needed for confirmation.

Adenoma↗

PubMed1994

The Psychological Screening Inventory's usefulness as a screening instrument for adolescent inpatients.

Two studies assessing the validity of the Psychological Screening Inventory (PSI; Lanyon, 1970) as a screening inventory for adolescent inpatients are reported. Results were mixed. Significant differences in mean scores between adolescent normals and inpatients were found on three scales of the PSI (Alienation, Social Nonconformity, and Discomfort); however, no significant differences in mean scores on any of the five scales were found between hospital referrals deemed appropriate for hospitalization and referrals deemed inappropriate for hospitalization. Further, five alternative rules for using the PSI as a psychiatric screening instrument for referrals were tested. Hit rates using these rules were unacceptable.

Adaptation, Psychological↗

PubMed2005

[High throughput screening of pharmacokinetics and metabolism in drug discovery (II)--investigation on in vitro and in vivo correlation in drug metabolism screening].

Metabolic screening using liver microsomes of rats and humans is an indispensable tool to optimize a lead structure and to select compounds for in vivo study. Elucidating the relationship between in vitro intrinsic clearance (CL(int, app)) and in vivo clearance (CL(b)) is a prerequisite for screening. We investigated the relationship between CL(int, app) in rat liver microsomes and CL(b) after intravenous administration in rats in eight projects. No relationship between these two parameters was found across all of the projects examined. However, there was a certain relationship in the same core structure of six projects, but not in the other two projects. The poor correlation in the projects was improved by considering serum protein binding or microsomal binding in the estimation of in vitro clearances. Although the binding assay was labor intensive, unlike metabolic screening, the introduction of the equilibrium dialysis method using a 96-well format increased the throughput. Optimization of metabolic stability was conducted on the basis of the structure-metabolic stability relationship (SMR) in one of the projects, showing a good correlation without the binding factors. The replacement of the piperazine with a homopiperazine moiety improved metabolic stability in the rat and human liver microsomes. The compound also showed a desirable in vivo pharmacokinetic profile in rats, suggesting that the SMR study on the confirmed in vitro and in vivo correlation is essential to the optimization.

Animals↗

PubMed2003

A screening measure for BPD: the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD).

Borderline personality disorder (BPD) is a common psychiatric disorder that is often overlooked in treatment settings. This report describes the validation of a new self-report screening measure for DSM-IV BPD--the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD). Two hundred subjects with treatment histories whose ages ranged from 18 to 59 filled out the MSI-BPD. Each subject was then interviewed, blind to MSI-BPD results, with the BPD module of the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV; Zanarini, Frankenburg, Sickel, & Yong, 1996). Of these 200 subjects, 139 (69.5%) met DSM-IV criteria for BPD as assessed by the BPD module of the DIPD-IV and the remaining 61 subjects (30.5%) did not. Using logistic regression analyses, an MSI-BPD cutoff of 7 or more of the measure's 10 items was judged to be the best cutoff. This was so because it yielded both good sensitivity (.81; percentage of correctly identified cases) and specificity (.85; percentage of correctly identified noncases) for the diagnosis of DSM-IV BPD. For younger subjects, diagnostic efficiency was even greater. For example, sensitivity was .90 and specificity was .93 at a cutoff of 7 for the 63 subjects who were 25 years old or younger. The results of this study suggest that the MSI-BPD may be a useful screening instrument for the presence of DSM-IV borderline personality disorder.

Adolescent↗

PubMed2000

A brief screening instrument for problem drinking in the emergency room: the RAPS4. Rapid Alcohol Problems Screen.

OBJECTIVE: While a number of brief screening instruments for identifying problem drinkers have been tested in clinical settings, instruments have not been found to perform as well for women as for men, or to perform uniformly across ethnic groups. The purpose of this study was to evaluate a shortened version of the RAPS (Rapid Alcohol Problems Screen) in an emergency room (ER) sample (N = 1,429; 51% female) and to determine the most efficient ordering of the items. METHOD: The sensitivity and specificity of each of the RAPS items were examined against current ICD-10 and DSM-IV criteria for alcohol dependence, and separately for harmful drinking or abuse. A four-item version of the RAPS (the RAPS4) was analyzed separately for men and for women, and for blacks, Hispanics and whites/others. RESULTS: Among the five original RAPS items, four items were found to be most efficient, with the single item of feeling guilt or remorse after drinking identifying 83% of those with alcohol dependence and 44% of those meeting criteria for harmful drinking or abuse. A positive response to any one of the four items (RAPS4) gave a sensitivity of 93% and specificity of 87% for alcohol dependence, and sensitivity and specificity were consistently high across gender and ethnic subgroups. Sensitivity and specificity for harmful drinking or abuse were lower (55% and 79%, respectively). CONCLUSIONS: Because of its brevity and high performance across demographic subgroups, the RAPS4 may hold promise in screening for alcohol use disorders in patient populations, and its utility warrants further evaluation in clinical settings.

