Prescribers’ perceptions of benefits and limitations of direct acting oral anticoagulants in non-valvular atrial fibrillation.

Background: There is an acknowledged lack of robust and rigorous research focusing on the perspectives of those prescribing direct acting oral anticoagulants (DOACs) for non-valvular atrial fibrillation (AF). Objective: The objective was to describe prescribers’ experiences of using DOACs in the management of non-valvular AF, including perceptions of benefits and limitations. Methods: A cross-sectional survey of prescribers in a remote and rural area of Scotland. Among other items, the questionnaire invited free-text description of positive and negative experiences of DOACs, and benefits and limitations. Responses were independently analysed by two researchers using a summative content analysis approach. This involved counting and comparison, via keywords and content, followed by interpretation and coding of the underlying context into themes. Results: One hundred and fifty-four responses were received, 120 (77.9%) from physicians, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 unidentified professions). Not having to monitor INR was the most cited benefit, particularly for prescribers and patients in remote and rural settings, followed by potentially improved patient adherence. These benefits were reflected in respondents’ descriptions of positive experiences and patient feedback. The main limitations were the lack of reversal agents, cost and inability to monitor anticoagulation status. Many described their experiences of adverse effects of DOACs including fatal and non-fatal bleeding, and upper gastrointestinal disturbances. Conclusions: While prescribers have positive experiences and perceive benefits of DOACs, issues such as adverse effects and inability to monitor anticoagulation status merit further monitoring and investigation. These issues are particularly relevant given the trajectory of increased prescribing of DOACs

Prescribers' views and experiences of using direct acting oral anticoagulants in the management of nonvalvular atrial fibrillation: a survey in remote and rural Scotland.

A recent systematic review highlighted the lack of robust studies on prescribers' perspectives of direct-acting oral anticoagulants (DOACs) for non-valvular atrial fibrillation (AF). The aim was to determine prescribers' views and experiences of prescribing DOACs. A cross-sectional survey of prescribers in a remote and rural area of Scotland. Survey items were: demographics; prescribing of DOACs; views of potential influences on DOAC prescribing; knowledge of prescribing guidelines; and experiences. Items on potential influences were based on the Theoretical Domains Framework (TDF). Data were analysed using descriptive and inferential statistics, and content analysis of responses to open questions. Principal component analysis (PCA) was performed on the items of potential influences. One hundred and fifty-four responses were received, 120 (77.9%) from doctors, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 missing). PCA of the TDF items of potential influences gave four components. Component scores for (i) role of professionals, their knowledge and skills and (ii) influences on prescribing were positive. Those for (iii) consequences of prescribing and (iv) monitoring for safety and effectiveness were more neutral. There were low levels of agreement for statements relating to DOACs being more effective, safer and cost-effective than warfarin. There were similar responses around the complexity of bleeding management and detection of over and under-anticoagulation. This study has identified several key issues of DOAC prescribing (e.g. bleeding management) hence further emphasis is required in continuing professional development and during guideline implementation and evaluation

Healthcare professional and patient views, behaviours and experiences surrounding novel oral anticoagulants (NOACs) for the management of non-valvular atrial fibrillation (AF): a systematic review protocol.

While there is a wealth of evidence on aspects such as efficacy, effectiveness, cost-effectiveness and safety, there is less evidence on the use of NOACs in clinical practice. A scoping search of MEDLINE for the years 2007-2015 has identified a number of relevant primary research. However, to date, no systematic reviews of health professional or patient views, behaviours and experiences have been published. Furthermore, a search of the Cochrane Collaboration, the Centre for Reviews and Dissemination and the Joanna Briggs Institute did not identify any registered systematic review protocols focusing on these aspects. To achieve optimal benefit and outcomes comparable to those observed in clinical trials, it is essential that NOACs are used appropriately by health professionals and patients. The evidence generated through systematic review will provide a robust and rigorous evidence base around appropriate use and hence best possible patient outcomes

Measuring Individual Material Well-Being Using Multidimensional Indices: An Application Using the Gender and Generation Survey for Russia

