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Interim results from phase III trials of the vaccine developed by the University of Oxford and AstraZeneca were announced through press releases on 23 November. Much has been made of an apparent difference in efficacy between the intended regimen (two full doses of the vaccine) and another regimen (a half dose followed by a full dose). Whereas the efficacy …

BACKGROUND An unethical clinical study that entailed withholding treatment from women diagnosed with cervical intraepithelial neoplasia 3 (CIN3) was conducted at National Women's Hospital, Auckland, New Zealand. Women with microinvasive carcinoma of the cervix also had treatment withheld. AIMS To describe the management and outcomes for women with microinvasive carcinoma for many of whom conventional treatment was withheld. MATERIALS AND METHODS Retrospective cohort study of women with a diagnosis of stage 1A cervical carcinoma at National Women's Hospital. Medical records, cytology and histopathology were reviewed and data linked with cancer and death registries up to December 2000. RESULTS Between 1955 and 1976, 62 women were initially diagnosed with stage 1A cervical cancer and 20 were diagnosed during follow up (to 1995). Sixty of the 82 women had initial management characterised as 'probably non-curative'; 20 of these received only a small diagnostic excision. Women in the latter group were more likely to: (i) subsequently have positive cytology (P

Background. The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed about 90% of the worldwide epidemiological evidence on the relation between risk of breast cancer and use of hormone replacement therapy (HRT). Methods. Individual data on 52,705 women with breast cancer and 108,411 women without breast cancer from 51 studies in 21 countries were collected, checked, and analysed centrally. The main analyses are based on 53,865 postmenopausal women with a known age at menopause, of whom 17,830 (33%) had used HRT at some time. The median age at first use was 48 years, and 34% of ever-users had used HRT for 5 years or longer. Estimates of the relative risk of breast cancer associated with the use of HRT were obtained after stratification of all analyses by study, age at diagnosis, time since menopause, body-mass index, parity, and the age a woman was when her first child was born. Findings. Among current users of HRT or those who ceased use 1-4 years previously, the relative risk of having breast cancer diagnosed increased by a factor of 1.023 (95% CI 1.011-1.036; 2p = 0.0002) for each year of use; the relative risk was 1.35 (1.21-1.49; 2p = 0.00001) for women who had used HRT for 5 years or longer (average duration of use in this group 11 years). This increase is comparable with the effect on breast cancer of delaying menopause, since among never-users of HRT the relative risk of breast cancer increases by a factor of 1.028 (95% CI 1.021-1.034) for each year older at menopause. 5 or more years after cessation of HRT use, there was no significant excess of breast cancer overall or in relation to duration of use. These main findings did not vary between individual studies. Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast dancer associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body-mass index. There was no marked variation in the results according to hormonal type or dose but little information was available about long durations of use of any specific preparation. Cancers diagnosed in women who had ever used HRT tended to be less advanced clinically than those diagnosed in never-users. In North America and Europe the cumulative incidence of breast cancer between the ages of 50 and 70 in never-users of HRT is about 45 per 1000 women. The cumulative excess numbers of breast cancers diagnosed between these ages per 1000 women who began use of HRT at age 50 and used it for 5, 10, and 15 years, respectively, are estimated to be 2 (95% CI 1-3), 6 (3-9), and 12 (5-20). Whether HRT affects mortality from breast cancer is not known. Interpretation. The risk of having breast cancer diagnosed is increased in women using HRT and increases with increasing duration of use. This effect is reduced after cessation of use of HRT and has largely, if not wholly, disappeared after about 5 years. These findings should be considered in the context of the benefits and other risks associated with the use of HRT.

BackgroundNocturnal enuresis has been reported in patients taking clozapine, but the incidence has not been accurately established. The incidence of enuresis in patients taking risperidone, olanzapine or quetiapine is unknown.AimsTo compare nocturnal enuresis in patients taking clozapine with that in patients taking risperidone, olanzapine or quetiapine.MethodObservational cohort study using prescription event monitoring methods. Patients prescribed atypical antipsychotic medicines were followed up by questionnaires that were sent to their medical practitioner. Practitioners were asked to directly ask their patients about bed-wetting.ResultsNocturnal enuresis was reported by 17 of 82 (20.7%) patients taking clozapine, 11 of 115 (9.6%) taking olanzapine, 7 of 105 (6.7%) taking quetiapine and 12 of 195 (6.2%) taking risperidone. Compared with clozapine, the risk of nocturnal enuresis was significantly lower in patients taking olanzapine (odds ratio, OR = 0.43, 95% CI 0.19–0.96), quetiapine (OR = 0.33, 95% CI 0.13–0.59) or risperidone (OR = 0.27, 0.12–0.59), with odds ratios adjusted for age, gender and duration of treatment.ConclusionsApproximately one in five patients prescribed clozapine experienced bed-wetting. This was significantly higher than the rate of nocturnal enuresis in patients taking olanzapine, quetiapine or risperidone.

