Pharmacy undergraduate programs: Development of an adaptive curriculum for student success.

Objectives: Applicants for graduate work in Pharmacy on paper appear competitive, but upon entering a Doctor of Pharmacy (PharmD) program many students struggle with course work, course load, and pharmacologic topics in their first-year studies. In addition to math and science, undergraduate candidates need to have skills that enable them to be adaptable and creative learners. The Pharmacy Undergraduate Program (PUP) at the University of Southern California (USC) has been attentive to these educational needs. In this manuscript we will show how our program has been successful in generating well-prepared and successful candidates for graduate programs (pharmaceutical, clinical, medical, and other) and employment in pharmaceutical fields. Methods: A review of current student enrollments (N = 121), graduated student annual survey data (N = 50), student research data (N = 68), and ongoing course surveys have been used to detail information related to PUP. Results: Students who have graduated from PUP have been successful post-graduation. Graduates of PUP have gone on to PharmD programs 44% (22/50); medical school 16% (8/50); PhD programs 24% (12/50); full-time employment 6% (3/50); internship/volunteer positions 10% (5/50); taken a gap year 4% (2/50); and MS/MA program 2% (1/50). Conclusions: PUP has been successful in helping the admission of our students into graduate degree programs related to pharmaceutical sciences and medicine. This success can be attributed to the dynamic nature of the course offerings and the creativity of the teaching faculty, which leads to students being well-prepared to tackle the rigors of their graduate studies after leaving the program.

Experiences and opinions of multi-professional non-medical oncology prescribers on post-qualification training: a qualitative study.

BACKGROUND: Within the UK, a non-medical prescriber is a non-medical healthcare professional who has undertaken post-registration training to gain prescribing rights. Lack of post-qualification NMP training has previously been identified as a barrier to the development of oncology non-medical prescribing practice. AIM: To explore the experiences and opinions of multi-professional non-medical oncology prescribers on post-qualification training. METHOD: Nine out of 30 oncology non-medical prescribers (three nurses, three pharmacists and three radiographers) from a single cancer centre in Wales, were selected from a study site NMP database using randomisation sampling within Microsoft® Excel. Participants were interviewed using a validated and piloted semi-structured interview design on the topic of post-qualification training for non-medical prescribers. Participants were invited via organisational email. Interviews were audio-recorded and transcribed verbatim. Anonymised data were thematically analysed aided by NVivo® software. RESULTS: Main themes identified: experience related to training, competency, support and training methods. Competency assessment methods discussed were the annual non-medical prescriber appraisal, peer review and a line manager's overarching appraisal. Support requirements identified included greater consultant input to help non-medical prescribers identify training and peer support opportunities. Organisational support was requested regarding regular study leave and governance around clinical judgement and errors. The need for regular structured in-house training related to non-medical prescriber's level of experience was identified. CONCLUSION: Development of organisation-led governance strategies and in-house training programmes will support training equity for all non-medical prescribers within the organisation.

Community pharmacy role in children's health in England: Experiences and opinions of parents and young people.

Little is known about the reason behind the underutilisation of community pharmacy (CP) for children. This study explored the experiences, barriers and recommendations of parents/carers and young people regarding their use of CP services for children. Two-stage facilitated, structured, audio-recorded interviews were conducted at each of four CPs in London, England, between May and November 2019 [1 month in each CP]. Parents/carers or young persons (aged 16-18 years) who visited CP for a child-related matter were invited to participate. Interviews were transcribed verbatim. Data were analysed both quantitatively and qualitatively, using thematic analysis to identify themes. In total, 249 (58.2% of 428 eligible) customers agreed to participate and completed the two interviews. Out of these, 82.3% (205/249) reported positive experiences with the CP. The general practitioner (GP) was the preferred healthcare provider for minor ailments (44.6%,111/249), while 35.7% (89/249) would choose CP. Eighty-two participants (33%) visited an Emergency Department in the last 12 months, with 13.4% (11/82) of them visited for cold and cough reasons. Where a child was present with parents/carer (128/249), there was a low level of interaction between children and pharmacists (13.3%, 17/128). Lack of awareness about the CP services provided for children and privacy were among the barriers identified by participants. Advertising of CP services and creating a child-friendly environment were recommendations suggested by participants. The findings of this paper show that CP remains an underutilised health service for children by parents/carers and young persons. More work is needed to increase public awareness of the roles of CP in children's health and well-being.

