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Comparison of total prostate-specific antigen and derivative levels in a screening population of black, white, and Korean-American men.

Numerous studies have assessed serum total PSA (tPSA) levels among different races. We extended the serum biomarker profiling using prostate-specific antigen (PSA) derivatives in age-matched screening populations that included white, black, and Korean-American patients. The median ages were 61 years for white and black patients and 63 years for Korean-American patients. Serum samples from 70 men in each ethnic group were analyzed using 3 different tPSA assays (Tosoh AIA 600II, Bayer Immuno-1, Roche Elecsys 2010). The percentage of free PSA (fPSA) was measured directly by Roche Elecsys 2010 immunoassay and then calculated from complexed PSA (cPSA) and tPSA results determined with the Bayer Immuno-1. The percentage of cPSA was determined using cPSA and tPSA assayed by the Immuno-1 method. Statistical analyses included nonparametric Kruskal-Wallis and analysis of variance (ANOVA) evaluations. There were no differences noted in the tPSA values based on ANOVA among the 3 races irrespective of the assay platform methodology employed. Also, the PSA derivatives, percentages of fPSA and cPSA, evaluated using the Kruskal-Wallis test, showed no significant differences for either derivative assayed on 2 different assay platforms among the 3 groups. In a contemporary screening population comparing tPSA, percentage of fPSA, and percentage of cPSA levels in 3 races, there were no significant differences identified among the groups.

Black or African American↗

Determination of Chlamydia trachomatis prevalence in an asymptomatic screening population: performances of the LCx and COBAS Amplicor tests with urine specimens.

This study determined the performances of the LCx (Abbott) and COBAS Amplicor (Roche) tests with urine specimens for the detection of Chlamydia trachomatis in an asymptomatic screening population. Randomly selected women and men (age range, 15 to 40 years) registered in 20 general practices in Amsterdam, The Netherlands, were invited to participate in this study. Urine specimens (n = 2, 906; 1,138 specimens from men and 1,717 specimens from women) were tested for C. trachomatis by the COBAS Amplicor (Roche) and LCx (Abbott) tests. Samples which were positive by only one assay were subjected to discrepant analyses by a third assay (in-house plasmid PCR). By the LCx assay C. trachomatis DNA was detected in urine specimens from 46 of 1,717 women and 29 of 1,138 men, while the COBAS Amplicor detected C. trachomatis DNA in 52 and 35 specimens, respectively. When comparing the LCx and COBAS Amplicor tests, 32 test results (20 for women and 12 for men) were discrepant. After discrepant analyses the following sensitivities, specificities, and positive predictive values were found for the LCx and COBAS Amplicor tests: 78.6 versus 98.8%, 99.7 versus 99.9%, and 88.0 versus 95.4%, respectively. No prominent differences were found between men and women with regard to the test performances. After discrepant analyses the overall prevalences of C. trachomatis in women and men were 3.0 and 2.8%, respectively. For both women and men the prevalence in the younger age groups was higher than that in the older age groups. In conclusion, the COBAS Amplicor tests shows better diagnostic characteristics than the LCx assay for the detection of C. trachomatis in urine specimens from an asymptomatic screening population. In this asymptomatic population the overall prevalence of C. trachomatis was 2.9%.

Adolescent↗

Population screening for single genes that codetermine common diseases in adulthood had limited effects.

BACKGROUND AND OBJECTIVE: Familial hemochromatosis (FHEM), familial hypercholesterolemia (FH), familial mediterranean fever (FMF), and familial thrombophilia (FT) are relatively common genetically determined diseases of (early) adulthood. Chances, shortcomings, and practical aspects of population screening were considered. METHODS: The literature, as well as existing data concerning the treatment of these diseases in The Netherlands, were studied. RESULTS: In these four diseases there are so many modifying genes and environmental and lifestyle influences that accurate predictive testing at the population level is currently not sufficiently effective. The data indicate that the implementation of family clinics for FHEM and FH are necessary. There is need for further sociologic studies in the moslim population of Mediterranean and North African origin about acceptance of DNA diagnostics in relation to consanguinity and into the problem of "pseudodominance." There seems no need for early detection and preventive measures for FT in asymptomatic persons. CONCLUSION: No population screening for these four genetically determined diseases of (early) adulthood is sufficiently effective at the present time. We propose to call these diseases "chronic diseases with a single gene component."

Familial Mediterranean Fever↗

Cost-effectiveness of population screening for alpha-1 antitrypsin deficiency: a decision analysis.