Circumcision has been reported to protect against infection with human papillomavirus (HPV) in men, but results have been inconsistent. We followed males in a birth cohort born in Dunedin, New Zealand, in 1972 and 1973 from age 3 to 32 years. Seropositivity at age 32 years for the oncogenic types HPV-16 and 18, and the nononcogenic types 6 and 11, was studied in relation to maternal reports of circumcision status at age 3 for 450 men. Seropositivity to any of these types was associated with lifetime number of sexual partners (P = 0.03), and lower moral-religious emphasis of the family of origin (P < 0.001). Circumcision was not found to be protective, with the adjusted odds ratio (95% confidence interval) for HPV6/11/16/18 seropositivity among the circumcised compared with the uncircumcised being 1.4 (0.89-2.2). (Cancer Epidemiol Biomarkers Prev 2009;18(1):177–83)

The associations of body piercing with other social characteristics, personality, and sexual behavior were investigated in a population-based sample of young adults, in light of the theory that body piercing has meaning in terms of a corporeal expression of the self. At age 26 years, 966 (95%) of 1019 members of the birth-cohort of the Dunedin Multidisciplinary Health and Development Study were asked about body piercing (at interview) and sexual behavior (questions presented by computer). Assessment of personality traits was conducted at ages 18 or 21 years. In total, 183 participants (9% of the men and 29% of the women) had piercings at a site other than the earlobes. People who lived outside New Zealand or who were of Maori descent were more likely to be pierced, but unemployment and low occupational status were not significantly related to piercing. Women who were pierced, compared with those without piercings, were more likely to have personality traits of low constraint or high negative emotionality. Women with piercings were also more likely to report having had, during the previous year, five or more heterosexual partners (odds ratio, 5.8, 95% CI: 2.3-14.6) or any same-sex partner involving genital contact (odds ratio, 10.3, CI: 2.9-37.2). The associations with sexual behavior in men were weaker and not statistically significant. In this population, body piercing in women was associated with sexual behavior. Having multiple heterosexual partners or any same-sex partner was very rare among women without piercings. The theory of meaning for body piercing was generally supported, offering the possibility of a richer understanding of this phenomenon in the general population.

SummaryAlthough long-distance air travel is commonly regarded as a risk factor for venous thromboembolism, the risk of clinically important events has not been well defined. We estimated the absolute risk of dying from pulmonary embolism following longdistance air travel in a national population-based descriptive study of 121 men and women who were aged 15–59 years (the age range in which the majority of international arrivals are found) and whose underlying cause of death was certified as codes 415.1, 451, or 453 of the International Classification of Diseases (ninth revision). Eleven cases had undertaken longdistance air travel in the four weeks before the onset of the fatal episode. The estimated risks of fatal pulmonary embolism following a flight of at least three hours’ duration were 0.5 (95% CI 0.2–1.2) and 0.6 (95% CI 0.2–1.4) per million arrivals for overseas visitors and New Zealand residents, respectively. For air travel of more than eight hours’ duration, the risk in New Zealand residents was 1.3 (95% CI 0.4–3.0) per million arrivals. We also conducteda case-control study based on those cases who were normally resident in New Zealand and registered on the electoral roll (n=99). For each case, four controls matched for sex, age, and electorate, were randomly selected from the electoral roll. In the key analysis (based on 88 cases and 334 controls), the adjusted odds ratio for travellers who had flown for more than eight hours was 7.9 (95% CI 1.1–55.1) compared with those who did not undertake a long-distance flight. Longdistance air travellers have a higher risk of dying from pulmonary embolism than non-travellers, but the absolute risk in people aged 15–59 years appears to be very small.

Objective: To investigate the use of digital rectal examination and prostate specific antigen (PSA) testing in a population-based sample of men in New Zealand. Methods: A random selection of men aged 40–74 years, weighted by age, was chosen from the general electoral roll of New Zealand. Only men with a telephone who had been married at some time were eligible. Telephone interviews were conducted using a standard questionnaire. Crude and age-adjusted proportions were calculated. Logistic regression was used to explore associations between socio-demographic factors and digital rectal examination or PSA testing. Results: Interviews were completed for 85% of the 1,486 eligible men and analyses were confined to the 1,225 European men. Many more men reported having a digital rectal examination (41%; 95% CI 33.8–48.2) than a PSA test (9%; 95% CI 4.2–14.2). Men in the lowest social class were significantly less likely to have had a digital rectal examination (OR 0.30; 95% CI 0.18–0.50) or PSA test (OR 0.25; 95% CI 0.11–0.60) compared with those in the highest social class. Men with vocational training or no post-school qualifications were approximately half as likely to report a digital rectal examination or a PSA test compared with men with degrees or diplomas. Conclusions: Although current New Zealand recommendations are that population screening for prostate cancer should not be introduced, many men are still having digital rectal examinations and PSA tests in the absence of symptoms. The frequency of PSA testing is considerably lower than in Australia and appears to be largely influenced by a man's social class.

Toxicological studies and clinical trials cannot be expected to predict all important adverse effects of medicines and contraceptives. Post-marketing surveillance is essentially an epidemiological task that involves detecting associations between drugs and events. The first alerts about drug safety problems have often come from case reports, but epidemiological studies are needed to confirm adverse (or beneficial) effects and to provide quantitative information. This article illustrates methodological principles by considering three examples from the field of contraceptive safety: oral contraceptives and breast cancer, intrauterine contraception and pelvic inflammatory disease, and newer oral contraceptives and venous thromboembolism. Key issues that emerge include bias and confounding, the place of subgroup analyses, random error, and the use of computerized databases. In research on contraceptive and drug safety, conclusions usually need to be based on careful assessment of multiple observational studies.

