Jump to Volume 4, Issue 1, March 1997
Jump to Volume 4, Issue 2, June 1997
Jump to Volume 4, Issue 4, December 1997

Editorial
Screening for neuroblastoma in children.
J Morris. J Med Screen 1997 4: 115-116

Journal Articles
An appraisal of the efficacy and cost effectiveness of antenatal screening for hepatitis B.
R Jordan and M Law. J Med Screen 1997 4: 117-127.
In this review published data are used to determine the benefits and costs of antenatal screening for hepatitis B carriers to prevent the later occurrence of hepatoma and chronic liver disease in their offspring. In Britain, babies born to carrier mothers have a 25% risk of perinatal infection and of becoming carriers themselves (the risk is 82% if their mothers are positive for the e antigen and 10% if negative). The carrier state increases the risk of hepatoma an estimated 86 times and the risk of chronic liver disease 20 times. Life table analysis showed that there is an 11% lifetime risk in carriers in Britain of dying from hepatoma (which results in seven years of life lost on average) and a 7% risk of chronic liver disease (14 years of life lost). Neonatal vaccination reduces the risk of the infant becoming a carrier by about 90%. Perinatal transmission occurs in 38 of every 100,000 neonates in Britain. Antenatal screening of all women and vaccinating babies of carrier mothers would prevent perinatal transmission in 34 of the 38 children (90%), or 255 per year in Britain. Of these 34, 8.4 children would be Chinese in ethnic origin, 4.2 African, 11.5 South Asian (from the Indian subcontinent), 2.0 Caribbean, and 7.3 would be white. Six deaths in the 34 from hepatoma or chronic liver disease caused by hepatitis B would then be prevented. The direct cost in Britain of screening all women, irrespective of ethnicity, at their first pregnancy only, would be 1300 pounds for each year of life saved (undiscounted) or 2500 pounds if screening at every pregnancy. Screening just Chinese, Africans, and South Asians, at first pregnancy only, would cost 330 pounds for each year of life saved but would prevent only 64% of these deaths. Vaccinating the infants of carrier mothers is likely also to prevent horizontal transmission of hepatitis B in early childhood and prevent the carrier state developing in an estimated three extra children for each child protected from vertical transmission. When this is taken into account the number of deaths prevented increases fourfold, reducing the cost for each year of life saved by 75%. Screening all women at first pregnancy only is an acceptably cost effective policy in Britain (1300 pounds for each year of life saved), actually preventing 45 deaths a year from hepatoma and chronic liver disease (or about 180 deaths if those horizontally infected are included), at a total cost of 540,000 pounds a year. It has the advantage of being comprehensive, equitable, and easier to implement than a policy based on screening of high risk ethnic groups.

Adverse effects of screening for gestational diabetes: a prospective cohort study in Toronto, Canada.
D Kerbel, R Glazier, S Holzapfel, M Yeung, and S Lofsky. J Med Screen 1997 4: 128-132.
OBJECTIVE: To investigate the adverse effects associated with a false positive 50 g glucose challenge test for gestational diabetes mellitus (GDM).
SETTING: Consecutive women attending a prenatal registration clinic at a large community hospital in suburban Toronto, Canada.
METHODS: Prospective cohort study of women between 12 and 24 weeks' gestation with no previous history of diabetes mellitus or GDM. Main outcome measures included anxiety (Spielberger's State-Trait Anxiety Inventory), depression (Centers for Epidemiologic Studies Depression Scale), perceived maternal health, and concern about health of the newborn.
RESULTS: Among 2564 eligible subjects, there were 897 subjects with complete data at enrollment and at 32 weeks' gestation, including 88 who had false positive glucose challenge test results. At 32 weeks, only 20% (95% confidence limits 11%, 28%) of women with false positive glucose challenge test results rated their health as excellent, compared with 38% (35%, 42%) of those having negative results and those not tested (P = 0.001). These results were sustained at 36 weeks. There was no association between glucose challenge test result and the change in anxiety (P = 0.57), depression (P = 0.09) or concern about health of the newborn (P = 0.91) between baseline and 32 weeks' gestation, nor were these associations found at 36 weeks.
CONCLUSIONS: False positive glucose challenge test results are about six times more likely than true positive results in the general population. Pregnant women with false positive GDM screening results experience a significant decline in their perception of their own health. These adverse effects should be taken into account when deciding about a policy of screening all pregnant women for gestational diabetes.