An industry survey of implementation strategies for clinical supply chain management of cell and gene therapies.

BACKGROUND AIMS: The novelty of cell and gene therapies (CGTs) has introduced unique supply chain challenges and considerations not seen by chemically synthesized (small-molecule) drugs. These complexities increase during the clinical phases, where drug safety and efficacy milestones are still underdeveloped. For example, for autologous therapies such as chimeric antigen receptor T-cell therapies, in which the treatment is developed from the patient's own cells, supply chain management plays an integral role in chemistry, manufacturing and control processes. Supply chain management requires proactive planning because of the strict cold chain requirements and time sensitivity of CGTs. This research examines strategies and responses to challenges experienced by industry stakeholders (e.g., sponsors and manufacturers) during the implementation phases of clinical supply chain management. This research further evaluates the adequacy of the current regulatory framework for distribution and supply chain management of CGTs in the US. METHODS: A survey methodology was used to query subject matter experts from the biopharmaceutical industry who were familiar with the clinical supply management of CGTs in the US. The survey instrument was developed using an implementation framework and disseminated electronically to mid- and senior-level subject matter experts who had experience with clinical trials, supply chain management and CGTs. RESULTS: A total of 128 respondents accessed the survey, and 105 respondents answered at least one question. Seventy-five respondents completed the survey. Results showed that a lack of harmonization in regulations across the supply chain, limited resources, challenges with vendor management, high costs and complexities in the supply chain due to product specificity and customization proved to be impediments for the industry. In addition, the coronavirus disease 2019 pandemic had a significant impact on supply chain implementation. The results revealed that less than half of the respondents had business continuity plans in place. These challenges increased for smaller and mid-size organizations. Thirty percent of small and mid-size organizations were less prepared to scale up than larger companies. CONCLUSIONS: Suggestions from industry stakeholders were to adopt and enforce Good Distribution Practices in the US (81%), pre-plan distribution strategies with internal and external stakeholders along the supply chain and develop agile systems and robust processes end to end. Hurdles in scaling up and scaling out from the clinical to commercial phases for time- and temperature-sensitive CGT products make it difficult to predict the supply chain's long-term feasibility. Although there are initiatives to improve these impediments, such as improving industry partnerships and creating global CGT transportation standards, there are still regulatory knowledge gaps present for CGTs. Therefore, it is essential to establish a baseline and foundation for CGT supply chains extending beyond the loading dock.

UK multisite evaluation of the impact of clinical educators in EDs from a learner's perspective.

BACKGROUND: In England, demand for emergency care is increasing while there is also a staffing shortage. The Royal College of Emergency Medicine (RCEM) suggested that appointment of senior doctors as clinical educators (CEs) would enable support and development of learners in EDs and improve retention and well-being. This study aimed to evaluate the impact of CEs in ED on learners. METHODS: CEs were placed in 54 NHS Acute Trust EDs for a pilot beginning July 2018 and ending October 2020. Learners from multiple disciplines working at 54 NHS Acute Trust EDs where CEs were deployed were invited to complete an online survey designed to identify the impact of CEs in July of 2019, as part of an interim service evaluation. RESULTS: Respondents numbered 493 from 49 of 54 study sites, including 286 (58%) medical (non-consultant) and 72 (14.6%) all other nursing, allied health professionals. 9 out of 10 learners reported having experienced a change to their learning as a result of the deployment of CEs in their department. 49.9% (246/493) reported that CEs had a positive impact on their well-being. 95% (340/358) reported an improved accessibility to undertaking clinical based assessments. 78% (281/358) perceived that access to CEs increased likelihood of passing assessments. Of those responding, 80.9% (399/493) reported they would remain/return to the same ED with a CE, and 92.5% (456/493) responded that they would prefer to go to a Trust with a CE. CONCLUSIONS: According to survey respondents, deployment of CEs across NHS Trusts has resulted in improvement and increased accessibility of learning and assessment opportunities for learners within ED. The impact of CEs on well-being is uncertain with half reporting improvement and the remaining half unsure. Further evaluation within the project will continue to explore the service benefit and workforce impact of the CEED intervention.

