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PubMed1996

[Preconception screening for carrier state in cystic fibrosis; testing against Health Council's criteria for genetic screening].

OBJECTIVE: To determine if preconceptional screening for carriership of cystic fibrosis (CF) meets the requirements formulated by the Committee for Screening for Hereditary and Congenital Disorders of the Health Council. DESIGN: Theoretical evaluation. METHOD: Preconceptional screening for CF carriership by means of direct mutation analysis in a blood sample, cheek smear or mouth rinse sample of both partners of pairs desiring children was tested against the criteria of the Health Council. RESULTS: Preconceptional screening for CF carriership proves to meet most of the requirements for genetic screening. Current problems are the inadequate sensitivity of the screening (72% for pairs, 85% for individuals), the consequences of this for the meaning of the test results and reaching of the target group. Much attention is required for provision of information at all stages of the screening procedure. The desirability, feasibility and psychosocial effects of this type of screening have not yet been investigated sufficiently in the Netherlands.

Clinical Protocols↗

PubMed1998

Screen compliance rates in 14-years annual screening program for colorectal cancer with immunochemical fecal occult blood test-- identification of higher priority subjects in health education.

OBJECTIVES: The present study was carried out to assess compliance rates with annual colorectal cancer screening for fecal occult blood, and to identify the subjects with higher priority in health education to increase screen compliance. DESIGN AND SETTING: A screening program for colorectal cancer was conducted between 1982 and 1995 in a Japanese villlage. Screen compliance rates in this program were summarised related to sex distribution as well as 10-year age cohorts. MAIN RESULTS: Screen compliance declined slowly during 14 years time period, and averaged 55.4%. Mean screen compliance was significantly higher in women (56.8%) than in men (53. 8%), and also in aged 50-79 (63.5%) than in aged 50 or less (43.8%), and those 80 and older(12.3%). Subjects who experienced a negative result on colonoscopic examination had significantly lower compliance with screening. CONCLUSIONS: These findings indicate that the youngest as well as oldest subjects, and the subjects with negative results of fecal occult blood test should be given higher priority in health education to improve screen compliance.

Aged↗

PubMed2024

Cost-effectiveness of population-wide genomic screening for Lynch Syndrome and polygenic risk scores to inform colorectal cancer screening.

PURPOSE: Genomic screening to identify individuals with Lynch Syndrome (LS) and those with a high polygenic risk score (PRS) promises to personalize colorectal cancer (CRC) screening. Understanding its clinical and economic impact is needed to inform screening guidelines and reimbursement policies. METHODS: We developed a Markov model to simulate individuals over a lifetime. We compared LS+PRS genomic screening with standard of care (SOC) for a cohort of US adults at age 30. The Markov model included health states of no CRC, CRC stages (A-D), and death. We estimated incidence, mortality, and discounted economic outcomes of the population under different interventions. RESULTS: Screening 1000 individuals for LS+PRS resulted in 1.36 fewer CRC cases and 0.65 fewer deaths compared with SOC. The incremental cost-effectiveness ratio was $124,415 per quality-adjusted life year; screening had a 69% probability of being cost-effective using a willingness-to-pay threshold of $150,000/quality-adjusted life year . Setting the PRS threshold at the 90th percentile of the LS+PRS screening program to define individuals at high risk was most likely to be cost-effective compared with 95th, 85th, and 80th percentiles. CONCLUSION: Population-level LS+PRS screening is marginally cost-effective, and a threshold of 90th percentile is more likely to be cost-effective than other thresholds.

Humans↗

PubMed2001

Application of population screening principles to genetic screening for adult-onset conditions.

Recent advances in molecular genetics have highlighted the potential use of genetic testing to screen for adult-onset chronic diseases. Several issues must be addressed, however, before such tests can be recommended for population-based prevention programs. These issues include the adequacy of the scientific evidence, the balance of risks and benefits, the need for counseling and informed consent, and the costs and resources required. Ongoing assessment of the screening program and quality assurance of laboratory testing are also needed. This paper considers the application of general principles for mass screening to genetic testing for susceptibility to adult-onset chronic diseases. Evaluation of proposals for genetic screening in context of these principles reveals that needed evidence is often absent, particularly with respect to the predictive value of tests, efficacy of interventions, and social consequences of testing. The principles of population screening are developed into a framework for public health policy on genetic screening that has three stages: assessment of the screening test and interventions for those who test positive, including assessment of risks and costs, policy development, and program evaluation. Essential elements are identified, including evaluation of evidence and processes for consensus development and program evaluation. The proposed framework for public health policymaking outlined in this commentary, when combined with future efforts that involve an authoritative consensus process, may be useful for the evaluation and planning of genetic screening programs aimed at reducing morbidity and mortality from adult-onset chronic diseases.