Heterozygosity for Tay-Sachs and Sandhoff diseases among Massachusetts residents with French Canadian background.
EM Prence, CA Jerome, BL Triggs-Raine, and MR Natowicz. J Med Screen 1997 4: 133-136.
OBJECTIVES: The frequency of Tay-Sachs disease (TSD) heterozygosity is increased among French Canadians in eastern Quebec. A large proportion of the New England population has French Canadian heritage; thus, it is important to determine if they too are at increased risk for TSD heterozygosity. This prospective study was designed to assess the TSD heterozygote frequency among people with French Canadian background living in Massachusetts. A simultaneous screen for heterozygosity for Sandhoff disease, a related genetic disorder, was also undertaken.
METHODS: 1260 non-pregnant subjects of French Canadian background were included in the study. beta hexosaminidase activity was measured in blood samples, and results were evaluated for TSD and Sandhoff disease heterozygosity. Samples from the TSD heterozygotes were also subjected to mutation analysis.
RESULTS: Of the 1260 samples studied, 22 (1 in 57; CI 1 in 41, 1 in 98) were identified as TSD heterozygotes by enzymatic analyses and 11 subjects (1 in 114; CI 1 in 72, 1 in 280) were identified as Sandhoff disease heterozygotes. Three of the 22 TSD heterozygotes were found to have benign pseudodeficiency mutations, resulting in a maximum TSD heterozygote frequency of 19 in 1260 (1 in 66; CI 1 in 46, 1 in 120). Together, these data provide a maximum frequency of heterozygosity for TSD or Sandhoff disease of 30 in 1260 (1 in 42; CI 1 in 31, 1 in 64) in this population.
CONCLUSIONS: Simultaneous screening for TSD and Sandhoff disease heterozygosity by assay of beta hexosaminidases A and B activities provides a possible method for use with subjects of French Canadian background. The relevance of some of the novel mutations identified in this group needs further study. However, the comparatively high combined frequency of TSD and Sandhoff disease heterozygosity indicates a need for discussion regarding the appropriateness of carrier testing for these disorders for persons of French Canadian background in Massachusetts.

Evaluation of surveillance programmes for colorectal cancer in ulcerative colitis patients by case-control studies: methodological considerations.
MM Zack, A Ekbom, PG Persson, and HO Adami. J Med Screen 1997 4: 137-141.
OBJECTIVES: The evaluation of the efficacy of colonoscopy screening in patients with ulcerative colitis for colorectal cancer is associated with methodological difficulties. Case-control studies can, however, be used to determine the efficacy of such a programme and the outline of the methodology in such a programme is presented.
METHODS: The randomised controlled trial provides perspective for case-control studies of screening efficacy. Cases are selected from persons who have ulcerative colitis with manifestations of colorectal cancer: for example, those who have died of colorectal cancer or have symptomatic metastases. Controls are selected from persons who have ulcerative colitis, who had been alive when the case died of colorectal cancer, and who had been subject to the risk of dying from, but had not had, colorectal cancer diagnosed when the case was diagnosed with colorectal cancer. The relevant screening history for cases begins with the case's diagnosis of ulcerative colitis and ends with the cases diagnosis of colorectal cancer; that for controls should be comparable to that for cases to avoid bias. Cases and controls are compared with respect to their "exposure" to colonoscopy during their screening histories: the occurrence of any screening, which took place during the period of time that an occult tumour (or an identifiable lesion) may plausibly have been present.
CONCLUSION: The proposed methodology can evaluate the efficacy of a screening programme rapidly, practically, and ethically.

Cost analysis in a population based screening programme for colorectal cancer: comparison of immunochemical and guaiac faecal occult blood testing.
G Castiglione, M Zappa, G Grazzini, C Sani, A Mazzotta, P Mantellini, and S Ciatto. J Med Screen 1997 4: 142-146.
OBJECTIVE: To compare the costs of colorectal cancer (CRC) screening by two faecal occult blood tests (FOBT)-namely, Hemoccult (guaiac based) and reversed passive haemagglutination (RPHA) tests. RPHA was interpreted according to two positivity thresholds (+ or +/-).
METHODS: Attenders performed both tests. Subjects with a positive FOBT test were invited to have a complete exploration of the colon. The total costs for every 10,000 screened subjects and costs for each unit of result (screened subject, or patient with adenoma/s or cancer detected) were calculated for both tests.
RESULTS: 8353 subjects were enrolled. A total of 2109 repeated screening after two years. RPHA(+ and +/-) showed the highest and RPHA(+) the lowest positivity rate at first screening. The Hemoccult positivity rate was highest at repeat screening. Total costs of screening by RPHA(+ and +/-) were highest as this method had the highest recall rate. Screening by RPHA(+) was the least costly. Costs for each screened subject were highest for RPHA(+ and +/-) and lowest for RPHA(+). Costs for each cancer detected were lowest for RPHA(+) and highest for Hemoccult or RPHA(+ and +/-) in subjects aged > 49 or <50, respectively. Costs for subjects with detected adenoma/s of > 9 mm were lowest for RPHA(+ and +/-) and highest for Hemoccult. At repeat screening total costs of RPHA(+ and +/-) were lower than at first screening, whereas for each subject with cancer or adenoma/s costs were increased.
CONCLUSIONS: Our data confirm that screening by RPHA is more cost effective than by Hemoccult.

Participation in faecal occult blood screening for colorectal cancer in a well defined French population: results of five screening rounds from 1988 to 1996.
MA Tazi, J Faivre, F Dassonville, J Lamour, C Milan, and G Durand. J Med Screen 1997 4: 147-151.
OBJECTIVE: To evaluate the influence on compliance of demographic variables and of the way of proposing a faecal occult blood test in a colorectal cancer mass screening programme.
SETTING: Well defined population in Burgundy (France).
METHODS: From 1988 to 1996 five screening rounds were conducted in people aged 45 to 74 on entering the study. The screening test was provided free of charge by primary care physicians over a four month period, then mailed to non-consultants, followed by a potential reminder letter. The whole population was invited to participate in each screening campaign.
RESULTS: During the five successive rounds, compliance was 52.8%, 54.0%, 57.3%, 58.3%, and 56.2%. It was higher in women than in men, in those initially aged 50 to 69 than in the extreme age groups, and in urban than in rural areas. Overall, 68.7% of the invited population completed at least one screening test and 37.2% completed the five rounds. Among those who participated once in a screening campaign, between 79.6% and 87.6% participated in the succeeding ones. Compliance was higher when the test was proposed by GPs (varying between 85.2% and 94.0% according to the screening campaign) than when it was sent by post (varying between 26.0% and 33.7%).
CONCLUSION: In France, a participation rate of over 50% can be achieved in colorectal cancer screening by means of a faecal occult blood test. To achieve this, primary care physicians have to play an active part in the programme and the test must be mailed to non-consultants.

Breast screening: adverse psychological consequences one month after placing women on early recall because of a diagnostic uncertainty. A multicentre study.
G Ong, J Austoker, and J Brett. J Med Screen 1997 4: 158-168.
BACKGROUND: It was the original intention of the UK National Health Service Breast Screening Programme (NHSBSP) to place women who were not diagnosed with cancer on three yearly routine recall (RR). In 1994-5 approximately 16,500 women, aged 50 to 64, were placed on early recall (ER) at a shorter time interval, of which about 98% will have a normal result. This large number exceeds the expectations of the NHSBSP.
OBJECTIVE: To establish the adverse psychological consequences (PCs) for women one month after placement on ER because of a diagnostic uncertainty, and if detected, to suggest practical solutions to reduce them.
METHODS: Thirteen breast screening centres throughout the UK participated in the study. From March to October 1995 all women who were placed on ER because of a diagnostic uncertainty were identified and compared with groups of women placed on RR (after mammography, assessment, fine needle aspiration, and a benign biopsy). These women were invited to complete a postal questionnaire one month after they were placed on ER or RR. One reminder was sent.
RESULTS: Overall 75% of women completed the questionnaire. The adverse PCs of placing women on ER because of a diagnostic uncertainty were higher (63%; n = 81 of 130) than those of women placed on RR after mammography (29%; n = 38 of 130) (P <0.00001) or assessment (50%; n = 64 of 128) (P <0.05), but lower than the adverse PCs of women who underwent a benign biopsy (87%; n = 26 of 30) (P <0.05). Factors that were significantly associated with subsequent adverse PCs were identified.
CONCLUSIONS: The adverse PCs of being placed on ER because of a diagnostic uncertainty were significantly higher than those of women who turned out to have a false-positive mammographic result after assessment. Possible practical solutions are discussed.