Screening for distress and needs: Findings from a multinational validation of the Adolescent and Young Adult Psycho-Oncology Screening Tool with newly diagnosed patients.

OBJECTIVE: Adolescents and young adults (AYAs) diagnosed with cancer commonly experience elevated psychological distress and need appropriate detection and management of the psychosocial impact of their illness and treatment. This paper describes the multinational validation of the Distress Thermometer (DT) for AYAs recently diagnosed with cancer and the relationship between distress and patient concerns on the AYA-Needs Assessment (AYA-NA). METHODS: AYA patients (N = 288; 15-29 years, Mage  = 21.5 years, SDage  = 3.8) from Australia (n = 111), Canada (n = 67), the UK (n = 85) and the USA (n = 25) completed the DT, AYA-NA, Hospital Anxiety Depression Scale (HADS) and demographic measures within 3 months of diagnosis. Using the HADS as a criterion, receiver operating characteristics analysis was used to determine the optimal cut-off score and meet the acceptable level of 0.70 for sensitivity and specificity. Correlations between the DT and HADS scores, prevalence of distress and AYA-NA scores were reported. RESULTS: The DT correlated strongly with the HADS-Total, providing construct validity evidence (r = 0.65, p < 0.001). A score of 5 resulted in the best clinical screening cut-off on the DT (sensitivity = 82%, specificity = 75%, Youden Index = 0.57). Forty-two percent of AYAs scored at or above 5. 'Loss of meaning or purpose' was the AYA-NA item most likely to differentiate distressed AYAs. CONCLUSIONS: The DT is a valid distress screening instrument for AYAs with cancer. The AYA-POST (DT and AYA-NA) provides clinicians with a critical tool to assess the psychosocial well-being of this group, allowing for the provision of personalised support and care responsive to individuals' specific needs and concerns.

Pharmacists in advanced clinical practice roles in emergency departments (PARED).

Background Following evidence published in the Pharmacists in Emergency Departments (PIED 2016) study Health Education England funded novel advanced clinical practitioner training for pharmacists (ACP-p), to support service delivery.Objective To explore experiences and clinical activity of trainee ACP-p, and opinions and recommendations of both trainees and clinical supervisors.Setting Five Urgent/Emergency Care Departments in London UK.Method Longitudinal mixed-methods study in three phases of registered UK pharmacists appointed as trainee ACP-p. Phase 1 (May-July 2019) - early semi-structured interviews and focus group using an experiences, opinions and recommendations (EOR) framework, Phase 2 (January-December 2019) - prospective recording of trainee clinical activity, standardised using bespoke spreadsheet, Phase 3 (November-December 2019) - as Phase 1 but at conclusion of training.Main outcome measure Experiences, clinical activity, opinions and recommendations of study participants.Results Twelve (92 %) eligible trainee ACP-p and five supervisors were recruited. Identified themes were: trainee personality, educational components, length of programme, support/supervision, career transition, university and placement training alignment, recommendations. Success was dependent on effective support and supervision. Clinical supervisors should be allocated adequate supervision time. Trainees, their supervisors and emergency department staff should be given a clear brief. Study participants agreed that the programme could be successful. Trainee ACP-p reported that they could manage 82 % of 713 pre-selected clinical presentations. Additional training needs include: ECGs, X-rays and CT scans.Conclusions Pharmacists can successfully train as ACP-p in this setting over a two-year period. This career transition needs careful management and clear structures. Training ACP-p is a useful way of enhancing skills and supporting clinical services to large numbers of patients.

Feasibility of developing children's Pill School within a UK hospital.

