The receptor for advanced glycation endproducts (RAGE) is an ubiquitous, transmembrane, immunoglobulin-like receptor that exists in multiple isoforms and binds to a diverse range of endogenous extracellular ligands and intracellular effectors. Ligand binding at the extracellular domain of RAGE initiates a complex intracellular signaling cascade, resulting in the production of reactive oxygen species (ROS), immunoinflammatory effects, cellular proliferation, or apoptosis with concomitant upregulation of RAGE itself. To date, research has mainly focused on the correlation between RAGE activity and pathological conditions, such as cancer, diabetes, cardiovascular diseases, and neurodegeneration. Because RAGE plays a role in many pathological disorders, it has become an attractive target for the development of inhibitors at the extracellular and intracellular domains. This review describes the role of endogenous RAGE ligands/effectors in normo- and pathophysiological processes, summarizes the current status of exogenous small-molecule inhibitors of RAGE and concludes by identifying key strategies for future therapeutic intervention.

Aim: The receptor for advanced glycation end products (RAGE) is a viable target for early Alzheimer’s disease (AD) diagnosis using positron emission tomography (PET) as RAGE overexpression precedes Aβ plaque formation. The development of a carbon-11 analog of FPS-ZM1 (N-benzyl-4-chloro-N-cyclohexylbenzamide, [11C]FPS-ZM1), possessing nanomolar affinity for RAGE, may enable the imaging of RAGE for early AD detection. Methodology & results: Herein we report an optimized [11C]CO2-to-[11C]CO chemical conversion for the synthesis of [11C]FPS-ZM1 and in vitro brain autoradiography. The [11C]CO2-to-[11C]CO conversion via 11C-silanecarboxylate derivatives was achieved with a 57% yield within 30 s from end of [11C]CO2 delivery. [11C]FPS-ZM1 was obtained with a decay-corrected isolated radiochemical yield of 9.5%. Conclusion: [11C]FPS-ZM1 distribution in brain tissues of wild-type versus transgenic AD model mice showed no statistically significant difference and high nondisplaceable binding.

Background The ‘Clinical Pharmacists in General Practice’ (CPGP) pilot provided a template for general practice pharmacy professionals’ (GPPPs) roles encouraging NHS England to fund >2000 practice-based pharmacists. However, many GPPPs work outside the CPGP initiative and little is known about the services they provide. Objectives To explore services provided by all UK GPPPs (pharmacists/pharmacy technicians), including the types of services, perceived benefits and barriers to role development. Methods A 26-item electronic questionnaire was developed using SurveyMonkey and piloted during cognitive interviews. A cross-sectional survey was conducted via social media, primary care organisations and emails to CPGP pilot sites between November 2018 and March 2019. Three reminders were sent 1 week apart. Key findings Ninety-one complete responses were received (81 pharmacists; 10 technicians). Over 80% of pharmacists provided clinical services, such as medication reviews or management of long-term conditions. More pharmacists within CPGP pilot managed repeat prescribing requests (P = 0.035). Technicians took responsibility for primarily non-clinical roles, including commissioning or safety alerts/drug recalls. A third of GPPPs wished to develop care home services. Perceived benefits of GPPPs’ services included improved utilisation/development of professional skills, identifying medicines-related issues and reduction in medication waste. Respondents were satisfied with professional relationships but reported workload issues, limited patient awareness of their roles and restricted opportunities to contribute to service development, which was associated with unsatisfactory support/mentorship (P < 0.001). Conclusion General practice pharmacy professionals deliver clinical and non-clinical services which may benefit patients, general practice and the healthcare system. General practices and national organisations should provide GPPPs with tailored support and exploit the combined strengths of pharmacists and pharmacy technicians to tackle increased workload.

