Method for identifying eligible individuals for a prevalence survey in the absence of a disease register or population register.

BACKGROUND: Identifying eligible individuals for a prevalence survey is difficult in the absence of a disease register or a national population register. AIM: To develop a method to identify and invite eligible individuals to participate in a national prevalence survey while maintaining confidentiality and complying with privacy legislation. METHODS: A unique identifier (based on date of birth, sex and initials) was developed so that database holders could identify eligible individuals, notify us and invite them on our behalf to participate in a national multiple sclerosis prevalence survey while maintaining confidentiality and complying with privacy legislation. RESULTS: Several organisations (including central government, health and non-governmental organisations) used the method described to assign unique identifiers to individuals listed on their databases and to forward invitations and consent forms to them. The use of a unique identifier allowed us to recognise and record all the sources of identification for each individual. This prevented double counting or approaching the same individual more than once and facilitated the use of capture-recapture methods to improve the prevalence estimate. Capture-recapture analysis estimated that the method identified over 96% of eligible individuals in this prevalence survey. CONCLUSIONS: This method was developed and used successfully in a national prevalence survey of multiple sclerosis in New Zealand. The method may be useful for prevalence surveys of other diseases in New Zealand and for prevalence surveys in other countries with similar privacy legislation and lack of disease registers and population registers.

Breast cancer and cytomegalovirus.

PURPOSE: To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus. METHODS: We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus. RESULTS: Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus. CONCLUSIONS: Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development.

Intrafraction monitoring of prostate motion during radiotherapy using the Clarity® Autoscan Transperineal Ultrasound (TPUS) system.

INTRODUCTION: Implementation of the Clarity® Autoscan (Elekta) Transperineal Ultrasound (TPUS) system in Bristol is the first of its kind in the UK and we have already shown its utility in interfractional Image Guided Radiotherapy (IGRT).14 This study establishes the extent of intrafraction prostate motion as measured by Clarity and explores the potential benefits of TPUS for intrafraction monitoring. METHODS: Monitoring data was analysed for 526 fractions from 20 localised prostate cancer patients. Intrafraction prostate displacements exceeding thresholds of 3 mm, 7 mm and 10 mm along patient axes were assessed for frequency and duration of motion. RESULTS: Prostate motion exceeds the above displacement thresholds during 52%, 8%, and 2% of fractions analysed. Displacement at the 3 mm threshold occurred for 100% of patients, 60% at 7 mm and 35% at 10 mm. The mean frequency and duration of displacements is low for the overall population. In contrast specific patients exhibit much higher displacement values. Posterior motion is most common, averaging at 24% of the treatment time at 3 mm, 3% at 7 mm and 1% at 10 mm, ranging up to 92%, 35% and 10% for individual patients. CONCLUSIONS: Intrafraction monitoring with Clarity has the potential to improve accuracy through application of in-treatment motion correction. This is most beneficial for specific patients who exhibit a higher frequency and/or duration of prostate motion. Consideration must be given to the added time implications and radiographer workload in clinical practice to correct for prostate motion. Clarity could help facilitate future protocols using tighter treatment margins, although further research is required.

Extraction of tumor-specific antigen from cells and plasma membranes of line-10 hepatoma.

Tumor-specific antigen was extracted with 3 M KCl from line-10 guinea pig hepatoma cells. The yield of antigenic activity, estimated by production of delayed cutaneous hypersensitivity reactions in line-10 immune guinea pigs, was 10-30% of the antigen present in intact cells. By ultracentrifugation criteria, the extracted antigen was soluble. Gel filtration, ion exchange chromatography, and salting-out studies showed that the antigen was heterogeneous in size and net charge. The possibility that 3 M KCl extracted a homogeneous population of molecules associating into polymers of various sizes at low ionic strength was ruled out by heterogeneity on Sephadex G-200 chromatography at high ionic strength. After osmotic lysis of sucrose-loaded line-10 cells, whole plasma membranes or large membrane fragments were obtained in a yield of about 20%. The isolation procedure did not cause detectable loss of membrane antigenic activity. The membranes had 33 skin test U/mg membrane protein, compared to the intact cell value of 1.7 skin test U/mg cell protein. Extracts of plasma membranes had 10-20% of the antigenic activity of the starting membrane material. In contrast to the wide variety of proteins liberated from intact cells, much of the protein extracted from the membranes was in the molecular weight range above 250,000.

Biphasic dose-response effect of baclofen on haloperidol catalepsy in the rat.

