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Chimeric structural isomer fragments as cost-efficient internal standards for amino acid quantification by mass spectrometry.

Amino acid (AA) profiles from body fluids such as blood and urine are clinical indicators for diagnosing metabolic and hepatic diseases. Current quantitative methods, such as liquid chromatography-mass spectrometry (LC-MS) with isotopically labelled internal standards (ISs), are costly and technically demanding. This study proposes a cost-efficient alternative using structural isomers as ISs in a direct liquid infusion (DLI) tandem mass spectrometry (MS/MS) approach. The method leverages chimeric spectra and fragment intensity ratios to quantify AAs, demonstrating high linearity and precision even with a 3D ion trap mass analyser. This approach offers a viable strategy for AA quantification in preventive medicine, particularly for screening metabolic diseases such as phenylketonuria, diabetes, and liver dysfunction.

Amino Acids↗

Computer-aided diagnosis for CT colonography.

CT colonography, or virtual colonoscopy, is a promising alternative screening tool for colon cancer. Computer-aided diagnosis (CAD) for CT colonography has the potential to increase radiologists' diagnostic performance in the detection of polyps and to reduce variability of the diagnostic accuracy among readers. Technical developments have advanced CAD for CT colonography substantially during the last several years. This paper describes the key techniques used for CAD for detection of polyps and masses in CT colonography, the current detection performance, and challenges and the future of CAD.

Colonic Polyps↗

Assessing technical performance at diverse ambulatory care sites.

The purpose of the large study reported here was to develop and test methods for assessing the quality of health care that would be broadly applicable to diverse ambulatory care organizations for periodic comparative review. Methodological features included the use of an age-sex stratified random sampling scheme, dependence on medical records as the source of data, a fixed study period year, use of Kessner's tracer methodology (including not only acute and chronic diseases but also screening and immunization rates as indicators), and a fixed tracer matrix at all test sites. This combination of methods proved more efficacious in estimating certain parameters for the total patient populations at each site (including utilization patterns, screening, and immunization rates) and the process of care for acute conditions than it did in examining the process of care for the selected chronic condition. It was found that the actual process of care at all three sites for the three acute conditions (streptococcal pharyngitis, urinary tract infection, and iron deficiency anemia) often differed from the expected process in terms of both diagnostic procedures and treatment. For hypertension, the chronic disease tracer, medical records were frequently a deficient data source from which to draw conclusions about the adequacy of treatment. Several aspects of the study methodology were found to be detrimental to between-site comparisons of the process of care for chronic disease management. The use of an age-sex stratified random sampling scheme resulted in the identification of too few cases of hypertension at some sites for analytic purposes, thereby necessitating supplementary sampling by diagnosis. The use of a fixed study period year resulted in an arbitrary starting point in the course of the disease. Furthermore, in light of the diverse sociodemographic characteristics of the patient populations, the use of a fixed matrix of tracer conditions for all test sites is questionable. The discussion centers on these and other problems encountered in attempting to compare technical performance within diverse ambulatory care organizations and provides some guidelines as to the utility of alternative methods for assessing the quality of health care.

Adolescent↗

Challenges of developing a cervical screening information system: the Ontario pilot project.

OBJECTIVE: To create a cervical screening information and reporting system in 2 geographic areas of Ontario. DESIGN: A pilot project involving access to, and linkage of, cervical screening-related cytology, colposcopy and histopathology records for women in the study areas, followed by development and production of woman-specific and aggregate reports. SETTING: Hospital cytology and pathology departments, colposcopy clinics, private cytology laboratories, and the provincial cancer agency (Cancer Care Ontario, formerly the Ontario Cancer Treatment and Research Foundation). MAIN OUTCOME MEASURES: Access to required records; data quality (i.e., standardization, completeness, accuracy); quality of record linkage; utility of reports to evaluators, data sources and physicians. RESULTS: The pilot project was not completed because of a number of major challenges, including multiple data sources requiring separate investigation and negotiations for access; variations in reporting terminology and coding; incompatibility or lack of computer systems; incompleteness of identifiers for record linkage; variation in legislation permitting data access and sharing and in its interpretation; and major financial, resource and time requirements. CONCLUSIONS: Although sufficient will and resources can overcome technical obstacles, changes in legislation will be required to overcome other challenges. Strong links with all sectors involved in cervical screening and attention to changes in the health care system are essential.

Colposcopy↗

Initial experience with the advanced breast biopsy instrumentation device.

