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PubMed2003

Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening.

BACKGROUND: The long term effect of mammographic service screening is not well established. We aimed to assess the long-term effect of mammographic screening on death from breast cancer, taking into account potential biases from self-selection, changes in breast cancer incidence, and classification of cause of death. METHODS: We compared deaths from breast cancer diagnosed in the 20 years before screening was introduced (1958-77) with those from breast cancer diagnosed in the 20 years after the introduction of screening (1978-97) in two Swedish counties, in 210000 women aged 20-69 years. We also compared deaths from all cancers and from all causes in patients diagnosed with breast cancer in the 20 years before and after screening was introduced. In the analysis, data were stratified into age-groups invited for screening (40-69 years) and not invited (20-39 years), and by whether or not the women had actually received screening. We also analysed mortality for the 40-49-year age-group separately. FINDINGS: The unadjusted risk of death from breast cancer dropped significantly in the second screening period compared with the first in women aged 40-69 years (relative risk [RR] 0.77 [95% CI 0.7-0.85]; p<0.0001). No such decline was seen in 20-39 year olds. After adjustment for age, self-selection bias, and changes in breast-cancer incidence in the 40-69 years age-group, breast-cancer mortality was reduced in women who were screened (0.56; 0.49-0.64 p<0.0001), in those who were not screened (0.84 [0.71-0.99]; p=0.03), and in screened and unscreened women combined (0.59 [0.53-0.66]; p<0.0001). After adjustment for age, self-selection bias, and changes in incidence in the 40-49-year age-group, deaths from breast cancer fell significantly in those who were screened (0.52 [0.4-0.67]; p<0.0001); and in all women, screened and unscreened combined (0.55 [0.44-0.7] p<0.0001) but not in unscreened women (p=0.2). In both 40-69-year and 40-49-year age-groups, reductions in deaths from all cancers and from all-causes in women with breast cancer were consistent with these results. INTERPRETATION: Taking account of potential biases, changes in clinical practice and changes in the incidence of breast cancer, mammography screening is contributing to substantial reductions in breast cancer mortality in these two Swedish counties.

Adult↗

PubMed2005

Comparison of 1- and 2-year screening intervals for women undergoing screening mammography.

We compared the long-term impact of 1- and 2-year screening mammography intervals using prognostic, screening, and outcome information for women aged 50-74 years obtained from the Screening Mammography Program of British Columbia in two time periods, prior to 1997 (policy of annual mammography) and after 1997 (biennial mammography). Survival was estimated for both periods using a prognostic model and the expected rate of interval and screen-detected cancers. The likelihood of a screen-detected cancer with annual screening was 2.32 per thousand screens and with biennial screening was 3.32 per thousand screens. The prognostic profile of screen-detected cancers was better than that of interval cancers. Among both screen-detected and interval cancers, the prognostic profiles with annual and biennial screening were similar. The estimated breast cancer-specific survival rates for women undergoing annual and biennial screening mammography were 95.2 and 94.6% at 5 years, and 90.4 and 89.2% at 10 years, respectively. Annual compared to biennial mammography was associated with a 1.2% increase in the estimated 10-year breast cancer-specific survival for women aged 50-74 years, diagnosed with invasive breast cancer after screening programme attendance.

Aged↗

PubMed1996

The influence of risk factors on breast carcinoma screening of Medicare-insured older women. National Cancer Institute Breast Cancer Screening Consortium.

