Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study

Combined oral contraceptives,oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women.The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47).Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users

Complexities in the palaeoenvironmental and archaeological interpretation of isotopic analyses of the Mud Shell Geloina erosa (Lightfoot, 1786)

Isotope signals derived from molluscan shell carbonates allow researchers to investigate palaeoenvironments and the timing and periodicity of depositional events. However, it cannot be assumed that all molluscan taxa provide equally useful data owing to species-specific biological and ecological traits. The Mud Shell, Geloina erosa (Lightfoot, 1786) (syn. Polymesoda coaxans, syn. Polymesoda erosa), an infaunal mangrove bivalve, is a common component of archaeological deposits along Australia's tropical north coast and throughout the Indo-West Pacific. The ubiquity of G. erosa has led to numerous researchers incorporating this taxon into interpretations of associated deposits, particularly in the generation of radiocarbon chronologies and as a palaeoenvironmental proxy. Despite this, concerns have been expressed regarding the impact of G. erosa physiology and ecology on associated geochemical signals. Adaptations allowing the survival of this species within its highly changeable mangrove environment may introduce complexities into radiocarbon and environmental data archived within its shell. This study combines local environmental and hydrological data with isotopic analysis (δ18O, δ13C, and 14C) of live-collected specimens to explore the interpretability of geochemical proxies derived from G. erosa. Results suggest a number of factors may impact geochemical markers in unpredictable ways, eroding the usefulness of associated interpretations

24-hour human urine and serum profiles of bisphenol A following ingestion in soup: Individual pharmacokinetic data and emographics

AbstractHere we present data to evaluate potential absorption of Bisphenol A through non-metabolizing tissues of the upper digestive tract. Concurrent serum and urine concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were measured over a 24h period in 10 adult male volunteers following ingestion of 30μg d6-BPA/kg body weight in soup. The pharmacokinetic behavior of BPA and its metabolites in this cohort (rapid absorption, complete elimination, evidence against sublingual absorption) was reported. This Data in Brief article contains the corresponding individual pharmacokinetic data, reports the demographics of the cohort and provides additional details related to the analytical methods employed and is related to [4]

Genome scale evolution of myxoma virus reveals host-pathogen adaptation and rapid geographic spread

The evolutionary interplay between myxoma virus (MYXV) and the European rabbit (Oryctolagus cuniculus) following release of the virus in Australia in 1950 as a biological control is a classic example of host-pathogen coevolution. We present a detailed genomic and phylogeographic analysis of 30 strains of MYXV, including the Australian progenitor strain Standard Laboratory Strain (SLS), 24 Australian viruses isolated from 1951 to 1999, and three isolates from the early radiation in Britain from 1954 and 1955. We show that in Australia MYXV has spread rapidly on a spatial scale, with multiple lineages cocirculating within individual localities, and that both highly virulent and attenuated viruses were still present in the field through the 1990s. In addition, the detection of closely related virus lineages at sites 1,000 km apart suggests that MYXV moves freely in geographic space, with mosquitoes, fleas, and rabbit migration all providing means of transport. Strikingly, despite multiple introductions, all modern viruses appear to be ultimately derived from the original introductions of SLS. The rapidity of MYXV evolution was also apparent at the genomic scale, with gene duplications documented in a number of viruses. Duplication of potential virulence genes may be important in increasing the expression of virulence proteins and provides the basis for the evolution of novel functions. Mutations leading to loss of open reading frames were surprisingly frequent and in some cases may explain attenuation, but no common mutations that correlated with virulence or attenuation were identified.This work was funded in part by grant R01 AI093804 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. E.C.H. is funded by an NHMRC Australia Fellowship. D.C.T. is funded by an ARC Future Fellowship

24-hour human urine and serum profiles of bisphenol A: Evidence against sublingual absorption following ingestion in soup