OBJECTIVE: The Advanced Breast Biopsy Instrumentation (ABBI) device (United States Surgical; Norwalk, CT) is designed to percutaneously excise nonpalpable breast lesions. Because this is a new technique, we report our initial experience with regard to technical success, complications, and histologic margins for malignancies. SUBJECTS AND METHODS: From May 14, 1997, until March 4, 1998, 89 consecutive patients elected to undergo the ABBI procedure. Preprocedure imaging included screening mammography and additional mammographic and sonographic studies when deemed necessary. Lesions were targeted by the surgeons. Specimen radiography was performed for all lesions, and the images were interpreted by radiologists. Pathologic analysis was provided or reviewed by a dedicated breast pathologist. Parameters analyzed included technical success, complications, lesion size, histologic diagnosis, and margin status for malignant lesions. RESULTS: There were 29 patients with 30 noncalcified masses, 53 patients with clustered calcifications, three patients with masses and calcifications, three patients with asymmetric densities, and one patient with architectural distortion. Eighteen ABBI procedures were aborted, converted to core biopsy, or failed to remove the targeted lesion. Fifteen patients experienced a total of 19 complications; 10 of the complications required treatment and follow-up after the biopsy. Of 11 malignant tumors revealed by ABBI, four had negative margins. Seven of these 11 malignant tumors had positive margins. CONCLUSION: The ABBI procedure had a high number of complications and technical failures and did not reliably provide cancer-free margins for malignant tumors. Women with nonpalpable breast lesions that need a tissue diagnosis are better treated by stereotactic or sonographically guided needle biopsy.

Aged↗

[How to read a screening mammography (mammotest)].

The purpose of this chapter is to give to the radiologist some practical information in order to be able to read the mammotests, as they are performed in mass screening for breast cancer in France. The examples shown must help to detect as many small cancers as possible, without inflating the false positive rate. Screening mammotests can be read one by one (first reading), or by large series (second or third reading). To improve both the sensitivity and the specificity, reading technique should be strict, with correct fitting (viewboxes, ambiant light). For each case, a technical evaluation is performed (sharpness, contrast, breast projection), followed by the detection phase (asymmetry, abnormal density or calcifications or distorsion). Then, the image is analyzed (eliminating the typical benign conditions), and finally encoded to formalize the result: normal/suspicious for breast cancer. A good working method and a perfect knowledge of normal and pathologic appearances, allow us to reach the recommended rates for detected cancers and positive tests.

Artifacts↗

Urine testing in the detection of drugs of abuse.

It is vital that physicians are alert to signs and symptoms of arcane drug use by their patients and be prepared to order appropriate laboratory tests that will assist in differentiating problems associated with drug use from those stemming from other causes. Physicians should be familiar with the advantages and disadvantages of the more common screening procedures for drugs of abuse. As a result of recent technical improvements in the instrumentation and reagents used to test for drugs of abuse in urine specimens, these tests, properly performed, are highly accurate for cannabinoids and cocaine, the two most frequently abused drugs; a positive test for opiates and amphetamines is much less specific. By using a two-tiered system of confirmation of positive screening tests that employs techniques such as gas chromatography with mass spectrometry, the incidence of false-positive results is minimal. This article presents guidelines for determining when to order a drug screen; a lexicon of terms commonly used in discussions of screening tests; a description of the advantages, disadvantages, technique, and means of interpreting the more widely used tests; and a section on each of the most frequently abused drugs that describes common errors in test interpretation.

Chromatography, Thin Layer↗

Evaluation of cytomegalovirus (CMV) antibody screening tests for blood donors.

Four technics were compared to find the most suitable screening test for the cytomegalovirus (CMV) antibody status in blood donors. One hundred thirty-five donor samples were tested by two enzyme immunoassays, EIA(Litton) and EIA(Abbott), and by latex agglutination (LA) and complement fixation (CF). The seroreactivity of the tests were judged by concordance of three or more methods. The authors found that the test performance of the EIA(Litton) could be improved with adjustment of sample color variation, which increased the test sensitivity and specificity from 48.8% and 87.2% to 83.8% and 96.4%, respectively. Both the EIA(Abbott) and LA technics proved to be ideal screening tests with 100% sensitivity and negative predictive values. However, the rapid turnaround time and the simplicity in technics and equipment used with the LA test make it the test of choice for blood donor screening.

Antibodies, Viral↗

Technology of a regional Guthrie test service.

Investigations were undertaken to discover the effect and importance of technical factors in the Guthrie test and to determine the most satisfactory materials available. These findings were used in setting up the screening service for phenylketonuria for the South West Metropolitan Region.

Agar↗

[Evaluation of post-menopausal osteoporosis using ultrasound].