Adult↗

PubMed1998

Hepatitis C infection risk analysis: who should be screened? Comparison of multiple screening strategies based on the National Hepatitis Surveillance Program.

OBJECTIVES: Hepatitis C, an infection of high prevalence worldwide, is insidiously progressive in many. Reduction of person-to-person spread is possible, and treatment is possible for many, particularly if offered before cirrhosis develops. Screening for hepatitis C (HCV) would be appropriate if strategies could be developed to afford adequate sensitivity and specificity at reasonable cost. We evaluated the performance characteristics of several screening strategies to determine the best balance between cost and performance. METHODS: The database of a national hepatitis screening program was used to define risk factors for HCV. Features associated with increased risk for HCV by multivariable analysis were combined in various ways to construct HCV screening models. Screening Model 1 employed a mathematical model constructed to predict the probability of hepatitis C. Using this model, testing for HCV was done if the probability of HCV was determined to be higher than 7%. Models 2 and 3 called for HCV testing if certain risk factors, stratified as socially intrusive, or nonintrusive in nature, were present. Model 4 calls for testing for HCV only when ALT values are elevated. Costs per case discovered were calculated for each model. RESULTS: Nine thousand two-hundred sixty-nine individuals from a database of 13,997 has sufficient information to be included in the modeling studies. Risk factors considered socially intrusive were intravenous (i.v.) drug use and sex with an i.v. drug user. Risk factors considered not socially intrusive were: history of blood transfusion, age 30-49 yrs, and male gender. The sensitivity of Models 1-4 were 65%, 69%, 53%, and 63%, respectively. Specificities were 84%, 74%, 77%, and 92%, respectively. The cost per case detected was lowest when Models 1 or 2 were used ($357 and $439, respectively) and higher for models 3 and 4 ($487 and $1047, respectively). CONCLUSIONS: The yield and cost of screening for HCV compares favorably with accepted current screening practices for other diseases. Models 1, 2, and 3 may be appropriate in certain clinical and epidemiological settings. Selective screening by a risk factor questionnaire (first three models) is more cost-effective than blood testing with ALT (Model 4).

Adult↗

PubMed1988

Visual and clinical analysis of Bac-T-Screen urine screen results.

Of 337 urine specimens evaluated, 75 of the 113 that showed positive readings on the Bac-T-Screen urine-screening instrument were found by subsequent semiquantitative culture to yield either less than 10,000 CFU of mixed bacteria per ml or no growth (less than 100 CFU/ml by our criteria). We tried to determine what factors contributed to the positive Bac-T-Screen results by examining the 75 Bac-T-Screen-positive urine specimens with three visual methods: Gram staining, hemacytometer chamber counting, and filtering through a 5.0-microns-pore-size nitrocellulose filter with subsequent microscopic examination of the stained filter. Somatic cells and other particles present in those urine specimens that yielded positive readings by the Bac-T-Screen included epithelial cells in 43%, crystals and amorphous material in 33%, and leukocytes in 17% of the specimens. There was no relationship between the numbers of particles seen in urine and the magnitude of the relative absorbance reading obtained with the Bac-T-Screen. A retrospective chart review was conducted for patients with positive Bac-T-Screen results and negative cultures. Of the 75 patients, 6 were thought to have urinary tract infections on the basis of clinical criteria; the majority of the remaining 69 patients had clinical histories revealing systemic or urogenital conditions consistent with shedding of particles in the urine. A positive reading by the Bac-T-Screen system seemed to be related to the presence of somatic cells and other particles in urine; bacteriuria was not always detectable in these cases.

Bacteriuria↗

PubMed2004

Screening for inhibitors of histone deacetylase by incorporating a spraying method to micro-arrayed compound screening.

