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[Diagnosis and treatment of invasive cervical cancer in Cambodia (apropos of 35 cases)].

Uterine cervix cancer is an important public health problem in developing countries. In Cambodia, incidence (24. 10-5) and mortality (12,77. 10-5) rates due to this cancer are higher than in other southeast Asian countries. 35 consecutive women with a diagnosis of invasive cervical cancer were identified from the histology laboratory of the Institut Pasteur in Phnom Penh. Information on history, clinical findings, ancillary investigations and treatment were obtained by clinical files review. Patients were from Phnom Penh, the main city and from outlying provinces. The mean age was 50 years, 2 months. They all presented with clinical symptoms at the time of diagnosis, and lesions had spread beyond the uterus in nearly half of the cases. Squamous cell carcinoma (80%) was more frequent than adenocarcinoma (14%). Microinvasive squamous cell carcinomas were rare (2.8%). Treatment was mainly surgical, but lacked standardization, as radical hysterectomy including lymphadenectomy was not systematic, even when the tumor spread beyond the uterine cervix. Few women that required adjuvant radiotherapy received it as this technique has only recently been introduced in Cambodia. Many patients were lost to follow-up. None of the cases was detected by pap smear. This technique is not in general use in the country. Cervical cancer screening could be carried out by visual inspection of the cervix with acetic acid wash that is less expensive and nearly as sensitive as pap smear. Treatments are still insufficiently standardized, due to the lack of technical means, and lack of patient compliance.

Acetic Acid↗

Solitary breast papilloma: comparison of mammographic, galactographic, and pathologic findings.

OBJECTIVE: Our purpose was to determine the mammographic/galactographic features of solitary breast papillomas and to correlate these features with the pathologic findings. MATERIALS AND METHODS: Retrospective review of pathology files revealed 72 women in whom breast biopsy reports described a solitary papilloma. All patients with additional pathologic abnormalities were excluded from this study. Patients meeting the pathologic criteria and for whom mammograms, galactograms, or both were available and had been obtained within 6 months before biopsy were included. Twenty-four women met these criteria and form the basis of this study. Presenting clinical signs and symptoms were reviewed. Abnormal mammographic/galactographic findings were correlated with pathologic features. RESULTS: Nipple discharge was present in 21 (88%) of 24 patients, two (8%) of 24 patients had abnormal findings on screening mammography, and one patient had a palpable mass that was visible on mammograms. Eight (42%) of 19 mammograms had abnormal findings, including dilated duct(s) in five cases (26%), nodules in two cases (11%), and microcalcifications in one case (5%). All technically adequate galactograms (13/15) had abnormal findings, with 12 (92%) of 13 showing an intraluminal filling defect. The other technically adequate galactogram (8%) showed only a solitary obstructed duct. Ductal dilatation was greatest at or central to the papilloma on 12 (92%) of 13 galactograms. Imaging features correlated well with the histologic findings. CONCLUSION: Patients with solitary papillomas most commonly have nipple discharge, normal mammographic findings, and a galactographic filling defect. Galactography is useful for localizing papillomas.

Adult↗

Outcomes from tandem mass spectrometry (MS/MS) workshops in the United States and the performance evaluation of MS/MS laboratories.

Disorders of fatty acid oxidation and organic acid metabolism produce serious clinical problems including death. Introduction of MS/MS technology for newborn screening allowed detection of these disorders in a single process, more than doubling the number of disorders that can be detected from dried-blood spots in newborn screening. Expanded newborn screening has become a critical issue with increased public awareness and demands. Screening by MS/MS is operational in several private testing and public health laboratories. Guidelines and quality assurance services are essential to enhance program expansions. The first of two workshops was organized in June 2000 and the second in September of 2001 to discuss procedures for integrating MS/MS into newborn screening programs. Both workshops addressed technical problems encountered with implementing MS/MS testing. One outcome of the first workshop was a pilot survey for assessing performance of MS/MS laboratories worldwide, which occurred in September 2000. This pilot survey led to the expansion of the proficiency testing services to include MS/MS testing. There are 32 participating laboratories, three of the ten countries represented are from the Asia-Pacific Region.

Education, Medical, Continuing↗

Screening for neuroblastoma in France: methodological aspects and preliminary observations.