Breast cancer is more common in Maori than in non-Maori women under the age of 40 years and is equally common in older women, despite Maori being generally of lower socioeconomic status and having had a higher fertility rate than non-Maori.Data from a nationwide population-based case-control study of breast cancer in New Zealand women aged 25-54 years were used to compare the age-adjusted distribution of reproductive and other risk factors for breast cancer in self-identified Maori and non-Maori women from the control group. Separate analyses also were carried out for women aged 25-39 years and for those aged 40-54 years. The risk of breast cancer according to the proportion of Maori ancestry was estimated using multiple logistic regression simultaneously adjusting for several risk factors.Significant differences were found between self-identified Maori and non-Maori women in the age-adjusted frequencies for education level, socioeconomic status, age at first full-term pregnancy, parity, and duration of breastfeeding; the profile in all instances suggesting a lower risk of breast cancer for Maori than for non-Maori. There were no significant differences with respect to age at menarche, surgery for benign breast disease or a family history of breast cancer. Significantly more Maori than non-Maori were in the highest quartile of recent body mass index. Women self-identified as Maori has an approximately twofold higher risk of breast cancer than non-Maori women.Maori have high rates of breast cancer despite having a more favourable profile than non-Maori for most identified risk factors.National statistics collected in New Zealand since the mid-1960s have identified higher rates of breast cancer in Maori women under 40 years of age than their non-Maori counterparts, despite their low socioeconomic status and high fertility. Data from a nationwide population-based case-control study of breast cancer in New Zealand women 25-54 years of age were used to compare the age-adjusted distribution of reproductive and other risk factors for breast cancer in self-identified Maori (n = 89) and non-Maori women (n = 1771) from the control group. Compared with women with no Maori ancestors, women 25-39 years old with at least half Maori ancestry had a two-fold higher risk of breast cancer after adjustment for known risk factors (odds ratio, 2.2; 95% confidence interval, 1.2-4.2). However, when data from the control group were analyzed, Maori women had a significantly more favorable profile in terms of breast cancer risk than their non-Maori counterparts in terms of education level, socioeconomic status, age at first full-term pregnancy, parity, and duration of breast feeding. The only exception to this pattern was body mass index. 62.1% of Maori controls 25-54 years old, compared with 23.1% of their non-Maori counterparts, were in the highest quartile of recent body mass index (p 0.001). The excess of breast cancer in young Maori may reflect unknown genetic factors that increase susceptibility.

A nationwide case-control study was conducted in New Zealand, to test hypotheses about the role of infections in the aetiology of childhood leukaemia. Children aged 0–14 years with leukaemia were matched on age and sex to controls selected from birth records. Case ascertainment was virtually complete and 121 (92%) of 131 eligible case families took part. The participation rate among the 303 first-choice eligible controls was 69%. Home interviews and serological tests were conducted. Adjusted relative risks were estimated by logistic regression. There was an increased risk of leukaemia in relation to reported influenza infection of the child during the first year of life (adjusted odds ratio 6.8, 95% confidence interval 1.8–25.7). This could be a chance finding due to multiple comparisons, and it should be tested elsewhere. Some key variables relevant to Greaves' hypothesis were not associated with B-cell precursor acute lymphoblastic leukaemia (numbers of infections and vaccinations, firstborn status, attendance at preschool groups), although a small effect could not be ruled out with a study of this size. Leukaemia risk was higher among children in poorer social circumstances, and this was true for all eligible children as well as for the participants. © 1999 Cancer Research Campaign

Objectives: To assess childhood cancer risks for electromagnetic field (EMF) exposures. Methods: A case-control study was conducted in New Zealand. Cases (aged from zero to 14 years) were ascertained from national databases including the New Zealand Cancer Registry; 303 took part (participation rate, 88 percent). The 303 age- and gender-matched controls were selected randomly from birth records (participation, 69 percent). Mothers were interviewed about appliance exposures (all cases and controls), and 24-hour residential measurements of EMFs were made (leukemia cases and matched controls). Results: For the various appliance exposures, there were some odds ratios (OR) above 1.0 and others below 1.0. For electric blanket use by the child before diagnosis, the adjusted ORs were: leukemia, 2.2 (95 percent confidence interval [CI] = 0.7-6.4); central nervous system cancers, ORs = 1.6 (CI = 0.4-7.1); and other solid cancers, OR = 2.4 (CI = 1.0-6.1). Leukemia risk was increased for the highest category of the mean measured bedroom magnetic field (≥ 0.2 µT cf < 0.1 µT), with an adjusted OR of 15.5 (CI = 1.1-224). A gradient in OR with exposure was not shown (middle category: OR 1.4, CI = 0.3-7.6), and there was no association with exposure categorized into thirds based on controls' exposure. The adjusted OR for leukemia in relation to the measured daytime room magnetic field (≥ 0.2 µT cf < 0.1 µT) was 5.2 (CI = 0.9-30.8). Conclusions: This was a small study and multiple comparisons were made. The positive findings thus should be interpreted cautiously. Cancer Causes and Control 1998, 9, 299-309

A national population-based case-control study was used to assess the influence on breast cancer risk of a family history of the disease and the possibility of an interaction with reproductive risk factors. A total of 891 women aged 25-54 years with a first diagnosis of breast cancer and 1,864 control subjects randomly selected from the electoral rolls were interviewed. Age-adjusted relative risks (RR) of breast cancer were similar for mothers (RR = 2.3) and sisters (RR = 2.7) but somewhat higher for first-degree (RR = 2.6) than for second-degree (RR = 1.7) relatives. Cases reporting a first- or second-degree relative with breast cancer were no more likely to be diagnosed at an early age than those with no family history. With regard to the age at diagnosis of the relative, the RR was higher if breast cancer had been diagnosed before the age of 45 years than later; this was true for first-degree as well as for second-degree relatives. In women with no family history, the falling RRs with increasing age at menarche reflected the usual pattern, but no such trend was apparent in those reporting a mother or sister with breast cancer. For age at first full-term pregnancy, parity, breast-feeding, menopausal status, infertility, history of benign breast disease and body mass index, no evidence was seen of effect modification by a family history of breast cancer. Mothers of cases had about twice the cumulative rate of breast cancer as mothers of controls, a similar difference being seen between sisters of cases and sisters of controls.

