Emergency supply of prescription-only medicines to patients by community pharmacists: a mixed methods evaluation incorporating patient, pharmacist and GP perspectives

Objective To evaluate and inform emergency supply of prescription-only medicines by community pharmacists (CPs), including how the service could form an integral component of established healthcare provision to maximise adherence. Design Mixed methods. 4 phases: prospective audit of emergency supply requests for prescribed medicines (October–November 2012 and April 2013); interviews with CPs (February–April 2013); follow-up interviews with patients (April–May 2013); interactive feedback sessions with general practice teams (October–November 2013). Setting 22 community pharmacies and 6 general practices in Northwest England. Participants 27 CPs with experience of dealing with requests for emergency supplies; 25 patients who received an emergency supply of a prescribed medicine; 58 staff at 6 general practices. Results Clinical audit in 22 pharmacies over two 4-week periods reported that 526 medicines were requested by 450 patients. Requests peaked over a bank holiday and around weekends. A significant number of supplies were made during practice opening hours. Most requests were for older patients and for medicines used in long-term conditions. Difficulty in renewing repeat medication (forgetting to order, or prescription delays) was the major reason for requests. The majority of medicines were ‘loaned’ in advance of a National Health Service (NHS) prescription. Interviews with CPs and patients indicated that continuous supply had a positive impact on medicines adherence, removing the need to access urgent care. General practice staff were surprised and concerned by the extent of emergency supply episodes. Conclusions CPs regularly provide emergency supplies to patients who run out of their repeat medication, including during practice opening hours. This may aid adherence. There is currently no feedback loop, however, to general practice. Patient care and interprofessional communication may be better served by the introduction of a formally structured and funded NHS emergency supply service from community pharmacies, with ongoing optimisation of repeat prescribing

Variation in extubation failure rates after neonatal congenital heart surgery across Pediatric Cardiac Critical Care Consortium hospitals

OBJECTIVE: In a multicenter cohort of neonates recovering from cardiac surgery, we sought to describe the epidemiology of extubation failure and its variability across centers, identify risk factors, and determine its impact on outcomes. METHODS: We analyzed prospectively collected clinical registry data on all neonates undergoing cardiac surgery in the Pediatric Cardiac Critical Care Consortium database from October 2013 to July 2015. Extubation failure was defined as reintubation less than 72 hours after the first planned extubation. Risk factors were identified using multivariable logistic regression with generalized estimating equations to account for within-center correlation. RESULTS: The cohort included 899 neonates from 14 Pediatric Cardiac Critical Care Consortium centers; 14% were premature, 20% had genetic abnormalities, 18% had major extracardiac anomalies, and 74% underwent surgery with cardiopulmonary bypass. Extubation failure occurred in 103 neonates (11%), within 24 hours in 61%. Unadjusted rates of extubation failure ranged from 5% to 22% across centers; this variability was unchanged after adjusting for procedural complexity and airway anomaly. After multivariable analysis, only airway anomaly was identified as an independent risk factor for extubation failure (odds ratio, 3.1; 95% confidence interval, 1.4-6.7; P = .01). Neonates who failed extubation had a greater median postoperative length of stay (33 vs 23 days, P < .001) and in-hospital mortality (8% vs 2%, P = .002). CONCLUSIONS: This multicenter study showed that 11% of neonates recovering from cardiac surgery fail initial postoperative extubation. Only congenital airway anomaly was independently associated with extubation failure. We observed a 4-fold variation in extubation failure rates across hospitals, suggesting a role for collaborative quality improvement to optimize outcomes

Metagenomic sequencing suggests a diversity of RNA interference-like responses to viruses across multicellular eukaryotes