A pilot study of neuroblastoma mass screening was initiated in January 1990 in the Rhône French district. The expected number of births per year is 26,000. The study is designed for a 5-year period with three major goals: 1) measurement of the compliance rate of a voluntary test at 4 months of age; 2) evaluation of the technical value of high-pressure liquid chromatography (HPLC) as a screening method; and 3) detailed biological characterization of all detected tumors. 61,551 children were screened between May 1, 1990 and December 31, 1993. Participation was 69% in 1990, 81.5% in 1991, and over 83% in 1992. HPLC was a satisfactory assay method. The number of clinical examinations required for positive tests as defined in the protocol is 1 per 3,621 tests. The false positive rate is 1 per 3,583 tests. Eight neuroblastomas were discovered by-screening (one stage I, three stage II, one stage III, three stage IVs). All are alive and well but were good prognosis cases according to the main prognostic factors. Five patients were discovered before screening (so called Halo effect): one stage I, one stage III, three stage IVs. One died of disease and four are alive in complete remission after treatment. Two patients were false negative (one stage III with N-myc amplification, one stage IV with bad prognosis features) and three cases of neuroblastoma were missed because of noncompliance with the screening program. This pilot study concludes on the feasibility of a mass screening program in France. The estimated cumulative incidence of neuroblastoma at 3 years is 1 per 4,375 living births and overdiagnosis is probable. All the detected cases were of good prognosis and the false negative ones were poor prognosis cases.

Child, Preschool↗

Virtual colonoscopy: a novel imaging modality for colorectal cancer.

Advances in computed tomography (CT) technology and computer capabilities have contributed to the development of a new imaging modality for colorectal lesions called CT colonography or virtual colonoscopy. Virtual colonoscopy is a rapid, minimally invasive scan of the cleansed and distended colon. Early work has demonstrated that this test is safe and well tolerated, and that it may be sensitive and specific enough to identify most significant precancerous or cancerous lesions. A number of technical and practical problems remain before virtual colonoscopy can be applied at a population level.

Colonoscopy↗

Development of a protocol for newborn screening for disorders of the galactose metabolic pathway.

The protocol evaluated in this paper employs an enzymatic assay of galactose metabolites, thin layer chromatography, and an assay of galactose-1-phosphate uridyl transferase on a single sample of blood collected routinely for newborn screening. Its effectiveness was tested by a retrospective study of known galactosemic blood samples, and also by a prospective study of 207,000 newborn samples from which 6 infants with severe transferase deficient galactosaemia and 2 infants with red cell epimerase deficiency were identified. The detection rate for severe transferase deficiency in the newborn population was 1:35,000. Advantages include low false positive rate, definitive diagnosis within 6 hours of sample receipt, and the use of technically simple and robust procedures. This protocol overcomes the difficulties encountered with previously described procedures.

Australia↗

Detection of unsuspected abnormalities by PAPNET-assisted review.

OBJECTIVE: To determine the positive predictive value of abnormalities detected by PAPNET-assisted review of slides considered to show no abnormality on two manual screenings and to evaluate the repeatability of technical codes assigned by the PAPNET scanner. STUDY DESIGN: PAPNET-assisted review was performed on 19,805 slides that had been assessed as showing no abnormality on two occasions by manual screening plus 195 slides with abnormal cells seeded at random. Abnormalities detected by cytotechnologists were graded by cytopathologists and compared with the findings of later histology/cytology. RESULTS: On PAPNET-assisted review, the cytotechnologists identified 212 slides as containing unsuspected abnormalities; cytopathologists agreed with 76% (162/212) of these predictions. Later histology/cytology confirmed 54% (14/26) and 32% (33/102) of the predictions of high and low grade abnormality, respectively. The PAPNET scanner gave concordant technical codes for 94.8% of 2,690 slides that were submitted twice for scanning. CONCLUSION: Some additional abnormalities will be detected by a PAPNET-assisted review, even among slides considered negative on two manual screenings. However, many of these abnormalities will not be confirmed on later investigation and will thus appear to represent false positive cytology. The assigning of technical codes by the PAPNET machine is subject to a degree of variation on repeat evaluation of the same slides.

Artifacts↗

Flexible sigmoidoscopy for colorectal cancer screening in the elderly.