BACKGROUND: It is not certain whether older women with additional breast carcinoma risk factors are adequately screened or whether they are more likely to undergo screening than other older women. This study was conducted to determine whether selected risk factors influence the breast carcinoma screening rates of Medicare-insured older women (i.e., age 65 years or older). METHODS: Self-reported rates of screening mammography and clinical breast examination in the previous year were compared for women with benign breast disease, women with a family history of breast carcinoma, and women lacking these risks, using samples of non-Hispanic white, Medicare-insured women surveyed at the 5 National Cancer Institute Breast Cancer Screening Consortium sites in 1991 (n = 5376, mean age = 69.7 years) and 1994 (n = 5086, mean age = 69.7 years). RESULTS: In 1993, rates of screening mammography reported in the previous year at the 5 Consortium sites had a range of 46-61% for women with a family history of breast carcinoma, 49-66% for women with benign breast disease, and 31-43% for women lacking these risks. Women with a positive family history or a personal history of benign breast disease were also more likely to report having had a clinical breast examination in the previous year and having received a physician's mammography recommendation. A substantial proportion of older women with a positive family history remain inadequately screened, however. Between 25% and 35% of women in this group had not had a screening mammogram in the previous 2 years, while at some Consortium sites more than 20% reported never having had a mammogram in their lives. CONCLUSIONS: Older women with additional risk factors are more likely to undergo screening mammography. This is due partly to more frequent physician recommendations for screening and partly to more frequent provision of clinical breast examinations. However, a substantial proportion of high risk older women remain inadequately screened, despite widespread clinical consensus that these women should be regularly screened. Interventions that target older women with risk factors and their physicians appear warranted. Understanding the mechanisms by which risk factors influence screening is an important area for future research.

Aged↗

PubMed1989

Screening for breast cancer in Nijmegen. Report of 6 screening rounds, 1975-1986.

A population-based screening programme for breast cancer was initiated in Nijmegen in 1975 with mammography as the only screening procedure. Up to January 1987, 6 screening rounds were carried out with a 2-year screening interval. Rates of attendance, referral, biopsy and detection were calculated and numbers of interval cancers are presented in order to give a clear view of what repeated screening can accomplish in a population. At the first screening round the attendance rate was 87% for women under age 50 and 83% for women aged 50-64. For women aged 65 or over the initial attendance rate was 40%. Rates of attendance declined in subsequent years. Detection rates were highest for elderly women at their first examination: 9.5 per 1,000 screened women. Corresponding rates were 5.6 and 2.3 per 1,000 for women aged 50-64 and below 50 respectively. The positive predictive value for referral was, on average, 20% for women under age 50 and 50% for elderly women, although a sharp increase was seen in the last 2 screening examinations for all age-groups. Predictive values for biopsy were higher: 30% on average for women aged under 50 and 60%-70% for elderly women, again with a sharp increase in the last 2 screening rounds. Interval cancer rates, calculated as the number of cancers occurring within 2 years among negatively screened women at risk, showed no particular trend and varied between 0.9-1.3 per 1,000 woman-years after each screening round. Compared to screen-detected cancers, interval cancers occurred more frequently in younger women. In women under age 50, the ratio between screen-detected and interval cancer was about 1:1, while it was about 2:1 for elderly women.

Adult↗

PubMed2004

[Universal hearing screening in newborns. Recommendations for organizing and conducting universal hearing screening for congenital hearing loss in Germany].

The Interdisciplinary Consensus Conference for Newborn Hearing Screening (IKKNHS) has worked out joint recommendations for universal hearing screening of newborns. In the consensus paper, 11 professional associations and scientific societies in the fields of gynecology and obstetrics, ENT, pediatrics, and phoniatrics and pedaudiology came to an agreement on how to implement newborn hearing screening in Germany. The paper deals with the following topics: goals of universal newborn hearing screening, target group of hearing screening, schedule for screening, personnel involved in the screening program, technologies and framework conditions of hearing screening, documentation, continuous quality control of screening, confirmation diagnostics for conspicuous test subjects, motivation to take part in screening, information on newborn hearing screening, tracking, various infrastructural situations in urban and rural regions, follow-up care, in-patient vs. out-patient screening, cost factors of screening, reporting children with permanent hearing loss to the German Central Registry for hearing loss in children.

Genetic Testing↗

PubMed2006

A comparison between the short term and long term benefits of screening for abdominal aortic aneurysms from the Huntingdon Aneurysm screening programme.

