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Comment
Screening for neuroblastoma in children.
J Morris. J Med Screen 1994 1: 141-142.

Why screen for HIV infection in pregnancy?
ML Newell. J Med Screen 1994 1: 143.

Journal Articles
Encouraging attendance at a screening mammography programme: determinants of response to different recruitment strategies.
PE Schofield, J Cockburn, DJ Hill, and D Reading. J Med Screen 1994 1: 144-149.
OBJECTIVES: To predict attendance at a mammographic screening programme after a community health promotion campaign and attendance after a personal invitation in addition to that campaign.
SETTING: A pilot mammographic screening programme in Melbourne, Australia.
METHODS: Attendance was encouraged by a community health promotion campaign and one year later, a personal invitation was sent to all women who had not yet attended. Drawn from two regions of a defined area (close to and distant from the screening centre), 618 women were interviewed before the programme started, and subsequent attendance at the programme was recorded.
RESULTS: Over half of the women (58%) in the sample residing close to the screening centre and 44% of women in the more distant sample attended. The personal invitation boosted attendance, particularly in the distal sample where attendance was predicted by ease of access to the programme; positive intention to attend; moderate experience of, perceived susceptibility to, concern about, and knowledge of breast cancer; adoption of other preventive health behaviours; having a job; and older age. Proximity to the programme, positive initial intentions, having heard of a mammogram, no concern about radiation from a mammogram, high personal control over health, and belonging to a club were associated with attendance after exposure to only the health promotion campaign. A personal invitation encouraged attendance among women without these characteristics.
CONCLUSION: A personal invitation in addition to a community promotion campaign seems to overcome many barriers to attendance. Attendance may be further increased by informing women of the benefits of early detection and improving access to the screening centre.

Effectiveness of three community based strategies to promote screening for cervical cancer.
JE Byles, RW Sanson-Fisher, S Redman, JA Dickinson, and S Halpin. J Med Screen 1994 1: 150-158.
OBJECTIVE: Evaluation of three potential methods for increasing Pap smear use: television media, television media combined with letter based recruitment, and television media combined with general practitioner based (GP based) recruitment.
SETTING: A trial of each intervention was carried out in three postal regions in New South Wales, Australia-a rural locality (containing about 1000 women), a country town (about 3000 women), and a major rural centre (about 10,000 women). Three control regions were selected to be demographically similar to the corresponding intervention regions.
METHODS: Outcome data on regional Pap smear rates were obtained from government health insurance claims for cervical screening, and from pathology service records. Expected Pap smear rates for the three months after the intervention were predicted from 45 pre-intervention months and were compared with observed rates for this period.
RESULTS: Television media alone was associated with a significant increase in attendances for screening in one of the three regions where a trial was carried out: 13.3% in the rural centre. The media/letter based campaign was associated with a significant increase in attendances in two out of three regions: 52.7% in the rural locality, 43.2% in the rural centre. The media/GP based campaign was associated with significant increases in attendances in all three regions: 50.2% in the rural locality, 80.8% in the country town, 15.7% in the rural centre. All three interventions were associated with significant increases in the number of women attending for cervical screening above those observed in the control regions. Furthermore, these increases were not restricted to women at low risk. They were also found for older women (aged 50-69 years) and women who had not had a Pap smear within the past three years.

Cascade testing for the identification of carriers of cystic fibrosis.
S Holloway and DJ Brock. J Med Screen 1994 1: 159-164.
It has been suggested that cascade testing, in which relatives of a person affected with cystic fibrosis (CF) are tested for carrier status, is preferable to screening individuals in the general population. This idea was examined by calculating the number of relatives requiring testing, assuming that it is necessary to identify all those of reproductive age no more distantly related to the proband than second cousins. Two hypothetical programmes were used, in each of which only blood relatives of an affected proband were tested and subsequent analysis applied to relatives of those with a positive result. If started in the grandparental generation, cascade testing of about 28 relatives for each proband would detect 86.4% of carriers in the family. If only carried out for the parental generation and their descendants, testing of about 35 relatives for each proband would detect 92.1% of carriers in the family. If cascade testing were restricted to the second cousin level, however, these programmes would only detect between 8 and 24% of all carrier couples. This contrasts with the 50% detection rate that has already been demonstrated for antenatal CF screening.