OBJECTIVE: We assessed the feasibility of introducing an intervention (children's Pill School-PS) within a UK hospital to provide swallowing training for children, identified the proportion of children who can be switched from oral liquid medicines to pills and assessed children/parents' opinions about the PS training. METHODS: 30 inpatient children (aged 3-18 years; taking oral liquid medicines; their liquid medications assessed suitable for switching to pills; can (and their parents) speak/understand English were included. Training sessions were delivered using hard sweets of different sizes. RESULTS: 87% (26) of children successfully learnt how to swallow pills after one training session (mean duration 14.5 min), and 92% (24) were discharged on pills. 75 prescribed oral liquid medications were deemed suitable for switching to pills. Of these, 89% (67) were switched successfully. CONCLUSION: Children as young as 3 years were successful in swallowing pills after training. Providing children PS training session within hospital is feasible and acceptable to children and their parents.

Literature review of medication administration problems in paediatrics by parent/caregiver and the role of health literacy.

OBJECTIVE: To identify studies that highlighted medication administration problems experienced by parents and children, which also looked at health literacy aspect using a validated tool to assess for literacy. STUDY DESIGN: Ten electronic databases were systematically searched and supplemented by hand searching through reference lists using the following search terms: (1) paediatric, (2) medication error including dosing error, medication administration error, medication safety and medication optimisation and (3) health literacy. RESULTS: Of the (1230) records screened, 14 studies were eligible for inclusion. Three analytical themes emerged from the synthesis. The review highlighted that frequencies and magnitudes of dosing errors vary by the measurement tools used, the dose prescribed and by the administration instruction provided. Parent's sociodemographic, such as health literacy and language, is a key factor to be considered when designing an intervention aimed at averting medication administration errors at home. The review summarised some potential strategies that could help in reducing medication administration errors among children at home. Among these recommendations is to show the prescribed dose to the parents or young people along with the verbal instructions, as well as to match the prescribed dose with the measuring tool dispensed, to provide an explicit dose intervals and pictographic dosing instructions. CONCLUSION: The findings suggest that in order to optimise medication use by parents, further work is needed to address the nature of these issues at home. Counselling, medication administration instructions and measurement tools are some of the areas in addition to the sociodemographic characteristics of parents and young people that need to be considered when designing any future potential intervention aimed at reducing medication errors among children and young people at home.

Discovery of small molecule antagonists of chemokine receptor CXCR6 that arrest tumor growth in SK-HEP-1 mouse xenografts as a model of hepatocellular carcinoma.

The chemokine system plays an important role in mediating a proinflammatory microenvironment for tumor growth in hepatocellular carcinoma (HCC). The CXCR6 receptor and its natural ligand CXCL16 are expressed at high levels in HCC cell lines and tumor tissues and receptor expression correlates with increased neutrophils in these tissues contributing to poor prognosis in patients. Availability of pharmacologcal tools targeting the CXCR6/CXCL16 axis are needed to elucidate the mechanism whereby neutrophils are affected in the tumor environment. We report the discovery of a series of small molecules with an exo-[3.3.1]azabicyclononane core. Our lead compound 81 is a potent (EC50 = 40 nM) and selective orally bioavailable small molecule antagonist of human CXCR6 receptor signaling that significantly decreases tumor growth in a 30-day mouse xenograft model of HCC.

Biobank Continuity Management: A Survey of Biobank Professionals.

Academic biobanks face challenges that call for continuity and disaster planning. However, current regulations do not require such planning, so it is unclear if and how biobanks have prepared themselves to deal with future crises. This exploratory study used mixed methods to understand the state of continuity planning in U.S. biobanks. It first reviewed the current state of regulatory and implementation requirements that drive and challenge continuity planning. A survey instrument was then developed and critiqued by a focus group of experienced practitioners in biobanking. The refined survey was disseminated to a targeted group of respondents employed at biobanks across the United States. Most respondents were associated with relatively mature biobanks in operation for more than 6 years and these typically had some form of continuity plan in place. More commonly, continuity planning was reported to be focused on countering natural disasters rather than organization- or personnel-related crises. Respondents identified their most common limitation to be financial resources affecting all phases of implementation. Although many respondents appeared to be aware of some guidance documents and standards for continuity planning, many reported that they did not use or reference them when constructing their biobank continuity plans. Furthermore, nearly 25% of surveyed biobanks did not have a continuity plan and 61% indicated concern in having a mandated continuity plan. Results suggested academic organizations would benefit from a continuity plan template and best practice guidelines for plan development and implementation.

