Capturing pharmacists' impact in general practice: an e-Delphi study to attempt to reach consensus amongst experts about what activities to record

Background: In the UK, there is ongoing integration of pharmacists into general practice as a new healthcare service in primary care. Evaluation of the service involves national measures that require pharmacists to record their work, on the general practice clinical computer systems, using electronic activity codes. No national agreement, however, has been established on what activities to record. The purpose of this study was to attempt to reach consensus on what activities general practice-based pharmacists should record. Methods: The e-Delphi method was chosen as it is an excellent technique for achieving consensus. The study began with an initial stage in which screening of a general practice clinical computer system and discussion groups with pharmacists from two ‘pharmacists in general practice’ sites identified 81 codes potentially relevant to general practice-based pharmacists’ work. Twenty-nine experts (pharmacists and pharmacy technicians from the two sites along with experts recruited through national committees) were then invited by e-mail to participate as a panel in three e-Delphi questionnaire rounds. In each round, panellists were asked to grade or rank codes and justify their choices. In every round, panellists were provided with anonymised feedback from the previous round which included their individual choices along with their co-panellists’ views. Final consensus (in Round 3) was defined as at least 80% agreement. Commentaries on the codes from all e-Delphi rounds were pooled together and analysed thematically. Results: Twenty-one individual panellists took part in the study (there were 12 responses in Round 1, 18 in Round 2 and 16 in Round 3). Commentaries on the codes included three themes: challenges and facilitators; level of detail; and activities related to funding. Consensus was achieved for ten codes, eight of which related to activities (general and disease specific medication reviews, monitoring of high-risk drugs and medicines reconciliation) and two to patient outcomes (presence of side effects and satisfactory understanding of medication). Conclusions: A formal consensus method revealed general practice-based pharmacists’ preferences for activity coding. Findings will inform policy so that any future shaping of activity coding for general practice-based pharmacists takes account of pharmacists’ actual needs and preferences

Patients’ experiences of pharmacists in general practice: an exploratory qualitative study

Background: Since 2015, pharmacists have been integrating into English general practices and more recently into primary care networks. General practice-based pharmacists provide a range of patient-facing services, such as medication reviews, management of long-term conditions and minor ailments, prescribing duties and answering queries over the telephone. Literature reports patients’ satisfaction with general practice-based pharmacists’ services, however, previous research captured only limited experiences. The aim of the current study was to pursue an extensive exploration of patients’ experiences of pharmacists in general practice. Methods: General practice-based pharmacists, working in practices in West London, Surrey and Berkshire, handed invitation packs to patients seen during consultations. Patients that wanted to take part in the study were invited to undertake a qualitative, in-depth, face-to-face, semi-structured interview within the practice with which each patient was registered. Interviews lasted from 15 minutes to more than one hour and were audio-recorded. Recruitment continued until data saturation. Audio-recordings were transcribed verbatim and transcripts analysed thematically. Results: Twenty participants were interviewed. Four themes were discerned: awareness (“I had been coming to this practice for 24 years and I didn’t know that there was a pharmacist”); accessibility (“People ring for a GP [general practitioner] appointment … it’s Monday and they [receptionist] tells you ‘We can slot you in on Friday’ … with a pharmacist on board, they can [instantly] look at you”); interactions (“I’ve always had a really good interaction with them [pharmacists] and they listen and they take on board what I’m trying to say”); and feedback (“It’s easier [to collect feedback instantly] because I could have forgotten half of what they [pharmacists] have told me in an hour or so’s time”). Conclusions: Findings indicate that pharmacists’ integration into general practices could improve accessibility to, and the quality of, care received. The findings will assist policy development to provide general practice-based pharmacists’ services as per patients’ needs

Pharmacists in general practice: a qualitative interview case study of stakeholders’ experiences in a West London GP Federation

