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[Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience].

The results and the significance of neonatal mass-screening programmes for inborn errors of metabolism, conducted by the National Research Institute of Mother and Child (NRIMC), are discussed. As the first in Poland, in 1964, mass-screening for phenylketonuria (PKU) was introduced. The BIA-Guthrie test was used. Other Guthrie tests (GBIA) were applied in homocystinuria, tyrosinemia, histidinemia and leucinosis (Maple Syrup Urine Disease-MSUD). In the middle of the 60. the Beutler and Baluda test was introduced for galactosaemia, as well as the Efron urine test in infant screening for different inborn errors of metabolism. In the middle of the 70., neonatal mass-screening for cystic fibrosis (CF, mucoviscidosis) was started. Meconium tests and the sweat test with ion selective chloride electrode were used. Apart from inborn errors of metabolism, we also introduced a screening programme for neuroblastoma in which vaniline mandelic acid (VMA) in urine was estimated and for congenital hypothyroidism were TSH level was assessed. The results of screening are shown in the tables and in the figures. In our opinion the best clinical results are obtained with screening for congenital hypothyroidism and for PKU, since very early detection and treatment in these diseases prevents severe mental retardation. We therefore consider that both these screening programmes should be treated as obligatory examinations in all neonates. Taking into consideration the fact that there are different types of hyperhenylalaninemias, the principles of differential diagnosis are discussed. Molecular genetic investigations, carried out in the NRIMC Department of Genetics proved to be a very important procedure in the verification of diagnosis of different mutations. The authors also discuss the problem of dietary treatment duration in PKU. In our opinion the hypophenyloalanine diet regimen in girls, should not be discontinued during adolescence, since there is the problem of maternal PKU and the possibility of foetal damage. The results of our own investigations of maternal PKU are discussed. The significance of mass-screening for galactosemia is still under discussion. In our opinion, mass-screening for galactosemia is not useful and we have discontinued it. Selective screening has been started combined with molecular genetic studies in high risk families. In the future, we plan to prepare guidelines on the principles of diagnosis and treatment of galactosemia in children and women in the reproductive age. Mass-screening for cystic fibrosis is also still under discussion. The results of the early screening programmes were not satisfactory and the tests were discontinued. In 1998, after reorganisation of the whole system, CF screening, using tripsin-radioimmune assays, was started again. The new screening programme is combined with molecular genetic investigation of different mutations. It is still too early to assess the importance and success of this CF mass-screening programme. We decided to discontinue the screening for homocystinuria, histidinemia, tyrosinemia, leucinosis and for neuroblastoma, since these programmes did not comply with criteria of mass-screening. In 1997, major reorganisation of screening programmes for inborn errors of metabolism, at NRIMC, was undertaken. The Guthrie test for PKU was changed to a quantitative colorimetric method. The immuno-luminometric method is used for TSH estimation. The whole system is based on complete computer control of all the steps of screening, from blood sampling on filter paper until the final diagnosis. The advantages of this modern system of organisation of the screening programme are discussed.

Decision Trees↗
PubMedDate not supplied

Assessment of cervical cancer screening and follow-up programs.

There is essentially no debate about the benefits of cervical cancer screening. The current debate centers around periodicity, the appropriate interval for repeated testing, and the age at which screening should be discontinued. As the frequency of screening is increased within a defined population, there is a gain in survival (life-years) depending upon the risk status of the population segment screened. However, each increment in survival comes at an increasingly high cost. Significant gains have been made in improving screening and detection services through widespread availability of the Papanicolaou test. However, there has been concern raised that the cost-effectiveness of cervical cancer screening has not been clearly demonstrated. This report analyzes the current status of the literature on screening for cervical cancer with a focus on cost-effectiveness and cost-benefit analyses of screening using the Pap test. A relatively small group of studies was located which directly addressed the cost-effectiveness question. All of the studies cited attempted in some manner to describe the relationship between benefits of cervical cancer screening and costs. Two studies reported a program design with net positive monetary benefits, while one estimated that the direct cost of medical care avoided through screening was approximately equal to the cost of the screening program. In general, however, screening for cervical cancer is viewed as an investment in extending life (a net cost per year of life gained). Most analysts ascribe a net monetary cost to cervical cancer screening programs. Then the question becomes one of cost-effectiveness--designing a program so as to optimize the result obtained. With respect to optimizing screening, the literature leaves no doubt of the value of cervical cancer screening in general. From a cost-effectiveness perspective, screening no more frequently than every 3-5 years appears reasonable. It is important to think in terms of a total program and how effectively the population at risk is being reached. The literature reviewed spans a period of more than twenty years and reflects studies across the globe. While the quality is uneven, from this body of work a consensus emerges: screening is effective, but the frequency of screening in the United States is probably too high. In addition, those who are most intensively screened are probably at the lowest risk. Outreach and targeting of at-risk population groups needs to be addressed in order to improve cost-effectiveness of cervical cancer screening. The effectiveness of the screening technology (the Pap test) is taken for granted, but this may be a mistake.(ABSTRACT TRUNCATED AT 400 WORDS)

Cost-Benefit Analysis↗
PubMed2004

An outcomes analysis of five prenatal screening strategies for trisomy 21 in women younger than 35 years.