The objective was to assess the cost-effectiveness of population screening for alpha-1 antitrypsin (AAT) deficiency. The design was a Markov-based decision analytic model. Hypothetical cohorts were analyzed from birth and followed over time until death using Monte Carlo simulation. The following strategies were compared: 1) screen all newborns, 2) screen all 10-year-old children, and 3) do not screen. Screenees found to have PI*ZZ AAT deficiency received the benefits of lower smoking rates and were offered augmentation therapy. In keeping with reported experience, most (96%) non-screened AAT deficient individuals remained undiagnosed and, therefore, missed these benefits. Under base conditions, screening all newborns cost nearly $422,000 per quality-adjusted life-year (QALY) gained; this estimate fell to $92,135 per QALY when the cost of screening was minimized to $6 in the model. Delaying screening until age 10 decreased the incremental cost-effectiveness ratio (ICER) to nearly $317,000. In sensitivity analysis, when the prevalence of PI*ZZ individuals increased from a baseline of 1.96 to 16 per 10,000, the ICER for newborn screening decreased below $100,000 per QALY. When the cost of screening and augmentation therapy were decreased simultaneously with increasing PI*ZZ prevalence, there were many scenarios in which the ICER decreased below $50,000. While population-based screening for AAT deficiency is not cost-effective under current conditions, cost-effectiveness criteria could be satisfied when case-finding in a high prevalence population is undertaken.

Cost-Benefit Analysis↗

Population screening for hemochromatosis by PCR using sequence-specific primers.

Over 90% of patients with hemochromatosis in the United Kingdom are homozygous for the C282Y mutation on the HFE gene. The Centers for Disease Control (CDC) in the United States has recommended that adults should be screened for HFE mutations to identify susceptible individuals before onset of disease. The aim of this study was to evaluate the polymerase chain reaction using sequence-specific primers (PCR-SSP) as a method of large-scale population screening for the common HFE gene mutations, H63D and C282Y. A total of 10,583 consenting blood donors were tested using nonautomated procedures. Three alleles, termed HFE-1, -2, and -3, were detected with phenotype frequencies of 94.56%, 28.33%, and 15.79%, respectively, and gene frequencies of 0.76421, 0.15342, and 0.08237, respectively. All donors identified as homozygous for the C282Y mutation or heterozygous for both the H63D and C282Y mutations were confirmed by heterduplex analysis and/or PCR-SSP. The number of technical failures that affected the identification of donors homozygous for the C282Y mutation was 390 giving an overall repeat rate 3.7%, although this fell to 1% over the last quarter of the study. This study demonstrates that PCR-SSP may be used for large-scale population screening for the C282Y genotype associated with hemochromatosis.

Blood Donors↗

The effect of ejaculation on prostate-specific antigen in a prostate cancer-screening population.

OBJECTIVES: To measure the impact of ejaculation on the serum levels of prostate-specific antigen (PSA) in a prostate cancer-screening population. METHODS: Questionnaires regarding history of ejaculation were administered to all participants in a prostate cancer-screening trial. Two groups were analyzed. The first cohort consisted of 618 men who answered the questionnaire, and their serum PSA values were compared according to time since last ejaculation. The second cohort consisted of 89 volunteers who agreed to come back for a postejaculation PSA for whom a before and after ejaculation PSA was measured. Regression analysis was conducted between change in PSA and time since ejaculation as well as in the magnitude of change and baseline PSA. RESULTS: The mean (+/-SD) age of the studied population was 60.43 +/- 9.23 years. A non-statistically significant difference in PSA levels was observed for either cohort. For the 89 volunteers the mean PSA change after ejaculation was -0.62 +/- 0.75 (not significant). Initially, the PSA decreased, and then after 9 hours a steady increase was observed. After 12 hours, the serum PSA returns to baseline. The regression analysis between baseline PSA and magnitude of change showed a strong correlation (r = .557). The higher the baseline PSA, the greater the magnitude of change. CONCLUSIONS: FOR the total screened population, ejaculation has no clinically significant effect. Men should not be asked to abstain from sexual activities before a PSA-screening test.

Adult↗

Automated detection of diabetic retinopathy in a fundus photographic screening population.

