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Editorials
What is genetic screening anyway?
NJ Wald. J Med Screen 1996 3: 57.

Journal Articles
Second trimester levels of maternal serum inhibin A, total inhibin, alpha inhibin precursor, and activin in Down's syndrome pregnancy.
GM Lambert-Messerlian, JA Canick, GE Palomaki, and AL Schneyer. J Med Screen 1996 3: 58-62.
OBJECTIVE: To determine the levels of various biochemical forms of the placental protein, inhibin (total inhibin, inhibin A, and alpha inhibin precursor) and activin in maternal serum samples from fetal Down's syndrome, and to determine which of these analytes most effectively identifies samples from affected pregnancies.
METHODS: Maternal serum samples were collected from 100 unaffected pregnancies and 20 cases of fetal Down's syndrome during gestational weeks 15-20 for routine triple marker screening, and were stored frozen after clinical assay. Levels of inhibin A, total inhibin, alpha inhibin precursor (pro-alphaC), and activin were compared retrospectively in the Down's syndrome cases and control samples.
RESULTS: There was no association of the inhibin or activin levels with gestational age or length of freezer storage, and therefore single median values were determined for the unaffected pregnancies for each analyte. Multiples of the unaffected median (MoM) values were calculated for all cases, showing that inhibin A (1.95 MoM) provided the best discrimination between cases and controls, followed by total inhibin (1.37 MoM). Mann-Whitney U analysis showed significant group differences in inhibin A (P = 0.0001) and total inhibin (P = 0.0005). In contrast, alpha inhibin precursor (0.81 MoM) and activin (1.16 MoM) levels in Down's syndrome cases were not significantly different from those in unaffected patients.
CONCLUSIONS: Levels of inhibin A and total inhibin, but not alpha inhibin precursor or activin, are significantly raised in maternal serum from cases of fetal Down's syndrome. These data, taken together, indicate that inhibin A levels are specifically raised in Down's syndrome pregnancy. 45% of the inhibin A levels in the Down's syndrome samples were above the 90th centile of unaffected levels, indicating that inhibin A may be as good a marker as human chorionic gonadotrophin, the most informative serum marker currently in use.

Validity of immunological faecal occult blood screening for colorectal cancer: a follow up study.
H Nakama, N Kamijo, AS Abdul Fattah, and B Zhang. J Med Screen 1996 3: 63-65.
OBJECTIVES: Immunological faecal occult blood testing has been recognised as a useful method for wide scale screening of colorectal cancer in Japan during the past few years. This study was carried out to evaluate the validity of an immunological faecal occult blood test for colorectal cancer screening.
METHODS: A screening programme for colorectal cancer using an immunological faecal occult blood test was conducted on 3365 residents of regions within Nagano prefecture in 1991, and all the subjects were followed up for three years by verification from cancer registration. Based on the incidence of false negative cases among those who had been evaluated as normal by this screening, but were diagnosed as having colorectal cancer, the sensitivity and the specificity of this test were estimated.
RESULTS: Four false negative cases were found during the subsequent three year follow up period after screening. Among these four cases, one case was within the first follow up year, one case within the second year, and two cases within the third year. Accordingly, the sensitivity of this test was calculated as 90.9% within one year, 83.3% within two years, and 71.4% within three years, while the specificity was found to be 95.6%, indicating a validity higher than that achieved by a chemical occult blood test.
CONCLUSION: These findings suggest that the immunological faecal occult blood test has a high diagnostic accuracy and is a useful strategy for colorectal cancer screening.

Estimation of the optimal cut off point in a new immunological faecal occult blood test in a corporate colorectal cancer screening programme.
M Itoh, K Takahashi, H Nishida, K Sakagami, and T Okubo. J Med Screen 1996 3: 66-71.
OBJECTIVE: To estimate the optimal cut off point in a new immunological
METHod (OC-Hemodia) for faecal occult blood testing (FOBT).
SETTING: A corporate colorectal cancer screening programme in Japan.
METHOD - The screening programme targeted colorectal cancer and adenomatous polyps > or = 10 mm, and was conducted on 27 860 participants (age > or = 40) during 1991-92. The follow up consisted of diagnostic management by total colonoscopy on positive screened subjects exceeding the manufacturer recommended cut off level of 50 ng/ml faecal haemoglobin, and the identification of false negative cases by health insurance claims. The optimal cut off point was estimated by the positive predictive value, receiver operating characteristic (ROC) curve, and a cost effectiveness analysis. In this study evaluation was carried out only for cancer as the target disease.
RESULTS:- At the current cut off level of 50 ng/ml the sensitivity and specificity were 86.5% and 94.9%. When the optimal cut off point was estimated the highest positive predictive value was obtained at 250-350 ng/ml. The ROC curve showed that the sum of sensitivity and specificity is maximised at 50 ng/ml, but evaluation of the ratio, change in sensitivity/change in false positive rate, pointed to higher optimal cut off points, showing marked changes occurring at about 200 ng/ml. The average cost per case was lowest at 250-300 ng/ml. Overall, the optimal cut off point was estimated to be about 200 ng/ml, at which the sensitivity and specificity of the test would be 77.5% and 98.9%, respectively.
CONCLUSION: The optimal cut off point of the new immunological
METHod of FOBT was estimated to be about 200 ng/ml, a value which, more than the current cut off value, favours specificity over sensitivity.