BACKGROUND: The UK Multicentre Aneurysm Screening Study (MASS) showed a 44% reduction in AAA-related mortality after 4 years and predicted an increased number of deaths prevented in the longer term. We aim to compare the 5 and 13 years benefit from aneurysm screening in the Huntingdon Aneurysm screening programme. METHODS: Incidence and mortality of ruptured AAA (RAAA) after 5 and 13 years of screening in a population based aneurysm screening program. RESULTS: Five years of screening resulted in a reduction in the incidence of RAAA of 49% (95% CI: 3-74%). Nine out of 11 ruptures in the invited group did not survive (mortality 82%; 95% CI: 48-98%) compared to 38 non-survivors from 51 ruptures in the control group (mortality 75%; 95% CI: 60-86%). Five years of screening resulted in an RAAA-related mortality reduction of 45% (95% CI: -15 to 74%). After 13 years of screening the incidence of RAAA was reduced by 73% (95% CI: 58-82%). Twenty-one out of 29 ruptures in the invited group did not survive (mortality 72%; 95% CI: 53-87%) compared to 64 non-survivors from 82 ruptures in the control group (mortality 78%; 95% CI: 68-86%). Thirteen years screening resulted in a reduction of mortality from RAAA of 75% (95% CI: 58-84%). The number needed to screen to prevent one death reduced from 1380 after 5 years to 505 after 13 years. The number of elective AAA operations needed to prevent one death reduced from 6 after 5 years to 4 after 13 years. CONCLUSION: AAA screening becomes increasingly beneficial as screening continues over the longer term. Benefits continue to increase after screening has ceased.

Aortic Aneurysm, Abdominal↗

PubMed2004

Mammography screening in the Netherlands: delay in the diagnosis of breast cancer after breast cancer screening.

In a prospective study we determined the frequency and causes of delay in the diagnosis of breast cancer after suspicious screening mammography. We included all women aged 50-75 years who underwent biennial screening mammography in the southern breast cancer screening region of the Netherlands between 1 January 1996 and 1 January 2002. Clinical data, breast imaging reports, biopsy results and breast surgery reports were collected of all women with a positive screening result with a minimum of 2-year follow-up. Of 153 969 mammographic screening examinations, 1615 (1.05%) were positive screens. Breast cancer was diagnosed in 770 (47.9%) of 1607 women for whom follow-up information was available, yielding a cancer detection rate of 5.0 per 1000 women screened. Breast cancer was diagnosed within 3 months following a positive screen in 722 cases (93.8%). The diagnostic delay was 4-6, 7-12 and 13-24 months, respectively, in 11 (1.4%), 24 (3.1%) and nine (1.2%) patients. In four other patients (0.5%), breast cancer was diagnosed after a repeat positive screen, resulting in a diagnostic delay of 25-27 months. Reasons for a diagnostic delay >3 months were erroneous mammographic interpretation of suspicious lesions as benign or probably benign lesions (33 cases), benign biopsies from a malignant lesion (10), and omission to biopsy or remove a lesion that was suspicious at breast imaging (4) or core biopsy (1). We conclude that there is room for improvement in the workup of patients with a positive screening mammography, as seen from data in this screening region. To improve the workup, we suggest that other breast cancer screening programmes also identify delay in breast cancer diagnosis after a positive screen.

Aged↗

PubMedDate not supplied

Knowledge of cervical cancer screening and use of cervical screening facilities among women from various socioeconomic backgrounds in Durban, Kwazulu Natal, South Africa.