PURPOSE: To evaluate the performance of an automated fundus photographic image-analysis algorithm in high-sensitivity and/or high-specificity segregation of patients with diabetes with untreated diabetic retinopathy from those without retinopathy. METHODS: This was a retrospective cross-sectional study of 260 consecutive nonphotocoagulated eyes in 137 diabetic patients attending routine photographic retinopathy screening. Mydriatic 60 degrees fundus photography on 35-mm color transparency film was used, with a single fovea-centered field. Routine grading was based on visual examination of slide-mounted transparencies. Reference grading was performed with specific emphasis on achieving high sensitivity. Computer-assisted automated red lesion detection was performed on digitized transparencies. RESULTS: When applied in a screening population comprising patients with diabetes with untreated diabetic retinopathy in any eye and patients with diabetes without retinopathy, the automated lesion detection correctly identified 90.1% of patients with retinopathy and 81.3% of patients without retinopathy. A per-eye analysis for methodological purposes demonstrated that the automated lesion detection could be adapted to simulate various visual evaluation strategies. When adapted at high sensitivity, the automated system demonstrated sensitivity at 93.1% and specificity at 71.6%. When adapted at high specificity the automated system demonstrated sensitivity at 76.4% and specificity at 96.6%, closely matching routine visual grading at sensitivity 76.4% and specificity 98.3%. CONCLUSIONS: Automated detection of untreated diabetic retinopathy in fundus photographs from a screening population of patients with diabetes can be made with adjustable priority settings, emphasizing high-sensitivity identification of diabetic retinopathy or high-specificity identification of absence of retinopathy, covering opposing extremes of visual evaluation strategies demonstrated by human observers.

Aneurysm↗

Cost effectiveness of population screening and rescreening for cervical cancer in the Netherlands.

In a screening program for cervical cancer held in the western part of the Netherlands in 1978, it was shown that the incidence of positive cases dropped from 8.0% to 1.4% when repeat screening was performed within two years; however, the incidence of mild dysplasia remained the same (13.0%). Forty percent of the allocated funds were used for canvassing. Recanvassing of the no-response group did not result in the finding of positive cases. Of the ten positive cases in the rescreened group, four had had inadequate negative smears previously, and two had had adequate negative smears; in two cases the previous smears were reclassified as dysplasias, and in the two remaining cases endocervical carcinoma cells were found in the additional endocervical smear. In light of the high canvassing costs of population screening and the low detection rate of positive cases in the rescreened group, as described in this paper, it appears overly costly to repeat population screening with two years.

Adult↗

Finding, confirming, and managing gonorrhoea in a population screened for chlamydia using the Gen-Probe Aptima Combo2 assay.

OBJECTIVES: To identify the prevalence of Neisseria gonorrhoeae (NG) within a population screened for Chlamydia trachomatis (CT). To monitor confirmatory microscopy, culture, and partner findings following reactive Aptima Combo2 assay (AC2) gonorrhoea screening tests. METHODS: Between June and December 2004, all gonorrhoea screening tests performed using AC2 for clients taking part in the Liverpool Chlamydia Screening Programme were monitored. Clients with AC2 NG reactive results were referred to a local genitourinary medicine (GUM) department for confirmatory microscopy, culture, treatment, and partner follow up. RESULTS: 47 (1%) of 4680 women and eight (1.7%) of 473 men had AC2 reactive gonorrhoea screening tests. Of those clients who agreed to follow up and were tested before any treatment, supportive evidence for a gonorrhoea diagnosis was found in 37 (97%) of 38 women and all five men. In the population opportunistically screened for chlamydia, CT prevalence rates were 12% for women and 15.7% for men. Although both women and men showed a higher relative risk for NG if chlamydia positive, of the 47 women who were reactive for NG by AC2, 55% (26) were negative for chlamydia. CONCLUSIONS: Sexually transmitted infections are rising in England and reduction of gonorrhoea rates is an objective of the Department of Health Sexual Health and HIV Strategy. AC2 tests provide an acceptable and accurate means of testing for gonorrhoea in an asymptomatic population in the community. AC2 had a higher positive predictive value than might be suggested by previous clinical trials in this low prevalence population. Although antibiotic sensitivity must be monitored, AC2 testing may offer a more acceptable alternative to microscopy and culture for NG in some populations.

Adolescent↗

[Population screening for colorectal carcinoma by examining feces for occult hemorrhage].

Colorectal carcinoma is in the western world one of the most frequent deaths from malignant disease. A reliable way how to reduce the mortality from this disease is early diagnosis by screening in the population, the most suitable method being examination of the faeces for occult bleeding. During the last five years in the world literature results of several long-term and well elaborated studies were published focused on screening of colorectal carcinoma by detection of occult haemorrhage in the faeces. There were three American and four European papers from which ensued: 1. In the examined population in the mentioned investigations a reduction of the mortality from colorectal carcinoma was recorded as compared with a control group. 2. In the investigated population also a reduced incidence of advanced colorectal carcinoma was observed (Dukes D). 3. The optimal ratio of sensitivity and specificity was obtained by the HemeSelect test (immunodiagnosis of human haemoglobin) and the combined test (Hemoccult II Sensa + HemeSelect). Large scale examination by these tests was not verified in major population surveys so far. 4. Increasing of the sensitivity of tests using guaiacum resin by rehydration leads to a drop of the specificity of the examination and an enormous increase of coloscopic examinations and the cost of screening. 5. Part of the population with a high risk of colorectal carcinoma should be subjected to large scale examination. The problem remains its correct selection. 6. The adherence of patients to the examination differed in different trials. The increasing number and pretentiousness (dietary restrictions) of the examination reduces proportionately the percentage of cooperating subjects. Examination of the faeces for occult haemorrhage thus can be recommended for national programmes for screening of colorectal cancer.