Higher Volume Surgeons Have Lower Medicare Payments, Readmissions, and Mortality After THA.

BACKGROUND: The advent of value-based care, in which surgeons and hospitals accept more responsibility for clinical and financial results, has increased the focus on surgeon- and hospital-specific outcomes. However, methods to identify high-quality, low-cost surgeons are not well developed. QUESTIONS/PURPOSES: (1) Is there an association between surgeon THA volume and 90-day Centers for Medicare & Medicaid Services (CMS) Part A payments, readmissions, or mortality? (2) What proportion of THAs in the United States is performed by low- and high-volume surgeons? METHODS: We performed a retrospective analysis of the CMS Limited Data Set on all primary elective THAs performed in the United States (except Maryland) between January 2013 and June 2016 on patients insured by Medicare. This represented 409,844 THAs totaling more than USD 7.7 billion in direct CMS expenditures. Surgeons were divided into five groups based on annualized volume of CMS elective THAs over the study period. Using linear and logistic regression, we calculated and compared 90-day CMS Part A payments, readmissions, and mortality among the groups. For each episode, demographic information (age, sex, and race), geographic location, and Elixhauser comorbidities were calculated to control for major confounding factors in the regression. RESULTS: When compared with the highest volume group, each lower volume group had increased payments, increased readmission rates, and increased mortality rates in a stepwise fashion when controlling for patient-specific variables including Elixhauser comorbidity index, demographic information, region, and background trend. The lowest volume group resulted in 27.2% more CMS payments per case (p < 0.001; 95% confidence interval [CI], 26.6%-27.8%), had an increased readmission odds ratio (OR) of 1.8 (p < 0.001; 95% CI, 1.7-1.9), and an increased mortality OR of 4.7 (p < 0.001; 95% CI, 4.0-5.5) when compared with the highest volume group. There was also variation within volume groups: some lower volume surgeons had lower payments, readmissions, and mortality than some higher volume surgeons despite the general trend. In terms of CMS volume, surgeons who were at least moderate volume (11+ annual cases) performed 78% of THAs and represented 26% of operating surgeons. The low- and lowest volume surgeons (10 or fewer annual cases) performed only 22% of THAs in the United States while representing 74% of unique operating surgeons. CONCLUSIONS: There is a strong association between a surgeon's Medicare volume and lower CMS payments, readmissions, and mortality. Furthermore, the majority of Medicare THAs in the United States are performed by surgeons who perform > 10 CMS operations annually. Compared with previous work, these results suggest a trend toward higher volume surgeons in the Medicare population. The results also suggest a benefit to the shift toward higher volume surgeons in reducing payments, readmissions, and mortality for elective THA in the United States. However, given that payments, readmission, and mortality of surgeons varied widely, it is important to note that available individual CMS data can be used to directly evaluate each individual surgeon based on their actual results well as through association with volume. LEVEL OF EVIDENCE: Level III, therapeutic study.

Identification and characterization of small molecule inhibitors of the ubiquitin ligases Siah1/2 in melanoma and prostate cancer cells.

Inhibition of ubiquitin ligases with small molecule remains a very challenging task, given the lack of catalytic activity of the target and the requirement of disruption of its interactions with other proteins. Siah1/2, which are E3 ubiquitin ligases, are implicated in melanoma and prostate cancer and represent high-value drug targets. We utilized three independent screening approaches in our efforts to identify small-molecule Siah1/2 inhibitors: Affinity Selection-Mass Spectrometry, a protein thermal shift-based assay and an in silico based screen. Inhibitors were assessed for their effect on viability of melanoma and prostate cancer cultures, colony formation, prolyl-hydroxylase-HIF1α signaling, expression of selected Siah2-related transcripts, and Siah2 ubiquitin ligase activity. Several analogs were further characterized, demonstrating improved efficacy. Combination of the top hits identified in the different assays demonstrated an additive effect, pointing to complementing mechanisms that underlie each of these Siah1/2 inhibitors.