OBJECTIVE: This study was undertaken to examine the cost-effectiveness and procedural-related losses associated with 5 prenatal screening strategies for fetal aneuploidy in women under 35 years old. STUDY DESIGN: Five prenatal screening strategies were compared in a decision analysis model: triple screen: maternal age and midtrimester serum alpha-fetoprotein, human chorionic gonadotropin (hCG), and unconjugated estriol; quad screen: triple screen plus serum dimeric inhibin A; first-trimester screen: maternal age, serum pregnancy-associated plasma protein A and free beta-hCG and fetal nuchal translucency at 10 to 14 weeks' gestation; integrated screen: first-trimester screen plus quad screen, but first-trimester results are withheld until the quad screen is completed when a composite result is provided; sequential screen: first-trimester screen plus quad screen, but the first-trimester screen results are provided immediately and prenatal diagnosis offered if positive; later prenatal diagnosis is available if the quad screen is positive. Model estimates were literature derived, and cost estimates also included local sources. The 5 strategies were compared for cost, the numbers of Down syndrome fetuses detected and live births averted, and the number of procedure-related euploid losses. Sensitivity analyses were performed for parameters with imprecise point estimates. RESULTS: In the baseline analysis, sequential screening was the least expensive strategy ($455 million). It detected the most Down syndrome fetuses (n=1213), averted the most Down syndrome live births (n=678), but led to the highest number of procedure-related euploid losses (n=859). The integrated screen had the fewest euploid losses (n=62) and averted the second most Down syndrome live births (n=520). If fewer than 70% of women diagnosed with fetal Down syndrome elect to abort, the quad screen became the least expensive strategy. CONCLUSION: Although sequential screening was the most cost-effective prenatal screening strategy for fetal trisomy 21, it had the highest procedure-related euploid loss rate. The patient's perspective on detection versus fetal safety may help define the optimal screening strategy.

Cohort Studies↗
PubMed2003

Screening men for prostate and colorectal cancer in the United States: does practice reflect the evidence?

CONTEXT: The debate about the efficacy of prostate-specific antigen (PSA) screening for prostate cancer has received substantial attention in the medical literature and the media, but the extent to which men are actually screened is unknown. If practice were evidence-based, PSA screening would be less common among men than colorectal cancer screening, a preventive service of broad acceptance and proven efficacy. OBJECTIVE: To compare the prevalences of PSA and colorectal cancer screening among US men. DESIGN, SETTING, AND POPULATION: The 2001 Behavioral Risk Factor Surveillance System, an annual population-based telephone survey of US adults conducted by the Centers for Disease Control and Prevention, was used to gather data on a representative sample of men aged 40 years or older from all 50 states and the District of Columbia (n = 49 315). MAIN OUTCOME MEASURES: Proportions of men ever screened and up to date on screening for prostate cancer (with PSA testing) and colorectal cancer (with fecal occult blood testing, flexible sigmoidoscopy, or colonoscopy). RESULTS: Overall, men are more likely to report having ever been screened for prostate cancer than for colorectal cancer; 75% of those aged 50 years or older have had a PSA test vs 63% for any colorectal cancer test (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.18-1.21). Up-to-date PSA screening is also more common than colorectal cancer screening for men of all ages. Among men aged 50 to 69 years (those for whom there is the greatest consensus in favor of screening), 54% reported an up-to-date PSA screen, while 45% reported up-to-date testing for colorectal cancer (RR, 1.19; 95% CI, 1.16-1.21). In state-level analyses of this age group, men were significantly more likely to be up to date on prostate cancer screening compared with colorectal cancer screening in 27 states, while up-to-date colorectal cancer screening was more common in only 1 state. CONCLUSION: Among men in the United States, prostate cancer screening is more common than colorectal cancer screening. Physicians should ensure that men who choose to be screened for cancer are aware of the known mortality benefit of colorectal cancer screening and the uncertain benefits of screening for prostate cancer.

Adult↗
PubMed2004

Examining the cost-effectiveness of cancer screening promotion.

Cost-effectiveness analyses (CEAs) can help to quantify the contribution of the promotion of a screening program to increased participation in screening. The cost-effectiveness (C/E) of screening promotion depends in large part on the endpoints of interest. At the most fundamental level, the C/E of a strategy for promoting screening would focus on the attendance rate, or cost per person screened, and the C/E would be influenced by the costs of promotion, as well as by the size and responsiveness of the target population. In addition, the costs of screening promotion (measured as the cost per additional participant in screening) can be included in a CEA estimate of the screening technology. In this case, depending on the efficacy of the screening test and the costs and influence of the promotion, the C/E of screening may improve or become poorer. In the current study, the authors reviewed the literature on the C/E of cancer screening promotion. The following lessons were learned regarding the C/E of screening and its promotion: 1) high-quality information on the C/E of screening is increasingly available; 2) cost-effective promotion of screening is dependent on cost-effective screening strategies; 3) quality-of-life effects may be important in assessing the overall C/E of screening programs; 4) research efforts aimed at identifying cost-effective approaches to screening promotion are useful but sparse; 5) C/E studies should be better incorporated into well designed effectiveness research efforts; 6) variations in C/E according to intervention characteristics, population characteristics, and context should be evaluated in greater depth; 7) the long-term effects of screening promotion are critical to assessing C/E; 8) the effects of promotion on costs of screening must be better understood; and 9) CEA must be interpreted in light of other information. The authors showed that CEA can be a valuable tool for understanding the merits of health promotion interventions and that CEA is particularly valuable in identifying screening strategies that might be promoted most cost-effectively.