Colorectal Neoplasms↗

Iron overload, public health, and genetics: evaluating the evidence for hemochromatosis screening.

Population screening for hemochromatosis done by using the transferrin saturation test has been advocated by experts to permit the initiation of therapeutic phlebotomy before the onset of clinical disease. The discovery of a gene associated with hemochromatosis has made DNA testing another option for screening and diagnosis. In this paper, U.S. Preventive Services Task Force criteria are used to evaluate the evidence for the usefulness of population screening done by using iron measures or genetic testing. Published clinical research offers little evidence to suggest that population screening for hemochromatosis done by using genetic testing improves clinical outcomes. Although one recently discovered mutation, C282Y, accounts for 60% to 92% of cases of the disease in series of patients with hemochromatosis, uncertainties remain about the clinical penetrance of various genotypes; the accuracy of genetic testing; and the ethical, legal, and social effects of genetic testing. Before population screening for hemochromatosis done by using transferrin saturation testing can be recommended, laboratory standardization needs to be addressed and questions about risk for clinical disease in asymptomatic persons with mutations or early biochemical expression of disease require resolution. Evidence from case series suggests that hemochromatosis may be associated with liver cancer, other liver disease, diabetes, bradyarrhythmias, and arthritis. In all studies but one, however, estimation of the magnitude and significance of this risk is limited by lack of adequate comparison groups. The need for population data to answer questions about penetrance among asymptomatic persons should not impede efforts to increase the detection and treatment of hemochromatosis in persons found to have elevated iron measures a family history of hemochromatosis, or consistent early signs and symptoms of the disease.

Hemochromatosis↗

Cyclical mastalgia: clinical and mammographic observations in a screened population.

The incidence of cyclical mastalgia in well women presenting for breast screening was 69 per cent. The incidence of cyclical mastalgia increases with age up to the menopause. There was a higher incidence of 'high risk' mammographic patterns and a lower incidence of 'low risk' patterns, according to the Wolfe classification, in women with cyclical mastalgia compared with the rest of the screened population. This finding correlated with the severity, duration and need for treatment. The differences in breast pattern did not persist after the menopause. The question of whether or not cyclical mastalgia can be regarded as a risk factor for breast cancer is uncertain and needs further evaluation.

Adult↗

[The ThinPrep Pap test in population screening].

The ThinPrep technique has been applied to Pap tests in a population screening program in Imola, Italy. A significative decrease in the number of inadequate tests has been observed, while the distribution of the Bethesda diagnostic categories was not different in comparison to the previous year, when conventional Pap tests were used with the adoption of the ThinPrep technique, the productivity of the screening program increased without any need to modify the screening protocol.

Adult↗

Multiple high risk HPV infections are common in cervical neoplasia and young women in a cervical screening population.

AIMS: If human papillomavirus (HPV) testing is to be included within cervical screening programmes, the importance of multiple HPV infections in cervical neoplasia needs to be determined. This study investigated the diversity of multiple HPV types in a routine cervical screening population, and assessed associations with cervical neoplasia. METHODS: Overall HPV prevalence, type specific prevalence, and extent of multiple infection were assessed in residual material from 3444 liquid based cytology samples, using real time GP5+/GP6+ polymerase chain reaction for screening and linear array assay for genotyping. HPV status was studied in relation to age and concurrent cytological evidence of dyskaryosis. RESULTS: Twenty per cent of samples were HPV positive. HPV type diversity was broad, and multiple HPV infections occurred in half of the HPV positive samples. Younger women were significantly more likely to harbour multiple high risk HPV (HR-HPV) infections. Infections with multiple HR-HPV types were found in 3.4% of samples negative for neoplasia and in 33.3%, 41.8%, and 40.4% of samples with borderline, mild, or high grade dyskaryosis, respectively. Single HR-HPV infections were found in 4.9%, 38.6%, 45.0%, and 51.1% of negative, borderline, mild, or high grade dyskaryosis samples, respectively. CONCLUSIONS: Multiple HR-HPV infections were most prevalent in young women. Multiple HR-HPV infections were not more frequent in high grade than in low grade cervical neoplasia, reflecting common sexual transmission of multiple HR-HPV. Prospective cohort studies linking sequential loss or gain of HPV types with cytological analysis are required to assess the impact of multiple HR-HPV infections on neoplastic progression.

