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PubMed1989

The prospects for mass population screening in colorectal cancer.

Screening leads to an increased detection of tumours localized to the bowel at the time of surgical treatment which are likely to have an improved prognosis. However, because of the biases associated with screening it would be unwise to advocate a nationwide programme until the results of the controlled trials now in progress are available. At the present time the detection of occult blood in the faeces is the only feasible method of population screening. Haemoccult is a reliable, well tried test but lacks sensitivity. Several new chemical and immunological tests are available but require further evaluation.

Aged↗

PubMed1980

Proliferative disorders of the breast as risk factors for breast cancer in a self-selected screened population: pathologic markers.

A study was done to quantify the pathologic risk of subsequent breast cancer in women whose biopsies demonstrated proliferative histologic conditions. Out of a total of 10,530 patients, 1,408 had biopsies which were classified as either bland fibrocystic or hyperplastic. The behavior of the disease in these patients was compared to that of the general screened population. It was concluded that women whose biopsies reveal hyperplastic disorder, primarily atypical hyperplasia and fibroadenoma, run the greatest risk of getting cancer. For women with atypical hyperplasia, the risk is 13 times that of the general population, and for those with fibroadenoma it is three times greater.

Breast Diseases↗

PubMed1995

Errors in transrectal ultrasonic planimetry of the prostate: computer simulation of volumetric errors applied to a screening population.

Three systemic errors in routine ultrasonic planimetric volume measurements of the prostate were assessed. A computer model using ellipsoids was used to simulate the step section technique and different forms of rotational movements of the prostate during planimetry. The planimetric volume was up to 12% smaller than the exact volume, depending on the degree of rotational movement, the shape, and the length of the ellipsoid. In vivo study of a screening population showed that it is worthwhile to compare caliper length with the number of planimetric steps, as the difference might be an indication of the difference between planimetric and caliper measured volume. In shorter prostates the planimetric volume was smaller than the prolate spheroid volume when compared to longer prostates, as was seen in the computer simulation.

Computer Simulation↗

PubMedDate not supplied

Population screening and referral for hypercholesterolemia.

To determine the potential effect of screening on referral patterns, an adult population sample (4,404 men, 5,164 women, 20-69 years of age) was systematically recruited and screened for hypercholesterolemia and then analyzed by different cholesterol referral recommendations. Using levels suggested by the Lipid Research Clinics Coronary Primary Prevention Trial (greater than or equal to 265 mg/dL), 7.3% of men and 5.8% of women would be referred for follow-up. With the suggested recommendations of the National Cholesterol Education Program (NCEP), (greater than or equal to 200 mg/dL), 49.2% of men and 40.2% of women would be referred. The use of age-related definitions of the NIH Consensus Conference on Lipid Lowering results in 28.0% referrals in men and 21.8% in women. From this population, hypercholesterolemia subjects (greater than or equal to 265 mg/dL at screening; n = 624) were invited for a second cholesterol determination (58% returned), which found 36% below the 265 mg/dL level. Population screening for cholesterol is likely to produce large numbers of patients for follow-up, with the actual numbers strongly dependent on cutoff levels and age-sex distributions. Referral and follow-up of these patients may place a significant load on an unprepared health care community.

Adult↗

PubMed2001

The problem of cutoff levels in a screened population: appropriateness of informing screenees about their risk of having prostate carcinoma.

BACKGROUND: Transrectal prostate biopsy decisions often have been based on absolute cutoff values for total and free prostate-specific antigen (PSA). The authors decided that it would be more appropriate to develop risk profiles for the individual patient to allow him to decide whether to undergo a prostate biopsy. METHODS: To develop risk profiles, the authors first used multivariate logistic regression analysis to analyze 2054 males who were part of the Tyrol (Austria) PSA Screening Project. Second, artificial neural network (ANN) analyses were performed using data from 3474 males who also were part of the Tyrol PSA Screening Project and who had undergone prostate biopsy. These analyses were compared with standard cutoff levels of specificity for the detection of prostate carcinoma. RESULTS: To the authors' knowledge, this was the first time that multivariate logistic regression analysis was used to decide whether to perform prostate biopsies based on risk profiles rather than on single cutoff levels. For the detection of prostate carcinoma, at sensitivity levels of 90--95%, the ANN was 150--200% more specific than the standard cutoff points. For screened volunteers with total PSA levels below 4 ng/mL, ANN showed a lower cancer predictive ability in comparison with volunteers with total PSA levels above 4 ng/mL. However, the ANN was approximately 150--200% more specific than the standard cutoff levels in both groups. CONCLUSIONS: At high sensitivity levels, ANN increased the specificity for prostate carcinoma detection in a PSA-based screened population. The improvement in specificity between standard cutoff levels and ANN ranged between 150--200% and was not affected by the presence of benign prostatic hyperplasia or prostatitis.