Reliability of the Barlow and Ortolani tests for neonatal hip instability.
M el-Shazly, B Trainor, WG Kernohan, I Turner, PE Haugh, AF Johnston, and RA Mollan. J Med Screen 1994 1: 165-168.
OBJECTIVE: To investigate if those responsible for screening for neonatal hip instability are using acceptable manual hip stress tests as described by Ortolani and Barlow.
METHOD: A video camera was used to record the technique of 35 personnel who were responsible for screening. They examined both a baby and a simulator. The study comprised five groups, classified by experience and practice: senior orthopaedic surgeons, senior paediatric staff, junior paediatric staff, nurses, community staff.
RESULTS: The seven authors together with six independent expert observers viewed the video and marked the performance with the aid of a specially designed proforma. Although there was some variation between these expert observers, the results showed differences in the scores obtained by the different groups of examiners over all aspects of the test procedure.
CONCLUSION: Video recording for critical analysis and feedback is a useful technique in this situation. Overall, the results suggest that testing for neonatal hip instability was inadequate. A variety of hip stress manoeuvres were being performed. The ability of each subject to perform satisfactory tests seemed to depend on their experience and education. More "hands on" training and experience of testing might provide the necessary competency for screening.

Screening for neuroblastoma: a review of the evidence.
J Chamberlain. J Med Screen 1994 1: 169-175.
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.

Use of anonymous newborn serosurveys to evaluate antenatal HIV screening programmes.
FJ Holland, AE Ades, CF Davison, S Parker, T Berry, M Hjelm, AH Wilcox, D Cubitt, CN Hudson, and CS Peckham. J Med Screen 1994 1: 176-179.
OBJECTIVE: To evaluate the extent to which antenatal HIV screening programmes identify HIV infected women who go to term.
DESIGN: Comparison of results of two surveillance systems. An anonymous neonatal HIV serosurvey was used to estimate the numbers of HIV infected women giving birth; reporting by obstetricians was used to assess the proportion who had been identified.
SETTING: Three Thames regions.
RESULTS: 729,105 neonatal blood samples were tested, of which 484 were HIV seropositive. Newborn HIV seroprevalence is increasing, at different rates, in inner London, suburban London, and in non-metropolitan districts. During the past four years the proportion of infected women who have been identified before delivery is 16.9%, but less than half of these were diagnosed during pregnancy. In 1993 only five of the 128 (4%) previously undiagnosed infected women delivering babies were identified by antenatal screening.
CONCLUSION: Despite increased emphasis on antenatal testing for HIV in areas of higher prevalence the number of undiagnosed women delivering babies continues to increase. Consideration should be given to alternative strategies for offering antenatal HIV testing. Antenatal screening programmes should be monitored continuously by comparing anonymous neonatal seroprevalence with clinical reports from obstetricians.

Impact of a regional screening programme using maternal serum alpha fetoprotein (AFP) and human chorionic gonadotrophin (hCG) on the birth incidence of Down's syndrome in the west of Scotland.
JA Crossley, DA Aitken, E Berry, and JM Connor. J Med Screen 1994 1: 180-183.
OBJECTIVES: To evaluate the impact of a large scale population screening programme on the birth incidence of Down's syndrome in the west of Scotland over a 12 month period.
METHODS: Biochemical screening for Down's syndrome using maternal serum alpha fetoprotein, chorionic gonadotrophin, and maternal age was offered to a pregnant population of 37,226 women in the west of Scotland between 1991 and 1992. The combined risk of Down's syndrome pregnancy was reported for each of the 30,084 women who opted for screening.
RESULTS: When a threshold risk of 1:220 was used 1523 women (5.1% of the screened population) were assigned to the high risk group, of whom 1070 (70%) proceeded to diagnostic amniocentesis or midtrimester chorionic villus sampling. When multiple sources of ascertainment were used 37 Down's syndrome pregnancies were identified within the screened population, 26 (70%) of which were within the high risk group and 21 (57%) of which were prenatally diagnosed. In addition, three Down's syndrome pregnancies were diagnosed by first trimester chorionic villus sampling before biochemical screening. A further 10 Down's syndrome pregnancies were identified at birth, eight to women who had not had a screening test and two to women who had moved into the area, making a total of 50 Down's syndrome pregnancies in the whole pregnant population of 37,226. Thus the potential prenatal detection rate in the screened population was 70% (26/37), the actual prenatal detection rate in the screened population was 57% (21/37), and the overall prenatal detection rate in the total (screened and unscreened) population was 48% (24/50). CONCLUSION: Biochemical screening for Down's syndrome is practical and effective in routine clinical practice, enabling women to make an informed choice about prenatal diagnosis and providing better use of scarce resources when a suitable protocol is applied to the whole pregnant population. Its maximum potential for the reduction of the birth incidence of Down's syndrome is limited by incomplete uptake of screening and compliance with diagnostic testing in the high risk group.

