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PubMed1993

Will screening for breast cancer reduce mortality? Evidence from the first year of screening in Avon.

In the first year of screening in Avon, 93 malignant lesions were detected of which one-half were impalpable. Of the impalpable lesions, one-half were in situ or showed areas of microinvasion only. One-fifth of the malignant lesions were invasive tumours of special histological type which are known to carry a good prognosis even when not detected by screening. One-quarter of the lesions had clinical or pathological features which would be expected to confer a poor prognosis. Only 16 invasive ductal carcinomas measuring 1 cm or less in diameter were detected--a small proportion of the total number of malignant lesions. Although these early figures suggest that the effect of screening on mortality from breast cancer may be small, continued high-quality screening and careful detailed analysis are essential to determine the effect of screening on the mortality from breast cancer and the effect on the population as a whole.

Breast Neoplasms↗

PubMed1993

[Leipzig neonatal screening center--experiences with introduction of screening for congenital hypothyroidism].

The development of neonatal screening for congenital hypothyroidism in the GDR and particularly in Saxony after German reunification is described in this paper. The results of the studies and the experiences in respect of realisation and organisation of the screening for hypothyroidism in the screening centre of Leipzig are discussed. Measurement of TSH in the blood spot of about 65,000 newborn yielded an incidence rate of congenital hypothyroidism of 1:3,200. The onset of therapy within the first three weeks of life has been ensured until now since no children with congenital hypothyroidism were involved in cases of occasionally delayed blood sampling and/or postal delay. However, there has been some organisational disparity due to individually different handling of health insurance fund payments of screening fees for hypothyroidism in Saxony and also in the other federal states. The disadvantages of this lack of uniform regulations are explained. Neonatal screening for evidence of congenital adrenal hyperplasia by determining 17-alpha-hydroxyprogesterone, is under preparation.

Congenital Hypothyroidism↗

PubMed1996

[Mammographic screening in the municipality of Copenhagen. Results of the first screening round].

The aim of the study was to evaluate the results from the prevalence round of the mammography screening programme in the Municipality of Copenhagen. All women who by 1 April 1991 were 50-69 years old, and who lived in the Municipality of Copenhagen, were during the period 1 April 1991-24 April 1993 offered a mammography. Those with suspect findings were recalled for further examination and possible biopsy. Women with breast cancer were offered treatment according to the standard national protocols (DBCCG). The participation rate was 71% (30,416/43,087). Among these 2043 (6.7%) were re-examined and 592 (1.9%) underwent surgical biopsy. Breast cancer was revealed in 359 (1.2%) women, of whom 88% had an invasive breast cancer. Prevalence of breast cancer increased significantly with increasing age. The positive predictive value for breast cancer among those re-examined was 18% and for those who had a surgical biopsy 61%. Among women with an invasive breast cancer 41% had a tumour of 10 mm or less, 80% had negative lymph node status and 56% had breast conserving surgery. During the following 12 months 14 women with a normal mammogram at the screening round developed breast cancer giving a sensitivity of 96%. It is concluded that the first mammography screening in Denmark showed the highest breast cancer prevalence published so far. A possible explanation could be a high sensitivity of the screening method, indicated by a relatively high frequency of small cancers. The screening programme was fully comparable with international standards.

Aged↗

PubMedDate not supplied

Screening helical CT for mass screening of lung cancer: application of low-dose and single-breath-hold scanning.

PURPOSE: To investigate the usefulness of helical CT with low-dose and single-breath-hold scanning for lung cancer screening. MATERIALS AND METHODS: Twenty-four helical CT scans of the lung were performed using various parameters in 10 healthy volunteers. The effects of tube current and pitch were evaluated by assessment of image quality and detection of simulated nodules. Screening helical CT was performed at 120 kVp, 50 mA, 1 sec/rotation, 10 mm collimation, and a pitch of 2.0 in 110 patients. The ability of this method to detect nodules and masses, focal parenchymal opacities, and diffuse fibrotic changes was evaluated using conventional CT as the gold standard. RESULTS: A reduction in tube current to 50 mA did not significantly change the assessment of image quality or detection of simulated nodules. Although these factors were degraded by increasing the pitch, there was no significant difference between 1.5 and 2.0. Screening helical CT permitted the entire lung to be scanned with ease during a single-breath-hold in all patients. This method detected 177 of 196 nodules and masses (87 of 91 lesions greater than 5 mm in diameter), 54 of 57 focal parenchymal opacities, and 15 of 15 cases with fibrotic changes. CONCLUSION: Screening helical CT with low-dose and single-breath-hold scanning shows promise for lung cancer screening.

