Drug interactions and pharmacogenetic factors contribute to variation in apixaban concentration in atrial fibrillation patients in routine care

Factor Xa-inhibitor apixaban is an oral anticoagulant prescribed in atrial fibrillation (AF) for stroke prevention. Its pharmacokinetic profile is known to be affected by cytochrome P450 (CYP)3A metabolism, while it is also a substrate of the efflux transporters ATP-binding cassette (ABC)B1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein, BCRP). In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2, ABCB1, CYP3A4*22, CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average 77.2 years old, 85.5 kg, and had a serum creatinine of 103.1 µmol/L. Concomitant amiodarone, an antiarrhythmic agent and moderate CYP3A/ABCB1 inhibitor, the impaired-function variant ABCG2 c.421C \u3e A, and sex predicted higher apixaban concentrations when controlling for age, weight and serum creatinine (multivariate regression; R2 = 0.34). Our findings suggest that amiodarone and ABCG2 genotype contribute to interpatient apixaban variability beyond known clinical factors

Virtual wobble spaces: A pilot study of the outcomes of online therapeutic spaces on practitioner well-being and social work practice

Stress, emotional exhaustion and job dissatisfaction have been prevailing issues in social work for decades, with recent research by BASW demonstrating poor psychological outcomes for social workers, amidst inadequate levels of staff retention and high burn out rates. The Covid-19 pandemic added to these existing stresses, with social workers experiencing multiple losses, including bereavements and changes to working practices. As a response to the pandemic, many hospitals and health care settings established bespoke wobble spaces, dedicated to enhancing staff well-being. However, despite the reported success of these wobble spaces, results from a literature review show that they have not been established within social work. The pilot study discussed in this article explored and evaluated the impacts of a virtual wobble space provided for social workers over three months at fortnightly intervals. The research design was purposefully creative and aimed at focussing on positivity and fun as a counter to much of the existing literature on stress and burnout in social work. The study is limited by a small sample size but nevertheless the unanimously positive findings and wider interest, suggest there may be a broader role for wobble space provision in social work

Malaria vectors in South America: current and future scenarios

Abstract Background Malaria remains a significant public health issue in South America. Future climate change may influence the distribution of the disease, which is dependent on the distribution of those Anopheles mosquitoes competent to transmit Plasmodium falciparum. Herein, predictive niche models of the habitat suitability for P. falciparum, the current primary vector Anopheles darlingi and nine other known and/or potential vector species of the Neotropical Albitarsis Complex, were used to document the current situation and project future scenarios under climate changes in South America in 2070. Methods To build each ecological niche model, we employed topography, climate and biome, and the currently defined distribution of P. falciparum, An. darlingi and nine species comprising the Albitarsis Complex in South America. Current and future (i.e., 2070) distributions were forecast by projecting the fitted ecological niche model onto the current environmental situation and two scenarios of simulated climate change. Statistical analyses were performed between the parasite and each vector in both the present and future scenarios to address potential vector roles in the dynamics of malaria transmission. Results Current distributions of malaria vector species were associated with that of P. falciparum, confirming their role in transmission, especially An. darlingi, An. marajoara and An. deaneorum. Projected climate changes included higher temperatures, lower water availability and biome modifications. Regardless of future scenarios considered, the geographic distribution of P. falciparum was exacerbated in 2070 South America, with the distribution of the pathogen covering 35-46 % of the continent. As the current primary vector An. darlingi showed low tolerance for drier environments, the projected climate change would significantly reduce suitable habitat, impacting both its distribution and abundance. Conversely, climate generalist members of the Albitarsis Complex showed significant spatial and temporal expansion potential in 2070, and we conclude these species will become more important in the dynamics of malaria transmission in South America. Conclusions Our data suggest that climate and landscape effects will elevate the importance of members of the Albitarsis Complex in malaria transmission in South America in 2070, highlighting the need for further studies addressing the bionomics, ecology and behaviours of the species comprising the Albitarsis Complex

Factors associated with screening positive for high falls risk in fragility fracture patients: a cross-sectional study

Abstract Background We sought to report the prevalence of fragility fracture patients who were screened at high falls risk using a large provincial database, and to determine the characteristics associated with being screened at high falls risk. Methods The study population included fragility fracture patients 50+ years of age who were screened at 35 hospital fracture clinics in Ontario over a 3.5 year period. The outcome was based on two screening questions measuring the risk of falling, both adapted from the STEADI (Stopping Elderly Accidents, Deaths & Injuries) tool. Multivariable associations of sociodemographic, fracture-related, and health-related characteristics were evaluated using logistic regression. Results Of the sample, 9735 (44.5%) patients were classified as being at high falls risk, and 12,089 (55.3%) were not. In the multivariable logistic regression, being 80+ years of age (vs. 50–64 years of age), non-community dwelling (vs. living with spouse, family member, roommate), having a mental/physical impairment (vs. none), and taking multiple medications, were all strongly associated with being screened at high falls risk. Conclusions Living in a non-community dwelling and taking 4+ medications were the variables most strongly associated with being screened at high falls risk. These are potentially modifiable characteristics that should be considered when assessing falls risk in fragility fracture patients, and particularly when designing interventions for preventing subsequent falls. Ongoing work to address the higher risk of falls in the fragility fracture population is warranted

The basement membrane of hair follicle stem cells is a muscle cell niche

SummaryThe hair follicle bulge in the epidermis associates with the arrector pili muscle (APM) that is responsible for piloerection (“goosebumps”). We show that stem cells in the bulge deposit nephronectin into the underlying basement membrane, thus regulating the adhesion of mesenchymal cells expressing the nephronectin receptor, α8β1 integrin, to the bulge. Nephronectin induces α8 integrin-positive mesenchymal cells to upregulate smooth muscle markers. In nephronectin knockout mice, fewer arrector pili muscles form in the skin, and they attach to the follicle above the bulge, where there is compensatory upregulation of the nephronectin family member EGFL6. Deletion of α8 integrin also abolishes selective APM anchorage to the bulge. Nephronectin is a Wnt target; epidermal β-catenin activation upregulates epidermal nephronectin and dermal α8 integrin expression. Thus, bulge stem cells, via nephronectin expression, create a smooth muscle cell niche and act as tendon cells for the APM. Our results reveal a functional role for basement membrane heterogeneity in tissue patterning.PaperCli

Additional file 4: Table S4. of Malaria vectors in South America: current and future scenarios

Description of environmental variables utilized in simulations of future scenarios of the niche model of P. falciparum and Anopheles vectors in South America, 2070. (DOCX 15 kb

Additional file 1: of Malaria vectors in South America: current and future scenarios

Tabular data in Excel Spreadsheet. Anopheles darlingi Occurrence Data. (XLSX 12 kb

Additional file 7: Table S5. of Malaria vectors in South America: current and future scenarios

Relative contribution (%) of environmental variables to predicted values in the MaxEnt algorithm and Boosted Regression Trees (BRT) for each species in South America. (DOCX 16 kb

Additional file 6: Figure S11. of Malaria vectors in South America: current and future scenarios

Environmental variables (bioclimatic data, topographic and terrestrial biomes) under global climate change scenario 2. Sources: the ENES Met Office Hadley Centre [53], the Shuttle Radar Topography Mission [42] and Lapola et al. [31]. (PDF 321 kb