Evaluation of the effect on breast cancer mortality of population based mammography screening programmes.
S Tornberg, J Carstensen, T Hakulinen, P Lenner, T Hatschek, and B Lundgren. J Med Screen 1994 1: 184-187
OBJECTIVE: To evaluate, by analysis of breast cancer mortality data from all the 26 Swedish counties for the years 1971 to 1990, whether the effect of the introduction of mammography screening in Sweden can be assessed by observation from existing mortality data.
METHODS: A Poisson regression model was used to study whether a decrease in breast cancer mortality among women aged 50-74 years was associated with the extent of mammography screening in different counties and periods.
RESULTS: In regions where mammography screening had been introduced, breast cancer mortality tended to be decreased, on average, compared with regions without screening. If a 10 year time lag between the start of screening and its full effect on mortality is assumed then the estimated reduction in breast cancer mortality associated with introduction of screening was 19% with a 95% confidence interval ranging from -3% to 37%.
CONCLUSIONS: The results suggest that the effect of mammography screening may be studied using existing routine mortality data and appropriate statistical modelling. This way of assessing the outcome of the screening is valuable when continuously monitoring a screening programme that has become a public health routine.

Assessment of lesions detected at mammographic screening: performance at first or repeat screening in the Florence programme.
S Ciatto, MR Del Turco, D Giorgi, D Morrone, S Catarzi, D Ambrogetti, E Paci, and M Zappa. J Med Screen 1994 1: 188-192.
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.

Clinical Trials
Survival of patients with breast cancer diagnosed in the United Kingdom trial of early detection of breast cancer. United Kingdom Trial of Early Detection of Breast Cancer Group.
SM Moss, R Ellman, D Coleman, and J Chamberlain. J Med Screen 1994 1: 193-198.
OBJECTIVE: To examine the survival of patients with breast cancer diagnosed in different centres and by different methods in the United Kingdom trial of early detection of breast cancer, in order to investigate the contribution of different factors to the previously observed reductions in breast cancer mortality.
SETTING: A non-randomised trial of the early detection of breast cancer, in which women aged 45-64 in two districts were offered annual screening for seven years, women in a further two districts were offered education about breast self examination (BSE), and those in four districts formed a comparison group.
METHODS: Patients with breast cancer are classified according to the type of centre, method of detection, and attendance for BSE education. Univariate and multivariate survival analyses are carried out, including tumour size, dissemination status, and use of adjuvant treatment as additional variables.
RESULTS: In the univariate analysis, patients with breast cancer who are non-attenders for screening have a significantly worse prognosis than those in the comparison centres. Patients whose cancer is detected by mammography have the best survival rate. The inclusion of size and dissemination status in the multivariate analysis explains only about one third of the improved prognosis in these cases. There is a significant difference between prognosis in the two BSE centres.
CONCLUSIONS: The use of prognostic factors as recorded in this trial to predict breast cancer mortality may be inadequate.

Improving breast screening uptake: persuading initial non-attenders to attend.
KM Turner, BJ Wilson, and FJ Gilbert. J Med Screen 1994 1: 199-202.
OBJECTIVES: Firstly, to determine whether the acceptance rate of the second invitation for breast screening (sent to women who have failed to attend after the first invitation) might be increased by an accompanying letter from a general practitioner (GP letter). Secondly, to identify the additional costs of sending such a letter.
METHODS: 465 women registered with four practices in a single health centre were recruited into a randomised controlled trial in which the intervention was the inclusion of a standard, photocopied letter signed by the non-attender's doctor with the second invitation to attend for breast screening. The control group received only the standard invitation from the breast screening centre. The costs associated with the intervention were assessed from data supplied by the breast screening centre, supplemented by direct observation of the preparation of second invitations and semistructured interviews with the staff taking part.
RESULTS: The attendance rate of the test group one month after the second invitation for screening was significantly higher than that of the control group (21% v 10%, P < 0.01). The average cost of a GP letter included with the invitation was 1.1 pence and the marginal cost for each extra attender was 9.6 pence. No non-monetary costs were identified.
CONCLUSIONS: The inclusion of a GP letter appeared to be effective and feasible in increasing the attendance rate to the second invitation. This intervention should be tested in other screening groups to confirm the effectiveness of a GP letter and its cost effectiveness.

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