Interval breast cancers in the NHS Breast Screening Programme: does the current definition exclude too many?
AM Faux, DC Richardson, GM Lawrence, ME Wheaton, and MG Wallis. J Med Screen 1997 4: 169-173.
OBJECTIVES: To examine the impact of the definition of interval breast cancers on interval cancer rates arising from the prevalent (first) screening round.
DESIGN: Interval breast cancers arising from the prevalent (first) screening round at the Warwickshire, Solihull and Coventry Breast Screening Unit (17 April 1989 to 31 March 1992) were identified by comparison of data held at the unit with records at the West Midlands Cancer Intelligence Unit. Exclusion criteria used in National statistics were applied to this sample to quantify their impact on achieved interval cancer rates. The round lengths experienced by individual women at the unit were determined from the prevalent and incident invitation dates for 155 women with incident (re-screen) breast cancers detected in the second round.
SETTING: Warwickshire, Solihull and Coventry Breast Screening Unit.
SUBJECTS: 59,017 women screened between 17 April 1989 and 31 March 1992 with a negative screening result and 155 women with incident screen detected cancers.
RESULTS: A total of 278 interval cancers were identified, giving an overall rate from the prevalent screening round of 47.1/10,000 women screened. Of these, 213 met the criteria used in the definition of interval cancers for National statistics and were termed "core" interval cancers. The overall "core" interval rate was 36.1/ 10,000 women screened, similar to interval cancer rates found in the north west of United Kingdom. Thus applying commonly used exclusion criteria produced a 23.4% reduction in the apparent interval cancer rate, with the largest decrease resulting from the exclusion of cancers arising at 36 months or more from the last screen.
CONCLUSIONS: The exclusion criteria used in the definition of interval cancers have a significant impact on observed interval cancer rates. Of particular concern is the exclusion in the current National definitions of cancers arising at 36 months or more from the last screen, which may mask a problem with significant implications for the success of the NHSBSP.

Screening for diabetic retinopathy in primary care: retinal photography alone can be used efficiently and effectively to exclude those with sight threatening lesions.
PM Evans, TS Purewal, A Hopper, H Slater, DR Jones, and JP O'Hare. J Med Screen 1997 4: 174-176.
BACKGROUND: Good screening performance of retinal photography and ophthalmoscopy together in screening for diabetic retinopathy in primary care have been reported. This study reanalysed the data to evaluate the screening performance of photography alone.
METHODS: One thousand and ten patients screened by fundal photography and ophthalmoscopy were studied retrospectively. Fundal photographs were quality graded with poor quality pictures being excluded from the analysis. Each patient was reviewed initially by both retinal photographs and ophthalmoscopy by an ophthalmologist, the "gold standard". Six months later the fundal photographs were reviewed and reported in a blinded manner by the ophthalmologist.
RESULTS: Two thousand and fourteen photographs were obtained, of which 162 (8%) had to be excluded because of poor quality. On review of the remaining 1852 photographs in isolation, of 77 cases of severe retinopathy as determined by the "gold standard", 67 had severe changes on photography--detection rate 87%. Of the 1775 cases without sight threatening retinopathy only five were judged to have sight threatening changes on photography--false positive rate 0.3%. Considering sight threatening and background retinopathy together, the detection rate was 69% (257 of 375) and the false positive rate 1.6% (23 of 1477).
CONCLUSION: Good quality fundal photographs alone seem specific enough to screen for sight threatening diabetic retinopathy, but will underdetect background retinopathy.

Clinical Trial
Screening status in relation to biological and chronological characteristics of breast cancers: a cross sectional survey.
FE Alexander, TJ Anderson, and AL Hubbard. J Med Screen 1997 4: 152-157.
OBJECTIVE: To determine the pathological and biological characteristics of breast cancers diagnosed by screening and examined at the Edinburgh University pathology department.
METHODS: These cancers were classified by screening status: never screened (n = 111), prevalence screen detected (n = 105), and previously screened (n = 74). The last category arose in women who had been regularly screened during the trial; the cancers were diagnosed as interval cases before the first invitation to service screening (n = 33) or were incidence screen detected at that time (n = 41).
RESULTS: Association (for operable invasive cancers, n = 250) of cancer characteristics with screening status reflects influences of biology (aggressiveness) or chronology (time of diagnosis), or both. The prognostic indicators tumour grade, histological type, and oestrogen receptor status were found in a smaller percentage of the patients with poor prognosis among the prevalence screen detected cases (9%, 77%, 18%) than among those previously screened (29%, 84%, 35%). The chronological factors size and node status were found in a smaller percentage of patients with poor prognosis among women previously screened (31%, 24%) than among those never screened (62%, 39%). Apart from these two, no other factors improved the diagnosis in the previously screened group compared with the never screened group.
CONCLUSIONS: These results suggest that favourable characteristics of screen detected cases are often due to the effects of length bias on "biological factors" and fail to show that current local screening practice has succeeded in advancing the diagnosis of breast cancers to a less aggressive phase.

Comment
Why the term "carrier screening" should not be abandoned.
D Zeuner. J Med Screen 1997 4: 176.

Jump to top