“Everyone needs to understand each other’s systems”: Stakeholder views on the acceptability and viability of a Pharmacist Independent Prescriber role in care homes for older people in the UK

The role of an innovative Pharmacist Independent Prescriber (PIP) for care homes to optimise medications has not been examined. We explored stakeholders’ views on issues and barriers that the PIP might address to inform a service specification for the PIP intervention in older people's care homes. Focus groups (n = 72 participants) and semi‐structured interviews (n = 13) undertaken in 2015 across four sites in the United Kingdom captured the views of doctors, pharmacists, care‐home managers and staff, residents and relatives. Stakeholders identified their expectations of what service should be provided by PIPs, what might affect their support for the role, and barriers and enablers to providing the service. Transcripts were analysed using the Theoretical Domains Framework to identify key components, which were reviewed by stakeholders in 2016. A PIP service was envisaged offering benefits for residents, care homes and doctors but stakeholders raised challenges including agreement on areas where PIPs might prescribe, contextual barriers in chronic disease management, PIPs’ knowledge of older people's medicine, and implementation barriers in integrated team‐working and ensuring role clarity. Introducing a PIP was welcomed in principle but conditional on: a clearly defined PIP role communicated to stakeholders; collaboration across doctors, PIPs and care‐home staff; dialogue about developing the service with residents and relatives, based on trust and effective communication. To embed a PIP service within increasingly complex care‐homes provision, the overarching theme from this research was that everyone must “understand each other's systems”

Systematic review and narrative synthesis of pharmacist provided medicines optimisation services in care homes for older people to inform the development of a generic training or accreditation process

Objectives: To develop a training programme to enable pharmacists with prescribing rights to assume responsibility for the provision of pharmaceutical care within care homes, a systematic review and narrative synthesis was undertaken to identify reported approaches to training pharmacists and use this literature to identify potential knowledge requirements. Methods: A PROSPERO‐registered systematic review was performed using key search terms for care homes, pharmacist, education, training and pharmaceutical care. Papers reporting primary research focussed on care of the older person within the care home setting were included. No restrictions were placed on methodology. Two researchers independently reviewed titles, abstracts and papers. Agreement on inclusion was reached through consensus. Data on titles, training and activities undertaken were extracted and knowledge requirements identified. Findings were synthesised and reported narratively. Key findings: Fifty‐nine papers were included, most of which were uncontrolled service evaluations. Four papers reported an accreditation process for the pharmacist. Thirteen papers reported providing tools or specific training on a single topic to pharmacists. The main clinical and therapeutic areas of activity (requiring codified knowledge) were dementia, pain, antipsychotic and cardiovascular medication. Provision of pharmaceutical care, effective multidisciplinary working and care home staff training represented the main areas of practical knowledge. Conclusions: Information regarding training and accreditation processes for care home pharmacists is limited. This study provides insight into potential codified and practical knowledge requirements for pharmacists assuming responsibility for the provision of pharmaceutical care within care homes. Further work involving stakeholders is required to identify the cultural knowledge requirements and to develop a training and accreditation process

Mechanisms driving variability in the ocean forcing of Pine Island Glacier

Pine Island Glacier (PIG) terminates in a rapidly melting ice shelf, and ocean circulation and temperature are implicated in the retreat and growing contribution to sea level rise of PIG and nearby glaciers. However, the variability of the ocean forcing of PIG has been poorly constrained due to a lack of multi-year observations. Here we show, using a unique record close to the Pine Island Ice Shelf (PIIS), that there is considerable oceanic variability at seasonal and interannual timescales, including a pronounced cold period from October 2011 to May 2013. This variability can be largely explained by two processes: cumulative ocean surface heat fluxes and sea ice formation close to PIIS; and interannual reversals in ocean currents and associated heat transport within Pine Island Bay, driven by a combination of local and remote forcing. Local atmospheric forcing therefore plays an important role in driving oceanic variability close to PIIS

Pharmacist Independent Prescriber (PIP) deprescribing in UK care homes: Contextual factors associated with increased activity

