Safety perspectives on presently considered drugs for the treatment of COVID‐19

Intense efforts are underway to evaluate potential therapeutic agents for the treatment of COVID‐19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm–benefit ratios that may be encountered when treating COVID‐19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life‐threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID‐19

Birth preparation acupuncture for normalising birth: An analysis of NHS service routine data and proof of concept

A number of studies show that acupuncture may help with labour and delivery. An NHS maternity acupuncture service providing birth preparation acupuncture has assessed its routine hospital maternity annual data from 2014 to 2016 to see what effect it had on labour and delivery outcomes. The data from this service was analysed and women who had birth preparation acupuncture were compared with those who did not receive it. Maternal age, parity and socio-economic status were considered confounders and were adjusted for in the analysis. Women who received acupuncture had more normal births (less surgical births) [OR 0.76 (0.64, 0.91)], required less intrapartum analgesia [OR 0.74 (0.63, 0.86)], fewer components of an induction of labour [OR 0.74 (0.61, 0.91)] and a reduced length of a hospital stay [OR 0.91 (0.87, 0.95)]. The patients highly valued the availability of acupuncture within the maternity service as it enhanced their patient journey.Impact statement What is already known on this subject? Numerous studies provide evidence for the effects of acupuncture in normalising pregnancy and birth. These effects include musculoskeletal preparation of the pelvis, cervical ripening, enhancing endogenous oxytocin release, and analgesic properties. What do the results of this study add? Our analysis shows that women who received birth preparation acupuncture had fewer surgical births, required less intrapartum analgesia, less components of induction of labour and had a reduced length of hospital stay, supporting the use of maternity acupuncture in normalising birth outcomes. What are the implications of these findings for clinical practice and/or further research? The findings show that acupuncture, by potentially normalising birth, may lead to reductions in costs of service. Further, additional research is required to see whether acupuncture is cost effective and could have an adjunctive role as a complementary therapy for improving birth outcomes and a woman’s experience of childbirth

Breast cancer in relation to childhood parental divorce and early adult psychiatric disorder in a British birth cohort

Background. Jacobs and Bovasso reported (Psychological Medicine 2000, 30, 669-678) that maternal death in childhood and chronic severe depression in adulthood were associated with subsequent breast cancer. We have examined the effects of parental loss in childhood and psychiatric disorder in adult life on breast cancer risk using a national birth cohort study. Method. Eighty-three cases of breast cancer were diagnosed in a study of 2253 women followed from birth to age 59 years. Cox proportional hazards models were used to test whether breast cancer rates were higher in women who experienced parental death and divorce before age 16, psychiatric disorders between 15 and 32 years, symptoms of anxiety and depression at 36 years, or use of antidepressant medication at 31 or 36 years than in women who did not have these experiences. Results. There was no overall association between parental death, parental divorce or psychiatric disorder and the incidence of breast cancer. There was some evidence that women with more severe psychiatric disorders between the ages of 15 and 32 years were more likely to develop breast cancer early. The interaction between parental divorce and severe psychiatric disorder was non-significant (p = 0.1); however, the group who experienced both these events had an increased breast cancer risk compared with those who experienced neither [hazard ratio (HR) 2-64, 95 % confidence interval (CI) 1.13-6.19]. Conclusions. Our study does not provide strong support for the hypothesis that early loss or adult psychiatric disorders are associated with breast cancer. A meta-analysis is needed that uses data from all available cohort studies and investigates possible interactive effects on breast cancer ris

Natural selection of human embryos: impaired decidualization of endometrium disables embryo-maternal interactions and causes recurrent pregnancy loss

BackgroundRecurrent pregnancy loss (RPL), defined as 3 or more consecutive miscarriages, is widely attributed either to repeated chromosomal instability in the conceptus or to uterine factors that are poorly defined. We tested the hypothesis that abnormal cyclic differentiation of endometrial stromal cells (ESCs) into specialized decidual cells predisposes to RPL, based on the observation that this process may not only be indispensable for placenta formation in pregnancy but also for embryo recognition and selection at time of implantation.Methodology/Principal FindingsAnalysis of mid-secretory endometrial biopsies demonstrated that RPL is associated with decreased expression of the decidual marker prolactin (PRL) but increased levels of prokineticin-1 (PROK1), a cytokine that promotes implantation. These in vivo findings were entirely recapitulated when ESCs were purified from patients with and without a history of RPL and decidualized in culture. In addition to attenuated PRL production and prolonged and enhanced PROK1 expression, RPL was further associated with a complete dysregulation of both markers upon treatment of ESC cultures with human chorionic gonadotropin, a glycoprotein hormone abundantly expressed by the implanting embryo. We postulated that impaired embryo recognition and selection would clinically be associated with increased fecundity, defined by short time-to-pregnancy (TTP) intervals. Woman-based analysis of the mean and mode TTP in a cohort of 560 RPL patients showed that 40% can be considered “superfertile”, defined by a mean TTP of 3 months or less.ConclusionsImpaired cyclic decidualization of the endometrium facilitates implantation yet predisposes to subsequent pregnancy failure by disabling natural embryo selection and by disrupting the maternal responses to embryonic signals. These findings suggest a novel pathological pathway that unifies maternal and embryonic causes of RPL.<br/