Estimating the prevalence of potential and actionable drug-gene interactions in Irish primary care: A cross-sectional study.

AIMS: Pharmacogenetics (PGx) is increasingly recognized as a strategy for medicines optimisation and prevention of adverse drug reactions. According to guidelines produced by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG), most medicines with drug-gene interactions (DGIs) are prescribed in primary care. This study aimed to estimate the prevalence of potential and actionable DGIs involving all medicines dispensed in Irish primary care. METHODS: Dispensings of 46 drugs to General Medical Services (GMS) patients in the Health Service Executive Primary Care Reimbursement Service Irish pharmacy claims database from 01 January 2021 to 31 December 2021 were analysed to estimate the national prevalence of total dispensings and incidence of first-time dispensings of drugs with potential DGIs according to the CPIC and/or DPWG guidelines. Phenotype frequency data from the UK Biobank and the CPIC were used to estimate the incidence of actionable DGIs. RESULTS: One in five dispensings (12 443 637 of 62 754 498, 19.8%) were medicines with potential DGIs, 1 878 255 of these dispensed for the first time. On application of phenotype frequencies and linked guideline based therapeutic recommendations, 2 349 055 potential DGIs (18.9%) required action, such as monitoring and guarding against maximum dose, drug or dose change. One in five (369 700, 19.7%) first-time dispensings required action, with 139 169 (7.4%) requiring a change in prescribing. Antidepressants, weak opioids and statins were most commonly identified as having actionable DGIs. CONCLUSIONS: This study estimated a high prevalence of DGIs in primary care in Ireland, identifying the need and opportunity to optimize drug therapy through PGx testing.

What affected UK adults' adherence to medicines during the COVID-19 pandemic? Cross-sectional survey in a representative sample of people with long-term conditions.

Aim: Medicines non-adherence is associated with poorer outcomes and higher costs. COVID-19 affected access to healthcare, with increased reliance on remote methods, including medicines supply. This study aimed to identify what affected people's adherence to medicines for long-term conditions (LTCs) during the pandemic. Subject and methods: Cross-sectional online survey of UK adults prescribed medicines for LTCs assessing self-reported medicines adherence, reasons for non-adherence (using the capability, opportunity and motivation model of behaviour [COM-B]), medicines access and COVID-19-related behaviours. Results: The 1746 respondents reported a mean (SD) of 2.5 (1.9) LTCs, for which they were taking 2.4 (1.9) prescribed medicines, 525 (30.1%) reported using digital tools to support ordering or taking medicines and 22.6% reported medicines non-adherence. No access to at least one medicine was reported by 182 (10.4%) respondents; 1048 (60.0%) reported taking at least one non-prescription medicine as a substitute; 409 (23.4%) requested emergency supply from pharmacy for at least one medicine. Problems accessing medicines, being younger, male, in the highest socioeconomic group and working were linked to poorer adherence. Access problems were mostly directly or indirectly related to the COVID-19 pandemic. Respondents were generally lacking in capabilities and opportunities, but disruptions to habits (automatic motivation) was the major reason for non-adherence. Conclusion: Navigating changes in how medicines were accessed, and disruption of habits during the COVID-19 pandemic, was associated with suboptimal adherence. People were resourceful in overcoming barriers to access. Solutions to support medicines-taking need to take account of the multiple ways that medicines are prescribed and supplied remotely. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01813-0.

Benefits of pharmacist-led flu vaccination services in community pharmacy.

Seasonal influenza is a major cause of excess winter deaths and increased hospital admissions. There is a high level of economic burden associated with the infection. Although vaccination targets have been set to tackle this international issue, many countries struggle to reach these coverage targets for their at-risk populations using traditional delivery methods. Traditional providers include family doctors and nurses; however, pharmacist-led influenza vaccination has become a more commonly utilised aid to support vaccination targets. Community pharmacies are convenient and widely accessible and evaluations consistently demonstrate that patients are satisfied with pharmacist-led vaccinations. Allowing community pharmacists to administer influenza vaccination as an alternative option for delivery helps to increase the coverage rate of vaccination. In addition, commissioning community pharmacists to provide this service has been shown to contribute to achieving targets for those at-risk. Pharmacist-led influenza vaccination services can create value for payors and reduce pressure on health systems. This review aims to demonstrate the success of pharmacy-led influenza vaccinations, and the impact it has had in driving up immunisation rates within other countries. Experiences of countries such as England, Portugal and the United States provide evidence to demonstrate the benefit to both the patient and the health system.

Implementation of flu vaccination in community pharmacies: Understanding the barriers and enablers.

Improving influenza vaccination coverage has been, and still remains a challenge internationally. There are now many examples where countries have pursued a pharmacist-led influenza vaccination service in order to enhance vaccination coverage of at-risk populations. England, Portugal and the United States are successful examples where their experience implementing this service can now be explored retrospectively and learnt from. This review aims to provide evidence to help overcome barriers to commissioning and implementation of such services in countries new to the experience. Implementation is influenced by differing regulatory frameworks underpinning the provision of pharmacist-led influenza vaccination, methods of remuneration, training, and operating procedures. Practical aspects such as the facilities required, how patient records are maintained and how patients and other healthcare professionals are engaged also have an impact. These examples illustrate how community pharmacists can be trained to deliver influenza vaccinations safely, and coupled with their accessibility and convenience, can provide a complementary service to that already provided by family doctors and nurses to deliver influenza vaccinations for the benefit of patients.