Quantitative ultrasound (QUS) has recently been proposed for evaluating bone mineral density. Several QUS units are now commercially available. They measure both the attenuation and velocity of the US beam, in a transmission mode, mainly at the calcaneum and phalanges. These parameters are mainly related to bone density, but may also, in theory, be affected by non-quantitative properties of bone such as elasticity and anisotropy. Values measured at QUS are lowered in osteoporotic patients compared to normal control subjects. The predictive value for hip fracture in an elderly population is similar for QUS measurements and conventional techniques of bone mineral density measurements. The reproducibility of measurements with QUS is good, but the variation to be measured is only minimal. Thus, QUS cannot yet be recommended for follow up of patients or evaluation of response to treatment. Technical advances are to be expected. Because this technique is non-invasive and simple, it represents a promising tool for the screening of patients at risk for osteoporosis.

Aged↗

Validity of screening.

The technical aspects of evaluation of screening programs to detect early disease are discussed. Screening is differentiated from diagnosis. The practical importance of specificity and sensitivity of screening tests is illustrated. The concept of evaluation of the total program is introduced. The determinants of successful programs are discussed with illustrations.

Epidemiologic Methods↗

Meconium screening for cystic fibrosis.

In our hands, the BMC-Test Meconium has been a significant step towards the goal of developing an ideal newborn screening test for CF. It is easily performed, is highly specific, has reasonably high sensitivity, and--given its limitation of identifying only patients with CF who have intrauterine pancreatic insufficiency--is the best method of screening newborns for CF that has been devised to date. Many technical problems remain to be solved before the test can be endorsed without reservation. Because the test, as currently constituted, does not identify all potential subjects for further testing who might have CF, it should not be made mandatory. It is, however, better than other available screening methods for CF and can be praised for that benefit. The concept has indicated a valuable new direction for mass-screening possibilities and perhaps can, by future modification, be made sensitive enough to warrant universal usage.

Albumins↗

[Value of immunology in the diagnosis of cutaneous onchocerciasis].

In a study of 135 cases, the authors present the dermatologic lesions occasioned by onchocercosis, study and discuss the value of the following three diagnostic procedures: the skin Snip technic, the Mazzotti test, and indirect fluorescent antibody test as used in a region of Africa where onchocercosis is, with dipetalonemosis, the principal filariasis. The skin Snip showed positive in only 11,8% of cases while each of the other technics permitted diagnosis of more than 80% of cases studied. Use of the Mazzotti test in conjunction with indirect fluorescent antibody test proved the origin of dermatologic lesions to be onchocercotic in 100% of the study group while both tests remained negative for subjects in the control group. The authors conclude that, in individual practice the 3 tests should be used conjointly, while, for purposes of mass screening, the determination of fluorescent antibodies must be performed as an adjunct to clinical examination and skin Snip.

Adolescent↗

[The proposed position statement on the preliminary screening of hepatitis B and hepatitis C of tentative intra-couple medically assisted reproduction. The BLEFCO Federation].

Within the context of routine screening before intra-couple Medically Assisted Procreation attempt, French Bioethical law of July 1994 makes provision for health security rules by announcing a State Council statutory order, not published at the moment. The infectious transmissibility risk in matter of MAP is much debated, especially for hepatitis virus and assisted fertilization. The attitude proposed take account of well-known transmission modes, potential risks, biological technics for screening at our disposal, ethical considerations and legal context, for this activity within the limits of therapeutic.

Bioethics↗

High-throughput classification of yeast mutants for functional genomics using metabolic footprinting.

Many technologies have been developed to help explain the function of genes discovered by systematic genome sequencing. At present, transcriptome and proteome studies dominate large-scale functional analysis strategies. Yet the metabolome, because it is 'downstream', should show greater effects of genetic or physiological changes and thus should be much closer to the phenotype of the organism. We earlier presented a functional analysis strategy that used metabolic fingerprinting to reveal the phenotype of silent mutations of yeast genes. However, this is difficult to scale up for high-throughput screening. Here we present an alternative that has the required throughput (2 min per sample). This 'metabolic footprinting' approach recognizes the significance of 'overflow metabolism' in appropriate media. Measuring intracellular metabolites is time-consuming and subject to technical difficulties caused by the rapid turnover of intracellular metabolites and the need to quench metabolism and separate metabolites from the extracellular space. We therefore focused instead on direct, noninvasive, mass spectrometric monitoring of extracellular metabolites in spent culture medium. Metabolic footprinting can distinguish between different physiological states of wild-type yeast and between yeast single-gene deletion mutants even from related areas of metabolism. By using appropriate clustering and machine learning techniques, the latter based on genetic programming, we show that metabolic footprinting is an effective method to classify 'unknown' mutants by genetic defect.

Cells, Cultured↗