<div><p>RNA interference (RNAi)-related pathways target viruses and transposable element (TE) transcripts in plants, fungi, and ecdysozoans (nematodes and arthropods), giving protection against infection and transmission. In each case, this produces abundant TE and virus-derived 20-30nt small RNAs, which provide a characteristic signature of RNAi-mediated defence. The broad phylogenetic distribution of the Argonaute and Dicer-family genes that mediate these pathways suggests that defensive RNAi is ancient, and probably shared by most animal (metazoan) phyla. Indeed, while vertebrates had been thought an exception, it has recently been argued that mammals also possess an antiviral RNAi pathway, although its immunological relevance is currently uncertain and the viral small RNAs (viRNAs) are not easily detectable. Here we use a metagenomic approach to test for the presence of viRNAs in five species from divergent animal phyla (Porifera, Cnidaria, Echinodermata, Mollusca, and Annelida), and in a brown alga—which represents an independent origin of multicellularity from plants, fungi, and animals. We use metagenomic RNA sequencing to identify around 80 virus-like contigs in these lineages, and small RNA sequencing to identify viRNAs derived from those viruses. We identified 21U small RNAs derived from an RNA virus in the brown alga, reminiscent of plant and fungal viRNAs, despite the deep divergence between these lineages. However, contrary to our expectations, we were unable to identify canonical (i.e. <i>Drosophila-</i> or nematode-like) viRNAs in any of the animals, despite the widespread presence of abundant micro-RNAs, and somatic transposon-derived piwi-interacting RNAs. We did identify a distinctive group of small RNAs derived from RNA viruses in the mollusc. However, unlike ecdysozoan viRNAs, these had a piRNA-like length distribution but lacked key signatures of piRNA biogenesis. We also identified primary piRNAs derived from putatively endogenous copies of DNA viruses in the cnidarian and the echinoderm, and an endogenous RNA virus in the mollusc. The absence of canonical virus-derived small RNAs from our samples may suggest that the majority of animal phyla lack an antiviral RNAi response. Alternatively, these phyla could possess an antiviral RNAi response resembling that reported for vertebrates, with cryptic viRNAs not detectable through simple metagenomic sequencing of wild-type individuals. In either case, our findings show that the antiviral RNAi responses of arthropods and nematodes, which are highly divergent from each other and from that of plants and fungi, are also highly diverged from the most likely ancestral metazoan state.</p></div

Development and validation of the DIabetes Severity SCOre (DISSCO) in 139 626 individuals with type 2 diabetes: a retrospective cohort study

OBJECTIVE: Clinically applicable diabetes severity measures are lacking, with no previous studies comparing their predictive value with glycated hemoglobin (HbA1c). We developed and validated a type 2 diabetes severity score (the DIabetes Severity SCOre, DISSCO) and evaluated its association with risks of hospitalization and mortality, assessing its additional risk information to sociodemographic factors and HbA1c. RESEARCH DESIGN AND METHODS: We used UK primary and secondary care data for 139 626 individuals with type 2 diabetes between 2007 and 2017, aged ≥35 years, and registered in general practices in England. The study cohort was randomly divided into a training cohort (n=111 748, 80%) to develop the severity tool and a validation cohort (n=27 878). We developed baseline and longitudinal severity scores using 34 diabetes-related domains. Cox regression models (adjusted for age, gender, ethnicity, deprivation, and HbA1c) were used for primary (all-cause mortality) and secondary (hospitalization due to any cause, diabetes, hypoglycemia, or cardiovascular disease or procedures) outcomes. Likelihood ratio (LR) tests were fitted to assess the significance of adding DISSCO to the sociodemographics and HbA1c models. RESULTS: A total of 139 626 patients registered in 400 general practices, aged 63±12 years were included, 45% of whom were women, 83% were White, and 18% were from deprived areas. The mean baseline severity score was 1.3±2.0. Overall, 27 362 (20%) people died and 99 951 (72%) had ≥1 hospitalization. In the training cohort, a one-unit increase in baseline DISSCO was associated with higher hazard of mortality (HR: 1.14, 95% CI 1.13 to 1.15, area under the receiver operating characteristics curve (AUROC)=0.76) and cardiovascular hospitalization (HR: 1.45, 95% CI 1.43 to 1.46, AUROC=0.73). The LR tests showed that adding DISSCO to sociodemographic variables significantly improved the predictive value of survival models, outperforming the added value of HbA1c for all outcomes. Findings were consistent in the validation cohort. CONCLUSIONS: Higher levels of DISSCO are associated with higher risks for hospital admissions and mortality. The new severity score had higher predictive value than the proxy used in clinical practice, HbA1c. This reproducible algorithm can help practitioners stratify clinical care of patients with type 2 diabetes