Extensive first-pass metabolism of ingested bisphenol A (BPA) in the gastro-intestinal tract and liver restricts blood concentrations of bioactive BPA to < 1% of total BPA in humans and non-human primates. Absorption of ingested BPA through non-metabolizing tissues of the oral cavity, recently demonstrated in dogs, could lead to the higher serum BPA concentrations reported in some human biomonitoring studies. We hypothesized that the extensive interaction with the oral mucosa by a liquid matrix, like soup, relative to solid food or capsules, might enhance absorption through non-metabolizing oral cavity tissues in humans, producing higher bioavailability and higher serum BPA concentrations. Concurrent serum and urine concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were measured over a 24 hour period in 10 adult male volunteers following ingestion of 30 μg d6-BPA/kg body weight in soup. Absorption of d6-BPA was rapid (t₁/₂ = 0.45 h) and elimination of the administered dose was complete 24 h post-ingestion, evidence against any tissue depot for BPA. The maximum serum d6-BPA concentration was 0.43 nM at 1.6 h after administration and represented < 0.3% of total d6-BPA. Pharmacokinetic parameters, pharmacokinetic model simulations, and the significantly faster appearance half-life of d6-BPA-glucuronide compared to d6-BPA (0.29 h vs 0.45 h) were evidence against meaningful absorption of BPA in humans through any non-metabolizing tissue (< 1%). This study confirms that typical exposure to BPA in food produces picomolar to subpicomolar serum BPA concentrations in humans, not nM concentrations reported in some biomonitoring studies.This is the publisher’s final pdf. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/toxicology-and-applied-pharmacology/Keywords: Pharmacokinetics, Sublingual, Endocrine disruptors, Oral, Bisphenol A, ExposureKeywords: Pharmacokinetics, Sublingual, Endocrine disruptors, Oral, Bisphenol A, Exposur

Percutaneous & Mini Invasive Achilles tendon repair

Rupture of the Achilles tendon is a considerable cause of morbidity with reduced function following injury. Recent studies have shown little difference in outcome between the techniques of open and non-operative treatment using an early active rehabilitation programme. Meta-analyses have shown that non-operative management has increased risk of re-rupture whereas surgical intervention has risks of complications related to the wound and iatrogenic nerve injury. Minimally invasive surgery has been adopted as a way of reducing infections rates and wound breakdown however avoiding iatrogenic nerve injury must be considered. We discuss the techniques and outcomes of percutaneous and minimally invasive repairs of the Achilles tendon

Supportive care for older people with frailty in hospital: An integrative review

BACKGROUND: Growing numbers of older people living with frailty and chronic health conditions are being referred to hospitals with acute care needs. Supportive care is a potentially highly relevant and clinically important approach which could bridge the practice gap between curative models of care and palliative care. However, future interventions need to be informed and underpinned by existing knowledge of supportive care. AIM: To identify and build upon existing theories and evidence about supportive care, specifically in relation to the hospital care of older people with frailty, to inform future interventions and their evaluation. DESIGN: An integrative review was used to identify and integrate theory and evidence. Electronic databases (Cochrane Medline, EMBASE and CIHAHL) were searched using the key term 'supportive care'. Screening identified studies employing qualitative and/or quantitative methods published between January 1990 and December 2015. Citation searches, reference checking and searches of the grey literature were also undertaken. DATA SOURCES: Literature searches identified 2733 articles. After screening, and applying eligibility criteria based on relevance to the research question, studies were subject to methodological quality appraisal. Findings from included articles (n=52) were integrated using synthesis of themes. RESULTS: Relevant evidence was identified across different research literatures, on clinical conditions and contexts. Seven distinct themes of the synthesis were identified, these were: Ensuring fundamental aspects of care are met, Communicating and connecting with the patient, Carer and family engagement, Building up a picture of the person and their circumstances, Decisions and advice about best care for the person, Enabling self-help and connection to wider support, and Supporting patients through transitions in care. A tentative integrative model of supportive care for frail older people is developed from the findings. CONCLUSION: The findings and model developed here will inform future interventions and can help staff and hospital managers to develop appropriate strategies, staff training and resource allocation models to improve the quality of health care for older people

Global phylogeography and ancient evolution of the widespread human gut virus crAssphage

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome

A realistic evaluation of fines for hospital discharges: Incorporating the history of programme evaluations in the analysis

Programmes and policies transform over time and locations. Evaluation projects can apprehend only temporal and contextualized sections of the social world. This article uses a realist evaluation of financial incentives in English hospital discharge policy to illustrate how previous evaluations of the same programme theory were inspected for evidence to construct context, mechanisms and outcomes. Following the discharges of a reduced number of patients with a case study approach, the preliminary programme theory ('fines reduce delays') was modified into a redefined theory on how fines operate locally in practice. This identified other mechanisms contemporaneous to the fines which are more or as likely to reduce delays. This article aims to contribute to the development of the realist evaluation strategy by introducing programme's transformations as key evidence when trying to understand how complex interventions work in particular contexts