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.

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...