2018 John Charnley Award: Analysis of US Hip Replacement Bundled Payments: Physician-initiated Episodes Outperform Hospital-initiated Episodes.

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) launched the Bundled Payment for Care Improvement (BPCI) initiative in 2013 to create incentives to improve outcomes and reduce costs in various clinical settings, including total hip arthroplasty (THA). This study seeks to quantify BPCI initiative outcomes for THA and to determine the optimal party (for example, hospital versus physician group practice [PGP]) to manage the program. QUESTIONS/PURPOSES: (1) Is BPCI associated with lower 90-day payments, readmissions, or mortality for elective THA? (2) Is there a difference in 90-day payments, readmissions, or mortality between episodes initiated by PGPs and episodes initiated by hospitals for elective THA? (3) Is BPCI associated with reduced total Elixhauser comorbidity index or age for elective THA? METHODS: We performed a retrospective analysis on the CMS Limited Data Set on all Medicare primary elective THAs without a major comorbidity performed in the United States (except Maryland) between January 2013 and March 2016, totaling more than USD 7.1 billion in expenditures. Episodes were grouped into hospital-run BPCI (n = 42,922), PGP-run BPCI (n = 44,662), and THA performed outside of BPCI (n = 284,002). All Medicare Part A payments were calculated over a 90-day period after surgery and adjusted for inflation and regional variation. For each episode, age, sex, race, geographic location, background trend, and Elixhauser comorbidities were determined to control for major confounding variables. Total payments, readmissions, and mortality were compared among the groups with logistic regression. RESULTS: When controlling for demographics, background trend, geographic variation, and total Elixhauser comorbidities in elective Diagnosis-Related Group 470 THA episodes, BPCI was associated with a 4.44% (95% confidence interval [CI], -4.58% to -4.30%; p < 0.001) payment decrease for all participants (USD 1244 decrease from a baseline of USD 18,802); additionally, odds ratios (ORs) for 90-day mortality and readmissions were unchanged. PGP groups showed a 4.81% decrease in payments (95% CI, -5.01% to -4.61%; p < 0.001) after enrolling in BPCI (USD 1335 decrease from a baseline of USD 17,841). Hospital groups showed a 4.04% decrease in payments (95% CI, -4.24% to 3.84%; p < 0.01) after enrolling in BPCI (USD 1138 decrease from a baseline of USD 19,799). The decrease in payments of PGP-run episodes was greater compared with hospital-run episodes. ORs for 90-day mortality and readmission remained unchanged after BPCI for PGP- and hospital-run BPCI programs. Patient age and mean Elixhauser comorbidity index did not change after BPCI for PGP-run, hospital-run, or overall BPCI episodes. CONCLUSIONS: Even when controlling for decreasing costs in traditional fee-for-service care, BPCI is associated with payment reduction with no change in adverse events, and this is not because of the selection of younger patients or those with fewer comorbidities. Furthermore, physician group practices were associated with greater payment reduction than hospital programs with no difference in readmission or mortality from baseline for either. Physicians may be a more logical group than hospitals to manage payment reduction in future healthcare reform. LEVEL OF EVIDENCE: Level II, economic and decision analysis.

The treatment-related experiences of parents, children and young people with regular prescribed medication.

Background Taking regular medication has been shown to have an impact on the daily lives of patients and their families. Objective To explore the medication-related experiences of patients and their families when a child or young person is prescribed regular medication. Setting A specialist U.K. paediatric hospital. Method Semi-structured face-to-face interviews of 24 parents/carers, children or young people, who had been taking two or more medications for 6 weeks or longer. The themes explored included the medication regimen, formulation, supplies, social aspects and adverse effects. The data was analysed using NVIVO version 11. Main outcome measure The experiences of patients, and their parents/carers, when a child/young person takes regular medication. Results Participants described a range of experiences associated with taking regular medication. Medication-related challenges were experienced around the timing of administration which was managed over 24 h rather than waking hours. Updating medication doses for administration at school was often delayed. Unintended nonadherence was cited as the biggest challenge with a range of strategies employed to manage this. The internet was commonly used as a source of additional information accessed for reassurance and adverse effects but there were varying experiences of using patient forums/help groups. Other challenges included the adequacy of information, travelling with medication, formulation issues, arranging supplies and adverse effects. Conclusion Patients and parents experience many challenges with children's medication. Individualised treatment options should be considered. Further research is required to determine how these experiences may be managed including the role of paediatric medication review.

