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Computational methods in medical decision making: to screen or not to screen?

Screening for a disease such as cancer is often regarded as a beneficial and successful strategy for reducing mortality. However, as with any clinical treatment or intervention, benefit cannot be assumed, and screening can entail both costs and harms, so the screening as a 'treatment' must undergo evaluation. An evaluation requires a definition of the treatment 'benefit', design of studies to measure that benefit with as little bias and variance as possible, and the development of methods for estimating the potential benefit. In screening studies, the factors most central to the evaluation are unobservable (e.g. earliest point in time at which disease becomes detectable, or 'preclinical'; time at which disease might have been detected in the absence of screening; test sensitivity). Thus, screening programs should be evaluated on scenarios in which these factors are varied, to ensure the robustness of the estimated benefit under a variety of circumstances. This article describes the importance of computational methods and simulations to assess the benefit of screening programs, particularly for cancer, based on randomized screening trials, with special attention to benefit time, lead time, and bias due to length-biased sampling.

Computer Simulation↗

Evaluation of a population-based screening for type 2 diabetes: a community-based screening project in Puli, Taiwan.

BACKGROUND: A Markov method incorporating the relationships between prevalence, incidence, and mortality with respect to type 2 diabetes was used to assess a population-based screening for this disease. METHODS: Data from a population-based screening project for residents of Puli, Taiwan, over 30 years of age (n= 1,219) were used to estimate the annual incidence of asymptomatic type 2 diabetes, the prevalence to incidence (P/I) ratio, and the hazard rate of death due to type 2 diabetes. These parameters were employed to develop a Markov process to evaluate the effects of early detection of type 2 diabetes on the risk of death from this disease in a simulated population (n= 10,000) receiving biennial, 5-year interval, or no screening. RESULTS: The estimated annual incidence, average duration from asymptomatic to symptomatic type 2 diabetes (P/I ratio), and hazard rate for death from this disease were 0.86% (95% CI 0.50-1.48), 10 years (95% CI 7.69-14.01), and 1.1% per year, respectively. This yields an optimal screening interval of 5 years. Simulation of a 5-year interval screening regimen versus no screen ing yielded a relative risk reduction of 31% (95% CI 12-46%). A similar value was found for a biennial screening regime. CONCLUSIONS: The results suggest that early detection of type 2 diabetes via a community-based screening project in developing countries with high prevalence is worthwhile.

Adult↗

Are patients of women physicians screened more aggressively? A prospective study of physician gender and screening.

OBJECTIVE: To determine the effects of physician gender on rates of Pap testing, mammography, and cholesterol testing when identifying and adjusting for demographic, psychosocial, and other patient variables known to influence screening rates. DESIGN: A prospective design with baseline and six-month follow-up assessments of patients' screening status. SETTING: Twelve community-based group family practice medicine offices in North Carolina. PARTICIPANTS: 1,850 adult patients, aged 18-75 years (six-month response rate, 83%), each of whom identified one of 37 physicians as being his or her regular care provider. MAIN RESULTS: Where screening was indicated at baseline, the patients of the women physicians were 47% more likely to get a Pap test [odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.05, 2.04] and 56% more likely to get a cholesterol test (OR = 1.56, 95% CI = 1.08, 2.24) during the study period than were the patients of the men physicians. For mammography, the younger patients (aged 35-39 years) of the women physicians were screened at a much higher rate than were the younger patients of the men physicians (OR = 2.69, 95% CI = 0.98, 7.34); however, at older ages, the patients of the women and the men physicians had similar rates of screening. CONCLUSIONS: In general, the patients of the women physicians were screened at a higher rate than were the patients of the men physicians, even after adjusting for important patient variables. These findings were not limited to gender-specific screening activities (e.g., Pap testing), as in some previous studies. However, the patients of the women physicians were aggressively screened for breast cancer at the youngest ages, where there is little evidence of benefit from mammography. Larger studies are needed to determine whether this pattern of effects reflects a broader phenomenon in primary care.

Adolescent↗

Barriers to mammography and Pap smear screening among women who recently had neither, one or both types of screening.

There is legitimate concern about whether cancer screening programs and other types of prevention and early detection programs are designed to reach those most in need of services. Previous research on barriers to screening has generally addressed screening for specific cancers. The purpose of this study was to evaluate and compare the types and strengths of barriers to both mammography and Pap smear screening experienced by three groups of women. Five hundred and twenty-two women, aged 52-69, who were members of a large health maintenance organization (HMO), completed a survey about cancer screening and associated barriers. Women with no mammogram in the preceding 2 years and with no Pap smear in 3 years were classified into a "safety net" program. We classified women as falling into both (Pap smear and mammography), one (Pap smear or mammography), or neither safety nets. Results consistently revealed that women needing both tests had more numerous and more intense barriers than other women to both types of screening. Factor analyses and descriptive analyses both showed that the types of barriers experienced were very similar for mammography and Pap smear screening. The discussion addresses intervention implications and the additional research needed on women who need both mammogram and Pap smear screening and who have much higher cancer risk than other women.