The value of screening for cervical cancer has been proven. Such screening in developed countries has achieved a decrease in incidence and mortality by about 80%. Although screening facilities are available in certain parts of developing countries, the incidence of cervical cancer remains very high and many patients present with late stage disease. The study was performed among women from different socioeconomic circumstances (low, middle, and upper social/financial backgrounds). The assessment was performed by means of a questionnaire. The majority of patients from lower socio-economic circumstances with multiple risk factors were not aware of cervical screening or facilities available for this purpose. However, in spite of knowledge of cervical screening and the availability of such services, the majority of women (87%) from higher social and educational backgrounds did not undergo cervical screening. Most patients resided within a 12-kilometer radius of a facility that either provided or could potentially provide screening. Although some patients (36.7%) had had a screening test performed at some time in the past, only 27.3% of patients reported having had a Pap test. This was due to failure on the part of the healthcare giver to disseminate information to the patient regarding the reason and value of cervical screening. Among women from higher socioeconomic groups, the level of education was better and knowledge of the Pap test was not age-dependent. We conclude that the mere provision of a cervical cancer screening service is not sufficient to ensure successful uptake since screening is a multifaceted entity. Improvement of socioeconomic and educational circumstances should improve the uptake of a screening program only if the healthcare giver provides appropriate information to the patient and the patient takes the initiative to avail themselves of such screening.

Adolescent↗

PubMed2005

[Universal hearing screening in newborns -- recommendations for organizing and conducting universal hearing screening for congenital hearing loss in Germany].

The Interdisciplinary Consensus Conference for Newborn Hearing Screening (IKKNHS) has worked out joint recommendations for universal hearing screening of newborns. In the consensus paper, 11 professional associations and scientific societies in the fields of gynecology and obstetrics, ENT, pediatrics, and phoniatrics and pedaudiology came to an agreement how to implement newborn hearing screening in Germany. The paper deals with the following topics: goals of universal newborn hearing screening, target group of hearing screening, schedule for screening, personnel involved in the screening program, technologies and framework conditions of hearing screening, documentation, continuous quality control of screening, confirmation diagnostics for conspicuous test subjects, motivation to take part in screening, information on newborn hearing screening, tracking, various infrastructural situations in urban and rural regions, follow-up care, in-patient vs. out-patient screening, cost factors of screening, reporting children with permanent hearing loss to the German Central Registry for hearing loss in children.

Animals↗

PubMed2003

Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND: Screening for prostate cancer advances the time of diagnosis (lead time) and detects cancers that would not have been diagnosed in the absence of screening (overdetection). Both consequences have considerable impact on the net benefits of screening. METHODS: We developed simulation models based on results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified, and on baseline prostate cancer incidence and stage distribution data. The models were used to predict mean lead times, overdetection rates, and ranges (corresponding to approximate 95% confidence intervals) associated with different screening programs. RESULTS: Mean lead times and rates of overdetection depended on a man's age at screening. For a single screening test at age 55, the estimated mean lead time was 12.3 years (range = 11.6-14.1 years) and the overdetection rate was 27% (range = 24%-37%); at age 75, the estimates were 6.0 years (range = 5.8-6.3 years) and 56% (range = 53%-61%), respectively. For a screening program with a 4-year screening interval from age 55 to 67, the estimated mean lead time was 11.2 years (range = 10.8-12.1 years), and the overdetection rate was 48% (range = 44%-55%). This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4% to 10.6%, a relative increase of 65% (range = 56%-87%). In annual screening from age 55 to 67, the estimated overdetection rate was 50% (range = 46%-57%) and the lifetime prostate cancer risk was increased by 80% (range = 69%-116%). Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinically relevant cancer detected. CONCLUSIONS: These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year.

Aged↗

PubMed2000

New York State universal newborn hearing screening demonstration project: effects of screening protocol on inpatient outcome measures.