Aims The Care Home Independent Pharmacist Prescriber Study (CHIPPS) process evaluation hypothesized that contextual factors influenced the likelihood of deprescribing by pharmacist-independent prescribers. The aim of this paper is to test this hypothesis. Methods From CHIPPS study data, medications deprescribed totalled 284 for 370 residents in UK care homes. Regression analysis was used to describe the relationship between the number of medicines stopped and contextual factors (number of residents cared for, pharmacist employment within associated medical practice, previous care home experience, hours active within trial, years’ experience as a pharmacist and as a prescriber). Results Number of residents and pharmacist-independent prescriber employment within a medical practice were positive predictors of deprescribing. Conclusion Previous experiences were not related to deprescribing likelihood. Increasing the number of residents increases the opportunity for deprescribing and therefore this relationship is intuitive. The location within a medical practice is an interesting finding that requires further exploration to understand its exact nature

West Antarctic ice loss influenced by internal climate variability and anthropogenic forcing

Recent ice loss from the West Antarctic Ice Sheet has been caused by ocean melting of ice shelves in the Amundsen Sea. Eastward wind anomalies at the shelf break enhance the import of warm Circumpolar Deep Water onto the Amundsen Sea continental shelf, which creates transient melting anomalies with an approximately decadal period. No anthropogenic influence on this process has been established. Here, we combine observations and climate model simulations to suggest that increased greenhouse gas forcing caused shelf-break winds to transition from mean easterlies in the 1920s to the near-zero mean zonal winds of the present day. Strong internal climate variability, primarily linked to the tropical Pacific, is superimposed on this forced trend. We infer that the Amundsen Sea experienced decadal ocean ariability throughout the twentieth century, with warm anomalies gradually becoming more prevalent, offering a credible explanation for the ongoing ice loss. Existing climate model projections show that strong future greenhouse gas forcing creates persistent mean westerly shelf-break winds by 2100, suggesting a further enhancement of warm ocean anomalies. These wind changes are weaker under a scenario in which greenhouse gas concentrations are stabilized

miR-34a Repression in Proneural Malignant Gliomas Upregulates Expression of Its Target PDGFRA and Promotes Tumorigenesis

Glioblastoma (GBM) and other malignant gliomas are aggressive primary neoplasms of the brain that exhibit notable refractivity to standard treatment regimens. Recent large-scale molecular profiling has revealed distinct disease subclasses within malignant gliomas whose defining genomic features highlight dysregulated molecular networks as potential targets for therapeutic development. The “proneural” designation represents the largest and most heterogeneous of these subclasses, and includes both a large fraction of GBMs along with most of their lower-grade astrocytic and oligodendroglial counterparts. The pathogenesis of proneural gliomas has been repeatedly associated with dysregulated PDGF signaling. Nevertheless, genomic amplification or activating mutations involving the PDGF receptor (PDGFRA) characterize only a subset of proneural GBMs, while the mechanisms driving dysregulated PDGF signaling and downstream oncogenic networks in remaining tumors are unclear. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that regulate gene expression by binding loosely complimentary sequences in target mRNAs. The role of miRNA biology in numerous cancer variants is well established. In an analysis of miRNA involvement in the phenotypic expression and regulation of oncogenic PDGF signaling, we found that miR-34a is downregulated by PDGF pathway activation in vitro. Similarly, analysis of data from the Cancer Genome Atlas (TCGA) revealed that miR-34a expression is significantly lower in proneural gliomas compared to other tumor subtypes. Using primary GBM cells maintained under neurosphere conditions, we then demonstrated that miR-34a specifically affects growth of proneural glioma cells in vitro and in vivo. Further bioinformatic analysis identified PDGFRA as a direct target of miR-34a and this interaction was experimentally validated. Finally, we found that PDGF-driven miR-34a repression is unlikely to operate solely through a p53-dependent mechanism. Taken together, our data support the existence of reciprocal negative feedback regulation involving miR-34 and PDGFRA expression in proneural gliomas and, as such, identify a subtype specific therapeutic potential for miR-34a

Potential Economic Viability of Two Proposed Rifapentine-Based Regimens for Treatment of Latent Tuberculosis Infection

Rationale: Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives: To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods: We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/ rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of ‘‘no treatment’ ’ used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results: Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions: Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)