Aged↗

The study of the mass screening of persons without symptoms and of the screening of outpatients with gastrointestinal complaints or icterus for pancreatic cancer in Japan, using CA19-9 and elastase-1 or ultrasonography.

To investigate the possibility of detecting carcinomas of the pancreas at an early stage by mass screening of persons without symptoms or by screening the outpatients with gastrointestinal complaints or jaundice, we performed a multicentral study of the mass screening of 10,162 persons at five local areas and of the outpatient screening of 4506 at 17 hospitals for pancreatic cancer in Japan for two years from 1984 to 1985, using serum CA19-9 and elastase-1 determinations or ultrasonography. Mass screening of 10,162 persons over 40 years old found only four (0.04%) cases of pancreatic cancer, including one case that was curatively treated. According to the screening of 4506 outpatients with gastrointestinal complaints or icterus, 85 (1.9%) patients were found to have pancreatic cancer. Of these 85 patients, 28 could undergo curative treatment. In addition to them, 73 (1.6%) patients with other digestive organ cancer were found. Our results suggest that the mass screening of persons without symptoms is not worthwhile in the early detection of pancreatic cancer, but outpatient screening is useful for detecting curative cancers of the pancreas.

Adult↗

Blood cholesterol screening in several environments using a portable, dry-chemistry analyzer and fingerstick blood samples. Lipid Research Clinics Cholesterol Screening Study Group.

A multicenter study of blood cholesterol screening was performed in several typical environments, such as community sites (shopping malls and a supermarket), health care sites, work sites, a blood bank and a school. Cholesterol was measured with a portable, dry-chemistry analyzer using capillary blood obtained by fingerstick. Data are reported from a total of 13,824 participants, spanning the entire age spectrum. Overall, 25% of screened subjects had blood cholesterol levels above the age-specific cutpoints used in the current study. Although in the aggregate this screening experience very closely approximates the expected level of referrals, the proportion of referred screened subjects differed significantly among the 5 types of screening environments and by gender. Follow-up telephone interviews indicated that 53% of referrals had initiated a physician contact. More than 75% of those who had seen a physician reported that the diagnosis of hypercholesterolemia had been confirmed, and almost 72% had been prescribed a diet. A large proportion of referred screened subjects reported having modified their diet, particularly when recommended to do so by a physician. This study has yielded encouraging evidence that physicians gave referred screened subjects appropriate initial advice for managing hypercholesterolemia. The new technology for blood cholesterol measurement evaluated in the current study has proven to be a feasible and reliable means for measuring blood cholesterol in typical screening settings.

Adult↗

Cervical cancer screening among low-income women: results of a national screening program, 1991-1995.

OBJECTIVE: To evaluate the results of cervical cytology screening in the National Breast and Cervical Cancer Early Detection Program and to compare the findings with results from other screening programs. METHODS: We analyzed data on 312,858 women aged 18 years and older who received one or more Papanicolaou smears, and follow-up if indicated, from October 1991 through June 1995 at screening sites across the United States providing comprehensive National Breast and Cervical Cancer Early Detection Program services. RESULTS: Of the women screened, more than half were 40 years or older; slightly less than half (44%) were of racial and ethnic minorities. During the first screening cycle, 3.8% of Papanicolaou tests were reported as abnormal (squamous intraepithelial lesion [SIL] or squamous cell cancer); proportions of abnormals decreased with increasing age. The age-adjusted rate of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or worse among women screened was 7.4 per 1000 Papanicolaou tests; rates of CIN were highest among young women, but cancer rates peaked among women in their 50s and 60s. The percentages of first screening cycle-Papanicolaou tests interpreted as high-grade SIL and squamous cell carcinoma associated with biopsy-confirmed CIN II or worse (the positive predictive value) were 56.0% for CIN II/III and 3.7% for invasive cancer. Of the 150 invasive cancers diagnosed, 54.0% were classified as local disease. CONCLUSION: Observed results emphasize the duality of cervical neoplasia-CIN in younger women and invasive cancer in older women. This finding points to the importance of reaching both younger and older women for cervical cancer screening.