Cost-Benefit Analysis↗
PubMed2002

A breast cancer screening programme operating in a liberal health care system: the Luxembourg Mammography Programme, 1992-1997.

The national breast cancer screening programme in Luxembourg, the Mammography Programme (MP), was launched in 1992. Its primary goal was to set up an organised breast cancer screening with biennial invitation-reinvitation of women 50-64 years, 2-view mammography, technical quality assurance, double-reading procedures and close monitoring of performance. In 1994, the decision was taken by health authorities to only reimburse screening mammograms done within the MP. We evaluated the performance of 3 screening rounds that took place in 1992-1997. In 1992, 4,815 women had opportunistic screening and 4,790 attended the MP. In 1997, 861 women had opportunistic screening and 8,603 attended the MP. In 1997, the participation rate in the MP reached 50%. The referral rate in the MP was 10% for initial screening and 5% for subsequent screening. Echographic examinations accounted for 71% of referrals. Per 1,000 screened women, biopsy and cancer rates were 18.0 and 8.0 for initial screening and 10.3 and 5.8 for subsequent screening. Twenty-one percent of the breast cancers diagnosed in screened women were interval cancers. The age-adjusted proportion of tumours >20 mm was 56.1% before 1992, 45.1% for women not (yet) screened by the MP, 27.0% for interval cancers, 26.6% for initial screening and 12.0% for subsequent screenings. Tumour size distribution was similar to that observed in the Dutch Breast Cancer Screening Programme, 1990-1993, except that in the latter programme, no difference was observed between initial and subsequent screening. The Luxembourg experience shows that in a liberal health care system, a policy of organising the screening process by reimbursing only those mammograms done within the context of the organised screening programme can drastically reduce opportunistic screening. Further efforts in the Mammography Programme will aim at increasing participation and look at ways to decrease referrals to echography.

Aged↗
PubMed2001

Screening for skin cancer.

CONTEXT: Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past 2 decades. Nonmelanoma skin cancer is seldom lethal, but, if advanced, can cause severe disfigurement and morbidity. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of nonmelanoma skin cancer might prevent major disfigurement and to a lesser extent prevent mortality. Current recommendations from professional societies regarding screening for skin cancer vary. OBJECTIVE: To examine published data on the effectiveness of routine screening for skin cancer by a primary care provider, as part of an assessment for the U.S. Preventive Services Task Force. DATA SOURCES: We searched the MEDLINE database for papers published between 1994 and June 1999, using search terms for screening, physical examination, morbidity, and skin neoplasms. For information on accuracy of screening tests, we used the search terms sensitivity and specificity. We identified the most important studies from before 1994 from the Guide to Clinical Preventive Services, second edition, and from high-quality reviews. We used reference lists and expert recommendations to locate additional articles. STUDY SELECTION: Two reviewers independently reviewed a subset of 500 abstracts. Once consistency was established, the remainder were reviewed by one reviewer. We included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost effectiveness. DATA EXTRACTION: We abstracted the following descriptive information from full-text published studies of screening and recorded it in an electronic database: type of screening study, study design, setting, population, patient recruitment, screening test description, examiner, advertising targeted at high-risk groups or not targeted, reported risk factors of participants, and procedure for referrals. We also abstracted the yield of screening data including probabilities and numbers of referrals, types of suspected skin cancers, biopsies, confirmed skin cancers, and stages and thickness of skin cancers. For studies that reported test performance, we recorded the definition of a suspicious lesion, the "gold-standard" determination of disease, and the number of true positive, false positive, true negative, and false negative test results. When possible, positive predictive values, likelihood ratios, sensitivity, and specificity were recorded. DATA SYNTHESIS: No randomized or case-control studies have been done that demonstrate that routine screening for melanoma by primary care providers reduces morbidity or mortality. Basal cell carcinoma and squamous cell carcinoma are very common, but detection and treatment in the absence of formal screening are almost always curative. No controlled studies have shown that formal screening programs will improve this already high cure rate. While the efficacy of screening has not been established, the screening procedures themselves are noninvasive, and the follow-up test, skin biopsy, has low morbidity. Five studies from mass screening programs reported the accuracy of skin examination as a screening test. One of these, a prospective study, tracked patients with negative results to determine the number of patients with false-negative results. In this study, the sensitivity of screening for skin cancer was 94% and specificity was 98%. Several recent case-control studies confirm earlier evidence that risk of melanoma rises with the presence of atypical moles and/or many common moles. One well-done prospective study demonstrated that risk assessment by limited physical exam identified a relatively small (<10%) group of primary care patients for more thorough evaluation. CONCLUSIONS: The quality of the evidence addressing the accuracy of routine screening by primary care providers for early detection of melanoma or nonmelanoma skin cancer ranged from poor to fair. We found no studies that assessed the effectiveness of periodic skin examination by a clinician in reducing melanoma mortality. Both self-assessment of risk factors or clinician examination can classify a small proportion of patients as at highest risk for melanoma. Skin cancer screening, perhaps using a risk-assessment technique to identify high-risk patients who are seeing a physician for other reasons, merits additional study as a strategy to address the excess burden of disease in older adults.

Basal Cell Carcinoma↗
PubMed2003

Developments in the screening for Chlamydia trachomatis: a review.