OBJECTIVE: To examine differences among various test protocols on the fail rate at hospital discharge for infants in the well-baby nursery (WBN) and neonatal intensive care unit (NICU) who received hearing screening through a universal newborn hearing screening demonstration project. DESIGN: The outcomes of several screening protocols were examined. Two technologies were used: transient evoked otoacoustic emissions (TEOAEs) alone or in combination with the auditory brain stem response (ABR). The performance of test protocols in both nurseries within eight hospitals was examined over a 2- to 3-yr period. In the WBN, six hospitals used a screening protocol of TEOAE technology first followed by an ABR (automated or conventional) technology screening for newborns who referred on TEOAE screening. Two hospitals used TEOAE only in the WBN. Seven hospitals used screening protocols in the NICU that used a combination of TEOAE and ABR technologies (TEOAE technology administered first or second, before or after TEOAE, or TEOAE and ABR tests on all infants). Only one hospital used TEOAE technology exclusively for hearing screening. RESULTS: Significant differences among screening protocols were found across hospitals in the first, second, and third years of the program. The combination of TEOAE technology and ABR technology (a two-technology screening protocol) resulted in a significantly lower fail rate at hospital discharge than the use of a single-technology (TEOAE). Fail rates at discharge were twice as high using the one-technology protocol versus two-technology protocol, even when the best outcomes from program year 3 were considered exclusively. Results of two-technology versus one-technology protocols were similar in the NICU. Use of a second technology for screening TEOAE fails significantly reduced every hospital that used the protocol's fail rate at discharge. CONCLUSIONS: A two-technology screening protocol resulted in significantly lower fail rates at hospital discharge in both the WBN and NICU nurseries than use of a single-technology (TEOAE) hearing screening protocol.

Evoked Potentials, Auditory, Brain Stem↗

PubMed1998

Effect on attendance at breast cancer screening of adding a self administered questionnaire to the usual invitation to breast screening in southern England.

STUDY OBJECTIVE: The primary aim of the research described in this paper was to ascertain whether inclusion of a self administered questionnaire with the usual invitation to routine breast screening affected screening uptake. Secondary aims included establishing appropriate questionnaire distribution and collection methods within the framework of the National Health Service Breast Screening Programme and optimisation of questionnaire design. DESIGN: Randomised study. SETTING: Oxfordshire and West of London Breast Screening Units. PARTICIPANTS/METHODS: 6400 women invited for routine screening mammography were individually randomised to receive either the usual breast screening invitation alone, or to receive the usual invitation accompanied by a self administered questionnaire, to be returned at the time of screening. Participants were then followed up and attendance rates at screening were compared between groups. MAIN RESULTS: Screening attendance rates were similar in women who did and did not receive a questionnaire (71% in each group). Of those who were sent a questionnaire and attended for screening, 77% returned a completed questionnaire. Screening uptake was not affected by the way in which the questionnaire was returned or by whether or not personal details and signed permission for follow up were requested. CONCLUSIONS: The inclusion of a self administered questionnaire accompanying the invitation to breast screening did not adversely affect screening uptake. A high proportion of women completed the questionnaire.

Breast Neoplasms↗

PubMed2000

Telling people about screening programmes and screening test results: how can we do it better?

To make an informed choice about whether to be screened, people need information that allows them to weigh up the benefits and harms of screening. To understand their screening test results they require even more information. Yet currently, people attending a screening programme or considering a screening test may only be told that the test can detect disease or risk factors for disease, and that early intervention improves outcomes. When given their test results, people are generally only told the test was abnormal ("positive") or normal ("negative"). We believe that information given before and after the screening test can, and should, be improved. This will probably require information that includes both the benefits and harms of screening and is probabilistic. Indeed, we believe the traditional dichotomisation of screening test results into positive and negative is problematic, and could be replaced by standard use of risks or probabilistic data before and after screening. The relevant risk data could be explained in a range of ways, for example, quantitatively, qualitatively, and/or by "anchoring" to everyday experiences. In this paper we explore why dichotomisation of screening test results is problematic and look at the adverse consequences of presenting test results in terms of true and false, positive and negative. We present some ideas on alternative ways of providing information on screening programmes and screening test results. Our aim is to stimulate debate about these issues and to provide some starting points which could be further developed and evaluated in a wide range of screening programmes.

Adult↗

PubMed2006

Breast cancer screening, outside the population-screening program, of women from breast cancer families without proven BRCA1/BRCA2 mutations: a simulation study.

