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Background Exposure to high doses of ionizing radiation is among the few well-established brain tumour risk factors. We used data from the Interphone study to evaluate the effects of exposure to low-dose radiation from diagnostic radiological examinations on glioma, meningioma and acoustic neuroma risk. Methods Brain tumour cases (2644 gliomas, 2236 meningiomas, 1083 neuromas) diagnosed in 2000–02 were identified through hospitals in 13 countries, and 6068 controls (population-based controls in most centres) were included in the analysis. Participation across all centres was 64% for glioma cases, 78% for meningioma cases, 82% for acoustic neuroma cases and 53% for controls. Information on previous diagnostic radiological examinations was obtained by interviews, including the frequency, timing and indication for the examinations. Typical brain doses per type of examination were estimated based on the literature. Examinations within the 5 years before the index date were excluded from the dose estimation. Adjusted odds ratios were estimated using conditional logistic regression. Results No materially or consistently increased odds ratios for glioma, meningioma or acoustic neuroma were found for any specific type of examination, including computed tomography of the head and cerebral angiography. The only indication of an elevated risk was an increasing trend in risk of meningioma with the number of isotope scans, but no such trends for other examinations were observed. No gradient was found in risk with estimated brain dose. Age at exposure did not substantially modify the findings. Sensitivity analyses gave results consistent with the main analysis. Conclusions There was no consistent evidence for increased risks of brain tumours with X-ray examinations, although error from selection and recall bias cannot be completely excluded. A cautious interpretation is warranted for the observed association between isotope scans and meningioma.

The influence of pregnancy in multiple sclerosis has been a matter of controversy for a long time. The Pregnancy in Multiple Sclerosis (PRIMS) study was the first large prospective study which aimed to assess the possible influence of pregnancy and delivery on the clinical course of multiple sclerosis. We report here the 2-year post-partum follow-up and an analysis of clinical factors which might predict the likelihood of a relapse in the 3 months after delivery. The relapse rate in each trimester up to the end of the second year post-partum was compared with that in the pre-pregnancy year. Clinical predictors of the presence or absence of a post-partum relapse were analysed by logistic regression analysis. Using the best multivariate model, women were classified as having or not having a post-partum relapse predicted, and this was compared with the observed outcome. The results showed that, compared with the pre-pregnancy year, there was a reduction in the relapse rate during pregnancy, most marked in the third trimester, and a marked increase in the first 3 months after delivery. Thereafter, from the second trimester onwards and for the following 21 months, the annualized relapse rate fell slightly but did not differ significantly from the relapse rate recorded in the pre-pregnancy year. Despite the increased risk for the 3 months post-partum, 72% of the women did not experience any relapse during this period. Confirmed disability continued to progress steadily during the study period. Three indices, an increased relapse rate in the pre-pregnancy year, an increased relapse rate during pregnancy and a higher DSS (Kurtzke's Disability Status Scale) score at pregnancy onset, significantly correlated with the occurrence of a post-partum relapse. Neither epidural analgesia nor breast-feeding was predictive. When comparing the predicted and observed status, however, only 72% of the women were correctly classified by the multivariate model. In conclusion, the results for the second year post-partum confirm that the relapse rate remains similar to that of the pre-pregnancy year, after an increase in the first trimester following delivery. Women with greater disease activity in the year before pregnancy and during pregnancy have a higher risk of relapse in the post- partum 3 months. This is, however, not sufficient to identify in advance women with multiple sclerosis who are more likely to relapse, especially for planning therapeutic trials aiming to prevent post-partum relapses.

In the context of a prospective assessment of exposure for epidemiology, our objective is to obtain an optimal group-based design of allocation of a fixed total number of measurements. Such a design has been described by Ashford [Ashford JR. (1958) The design of a long-term sampling programme to measure the hazard associated with an industrial environment. J R Statist Soc A; 121: 331-47]. As this strategy is not operational, we developed three series of strategies: the first based on simplifications of Ashford's strategy; the second based on a pilot study; and the third on an iterative assessment of the group specific standard deviation of exposure. These strategies are compared by simulating a day-to-day individual exposure in several industrial sites and the resulting health effect. Our criteria for comparing strategies are the mean squared error of the estimated exposure in each group weighted by the number of subjects and the mean squared error of the estimated linear regression coefficient in the dose-response relationship. Strategies relying on an iterative approach have been found to perform best whatever the circumstances, nearly as well as Ashford's optimal strategy.