Adult↗

PubMed2005

Perceptions of insurance coverage for screening mammography among women in need of screening.

BACKGROUND: Breast carcinoma remains a significant health problem in the U.S., especially among underserved populations. Although screening mammography is recommended for early detection, in 2002, approximately 25% of women age > 40 years had not had a mammogram within the past 2 years. The current study examined perceptions of insurance coverage and cost as barriers to screening mammography within an underserved, predominantly low-income population of women in need of a mammogram. METHODS: Between 1998 and 2002, face-to-face interviews were conducted with 897 women age > or = 40 years. All women were part of a randomized, controlled study evaluating a health education intervention designed to improve mammography screening. They were asked questions at baseline about cost and insurance coverage as barriers to mammography screening. Women's reports of their level of insurance coverage for mammography were compared with actual coverage by their insurance type to determine the accuracy of their perception of insurance coverage for mammography. The relation between perception of insurance coverage and the barrier of cost was investigated. RESULTS: Greater than half of the women who needed a mammogram identified cost as a barrier to mammography; however, 40% of these women had an inappropriate perception of their insurance coverage. Underestimating or not knowing the level of mammography coverage was strongly associated with reporting cost-related difficulty (odds ratio [OR] = 4.57, 95% confidence interval [95% CI], 1.95-10.70 for the underestimate category; OR = 4.42, 95% CI, 1.80-10.88 for the don't know category), regardless of true coverage levels. CONCLUSIONS: Providing women with information regarding their actual coverage for mammograms may reduce the impact of cost as a barrier to screening mammography.

Adult↗

PubMed2006

Should children at risk for familial adenomatous polyposis be screened for hepatoblastoma and children with apparently sporadic hepatoblastoma be screened for APC germline mutations?

BACKGROUND: Hepatoblastoma (HB) is the most frequent liver tumor in childhood, occurring in the first few years of life. Surgery combined with chemotherapy has resulted in dramatic improvements in prognosis. However, even today, about one quarter of affected children do not survive the disease. Compared to the general population, the risk of HB is 750-7,500 times higher in children predisposed to familial adenomatous polyposis (FAP), an autosomal-dominant cancer predispostion syndrome caused by germline mutations in the tumor suppressor gene APC. Only limited data exist about the frequency of APC germline mutations in cases of apparently sporadic HB without a family history of FAP. PROCEDURE: In our sample of 1,166 German FAP families, all known cases of HB were registered. In addition, 50 patients with apparently sporadic HB were examined for APC germline mutations. RESULTS: In the FAP families, seven unrelated cases of HB are documented; three had been detected at an advanced stage. In patients with apparently sporadic HB, germline mutations in the APC gene were identified in 10%. CONCLUSIONS: These data raise the issue of the appropriate screening for HB in children of FAP patients. To date, the efficiency of surveillance for HB is unclear. In Beckwith-Wiedemann syndrome (BWS), recent studies suggest an earlier detection of both Wilms tumor and HB by frequent screening. We discuss the rationale and implications of a screening program; besides the examination procedure itself, screening for HB in children of FAP patients would have important consequences for the policy of predictive testing in FAP. In a substantial fraction of sporadic HB, the disease is obviously the first manifestation of a de novo FAP. These patients should be identified by routine APC mutation screening and undergo colorectal surveillance thereafter.

Adenomatous Polyposis Coli↗

PubMed1999

Screening tests for antinuclear antibodies (ANA): selective use of central nuclear antigens as a rational basis for screening by ELISA.

Rational, fully automated ELISA screening tests for ANA have become accessible for routine use. Full length, recombinant or purified naturally expressed antigens can be selected to deliver well defined screening tests, designed to detect ANAs of established clinical significance, while unknown specificities with no clear biological impact are omitted. By comparing results of ANA screening by immunofluorescence (IIF) on tissue section with HEp-2 cells, a correlation of 88% was revealed, while 86% of HEp-2-positive sera bound tissue sections. Eighty-nine percent of HEp-2 ANA-positive sera bound in ANA ELISA I. Seventy-five percent of ANAs detected in ELISA I also bound in ELISA II. These correlations were statistically significant. ANAs detected in ANA ELISA I were all detected upon retesting in both ANA screening ELISA systems, and also by antigen-specific ELISAs. Specific ANAs defined by ELISA, immunodiffusion or Crithidia tests were detected in both ANA ELISA tests. These data demonstrate that most ANAs detected by immunofluorescence tests contain a dominating repertoire of specificities covered by the ANA ELISA systems. The sensitivity of the different ELISA tests can easily be adjusted to internationally defined consensus levels, and screening for ANA using both ELISA systems detects expected ANA specificities in ongoing international quality assessment programs.