Many studies have evaluated selective screening criteria for women in various settings. Most have concluded and all guidelines recommend that all women aged < 25 be screened yearly for C. trachomatis infection. Behavioral criteria, such as the number of sex partners, new or more than one sex partners, and previous infection, also can serve as criteria for screening women aged > 25. Because re-infection rates are high and occur within a few months, complications may be reduced further if partners are treated and women rescreened 4 to 6 months after initial infection. Revised recommendations for C. trachomatis screening programs have stated that more frequent screening may be considered among women < 20 and those with recent infection. Screening in nontraditional settings and careful evaluation of local prevalence and risk factor information should be encouraged. Private providers and emergency room providers should discuss screening recommendations and adopt a C. trachomatis screening policy for the population they serve. The HEDIS measure should serve to encourage at least annual screening of 15- to 25-year-old sexually active females through providers linked to managed care organizations. In general, high yields (ie, percentage of tests that are positive) in nontraditional settings and enhanced feasibility and acceptability of urine-based tests may encourage further innovative approaches to reach and screen populations at risk. Several issues remain to be addressed to increase the effectiveness of screening efforts. If more sensitive amplification tests are used widely, more infected persons will be identified and treated, and transmission patterns may change, particularly if partner treatment also occurs. Current screening criteria should continue to be re-evaluated. An important issue that affects testing methods includes the possible need for confirmation testing when using NAATs if the prevalence of C. trachomatis is less than 2%. If the sensitivity of an NAAT is 85% and specificity is 99%, in a hypothetical population of 10,000 with a prevalence of 2%, the positive predictive value is 170/268 (63%). A second important issue affecting testing methods and feasibility of using NAATs for screening large numbers of individuals is the pooling of urine specimens, which has been evaluated in several studies and found to be very effective for reducing costs. A research issue for pooling is the determination of the most cost-effective prevalence levels for pooling. An additional research question is in which populations should a NAAT be used for detection of C. trachomatis and N. gonorrhoeae. There are no recommendations for the routine screening of men because of the paucity of data showing that this strategy can reduce sequelae. The CDC is conducting a multisite study to examine the feasibility, acceptability, and usefulness of screening of asymptomatic men. There are a few studies have determining cost-effective prevalence threshold levels, particularly with NAATs. A recently developed decision analysis model by CDC designed to maximize the effectiveness of screening strategies for C. trachomatis infections may be useful for decision makers. It is intended to serve as an easy and flexible tool to determine cost effectiveness at a local level and takes into account positivity rates and test performance characteristics (SOCRATES). It is unclear if recurrent infection is caused by true re-infection by the same or a different partner or recurrence of initial infection. Recurrence may be caused by persistence of C. trachomatis or antibiotic resistance. This distinction is of scientific interest because the appropriate intervention differs (eg, identification of risk factors for the former and microbiologic investigations for the latter). Effective partner management and retesting are critical to reducing sequelae of C. trachomatis infection. Screening for C. trachomatis infection remains an essential component of C. trachomatis control. It is cost effective, most infections are asymptomatic, and symptom-based health care seeking and testing identify few of those infected. The likelihood that opportunities for screening are missed is high particularly in non-STD clinic settings. Local studies using NAATs to determine C. trachomatis prevalence and risk factors are helpful to health care providers so they can make evidence-based decisions on who to screen. The use of nontraditional, non-clinic-based test settings should be explored further. We have focused on summarizing the medical evidence regarding recommendations for screening for C. trachomatis. High-risk populations for C. trachomatis infection may overlap with populations for other STDs, and comprehensive STD prevention programs that involve a range of STD service providers are needed to successfully reduce the STD-related health burden in the population.

Chlamydia Infections↗
PubMed2005

Two approaches to maternal depression screening during well child visits.

The US Preventive Services Task Force (USPSTF) has recommended depression screening for adults. Screening mothers has special importance to pediatricians because of the impact of maternal depression on children. The two screening questions endorsed by the USPSTF may allow pediatricians to screen mothers during routine well child care. This study explores the feasibility and yield of interview- and paper-based pediatric screening for maternal depression during well child visits. A structured interview script was developed to inquire about maternal depression. It included the two-question screen and required less than 1 minute to administer. An alternative paper-based screen asked the two questions after a brief written introduction providing the rationale. Four community pediatric practices in New Hampshire and Maine were trained in both screening approaches and developed plans on how to respond to positive screens (either question positive). The 11 providers at these sites tested the two approaches on two different series of mothers at well child visits. The pediatricians also reported barriers to the screening inquiries, maternal responses, and subsequent clinician actions and referrals. The pediatricians screened 250 mothers via the scripted interview. In a second trial, 223 women had paper-based depression screening. Yields from the paper-based screen were 22.9% versus 5.7% for the interview-based screener. Pediatricians also took on the new role of discussion of possible depression in about two thirds of cases. Subsequently, 7.6% of all women with paper-based screening were referred to mental health versus 1.6% with the interview-based screening. With the interview, mothers of children younger than 1 year of age were less likely to screen positive than those with older children (1.9% vs. 8.5%, p = .04). With the paper-based screener, no age differences in positive screen rates occurred. While both approaches to screening were feasible in primary care, the yield from the two different approaches differed substantially. This finding deserves exploration in future studies. With either of these screening approaches, pediatricians could enhance their detection of mothers at risk of depression. The outcomes of pediatrician screening and the best approach to follow-up care still need to be determined.