This paper suggests a new and comprehensive approach to the assessment of the material well-being at the individual level by constructing a multidimensional index. Using this approach, material well-being is understood as a generic notion that covers a number of different domains, whereas the concept of domain is used to distinguish between different aspects of people’s resources, including income security, basic needs, durables, housing and subjective material well-being. Each dimension is measured independently, using the best indicators available, to generate a score or domain index for each aspect of material well-being. The procedure of re-weighting the indicators within the separate domains enables us to account for the disparity in resources and consumer preferences across different population subgroups. The final domain scores, combined with explicit weighting, are then used to generate a summary material well-being index. The domain indices and the summary material well-being index are validated by exploring their relationships to key socio-economic attributes, which were previously shown to be strongly associated with individual material well-being. The results showed that the summary indices of material well-being are characterized by greater differentiation in relation to such measures, as occupational class and judgments of satisfaction with one’s life. This allows us to conclude that our summary indices capture the latent concept of material well-being better than any of our domain indices used separately. Although the index is constructed using the Russian Gender and Generation Survey data for 2007, the methodological approach that we applied can be easily replicated in other surveys which contain information on several aspects of material well-being

The pig X and Y Chromosomes: structure, sequence, and evolution.

We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution.This work was funded by BBSRC grant BB/F021372/1. The Flow Cytometry and Cytogenetics Core Facilities at the Wellcome Trust Sanger Institute and Sanger investigators are funded by the Wellcome Trust (grant number WT098051). K.B., D.C.-S., and J.H. acknowledge support from the Wellcome Trust (WT095908), the BBSRC (BB/I025506/1), and the European Molecular Biology Laboratory. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 222664 (“Quantomics”).This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via http://dx.doi.org/10.1101/gr.188839.11

Effect of Acute Plasmodium falciparum Malaria on Reactivation and Shedding of the Eight Human Herpes Viruses

Human herpes viruses (HHVs) are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno-compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8). We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0) and 14 days later (after treatment), or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria

The auxin-regulated CrRLK1L kinase ERULUS controls cell wall composition during root hair tip growth

Root hairs facilitate a plant’s ability to acquire soil anchorage and nutrients. Root hair growth is regulated by the plant hormone auxin and dependent on localized synthesis, secretion and modification of the root hair tip cell wall. However, the exact well wall regulators in root hairs controlled by auxin have yet to be determined. In this study, we describe the characterization of ERULUS (ERU), an auxin-induced Arabidopsis receptor-like kinase whose expression is directly regulated by ARF7 and ARF19 transcription factors. ERU belongs to the Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE (CrRLK1L) subfamily of putative cell wall sensor proteins. Imaging of a fluorescent fusion protein revealed that ERU is localized to the apical root hair plasma membrane. ERU regulates cell wall composition in root hairs and modulates pectin dynamics through negative control of pectin methylesterase (PME) activity. Mutant eru (-/-) root hairs accumulate de-esterified homogalacturonan and exhibit aberrant pectin Ca²⁺ binding site oscillations and increased PME activity. Up to 80% of the eru root hair phenotype is rescued by pharmacological supplementation with a PME inhibiting catechin extract. ERU transcription is altered in specific cell wall-related root hair mutants, suggesting it is a target for feedback regulation. Loss of ERU alters the phosphorylation status of FERONIA and H⁺-ATPases 1/2, regulators of apoplastic pH. Furthermore, H⁺-ATPases 1/2 and ERU are differentially phosphorylated in response to auxin. We conclude that ERULUS is a key auxin-controlled regulator of cell wall composition and pectin dynamics during root hair tip growth

School-based prevention for adolescent Internet addiction: prevention is the key. A systematic literature review

Adolescents’ media use represents a normative need for information, communication, recreation and functionality, yet problematic Internet use has increased. Given the arguably alarming prevalence rates worldwide and the increasingly problematic use of gaming and social media, the need for an integration of prevention efforts appears to be timely. The aim of this systematic literature review is (i) to identify school-based prevention programmes or protocols for Internet Addiction targeting adolescents within the school context and to examine the programmes’ effectiveness, and (ii) to highlight strengths, limitations, and best practices to inform the design of new initiatives, by capitalizing on these studies’ recommendations. The findings of the reviewed studies to date presented mixed outcomes and are in need of further empirical evidence. The current review identified the following needs to be addressed in future designs to: (i) define the clinical status of Internet Addiction more precisely, (ii) use more current psychometrically robust assessment tools for the measurement of effectiveness (based on the most recent empirical developments), (iii) reconsider the main outcome of Internet time reduction as it appears to be problematic, (iv) build methodologically sound evidence-based prevention programmes, (v) focus on skill enhancement and the use of protective and harm-reducing factors, and (vi) include IA as one of the risk behaviours in multi-risk behaviour interventions. These appear to be crucial factors in addressing future research designs and the formulation of new prevention initiatives. Validated findings could then inform promising strategies for IA and gaming prevention in public policy and education