The effect of oral contraceptive (OC) use at older ages on the risk of breast cancer was examined in a national population-based case-control study conducted in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer, and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk (RR) of breast cancer for women aged 45 to 54 years at diagnosis who had ever used OCs was 1.0 (95 percent confidence interval [CI] = 0.77-1.3). There was no significant increase in risk of breast cancer among recent users of OCs of any age. Analyses according to age at first and last use among women aged 40 years and older at diagnosis showed no group with an elevated risk of breast cancer. Women who had used OCs for 10 years or longer after age 40 had an apparent increase in risk (RR = 2.7, CI = 0.97-7.5), but the trend in risk with duration of use was not significant. These findings suggest that OC use in older women does not affect their risk of breast cancer appreciably, but it is not possible to rule out a modest increase in risk with such use.

Monthly injectable contraceptives, containing a combination of a long-acting progestogen and an estrogen, have been used in Latin America and China for many years. While knowledge about the effects of other hormonal contraceptives on cancer risk is relevant, close analogies with monthly injectables cannot be made. The relation between use of these preparations and cancers of the breast and cervix has been examined in case-control studies, but no firm conclusions can be drawn because of limitations in sample size. Adequate studies of the influence of monthly injectable contraceptives on risk of neoplasia need to be carried out.Monthly injectable contraceptives containing long-acting progestogen and estrogen have been used in Latin America and China for many years. In Mexico and some other Latin American countries, several proprietary preparations containing dihydroxyprogesterone acetophenide and estradiol enanthate are available, with injections often administered by pharmacists. It is estimated that in the early 1980s more than one million ampoules per year were sold privately through pharmacies in Mexico. A large body of evidence exists, however, about the relationship between oral contraceptives and, to a lesser extent, DMPA and the risk of various tumors. The nature of the relationship between using the above monthly preparations and the risk of breast and cervical cancer remains to be determined. Toxicological studies in animals have proved to be of limited value in predicting the effects of contraceptive steroids on cancer risk in humans, but results have nonetheless delayed the introduction of monthly injectables in the US and other developed countries. The only studies which have examined associations between the use of monthly injectable contraceptives and cancer risk in women have been handicapped by limitations in sample size. There is clearly a significant and urgent need to conduct studies on the influence of monthly injectable contraceptives on the risk of cancer.

A retrospective cohort study was performed in 1063 women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (previously termed carcinoma in situ- CIS) in the National Women's Hospital, Auckland, New Zealand. The study describes the clinical management and outcomes for women with CIN3 diagnosed in the decade of 1965-1974, when treatment with curative intent was withheld in an unethical clinical study of the natural history of CIS. A comparison is made with women who were diagnosed earlier (1955-1964) and later (1975-1976).The aim of the study is to record the medical encounters, frequency and management of cytological abnormalities and the occurrence of invasive cancers. The medical records, cytology and histopathology were reviewed and data linked with cancer and death registers.Women diagnosed with CIN3 in 1965-1974 (n = 422), compared with those diagnosed earlier (n = 385) or later (n = 256): (i) were less likely to have initial treatment with curative intent (51% vs 95 and 85%, respectively); (ii) had more follow-up biopsies (P0.0005); (iii) were more likely to have positive cytology during follow-up (P0.005) and positive smears that were not followed within six months by a treatment with curative intent (P0.005); and (iv) experienced a higher risk of cancer of the cervix or vaginal vault (RR = 3.3 compared with the first period, 95% CI: 1.7-5.3). Among women diagnosed in 1965-1974, those initially managed by punch or wedge biopsy alone had a cancer risk ten times (95% CI: 3.9-25.7) higher than women initially treated with curative intent.During the 'clinical study' (1965-1974), women underwent numerous interventions that were aimed to observe rather than treat their condition, and their risk of cancer was substantially increased.

STUDY OBJECTIVE--The aim was to estimate the likely burden of cervical cancer in New Zealand over the next two decades, according to whether cervical screening services are made more effective. DESIGN--The study was based on national mortality and incidence data for the periods 1954-87 and 1954-86, respectively. An age-period-cohort model was used to estimate the contributions of age, time period, and birth cohort effects to the occurrence of cervical cancer. Using age specific estimates of the future female population of New Zealand, projections of cervical cancer mortality and incidence until the year 2008 were derived from the model. Projections were made assuming either that screening services will not be improved, or that an immediate improvement in the organisation of screening will lead to a decline in period effects for incidence of 15% per five year time period (with a slightly delayed effect on mortality). It was also assumed either that the risk in new birth cohorts will be similar to that in recent cohorts, or that their risk will be halved as a result of changes in sexual behaviour (due to education about AIDS or other factors). Combining these assumptions produced four sets of estimates, reflecting a range of possible scenarios. SETTING--Both the data used and the projections obtained related to the entire population of New Zealand women. MAIN RESULTS--For both mortality and incidence, projections were made of age specific rates, cumulative rates, and absolute numbers of deaths or new cases. With the first assumption about new birth cohorts, it was estimated that both mortality and incidence rates will increase if screening services are are not improved. In absolute terms, the present 100 deaths per year could increase to about 148 deaths per year, while there could be a much larger increase in incidence from 235 per year to about 440 per year). With improved screening, there could be a reduction in age specific mortality rates and a modest decline in the number of deaths, while a reduction in incidence rates would be accompanied by about the same number of new cases as at present. In comparison with improvements in screening, changes in the underlying risk in new birth cohorts would have much smaller effects on the occurrence of cervical cancer over the next two decades. CONCLUSIONS--Plausible improvements in cervical screening are likely to be accompanied by only small changes in the burden of cervical cancer over the next two decades. If screening services are not improved, however, there will be striking increases in both mortality and incidence.