Adolescent↗
PubMed2003

National survey of trauma surgeons' use of alcohol screening and brief intervention.

BACKGROUND: A variety of policy groups have recommended that screening and brief interventions (BIs) for alcohol disorders be widely implemented in health care settings. This study was conducted to determine the current status of screening and intervention programs in trauma centers and to evaluate specific barriers to implementation of screening and BIs. The hypotheses tested were that surgeons who support screening and brief interventions would be less likely to endorse the purported barriers to screening and intervention and would have a better understanding of the concept of brief interventions. METHODS: A postal survey of 711 members of the American Association for the Surgery of Trauma and the Western Trauma Association was performed to assess current screening and treatment practices, along with barriers to screening and intervention. Two logistic regression models were constructed to determine which factors result in support for screening and which factors predict support of BIs to help determine potentially modifiable issues to facilitate implementation. RESULTS: Three hundred eighty-three surgeons responded, 315 of whom are currently practicing trauma. The majority of surgeons (267 [83%]) agreed that a trauma center is an appropriate setting for addressing harmful alcohol consumption. Over two thirds frequently check a blood alcohol concentration, with one third of the group reporting that they always do. The use of formal screening questionnaires was much less frequent (25%). Nearly one half (49%) understood the concept of BIs. However, the majority report that less than one half of patients with a suspected alcohol problem at their center have their alcohol problem addressed while they are hospitalized. Several barriers to screening and BIs were identified. Although only 2% thought screening and counseling would significantly increase health care costs, 7% thought screening was too time consuming and 13.6% thought it would compromise patient confidentiality. Screening was perceived to threaten reimbursement by 27%. Over half (55%) stated their facility is currently performing screening. One third (36%) stated their facility is currently performing BIs. Logistic regression revealed that surgeons who support screening were those who thought patients with alcohol problems should be referred for professional alcohol treatment (odds ratio [OR], 6.5; 95% confidence interval [CI], 2.3-18.2) and that a trauma center is an appropriate setting for addressing alcohol disorders (OR, 6.2; 95% CI, 2.7-14.2). In the model of support for BIs, understanding the concept of BIs (OR, 5.7; 95% CI, 3.1-10.5) and lack of the belief that screening and intervention would increase cost too much (OR, 0.14; 95% CI, 0.02-0.96) were the most potent predictors of support for BIs. CONCLUSION: Trauma surgeons are screening for alcohol disorders more frequently than they were 5 years ago. Barriers to screening are not as prevalent as previously reported. Support for implementing screening and intervention programs depends on whether surgeons believe trauma centers are appropriate sites for addressing alcohol disorders, whether surgeons believe patients with alcohol problems should be referred for professional treatment, whether surgeons understand the concept of brief interventions, and whether they believe the cost constraints are not prohibitive. Widespread education in the effectiveness and methods of BIs would facilitate implementation of alcohol screening and intervention programs to help reduce recurrent alcohol-related injury.

Alcoholism↗
PubMed2003

Screening for fragile X syndrome: a literature review and modelling study.

OBJECTIVES: To compare the effectiveness, estimate the associated costs, and summarise available evidence about the feasibility and acceptability of different screening strategies in England and Wales. Also to establish a model for estimating effectiveness and costs of these different strategies. DATA SOURCES: Literature searches were restricted to MEDLINE and EMBASE, as well as citations in included papers. A broad search strategy was used involving all aspects of fragile X syndrome (FXS) and covered all relevant literature published between 1991 and 2001. REVIEW METHODS: An assessment was conducted of published literature and efforts focused on the development of a model that could be used to synthesise data from various sources, estimate cost-effectiveness of different strategies, and conduct sensitivity analyses according to different assumptions. RESULTS: The identified screening programmes were effective in detecting carriers, but a comparison of different strategies was not possible. Simulation results by the FXS Model showed that, over the first 10 years, 4% of premutation (PM) females and 70% of full mutation (FM) females could be detected by active cascade screening; it is 10% and 58%, respectively, by prenatal screening. The maximal detection rate for FM carriers by active cascade screening is higher than that by prenatal screening (91% versus 71%). However, the maximal rate of detection of female PM carriers by active cascade screening (6%) is much lower than that by prenatal screening (60%). During the first 10 years of simulation, the estimated direct cost per year to the NHS in England and Wales is 0.7-0.2 million pounds sterling by active cascade screening and 14.5-9.1 million pounds sterling by a programme of prenatal screening. The incremental cost per extra carrier detected (using current practice as the reference standard) is on average only 165 pounds sterling by active cascade screening and 7543 pounds sterling by prenatal screening. The incremental cost per FXS birth avoided is on average 8494 pounds sterling by active cascade screening and 284,779 pounds sterling by prenatal screening. CONCLUSIONS: The empirical evidence suggests that both prenatal screening and cascade screening are feasible and acceptable. Population-based prenatal screening is more efficacious, but it will cost more than active cascade screening. The active cascade screening of affected families is more efficient, cheaper, but less effective than a population-based prenatal screening. It is suggested that both strategies be evaluated in large-scale trials, which might also help to determine whether and how the different strategies could be simultaneously or sequentially combined.

England↗
PubMed1997

Effect of screening for cancer in the Nordic countries on deaths, cost and quality of life up to the year 2017.