Antibodies, Antinuclear↗

PubMed2001

Intensive Care Delirium Screening Checklist: evaluation of a new screening tool.

OBJECTIVE: Delirium in the intensive care unit is poorly defined. Clinical evaluation is difficult in the setting of unstable, often intubated patients. A screening tool may improve the detection of delirium. METHOD: We created a screening checklist of eight items based on DSM criteria and features of delirium: altered level of consciousness, inattention, disorientation, hallucination or delusion, psychomotor agitation or retardation, inappropriate mood or speech, sleep/wake cycle disturbance, and symptom fluctuation. During 3 months, all patients admitted to a busy medical/surgical intensive care unit were evaluated, and the scale score was compared to a psychiatric evaluation. RESULTS: In 93 patients studied, 15 developed delirium. Fourteen (93%) of them had a score of 4 points or more. This score was also present in 15 (19%) of patients without delirium, 14 of whom had a known psychiatric illness, dementia, a structural neurological abnormality or encephalopathy. A ROC analysis was used to determine the sensitivity and specificity of the screening tool. The area under the ROC curve is 0.9017. Predicted sensitivity is 99% and specificity is 64%. CONCLUSION: This study suggests that the Intensive Care Delirium Screening Checklist can easily be applied by a clinician or a nurse in a busy critical care setting to screen all patients even when communication is compromised. The tool can be utilized quickly and helps to identify delirious patients. Earlier diagnosis may lead to earlier intervention and better patient care.

APACHE↗

PubMed2001

Electrochemical characterization of screen-printed carbonaceous electrodes for the determination of peroxidase activity in novel screen-printed flow-through modules.

A novel totally screen-printed flow-through cell for immunoanalysis is presented. It contained screen-printed carbonaceous electrodes, which allowed the determination of peroxidase activity through the electrochemical reduction of p-benzoquinone. As different electrode materials differ strongly in their electrochemical properties, electrodes resulting from various screen-printable carbonaceous pastes were characterized using the hydroquinone/ p-benzoquinone redox couple. For most of the electrodes, cyclic voltammogram peak separations of between 550 and 670 mV were observed indicating only quasi-reversible electrochemical behavior. This was confirmed by variation of the peak separation with scan rate. Heterogeneous electron transfer rates of ca. 0.5 - 1 x 10(-3) cm s(-1) and electrochemical activation energies of ca. 20 kJ mol(-1) were found. These flow-through cells were not only applied to electrochemical peroxidase activity determinations but also, in combination with a separate detector, as affinity reactors. After biotinylation of screen-printed layers, streptavidin and then biotinylated peroxidase could be bound. However, as signals were only 10-20% of those obtained with a column filled with biotinylated glass beads, only the screen-printed electrochemical detector was applied to the detection of antibodies against the African Swine Fever Virus.

Animals↗

PubMed1995

Screening for alcohol problems in the emergency room: a rapid alcohol problems screen.

This paper compares the sensitivity and specificity of a five-item Rapid Alcohol Problems Screen (RAPS) optimized in this sample with the CAGE, brief MAST, AUDIT, TWEAK, History of Trauma Scale and breathalyzer reading against ICD-10 criteria for alcohol dependence or harmful drinking, by gender, ethnicity and injury status in a probability sample of emergency room patients (n = 1330) from the University of Mississippi Medical Center. The RAPS performed better than all other screening instruments for the total sample of current drinkers who reported ever having had three or more drinks at one time (sensitivity of 90%, specificity of 78%), and performed consistently better across all subgroups than any other single instrument, even at alternate cut points. The Rapid Alcohol Problems Screen may hold promise for use in clinical settings in identifying those who could benefit from a brief intervention or referral for problem drinking, particularly since the instrument is short and patients need not be asked additional questions after screening positive on one of the five items. Further research is necessary to analyze and compare the performance of the RAPS with other screening instruments across demographic subgroups in other emergency room and primary care settings.

Adult↗

PubMed2004

Screening for drug use disorders in the emergency department: performance of the rapid drug problems screen (RDPS).