Summary Background The invasive potential of cervical intraepithelial neoplasia 3 (CIN3; also termed stage 0 carcinoma) has been poorly defined. At the National Women's Hospital, Auckland, New Zealand, treatment of CIN3 was withheld from a substantial number of women between 1965 and 1974 as part of an unethical clinical study. The resulting variation in management allows comparison of the long-term risk of invasive cancer of the cervix in women whose lesion was minimally disturbed with those who had adequate initial treatment followed by conventional management. We aimed to estimate the long-term risk of invasive cancer in these two groups of women. A judicial inquiry referred for independent clinical review in 1988 all women for whom there remained doubt about the adequacy of their management. Methods Between February, 2001, and December, 2004, medical records, cytology, and histopathology were reviewed for all women with CIN3 diagnosed between 1955 and 1976, whose treatment was reviewed by judicial inquiry and whose medical records could be located, and linkages were done with cancer and death registers and electoral rolls. To take into account the probability that the CIN3 lesion had been completely removed, we classified adequacy of treatment by type of procedure, presence of CIN3 at the excision margin, and subsequent cytology. The primary outcome was cumulative incidence of invasive cancer of the cervix or vaginal vault. Follow-up continued until death or Dec 31, 2000, whichever came first. Analyses accounted for procedures during follow-up. Findings 1229 women whose treatment was reviewed by the judicial inquiry in 1987–88 were included. Of these, 48 records (4%) could not be located and 47 women (4%) did not meet the inclusion criteria. At histopathological review, a further 71 (6% of 1134) women were excluded because the review diagnosis was not CIN3. We identified outcomes in the remaining 1063 (86% of 1229) women diagnosed with CIN3 at the hospital in 1955–76. In 143 women managed only by punch or wedge biopsy, cumulative incidence of invasive cancer of the cervix or vaginal vault was 31·3% (95% CI 22·7–42·3) at 30 years, and 50·3% (37·3–64·9) in the subset of 92 such women who had persistent disease within 24 months. However, cancer risk at 30 years was only 0·7% (0·3–1·9) in 593 women whose initial treatment was deemed adequate or probably adequate, and whose treatment for recurrent disease was conventional. Interpretation This study provides the most valid direct estimates yet available of the rate of progression from CIN3 to invasive cancer. Women with untreated CIN3 are at high risk of cervical cancer, whereas the risk is very low in women treated conventionally throughout. Funding Cancer Society of New Zealand, Wellington, New Zealand.

Background An earlier case-control study from Western Australia reported a protective effect of maternal folic acid supplementation during pregnancy on the risk of childhood acute lymphoblastic leukaemia (ALL). The present study tested that association. Methods A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy. Results There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR) 1.1, 95% confidence interval (CI) 0.5–2.7). Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8–1.1). Conclusion Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.

The International Collaboration of Epidemiological Studies of Cervical Cancer has combined individual data on 11,161 women with invasive carcinoma, 5,402 women with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of full-term pregnancies, and age at first full-term pregnancy, were calculated conditioning by study, age, lifetime number of sexual partners and age at first sexual intercourse. Number of full-term pregnancies was associated with a risk of invasive cervical carcinoma. After controlling for age at first full-term pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76 (95% CI: 1.53-2.02) for > or => or =7 full-term pregnancies compared with 1-2. For CIN3/carcinoma in situ, no significant trend was found with increasing number of births after controlling for age at first full-term pregnancy among parous women. Early age at first full-term pregnancy was also associated with risk of both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling for number of full-term pregnancies, the RR for first full-term pregnancy at age or => or =25 years was 1.77 (95% CI: 1.42-2.23) for invasive cervical carcinoma, and 1.78 (95% CI: 1.26-2.51) for CIN3/carcinoma in situ. Results were similar in analyses restricted to high-risk human papilloma virus (HPV)-positive cases and controls. No relationship was found between cervical HPV positivity and number of full-term pregnancies, or age at first full-term pregnancy among controls. Differences in reproductive habits may have contributed to differences in cervical cancer incidence between developed and developing countries.

Statutory notification of cancer in New Zealand provided an opportunity to investigate risk factors for prostate cancer in a large national population-based case-control study. We analyzed data obtained from telephone interviews with 923 cases and 1,224 controls. For inclusion in the study, all subjects had to have been married at some time. We found an increased risk of prostate cancer among those with a history of prostate cancer in first degree relatives (RR 2.6; 95% CI, 1.9-3.7) and an increased risk of prostate cancer with length of marriage among men married only once and still married at interview. For a consecutive subgroup of 550 cases and 819 controls, data on height and weight at age 20 and at 5 years before interview were collected. Men less than or equal to 1.7 m in height at age 20 years had a lower risk of prostate cancer than men taller at that age. There was no association between weight or body mass index and risk of prostate cancer.