PURPOSE: We assessed the cost-effectiveness of mammography screening for women under the age of 50, from breast cancer families without proven BRCA1/BRCA2 mutations, because current criteria for screening healthy women from breast cancer families are not evidence-based. METHODS: We did simulation studies with mathematical models on the cost-effectiveness of mammography screening of women under the age of 50 with breast cancer family histories. Breast cancer screening was simulated with varying screening intervals (6, 12, 18, and 24 months) and screening cohorts (starting at ages 30, 35, 40, and 45, and continuing to age 50). Incremental costs of screening were compared with those of women ages 50 to 52 years, the youngest age group currently routinely screened in the nationwide screening program of the Netherlands, to determine cost-effectiveness. Sensitivity analyses were done to explore the effects of model assumptions. The cost-effectiveness of breast cancer screening for women over the age of 50 was not debated. RESULTS: The most effective screening interval was found to be 12 months, which, however, seems only to be cost-effective in a small group of women under the age of 50 with at least two affected relatives, including at least one affected in the first degree diagnosed under the age of 50. Significantly, early breast cancer screening never seemed to be cost-effective in women with only one affected first-degree or second-degree relative. CONCLUSION: Annual breast cancer screening with mammography for women under the age of 50 seems to be cost-effective in women with strong family histories of breast cancer, even when no BRCA1/BRCA2 mutation was found in affected family members.

Adult↗

PubMed1994

Assessment of lesions detected at mammographic screening: performance at first or repeat screening in the Florence programme.

OBJECTIVE: To evaluate the assessment criteria and the results achieved in the detection of breast lesions at mammographic screening. SETTING: Review of cases assessed in the last screening round of Florence city (FC--first screening round: 29,522 subjects) and Florence district (FD --repeat screening round: 13,268 subjects) programmes. METHODS: Referral and biopsy rates, predictive values, and prevalence of cancers detected by screening were determined, as well as the frequency of the diagnostic procedures used at assessment, and their contribution to the final diagnosis according to the mammographic appearance of the suspected lesion. Assessment costs were estimated. RESULTS: Referral rate (FC 4.2%; FD 1.8%), referral positive predictive value (FC 18.7%; FD 28.3%), surgical biopsy rate (FC 0.96%; FD 0.6%), benign/malignant biopsy ratio (FC 0.20; FD 0.13), and prevalence of cancers detected by screening (FC 0.78%; FD 0.5%) were all within the European Community (EC) recommended standards for screening performance. The benign biopsy rate was considerably lower than that of recommended standards. The cost for each subject assessed was 179,000 Italian lire at the first and 116,000 lire at repeat screening. The cost for each subject screened that was attributable to assessment was 7600 lire at the first or 2100 lire at repeat screening. CONCLUSIONS: Limited referral rates and costs were achieved and the proportion of cancers detected by screening was high. The number of referrals was further reduced at repeat screening, and assessment had a limited impact on total screening costs. Detail or magnification mammography, palpation, sonography, and fine needle aspiration cytology all contributed to the final diagnosis and should be immediately available at the assessment clinic. The observed benign biopsy rate was particularly low and suggests that EC recommended standards should be modified.

Aged↗

PubMed1998

[Medical behavior after colo-rectal cancer screening--comparison with that after stomach cancer screening].

