Prescribing during pregnancy and lactation with reference to the Swedish classification system

Aim. To assess the current prescribing pattern for 15,756 primiparae before, during, and after their pregnancies with reference to fetal and neonatal risk. Method. A prescription database study with linkage to The Danish Medical Birth Registry from 1991 to 1996. The drug subsidy system in Danish retail pharmacies, made it possible to identify prescriptions by individual use. All 34,334 prescriptions were set against the Swedish classification of risk of drug use in pregnancy and lactation. Results. During pregnancy, safe (group A), potentially harmful (group B3, C, and D), and non-classifiable drugs accounted for 40.9%, 26.6% and 28.7% respectively. The proportion of women who redeemed drugs was 29.2%, 8.6%, 18.7% and 0.9% from drug groups A, B, C and D respectively. The proportion of prescriptions from high risk groups declined during the course of pregnancy. Postpartum safe drugs (group I and II), drugs with possible harmful neonatal effects (group III), and non-classifiable drugs accounted for 43.5%, 4.8%, and 35.8% of the prescriptions, respectively. Conclusion. According to the Swedish classification system, we found that during pregnancy and lactation a high proportion of Danish women were exposed to one or more drugs in high risk groups; furthermore, knowledge regarding their safety for the fetus and neonate was limited for a large proportion of the prescriptions. Current evidence about long-term effects of prenatal exposure stresses the need for long-term follow-up of health and development among exposed children

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT)

Objectives: The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT). Methods: Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years. Results: As of May 2020, 296 patients have been randomized at 20 centers in Denmark. Conclusion: The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF

High-resolution palaeoclimatology of the last millennium: A review of current status and future prospects

This review of late-Holocene palaeoclimatology represents the results from a PAGES/CLIVAR Intersection Panel meeting that took place in June 2006. The review is in three parts: the principal high-resolution proxy disciplines (trees, corals, ice cores and documentary evidence), emphasizing current issues in their use for climate reconstruction; the various approaches that have been adopted to combine multiple climate proxy records to provide estimates of past annual-to-decadal timescale Northern Hemisphere surface temperatures and other climate variables, such as large-scale circulation indices; and the forcing histories used in climate model simulations of the past millennium. We discuss the need to develop a framework through which current and new approaches to interpreting these proxy data may be rigorously assessed using pseudo-proxies derived from climate model runs, where the 'answer' is known. The article concludes with a list of recommendations. First, more raw proxy data are required from the diverse disciplines and from more locations, as well as replication, for all proxy sources, of the basic raw measurements to improve absolute dating, and to better distinguish the proxy climate signal from noise. Second, more effort is required to improve the understanding of what individual proxies respond to, supported by more site measurements and process studies. These activities should also be mindful of the correlation structure of instrumental data, indicating which adjacent proxy records ought to be in agreement and which not. Third, large-scale climate reconstructions should be attempted using a wide variety of techniques, emphasizing those for which quantified errors can be estimated at specified timescales. Fourth, a greater use of climate model simulations is needed to guide the choice of reconstruction techniques (the pseudo-proxy concept) and possibly help determine where, given limited resources, future sampling should be concentrated