Medical Pharmacology and Therapeutics by Derek G. Waller and Anthony P. Sampson

A thorough and contemporaneous working knowledge of both pharmacology and therapeutics is integral to the current practice of pharmacy, and both disciplines form a significant and rudimentary part of the undergraduate curricula. It is vital that the student is able to formulate scientific rationale for the use of pharmacological agents in the treatment of disease, and that a sound underpinning knowledge of all relevant disciplines enables them to do so. Of equal importance is the ability of the teacher to present essential information about pharmacology and therapeutics as part of an integrated curricula in a way that engages the student and enhances their appreciation of the applicability of these various disciplines to clinical practice. Waller and Sampson’s ‘Medical Pharmacology and Therapeutics’ aims to encourage a deeper understanding of the principals of drug usage by explaining the basic science underpinning clinical application of pharmacological agents. This review seeks to investigate elements that are specific to the needs of the target audience and will explore the potential of this book in achieving those aims

Investigating inpatient insulin prescribing practice and intervention use in UK hospitals: a mixed methods study and realist synthesis

Insulin prescription errors are a common, costly problem in NHS hospitals in the United Kingdom (UK), and are a consistent source of unintentional harm to inpatients with diabetes. Prompted by the lack of large-scale quantitative and qualitative research conducted in the UK in this area, this research aimed to investigate inpatient insulin prescribing practice and the current use of interventions designed to prevent insulin prescription errors in UK hospitals. Following the conduct of a systematic review of interventions designed to reduce inpatient insulin prescribing errors, a questionnaire was developed, validated, and used as part of a cross-sectional survey of chief/diabetes pharmacists representing every NHS acute trust in the UK. Information was captured regarding the use, functionality and perceived effectiveness of insulin prescribing systems and interventions. Follow-up qualitative interviews were conducted with survey respondents to further analyse their experiences and opinions regarding insulin prescribing practice and intervention use. Realist synthesis was then undertaken to further understand how insulin self-administration policy interventions worked in different contexts. A participatory health research approach was taken throughout the research to maximise relevance and impact of the research for end-users, and a combination of middle-range theories were used throughout the research to aid the transferability of findings. Ninety-five hospital trusts responded to the survey (54%), 18 of whom participated in follow-up interviews. Results indicated that a wide range of prescribing systems with varying functionalities were in use, along with a diverse range and combination of error-prevention interventions. Intervention use was positively associated with the availability of specialist diabetes pharmacists (P=0.002), who worked with diabetes teams to improve insulin safety in their organisations. Although mandatory insulin training was used by only 46% of trusts, it was perceived to be very effective at preventing errors. This was due to the perceived lack of understanding and confidence prescribers have with insulin, but the difficulties associated with accessing staff to deliver training in hospital. The insulin passport was perceived to be ineffective and only used by 31% of trusts on account of faults in its design, incompatibility with existing systems, and unreliable use by patients. Self-administration policy interventions were used by 63% hospitals and were described as salient but complex to implement; The use of realist synthesis generated 10 programme theories to further explain how they work, for whom and in what circumstances. Key contexts, outcomes and mechanisms were identified, including hierarchical and blame cultures, patient empowerment, control, shared decision-making, and clarification of roles. As the first study to investigate insulin prescribing practice and intervention use at a multi-organisational level in the UK, this research contributes to the literature by describing and explaining how interventions may be used to improve the care received by inpatient with diabetes. Actionable findings are included that may help hospitals and policymakers implement interventions that are most likely to result in successful outcomes

Evaluating insulin information provided on discharge summaries in a secondary care hospital in the United Kingdom

Abstract Background: Prescribing errors at the time of hospital discharge are common and could potentially lead to avoidable patient harm, especially when they involve insulin, a high-risk medicine widely used for the treatment of diabetes mellitus. When information regarding insulin therapy is not sufficiently communicated to a patient’s primary care provider, continuity of care for patients with diabetes may be compromised. The objectives of this study were to investigate the nature and prevalence of insulin-related medication discrepancies contained in hospital discharge summaries for patients with diabetes. A further objective was to examine the timeliness and completeness of relevant information regarding insulin therapy provided on discharge summaries. Methods: The study was undertaken at a large foundation trust hospital in the North of England, UK. A retrospective analysis of discharge summaries of all patients who were being treated with insulin and were included in the 2016 National Inpatient Diabetes Audit was conducted. Insulin regimen information provided on discharge summaries was scrutinised in light of available medical records pertaining to the admission and current national recommendations. Results: Thirty-three (79%) out of the 42 patients included in the study had changes made to their insulin regimen during hospital admission. Eighteen (43%) patients were identified as having an error or discrepancy relating to insulin on their discharge summary. A total of 27 insulin errors or discrepancies were identified on discharge, most commonly involving non-communication of an insulin dose change (n = 8) and wrong insulin device (n = 7). Seventeen issues relating to completeness of insulin information were identified, including the omission of the prescribed time of insulin administration (n = 10) and unexplained insulin dose change (n = 4). Two patients who had insulin-related errors identified on their discharge summaries were readmitted to hospital within 30 days of discharge due to poor diabetic control. Conclusions: This small-scale study demonstrates that errors and discrepancies regarding insulin therapy on discharge persist despite current insulin safety initiatives. Poorly communicated information regarding insulin therapy may jeopardise optimal glycaemic control and continuity of patient care. Insulin-related information should be comprehensively documented at the point of discharge. This is to improve communication across the interface and to minimise risks to patient safet

The Ras/MAPK Pathway Is Required for Generation of iNKT Cells

iNKT cells derive from CD4+CD8+ DP thymocytes, and are selected by thymocyte-thymocyte interactions through signals from their invariant Vα14-Jα18 TCR and from the costimulatory molecules SLAMF1 and SLAMF6. Genetic studies have demonstrated the contribution of different signaling pathways to this process. Surprisingly, current models imply that the Ras/MAPK pathway, one of the critical mediators of conventional αβ T cell positive selection, is not necessary for iNKT cell development. Using mice defective at different levels of this pathway our results refute this paradigm, and demonstrate that Ras, and its downstream effectors Egr-1 and Egr-2 are required for positive selection of iNKT cells. Interestingly our results also show that there are differences in the contributions of several of these molecules to the development of iNKT and conventional αβ T cells

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Antiplatelet use in practice

Antiplatelets are widely used drugs that can prevent platelet activation and subsequent aggregation, inhibiting arterial thrombus formation that can contribute to the development of myocardial infarction and stroke. The use of antiplatelets for secondary prevention of cardiovascular disease is supported by a strong and compelling evidence base, with rigorous clinical trials supporting the use of varying combinations of antiplatelets for different indications. A sound understanding of how antiplatelets work is needed to promote their safe and effective use. This article briefly describes the process of platelet activation, aggregation and subsequent thrombus formation, and will discuss the mechanism of action of antiplatelets and their place in therapy. </jats:p