We have developed a method of spraying assay reagents onto a target gel in the Micro-Arrayed Compound Screening ( micro ARCS) format. After application of target gels to compound sheets, subsequent reagents can be applied by spraying onto the target gel. The spraying method conserves on assay reagents by up to 10-fold, eliminates the need for casting additional agarose gels, and increases the throughput of a screen by 3-fold. To demonstrate the efficacy of applying the spraying method to micro ARCS, we screened over 600,000 compounds for inhibitors of histone deacetylase (HDAC). Commercially available HDAC substrate and reaction developer were sprayed directly onto the gel to initiate the reaction and to amplify the signal, respectively. Picks in the primary screen were retested at a density of 384 compounds per sheet in the micro ARCS format. IC(50) values for active compounds were confirmed in a 96-well plate assay. The screen identified several small molecule inhibitors of the enzyme, including members of several classes of known HDAC inhibitors. The combination of the high-density format of micro ARCS, the efficiency of the spraying method, and a timed sequence of adding assay reagents permitted a screening throughput of 200,000 tests an hour. We present the details of the screening format and the analysis of the hits from the screen.

Drug Evaluation, Preclinical↗

PubMed2003

Fetuses with Down's Syndrome detected by prenatal screening are more likely to abort spontaneously than fetuses with Down's Syndrome not detected by prenatal screening.

OBJECTIVE: Pregnancy with Down's Syndrome is often terminated by miscarriage. We have investigated whether prenatal screening would lead preferentially to the identification of fetuses with Down's Syndrome prone to abort spontaneously. DESIGN: A comparison between the observed and the expected decrease in the prevalence of Down's Syndrome at term following extensive prenatal screening. SETTING: A study from 1990 to 1998 in a limited and well controlled area of western France (Basse Normandie), with a birth rate close to 20,000 a year. POPULATION: Women under 38 years of age among whom prenatal screening for Down's Syndrome using biochemical tests and ultrasound findings became progressively extensive in this era. METHODS: Our study was based on the registration of Down's Syndrome cases detected prenatally from screening, and live births with Down's Syndrome. Fetal loss rate in the population of prenatally detectable Down's Syndrome was evaluated by comparing the increase in detection of cases of Down's Syndrome following prenatal screening with the expected decrease in the number of cases of Down's Syndrome at birth. The results obtained were compared with published data on the rates of fetal losses postulated to occur among fetuses with Down's Syndrome. MAIN OUTCOME MEASURES: Comparison of the potential fetal loss rate in a population in whom Down's Syndrome was detected prenatally with the expected fetal loss rate of unselected ones. RESULTS: Prenatal screening resulted in a significant (42%) decrease (P < 0.001) in the prevalence at term of the disorder. Among the 53 fetuses with Down's Syndrome detected prenatally during the last three years of the study, about 50% would have aborted spontaneously if the pregnancy had been allowed to continue. This figure was significantly higher (P < 0.002) than expected on the basis of results from the literature, indicating that current estimates of miscarriage rates among fetuses with Down's Syndrome do not apply to the selected group of cases detectable from prenatal screening. CONCLUSIONS: Our results suggest that fetuses with Down's Syndrome detectable prenatally from screening are more likely to abort spontaneously than fetuses with Down's Syndrome which are not detected.

Abortion, Spontaneous↗

PubMed1986

Sensitivity of the Denver Developmental Screening Test in speech and language screening.

A retrospective study was undertaken to determine whether the Denver Developmental Screening Test (DDST) language sector is a sensitive screen of speech and language development. Seventy-one children between 18 and 66 months of age with suspected developmental problems were referred to screening clinics conducted by a child evaluation team. Each child was screened using the DDST (revised) and another screening measure of speech and language development. Statistically significant differences were found between the DDST language sector and the speech-language screening in identification of expressive language and articulation problems. No significant difference was found with receptive language. The DDST failed to identify more than one half of the children with expressive language and/or articulation problems. These results demonstrate that the DDST may fail to identify children with speech and language impairment. Professionals involved in developmental screening need to be advised of alternative speech and language screening measures.

Child↗

PubMed1992

Survival for clinical stage I lung cancer not surgically treated. Comparison between screen-detected and symptom-detected cases. The Japanese Lung Cancer Screening Research Group.