Haloperidol-induced catalepsy in rats is reduced by low dose baclofen and is potentiated by high dose baclofen. This biphasic behavioral effect is consistent with reported differences between presynaptic and postsynaptic GABA receptors. Low dose baclofen could have an anti-cholinergic effect by activating presynaptic GABA receptors that inhibit the release of acetylcholine. High dose baclofen could have an anti-dopamine effect by activating postsynaptic GABA receptors that inhibit the firing of dopamine neurons.

The distribution of household expenditures on health care.

AIMS: To find out whether New Zealand household expenditures on health care services vary according to the income of the household. To compare expenditures on health care in 1987 with 1991. METHODS: Information about household income and expenditure on health services was obtained from the Department of Statistics annual household expenditure and income surveys for the 1987 and 1991 financial years. Four categories of health expenditure were examined: general practitioner fees, dental fees, optician and optometrist fees, and spending on all health services combined. RESULTS: Spending on health care is unequally distributed across income groups. In particular, the highest income households spend six times as much on dental care as the lowest income households. The difference between high and low income households in the amount spent on all health services was greater in 1991 than in 1987. In 1991 high income households spent 3.6 times as much on health services as low income households, compared with three times as much in 1987. CONCLUSIONS: High income households spend substantially more on health care than do low income households. Households appear to assign a higher priority to medical care than dental care, although this may reflect the lack of any state subsidy on adult dental care.

The costs of mammography screening in New Zealand: evidence from the pilot programmes.

AIMS: To measure the public health service costs associated with New Zealand's pilot mammography screening programmes. To compare the early evidence on cost per woman screened and per cancer detected in those programmes to that of overseas screening programmes. To estimate the cost of introducing a national screening programme in New Zealand. METHODS: Costs in each screening centre were obtained by a careful examination of screening budgets and public health service accounts; these were inflation adjusted using a consumers price index, and analysed in terms of equivalent annual operating costs. RESULTS: In the first year of screening the cost per woman screened (in $1991) was $182 in Waikato and $178 in Otago/Southland. The cost per woman screened in the third year of screening (with an assumed full screening throughput of 8,000 women per annum) is estimated to fall to $106 and $113 for the Waikato and Otago/Southland programmes respectively. The cost per cancer detected in the first screening round differs between the two programmes. In the first year of screening the cost per cancer detected was $35,975 in Waikato and $21,908 in Otago/Southland. The difference was primarily attributable to a lower cancer detection rate in Waikato in that period (0.51% of women screened compared with 0.81% in Otago/Southland). CONCLUSIONS: The initial performance of the New Zealand pilot programmes, both in terms of cost per woman screened and cost per cancer detected, falls within the range indicated from overseas experience. An established national screening programme is estimated to add between $9.3 and $9.9 million dollars (in 1991 dollar terms) to health service costs each year. These costs will be partly offset by savings resulting from the earlier detection of cancers.

Factors affecting participation in mammography screening.

AIMS: To assess factors influencing attendance or nonattendance at the first round of a population based mammography screening programme, in New Zealand. METHOD: Representative samples of women who responded to an invitation to attend screening, and women who did not respond, were interviewed by telephone, by an interviewer independent of the screening programme. The response rates in those identified were 98% for attenders and 86% for nonattenders, giving final samples of 191 and 174 respectively. However, more nonattenders could not be contacted or had no known phone number. RESULTS: Reasons given for attendance were primarily the need for reassurance, to detect breast cancer early, and the fact that the programme was free, a pilot programme, or recommended by their family doctor. Seventeen percent of attenders had been influenced by positive reports from other women. Of the nonattenders, 7% were ineligible for mammography, 20% did not attend because of practical difficulties and convenience, and 20% expressed concern or fear of the procedure or were influenced by negative reports from other women. Attenders and nonattenders did not differ in regard to age, education, income, socioeconomic status, degree of worry when the invitation was received, or physical distance from their home to the screening centre, although nonattenders estimated the travel would take considerably longer than did attenders. Ninety percent of attenders intend to come to the second round of screening. Forty three percent of nonattenders intend to participate at future rounds of screening, this figure being 80% in those who did not attend because of logistic or convenience reasons, and 27% for those who did not attend because of fear or negative reports. CONCLUSIONS: The main reasons given for nonattendance are approximately equally divided between practical difficulty, and negative attitude towards the process. Most of those who did not attend for reasons of convenience intend to participate at future rounds, so that overall almost half of nonattenders intend to participate at future rounds. Therefore we recommend that invitations for future screening rounds should be sent to women who do not participate in the first round of population based screening.