Purpose To examine the association between the use of psychotropic drugs and fatal pulmonary embolism. Methods We conducted a national case-control study of fatal pulmonary embolism. Cases were 75 New Zealand men and women aged 15–59 years who died between 1 January 1990 and 31 December 1998, where the underlying cause of death was certified as codes 415.1, 451 or 453 of the International Classification of Diseases (9th Revision). Four controls, matched for sex and age, were selected from the general practice to which each case had belonged. Information was abstracted from the records of general practitioners, family planning clinics and psychiatric services. Odds ratios and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. The key analyses were restricted to cases (n = 62) and controls (n = 243) without major risk factors for venous thromboembolism. Results Compared to non-use, the adjusted odds ratio for current use of antipsychotic drugs was 13.3 (95% CI: 2.3–76.3). Low potency antipsychotics appeared to carry the highest risk (odds ratio: 20.8 [95% CI: 1.7–259.0]). The main drug involved was thioridazine. The odds ratio for current use of antidepressants was also increased, at 4.9 (95% CI: 1.1–22.5). Conclusions Our results for conventional antipsychotics are consistent with previous studies of non-fatal venous thromboembolism. The finding for antidepressants needs to be replicated in other studies. Copyright © 2003 John Wiley & Sons, Ltd.

Objective: To assess the financial impact of childhood cancer on families. Methods: This was a cross-sectional survey of parents caring for children who were diagnosed with cancer during the period 1990−1993. Self-administered questionnaires were completed by the parents of 237 children from throughout New Zealand with different types of cancer. Dollar amounts were adjusted to the equivalent of December 2000. Results: Eighty-six per cent of the 192 living children were well or in remission. A further 45 children had died. The average extra amount spent, because of the child's illness, by the family of a living child in the 30 days prior to participation in the study was NZ$220 (SD NZ$330). On average, this was 13% of the family income after tax. After reported entitlement to compensation from various sources was allowed for, families were left with a mean deficit of NZ$157 (SD NZ$278) for the 30 days. Twelve families had a shortfall of more than NZ$500, including three families that had a shortfall of more than NZ$1000. Expenditure was greater for those whose children spent more time in hospital (P = 0.003). There was no significant association between the total cost and the distance travelled to the treatment centre (P = 0.96). For 24 families, after-tax income in the month prior to participation in the study was at least NZ$500 lower than it had been in the month before the child's diagnosis. Thirty-seven per cent of families reported that they needed to borrow money because of the financial effects of the child's illness. Bereaved parents spent an average of NZ$3065 (SD NZ$2168) on funeral expenses. Conclusion: There is a large financial burden on families who have a child with cancer.

OBJECTIVE--To determine whether the prevalence of HIV infection among injecting drug users in New Zealand has remained low since the introduction of a needle and syringe exchange scheme in May 1988. DESIGN--Anonymous survey of intravenous drug users attending outlets of the exchange scheme, based on questionnaires and saliva testing. SETTING--Twelve pharmacies and community outreach organisation in six cities. SUBJECTS--Altogether 620 people provided saliva specimens and completed questionnaires. These represented 73% of those who visited exchange scheme outlets during a three month period in 1992. MAIN OUTCOME MEASURE--Saliva was tested for antibodies to HIV-1 and HIV-2 using an IgG-capture enzyme linked immunosorbent assay (GACELISA). RESULTS--Of 591 specimens eligible for inclusion, only three (0.5%) were repeatedly reactive in the GACELISA test, while two of these were also positive in a Western blot test. CONCLUSIONS--Although surveys show that sharing of needles and syringes was common in New Zealand until recently, the prevalence of HIV infection in intravenous drug users has remained low. This can probably be attributed to the success of educational campaigns and legislative action to allow a needle and syringe exchange scheme to be set up.

ContextVasectomy is a common method of contraception, but concern exists about a reported association with risk of prostate cancer.ObjectiveTo examine whether vasectomy increases risk of prostate cancer.Design, Setting, and ParticipantsNational population-based case-control study of 923 new cases of prostate cancer among men aged 40 to 74 years from the New Zealand Cancer Registry who were on the general electoral roll. Controls (n = 1224) were randomly selected from the general electoral roll, with frequency matching to cases in 5-year age groups. Cases (3-15 months after diagnosis) and controls were interviewed by telephone between January 1997 and November 1999.Main Outcome MeasuresRelative risk (RR) of prostate cancer for men who had had a vasectomy vs those who had not.ResultsThere was no association between prostate cancer and vasectomy (RR, 0.92; 95% confidence interval [CI], 0.75-1.14) nor with time since vasectomy (RR, 0.92; 95% CI, 0.68-1.23 for ≥25 years since vasectomy). Adjustment for social class, geographic region, religious affiliation, and a family history of prostate cancer did not affect these RRs.ConclusionsVasectomy does not increase the risk of prostate cancer, even after 25 years or more.

