Pharmacovigilance in hospice/palliative care: rapid report of net clinical effect of metoclopramide

Background: Understanding the performance of prescribed medications in day-to-day practice is important to minimize harm, maximize clinical benefits, and, eventually, better target the people who are most likely to benefit, especially in hospice/palliative care where there may be limited time to optimize prescribing. Metoclopramide, a benzamide prokinetic antiemetic, is widely used for a number of indications including nausea, vomiting, hiccups, and reflux. It has recently had a new ‘‘black box’’ warning issued by the Food and Drug Administration in relation to tardive dyskinesia to limit use to 12 weeks. Methods: A consecutive cohort of patients from 12 participating centers in two countries who were having metoclopramide initiated had data collected at three time points—baseline, 2 days (clinical benefit), and day 7 (clinical harm). Additionally, harms could be recorded at any time. Results: Of the 53 people included in the cohort, 23 (43%) reported benefit at 48 hours, but only 18 (34%) of these people were still using it one week after commencing it. For the other 5, the medication was ceased due to harms. The most frequent harms were akathisia (n = 4), headache (n = 4), and abdominal pain (n = 4). Nine people (17%) had no clinical benefit and experienced harms. Conclusion: Overall, one in three people gained net clinical benefit at one week. Limiting effects include sideeffects that need to be sought actively in clinical care

Computer simulation of defect clusters in UO2 and their dependence on composition

AbstractIt is recognised that point defects play a key role in the behaviour and properties of many technologically significant oxides. What is less well understood is how these defects cluster together and, crucially, the extent to which the clusters change with composition. We chose to investigate this phenomenon by considering UO2, a nuclear fuel material for which there is contradictory data in the literature concerning defect clustering as a function of oxygen content. Early studies of fluorite UO2+x proposed a model based on 2:2:2 Willis clusters whilst more recent research suggests cuboctahedral or split quad-interstitial defect clustering. Here we use the PBE+U functional to simulate defective UO2+x and find for 0.125<x<0.25, chains of edge-sharing 2:2:2 Willis clusters to be most stable. Below x=0.125 these chains destabilise, transforming in to split di-interstitial clusters, demonstrating that the type of oxygen cluster present is dependent on local environment and stoichiometry

Purified and specific cytoplasmic pollen extract: a non-hormonal alternative for the treatment of menopausal symptoms

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin (R). This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin (R) in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin (R), an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin (R) may also be a suitable option for the management of menopausal symptoms in women with breast cancer

Defect segregation facilitates oxygen transport at fluorite UO₂ grain boundaries

Data support article accepted for publication in Philosophical Transactions A. Data includes inputs and outputs for molecular dynamics simulations. Where impractical simulations can be rerun from the inputs provided

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome : a prospective randomized multinational study

BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. METHODS: Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. RESULTS: Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95 confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. CONCLUSIONS: Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.peer-reviewe

The disappearance and reappearance of optical emission lines and the drop in a Swift/XRT count rate during the recent rebrightening of TCP J21040470+4631129

We report the results of our continuing optical and X-ray monitoring of the bright WZ Sge-type dwarf nova TCP J21040470+4631129 (hereafter TCP2104) discovered on July 12, 2019 (for previous reports, see ATel #12947, #13009). Our optical photometric observations are mostly performed using 30-cm class telescopes, while spectroscopic data are obtained with the 2.1-m telescope at the OAN-SPM, the 2.5-m Isaac Newton Telescope on La Palma, and other smaller telescopes.peer-reviewe

A one-stop perineal clinic: our eleven-year experience.

INTRODUCTION AND HYPOTHESIS: The perineal clinic is a dedicated setting offering assessment for various childbirth-related presentations including obstetric anal sphincter injuries (OASIs), perineal wound complications, pelvic floor dysfunction and other conditions such as female genital mutilation(FGM). We describe the clinical presentation and outcomes of women from a tertiary perineal clinic based on data collected over an 11-year period. METHODS: This is a retrospective observational study. A one-stop outpatient service was offered to all women who sustained OASIs (postnatally and antenatally in a subsequent pregnancy), perineal complications (within 16 weeks postpartum), FGM and/or peripartum symptoms of urinary/anal incontinence or prolapse. Assessment included history with validated questionnaires, examination and anal manometry and endoanal ultrasound when appropriate. Outcomes were compared among different grades of OASIs. Management of each type of presentation was reported with outcomes. RESULTS: There were 3254 first attendance episodes between 2006 and 2016. The majority (58.1%) were for OASIs, followed by perineal wound complications. Compared to the lower grades, the higher grades of OASI were associated with poorer outcomes in terms of symptoms, investigations and complications. Women with OASIs had unrelated symptoms such as urinary incontinence, perineal pain and wound infections that needed further intervention. A high proportion(42%) of wound complications required further specialist management. CONCLUSION: We describe a dedicated, one-stop perineal clinic model for antenatal and postnatal women for management of perineal and pelvic floor disorders. This comprehensive and novel data will enable clinicians to better counsel women regarding of outcomes after OASI and focus training to minimize risks of morbidities