Little research is available on brief screening instruments for identify those meeting diagnostic criteria for drug dependence or abuse. A brief, four-item screening instrument, called the rapid drug problems screen (RDPS), was developed from a similar instrument for alcohol use disorders, the rapid alcohol problems screen (RAPS). Performance of the RDPS was evaluated against DSM-IV and ICD-10 criteria for drug dependence and for dependence or abuse in a sample of 703 emergency department patients in Mexico City. Among males, sensitivity and specificity were 91 and 96%, respectively, for dependence and 93 and 96%, respectively, for dependence or abuse. Neither of the two females meeting diagnostic criteria for dependence or abuse were identified by the RDPS. Area under the receiver-operating characteristic curve indicates an optimum cut point of 1. The data suggest that the RDPS may hold promise as a brief screening instrument for substance use among males, but should be tested in larger populations of females meeting diagnostic criteria for drug use disorders, and across ethnic subgroups in other geographic locales.

Adult↗

PubMed2004

Prostate-specific antigen velocity at low prostate-specific antigen levels as screening tool for prostate cancer: results of second screening round of ERSPC (ROTTERDAM).

OBJECTIVES: To study retrospectively whether the prostate-specific antigen (PSA) velocity, that is, the change in PSA level over time, might serve as a screening tool in this PSA range. It is estimated that 40% of detectable prostate cancers are present in men with a PSA level of 4.0 ng/mL or less. Digital rectal examination and/or transrectal ultrasonography have been used as screening tools at these low PSA levels, but this approach is not very efficient. METHODS: The possible predictors (including PSA velocity) for biopsy outcome were studied using univariate and multivariate logistic regression analysis in 774 men who underwent biopsy between November 1997 and January 2002 in the second screening round of the European Randomised Study of Screening for Prostate Cancer (ERSPC). The clinical stage of the tumors was determined, and the Gleason scores of the biopsies were studied. RESULTS: A total of 149 cancers were found (positive predictive value 19.2%). The odds ratio for the PSA velocity determined by univariate logistic regression analysis was 2.2 (95% confidence interval 0.7 to 6.9, P = 0.19) and was 0.73 (95% confidence interval 0.20 to 2.6, P = 0.64) by multivariate analysis. The distribution of the clinical stage of the detected tumors was 64.4% T1c, 32.2% T2, and 3.4% T3. The biopsy Gleason score was 6 in 84.5%, 7 in 14.2%, and 8 in 1.3%. CONCLUSIONS: The number of cancers detected in this study and the distribution of clinical stage and biopsy Gleason score confirmed that a relatively large proportion of potentially curable cancers can be found in the low PSA ranges. The PSA velocity did not appear to be a useful screening tool for the identification of these cancers.

Adenocarcinoma↗

PubMedDate not supplied

Parallel screening: a novel concept in pharmacophore modeling and virtual screening.

Parallel screening comprises a novel in silico method to predict the potential biological activities of a compound by screening it with a multitude of pharmacophore models. Our aim is to provide a fast, large-scale system that allows for virtual activity profiling. In this proof of principle study, carried out with the software tools LigandScout and Catalyst, we present a model work for the application of parallel pharmacophore-based virtual screening on a set of 50 structure-based pharmacophore models built for various viral targets and 100 antiviral compounds. The latter were screened against all pharmacophore models in order to determine if their biological targets could be correctly predicted via an enrichment of corresponding pharmacophores matching these ligands. The results demonstrate that the desired enrichment, that is, successful virtual activity profiling, was achieved for approximately 90% of all input molecules. We discuss descriptors for output validation, as well as various aspects influencing the analysis of the obtained activity profiles, and the effect of the utilized search modus for screening.

Antiviral Agents↗

PubMed2000

Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A promising alternative to random screening.

Random screening provided no suitable lead structures in a search for novel inhibitors of the bacterial enzyme DNA gyrase. Therefore, an alternative approach had to be developed. Relying on the detailed 3D structural information of the targeted ATP binding site, our approach combines as key techniques (1) an in silico screening for potential low molecular weight inhibitors, (2) a biased high throughput DNA gyrase screen, (3) validation of the screening hits by biophysical methods, and (4) a 3D guided optimization process. When the in silico screening was performed, the initial data set containing 350 000 compounds could be reduced to 3000 molecules. Testing these 3000 selected compounds in the DNA gyrase assay provided 150 hits clustered in 14 classes. Seven classes could be validated as true, novel DNA gyrase inhibitors that act by binding to the ATP binding site located on subunit B: phenols, 2-amino-triazines, 4-amino-pyrimidines, 2-amino-pyrimidines, pyrrolopyrimidines, indazoles, and 2-hydroxymethyl-indoles. The 3D guided optimization provided highly potent DNA gyrase inhibitors, e. g., the 3,4-disubstituted indazole 23 being a 10 times more potent DNA gyrase inhibitor than novobiocin (3).

Anti-Infective Agents↗

PubMed2005

Virtual screening of biogenic amine-binding G-protein coupled receptors: comparative evaluation of protein- and ligand-based virtual screening protocols.