Background Growing prevalence of atrial fibrillation (AF) in the ageing population and its associated life-changing health and resource implications have led to a need to improve its early detection. Primary care is an ideal place to screen for AF; however, this is limited by shortages in general practitioner (GP) resources. Recent increases in the number of clinical pharmacists within primary care makes them ideally placed to conduct AF screening. This study aimed to determine the feasibility of GP practice–based clinical pharmacists to screen the over-65s for AF, using digital technology and pulse palpation during the influenza vaccination season. Methods and findings Screening was conducted over two influenza vaccination seasons, 2017–2018 and 2018–2019, in four GP practices in Kent, United Kingdom. Pharmacists were trained by a cardiologist to pulse palpate, record, and interpret a single-lead ECG ( SL ECG). Eligible persons aged ≥65 years (y) attending an influenza vaccination clinic were offered a free heart rhythm check. Six hundred four participants were screened (median age 73 y, 42.7% male). Total prevalence of AF was 4.3%. All participants with AF qualified for anticoagulation and were more likely to be male (57.7%); be older; have an increased body mass index (BMI); and have a CHA 2 DS 2 -VASc (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke, Vascular disease, Age 65–74 years, Sex category) score ≥ 3. The sensitivity and specificity of clinical pharmacists diagnosing AF using pulse palpation was 76.9% (95% confidence interval [CI] 56.4–91.0) and 92.2% (95% CI 89.7–94.3), respectively. This rose to 88.5% (95% CI 69.9–97.6) and 97.2% (95% CI 95.5–98.4) with an SL ECG. At follow-up, four participants (0.7%) were diagnosed with new AF and three (0.5%) were initiated on anticoagulation. Screening with SL ECG also helped identify new non-AF cardiovascular diagnoses, such as left ventricular hypertrophy, in 28 participants (4.6%). The screening strategy was cost-effective in 71.8% and 64.3% of the estimates for SL ECG or pulse palpation, respectively. Feedback from participants (422/604) was generally positive. Key limitations of the study were that the intervention did not reach individuals who did not attend the practice for an influenza vaccination and there was a limited representation of UK ethnic minority groups in the study cohort. Conclusions This study demonstrates that AF screening performed by GP practice–based pharmacists was feasible, economically viable, and positively endorsed by participants. Furthermore, diagnosis of AF by the clinical pharmacist using an SL ECG was more sensitive and more specific than the use of pulse palpation alone. Future research should explore the key barriers preventing th...

Background The prevalence of atrial fibrillation (AF) amongst care home residents ranges from 7–19% with the number of undiagnosed cases five-fold above that of the general population. Clinical pharmacists providing services to care homes may offer opportunistic AF screening, improving residents' access to timely diagnosis and treatment. Purpose The aim of this feasibility study was to determine the prevalence of AF in UK care homes and to evaluate the feasibility of clinical pharmacist-led AF screening in this setting. It also aimed to ascertain the proportion of residents who could be screened using pulse palpation and single-lead electrocardiogram (ECG) and those with new AF who qualified for anticoagulant therapy. Methods This screening initiative was delivered in 4 care homes linked to 2 general practices in Kent (UK). The clinical pharmacist providing AF screening was trained by a cardiologist to pulse palpate and record a mobile ECG. A designated general practitioner (GP) assessed each resident's mental capacity to consent. Any residents with mental capacity and no pacemaker were offered a free heart rhythm check with the pharmacist. After written consent, each participant underwent a pulse palpation (1 min), followed by ECG (30 sec) and a provisional diagnosis. All ECGs were overread by a cardiologist within 72 hrs, and any residents requiring further investigation were referred to their GP. Results Fifty-three eligible individuals (mean age 90 years, 76% female) were screened between October 2018 and January 2019. Fifty-eight residents (52%) could not be screened due to lack of mental capacity. One participant with a regular pulse could not be tested with the ECG device due to severe hand tremor. The quality of 14 ECGs (27%) was determined as poor. Following the cardiologist's interpretation, 17 residents (33%) required a 12-lead ECG: 7 (14%) with possible AF and 10 (19%) with an inconclusive result. Amongst those with suspected AF, 5 had hypertension, 3 - chronic kidney disease and 2 - diabetes mellitus or peripheral vascular disease. Five had not been previously diagnosed with AF and all qualified for anticoagulant therapy (CHA2DS2-VASc ≥2). The device's algorithm displayed low sensitivity for AF (57%) despite greater agreement with the cardiologist's interpretation (Cohen's κ 0.70) than either the pharmacist's interpretation (0.56) or pulse palpation (0.44). Conclusion(s) This research was the first of its kind in UK care homes and identified a suspected AF prevalence >5 times higher than in the general population. Several barriers to AF screening in this setting, including mental incapacity and physical comorbidities, led to poor ECG quality, low diagnostic accuracy and 1 in 5 inconclusive diagnoses potentially limiting the economic viability of the intervention proposed. Future studies will explore the feasibility of using alternative strategies which may circumvent these barriers to AF screening in care homes. Acknowledgement/Funding This work was supported by Kent Surrey and Sussex Community Education Providers Network and Faculty of Science Research Funding, University of Kent.