Repurposing antimalarial aminoquinolines and related compounds for treatment of retinal neovascularization.

Neovascularization is the pathological driver of blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. The loss of vision resulting from these diseases significantly impacts the productivity and quality of life of patients, and represents a substantial burden on the health care system. Current standard of care includes biologics that target vascular endothelial growth factor (VEGF), a key mediator of neovascularization. While anti-VGEF therapies have been successful, up to 30% of patients are non-responsive. Therefore, there is a need for new therapeutic targets, and small molecule inhibitors of angiogenesis to complement existing treatments. Apelin and its receptor have recently been shown to play a key role in both developmental and pathological angiogenesis in the eye. Through a cell-based high-throughput screen, we identified 4-aminoquinoline antimalarial drugs as potent selective antagonists of APJ. The prototypical 4-aminoquinoline, amodiaquine was found to be a selective, non-competitive APJ antagonist that inhibited apelin signaling in a concentration-dependent manner. Additionally, amodiaquine suppressed both apelin-and VGEF-induced endothelial tube formation. Intravitreal amodaiquine significantly reduced choroidal neovascularization (CNV) lesion volume in the laser-induced CNV mouse model, and showed no signs of ocular toxicity at the highest doses tested. This work firmly establishes APJ as a novel, chemically tractable therapeutic target for the treatment of ocular neovascularization, and that amodiaquine is a potential candidate for repurposing and further toxicological, and pharmacokinetic evaluation in the clinic.

Current opinions and recommendations of paediatric healthcare professionals - The importance of tablets: Emerging orally disintegrating versus traditional tablets.

The appropriate prescribing of paediatric dosage forms is paramount in providing the desired therapeutic effect alongside successful medication adherence with the paediatric population. Often it is the opinion of the healthcare practitioner that dictates which type of dosage form would be most appropriate for the paediatric patient, with liquids being both the most commonly available and most commonly used. Orally disintegrating tablets (ODTs) are an emerging dosage form which provide many benefits over traditional dosage forms for paediatric patients, such as rapid disintegration within the oral cavity, and the reduction in the risk of choking. However the opinion and professional use of healthcare practitioners regarding ODT's is not known. This study was designed to assess the opinions of several types of healthcare professionals (n = 41) regarding ODTs, using a survey across two hospital sites. Results reaffirmed the popularity of liquids for prescribing in paediatrics, with 58.0% of participants preferring this dosage form. ODTs emerged as the second most popular dosage form (30.0%), with healthcare practitioners indicating an increasing popularity amongst patients in the hospital setting, belief with 63.0% of practitioners agreeing that many liquid formulations could be substituted with a suitable ODT. The desired properties of an ideal ODT were also identified by healthcare practitioners preferring a small, fast disintegrating tablet (90.2% and 95.1% respectively), with the taste, disintegration time and flavour being the three most important attributes identified (29.5%, 28.7% and 21.7% respectively). This study provided a pragmatic approach in assessing healthcare professional's opinions on ODTs, highlighting the ideas and thoughts of practitioners who are on the frontline of paediatric prescribing and treatment and gave an indication to their preference for ODT properties.

Children/young people taking long-term medication: a survey of community pharmacists' experiences in England.