Aged↗

PubMed1980

Cryotherapy of the uterine cervix: an inadequate treatment modality in a newly screened population.

A prospective trial of the efficacy of cryotherapy in cervical intra-epithelial neoplasia (CIN) was initiated at Baragwanath Hospital in Soweto, and incorporated 200 Black patients who had been evaluated by colposcopy and directed cervical biopsy before inclusion in the study. Only 52 patients (26%) achieved cytonegativity and adhered to the continuing follow-up schedule as advised (12 of these patients required repeat cryotherapy to achieve a cure). Another 39 patients (19,5%) were cytonegative when last seen, but did not fulfil the follow-up criteria required. Inclusive of this latter group, the cure rate achieved was 45,5% of the entire series, the average follow-up period being only 7,08 months. The results of the study demonstrated that cryotherapy cannot be regarded as the ideal form of management of CIN in a newly screened population, in whom the lesions detected are often extensive, with deep intraglandular involvement, and extension into the endocervical canal. For maximal therapeutic efficacy in any new cancer screening programme, it is advised that a policy of more liberal recourse to cold-knife conization be adopted, cryotherapy being reserved for patients with lesser degrees of CIN, in whom the lesion is confined to the surface epithelium of the ectocervix only

Adult↗

PubMed1993

Human hydatid disease: evaluation of an ELISA for diagnosis, population screening and monitoring of control programmes.

The routine use of ELISA and complement fixation tests in the diagnosis of suspected clinical cases of hydatid disease was evaluated. In the ELISA test, dialysed and filtered sheep cyst fluid was used as antigen and two positive cut-off points--+3SD and +2SD of the mean absorbance values of the control sera--were evaluated. The predictive values of ELISA tests were 82% and 90% for positive tests, and 86% and 82% for negative tests, respectively with the two cut-off points. In a population survey of blood donors and veterinary workers in Powys, 4% and 8%, respectively, had ELISA values above the lower cut-off point. However, it would not be appropriate to use the same test for diagnostic population screening in Wales since the predictive value of the test is likely to be very low in this setting. Serological surveys with the ELISA may be of use in monitoring the progress of the South Powys Hydatid Control Programme. The use of cumulative percentages was found to be a useful method of comparing whole distributions of results in different populations.

Animals↗

PubMedDate not supplied

Significance of linkage disequilibrium between mutation C282Y and a MseI polymorphism in population screening and DNA diagnosis of hemochromatosis.

An increasing number of studies demonstrate a lack of phenotypic expression in subjects found to be homozygous for the common hereditary hemochromatosis (HH) mutation, C282Y. In this study the impact of possible overestimation of C282Y homozygosity, as a consequence of a MseI polymorphism identified in intron 4 of the HFE gene, was investigated in South African subjects. Utilization of a modified polymerase chain reaction (PCR)-based assay highlighted the potential implications with respect to genotype/phenotype correlation studies, particularly in the general population. Mistyping rather than lack of disease association provides a plausible explanation for the phenomenon of C282Y homozygosity without iron overload. Reassessment of C282Y mutation status in such cases may result in justified population screening in HH.

DNA↗

PubMed2002

Mutation analysis of the human CYP3A4 gene 5' regulatory region: population screening using non-radioactive SSCP.