In this paper, we compare protein- and ligand-based virtual screening techniques for identifying the ligands of four biogenic amine-binding G-protein coupled receptors (GPCRs). For the screening of the virtual compound libraries, we used (1) molecular docking into GPCR homology models, (2) ligand-based pharmacophore and Feature Tree models, (3) three-dimensional (3D)-similarity searches, and (4) statistical methods [partial least squares (PLS) and partial least squares discriminant analysis (PLS-DA) models] based on two-dimensional (2D) molecular descriptors. The comparison of the different methods in retrieving known antagonists from virtual libraries shows that in our study the ligand-based pharmacophore-, Feature Tree-, and 2D quantitative structure-activity relationship (QSAR)-based screening techniques provide enrichment factors that are higher than those provided by molecular docking into the GPCR homology models. Nevertheless, the hit rates achieved when docking with GOLD and ranking the ligands with GoldScore (up to 60% among the top-ranked 1% of the screened databases) are still satisfying. These results suggest that docking into GPCR homology models can be a useful approach for lead finding by virtual screening when either little or no information about the active ligands is available.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2001

Prenatal screening for Down's syndrome: some psychosocial implications of a 'screening for all' policy.

The National Screening Committee of the Department of Health has made recommendations to the Government advising that prenatal screening for Down's syndrome should be offered to all pregnant women regardless of their age. As most women over 35 are already offered some form of testing, affected pregnancies in younger women will account for the majority of any increased overall detection rate. Therefore, while a 'screening for all' policy will offer wider reproductive choices to more women, it is likely to specifically increase the number of young women experiencing termination of pregnancy for abnormality. A number of inter-dependent factors predispose some women to high levels of psychological distress following termination, and a combination of these factors is most likely to be found in the very young. In addition, very young women often have little knowledge of prenatal testing and may be more likely to accept screening presented as 'routine' without considering the consequences. At the point where decisions about diagnostic testing or termination are made, more specialised support may be indicated for some very young women. If the UK National Screening Committee's recommendations are taken forward therefore, service providers should ensure suitable support is available for some of their more vulnerable clients.

Abortion, Induced↗

PubMed1999

Prevalence of cervical cancer and feasibility of screening in rural China: a pilot study for the Shanxi Province Cervical Cancer Screening Study.

For cervical cancer screening to be feasible in developing countries, it must be accurate, inexpensive, and easy to administer. We conducted a pilot study in rural Shanxi Province, People's Republic of China, to determine disease prevalence and study feasibility in preparation for a large-scale comparative trial of 6 screening tests. One-hundred and thirty-six nonpregnant women with no history of hysterectomy, pelvic radiation, or Papanicolaou tests were screened in a rural clinic. Ten percent of the women enrolled reported abnormal vaginal bleeding and 45% reported abnormal vaginal discharge. The tests were the Papanicolaou test (both conventional and ThinPrep), a self-administered swab test by Hybrid Capture II for high-risk human papillomavirus (HPV), a test for high-risk HPV from residual PreservCyt medium, fluorescence spectroscopy, and visual inspection of the cervix by a clinician. All women also underwent colposcopy and biopsies as the reference standard. Biopsies showed 12 of 136 women had >/= high-grade squamous intraepithelial lesions (HGSIL). Screening was completed in 5 half-day sessions, the procedures went smoothly, and local cooperation was enthusiastic. Disease prevalence in Xiangyuan and Yangcheng Counties, Shanxi Province, can be estimated at 8.8% (95% CI, 4.5% to 15.0%). Screening 1000-2000 patients would be sufficient to detect a 10% difference in accuracy between diagnostic tests. The proposed large-scale trial is feasible.

Journal Article↗

PubMed2001

Symptomatic women with normal screening mammograms: is assessment by the breast screening programme justifiable?

Since the commencement of screening in 1988, the West of Scotland Breast Screening Programme has invited women with symptoms, but normal screening mammograms, for assessment. This paper reviews the results of 344 such assessments. Malignancy was detected in three patients; two had invasive carcinoma and one Paget's disease of the nipple. One woman underwent a benign excision biopsy. Three women returned to routine recall were subsequently diagnosed with breast cancer; one had Paget's disease, a second developed a true interval cancer, and a third a screen detected cancer six years later. Cancer detection rate in this group of women was approximately 1% in those assessed. The two women with invasive breast carcinomas had dense breasts and one view only was taken on screening. No cancers were detected in women complaining of lumps or dimpling who had normal fatty or mixed density mammograms.

Journal Article↗