Medical behavior for intensive examination after colo-rectal cancer screening was examined in comparison with that after stomach cancer screening. Examinees who were positive in colo-rectal or stomach cancer screening, provided by an Occupational Health Organization from April 1993 to March 1994, were monitored for their medical behavior through notifications from physicians. The main results were as follows: 1. The proportion of those with the notification from a physician after colo-rectal cancer screening was half of that after stomach cancer screening. 2. Among those notified the rate of those who undertook intensive examination by the end of 12 weeks after the screening was 79.7% for a colo-rectal site and 87.0% for the stomach. The time interval from the screening to the intensive examination for the colo-rectal site was significantly longer than that for stomach. 3. For colo-rectal cancer screening, the proportion of those with the notification was lower in females than in males, and in those aged less than 50 than in those aged 50 or older. There were no differences in the proportion between those screened at the work site and those at the occupational health service center, and between those positive in the fecal occult blood test and those negative in the test but positive in the health interview. These results indicated, assuming that the probability of the physicians' notification was unrelated to the type of examination, a smaller proportion of the examinees positive in the colo-rectal cancer screening consulted a physician for the intensive examination later than those positive in the stomach cancer screening. It is therefore necessary to make colo-rectal cancer screening effective to establish a collaborating system which effectively facilitates the medical behavior of the screening positives.

Adult↗

PubMed2006

Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.

OBJECTIVES: To assess the risk of clinical complications associated with thrombophilia in three high-risk patient groups: women using oral oestrogen preparations, women during pregnancy and patients undergoing major orthopaedic surgery. To assess the effectiveness of prophylactic treatments in preventing venous thromboembolism (VTE) and adverse pregnancy outcomes in women with thrombophilia during pregnancy and VTE in patients with thrombophilia, undergoing major orthopaedic surgery. To evaluate the relative cost-effectiveness of universal and selective VTE history-based screening for thrombophilia compared with no screening in the three high-risk patient groups. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, and four other major databases were searched up to June 2003. REVIEW METHODS: In order to assess the risk of clinical complications associated with thrombophilia, a systematic review of the literature on VTE and thrombophilia in women using oral oestrogen preparations and patients undergoing major orthopaedic surgery; and studies of VTE and adverse obstetric complications in women with thrombophilia during pregnancy was carried out. Meta-analysis was used to calculate pooled odds ratios (ORs) associated with individual clinical outcomes, stratified by thrombophilia type and were calculated for each patient group. To assess the effectiveness of prophylaxis, a systematic review was carried out on the use of prophylaxis in the prevention of VTE and pregnancy loss in pregnant women with thrombophilic defects and the use of thromboprophylaxis in the prevention of VTE in patients with thrombophilia undergoing major elective orthopaedic surgery. Relevant data were summarised according to the patient groups and stratified according to the types of prophylaxis. A narrative summary was provided; where appropriate, meta-analysis was conducted. An incremental cost-effectiveness analysis was then carried out, from the perspective of the NHS in the UK. A decision analytical model was developed to simulate the clinical consequences of four thrombophilia screening scenarios. Results from the meta-analyses, information from the literature and results of two Delphi studies of clinical management of VTE and adverse pregnancy complications were incorporated into the model. Only direct health service costs were measured and unit costs for all healthcare resources used were obtained from routinely collected data and the literature. Cost-effectiveness was expressed as incremental cost-effectiveness ratios (ICERs); an estimate of the cost per adverse clinical complication prevented, comparing screening with no screening, were calculated for each patient group. RESULTS: In the review of risk of clinical complications, 81 studies were included, nine for oral oestrogen preparations, 72 for pregnancy and eight for orthopaedic surgery. For oral contraceptive use, significant associations of the risk of VTE were found in women with factor V Leiden (FVL); deficiencies of antithrombin, protein C, or protein S, elevated levels of factor VIIIc; and FVL and prothrombin G20210A. For hormone replacement therapy (HRT), a significant association was found in women with FVL. The highest risk in pregnancy was found for FVL and VTE, in particular, homozygous carriers of this mutation are 34 times more likely to develop VTE in pregnancy than non-carriers. Significant risks for individual thrombophilic defects were also established for early, recurrent and late pregnancy loss; preeclampsia; placental abruption; and intrauterine growth restriction. Significant associations were found between FVL and high factor VIIIc and postoperative VTE following elective hip or knee replacement surgery. Prothrombin G20210A was significantly associated with postoperative pulmonary embolism. However, antithrombin deficiency, MTHFR and hyperhomocysteinaemia were not associated with increased risk of postoperative VTE. In the review of the effectiveness of prophylaxis, based on available data from eight studies, low-dose aspirin and heparin was found to be the most effective in preventing pregnancy loss in thrombophilic women during pregnancy, while aspirin alone was the most effective in preventing minor bleeding. All the studies on thrombophilia and major elective orthopaedic surgery included in the review of risk complications were also used in the review of the effectiveness of thromboprophylaxis. However, there were insufficient data to determine the relative effectiveness of different thromboprophylaxis in preventing VTE in this patient group. For the cost-effectiveness analysis, of all the patient groups evaluated, universal screening of women prior to prescribing HRT was the most cost-effective (ICER pound6824). In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy (ICER pound202,402). Selective thrombophilia screening based on previous personal and/or family history of VTE was more cost-effective than universal screening in all the patient groups evaluated. CONCLUSIONS: Thrombophilia is associated with increased risks of VTE in women taking oral oestrogen preparations and patients undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy outcomes in women with thrombophilia during pregnancy. There is considerable difference in the magnitude of the risks among different patient groups with different thrombophilic defects. In women who are on combined oral contraceptives, the OR of VTE among those who are carriers of the FVL mutation was 15.62 (95% confidence interval 8.66 to 28.15). However, in view of the prevalence of thrombophilia and the low prevalence of VTE in non-users of combined oral contraceptives, the absolute risk remains low. Significant risks for VTE and adverse pregnancy outcomes have been established with individual thrombophilic defects. Thrombophilic defects including FVL, high plasma factor VIIIc levels and prothrombin G20210A are associated with the occurrence of postoperative VTE in elective hip or knee replacement therapy. These associations are observed in patients who were given preoperative thromboprophylaxis and are, therefore, of clinical significance. Universal thrombophilia screening in women prior to prescribing oral oestrogen preparations, in women during pregnancy and in patients undergoing major orthopaedic surgery is not supported by current evidence. The findings from this study show that selective screening based on prior VTE history is more cost-effective than universal screening. Large prospective studies should be undertaken to refine the risks and establish the associations of thrombophilias with VTE among hormone users and in patients undergoing orthopaedic surgery. The relative value of a thrombophilia screening programme to other healthcare programmes needs to be established.