Human CYP3A4 is the major cytochrome P450 isoenzyme in adult human liver and is known to metabolise many xenobiotic and endogenous compounds. There is substantial inter-individual variation in the hepatic levels of CYP3A4. Although, polymorphic mutations have been reported in the 5' regulatory region of the CYP3A4 gene, those that have been investigated so far do not appear to have any effect on gene expression. To determine whether other mutations exist in this region of the gene, we have performed a new population screen on a panel of 101 human DNA samples. A 1140 bp section of the 5' proximal regulatory region of the CYP3A4 gene, containing numerous regulatory motifs, was amplified from genomic DNA as three overlapping segments. The 300 bp distal enhancer region at -7.9kb containing additional regulatory motifs was also amplified. Mutation analysis of the resulting PCR products was carried out using non-radioactive single strand conformation polymorphism (SSCP) and confirmatory sequencing of both DNA strands in those samples showing extra SSCP bands. In addition to detection of the previously reported CYP3A4*1B allele in nine subjects, three novel alleles were found: CYP3A4*1E (having a T-->A transversion at -369 in one subject), CYP3A4*1F (having a C-->G tranversion at -747 in 17 subjects) and CYP3A4*15B containing a nine-nucleotide insertion between -845 and -844 linked to an A-->G transition at -392 and a G-->A transition in exon 6 (position 485 in the cDNA) in one subject. All the novel alleles were heterozygous. No mutations were found in the upstream distal enhancer region. Our results clearly indicate that this rapid and simple SSCP approach can reveal mutant alleles in drug metabolising enzyme genes. Detection and determination of the frequency of novel alleles in CYP3A4 will assist investigation of the relationship between genotype, xenobiotic metabolism and toxicity in the CYP3A family of isoenzymes.

5' Untranslated Regions↗

PubMed1999

Validating marker-based incidence estimates in repeatedly screened populations.

Disease incidence (new cases of disease per person per year) is usually measured by using longitudinal data. However, several recent proposals for measuring the incidence of human immunodeficiency virus (HIV) rely on cross-sectional data only. These methods assume each person is only sampled once; however, in some instances, it is necessary to consider these cross-sectional methods when individuals are represented more than once in the survey sample. We derive an extension of the cross-sectional incidence estimator that is valid for data from repeatedly screened populations and show under what conditions our new estimator reduces to the old estimator. An example involving estimation of HIV incidence among repeat blood donors is presented.

Biometry↗

PubMed1985

A comparison of an immunological faecal occult blood test Fecatwin sensitive/FECA EIA with Haemoccult in population screening for colorectal cancer.

Two faecal occult blood tests, a simple chemical test Haemoccult and an immunological test, Fecatwin Sensitive/Feca EIA, were offered to 3,225 asymptomatic individuals as screening for colorectal cancer. One thousand three hundred and four (44%) completed and returned the tests and of these 126 (9.7%) were found to be positive - Haemoccult 40 (3%) and Feca EIA 106 (8.1%). Five cancers (4 Dukes' Stage A, 1 Dukes' Stage C) and 23 adenomas greater than 1 cm were detected - rates of 3.8 per 1000 persons screened and 17.7 per 1000 persons screened respectively. Of the five cancers identified 5 were Feca EIA positive and 3 were Haemoccult positive. Of the 23 adenomas greater than 1 cm diameter identified, J1 were Feca EIA positive and 20 were Haemoccult positive. Seventy-eight Feca EIA positive subjects were investigated and no neoplastic disease was identified. Whilst this sensitive immunological test increases the yield of carcinomas, the high false positive rate makes it unsuitable for population screening for colorectal cancer in its present form.

Adenoma↗

PubMed1984

A filter paper dry blood spot procedure for acute intermittent porphyria population screening by use of whole blood uroporphyrinogen-I-synthase assay.

A filter paper dry blood spot procedure for the determination of whole blood uroporphyrinogen-I-synthase (UIS) activity is presented. The method is based on the concept of enzyme specific activity, the enzyme activity being related to the haemoglobin concentration of the assay sample. The diagnostic capacity with regard to the acute intermittent porphyria (AIP) gene carrier state is shown to be equivalent to that of a washed red cell reference method. On grounds of easy capillary blood sampling, uncomplicated and safe mail specimen transport and simple laboratory reception routines, the method is stated to be well adapted for use in AIP preadolescent population screening.