The aim of this study was to evaluate the effects of screening for cancer in the Nordic countries. There is sufficient scientific evidence to conclude that screening for cervical cancer, breast cancer and colorectal cancer will result in a reduction in mortality. The effects on mortality were predicted for the future up to the year 2017 assuming that the Nordic countries are covered by screening as a nation-wide population-based public health policy and comparing the predicted mortality trends with those assuming no screening programmes. For cervical cancer the programme as practised in Finland was used as a point of reference. For breast cancer and for colorectal cancer the results of randomized preventive trials were assumed in the absence of detailed results based on any public health policy, i.e., a reduction of 30% in mortality from breast cancer and 20% in mortality from colorectal cancer. The assumed ages and frequencies of screening ranged from 25 to 59 years at 5-year intervals for cervical cancer, from 50 to 69 at 2-year intervals for breast cancer and annual screening from 50 to 74 years for colorectal cancer. Data on incidence and incidence predicted up to the year 2012, mortality, survival and size of the general population were employed in the estimation. Age-cohort and age-period-cohort log-linear models were applied in predicting future mortality rates with and without screening. The choice of the models depended on the age distribution of deaths from each particular site of cancer, on changes in public health policy, such as establishment of mass-screening, and on the goodness of fit of the model. The screening policy assumed would result in 1600 annual deaths prevented out of the potential 13,600 deaths in the Nordic countries in 1995, corresponding to 11% of the deaths from the three primary sites. Only after the year 2010 will the ultimate effect of such a screening policy have as full an effect and in 2013-2017 the annual number of cancer deaths prevented will be 3900 out of 15,000 potential deaths, i.e., a 26% reduction. This is equal to 5.7% of all cancer deaths in the Nordic countries in 2013-2017 (2.0% for males and 9.7% for females). The predicted numbers of annual deaths prevented in 2013-2017 are 1500 for cervical cancer, 1000 for breast cancer and 1500 for colorectal cancer. Most (91%) of the cervical cancers can be prevented, whereas the proportion of breast cancer deaths (18%) and colorectal cancer deaths (18%) prevented will be much smaller. Costs of the screening programmes were estimated taking into consideration the direct costs of screening and savings from advanced disease treatment and terminal care. The total cost of screening for cervical, breast and colorectal cancer in the Nordic countries in the year 2010 is estimated to be $111 m. Cervical cancer screening is estimated to save $17 m yearly in the period 2008-2012. Screening for cervical cancer is approaching a phase when both the effect and costs are relatively stable and it was estimated to be cost-saving. The effect of screening for breast and colorectal cancers is expected to become apparent gradually during the predicted period due to the increasing number (and percentage) of patients diagnosed by screening. When the screening programmes are assumed to achieve the optimal effect, the reduction in mortality will increase and treatment costs fall, resulting in a substantial decrease in the cost-effectiveness ratio. In the last considered period (2008-2012) the costs per life year gained (breast cancer $15,400, colorectal cancer $5700) are approximately one half of those at the onset of screening. The differences in the costs per LYG were relatively small between the Nordic countries and mainly dependent on the differences in baseline risk of cancer. The total cost of the three screening programmes was estimated at $4400 per life years gained in the year 2010.(ABSTRACT TRUNCATED)

Aged↗
PubMed2001

Estimating the efficacy and efficiency of cascade genetic screening.

Screening for genetic variants that predispose individuals or their offspring to disease may be performed at the general population level or may instead be targeted at the relatives of previously identified carriers. The latter strategy has come to be known as "cascade genetic screening." Since the carrier risk of close relatives of known carriers is generally higher than the population risk, cascade screening is more efficient than population screening, in the sense that fewer individuals have to be genotyped per detected carrier. The efficacy of cascade screening, as measured by the overall proportion of carriers detected in a given population, is, however, lower than that of population-wide screening, and the respective inclusion rates vary according to the population frequency and mode of inheritance of the predisposing variants. For dominant mutations, we have developed equations that allow the inclusion rates of cascade screening to be calculated in an iterative fashion, depending upon screening depth and penetrance. For recessive mutations, we derived only equations for the screening of siblings and the children of patients. Owing to their mathematical complexity, it was necessary to study more extended screening strategies by simulation. Cascade screening turned out to result in low inclusion rates (<1%) when aimed at the identification of heterozygous carriers of rare recessive variants. Considerably higher rates are achievable, however, when screening is performed to detect covert homozygotes for frequent recessive mutations with reduced penetrance. This situation is exemplified by hereditary hemochromatosis, for which up to 40% of at-risk individuals may be identifiable through screening of first- to third-degree relatives of overt carriers (i.e., patients); the efficiency of this screening strategy was found to be approximately 50 times higher than that of population-wide screening. For dominant mutations, inclusion rates of cascade screening were estimated to be higher than for recessive variants. Thus, some 80% of all carriers of the factor V Leiden mutation would be detected if screening were to be targeted specifically at first- to third-degree relatives of patients with venous thrombosis. The relative cost efficiency of cascade as compared with population-wide screening (i.e., the overall savings in the extra managerial cost of the condition) is also likely to be higher for dominant than for recessive mutations. This notwithstanding, once screening has become cost-effective at the population level, it can be expected that cascade screening would only transiently represent an economically viable option.

Computer Simulation↗
PubMed2005

Screening for breast cancer.