Cost-Benefit Analysis↗

PubMed2000

[Nationwide breast cancer screening fully accomplished; results from the implementation phase 1990-1997. National Evaluation Team for Breast Cancer Screening].

OBJECTIVE: To present an overview of the main results of the nationwide breast cancer screening programme implemented in the Netherlands from 1990 to 1997 and providing a biennial mammography for all women aged 50-69 years. METHOD: Data on screening examinations were provided by the 9 regional screening organisations; data on interval cancers and on breast cancers in unscreened women were provided by the regional cancer registries after linkage of registry data with data on screened women. The results observed were compared with the expectations used in the cost effectiveness analysis before the start of the population screening. RESULTS: Of almost 4 million women invited, 78.5% attended for screening. The screening resulted in 13.1 referrals, 9.2 biopsies and 6.1 breast cancers detected per 1,000 initially screened women, and in 6.9 referrals, 4.5 biopsies and 3.5 detected breast cancers per 1,000 subsequently screened women. All these parameters showed a clear variation at regional level. In the first 2 years after initial screens 0.96 interval cancers per 1,000 women-years were diagnosed (0.93 per 1,000 women-years after subsequent screens). Of all screen-detected cancers 76% were ductal carcinomas in situ (13%) or invasive cancers < or = 20 mm in size (63%); 26% of the invasive cancers were lymph node positive. This stage distribution was clearly more favourable than that of interval cancers and of the breast cancers diagnosed in unscreened women. The detection of breast cancer at subsequent screening was lower than expected and the staging of the carcinomas was less favourable than expected; the other results were largely in accordance with the expectations.

Age Distribution↗