Adolescent↗

PubMed1997

Randomized trial of the addition of flexible sigmoidoscopy to faecal occult blood testing for colorectal neoplasia population screening.

BACKGROUND: Published data suggest that screening might reduce the mortality rate from colorectal neoplasia. Faecal occult blood (FOB) testing suffers from poor sensitivity and significant numbers of interval cancers, both of which should be improved by the addition of flexible sigmoidoscopy (FOS). METHODS: This prospective, randomized study aimed to assess the compliance and neoplasia yield of FOB testing and FOS compared with that of FOB testing alone. From general practitioner registers, 6371 asymptomatic patients (3124 men, 3247 women; age range 50-74 years) were invited for screening by means of FOB testing (3128 patients) performed at home, or a combination of FOB testing and FOS (3243 patients). RESULTS: Compliance with FOB testing alone was 50 per cent. In the FOB testing/FOS group, 48 per cent returned the FOB test but only 20 per cent went on to FOS. Despite the poor compliance, the neoplasia yield was four times greater in the FOB testing/FOS group. CONCLUSION: FOS increase the neoplasia yield but strategies to improve compliance must be identified for this to become a population screening test.

Aged↗

PubMedDate not supplied

Colorectal cancer: future population screening for early colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent cancers in Western countries. The identification of individuals at risk and the early diagnosis of CRC are of critical importance since a large proportion can be prevented or cured by surgical removal before metastasis has occurred. With increasing understanding of the genetic basis of hereditary and sporadic (non-hereditary) CRC, it becomes feasible to detect genetic alterations by molecular techniques. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), as well as early stages of spontaneous CRC, can be diagnosed by molecular characterisation of the adenomatous polyposis coli (APC) gene, the RAS oncogene and other genes in DNA from peripheral blood, stool or intestinal biopsies. With a better understanding of the genetic events leading to malignant transformation, molecular population screening should allow us to identify individuals at risk as well as patients with an early and potentially curable CRC. At present, careful patient and family history, physical examination and testing for occult blood as well as colonoscopy are still the key elements for clinical patient management. Molecular diagnosis will hopefully soon complement these analyses and should result in a reduction of morbidity and mortality from CRC.

Adenomatous Polyposis Coli↗

PubMed1994

The TRAndolapril Cardiac Evaluation (TRACE) study: rationale, design, and baseline characteristics of the screened population. The Trace Study Group.

The TRAndolapril Cardiac Evaluation (TRACE) study is evaluating the effect of angiotensin-converting enzyme inhibition with trandolapril on mortality (overall and cardiovascular) and cardiovascular morbidity in patients surviving myocardial infarction (MI) with reduced left ventricular (LV) function. TRACE is a randomized, double-blind, placebo-controlled study conducted in 27 centers in Denmark. Eligible patients had a MI verified by elevated cardiac enzymes, electrocardiographic changes, and/or chest pain as well as reduced LV function, as shown by echocardiographic evaluation of wall motion index < or = 1.2. (A wall motion index < or = 1.2 approximates to a left ventricular ejection fraction < or = 35%). Patients with residual ischemia and/or heart failure were not excluded. Trandolapril or placebo was added to conventional therapy 3-7 days after MI. Between May 1990 and June 1992, 6,674 patients (7,010 infarctions) were screened. A total of 2,614 patients had a wall motion index < or = 1.2; of these, 1,749 were included. Overall 1-year mortality of the patients entered into the study was 24%. Treatment will be continued for 2-4 years (mean, 3 years), ending in mid 1994. The design and organization of the study, the outcome of screening, and demographic features of the screened population are described.

Administration, Oral↗

PubMed2000

Maternal thyroid deficiency and pregnancy complications: implications for population screening.