In a national case-control study of fatal pulmonary embolism in New Zealand women of childbearing age, we estimated that current users of combined oral contraceptives had a relative risk of 9.6 (95% CI 3.1-29.1). From national distribution data, the absolute risk of death from pulmonary embolism in current users was estimated to be 10.5 per million woman-years.This national case-control study examined relative risk of fatal pulmonary embolism in childbearing-aged New Zealand women who use combined oral contraceptives (OCs). A total of 36 cases were identified from deaths between January 1990 and August 1998. Information about medical and contraceptive histories from the group practice and any family planning clinic records, were obtained by the same approach for cases and controls. Overall, it was estimated that users of combined OCs had a relative risk of 9.6 (95% confidence interval, 3.1-29.1). However, from the national distribution data, the absolute risk of death from pulmonary embolism in users was estimated to be 10.5 (6.2-16.6) per million woman-years. This death rate was higher than expected, because the annual incidence of venous thromboembolism in OC users has been estimated at 1 or 2 per 10,000 women, with a case fatality rate of only 1-2%. Given these findings, the authors concluded that deaths from pulmonary embolism are rare among OC users, but the absolute risk should still be considered as clinically important and significant to public health.

Breast cancer is the most common malignancy affecting women, and its incidence has been increasing in many countries. The aetiology of breast cancer is poorly understood, so there is concern as to which factors in our environment or lifestyle are responsible for the increase. There is a need for reliable risk assessment, which involves the steps of hazard identification, hazard evaluation, exposure evaluation and risk estimation. Short-term laboratory tests and long-term tests in animals are useful for priority-setting, but quantitative human risk assessment should preferably involve observations of humans. Epidemiological studies vary in the degree of reliance that can be placed on their results. The main types of epidemiological investigation are illustrated by recent examples from the literature on breast cancer. Careful judgement is required in assessing whether any association between a factor and a disease is likely to be causal. The injectable contraceptive, depot medroxyprogesterone acetate (DMPA, ‘Depo-Provera’), has been controversial because it caused malignant mammary tumours in beagle dogs. Two recent case-control studies found no overall association between DMPA and the risk of breast cancer in women. There was some evidence of increased risk in certain sub-groups of women, which could be interpreted with more confidence if there were a better understanding of the biology of human breast cancer. Nevertheless, the results do not support the prediction from beagle experiments that DMPA might increase the overall risk of breast cancer.

Controversy is an inevitable element of medical progress, but sometimes it degenerates into doubtful disputations. During the 1950s, as evidence mounted about the exceptionally strong association between smoking and lung cancer, ingenious theories were advanced about bias or confounding in the epidemiological studies. Sir Ronald Fisher, the renowned statistician, described the notion that cigarettes can cause lung cancer as “a catastrophic and conspicuous howler.” 1 It is small wonder that consensus is slow to develop about much weaker associations between drugs (or contraceptives) and adverse events. A recently completed trial in the English High Court raises the question of whether the judicial process can help us reach sensible conclusions. The action was brought against three pharmaceutical companies by women who believed they had been harmed by third generation oral contraceptives. In October 1995, the United Kingdom's Committeeon Safety of Medicines announced that such contraceptives (containing desogestrel or gestodene) carried a higher risk of venous thromboembolism than older formulations (containing levonorgestrel).Controversy raged for several years and, although the evidence has convinced many expert bodies—including a scientific group at the World Health Organization2 and the European Agency for the Evaluation of Medicinal Products3—the manufacturers and their …

This editorial discusses cofactors in the link between human papillomavirus (HPV) and cervical cancers. It notes that in this issue of the Lancet scientists associated with the International Agency for Research on Cancer (IARC) report their analysis of two of these cofactors parity and oral contraceptives. Both reports involve the pooling of data from case-control studies of invasive cervical cancer or carcinoma-in-situ from four continents. It was found that hormonal contraception for fewer that 5 years did not increase risk for cervical cancer but women reporting use of hormonal contraceptives for 5-9 years were found to have 2.8 times the risk of women who had never used them. The relative risk estimate was even higher (4.0) for those who had used such contraceptives for 10 years of longer. In addition the results reported by IARC are consistent with previous studies that suggested that high parity and long-term oral contraception are risk factors for cervical cancer.

General practice p 1190 Three months ago a paper in the BMJ analysed the incidence of venous thromboembolism before and after the warning from the UK Committee on Safety of Medicines about third generation oral contraceptives.1 Using computer records of general practitioners, Farmer et al found that the incidence among pill users had not dropped, and they concluded that their findings were not compatible with a doubling of risk in women using third generation contraceptives (compared with older preparations). Their paper received wide publicity because it called into question an emerging consensus about this issue.2 This week's BMJ contains another analysis of computer records from British general practice, conducted by a group in Boston (p 1190).3 Jick et al found that, both before and after the warning in October 1995, the risk of venous thromboembolism in women using third generation oral contraceptives was about twice that in users of preparations containing levonorgestrel. Moreover, fewer cases occurred after the warning than would have been expected if the prescribing of oral contraceptives had not changed. What is remarkable is that these two studies, reporting opposite conclusions, both used the same General Practice Research Database.4 …

Oral contraception is effective, convenient, and reversible. For most women it is also remarkably safe. Some people involved in family planning go further and imply that the oral contraceptive pill is almost free of risk. This creates an illusion that is shattered whenever adverse effects—however rare—are brought to light. In October 1995 the Committee on Safety of Medicines in the United Kingdom warned that oral contraceptives containing desogestrel or gestodene carried a small increase in risk of venous thromboembolism compared with older preparations. The chaos that followed in Britain (and a few other countries) may have stemmed partly from an illusion of absolute safety, as well as from the publicity triggered by the warning. The committee's announcement was followed by the publication of four well designed studies that gave a consistent picture: women using third generation oral contraceptives containing desogestrel or gestodene had about twice the risk of venous thromboembolism of women using preparations containing levonorgestrel.1 In the four years that have followed, a plethora of articles, reviews, and symposiums have implied that these reports were flawed and that reanalyses or new studies show no differences in the risk of …