OBJECTIVES: To determine whether community pharmacists undertake medication reviews with children/their carers and to identify the type of medication-related experiences presented to them when a child is taking long-term medication. METHODS: A 13 question semi-structured survey was posted to 354 England-based community pharmacists with telephone follow-up/repeat mailing of non-responders. Participants were asked about their practice as a community pharmacist over the preceding 12 months to children/young people, or their carers, taking long-term medication. The questionnaire covered: medication review, reported adherence, information requests, adverse effects, administration and obtaining medication supplies. The data were analysed using SPSS version 22 and NVivo version 10. RESULTS: The response rate was 76/354 (21.5%). Eighteen (23.7%) respondents had undertaken a Medicines Use Review (MUR) and 22 (28.9%) a New Medicines Service (NMS) medication review with a child/their carer. Participants reported that patients/their carers had presented to them with non-adherence including stopping medication (24, 31.6%) and changing the dose (28, 36.8%). Respondents were directly asked about the indication (59, 77.6%), dose regimen (63, 82.9%), administration (64, 84.2%) and adverse effects (58, 76.3%) of prescribed medication. Respondents reported patients/carers experiencing difficulties obtaining medication from their community pharmacy (47, 61.8%) and patients' family doctors declining to prescribe a medication recommended by a specialist (27, 35.5%). CONCLUSIONS: Medicines Use Review and NMS reviews are utilised by community pharmacists in children/their carers. The medication-related experiences presenting to community pharmacists could fall within the purview of a medication review (MUR or NMS). There is scope to further extend this service to this group of patients/carers.

Future enhanced clinical role of pharmacists in Emergency Departments in England: multi-site observational evaluation.

Background There are concerns about maintaining appropriate clinical staffing levels in Emergency Departments. Pharmacists may be one possible solution. Objective To determine if Emergency Department attendees could be clinically managed by pharmacists with or without advanced clinical practice training. Setting Prospective 49 site cross-sectional observational study of patients attending Emergency Departments in England. Method Pharmacist data collectors identified patient attendance at their Emergency Department, recorded anonymized details of 400 cases and categorized each into one of four possible options: cases which could be managed by a community pharmacist; could be managed by a hospital pharmacist independent prescriber; could be managed by a hospital pharmacist independent prescriber with additional clinical training; or medical team only (unsuitable for pharmacists to manage). Impact indices sensitive to both workload and proportion of pharmacist manageable cases were calculated for each clinical group. Main outcome measure Proportion of cases which could be managed by a pharmacist. Results 18,613 cases were observed from 49 sites. 726 (3.9%) of cases were judged suitable for clinical management by community pharmacists, 719 (3.9%) by pharmacist prescribers, 5202 (27.9%) by pharmacist prescribers with further training, and 11,966 (64.3%) for medical team only. Impact Indices of the most frequent clinical groupings were general medicine (13.18) and orthopaedics (9.69). Conclusion The proportion of Emergency Department cases that could potentially be managed by a pharmacist was 36%. Greatest potential for pharmacist management was in general medicine and orthopaedics (usually minor trauma). Findings support the case for extending the clinical role of pharmacists.

Paediatric Patient Safety and the Need for Aviation Black Box Thinking to Learn From and Prevent Medication Errors.

Since the publication of To Err Is Human: Building a Safer Health System in 1999, there has been much research conducted into the epidemiology, nature and causes of medication errors in children, from prescribing and supply to administration. It is reassuring to see growing evidence of improving medication safety in children; however, based on media reports, it can be seen that serious and fatal medication errors still occur. This critical opinion article examines the problem of medication errors in children and provides recommendations for research, training of healthcare professionals and a culture shift towards dealing with medication errors. There are three factors that we need to consider to unravel what is missing and why fatal medication errors still occur. (1) Who is involved and affected by the medication error? (2) What factors hinder staff and organisations from learning from mistakes? Does the fear of litigation and criminal charges deter healthcare professionals from voluntarily reporting medication errors? (3) What are the educational needs required to prevent medication errors? It is important to educate future healthcare professionals about medication errors and human factors to prevent these from happening. Further research is required to apply aviation's 'black box' principles in healthcare to record and learn from near misses and errors to prevent future events. There is an urgent need for the black box investigations to be published and made public for the benefit of other organisations that may have similar potential risks for adverse events. International sharing of investigations and learning is also needed.