Adult↗

Use of visual screening methods for cervical cancer screening.

This article has considered recent advances in visual screening methods. Devices that use electro-optical sensors offer great potential in various clinical roles, but considerable additional work is required to develop these devices and it is unlikely that they will come into widespread clinical use in the next 5 years. In contrast numerous studies, demonstrate that simple visual screening methods, such as DVI, have a sensitivity for the detection of women with biopsy-confirmed high-grade SIL (CIN 2,3) and cancer that is equivalent to that of conventional cervical cytology. The primary disadvantage of the simple visual screening methods is poor specificity. These methods classify up to 30% of all women screened as being test positive and as a result new strategies toward managing DVI positive women must be developed before simple visual screening methods can be adopted for routine screening. Enhanced visual methods that use cervicography and speculoscopy may be more specific and improve detection of biopsy-confirmed SIL, but the added time and expense to perform either of these methodologies must be considered and justified. Currently numerous studies are evaluating the best strategies for incorporating visual screening methods into cervical cancer screening programs. In the near future we should be able to determine whether these approaches should be incorporated into routine clinical care.

Acetic Acid↗

Prostate cancer screening: the problem of overdiagnosis and lessons to be learned from breast cancer screening.

Screening for prostate cancer is a relatively new procedure, still under experimental evaluation within prospective randomised trials. The design of prospective studies has been mainly based on the experience of other cancer screenings, particularly breast cancer, for which data of several controlled studies are available. Unfortunately, breast cancer is very different from prostate cancer, particularly for aspects such as early diagnosis and, thus the screening process, originally modelled on the basis of the lesson taught by breast cancer screening, needs continuous re-evaluation and adjustment, based on data which are now being produced from ongoing screening experiences. In this paper, we will consider the most controversial aspects of prostate cancer screening and compare prostate screening with breast cancer screening in order to promote a better understanding of the current problems and lessons to be learned.

Aged↗

Breast and cervical cancer screening for women between 50 and 69 years of age: what prompts women to screen?

The objective of this study was to examine mammography and cervical cancer screening rates among women aged 50 to 69 and to understand which prompts are effective for improving screening compliance. A self-administered survey was sent to 800 randomly selected participants in a health region in a relatively poor, rural province in Eastern Canada with a universal health care system. Since 1995, New Brunswick has instituted a biannual self-referral mammography screening program for women between 50 and 69 years of age. The response rate to the survey was 66%. Mammography screening compliance was 73% and was most significantly associated with annual clinical breast examinations, compliance with cervical cancer screening, and physician suggestion (p <.001). Cervical cancer screening compliance was 91% and was significantly associated with annual clinical breast examinations, compliance with mammography screening, and physician suggestion (p<.001). Contact with a physician is most effective for promoting screening compliance.

Aged↗

Comparison of the frequency doubling technology screening algorithm and the Humphrey 24-2 SITA-FAST in a large eye screening.

PURPOSE: To compare the Frequency Doubling Technology (FDT) C20-1 screening algorithm and the Humphrey Field Analyser II (HFA) 24-2 SITA-FAST in a large eye screening. METHODS: In a non-randomized, prospective, free eye screening, the FDT Screening Protocol (C20-1 Screening Algorithm) was administered to 574 attendees (422 men and 152 women, average age 64, range 17-89 years) of the 1998 Veterans of Foreign Wars (VFW) Convention in San Antonio, Texas. Individuals who failed the FDT (two or more misses out of 17 locations) immediately underwent white-on-white threshold visual field perimetry (HFA 24-2, SITA-FAST). Humphrey visual field analysis included STATPAC and masked evaluations by three glaucoma specialists. RESULTS: Approximately one-tenth of the VFW conference attendees voluntarily presented themselves for screening. Among these 574 volunteers, 69 (12%) failed the FDT and underwent HFA analysis. Eighty-one per cent (56/69) of these FDT failures had abnormal HFA Glaucoma Hemifield Tests. Eighty-eight per cent (61/69) were judged to have nerve fibre type visual field loss on HFA by at least two of three masked examiners. A positive correlation existed between the number of FDT locations missed and the HFA mean deviation (r = 0.5, P = 0.0001). A similar association was observed when FDT and HFA results were analysed by quadrant (r = 0.5, P < 0.0001). CONCLUSION: There was a low false positive rate and a good positive predictive value comparing the FDT screening algorithm to the HFA 24-2 SITA-FAST in this study. This supports the potential use of FDT as an economical screening device.

Adolescent↗

Newborn screening with tandem mass spectrometry: examining its cost-effectiveness in the Wisconsin Newborn Screening Panel.