To assess the extent of overdiagnosis bias in lung cancer screening, clinical Stage I lung cancer cases detected by chest radiograph examination, with histologic or cytologic evidence of malignancy and not treated by surgical operation, were followed up for more than 10 years. Of 1297 screen-detected and 1297 symptom-detected cases collected from 20 institutions, 42 screen-detected and 27 symptom-detected cases satisfied the study criteria. In about half of the cases, the patients had no contraindication for surgical treatment, but they refused surgical procedure. All such patients from the screen-detected and symptom-detected groups died within 122 and 67 months, respectively, of diagnosis. Among the screen-detected and symptom-detected cases, 80% and 81%, respectively, of the patients died of lung cancer. The median survival time was 25 and 13 months for those in the screen-detected and symptom-detected groups, respectively. The difference in survival was statistically significant between the two groups, which indicated the effect of lead time and length-biased sampling. Analysis of the causes of death other than lung cancer showed that there was no difference in the observed cumulative rates of deaths of other causes between the two groups, and these figures were almost the same as those expected from the general population. This indicates that overdiagnosis bias would be minimal in screen-detected lung cancer cases detected by chest radiograph examination.

Aged↗

PubMed2002

Decisions about amniocentesis by advanced maternal age patients following maternal serum screening may not always correlate clinically with screening results: need for improvement in informed consent process.

We evaluated the prenatal diagnosis utilization patterns of advanced maternal age (AMA) patients who underwent serum screening to assess how screening results correlated with their decisions regarding amniocentesis. A 6-year review (1994-1999) of laboratory records identified 2,456 AMA patients who underwent multiple-marker serum screening. The relationship between screening results and patients' decisions on whether or not to undergo amniocentesis was assessed. Among the 841 AMA patients with positive screens, more than half (52%) declined amniocentesis. Of the 1,615 patients with negative serum screening results, 208 (13%) opted for amniocentesis. We concluded that decisions by AMA patients regarding amniocentesis may not always correlate clinically with maternal serum screening results. Possible explanations, including how the state of informed consent may or may not contribute to these decisions, are discussed. It is suggested that understanding the reasons for these decisions may identify opportunities for improving service delivery to all pregnant patients considering prenatal testing. Use of a questionnaire is proposed as one mechanism for gaining a clearer understanding of the possible factors contributing to AMA patient decisions.

Adult↗

PubMed1992

A case-control study for evaluating lung-cancer screening in Japan. Japanese Lung-Cancer-Screening Research Group.

In order to evaluate the efficacy of lung-cancer screening, a case-control study was conducted using the data from 50 areas where population-based lung-cancer screening programmes have been operated by local municipalities. In most areas, chest X-ray examinations for all participants and sputum cytology for high-risk participants were offered annually. Case series consisted of 273 deceased lung-cancer cases. For each case, 2 to 5 controls (a total of 1,269 controls) were collected from those who were alive at the time of diagnosis of the corresponding case, matched by sex, age, smoking status and type of health insurance. Cases and controls were limited to a high-risk group for males and a non-high-risk group for females. Screening histories, which were obtained from the list of screenees, were compared between case and matched controls for the identical calendar period before the time of diagnosis of the case. The odds ratio of dying from lung cancer for those screened within 12 months vs. those not screened was 0.72 (95% confidence interval 0.50-1.03; p = 0.07). The odds ratio increased towards unity, as the length of time in which screening histories were compared increased. After adjusting for some other variables, which appeared to be associated with the opportunities of chest X-ray examination, the estimated odds ratio did not change. These results suggest some benefits from lung-cancer screening in terms of reduction of lung-cancer mortality and should be subject to further research.

Adult↗

PubMed1995

Nation-wide breast cancer screening in The Netherlands: support for breast-cancer mortality reduction. National Evaluation Team for Breast Cancer Screening (NETB).

