Changes in prescribing rates of sodium-containing medications in the UK from 2009 to 2018: a cross-sectional study with interrupted time series analysis

Objective: Effervescent, soluble, dispersible formulations contain considerable amounts of sodium. In 2013, we previously confirmed the association between sodium-containing medications and cardiovascular risks. This study aimed to determine the changes in the prescribing pattern in clinical practice following this publication. / Design: A longitudinal cross-sectional study. / Setting: Primary care in the UK from 2009 to 2018. / Participants: Prescribing information in The Health Improvement Network (THIN) and Prescription Cost Analysis (PCA) databases in the UK. / Outcome measurements: Prescription rates per 10 000 inhabitants were calculated using the number of prescriptions or the number of drug-using patients over the total number of inhabitants, and the prescription rates were measured at annual intervals. Prescribing trends from 2009 to 2018 were indexed with yearly data from THIN and PCA. Interrupted time series analysis (ITSA) was conducted with monthly data in THIN. / Results: From the THIN database, a total of 3 651 419 prescription records from 446 233 patients were included. The prescribing rate of sodium-containing medications changed from 848.3/10 000 inhabitants in 2009 to 571.6/10 000 inhabitants in 2018. The corresponding figures from PCA data were of 631.0/10 000 inhabitants in 2009 and 423.8/10 000 inhabitants in 2018. ITSA showed the prescribing trend reduced significantly during the postpublication period (prescribing rate: slope change=−0.26; 95% CI −0.45 to –0.07; p=0.009; proportion of patients: slope change=−0.22; 95% CI −0.35 to –0.09; p<0.001), but no change in postpublication level from baseline. The prescribing rates for the non-sodium-containing standard formulations were relatively stable over the study period. The reduction in the proportion of patients using sodium-containing medications was only significant in patients over 45 years old. / Conclusions: The prescribing of sodium-containing medications in the UK primary care has declined significantly during the postpublication period. Changes in the prescribing trends for sodium-containing medications varied across regions of the UK and patient age groups

Co-prescription of co-trimoxazole and spironolactone in elderly patients.

Although much effort goes into understanding the risks and benefits of recently licensed drugs, less is known about many of the older drugs that are prescribed widely

Lewis Base Passivation Mediates Charge Transfer at Perovskite Heterojunctions

Understanding interfacial charge transfer processes such as trap-mediated recombination and injection into charge transport layers (CTLs) is crucial for the improvement of perovskite solar cells. Herein, we reveal that the chemical binding of charge transport layers to CH3NH3PbI3 defect sites is an integral part of the interfacial charge injection mechanism in both n-i-p and p-i-n architectures. Specifically, we use a mixture of optical and X-ray photoelectron spectroscopy to show that binding interactions occur via Lewis base interactions between electron-donating moieties on hole transport layers and the CH3NH3PbI3 surface. We then correlate the extent of binding with an improvement in the yield and longer lifetime of injected holes with transient absorption spectroscopy. Our results show that passivation-mediated charge transfer has been occurring undetected in some of the most common perovskite configurations and elucidate a key design rule for the chemical structure of next-generation CTLs

C9ORF72 Deficiency Results in Neurodegeneration in the Zebrafish Retina

Hexanucleotide repeat expansions within the gene C9ORF72 are the most common cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This disease-causing expansion leads to a reduction in C9ORF72 expression levels in patients, suggesting loss of C9ORF72 function could contribute to disease. To further understand the consequences of C9ORF72 deficiency in vivo, we generated a c9orf72 mutant zebrafish line. Analysis of the adult female spinal cords revealed no appreciable neurodegenerative pathology such as loss of motor neurons or increased levels of neuroinflammation. However, detailed examination of adult female c9orf72−/− retinas showed prominent neurodegenerative features, including a decrease in retinal thickness, gliosis, and an overall reduction in neurons of all subtypes. Analysis of rod and cone cells within the photoreceptor layer showed a disturbance in their outer segment structure and rhodopsin mislocalization from rod outer segments to their cell bodies and synaptic terminals. Thus, C9ORF72 may play a previously unappreciated role in retinal homeostasis and suggests C9ORF72 deficiency can induce tissue specific neuronal loss

The comparative effectiveness of statin therapy in selected chronic diseases compared with the remaining population

Total cholesterol (TC) concentration is the most commonly used measure of statin efficacy in the UK. This study aimed to evaluate the effectiveness of statins in lowering TC, cardiovascular events (CV) and mortality five common chronic diseases (chronic obstructive pulmonary disease (COPD), osteoarthritis (OA), rheumatoid arthritis (RA), chronic kidney disease (CKD), and diabetes mellitus (DM)) and to compare effectiveness with the rest of the population not recorded as having these diseases

Association between cardiovascular events and sodium-containing effervescent, dispersible, and soluble drugs: nested case-control study

Objective: To determine whether patients taking formulations of drugs that contain sodium have a higher incidence of cardiovascular events compared with patients on non-sodium formulations of the same drugs. Design: Nested case-control study. Setting: UK Primary Care Patients registered on the Clinical Practice Research Datalink (CPRD). Participants: All patients aged 18 or over who were prescribed at least two prescriptions of sodium-containing formulations or matched standard formulations of the same drug between January 1987 and December 2010. Main outcome: measures Composite primary outcome of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death. We performed 1:1 incidence density sampling matched controls using the UK Clinical Practice Research Datalink (CPRD). For the secondary analyses, cases were patients with the individual components of the primary study composite endpoint of hypertension, incident heart failure, and all cause mortality. Results: 1 292 337 patients were included in the study cohort. Mean follow-up time was 7.23 years. A total of 61 072 patients with an incident cardiovascular event were matched with controls. For the primary endpoint of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death the adjusted odds ratio for exposure to sodium-containing drugs was 1.16 (95% confidence interval 1.12 to 1.21). The adjusted odds ratios for the secondary endpoints were 1.22 (1.16 to 1.29) for incident non-fatal stroke, 1.28 (1.23 to 1.33) for all cause mortality, 7.18 (6.74 to 7.65) for hypertension, 0.98 (0.93 to 1.04) for heart failure, 0.94 (0.88 to 1.00) for incident non-fatal myocardial infarction, and 0.70 (0.31 to 1.59) for vascular death. The median time from date of first prescription (that is, date of entry into cohort) to first event was 3.92 years. Conclusions: Exposure to sodium-containing formulations of effervescent, dispersible, and soluble medicines was associated with significantly increased odds of adverse cardiovascular events compared with standard formulations of those same drugs. Sodium-containing formulations should be prescribed with caution only if the perceived benefits outweigh these risks

Metabolic variability in seafloor brines revealed by carbon and sulphur dynamics

Brine fluids that upwell from deep, hot reservoirs below the sea bed supply the sea floor with energy-rich substrates and nutrients that are used by diverse microbial ecosystems. Contemporary hypersaline environments formed by brine seeps may provide insights into the metabolism and distribution of microorganisms on the early Earth or on extraterrestrial bodies. Here we use geochemical and genetic analyses to characterize microbial community composition and metabolism in two seafloor brines in the Gulf of Mexico: an active mud volcano and a quiescent brine pool. Both brine environments are anoxic and hypersaline. However, rates of sulphate reduction and acetate production are much higher in the brine pool, whereas the mud volcano supports much higher rates of methane production. We find no evidence of anaerobic oxidation of methane, despite high methane fluxes at both sites. We conclude that the contrasting microbial community compositions and metabolisms are linked to differences in dissolved-organic-matter input from the deep subsurface and different fluid advection rates between the two sites. DOI: 10.1038/NGEO47