OBJECTIVE: To examine the cost-effectiveness of tandem mass spectrometry (MS/MS) in a neonatal screening panel for 14 fatty acid oxidation and organic acidemia disorders in the Wisconsin Newborn Screening Program. STUDY DESIGN: An incremental cost-effectiveness analysis with a hypothetical cohort of 100,000 infants was performed. A threshold of $50,000/QALY (quality-adjusted life-year) was used to determine whether screening for medium-chain acyl-CoA dehydrogenase deficiency (MCAD) alone is cost-effective or whether additional disorders would need to be incorporated into the analysis to arrive at a conclusion regarding the overall cost-effectiveness of MS/MS. RESULTS: Under conservative assumptions, screening for MCAD alone yields an incremental cost-effectiveness ratio of $41,862/QALY. With the use of more realistic assumptions, screening becomes more cost-effective ($6008/QALY) and remains cost-effective so long as the incremental cost of screening remains under $13.05 per test. Adding the incremental costs of detecting the 13 other disorders on the screening panel still yields a result well within accepted norms for cost-effectiveness ($15,252/QALY). CONCLUSIONS: In Wisconsin, MS/MS screening for MCAD alone appears to be cost-effective. Future analyses should examine the cost-effectiveness of alternative follow-up and treatment regimens for MCAD and other panel disorders.

Acyl-CoA Dehydrogenase↗

Value of self-reportable screening criteria to identify asymptomatic individuals in the general population for urogential Chlamydia trachomatis infection screening.

Submission of samples from the home allows screening for Chlamydia trachomatis without preceding professional assessment of clinical risk factors. Therefore, a validation of self-reportable information for use as selective screening criteria is needed. We asked a total of 1175 women and 1033 men who participated in an in-home sampling screening study to provide information on behavior and sociodemographic characteristics. In a multivariate model, selective screening criteria were developed on the basis of information from a random part of the tested population (development group), and the validity was assessed for the remaining part of the tested population (validation group). To find all infections, 95% of the subjects had to be screened, and screening 63% of them would have detected 86% of infections. Low predictive values were found when selective screening criteria from other studies were assessed. Selective screening by means of in-home sampling strategies among men and women aged 21-23 years cannot be recommended in the area studied.

Adult↗

Energy imparted to fluorescent screens from primary and scattered radiation. Variations with atomic composition and screen thickness.

The effects of thickness and atomic composition of fluorescent screens on the impartation of primary and scattered radiation is analysed. Different fluorescent screens give rise to different quotients epsilon p/epsilon s of energy imparted from primary and scattered radiation respectively, due to their variation in atomic composition and thickness. The image contrast in a given radiation field therefore varies with the choice of screen. Energy imparted by primary and scattered radiation in different fluorescent screens has been calculated as a function of tube voltage using a simple analytical model. Comparison of the results for fluorescent screens of different thicknesses with hypothetical screens with both negligible and total absorption has been made. From the results it is evident that the image contrast increases with increased detector thickness if scattered radiation is present. The trends found in the calculations have been confirmed by measurements of the energy imparted from scattered and primary radiation for a number of fluorescent screens including both commercial and specially made screens. Differences in the ratio epsilon p/epsilon s of up to 50% have been measured, and differences reported by other authors are discussed. Their use of detectors with different response to scattered and primary radiation may explain the discrepancies found.

Calcium Compounds↗

The German cervical cancer screening model: development and validation of a decision-analytic model for cervical cancer screening in Germany.

BACKGROUND: We sought to develop and validate a decision-analytic model for the natural history of cervical cancer for the German health care context and to apply it to cervical cancer screening. METHODS: We developed a Markov model for the natural history of cervical cancer and cervical cancer screening in the German health care context. The model reflects current German practice standards for screening, diagnostic follow-up and treatment regarding cervical cancer and its precursors. Data for disease progression and cervical cancer survival were obtained from the literature and German cancer registries. Accuracy of Papanicolaou (Pap) testing was based on meta-analyses. We performed internal and external model validation using observed epidemiological data for unscreened women from different German cancer registries. The model predicts life expectancy, incidence of detected cervical cancer cases, lifetime cervical cancer risks and mortality. RESULTS: The model predicted a lifetime cervical cancer risk of 3.0% and a lifetime cervical cancer mortality of 1.0%, with a peak cancer incidence of 84/100,000 at age 51 years. These results were similar to observed data from German cancer registries, German literature data and results from other international models. Based on our model, annual Pap screening could prevent 98.7% of diagnosed cancer cases and 99.6% of deaths due to cervical cancer in women completely adherent to screening and compliant to treatment. Extending the screening interval from 1 year to 2, 3 or 5 years resulted in reduced screening effectiveness. CONCLUSIONS: This model provides a tool for evaluating the long-term effectiveness of different cervical cancer screening tests and strategies.