Monitoring the performance of breast screening programmes: use of indirect standardisation in evaluating the invasive cancer detection rate.
RG Blanks, NE Day, and SM Moss. J Med Screen 1996 3: 79-81.
Close monitoring of data from individual programmes is required to evaluate the potential of the breast screening programme to reach the Health of the Nation target of 25% reduction in breast cancer mortality in the invited age group by the year 2000. This paper outlines the use of indirect age standardisation techniques to compare the performance of individual programmes in terms of their invasive cancer detection rates. Expected invasive cancer detection rates are calculated by applying data from the Swedish two county study to estimated England and Wales background incidence rates for different age strata. If the national programme overall meets these targets then the required mortality reduction should be achieved. The same
METHod can be used by other (national) screening programmes by applying the relevant background incidence figures to produce internationally comparable data.

Monitoring the performance of breast screening programmes: allowing for geographical variation in breast cancer incidence.
RG Blanks and SM Moss. J Med Screen 1996 3: 82-84.
Among the myriad of problems associated with evaluating the performance of individual screening programmes in the National Health Service breast screening programme is that of correcting for background breast cancer incidence in the catchment areas of individual programmes. The background incidence will affect not only the expected cancer detection rate at screening, but also the interval cancer rates. This paper proposes a
METHod that can be used to correct for background incidence. The
METHod can be used either to correct the crude cancer detection rate or the age adjusted cancer detection rate using a measure such as the standardised detection ratio. Variation in background incidence and age distribution of screened women are the two major factors affecting the expected cancer detection rate for individual screening programmes. Control of these two variables should allow more effective evaluation of individual screening programme performance.

An overview of the Swedish randomised mammography trials: total mortality pattern and the representivity of the study cohorts.
L Nystrom, LG Larsson, S Wall, LE Rutqvist, I Andersson, N Bjurstam, G Fagerberg, J Frisell, and L Tabar. J Med Screen 1996 3: 85-87.
OBJECTIVES: To analyse the cause of death pattern in the cohorts of women included in the Swedish randomised mammography screening trials by comparing the groups of invited and control women both with each other and with the general population of Swedish women.
SETTING: Since 1977 four randomised trials of mammography screening have been performed in Sweden: Malmo, Kopparberg and Ostergotland (the two county trial), Stockholm, and Gothenburg.
DESIGN: Overview of four randomised mammography screening trials.
RESULTS: The total numbers of deaths in the invited and control groups respectively were 15 695 and 11 887 corresponding to a relative risk (RR) of 1.00. There were no significant differences between the invited and control groups for cause-specific mortality, except for breast cancer. When the total mortality in the invited and the control groups was compared with that for Swedish women in general the standardised mortality ratio was close to 100.
CONCLUSIONS: The cause of death pattern in the invited group was, except for breast cancer, very similar to that in the control group, showing that the groups were comparable. Similarly, the total mortality including breast cancer mortality in the control group was almost identical to that in Swedish women in general. The same was true, with the exception of breast cancer, for the invited group. These observations confirm that the trial cohorts are representative of Swedish women and indicate that the quantitative results from these trials may safely be generalised to the Swedish populations.

Effect of issuing an invitation for breast cancer screening to women aged 65 to 69.
PJ Hendry and C Entwistle. J Med Screen 1996 3: 88-89.
OBJECTIVE: Breast cancer screening is available to all women over 50 in the United Kingdom on the National Health Service breast screening programme. Only women aged between 50 and 64 receive a written invitation, with women over 64 being expected to self refer. Unfortunately, despite the higher incidence of breast cancer in the older age group only a very small proportion of women over 64 attend for screening. The aim of the study was to test the hypothesis that women between the ages of 65 and 69 will attend for screening if invited.
METHOD: Women aged 65 to 69 were invited for screening from general practices in the Inverness area and were treated in all respects as the usual screening age group.
RESULTS: An uptake of 76% was achieved with a cancer detection rate of 9.3 per thousand.
CONCLUSION: These results lend weight to the suggestion that women in this age group should receive a specific invitation for breast cancer screening.