BackgroundAtrial fibrillation (AF) affects up to 10% of people aged ≥65 years, yet a third of all cases remain undetected. Practice-based pharmacists are in an ideal position to facilitate opportunistic AF screening, while increasing general practice capacity at a time of workforce crisis.AimTo explore the perspectives of three stakeholder groups involved in the ‘Pharmacists Detecting Atrial Fibrillation’ (PDAF) study to elucidate the facilitators and barriers to pharmacist-led AF screening in general practice.Design & settingA qualitative study took place, comprising homogeneous focus groups with stakeholders in Kent, UK.MethodThe stakeholder groups — patients, general practice staff (GPS), and clinical pharmacists (CPs) — were recruited using convenience sampling. Audio-recordings were transcribed verbatim and analysed using a deductive Theoretical Domains Framework (TDF) approach.ResultsTwenty-five patients, four pharmacists, and nine practice staff participated in six focus groups. Three main themes were identified: knowledge and awareness; prioritisation of resources; and environmental considerations. The public’s lack of awareness of AF-related risks and pharmacist-led screening services was highlighted. Practice-based pharmacists were perceived as an underutilised educational resource which, together with novel electrocardiogram devices, enabled convenient access to screening while reducing GPs’ workload. Participants agreed that AF screening should be incorporated into personalised health checks and at-risk groups should be prioritised, such as care home residents. Patients favoured the general practice environment over the community pharmacy where concerns of privacy, staffing, and commercialisation were raised.ConclusionThe findings of this study support the introduction of pharmacist-led AF screening programmes in general practice surgeries. Commissioners should consider the added value of utilising CPs and focus on the delivery of AF screening within an integrated service.

Objective Increased demands from healthcare services have led to new roles for healthcare professionals (HCPs). Simulation based learning (SBL) can offer multidisciplinary HCPs and students a format to train for such emerging roles. The aim of this work was to adapt existing nursing SBL to involve pharmacy students and evaluate perceptions and effectiveness of SBL when used for interprofessional education (IPE). Methods Settings were a simulated hospital ward and a general practitioner (GP) practice. Participants were pharmacy and nursing students. Evaluation was by questionnaires and interviews. Ethical approval was obtained from the University Ethics Committee. Key Findings A total of 440 students participated. The majority of respondents (317/330;96%) found the sessions useful. All elements were highly rated: briefing (315/340;93%), setting (301/321;94%), scenario (325/338;96%), feedback (303/327;93%), interaction with the “patient” (328/338;97%), interactions with other HCP trainee (293/329;89%). The majority (304/327;93%) agreed that they felt the sessions had enhanced their skills. Significant (p ≤ 0.05) enhancement in communication confidence was perceived by the students. Students gained understanding of each other's roles, and appreciated practicing communication and teamwork. Conclusions Students recognised the importance, usefulness and need for IPE. SBL has the potential to support a variety of HCPs to facilitate uptake of new roles and working in multidisciplinary teams.

IntroductionAtrial fibrillation (AF) affects >6% of people aged 65 years or older. Left undetected and untreated, patients may develop significant cardiovascular complications and have a fivefold increased risk of suffering a stroke. For 40% of all sufferers, AF can be asymptomatic. Every year in the UK, £2.2 billion is spent on AF-related strokes, so there is an urgent need to improve early detection of AF. This study aims to determine the feasibility of using trained clinical pharmacists based in general practices, to screen for AF, using pulse palpation and a single-lead ECG device on participants aged 65 years or older, attending influenza vaccination clinics.Methods and analysisSeven clinical pharmacists will be trained by a cardiologist to pulse palpate and record single-lead ECGs using the AliveCor Kardia Mobile device. Quantitative analysis will assess the accuracy and ability of the clinical pharmacist to identify pulse irregularities using pulse palpation and to record and interpret a single-lead ECG. The level of agreement of pulse irregularities detected by pulse palpation will be compared with those detected by the single-lead ECG device, as will the level of agreement between the cardiologist and the device’s interpretation of the ECG. The proportion of people identified with AF (confirmed by the cardiologist) will be determined. Additional demographic data will be obtained from all participants through a questionnaire. Qualitative data will be captured from the participants, from the clinical pharmacists and from the general practitioners and practice staff to determine their views on this method of AF screening. We aim to recruit 600 participants across general practices within Kent.Ethics and disseminationThis protocol was approved by the London–Riverside Research Ethics committee. The findings of this study will be disseminated through forums including, but not limited to, peer-reviewed journals, national and international conferences.