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Arterial stiffness in chronic kidney disease: a modifiable cardiovascular risk factor?
No full textPURPOSE OF REVIEW
There is an inverse, graded relationship between worsening chronic kidney disease (CKD) and increasing cardiovascular risk independent of traditional cardiovascular risk factors. Increasing arterial stiffness is a powerful predictor of cardiovascular outcomes in CKD. Developing novel therapeutic strategies to reverse this process is an attractive concept. This review presents the results of a literature survey of the last 18 months to establish if arterial stiffness can be considered a reversible cardiovascular risk factor in patients with CKD.
RECENT FINDINGS
Multiple potential therapeutic approaches to reduce arterial stiffness have been proposed and tested. However, arterial stiffness and blood pressure (BP) have a very close bidirectional relationship. Any change in BP will have an effect on arterial stiffness and vice versa. At present, there is no robust evidence to support the notion that arterial stiffness can be considered reversible other than as a direct consequence of reduction in BP.
SUMMARY
For now, arterial stiffness should be considered an indirectly modifiable cardiovascular risk factor through optimal control of BP. Measures of arterial stiffness should be regarded as research and risk stratification tools rather than a therapeutic target in itself
Randomised controlled trial of a theory-based intervention to prompt front-line staff to take up the seasonal influenza vaccine.
No full textOBJECTIVE
To evaluate the effectiveness of reminder letters informed by social normative theory (a type of 'nudge theory') on uptake of seasonal influenza vaccination by front-line hospital staff.
DESIGN
Individually randomised controlled trial.
SETTING
A large acute care hospital in England.
PARTICIPANTS
Front-line staff employed by the hospital (n=7540) were randomly allocated to one of four reminder types in a factorial design.
INTERVENTIONS
The standard letter included only general information directing the staff to take up the vaccine. A second letter highlighted a type of social norm based on peer comparisons. A third letter highlighted a type of social norm based on an appeal to authority. A fourth letter included a combination of the social norms.
MAIN OUTCOME MEASURE
The proportion of hospital staff vaccinated on-site.
RESULTS
Vaccine coverage was 43% (812/1885) in the standard letter group, 43% (818/1885) in the descriptive norms group, 43% (814/1885) in the injunctive norms group and 43% (812/1885) in the combination group. There were no statistically significant effects of either norm or the interaction. The OR for the descriptive norms factor is 1.01 (0.89-1.15) in the absence of the injunctive norms factor and 1.00 (0.88-1.13) in its presence. The OR for the injunctive norms factor is 1.00 (0.88-1.14) in the absence of the descriptive norms factor and 0.99 (0.87-1.12) in its presence.
CONCLUSIONS
We find no evidence that the uptake of the seasonal influenza vaccination is affected by reminders using social norms to motivate uptake
Genomic Mutation Identification in Mice Using Illumina Sequencing and Linux-Based Computational Methods.
No full textGenetically modified mice are an essential tool for modeling disease-causing mechanisms and discovering gene function. SNP genotyping was traditionally used to associate candidate regions with traits in the mouse, but failed to reveal novel variants without further targeted sequencing. Using a robust set of computational protocols, we present a platform to enable scientists to detect variants arising from whole-genome and exome sequencing experiments. This article guides researchers on aligning reads to the mouse genome, quality-assurance strategies, mutation discovery, comparing mutations to previously discovered mouse SNPs, and the annotation of novel variants, in order to predict mutation consequences on the protein level. Challenges unique to the mouse are discussed, and two protocols use self-contained containers to maintain version control and allow users to adapt our approach to new techniques by upgrading container versions. Our protocols are suited for servers or office workstations and are usable by non-bioinformatics specialists. © 2019 by John Wiley & Sons, Inc
Effect of using fidaxomicin on recurrent Clostridium difficile infection.
No full textFidaxomicin is a macrocyclic antibiotic licensed for treating Clostridium difficile infection (CDI). In the UK, fidaxomicin is often reserved for severe CDI or recurrences. At Queen Elizabeth Hospital Birmingham, all courses of fidaxomicin during 2017/2018 were reviewed. Thirty-eight patients received fidaxomicin, of which 64% responded to treatment when fidaxomicin was given during the first episode of mild CDI. Conversely, all patients with recurrent CDI failed treatment with fidaxomicin. There were mixed results for the use of fidaxomicin for severe CDI, with only 42% of patients responding. These results suggest that fidaxomicin is best suited as a treatment for mild CDI during a patient's first episode
Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study.
No full textBACKGROUND
Few genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel genetic variants associated with moderate-to-severe asthma, see whether previously identified genetic variants for all types of asthma contribute to moderate-to-severe asthma, and provide novel mechanistic insights using expression analyses in patients with asthma.
