Application of therapeutic drug monitoring to the treatment of bacterial central nervous system infection: a scoping review

BackgroundBacterial central nervous system (CNS) infection is challenging to treat and carries high risk of recurrence, morbidity, and mortality. Low CNS penetration of antibiotics may contribute to poor clinical outcomes from bacterial CNS infections. The current application of therapeutic drug monitoring (TDM) to management of bacterial CNS infection was reviewed.MethodsStudies were included if they described adults treated for a suspected/confirmed bacterial CNS infection and had antibiotic drug concentration(s) determined that affected individual treatment.ResultsOne-hundred-and-thirty-six citations were retrieved. Seventeen manuscripts were included describing management of 68 patients. TDM for vancomycin (58/68) and the beta-lactams (29/68) was most common. Timing of clinical sampling varied widely between studies and across different antibiotics. Methods for setting individual PK-PD targets, determining parameters and making treatment changes varied widely and were sometimes unclear.DiscussionDespite increasing observational data showing low CNS penetration of various antibiotics, there are few clinical studies describing practical implementation of TDM in management of CNS infection. Lack of consensus around clinically relevant CSF PK-PD targets and protocols for dose-adjustment may contribute. Standardised investigation of TDM as a tool to improve treatment is required, especially as innovative drug concentration-sensing and PK-PD modelling technologies are emerging. Data generated at different centres offering TDM should be open access and aggregated to enrich understanding and optimize application

CSF1R+ Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, and most patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma and autochthonous models, with an important functional contribution to the squamous subtype of human PDAC. We targeted macrophages in a genetic PDAC model using AZD7507, a potent selective inhibitor of CSF1R. AZD7507 caused shrinkage of established tumors and increased mouse survival in this difficult-to-treat model. Malignant cell proliferation diminished, with increased cell death and an enhanced T cell immune response. Loss of macrophages rewired other features of the TME, with global changes in gene expression akin to switching PDAC subtypes. These changes were markedly different to those elicited when neutrophils were targeted via CXCR2. These results suggest targeting the myeloid cell axis may be particularly efficacious in PDAC, especially with CSF1R inhibitors

Tmetoceratidae (Ammonitina) fauna from the Gerecse Mts (Hungary)

Abstract Taxonomic and stratigraphic problems of the family Tmetoceratidae and the genera Dumortieria, Catulloceras, Cotteswoldia, Pleydellia and Tmetoceras included in it are briefly discussed. Fifteen species of Tmetoceratidae are described and illustrated from the Upper Toarcian-Aalenian ammonite assemblages of the Gerecse Mts (NE Transdanubian Range, Hungary). The fauna described here is closely allied to the Mediterranean Province of the Mediterranean-Caucasian Realm

Reproductive health and access to healthcare facilities: risk factors for depression and anxiety in women with an earthquake experience

<p>Abstract</p> <p>Background</p> <p>The reproductive and mental health of women contributes significantly to their overall well-being. Three of the eight Millennium Development Goals are directly related to reproductive and sexual health while mental disorders make up three of the ten leading causes of disease burden in low and middle-income countries. Among mental disorders, depression and anxiety are two of the most prevalent. In the context of slower progress in achieving Millennium Development Goals in developing countries and the ever-increasing man-made and natural disasters in these areas, it is important to understand the association between reproductive health and mental health among women with post-disaster experiences.</p> <p>Methods</p> <p>This was a cross-sectional study with a sample of 387 women of reproductive age (15-49 years) randomly selected from the October 2005 earthquake affected areas of Pakistan. Data on reproductive health was collected using the Centers for Disease Control reproductive health assessment toolkit. Depression and anxiety were measured using the Hopkins Symptom Checklist-25, while earthquake experiences were captured using the Harvard Trauma Questionnaire. The association of either depression or anxiety with socio-demographic variables, earthquake experiences, reproductive health and access to health facilities was estimated using multivariate logistic regression.</p> <p>Results</p> <p>Post-earthquake reproductive health events together with economic deprivation, lower family support and poorer access to health care facilities explained a significant proportion of differences in the experiencing of clinical levels of depression and anxiety. For instance, women losing resources for subsistence, separation from family and experiencing reproductive health events such as having a stillbirth, having had an abortion, having had abnormal vaginal discharge or having had genital ulcers, were at significant risk of depression and anxiety.</p> <p>Conclusion</p> <p>The relationship between women's post-earthquake mental health and reproductive health, socio-economic status, and health care access is complex and explained largely by the socio-cultural role of women. It is suggested that interventions that consider gender differences and that are culturally appropriate are likely to reduce the incidence.</p

An oribatid mite (Arachnida: Acari) from the Oxford Clay (Jurassic: Upper Callovian) of South Cave Station Quarry, Yorkshire, UK

A single specimen of a new species of oribatid mite belonging to the genus Jureremus Krivolutsky, in Krivolutsky and Krassilov 1977, previously described from the Upper Jurassic of the Russian Far East, is described as J. phippsi sp. nov. The mite is preserved by iron pyrite replacement, and was recovered by sieving from the Oxford Clay Formation (Jurassic: Upper Callovian) of South Cave, Yorkshire. It is the first record of a pre-Pleistocene mite, and the second species record of the family Cymbaeremaeidae, from the British Isles; also, it is only the third record of Acari from the Jurassic Period. The presence of a terrestrial mite in a sedimentary sequence of open marine origin is noteworthy, and suggestions for its mode of transport to the site of deposition are discussed