Adult↗

Population screening for cancer-related germline gene mutations.

Over the past 5 years, tests for germline (heritable) gene mutations associated with high risk of chronic diseases, such as breast cancer, have become increasingly available. Appropriately used, tests for such mutations could lead to reductions in disease morbidity and mortality. Population screening has been proposed for some cancer-related mutations; however, not all populations are suitable for such screening. The benefits of screening and preventive treatments for individuals with cancer-related mutations in different populations depend on the prevalence and penetrance of the mutation, the mortality associated with the disease, the age of the person screened at testing, and the potential effects of preventive measures on risk of developing the disease, quality of life, and costs. The criteria normally used to assess cancer screening tests can be applied, with some modifications, to tests for cancer-related genetic mutations and can help physicians, insurance companies, and health-policy makers to decide whether or not specific genetic tests should be used to screen specific populations.

Breast Neoplasms↗

[No major difference between population screening for cervical carcinoma at the present screening interval of 5 years and the former interval of 3 years].

OBJECTIVE: To assess the effect of extending the screening interval from 3 to 5 years on the detection of premalignant changes and invasive cervical carcinoma in the restructured population screening programme. DESIGN: Retrospective follow-up study. METHOD: The results were collected of the 1st round (1996-2000; 277, 377 women) and a part of the 2nd round (2001; 49,622 women; screening interval: 5 years) of the screening programme in Region West, the Netherlands. Histoscores for cervical intraepithelial neoplasia (CIN) 3 and squamous cell carcinoma (n/100 women investigated) and the hit count (sum of the histoscores for CIN 3, adenocarcinoma in situ and (micro)invasive cervical carcinoma) were calculated. Data of women with adenocarcinoma in situ and endocervical (adeno)carcinoma were recorded separately. The results of the 1st and 2nd round of the current screening programme (commenced in 1996) were compared with those of the historical screening programme that commenced in 1976 (screening interval: 3 years). RESULTS: From the 1st to the 2nd round of the historical screening programme that commenced in 1976, the histoscores for CIN 3 (3.33, 1.88) and squamous cell carcinoma (0.53, 0.19) and the hit count (3.92, 2.15) all diminished significantly. The current restructured programme, which commenced in 1996, showed low starting values for all three parameters, comparable to those in the 2nd round of the 1976 programme; a further reduction (0.16, 0.08; p < 0.01) was seen only in the histoscore for squamous cell carcinoma. In both rounds of both programmes, the histoscores for adenocarcinoma in situ (0.02, 0.02, 0.05, 0.04, respectively) and endocervical adenocarcinoma (0.04, 0.06, 0.05, 0.04) remained stable. CONCLUSION: In the current cervical carcinoma screening programme, with a screening interval of 5 years, the hit count of serious abnormalities remained constant while the incidence of squamous cell carcinoma decreased; this is in contrast to the historical screening programme (commenced in 1976), when both the hit count and the histoscore for CIN 3 diminished significantly. There were indications that cervical screening has no beneficial effect on the prevention of cervical adenocarcinoma.

Carcinoma↗

Population screening for autoimmune thyroid disease.

Whether or not healthy adults in the community would benefit from screening for autoimmune thyroid disease is controversial. Although the prevalence of unsuspected overt thyroid disease is low, a significant proportion of subjects tested will have evidence of mild thyroid failure or excess. This article assesses whether subclinical thyroid disease is of sufficient clinical importance to warrant screening and, once detected and confirmed, to justify therapy. Population screening for autoimmune thyroid disease is assessed against recently revised screening criteria, using data from epidemiologic studies. Recommendations are proposed that may be applied in any iodine-replete community.

Adolescent↗

The natural history of lung cancer in a periodically screened population.

A mathematical model of the progression kinetics of lung cancer in a periodically screened population is proposed and data collected by the Memorial Sloan-Kettering Cancer Center in New York are used for parameter estimation. It is assumed that the development of adenocarcinoma of lung is a stochastic process with two stages, early and advanced, characterized by mean times, detection probabilities, and cure probabilities. Confidence regions of these parameters are estimated using a number of novel techniques. It is found, surprisingly, that the mean duration of the early stage is at least 4 years, the detectability less than .2, and the curability less than .5. These estimates imply that annual radiographic screening from age 45 to 80 might decrease mortality from adenocarcinoma of lung by something less than 20%.

Adenocarcinoma↗