METHODS
In this genome-wide association study, we used a two-stage case-control design. In stage 1, we genotyped patient-level data from two UK cohorts (the Genetics of Asthma Severity and Phenotypes [GASP] initiative and the Unbiased BIOmarkers in PREDiction of respiratory disease outcomes [U-BIOPRED] project) and used data from the UK Biobank to collect patient-level genomic data for cases and controls of European ancestry in a 1:5 ratio. Cases were defined as having moderate-to-severe asthma if they were taking appropriate medication or had been diagnosed by a doctor. Controls were defined as not having asthma, rhinitis, eczema, allergy, emphysema, or chronic bronchitis as diagnosed by a doctor. For stage 2, an independent cohort of cases and controls (1:5) was selected from the UK Biobank only, with no overlap with stage 1 samples. In stage 1 we undertook a genome-wide association study of moderate-to-severe asthma, and in stage 2 we followed up independent variants that reached the significance threshold of p less than 1 × 10 in stage 1. We set genome-wide significance at p less than 5 × 10. For novel signals, we investigated their effect on all types of asthma (mild, moderate, and severe). For all signals meeting genome-wide significance, we investigated their effect on gene expression in patients with asthma and controls.
FINDINGS
We included 5135 cases and 25 675 controls for stage 1, and 5414 cases and 21 471 controls for stage 2. We identified 24 genome-wide significant signals of association with moderate-to-severe asthma, including several signals in innate or adaptive immune-response genes. Three novel signals were identified: rs10905284 in GATA3 (coded allele A, odds ratio [OR] 0·90, 95% CI 0·88-0·93; p=1·76 × 10), rs11603634 in the MUC5AC region (coded allele G, OR 1·09, 1·06-1·12; p=2·32 × 10), and rs560026225 near KIAA1109 (coded allele GATT, OR 1·12, 1·08-1·16; p=3·06 × 10). The MUC5AC signal was not associated with asthma when analyses included mild asthma. The rs11603634 G allele was associated with increased expression of MUC5AC mRNA in bronchial epithelial brush samples via proxy SNP rs11602802; (p=2·50 × 10) and MUC5AC mRNA was increased in bronchial epithelial samples from patients with severe asthma (in two independent analyses, p=0·039 and p=0·022).
INTERPRETATION
We found substantial shared genetic architecture between mild and moderate-to-severe asthma. We also report for the first time genetic variants associated with the risk of developing moderate-to-severe asthma that regulate mucin production. Finally, we identify candidate causal genes in these loci and provide increased insight into this difficult to treat population.
FUNDING
Asthma UK, AirPROM, U-BIOPRED, UK Medical Research Council, and Rosetrees Trust
Instrument-based Tests for Measuring Anterior Chamber Cells in Uveitis: A Systematic Review.
No full text: New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates. : Using standard systematic review methodology, we identified and tabulated the outcomes of studies reporting reliability and correlation between instrument-based measurements and clinician AC cell grading. : From 3470 studies, 6 reported correlation between an instrument-based AC cell count to clinician grading. The two instruments were optical coherence tomography (OCT) and laser flare-cell photometry (LFCP). Correlation between clinician grading and LFCP was 0.66-0.87 and 0.06-0.97 between clinician grading and OCT. OCT volume scans demonstrated correlation between 0.75 and 0.78. Line scans in the middle AC demonstrated higher correlation (0.73-0.97) than in the inferior AC (0.06-0.56). : AC cell count by OCT and LFP can achieve high levels of correlation with clinician grading, whilst offering additional advantages of speed, automation, and objectivity
Streamlining communication between nursing staff and medical teams regarding patients who are 'medical outliers'.
No full textMedical Misinformation on Social Media: Cognitive Bias, Pseudo-Peer Review, and the Good Intentions Hypothesis.
No full textResolving the fibrotic niche of human liver cirrhosis at single-cell level.
No full textCurrently there are no effective antifibrotic therapies for liver cirrhosis, a major killer worldwide. To obtain a cellular resolution of directly relevant pathogenesis and to inform therapeutic design, we profile the transcriptomes of over 100,000 human single cells, yielding molecular definitions for non-parenchymal cell types present in healthy and cirrhotic human liver. We uncover a novel scar-associated TREM2CD9 macrophage subpopulation, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define novel ACKR1 and PLVAP endothelial cells that expand in cirrhosis, are topographically scar-restricted and enhance leucocyte transmigration. Multi-lineage ligand-receptor modelling of interactions between the novel scar-associated macrophages, endothelial cells and PDGFRα collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides the conceptual framework required to discover rational therapeutic targets in liver cirrhosis