A feasibility service evaluation of screening and treatment of group A streptococcal pharyngitis in community pharmacies.

OBJECTIVES: The UK 5 year antimicrobial resistance strategy recognizes the role of point-of-care diagnostics to identify where antimicrobials are required, as well as to assess the appropriateness of the diagnosis and treatment. A sore throat test-and-treat service was introduced in 35 community pharmacies across two localities in England during 2014-15. METHODS: Trained pharmacy staff assessed patients presenting with a sore throat using the Centor scoring system and patients meeting three or all four of the criteria were offered a throat swab test for Streptococcus pyogenes, Lancefield group A streptococci. Patients with a positive throat swab test were offered antibiotic treatment. RESULTS: Following screening by pharmacy staff, 149/367 (40.6%) patients were eligible for throat swab testing. Of these, only 36/149 (24.2%) were positive for group A streptococci. Antibiotics were supplied to 9.8% (n = 36/367) of all patients accessing the service. Just under half of patients that were not showing signs of a bacterial infection (60/123, 48.8%) would have gone to their general practitioner if the service had not been available. CONCLUSIONS: This study has shown that it is feasible to deliver a community-pharmacy-based screening and treatment service using point-of-care testing. This type of service has the potential to support the antimicrobial resistance agenda by reducing unnecessary antibiotic use and inappropriate antibiotic consumption.

Identification of patients with atrial fibrillation in UK community pharmacy: an evaluation of a new service.

Background Many patients with atrial fibrillation (AF) are asymptomatic and diagnosed via opportunistic screening. Community pharmacy has been advocated as a potential resource for opportunistic screening and lifestyle interventions. Objective The objective of this evaluation is to describe the outcomes from an AF service, in terms of referrals and interventions provided to patients identified as not at risk. Methods Eligibility was assessed from pharmacy records and the completion of a short questionnaire. Once consented, patients were screened for AF and their blood pressure was measured. Results Of 594 patients screened, nine were identified as at risk of having AF and were referred to their GP. The service also identified 109 patients with undiagnosed hypertension, 176 patients with a Body Mass Index >30, 131 with an Audit-C score >5 and 59 smokers. Pharmacists provided 413 interventions in 326 patients aimed at weight reduction (239), alcohol consumption (123) and smoking cessation (51). Conclusion This evaluation characterises the interventions provided to, not only those identified with the target condition-in this case AF-but also those without it. The true outcome of these additional interventions, along with appropriate follow-up, should be the focus of future studies.

Allografts stimulate cross-reactive virus-specific memory CD8 T cells with private specificity.

Viral infections have been associated with the rejection of transplanted allografts in humans and mice, and the induction of tolerance to allogeneic tissues in mice is abrogated by an ongoing viral infection and inhibited in virus-immune mice. One proposed mechanism for this 'heterologous immunity' is the induction of alloreactive T cell responses that cross-react with virus-derived antigens. These cross-reactive CD8 T cells are generated during acute viral infection and survive into memory, but their ability to partake in the immune response to allografts in vivo is not known. We show here that cross-reactive, virus-specific memory CD8 T cells from mice infected with LCMV proliferated in response to allografts. CD8 T cells specific to several LCMV epitopes proliferated in response to alloantigens, with the magnitude and hierarchy of epitope-specific responses varying with the private specificities of the host memory T cell repertoire, as shown by adoptive transfer studies. Last, we show that purified LCMV-specific CD8 T cells rejected skin allografts in SCID mice. These findings therefore implicate a potential role for heterologous immunity in virus-induced allograft rejection.

Skin allograft maintenance in a new synchimeric model system of tolerance.

Treatment of mice with a single donor-specific transfusion plus a brief course of anti-CD154 mAb uniformly induces donor-specific transplantation tolerance characterized by the deletion of alloreactive CD8+ T cells. Survival of islet allografts in treated mice is permanent, but skin grafts eventually fail unless recipients are thymectomized. To analyze the mechanisms underlying tolerance induction, maintenance, and failure in euthymic mice we created a new analytical system based on allo-TCR-transgenic hemopoietic chimeric graft recipients. Chimeras were CBA (H-2(k)) mice engrafted with small numbers of syngeneic TCR-transgenic KB5 bone marrow cells. These mice subsequently circulated a self-renewing trace population of anti-H-2(b)-alloreactive CD8+ T cells maturing in a normal microenvironment. With this system, we studied the maintenance of H-2(b) allografts in tolerized mice. We documented that alloreactive CD8+ T cells deleted during tolerance induction slowly returned toward pretreatment levels. Skin allograft rejection in this system occurred in the context of 1) increasing numbers of alloreactive CD8+ cells; 2) a decline in anti-CD154 mAb concentration to levels too low to inhibit costimulatory functions; and 3) activation of the alloreactive CD8+ T cells during graft rejection following deliberate depletion of regulatory CD4+ T cells. Rejection of healed-in allografts in tolerized mice appears to be a dynamic process dependent on the level of residual costimulation blockade, CD4+ regulatory cells, and activated alloreactive CD8+ thymic emigrants that have repopulated the periphery after tolerization.