Data on performance characteristics of flexible sigmoidoscopy (FS) between age groups are limited. This study evaluates screening FS in subjects > or = 75 years of age (elderly) compared with ages 50-74 years (general screening population). Data were collected on patient characteristics, insertion depth, procedural difficulties, complications, and endoscopic findings. There was an increased rate of endoscopist-reported limitations (50.4% vs. 34.9%; P = 0.0001) and incomplete examinations (15.6% vs. 5.4%; P = 0.0001) in the elderly cohort relative to subjects aged 50-74. The complication rate (1.0% vs. 1.5%; P = 0.53), adenoma detection rate (7.2% vs. 5.6%; P = 0.213), and advanced adenoma detection rate (0.71% vs 0.65%; P = 0.86) were similar. More carcinomas were detected in the elderly (0.53% vs. 0.06%; P = 0.042). Factors associated with incomplete examinations in the elderly included age, female gender, and poor bowel preparation. Despite technical difficulties, FS in the elderly is safe and detects significant pathology.

Age Factors↗

Why do we go on screening?

As healthcare rules are becoming better organized and as vaccination against Human Papillomavirus (HPV) infections is arising, the conditions of cytological screening for cervical carcinoma may have to be modified in the near future. After reminding the Quality Control constraints of the Pap test and the technical and epidemiological conditions for the HPV detection as a precursor of cervical carcinoma, the present paper wishes to discuss the possible role of vaccine on the screening strategy.

Female↗

Asymptomatic cervical artery stenoses in Moscow.

The risk of stroke related to asymptomatic carotid artery stenosis is known to be increased in high-grade or rapidly progressive stenosis. Information of the prevalence in the general population is required for the recommendation of screening methods to detect patients needing prophylactic treatment. We studied the prevalence and the grade of severity of extracranial carotid and vertebral artery obstructions by means of Doppler sonography in 529 asymptomatic Russians (m: 343, f: 186; 36-84 years, mean: 58.4 years) living in Moscow city. Internal carotid artery obstructions of more than 50% stenosis were present in 22 (= 4.2%) subjects, 8 of them (1.5%) had bilateral lesions. Appropriate abnormal findings in vertebral arteries were found in 11 (= 2.1%) subjects, in 1 of them bilaterally. Affection of both the carotid and the vertebral arteries was noted in 4(= 0.8%) individuals. There were no sexual differences. The risk factor which correlated most significantly with cervical arterial lesions was hypertension. Carotid lesions were also significantly associated with age and smoking, but not with diabetes or hyperlipoproteinemia. The prevalence of cervical artery stenoses was found to be lower than in western reports, which may be due to different technical equipment and different study design.

Adult↗

Detection of beta-defensins secreted by human oral epithelial cells.

Human beta-defensins are antimicrobial peptides that may be critical in the innate immune response to infection. hBD1 and hBD2 are expressed in oral epithelial cells and are detected near the surface of oral tissue, consistent with a role in the epithelial protective barrier function. In this report, we examine secretion of beta-defensins in vitro and in biological fluid using ProteinChip(R) Array, surface enhanced laser desorption/ionization (SELDI) technology combined with time-of-flight mass spectrometry. We show that the 47-amino acid form of hBD1 and the 41-amino acid form of hBD2 are the major secreted forms. These forms are both expressed and secreted under conditions anticipated from previous analysis of beta-defensin mRNAs; specifically, hBD1 is detected in culture supernatant from both unstimulated and stimulated cells, and hBD2 is detected only in stimulated cells. Identity of hBD1 and hBD2 was confirmed by immunocapture on the ProteinChip surface. Both peptides are also present in gingival crevicular fluid that accumulates between the tissue and tooth surface, although hBD1 is also found in several smaller forms suggesting extracellular proteolysis. This methodology offers several technical advantages for detection of defensins in biological fluids, including ease and speed of screening, no need for HPLC preliminary processing, and small sample size.

Cells, Cultured↗

The national leprosy eradication programme in India.