CONTEXT: Breast cancer screening in community practices may be different from that in randomized controlled trials. New screening modalities are becoming available. OBJECTIVES: To review breast cancer screening, especially in the community and to examine evidence about new screening modalities. DATA SOURCES AND STUDY SELECTION: English-language articles of randomized controlled trials assessing effectiveness of breast cancer screening were reviewed, as well as meta-analyses, systematic reviews, studies of breast cancer screening in the community, and guidelines. Also, studies of newer screening modalities were assessed. DATA SYNTHESIS: All major US medical organizations recommend screening mammography for women aged 40 years and older. Screening mammography reduces breast cancer mortality by about 20% to 35% in women aged 50 to 69 years and slightly less in women aged 40 to 49 years at 14 years of follow-up. Approximately 95% of women with abnormalities on screening mammograms do not have breast cancer with variability based on such factors as age of the woman and assessment category assigned by the radiologist. Studies comparing full-field digital mammography to screen film have not shown statistically significant differences in cancer detection while the impact on recall rates (percentage of screening mammograms considered to have positive results) was unclear. One study suggested that computer-aided detection increases cancer detection rates and recall rates while a second larger study did not find any significant differences. Screening clinical breast examination detects some cancers missed by mammography, but the sensitivity reported in the community is lower (28% to 36%) than in randomized trials (about 54%). Breast self-examination has not been shown to be effective in reducing breast cancer mortality, but it does increase the number of breast biopsies performed because of false-positives. Magnetic resonance imaging and ultrasound are being studied for screening women at high risk for breast cancer but are not recommended for screening the general population. Sensitivity of magnetic resonance imaging in high-risk women has been found to be much higher than that of mammography but specificity is generally lower. Effect of the magnetic resonance imaging on breast cancer mortality is not known. A balanced discussion of possible benefits and harms of screening should be undertaken with each woman. CONCLUSIONS: In the community, mammography remains the main screening tool while the effectiveness of clinical breast examination and self-examination are less. New screening modalities are unlikely to replace mammography in the near future for screening the general population.

Breast Neoplasms↗
PubMed2004

A perspective from countries using organized screening programs.

Cancer screening may be offered to a population opportunistically, as part of an organized program, or as some combination of the preceding two options. Organized screening is distinguished from opportunistic screening primarily on the basis of how invitations to screening are extended. In organized screening, invitations are issued from centralized population registers. In opportunistic screening, however, due to the lack of central registers, invitations to screening depend on the individual's decision or on encounters with health care providers. The current article outlines key differences between organized and opportunistic screening. In the current study, literature searches were performed using PubMed and MEDLINE. Additional data were assembled from interviews with health officials in the five countries investigated and from the authors' personal files. Opportunistic screening was found to be distinguishable from organized screening on the basis of whether screening invitations were issued from centralized population registers. Organized screening programs also assumed centralized responsibility for other key elements of screening, such as eligibility requirements, quality assurance, follow-up, and evaluation. Organized programs focused on reducing mortality and morbidity at the level of the population rather than at the level of the individual. Thus, programs did not necessarily offer the most sensitive screening test for a particular cancer, and tests sometimes were offered at suboptimal intervals with respect to individual-level protection. Nonetheless, organized systems paid greater attention to the quality of screening, as measured by factors such as cancer detection rates, tumor characteristics, and false-positive biopsy rates. As a result, participants in organized screening programs received greater protection from the harmful effects associated with screening. In addition, organized programs worked more systematically toward providing value for money in an inevitably resource-limited environment. Although organized and opportunistic models of screening can yield similar uptake rates, organized programs exhibited greater potential ability to reduce cancer incidence and mortality, because of the higher levels of population coverage and centralized commitment to quality and monitoring; were more likely to be cost-effective; and offered greater protection against the harmful effects associated with poor quality or overly frequent screening.

Cost-Benefit Analysis↗
PubMed1996

Randomised controlled trial of faecal-occult-blood screening for colorectal cancer.

BACKGROUND: There is growing evidence that faecal-occult-blood (FOB) screening may reduce colorectal cancer (CRC) mortality, but this reduction in CRC mortality has not been shown in an unselected population-based randomised controlled trial. The aim of this study was to assess the effect of FOB screening on CRC mortality in such a setting. METHODS: Between February, 1981, and January, 1991, 152,850 people aged 45-74 years who lived in the Nottingham area of the UK were recruited to our study. Participants were randomly allocated FOB screening (76,466) or no screening (controls; 76,384). Controls were not told about the study and received no intervention. Screening-group participants were sent a Haemoccult FOB test kit with instructions from their family doctor. FOB tests were not rehydrated and dietary restrictions were imposed only for retesting borderline results. Individuals with negative FOB tests at the first screening, together with those who tested positive but in whom no neoplasia was found on colonoscopy, were invited to take part in further screening every 2 years. Screening was stopped in February, 1995, by which time screening-group participants had been offered FOB tests between three and six times. Screening-group participants who had a positive test were offered full colonoscopy. All participants were followed up until June, 1995. The primary outcome measure was CRC mortality. FINDINGS: Of the 152,850 individuals recruited to the study, 2599 could not be traced or had emigrated and were excluded from the analysis. Thus, there were 75,253 participants in the screening group and 74,998 controls. 44,838 (59.6%) screening-group participants completed at least one screening. 28,720 (38.2%) of these individuals completed all the FOB tests they were offered and 16,118 (21.4%) completed at least one screening but not all the tests they were offered. 30,415 (40.4%) did not complete any test. Of 893 cancers (20% stage A) diagnosed in screening-group participants (CRC incidence of 1.49 per 1000 person-years), 236 (26.4%) were detected by FOB screening, 249 (27.9%) presented after a negative FOB test or investigation, and 400 (44.8%) presented in non-responders. The incidence of cancer in the control group (856 cases, 11% stage A) was 1.44 per 1000 person-years. Median follow-up was 7.8 years (range 4.5-14.5). 360 people died from CRC in the screening group compared with 420 in the control group-a 15% reduction in cumulative CRC mortality in the screening group (odds ratio=0.85 [95%; CI 0.74-0.98], p = 0.026). INTERPRETATION: Our findings together with evidence from other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population.