A survey of urban and rural participants in the Otago-Southland pilot breast cancer screening programme.

AIMS: By surveying participants in a pilot breast cancer screening programme, to measure satisfaction with the screening service, to provide feedback for programme staff, to obtain an indication of future participation, and to collect information about costs to women. METHODS: A self administered questionnaire was posted to representative samples of urban and rural women (total 474) who had participated in the Otago-Southland pilot breast cancer screening programme in its first year of operation. RESULTS: There was a 93% response rate to the survey, after one reminder letter. Although some demographic characteristics of urban and rural women differed, their opinions about the screening programme were similar. Satisfaction with the service is extremely high, with 94% of respondents planning to participate again in two years. CONCLUSIONS: The Otago-Southland pilot programme provides a service which is regarded as satisfactory by the great majority of participants.

SmokeChange for changing smoking in pregnancy.

AIM: To measure the extent to which SmokeChange, a personalised intervene, enabled pregnant women to rede their exposure to tobacco smoke. METHODS: A cross-section of general medical practices was randomly selected. General Practitioners (GPs) were to register all pregnant women with the SmokeChange programme. Smoking women were contacted by a SmokeChange Educator, who visited them at home. The Educator worked with women and their families for up to twelve months in order to support cognitive, environmental and behavioural changes to smoking. RESULTS: GPs registered 1,390 pregnant women. Current smoking, was reported by 437 (31.4%) and 209 (47.8% of smokers) chose to enrol with the SmokeChange intervention programme. of these, 149 women (34.1% of smokers) continued with the programme for at least four visits. From this 'long' participation group, 28 (18.8%) had stopped smoking entirely by their last visit in pregnancy. Another 26 (17.4%) reported at least one cessation attempt, together with a reduction of smoking consumption by 63% at the end of pregnancy. The 95 (63.8%) continued smokers had reduced their smoking consumption by 40%. Substantial smokefree environment (homes and cars) changes were also made. CONCLUSIONS: The SmokeChange approach of personalised intervention, matched to individual readiness for change, was both acceptable to pregnant women and enabled participants to substantially reduce tobacco toxin exposure to themselves and their developing infants.

The effectiveness of breast cancer screening by mammography in younger women.

We reviewed the evidence relating to breast screening using mammography in younger women, primarily those aged 40 to 49. The best evidence comes from the 6 published randomized trials. We performed a metaanalysis, assessing the breast cancer death rates for each year of follow-up in each trial, and producing summary estimates of the cumulative and year-specific mortality rates. At 7 to 10 years, death rates in screened and unscreened groups are similar. This lack of benefit contrasts with the average 30% mortality reduction in women over age 50 in the same trials. This evidence provides no basis for the promotion of mammographic screening in women under age 50 in the general population. If mammography is to be offered to asymptomatic women of that age who request it, appropriate information including the fact that there has been no demonstrated ultimate benefit should be given. The difference in effectiveness may relate both to the greater difficulty in distinguishing normal from abnormal tissue, and to greater growth speed and different biological characteristics of tumors, in younger women. We also reviewed recommendations from major groups: in general multidisciplinary bodies which rely on structured evaluations do not recommend screening in younger women, while many other specialty associations and cancer societies do. Overall, the trials of screening of younger women show a small increase in mortality in those screened, and possible explanations of this are discussed. [corrected] Remaining questions concern the precise age at which effectiveness changes, the situation in high-risk women, and the impact of improved or more frequent screening.

Cytomegalovirus, Epstein-Barr virus and risk of breast cancer before age 40 years: a case-control study.

We investigated whether there is an association between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) IgG levels and risk of breast cancer before age 40 years. CMV and EBV IgG levels were measured in stored plasma from 208 women with breast cancer and 169 controls who participated in the Australian Breast Cancer Family Study (ABCFS), a population-based case-control study. CMV and EBV IgG values were measured in units of optical density (OD). Cases and controls did not differ in seropositivity for CMV (59 and 57% respectively; P=0.8) or EBV (97 and 96% respectively; P=0.7). In seropositive women, mean IgG values were higher in cases than controls for CMV (1.20 vs 0.98 OD, P=0.005) but not for EBV (2.65 vs 2.57 OD, P=0.5). The adjusted odds ratios per OD unit were 1.46 (95% CI 1.06-2.03) for CMV IgG and 1.11 (0.93-1.33) for EBV IgG. The higher mean CMV IgG levels found in women with breast cancer could be the result of a more recent infection with CMV, and may mean that late exposure to CMV is a risk factor for breast cancer.