PLoS medicine
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In situations of unmet medical need or in the interests of public health, expedited approval pathways, including conditional marketing authorisation (CMA) and accelerated assessment (AA), speed up European Medicines Agency (EMA) marketing authorisation recommendations for medicinal products. CMAs are based on incomplete benefit-risk assessment data and authorisation remains conditional until regulator-imposed confirmatory postmarketing measures are fulfilled. For products undergoing AA, complete safety and efficacy data should be available, and postauthorisation measures may include only standard requirements of risk management and pharmacovigilance plans. In the pivotal trials supporting products assessed by expedited pathways, surrogate endpoints reduce drug development time compared with waiting for the intended clinical outcomes. Whether surrogate endpoints supporting products authorised through CMA and AA pathways reliably predict clinical benefits of therapy has not been studied systematically. Our objectives were to determine the extent to which surrogate endpoints are used and to assess whether their validity had been confirmed according to published hierarchies. ⋯ The pivotal trial evidence supporting marketing authorisations for products granted CMA or AA was based dominantly on nonvalidated surrogate endpoints. EPARs and summary product characteristic documents, including patient information leaflets, need to state consistently the nature and limitations of endpoints in pivotal trials supporting expedited authorisations so that prescribers and patients appreciate shortcomings in the evidence about actual clinical benefit. For products supported by nonvalidated surrogate endpoints, postauthorisation measures to confirm clinical benefit need to be imposed by the regulator on the marketing authorisation holders.
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Observational Study
Progression to type 2 diabetes mellitus and associated risk factors after hyperglycemia first detected in pregnancy: A cross-sectional study in Cape Town, South Africa.
Global data indicate that women with a history of hyperglycemia first detected in pregnancy (HFDP) are at up to 7 times risk of progressing to type 2 diabetes mellitus (T2DM) compared with their counterparts who have pregnancies that are not complicated by hyperglycemia. However, there are no data from the sub-Saharan African region, which has the highest projected rise in diabetes prevalence globally. The aim of this study was to determine the proportion of women who progress to T2DM and associated risk factors 5 to 6 years after HFDP in Cape Town, South Africa. ⋯ The progression to T2DM in women with previous HFDP found in this study highlights the need for interventions to delay or prevent progression to T2DM after HFDP. In addition, interventions to prevent HFDP may also contribute to reducing the risk of T2DM.
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In September's Editorial, Vikram Patel and Pattie Gonsalves discuss suicide prevention, the focus of World Mental Health Day, 2019.
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Policy consensus in high-income countries supports offering pregnant women with previous cesarean section a choice between planning an elective repeat cesarean section (ERCS) or attempting a vaginal birth, known as a planned vaginal birth after previous cesarean (VBAC), provided they do not have contraindications to planned VBAC. However, robust comprehensive information on the associated outcomes to counsel eligible women about this choice is lacking. This study investigated the short-term maternal and perinatal outcomes associated with planned mode of delivery after previous cesarean section among women delivering a term singleton and considered eligible to have a planned VBAC. ⋯ Among women considered eligible to have a planned VBAC, planned VBAC compared to ERCS is associated with an increased risk of the mother having serious birth-related maternal and perinatal complications. Conversely, planned VBAC is associated with an increased likelihood of breastfeeding, whereas the effect on other maternal outcomes differs according to whether a woman has any prior vaginal deliveries and the number of prior cesarean sections she has had. However, the absolute risk of adverse outcomes is small for either delivery approach. This information can be used to counsel and manage the increasing number of women with previous cesarean section, but more research is needed on longer-term outcomes.
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Observational Study
Risk and protective factors for child development: An observational South African birth cohort.
Approximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities. ⋯ This study provides reliable developmental data from a sub-Saharan African setting in a well-characterised sample of mother-child dyads. Our findings highlight not only the important protective effects of maternal education, birth weight, and socioeconomic status for developmental outcomes but also sex differences in developmental outcomes and key risk and protective factors for each group.