OBJECTIVE: To examine the relation between certain pregnancy complications and thyroid stimulating hormone (TSH) measurements in a cohort of pregnant women. METHODS: TSH was measured in sera obtained from women during the second trimester as part of routine prenatal care. Information was then collected about vaginal bleeding, premature delivery, low birthweight, abruptio placentae, pregnancy induced hypertension, need for cesarean section, low Apgar scores, and fetal and neonatal death. RESULTS: Among 9403 women with singleton pregnancies, TSH measurements were 6 mU/l or greater in 209 (2.2%). The rate of fetal death was significantly higher in those pregnancies (3.8%) than in the women with TSH less than 6 mU/l (0.9%, odds ratio 4.4, 95% confidence interval 1.9-9.5). Other pregnancy complications did not occur more frequently. CONCLUSION: From the second trimester onward, the major adverse obstetrical outcome associated with raised TSH in the general population is an increased rate of fetal death. If thyroid replacement treatment avoided this problem this would be another reason to consider population screening.

Adult↗

PubMed2005

The predictive value of PSA in diagnosis of prostate cancer in non screened population.

INTRODUCTION: [corrected] PSA is the most important tumor marker in all solid tumor, indispensable in the management of prostate cancer. Screening for prostate cancer is still not recomended, although performed in many countries, which introduced questions about the usefulnes of PSA in detection of prostate cancer. The PSA treshold has also been changed, the value of PSA derivatives revised. Whether such changes are applicable in non scrrened population is questionable. Aim of this study was to evaluate the predictive value of PSA, free/ total PSA and PSA density in our non screened population. PATIENTS AND METHODS: TRUS guided prostate biopsy was performed in 579 patients. The number of cores was 6-12. Mean age of the patients was 67.5 years (30-90). PSA was ranging from 0.41 to 2250 (mean 38.6 ng/ml, median: 11.95, SD 140,45). Digitorectal examination was considered positive in 351 patients. Free PSA was measured in 352 patients with the index ranging from 0.02 to 0.88 (mean free/total PSA: 0.14, median: 0.13). The volume of the prostate was measured in all patients according the prostate ellipsoid model, and PSA density calculated according to the formula PSA/PV. Patients were stratified in 6 groups according to PSA value (I: PSA ng/ml, II: PSA 2.5-4, III: PSA 4-10, IV: PSA 10-20, V: PSA: 20 to 50, Group 6: PSA 50). RESULTS: Non homogenicity of the patients can be seen through the wide range of PSA which was from 0.4 to 2025). Prostate cancer was diagnosed in 233 pts (40.2%). As expected, the probability of detecting cancer was raised with PSA (p), and was extremely rare in pts with PSA below 4 ng/ml. PSA, free/total PSA, volume of the prostate and PSA density were significantly different according to the presence of cancer. Most of our patients had PSA between 4 and 20 ng/ml. Predictive value of PSA was 20.6% for pts with PSA from 4 to 10 and 32.7% for those with PSA from 10 to 20 ng/ml. Sensitivity, specificity, positive and negative predictive values for different cut off's of PSA (4, 10 and 20) was performed. The best results were obtained for PSA cut off of 10 ng/ml. In the group of patient with PSA, PSA density more reliable than free/total PSA index. CONCLUSION: PSA is still valuable marker for detection of prostate cancer in our non screened population. According to our results PSA treshold should not be lowered below 4 ng/ml. PSA density is a reliable PSA derivative, free/total PSA index having less importance in pts with PSA below 20 ng/ml.

Adult↗

PubMed1996

[Genetic hemochromatosis: importance of population screening?].

Genetic hemochromatosis is a metabolic autosomal-recessive disease characterized by an iron excessive absorption; its subsequent accumulation in the liver, hearth, pancreas and endocrine glands, gives rise to organ damage and dysfunction. Recent studies of both screening tests and natural history have shown that the illness, once thought to be rare and fatal, is quite frequent (up to 2-5 homozygotes for 1000 inhabitants) and when recognized and treated before onset of cirrhosis, subjects affected have a normal life expectancy. Consequently, in order to reduce mortality from genetic hemochromatosis, mainly due to liver cirrhosis, frequently complicated with hepatocellular carcinoma, or congestive hearth failure, early diagnosis and therapeutic phlebotomy are essential. In order to achieve these aims, besides high clinical suspicion and familiar study, is fundamental to conduct systematic screening since, at present, little use is being made of this, even though numerous studies have recently shown its low cost and efficacy. The Authors, after an extensive review of the literature, underline the feasibility of screening on the general population and its extremely advantageous cost/benefit ratio.

Adult↗