Background Increased patient demand for healthcare services coupled with a shortage of general practitioners necessitates changes in professional roles and service delivery. In 2016, NHS England began a three year pilot study of pharmacists in general practice, however, this is not an entirely new initiative. There is limited, current, evidence-based, UK research to inform the pilot so studies of pre-existing services must suffice until findings from a formal national evaluation are available. Methods The aim of this exploratory, descriptive interview study was to explore the experiences of stakeholders in eight general practices in the Ealing GP Federation, West London, where pharmacy services have been provided for several years. Forty-seven participants, including pharmacy team members (pre-registration and clinical pharmacists, independent prescribers and pharmacy technicians), general practitioners, patients, practice managers, practice nurses and receptionists took part in semi-structured, audio-recorded qualitative interviews which were transcribed verbatim, coded and analysed thematically to extract the issues raised by participants and the practicalities of providing pharmacy services in general practice. Results Findings are reported under the themes of Complementarity (incorporating roles, skills, education and workloads); Integration (incorporating relationships, trust and communication) and Practicalities (incorporating location and space, access, and costs). Participants reported the need for time to develop and understand the various roles, develop communication processes and build inter-professional trust. Once these were established, however, experiences were positive and included decreased workloads, increased patient safety, improved job satisfaction, improved patient relationships, and enhanced cost savings. Areas for improvement included patients’ awareness of services; pharmacists’ training; and regular, onsite access for practice staff to the pharmacy team. Conclusions Recommendations are made for the development of clear role definitions, identification of training needs, dedication of time for team building, production of educational materials for practice staff members and patients, and provision of on-site, full-time pharmacy services. Future work should focus on evaluation of various models of employing pharmacy teams in general practice; integration of pharmacists and pharmacy technicians into multidisciplinary general practice teams; relationships between local community pharmacy and general practice personnel and patients’ service and information needs. A formal national evaluation of the pilot scheme is overdue

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

How do pharmacists in English general practices identify their impact? An exploratory qualitative study of measurement problems

Background: In England, there is an ongoing national pilot to expand pharmacists’ presence in general practice. Evaluation of the pilot includes numerical and survey-based Key Performance Indicators (KPIs) and requires pharmacists to electronically record their activities, possibly by using activity codes. At the time of the study (2016), no national evaluation of pharmacists’ impact in this environment had been formally announced. The aim of this qualitative study was to identify problems that English pharmacists face when measuring and recording their impact in general practice. Methods: All pharmacists, general practitioners (GPs) and practice managers working across two West London pilot sites were invited, via e-mail, to participate in a focus group study. Appropriately trained facilitators conducted two audio-recorded, semi-structured focus groups, each lasting approximately one hour, to explore experiences and perceptions associated with the KPIs. Audio-recordings were transcribed verbatim and the data analysed thematically. Results: In total, 13 pharmacists, one GP and one practice manager took part in the study. Four major themes were discerned: inappropriateness of the numerical national KPIs (“whether or not we actually have positive impact on KPIs is beyond our control”); depth and breadth of pharmacists’ activity (“we see a huge plethora of different patients and go through this holistic approach - everything is looked at”); awareness of practice based pharmacists’ roles (“I think the really important [thing] is that everyone knows what pharmacists in general practice are doing”); and central evaluation versus local initiatives (“the KPIs will be measured by National Health Service England regardless of what we think” versus “what I think is more pertinent, are there some local things we’re going to measure?”). Conclusions: Measures that will effectively capture pharmacists’ impact in general practice should be developed, along with a set of codes reflecting the whole spectrum of pharmacists’ activities. Our study also points out the significance of a transparent, robust national evaluation, including exploring the needs/expectations of practice staff and patients regarding pharmacists’ presence in general practice

Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity

To increase understanding of the genomic landscape of acral melanoma, a rare form of melanoma occurring on palms, soles or nail beds, whole genome sequencing of 87 tumors with matching transcriptome sequencing for 63 tumors was performed. Here we report that mutational signature analysis reveals a subset of tumors, mostly subungual, with an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS, NF1, NOTCH2, PTEN and TYRP1. Mutations and amplification of KIT are also common. Structural rearrangement and copy number signatures show that whole genome duplication, aneuploidy and complex rearrangements are common. Complex rearrangements occur recurrently and are associated with amplification of TERT, CDK4, MDM2, CCND1, PAK1 and GAB2, indicating potential therapeutic options.This work was supported by a National Health and Medical Research Council of Australia (NHMRC) Program Grant (1093017, G.J.M., R.A.S., N.H., G.V.L., J.F.T.), an NHMRC project grant (APP1123217) and NHMRC Fellowship grants (R.A.S., N.K.H. - APP1139071, G.VL.). G.V.L is supported by an NHMRC Practitioner Fellowship and the University of Sydney Medical Foundation. R.A.S is supported by an NHMRC Practitioner Fellowship. J.S.W. is supported by a NHMRC early career fellowship (1111678). N.W. is supported by an NHMRC Senior Research Fellowship (1139071). N.K.H. is supported by an NHMRC Senior Principal Research Fellowship (1117663). P.M.F. was supported by the Deborah and John McMurtrie MIA Pathology Fellowship. T.J.D. was supported by the Jani Haenke Melanoma Pathology Fellowship. Support from Melanoma Institute Australia, the Royal Prince Alfred Hospital and New South Wales Health Pathology is also gratefully acknowledged

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies