Hypertonic Na+ accumulation in peripheral tissues is a recently described phenomenon: it has been associated with ageing, hypertension, diabetes, chronic kidney disease and heart failure, but its clinical meaning has yet to be determined. This concept conflicts with the classic physiological paradigm of constant balance between salt intake and excretion, and its water-independent nature is still a matter of debate.We developed a theoretical model explaining changes in the chemical composition of tissues as a function of extracellular volume fraction and excess extracellular fluid, i.e. oedema. The model suggests that the proportional increase in absolute Na+ content and concentration due to different degrees of oedema is higher than the parallel increase in water content, thus making Na+ a more sensitive index to detect this oedema.Our model would explain some of the recent findings of high tissue Na+ content in pathological conditions. More importantly, it prompts the reappraisal of tissue Na+ analysis from being a topic of niche interest to a potential diagnostic tool with broad applicability in the investigation of subclinical systemic and localized oedema.

/pdf/much-ado-about-n-atrium-modelling-tissue-sodium-as-a-highly-2fn7ggqx4x.pdf

Much Ado about N…atrium: modelling tissue sodium as a highly sensitive marker of subclinical and localized oedema

Background Most patients obtain medications from pharmacies by prescription, but rural general practices can dispense medications. The clinical implications of this difference in drug delivery are unknown. This study hypothesised that dispensing status may be associated with better medication adherence. This could impact intermediate clinical outcomes dependent on medication adherence in, for example, hypertension or diabetes. Aim To investigate whether dispensing status is associated with differences in achievement of Quality and Outcomes Framework (QOF) indicators that rely on medication adherence. Design and setting Cross-sectional analysis of QOF data for 7392 general practices in England. Method QOF data from 1 April 2016 to 31 March 2017 linked to dispensing status for general practices with list sizes ≥1000 in England were analysed. QOF indicators were categorised according to whether their achievement depended on a record of prescribing only, medication adherence, or neither. Differences were estimated between dispensing and non-dispensing practices using mixed-effects logistic regression, adjusting for practice population age, sex, deprivation, list size, single-handed status, and rurality. Results Data existed for 7392 practices; 1014 (13.7%) could dispense. Achievement was better in dispensing practices than in non-dispensing practices for seven of nine QOF indicators dependent on adherence, including blood pressure targets. Only one of ten indicators dependent on prescribing but not adherence displayed better achievement; indicators unrelated to prescribing showed a trend towards higher achievement by dispensing practices. Conclusion Dispensing practices may achieve better clinical outcomes than prescribing practices. Further work is required to explore underlying mechanisms for these observations and to directly study medication adherence rates.

/pdf/medication-adherence-and-clinical-outcomes-in-dispensing-and-3xj2xtsj4c.pdf

Medication adherence and clinical outcomes in dispensing and non-dispensing practices: a cross-sectional analysis.

National Institutes for Health Research (NIHR), portfolio of translational research of the NIHR Biomedical Research Centre at Barts. 
London School of Medicine and Dentistry, Queen Mary University of London .

/pdf/large-scale-genome-wide-pharmacogenetic-meta-analysis-of-2m02zhjdgi.pdf

Large-scale genome-wide pharmacogenetic meta-analysis of blood pressure response to antihypertensive drugs

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Large-scale genome-wide pharmacogenetic meta-analysis of blood pressure response to antihypertensive drugs