Adolescent↗

Progress in cancer screening over a decade: results of cancer screening from the 1987, 1992, and 1998 National Health Interview Surveys.

BACKGROUND: Screening to detect cancer early, an increasingly important cancer control activity, cannot be effective unless it is widely used. METHODS: Use of Pap smears, mammography, fecal occult blood tests (FOBTs), sigmoidoscopy, and digital rectal examination (DRE) was evaluated in the 1987, 1992, and 1998 National Health Interview Surveys. Levels and trends in screening use were examined by sex, age, and racial/ethnic group. The effects of income, educational level, and health care coverage were examined within age groups. Logistic regression analyses of 1998 data were used to develop a parsimonious, policy-relevant model. RESULTS: Use of all screening modalities increased over the period examined; for mammography and DRE, the increase was more rapid in the first half of the decade; for the Pap test and sigmoidoscopy, the increase was more rapid in the second half of the decade. Levels of colorectal cancer screening (both sigmoidoscopy and FOBTs) in 1998 were less than the level that prevailed a decade earlier for mammography. Patterns of change for all screening modalities differed between age, sex, and racial/ethnic groups, but prevalence of use during the study, within recommended time intervals, was consistently lower among groups with lower income and less education. Logistic regression analyses indicated that insurance coverage and, to a greater extent, usual source of care had strong independent associations with screening usage when age, sex, racial/ethnic group, and educational level were taken into account. CONCLUSIONS: While cancer screening is generally increasing in the United States, usage is relatively low for colorectal cancer screening and among groups that lack health insurance or a usual source of care.

Adult↗

Screening for breast cancer in Ireland: the Eccles Breast Screening Programme.

The Eccles Breast Screening Programme is a population-based screening programme for breast cancer, based at the Mater Misericordiae Hospital, Dublin. It began in 1989 simultaneously with similar programmes in Belgium, France, Greece, Portugal and Spain. The objectives of the Eccles Programme are: (i) to evaluate the impact of mammographic screening on morbidity and mortality from breast cancer in Irish women; and (ii) to address the feasibility and potential value of a national breast cancer screening programme. The specific group targeted for screening is women born in 1925 to 1940 inclusive, in a defined geographical area comprising north Dublin City and County, and Counties Cavan and Monaghan. The areas combined comprise 16% of the country's population; just over 29,000 women were invited for screening. An analysis of the demographic and socioeconomic features of the target population reveals that it represents the total population remarkably well. Participants were invited from a population register to attend one of two screening units. Follow-up treatment for those with abnormalities takes place predominantly at the Mater Hospital where the facilities of the Departments of Pathology, Surgery and Oncology have been made available to the programme. Almost 18,000 women had a mammogram in the first round of screening, an overall response rate of 62%. A total of 129 cancers were detected, a prevalence of breast cancer of 7.2 per 1,000. Of those, 15 (11.6%) were entirely intraduct, and an additional 7 (5.4%) had minimal invasion. This is considerably higher than the proportion of intraduct cancers seen in referral practice populations.

Aged↗

Reduction of clinically manifest colorectal cancer by endoscopic screening: empirical evaluation and comparison of screening at various ages.

Endoscopic screening (sigmoidoscopy, colonoscopy) with removal of precancerous lesions can prevent a large proportion of colorectal cancers (CRCs). However, there is lack of data regarding optimal age, time intervals and numbers of screening examinations. We developed and applied modified techniques of epidemiological analysis to evaluate the impact of various endoscopy-based screening strategies on prevention of clinically manifest CRCs between the ages of 50 and 79 in a population-based case-control study (294 cases, 254 controls) conducted in Saarland, Germany. We found a strong potential for reduction of CRC occurrence even with a single screening endoscopy. The optimal age for a single screening endoscopy appears to be around 55 (estimated potential for prevention of cases between the ages of 55 and 79 in case of 100% compliance: 77% (95% confidence interval (CI) 46-90%)). A single screening endoscopy at age 50 would have a lower impact due to failure to prevent CRC at higher ages. Similarly, screening at ages 60 or older would have a lower impact because it would fail to prevent CRC at lower ages. Repeated offers of screening examinations could provide substantial additional benefit with the levels of compliance to be expected in practice, but they would have to be weighed against the increased risks and costs.

Age Factors↗