Cascade sensitivity measures

In risk analysis, sensitivity measures quantify the extent to which the probability distribution of a model output is affected by changes (stresses) in individual random input factors. For input factors that are statistically dependent, we argue that a stress on one input should also precipitate stresses in other input factors. We introduce a novel sensitivity measure, termed cascade sensitivity, defined as a derivative of a risk measure applied on the output, in the direction of an input factor. The derivative is taken after suitably transforming the random vector of inputs, thus explicitly capturing the direct impact of the stressed input factor, as well as indirect effects via other inputs. Furthermore, alternative representations of the cascade sensitivity measure are derived, allowing us to address practical issues, such as incomplete specification of the model and high computational costs. The applicability of the methodology is illustrated through the analysis of a commercially used insurance risk model

The Magpie Trial: A randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for women at 2 years

Objective: The aim of this study was to assess long-term effects for women following the use of magnesium sulphate for pre-eclampsia. Design: Assessment at 2-3 years after delivery for women recruited to the Magpie Trial (recruitment in 1998-2001, ISRCTN 86938761), which compared magnesium sulphate with placebo for pre-eclampsia. Setting: Follow up after discharge from hospital at 125 centres in 19 countries across five continents. Population: A total of 7927 women were randomised at the follow-up centres. Of these women, 2544 were not included for logistic reasons and 601 excluded (109 at a centre where <20% of women were contacted, 466 discharged without a surviving child and 26 opted out). Therefore, 4782 women were selected for follow-up, of whom 3375 (71%) were traced. Methods: Questionnaire assessment was administered largely by post or in a dedicated clinic. Interview assessment of selected women was performed. Main outcome measures: Death or serious morbidity potentially related to pre-eclampsia at follow up, other morbidity and use of health service resources. Results: Median time from delivery to follow up was 26 months (interquartile range 19-36). Fifty-eight of 1650 (3.5%) women allocated magnesium sulphate died or had serious morbidity potentially related to pre-eclampsia compared with 72 of 1725 (4.2%) women allocated placebo (relative risk 0.84, 95% CI 0.60-1.18). Conclusions: The reduction in the risk of eclampsia following prophylaxis with magnesium sulphate was not associated with an excess of death or disability for the women after 2 years. © RCOG 2006 BJOG An International Journal of Obstetrics and Gynaecology.Articl

The Magpie Trial: A randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months

Objective: To assess the long-term effects of in utero exposure to magnesium sulphate for children whose mothers had pre-eclampsia. Design: Assessment at 18 months of age for children whose mothers were recruited to the Magpie Trial (recruitment 1998-2001 ISRCTN 86938761), which compared magnesium sulphate with placebo. Setting: Follow-up of children born at 125 centres in 19 countries across five continents. Population: A total of 6922 children were born to women randomised before delivery at follow-up centres. Of these, 2271 were not included for logistic reasons and 168 were excluded (101 at a centre where <20% were contacted, 40 whose death or disability was due to a problem at conception or embryogenesis and 27 whose parent/s opted out). Therefore, 4483 children were included in follow-up, of whom 3283 (73%) were contacted. Methods: Assessment by questionnaire, with interview and neurodevelopmental testing of selected children. Main outcome measures: Death or neurosensory disability at age of 18 months. Results: Of those allocated magnesium sulphate, 245/1635 (15.0%) were dead or had neurosensory disability at 18 months compared with 233/1648 (14.1%) allocated placebo (relative risk [RR] 1.06, 95% CI 0.90-1.25), and of survivors, 19/1409 (1.3%) had neurosensory disability at 18 months compared with 27/1442 (1.9%) (RR 0.72, 95% CI 0.40-1.29). There were no substantial differences in causes of death or in the risk of individual impairments or disabilities. Conclusions: The lower risk of eclampsia following prophylaxis with magnesium sulphate was not associated with a clear difference in the risk of death or disability for children at 18 months. © RCOG 2006 BJOG An International Journal of Obstetrics and Gynaecology.Articl