Adolescent↗

PubMed2006

Energy expenditure of sedentary screen time compared with active screen time for children.

OBJECTIVE: We examined the effect of activity-enhancing screen devices on children's energy expenditure compared with performing the same activities while seated. Our hypothesis was that energy expenditure would be significantly greater when children played activity-promoting video games, compared with sedentary video games. METHODS: Energy expenditure was measured for 25 children aged 8 to 12 years, 15 of whom were lean, while they were watching television seated, playing a traditional video game seated, watching television while walking on a treadmill at 1.5 miles per hour, and playing activity-promoting video games. RESULTS: Watching television and playing video games while seated increased energy expenditure by 20 +/- 13% and 22 +/- 12% above resting values, respectively. When subjects were walking on the treadmill and watching television, energy expenditure increased by 138 +/- 40% over resting values. For the activity-promoting video games, energy expenditure increased by 108 +/- 40% with the EyeToy (Sony Computer Entertainment) and by 172 +/- 68% with Dance Dance Revolution Ultramix 2 (Konami Digital Entertainment). CONCLUSIONS: Energy expenditure more than doubles when sedentary screen time is converted to active screen time. Such interventions might be considered for obesity prevention and treatment.

Child↗

PubMed1976

The worth of a screening program: an application of a statistical decision model for the benefit evaluation of screening projects.

A statistical decision model is applied to the benefit evaluation of screening projects to derive an expression which provides upper and lower limits for average benefits in terms of prevalance rates of screen positives and negatives, and the average cost of screening and referral. Possible applications of such a technique are discussed and a numerical example is given.

Bayes Theorem↗

PubMed1992

Colonoscopic screening examination of relatives of patients with colorectal cancer. I. A comparison with an endoscopically screened normal population.

First-degree relatives (n = 206) of patients operated on for colorectal cancer (CRC) (n = 181) were offered a colonoscopic screening examination; 169 relatives (82%) attended. The findings were compared with those in a normal population sample with no CRC in first-degree relatives (n = 308), aged 50-59 years, who had been screened by means of flexible sigmoidoscopy. Three carcinomas and 176 polyps were found in 56 of 95 male relatives (57%) and 34 of 74 female relatives (46%). The adenoma prevalence rate was 37 (39%) and 26 (35%) for male and female relatives, respectively. In the 50- to 59-year age group, the adenoma prevalence rates for both sexes collectively and for women separately were significantly higher among relatives than among the population without CRC relatives. Hyperplastic polyps were larger, whereas adenomas were similar in size among relatives compared with the normal population. Colonoscopy may be a suitable method of choice for screening first-degree relatives of patients with CRC.

Adenoma↗

PubMed1998

Validation of a fall-risk screening test, the Elderly Fall Screening Test (EFST), for community-dwelling elderly.

Falls are the most common type of injury among the elderly, and the source of both functional and psychological morbidity. The aim of this study was to validate the Elderly Fall Screening Test (EFST). In a community primary-care clinic, the members 60 years or older who were functionally independent were screened. Of the 568 elderly persons who met these criteria, 361 were interviewed once and 283 persons were re-interviewed a year later. The EFST, a five-item test, was used to divide participants into low- and high-risk groups. Concurrent criterion validity was assessed by physical examinations conducted by physicians who were blind as to the risk designation. Using data from the follow-up interview, predictive validity was assessed on both fall-related and general health measures. Based on the results of the EFST, 28% of the respondents were designated as being at high risk for falls (i.e. having a score of two or more risk items). The results of physicians' examinations corroborated the screening test results in 75% of the cases, with 83% sensitivity and 69% specificity. In the follow-up interview, the high-risk group, as compared to the low-risk group, was more likely to have high scores on EFST, a fall in the past month or year, frequent near falls, and an injurious fall. Those with high EFST scores were more likely to report four or more sick days in the past six months, a hospitalization in the past year, poor self-rated health, a decline in health in the past 6 months, and symptoms of depression. The EFST has both criterion and predictive validity. It can be useful in community-based prevention programmes with functionally independent elderly people.

Accidental Falls↗