Redox‐active hybrid polyoxometalate‐stabilised gold nanoparticles

We report the design and preparation of multifunctional hybrid nanomaterials through the stabilization of gold nanoparticles with thiol‐functionalised hybrid organic–inorganic polyoxometalates (POMs). The covalent attachment of the hybrid POM forms new nanocomposites that are stable at temperatures and pH values which destroy analogous electrostatically functionalised nanocomposites. Photoelectrochemical analysis revealed the unique photochemical and redox properties of these systems

Assessing the severity of Type 2 diabetes using clinical data-based measures:a systematic review

Aims To identify and critically appraise measures that use clinical data to grade the severity of Type 2 diabetes. Methods We searched MEDLINE, Embase and PubMed between inception and June 2018. Studies reporting on clinical data‐based diabetes‐specific severity measures in adults with Type 2 diabetes were included. We excluded studies conducted solely in participants with other types of diabetes. After independent screening, the characteristics of the eligible measures including design and severity domains, the clinical utility of developed measures, and the relationship between severity levels and health‐related outcomes were assessed. Results We identified 6798 studies, of which 17 studies reporting 18 different severity measures (32 314 participants in 17 countries) were included: a diabetes severity index (eight studies, 44%); severity categories (seven studies, 39%); complication count (two studies, 11%); and a severity checklist (one study, 6%). Nearly 89% of the measures included diabetes‐related complications and/or glycaemic control indicators. Two of the severity measures were validated in a separate study population. More severe diabetes was associated with increased healthcare costs, poorer cognitive function and significantly greater risks of hospitalization and mortality. The identified measures differed greatly in terms of the included domains. One study reported on the use of a severity measure prospectively. Conclusions Health records are suitable for assessment of diabetes severity; however, the clinical uptake of existing measures is limited. The need to advance this research area is fundamental as higher levels of diabetes severity are associated with greater risks of adverse outcomes. Diabetes severity assessment could help identify people requiring targeted and intensive therapies and provide a major benchmark for efficient healthcare services

No Evidence for XMRV Nucleic Acids, Infectious Virus or Anti-XMRV Antibodies in Canadian Patients with Chronic Fatigue Syndrome

The gammaretroviruses xenotropic murine leukemia virus (MLV)-related virus (XMRV) and MLV have been reported to be more prevalent in plasma and peripheral blood mononuclear cells of chronic fatigue syndrome (CFS) patients than in healthy controls. Here, we report the complex analysis of whole blood and plasma samples from 58 CFS patients and 57 controls from Canada for the presence of XMRV/MLV nucleic acids, infectious virus, and XMRV/MLV-specific antibodies. Multiple techniques were employed, including nested and qRT-PCR, cell culture, and immunoblotting. We found no evidence of XMRV or MLV in humans and conclude that CFS is not associated with these gammaretroviruses

Restoring habitat for fire-impacted species' across degraded Australian landscapes

In the summer of 2019-2020, southern Australia experienced the largest fires on record, detrimentally impacting the habitat of native species, many of which were already threatened by past and current anthropogenic land use. A large-scale restoration effort to improve degraded species habitat would provide fire-affected species with the chance to recover and persist in burnt and unburnt habitat. To facilitate this, decision-makers require information on priority species needs for restoration intervention, the suite of potential restoration interventions, and the priority locations for applying these interventions. We prioritize actions in areas where restoration would most likely provide cost-effective benefits to priority species (defined by each species proportion of habitat burned, threat status, and vulnerability to fires), by integrating current and future species habitat suitability maps with spatially modelled costs of restoration interventions such as replanting, removing invasive species, and implementing ecologically appropriate fire management. We show that restoring the top similar to 69% (112 million hectares) of the study region (current and future distributions of priority species) accounts for, on average, 95% of current and future habitat for every priority species and costs similar to AUD$73 billion yr(-1) (AUD$650 hectare(-1) yr(-1)) annualized over 30 years. This effort would include restoration actions over 6 million hectares of fire-impacted habitat, costing similar to AUD$8.8 billion/year. Large scale restoration efforts are often costly but can have significant societal co-benefits beyond biodiversity conservation. We also show that up to 291 MtCO2 (similar to 150 Mt DM) of carbon could be sequestered by restoration efforts, resulting in approximately AUD$253 million yr(-1) in carbon market revenue if all carbon was remunerated. Our approach highlights the scale, costs, and benefits of targeted restoration activities both inside and outside of the immediate bushfire footprint over vast areas of different land tenures