The nation-wide 2-yearly breast-cancer screening programme in The Netherlands, for women aged 50-69, started around 1988, and was predicted to result eventually in a 16% reduction in breast-cancer mortality in the total female population. We present the results of screening up to January 1, 1993, and compare these with the predicted results from the cost-effectiveness analysis, on which basis this mortality reduction has been calculated. At least 550,000 women aged 50-69 were invited to screening in 1990-1992, and 75% of these participated. Cancer was suspected from 5,162 examinations and further investigation was therefore required. Excision biopsy was done in 72% of referrals, and 2,515 breast cancers were detected. The results for 404,000 newly invited women compare favourably with expected values (in parentheses): 78% attendance rate (70%), 1.4% screen positive (1.6%), 6.8 cancers detected per 1,000 women screened (6.4) and 38% of these cancers were DCIS or invasive carcinomas smaller than 11 mm in diameter (36%). More data, e.g., on treatment and interval cancers, will follow in the years to come. These first results can be interpreted as strong early signs of a reduction in breast-cancer mortality of at least the predicted size. Screening has sufficiently advanced the diagnosis, as well as or better than expected. Breast cancers diagnosed in this age group without screening are diagnosed at a worse stage than expected. Unfavourable side-effects, especially false-positive referrals, might be kept lower than those reported in other countries.

Aged↗

PubMed2005

Population screening for fetal trisomy 21: easy access to screening should be balanced against a uniform ultrasound protocol.

OBJECTIVES: To evaluate the performance of a first-trimester fetal aneuploidy screening program, with a documented underestimation of nuchal translucency thickness measurements (NT) compared to the Fetal Medicine Foundation (FMF) reference range. METHODS: We analysed the data of Algemeen Medisch Laboratorium (AML) in Antwerp, Belgium, on combined screening with pregnancy-associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin (FB-hCG) and NT. NT-multiples of the median (MoM), relative to the FMF reference range, were used for risk calculations. RESULTS: The proportion of first-trimester screening tests in the total of serum screening tests increased from 1.3% (125/9424) in 2000 to 53.1% (6577/12 377) in 2003. Only 11.4% (1514/13 267) of NT measurements were performed according to FMF criteria. The 80.8% (21/26) trisomy 21 (T21) detection rate (DR) at cut off 1:300 resulted from maternal serum screening. NT measurements did not add to this DR, but reduced the false-positive rate from 16.8% (2212/13181) to 8.6% (1130/13181). Only 23.8% (5/21) of T21 detections were by FMF trainees. CONCLUSION: Easy access to screening and maternal serum parameters accounted for the majority of T21 detections in our first-trimester combined screening program.

Adult↗

PubMed2006

How to screen for depression and emotional problems in patients with diabetes: comparison of screening characteristics of depression questionnaires, measurement of diabetes-specific emotional problems and standard clinical assessment.

AIMS/HYPOTHESIS: We compared the screening performance of different measures of depression: the standard clinical assessment (SCA); the Beck Depression Inventory (BDI); the Center of Epidemiological Studies-Depression Scale (CES-D); and the Problem Areas in Diabetes (PAID) questionnaire, which assesses diabetes-specific distress. We also studied the ability of these measures to detect diabetes-related distress. MATERIALS AND METHODS: A total of 376 diabetic patients (37.2% type 1; 23.9% type 2 without insulin treatment, 38.8% type 2 with insulin) completed the BDI and CES-D; patients who screened positive participated in a diagnostic interview, the Composite International Diagnostic Interview (CIDI). Also, all patients completed the PAID questionnaire. Results of the SCA that related to depression diagnosis were reviewed to correct for false negative screening results. RESULTS: The prevalence of clinical depression was 14.1%, with an additional 18.9% of patients receiving a diagnosis of subclinical depression. Sensitivity for clinical depression in SCA (56%) was moderate, whereas BDI, CES-D and the PAID questionnaire showed satisfactory sensitivity (87, 79 and 81%, respectively). For subclinical depression, the sensitivity of the PAID questionnaire (79%) was sufficient, whereas that of SCA (25%) was poor. All methods showed low sensitivity for the detection of diabetes-specific emotional problems (SCA 19%, CIDI 34%, BDI 60%, CES-D 49%). CONCLUSIONS/INTERPRETATION: The screening performance of SCA for clinical and subclinical depression was modest. Additional screening for depression using the PAID or another depression questionnaire seems reasonable. The ability of depression screening measures to identify diabetes-related distress is modest, suggesting that the PAID questionnaire could be useful when screening diabetic patients for both depression and emotional problems.

Depression↗

PubMed2005

"Brain Screen": A self-referral, screening program for strokes, falls and dementia risk factors.

