Evaluating initiation and real-world tolerability of dapagliflozin for the management of HFrEF.

Untreated heart failure with reduced ejection fraction (HFrEF) has a one-year mortality rate of 40%. The DAPA-HF trial found that dapagliflozin reduces mortality and heart failure (HF) hospitalisation by 17% and 30%, respectively. We describe the initiation and real-world tolerability of dapagliflozin for the management of HFrEF at a large university teaching hospital in central London. We reviewed 118 HFrEF patients initiated on dapagliflozin from January to August 2021 in both inpatient and outpatient settings using the Trust's electronic records. A total of 69 (58.4%) patients were on optimised HF pharmacological therapy upon initiation of dapagliflozin. Dapagliflozin was discontinued in 12 (13.0%) patients. Twenty-three (42.6%) patients either discontinued or had a dose reduction in loop diuretics post-initiation of dapagliflozin. In clinical practice, early initiation of dapagliflozin is safe, well-tolerated and resulted in earlier discontinuation or dose reduction in loop diuretics, providing opportunities to further optimise other HF medicines. This retrospective observational study supports the safety of the updated European Society of Cardiology (ESC) guidelines to initiate all four key HF medicines to minimise delays in HF treatment optimisation, which could translate to reduced National Health Service healthcare costs through fewer HF hospitalisations.

Evaluation of the impact of the addition of a heart failure prescribing pharmacist to consultant-led heart failure ward round at a tertiary hospital.

OBJECTIVE: Pharmacists attending general medical post-admission ward rounds is established good practice. However, there is a lack of evidence on the impact of specialist heart failure (HF) prescribing pharmacists on consultant HF ward rounds. The aim of this study was to evaluate the impact on prescribing when a specialist HF prescribing pharmacist attended inpatient HF ward rounds. METHODS: A prospective service evaluation completed at a tertiary hospital between September and December 2020. The same HF prescribing pharmacist attended the HF consultant-led ward round once a week on 15 occasions. For each medicine change, the pharmacist documented: who suggested the intervention, the medicine, prescribing action, reason for review and the primary reason for change. Medicines were categorised into four groups (heart failure, cardiovascular, anticoagulation and other) for analysis. RESULTS: A total of 158 patients were reviewed and 226 individual changes suggested; 48% of these were consultant led (n=108) and 52% (n=118) due to pharmacist recommendations. All medicines interventions were prescribed on the round by the pharmacist. For consultants, the primary reason for medicine change was to ensure efficacy of HF medicines, 80% (n=73), followed by safety (HF medicines), 20% (n=18). For the pharmacist, the primary reason was safety across all the medicine groups, 36% (n=42), followed by efficacy relating to missing drug history items, 24% (n=28). CONCLUSIONS: HF consultants focused on ensuring patients have the most effective combination of HF medications. The addition of a specialist HF prescribing pharmacist ensured a wider range of medicines were reviewed for safety and optimisation, helping to deliver a holistic review of all medications.

Clinical pharmacy services in a London hospital, have they changed?

BACKGROUND: The development of clinical pharmacy, has created a need for pharmacists to demonstrate the service they provide to hospital boards. OBJECTIVES: To describe and compare the type and frequency of clinical pharmacy contributions to individual patients admitted to a large teaching hospital within a 1 week study period over four consecutive years 2009-2012. METHOD: This study was a prospective 1 week study over 4 years (2009-2012). Pharmacists used data collection sheets to record the primary reason and outcome of interventions made. RESULTS: The most frequent reasons for pharmacists intervening in patient care have been due to efficacy of medication and for safety to prevent an adverse drug reaction. The percentage of accepted interventions by the medical team was similar ranging from 85 to 92 %. CONCLUSIONS: Pharmacists consistently carried out interventions to patient care over a 4 year period and provide the Trust with a service that focuses on ensuring safety and efficacy of the medications administered. Impact of findings on practice Daily clinical pharmacy services in a UK teaching hospital allow pharmacists to contribute to protecting patients from the adverse effects of medications. Pharmacists most frequently intervene to patient care for the reasons of medication efficacy and safety and to prevent adverse drug reactions.

beta-Arrestin 2-mediated heterologous desensitization of IGF-IR by prolonged exposure of SH-SY5Y neuroblastoma cells to a mu opioid agonist.

Prolonged (12h) exposure of SH-SY5Y neuroblastoma cells to the mu-opioid receptor (MOPr) agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) causes homologous desensitization as well as heterologous desensitization of the extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation induced by insulin-like growth factor (IGF)-I. Brief (15 min) but not prolonged exposure to DAMGO transregulates the insulin-like growth factor-I (IGF-I) receptor, as evidenced by its phosphorylation in the absence of IGF-I. Silencing of beta-arrestin 2 uncouples the crosstalk between the two receptors, thus maintaining IGF-I-mediated receptor phosphorylation and ERK 1/2 activation even after prolonged DAMGO exposure. Furthermore, MOPr-induced activation of IGF-I receptor requires the tyrosine kinase c-Src.