In a national case-control study, 891 New Zealand women aged 25 to 54 with newly diagnosed breast cancer were compared with 1,864 control subjects selected at random from the electoral rolls. The relative risk of breast cancer for current drinkers of alcohol, compared with women who had never drunk alcohol, was 1.0 (95% confidence interval 0.64 to 1.7). For ex-drinkers the relative risk was 1.3 (95% confidence interval 0.74 to 2.5). Women drinking up to 14 drinks per week had no increase in risk, while the relative risk in those consuming more than 14 drinks per week was 1.8 (95% confidence interval 0.87 to 3.8). There was no evidence of effect modification by age at diagnosis, menopausal status, body mass index, or any of the other variables examined. While these results provide little support for the hypothesis that moderate alcohol consumption increases the risk of breast cancer, they are not inconsistent with the weak associations that have been found in many other studies. Possible explanations for such a relationship are considered.

A nationwide case-control study of childhood leukaemia in New Zealand included measurements of electric and magnetic fields in children's homes. There was no significant association between leukaemia and the time-weighted average of the 50 Hz magnetic or electric fields in the bedroom and living (or daytime) room combined.

A national population-based case-control study was conducted in New Zealand to assess the effects of hormonal contraception on breast-cancer risk. A total of 891 women aged 25 to 54 with a first diagnosis of breast cancer, and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk of breast cancer for women who had ever used oral contraceptives was 1.0 (95% confidence interval 0.82-1.3). There was no increase in risk with duration of use, even among women who had continued to use oral contraceptives for 14 or more years (relative risk = 1.1, 95% confidence interval 0.78-1.7). The risk of breast cancer was not increased by use of oral contraceptives for long periods before the first pregnancy or by starting use at a young age. Parity, age at menarche, family history of breast cancer, or history of benign breast disease did not modify the effect of oral contraceptives on breast-cancer risk. Relative risk estimates were slightly, although not significantly, increased during the first few years after starting oral contraception and in women under 35 years of age at diagnosis.A national population-based case-control study was conducted in New zealand to assess the effects of hormonal contraception of breast cancer risk. A total of 891 women ages 25-54 with a 1st diagnosis of breast cancer and 1864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk of breast cancer for women who had ever used oral contraceptives (OCs) was 1.0 (95% confidence interval 0.82-1.3). There was no increase in risk with duration of use, even among women who had continued to use OCs for 14 or more years (relative risk=1.1, 95% confidence interval 0.78-1.7). The risk of breast cancer was not increased by use of OCs for long periods before the 1st pregnancy or by beginning with OCs at a young age. Parity, age at menarche, family history of breast cancer, or history of benign breast disease did not modify the effect of OCs on breast cancer risk. Relative risk estimates were slightly, although not significantly, increased during the 1st few years after initiating use of OCs and in women under age 35 at diagnosis.

General practice p 96 Oral contraceptives have been studied more intensively than any other medication in history. Yet the recent brouhaha about third generation oral contraceptives and venous thromboembolism is only the latest in a series of “pill scares” over more than three decades. For some mysterious reason these periodic crises have been a particular feature of Britain; during the 1980s, for example, false alarms about major effects on breast cancer risk created greater consternation in Britain than elsewhere. While the British media have often produced more heat than light, scientists in Britain have contributed more than their share of evidence about the safety of oral contraceptives. One project that has become a landmark of epidemiology is the Royal College of General Practitioners' oral contraception study, and this week sees another publication from the study (p 96).1 In 1968Dr Clifford Kay and his colleagues persuaded 1400general practitioners to enrol 46000 women (half of whom were using oral contraceptives at the time) into a follow up study. Meticulous observations over many years have produced important information about many health outcomes. 23 In …

An analysis of the transmission dynamics of bovine spongiform encephalopathy (BSE) in Britain provides options for cattle-culling policy. Deciding which option to implement is another matter.

Background. —Although depot medroxyprogesterone acetate (DMPA) (Depo-Provera) has now been approved for marketing as a contraceptive in the United States, there are still unresolved issues about the relation between DMPA and risk of breast cancer. The two substantial case-control studies of this association yielded similar but inconclusive results. Because their designs were compatible, these studies were pooled to obtain more adequate data for analysis. Design. —Pooled results from two case-control studies. Setting. —New Zealand (entire country), Thailand (three centers), Mexico (one center), and Kenya (one center). Participants. —A total of 1768 women with breast cancer and 13905 controls, most of whom were younger than 55 years. Main Outcome Measure. —Relative risk (RR) of breast cancer in women who had used DMPA. Results. —The RR of breast cancer for women who had ever used DMPA was 1.1 (95% confidence interval [CI], 0.97 to 1.4). There was no increase in risk with increasing duration of use of DMPA, but RR estimates were higher in certain subgroups of women. Further analyses suggested that recent (or current) use was the key factor, with women who had started using DMPA within the previous 5 years estimated to have an RR of 2.0 (95% CI, 1.5 to 2.8). Conclusions. —The increased risk of breast cancer observed in recent (or current) users could be due to enhanced detection of breast tumors in women using DMPA or to acceleration of the growth of preexisting tumors. Women who had used DMPA more than 5 years previously had no increase in risk of breast cancer, regardless of their duration of use. (JAMA. 1995;273:799-804)