Role of screening in reducing invasive cervical cancer registrations in England.
R Fouquet and H Gage. J Med Screen 1996 3: 90-96.
OBJECTIVE: To estimate the effect of screening on invasive cervical cancer registrations in England.
SETTING: The Health of the Nation target for cervical cancer seeks to reduce the incidence of invasive cases (ICD 180) by at least 20% between 1986 and 2000.
METHOD: The available area-level statistics on invasive cervical cancer registrations, screening activity, and socioeconomic and behavioural characteristics for 145 district health authorities in England over the period 1985-91 were collected. A multiple regression analysis sought to explain variations in incidence rates by relating screening and socioeconomic and behavioural variables to registration rates.
RESULTS: Districts with higher unemployment levels and higher numbers of pregnancies in young women had higher registration rates for invasive cervical cancer. The cervical smear rate for women aged 35-64 in a district was positively related to registrations, whereas the relation was negative for the 20-34 age group.
CONCLUSIONS: The higher registration rates for invasive cervical cancer in districts with higher cervical smear rates for women aged 35-64 may reflect historically lower screening cover. The negative relation between the cervical smear rate and invasive cervical cancer registrations in women aged 20-34 is accompanied by high registration rates for preinvasive (CIN III) cervical cancer (ICD 233.1). For the advantages of the Pap test to be fully realised, and for invasive cervical cancer registrations to fall in line with the Health of the Nation targets, a comprehensive screening programme, with a high take up rate is required. The various changes to the screening programme introduced since 1988 should help to achieve this. Public health policy should focus on educating the population about the risk factors for cervical cancer and the significance of screening.

Human-figure drawing (HFD) in the screening of cognitive impairment in old age.
K Ericsson, P Hilleras, K Holmen, and B Winblad. J Med Screen 1996 3: 105-109.
OBJECTIVE: The aim of the study is to test the hypothesis that freehand human-figure drawing (HFD), can be used as a complementary screening instrument to differentiate between demented elderly people and healthy elderly controls in population based studies.
METHOD: HFD was examined in 668 elderly ( > or = 75 years of age) participants from an epidemiological study in Stockholm, who were asked to draw a human figure. The drawings were analysed on the content of body details and structural characteristics.
RESULT: The results show quite clearly that the body details and the height decrease with decreasing cognitive function, whereas the centredness (the distance in cm from the centre of the figure to the centre of the paper) increases with decreasing cognitive functioning. Demented people place their figures in the upper left corner of the sheet, compared with the mostly well centred figures of non-demented people. Age, on the other hand, has an influence on the HFD as after 90 years of age most of the variables show regressive changes.
CONCLUSION: The HFD can help to differentiate between demented and non-demented subjects as well as between dementia of different severity. The HFD does not help us, however, to discriminate between Alzheimer's disease and vascular dementia. Age has an influence on the HFD in the sense that after 90 years most of the variables regress to a smaller or more primitive form.

Clinical Trial
Screening for colorectal cancer by once only sigmoidoscopy: a feasibility study in Turin, Italy.
C Senore, N Segnan, FP Rossini, R Ferraris, M Cavallero, F Coppola, M Pennazio, and WS Atkin. J Med Screen 1996 3: 72-78.
OBJECTIVES: To assess the impact on compliance of three invitation methods, as well as the acceptability and efficacy of two bowel preparation regimens, for endoscopic screening in the general population.
METHODS: 1170 subjects (men and women aged 55 to 59, in the rosters of a sample of general practitioners (GPs) in Turin), were randomly allocated to one of three invitation groups (A: personal letter, signed by GP, with a pre-fixed appointment; B: same as for A + letter supporting the study by a well known scientist; C: letter signed by the study coordinator, NS) and two preparation regimens (i: one enema, self administered at home two hours before the test; ii: two enemas, administered the night before and two hours before the test). A postal reminder was mailed to non-attenders. A sample of non-responders was contacted for a telephone interview by a trained nurse. Written consent was obtained from all subjects undergoing the test.
RESULTS: A total of 278 subjects attended for sigmoidoscopic screening. An invitation from the GP alone produced the highest response rate (compliance: A = 29.3%; B = 24.9%; C = 26.8%). A single enema was as effective as two enemas in achieving satisfactory preparation for the test: the proportion of subjects invited to repeat the test was 8.1% in the single enema group, and 9.6% in the group receiving two enemas.
CONCLUSIONS: Compliance with this screening procedure tends to be low. One enema, self administered two hours before sigmoidoscopy, can ensure a satisfactory bowel preparation.

Guideline
Prospective evaluation plan for randomised trials of prostate cancer screening. The International Prostate Cancer Screening Trial Evaluation Group. A Auvinen, JB Rietbergen, LJ Denis, FH Schroder, and PC Prorok. J Med Screen 1996 3: 97-104.
To enable pooled analyses of continuing and planned randomised trials of prostate cancer screening, guidelines for minimal data required for such analyses were developed in the recent meeting of the International Prostate Screening Trial Evaluation Group (IPSTEG). The aim of the pooled analysis with data on individual level will be: (a) Estimation of the effect of screening on prostate cancer mortality with greater precision than individual studies; (b) Assessment of optimal screening procedures and interval; (c) Identification of subgroups within the populations that might receive most benefit from screening; (d) Evaluation of the quality of life effects and cost effectiveness of screening. All studies included in the combined analysis share a common core protocol with minimum data requirements. The protocol allows, however, adaptation of the procedures to local circumstances within defined options. It should be noted that the process is continuing and the protocol is subject to evaluation and revision in the meetings of the IPSTEG on a regular basis.

Letters
Diabetic retinopathy.
AD Penman and MM Engelgau. J Med Screen 1996 3: 111.

Case-finding.
W Holland. J Med Screen 1996 3: 111.

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