BACKGROUND: Falls, strokes and dementia can be predicted and their occurrence can be delayed or even prevented by treatment of risk factors. The value of screening self-referred adults is unknown. OBJECTIVES: To assess whether a screening program of self-referred adults provides new and valuable medical information on risk factors for falls, stroke and dementia. METHOD: We examined 514 self-referred people (59% women, mean age 68+/-8 years (range 44-89) and 14+/-3 years of education) in our "Brain Screen" program. Participants completed detailed questionnaires and underwent a neurological examination, computerized gait analysis, carotid Duplex, serum lipid and homocysteine levels, a computerized neuropsychological battery (NeuroTrax) and the Mini-Mental State Exam. Information that was detected by "Brain Screen" was compared with the self-reported data. RESULTS: Unknown vascular risk factors detected by ""Brain Screen" included: high cholesterol in 44%, homocysteine > 10 micromol/L in 20%, >1 mm carotid intima-media thickness in 13%, and carotid narrowing (> 30%) in 2.2%. Unknown risk factors for falls were detected in 66% of the subjects who never fell. Of the 205 subjects (44%) who complained of memory decline, 28% had objective memory disturbances compared with their age group. Mild cognitive impairment (amnestic MCI) was clinically diagnosed in 17% of the population and dementia in 5%. CONCLUSION: Screening self-referred adults for falls, strokes and dementia risk factors detected significant unknown risk factors that can be treated in more than one-third of the participants. A national "Brain Screen" program can have significant impact on the health of the aging population.

Accidental Falls↗

PubMed2007

Creation of a CT Image Library for the Lung Screening Study of the National Lung Screening Trial.

The CT Image Library (CTIL) of the Lung Screening Study (LSS) network of the National Lung Screening Trial (NLST) consists of up to three annual screens using CT imaging from each of 17,308 participants with a significant history of smoking but no evidence of cancer at trial enrollment (Fall 2002-Spring 2004). Screens performed at numerous medical centers associated with 10 LSS-NLST screening centers are deidentified of protected health information and delivered to the CTIL via DVD, external hard disk, or Internet/Virtual Private Network transmission. The collection will be completed in late 2006. The CTIL is of potential interest to clinical researchers and software developers of nodule detection algorithms. Its attractiveness lies in its very specific, well-defined patient population, scanned via a common CT protocol, and in its collection of evenly spaced serial screens. In this work, we describe the technical details of the CTIL collection process from screening center retrieval through library storage.

Clinical Protocols↗

PubMed2005

Screening histories of women with CIN 2/3 compared with women diagnosed with invasive cervical cancer: a retrospective analysis of the Norwegian Coordinated Cervical Cancer Screening Program.

OBJECTIVE: This study compares the screening history for women with cervical intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (ACIS) with women with different stages and subtypes of cervical carcinoma. METHODS: An analysis of the Norwegian Coordinated Cervical Screening Program comparing all cases with a CIN 2/3/ACIS (N=8586) with all ICC (N=777) in the period 2000-2002. All Pap smears since 1992 were used to characterise detection mode and screening history. Multinominal regression models estimated the risk associated with detection mode and adequate Pap smear history. RESULTS: A wide range of age at diagnosis, from 16 to 92 years of age was observed regardless of the stage of the disease. Fifty five percentage of the women diagnosed with CIN 2/3/ACIS had an adequate screening history. Of women diagnosed with SCC, 45.1% in stage I, and 10.5% in stage IV had an adequate history. The median age of women with CIN 2/3 (34 years) and squamous cervical carcinoma (SCC) stage I (37 years) given an adequate Pap smear history was not significantly different. For women with ACC, the proportion with adequate screening history was roughly 50% for all stages. After adjustment for detection mode and age, the OR for being diagnosed with ICC stage I compared to CIN 2/3 was 1.2 (95% CI: 1.0-1.5), while the OR of being diagnosed with ICC stage II-IV was 3.4 (95% CI: 2.3-4.8). CONCLUSIONS: Women with CIN 2/3 and ICC stage I were similar with respect to screening histories, i.e. detection mode and age at diagnosis, while women with ICC stage II-IV seldom had an adequate screening history and were diagnosed at a significantly higher age.

Adenocarcinoma↗