India has the largest leprosy problem in the world, with an estimated 4 million patients. The number of registered cases in the country was 2.4 million by June 1990, and the number of new cases detected during 1989-1990, 0.47 million. The disease prevalence varies widely from state to state and even among districts within states--8 of the 26 states contribute to 90% of all the registered cases. The country has a high priority for leprosy and the National Leprosy Eradication Programme (NLEP) aims to arrest the disease among all known cases in the country by the turn of the century through a strategy which includes multidrug therapy (MDT), early case detection, health education and rehabilitation. The specialized leprosy infrastructure in the country has a total of about 8,500 establishments including 719 leprosy control units, 244 district leprosy units and 49 training centres. By June 1990, 130 districts with 2.15 million patients had come under MDT. It is planned to cover 196 districts by 1992, ensuring coverage for 90% of the patients in the country. The country spends approximately 600 million rupees (US$ 33.3 million) per year on NLEP. In addition, a number of bilateral and international agencies including nongovernmental organizations participate in the programme. WHO supports the NLEP through technical inputs, monitoring and evaluation, and training. Plans to integrate leprosy control within primary health care, particularly after completion of the intensive phase of MDT, are being developed. Operational and technical constraints are constantly reviewed in order to find optimal solutions.

Communicable Disease Control↗

First trimester serum screening for Down's syndrome.

Screening for Down's Syndrome has been shown to be effective at 10 weeks of pregnancy. A multicentre study (the first trimester serum screening study) has shown that there are two biochemical markers of choice at this time in pregnancy, namely pregnancy associated placental protein A (PAPP-A) and the free beta-sub-unit of human chorionic gonadotrophin (free beta-hCG). When used together with maternal age these two biochemical markers have an estimated detection rate of 62% and a 5% false-positive rate. The results are consistent with those obtained from a systematic review of the world literature. Other markers are less predictive of Down's syndrome though there is still some uncertainty over the value of dimeric inhibin-A at 10 weeks of pregnancy. Nuchal translucency measurement, from an ultrasound examination performed at about 10 weeks of pregnancy, is associated with Down's syndrome and is emerging as an important potential screening marker. At present there is uncertainty over its quantitative performance and performance when combined with biochemical markers. The resolution of these issues is currently the subject of active research. Ten week screening for Down's syndrome is an advance that is now technically possible though there is still insufficient information to justify its use in routine screening practice.

Biomarkers↗

[Trypanosomiasis caused by T. b. gambiense: methods of control].

This paper reviews the different ways currently available for screening sleeping sickness. These ways are then integrated and discussed by the author in proposing different strategic and methodologic solutions after emphasizing the role of each of the technical stages. Altogether, there isn't one standard solution but adaptations around a main plan, according to contexts and having regard to efficiency and profitability. At all events, success depends on political will, community participation and the motivation and good training of the personnel.

Animals↗

Searching for consensus through multi-criteria decision analysis. Assessment of screening strategies for hemoglobinopathies in southeastern France.

Until now, no systematic strategy for the prevention of major hemoglobinopathies has been implemented in southeastern France, in spite of frequencies of beta-thalassemia trait and HbS trait as high as 2.5-8% in some ethnic populations. The purpose of the study was to help a group of experts, brought together by the Regional Center for Disease Control, to reach a consensus about screening for carriers of heterozygote hemoglobinopathies. A multicriteria decision-analysis model was used to take into account not only the costs and effectiveness of potential screening strategies, but also five other qualitative criteria: technical and practical feasibilities, ethical acceptability, information follow-up in time, and global impact on health education. Conclusions differ significantly from those of a pure cost-effectiveness analysis, but a multicriteria approach seems best suited to medical experts' preferences.

Costs and Cost Analysis↗

Screening for phenylketonuria mutations by DNA amplification with the polymerase chain reaction.

Single base substitutions have been identified in two mutant phenylalanine hydroxylase (PAH) alleles that cause phenylketonuria (PKU). The two mutant alleles are common among caucasians of northern European ancestry; detection in genomic DNA samples of patients and carriers by hybridisation with oligonucleotides specific for the respective mutant alleles requires fractionation of restriction-enzyme-digested genomic DNA samples by gel electrophoresis. This method is too cumbersome for mass screening of PKU carriers. Identification of carriers of the mutant alleles was achieved by direct analysis of their genomic DNA samples after specific amplification of a sub-genomic DNA fragment containing both mutation sites by polymerase chain reaction. The results suggest that it is technically feasible to develop a programme for carrier detection of the genetic trait in the population for individuals without a family history of PKU.

Alleles↗