Adenoma↗
PubMed1999

Screening for hepatocellular carcinoma in patients with cirrhosis in the United States: results of a national survey.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the dreaded complications of cirrhosis. Although there are no randomized controlled studies showing improved survival with screening, patients with cirrhosis are screened for HCC. Little is known about the practice of HCC screening in the United States. Our aim was to describe the practice of HCC screening in patients with cirrhosis in the United States. METHODS: In March 1998, we mailed a standard questionnaire to 1021 physician members of the American Association of Study for Liver Diseases and the same questionnaire was re-sent to nonrespondents 4 weeks later. RESULTS: We received a response from 554 members (54%). After excluding those not involved in active adult patient care, 473 responses were eligible for analysis. Eighty-four percent of the respondents routinely screened patients with cirrhosis for HCC (screening respondents). Nearly half of the screening respondents limited the HCC screening to patients with high-risk etiologies such as hepatitis B or C or hemochromatosis. Although alpha-fetoprotein (99.7%) and ultrasound (93%) were the two most frequently used screening methods, a sizable proportion of the screening respondents (25%) used abdominal computed tomography for routine screening. On multivariate analysis, the following variables predicted screening for HCC by the respondents: seeing more than one new cirrhotic per week (odds ratio [OR]: 5.4, 95% confidence interval [CI]: 2.5-11.7); practicing for < 10 yr (OR: 4.0, 95% CI: 1.2-13.4); an opinion that screening is cost-effective (OR: 6.4, 95% CI: 1.6-25); an opinion that screening prolongs survival (OR: 5.7, 95% CI: 1.8-17.9); and an opinion that not screening poses malpractice liability (OR: 9.3, 95% CI: 4.2-20.8). CONCLUSIONS: The majority of respondents routinely screen patients with cirrhosis for HCC. Approximately half of the screening respondents limit their screening to only patients with high-risk etiologies. On multivariate analysis, several variables predicted screening for HCC by the respondents.

Adult↗
PubMed1994

Screening for neuroblastoma: a review of the evidence.

Screening infants for the early detection of neuroblastoma is advocated by many paediatric oncologists and is practised in a limited number of places in the developed world, most notably in Japan where a national screening programme has been in operation since 1985. The screening test consists of measurements of the levels of vanillylmandelic acid and homovanillic acid in the urine; these metabolites of catecholamine are excreted in the urine of 92% of patients with clinically presenting neuroblastoma. The prognosis for children with symptomatic neuroblastoma is dependent both on age and stage, with children aged under 1 year and those with tumours of stages I, II, and IVS having a much better prognosis. Screening aims at detecting and treating during the first year those neuroblastomas which would otherwise present at an advanced stage in older children. Evidence from Japan shows that screening achieves the interim outcomes of a shift in the age distribution and stage distribution of neuroblastomas in populations for whom screening has been provided, and that survival of subjects detected by screening is over 90%, compared with around 50% for symptomatic subjects. However, there is not yet any clear evidence that screening results in a reduction in the incidence of advanced neuroblastoma in children over the age of 1, nor a reduction in mortality. Recent cross sectional analyses of age specific incidence and mortality suggest that screening may be having a limited effect, but as yet no analysis of these outcomes in cohorts for whom screening has been provided has been published. Other factors, such as improved chemotherapy, may also be contributing to lower mortality. A number of missed (interval) cancers have been diagnosed in children who screened negative both in the Japanese programme and in Canadian and English studies, indicating that there is a problem with the sensitivity of screening. But the screening test is highly specific with less than 0.1% of infants having false positive results requiring investigation. The natural history of neuroblastoma ranges from highly malignant tumours to biologically benign variants that regress without active treatment, the prevalence of the latter being inversely related to age. Serial measurements of biological markers, including ploidy, chromosome 1p deletion, and N-myc amplification, performed within the same patient at different times indicate that malignant potential does not progress over time. The distribution of these markers in cases detected by screening shows that they are inherently tumours with a good prognosis, whereas the reverse is true of interval cases. Thus screening is differentially picking up the tumours that are least likely to progress and failing to detect at least some tumours of those destined to die from the disease. Comparison of the yield of cancers detected by screening and the expected cumulative incidence of neuroblastoma throughout childhood suggest that screening "overdiagnoses" many non-progressive cases, with consequent physical and psychological morbidity. On balance present evidence suggests that the number of deaths that could be prevented by screening is small and the potential for overdiagnosis is great. Unless further evidence from Japan or the results of a current North American trial conclude otherwise, screening cannot be recommended.

Biomarkers↗