David C. G. Skegg

Minor tranquillisers and road accidents

In a prospective study of 43,117 people, prescriptions issued by general practitioners over two years were linked with records of hospital admissions and deaths. For 57 people injured or killed while driving cars, motorcycles, or bicycles the medicines that had been dispensed in the three months before were compared with those dispensed for 1,425 matched controls. There was a highly significant association between use of minor tranquillisers and the risk of a serious road accident (relative risk estimate 4.9). the increased risk of accidents to drivers given tranquillisers could be due to the known psychomotor effects of these drugs or to effects of the conditions being treated. Whatever the reason, patients taking drugs such as diazepam should be warned that they are at special risk.

Cervical carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies.

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 ≥≥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 <17 years compared with ≥≥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.

Infections, vaccinations, and the risk of childhood leukaemia.

SummaryA 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.

IMPORTANCE OF THE MALE FACTOR IN CANCER OF THE CERVIX

A womans risk of cervical cancer is generally thought to be related to her sexual behaviour. The sexual background of her male partners is also important. In some societies, a womans risk of cancer of the cervix will depend less on her own behaviour than on that of her partner. Male sexual behaviour, particularly in relation to prostitution, may account for two hitherto unexplained features of the epidemiology of this disease--the extremely high incidence in Latin America and the decline in mortality this century. If this is so and men carry the aetiological agent, it will be important to discover whether they do so for short or long periods.

Depot medroxyprogesterone acetate: Patterns of use and reasons for discontinuation

Little information is available from outside clinic settings about the acceptability of depot medroxyprogesterone acetate (DMPA, Depo-Provera) as an injectable contraceptive. In this national, population-based study, New Zealand women aged 25 to 54 years were selected at random from voter rolls. The 1864 subjects were interviewed by telephone after an initial approach by letter. More than 1 in 8 women (13.7%) had used DMPA at some time. The proportion was higher among Maori women and among those of lower income and education, but DMPA had been used by a substantial proportion of all socioeconomic groups. A quarter of all users reported receiving only a single injection of DMPA, and only 53% had used this method for a total of 12 months or more. Only 5 (1.6%) of discontinuations were attributed to contraceptive failure; this corresponds to a contraceptive failure rate of 0.9 per 100 woman-years. Side effects were given as the most common reasons for stopping, with menstrual disturbances and weight gain being cited most often. Other reasons for stopping included no further need for contraception or doubts about the appropriateness of DMPA. In this developed country population, DMPA is widely used for short periods but its acceptability is limited by the occurrence of side effects.

Oral contraceptives and fatal pulmonary embolism.

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.

Oral contraceptives and breast cancer: a national study.

In a population based case-control study 433 New Zealand women aged 25-54 with newly diagnosed breast cancer were compared with 897 women selected at random from the electoral rolls. The relative risk of breast cancer in women who had ever used oral contraceptives was 0.94 (95% confidence interval 0.70 to 1.25). The relative risk in women aged 25-34 at diagnosis was estimated to be 2.2 (95% confidence interval 0.47 to 9.9) and in older women less than 1. Analyses of risk by duration of use of oral contraceptives, age at first use, and time since first use showed no adverse effect of the pill. In particular, there was no increased risk in women who had used oral contraceptives before the age of 25 or before their first pregnancy, even for prolonged periods. Given the high prevalence of use in New Zealand, this study provides strong evidence against the hypothesis that use of oral contraceptives at young ages increases the risk of breast cancer.

Economic effects of childhood cancer on families.

Objective:  To assess the financial impact of childhood cancer on families.

Impact of childhood cancer on the mental health of parents

BACKGROUND When a child is diagnosed with cancer, the family experiences great stress and disruption to daily life. As part of a national study in New Zealand, we evaluated the mental health of mothers and fathers of children with cancer, making comparisons to parents of children from the general population. PROCEDURE This was a cross-sectional study. All children diagnosed with cancer at ages 0-14 years in New Zealand during a defined period were ascertained from the national cancer registry and other databases. The population-based comparison children were selected using national birth records. Parents from both groups completed self-administered questionnaires containing the General Health Questionnaire (GHQ-12) and other measures. The analyses included 218 mothers and 179 fathers of children with cancer, and 266 mothers and 224 fathers of children in the comparison group. Multivariate regression was used to adjust for demographic and socioeconomic characteristics, life events, and social support. RESULTS Mothers and fathers of children with cancer had poorer GHQ-12 and mood rating scores than those of controls. The adjusted difference in the mean total GHQ-12 score (comparing mothers of children with cancer to mothers of controls) was 2.2 (95% confidence interval 1.3-3.2). The 12 items of the GHQ were each scored 0-3, and the total score was the sum, so 2 points is a small difference. For fathers the difference was 1.5 (95% confidence interval 0.6-2.4). Some subgroups of cancer group parents had poorer emotional health scores than others, including those with poor social support and no paid employment and also those who were bereaved. CONCLUSIONS We found statistically significant but small differences between the mental health of parents of children with cancer and controls. The small differences suggest that as a group the parents of children with cancer are relatively resilient.

Depot medroxyprogesterone (Depo-Provera) and risk of breast cancer.

OBJECTIVE--To determine whether use of the injectable contraceptive depot medroxyprogesterone acetate (Depo-Provera) affects the risk of breast cancer in women. DESIGN--A population based case-control study. SETTING--Nationwide community study. SUBJECTS--891 Women aged 25-54 with newly diagnosed breast cancer were compared with 1864 women selected at random from the electoral rolls. INTERVENTION--Women were interviewed by telephone about past use of contraceptives and about possible risk factors for breast cancer. MAIN OUTCOME MEASURE--Relative risk of breast cancer in women who had used medroxyprogesterone. RESULTS--Medroxyprogesterone had been used by 110 patients and 252 controls. Overall, the relative risk of breast cancer associated with any duration of use was 1.0 (95% confidence interval 0.80 to 1.3). In women aged 25-34 the relative risk was 2.0 (1.0 to 3.8). The relative risk was highest in women aged 25-34 who had used the drug for six years or longer, although there were few women in this category. Women who had used it for two years or longer before age 25 had an increased risk of breast cancer (relative risk 4.6; 1.4 to 15.1). CONCLUSION--Despite the lack of an overall association these findings suggest that medroxyprogesterone may increase the risk of breast cancer in young women.