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Background: Symptoms of breathlessness, fatigue, and ankle swelling are common in general practice but deciding which patients are likely to have heart failure is challenging.Aim: To evaluate the performance of a clinical decision rule (CDR), with or without N-Terminal pro-B type natriuretic peptide (NT-proBNP) assay, for identifying heart failure.Design and Setting: Prospective, observational, diagnostic validation study of patients aged >55 years, presenting with shortness of breath, lethargy, or ankle oedema, from 28 general practices in England.Method: The outcome was test performance of the CDR and natriuretic peptide test in determining a diagnosis of heart failure. The reference standard was an expert consensus panel of three cardiologists.Results: Three hundred and four participants were recruited, with 104 (34.2%; 95% confidence interval [CI] = 28.9 to 39.8) having a confirmed diagnosis of heart failure. The CDR+NT-proBNP had a sensitivity of 90.4% (95% CI = 83.0 to 95.3) and specificity 45.5% (95% CI = 38.5 to 52.7). NT-proBNP level alone with a cut-off <400 pg/ml had sensitivity 76.9% (95% CI = 67.6 to 84.6) and specificity 91.5% (95% CI = 86.7 to 95.0). At the lower cut-off of NT-proBNP <125 pg/ml, sensitivity was 94.2% (95% CI = 87.9 to 97.9) and specificity 49.0% (95% CI = 41.9 to 56.1).Conclusion: At the low threshold of NT-proBNP <125 pg/ml, natriuretic peptide testing alone was better than a validated CDR+NT-proBNP in determining which patients presenting with symptoms went on to have a diagnosis of heart failure. The higher NT-proBNP threshold of 400 pg/ml may mean more than one in five patients with heart failure are not appropriately referred. Guideline natriuretic peptide thresholds may need to be revised. [ABSTRACT FROM AUTHOR]

A new recombination system for the production of live attenuated influenza-A vaccine strains is described. The attenuated parent is the Japanese strain A/Okuda/57 (HN) which has a known passage history and a good record of human safety. This virus has been recombined with two recent field isolates, A/England/42/72 and A/Finland/4/74, and in each case several recombinants were isolated and tested in volunteers. These recombinants differed in their degree of attenuation, but on each occasion it was possible to choose one that was suitably attenuated for a candidate vaccine strain. The genetic stability of such a recombinant produced with the A/England/42/72 strain was demonstrated by subjecting it to three successive human passages. A single intra-nasal dose of the A/Finland/4/74 recombinant vaccine gave a seroconversion rate of 75%. This recombination system offers considerable advantages for the production of live influenza virus vaccines. [ABSTRACT FROM PUBLISHER]

Recombination between influenza A viruses as a method of producing strains suitable for use in vaccines is discussed with particular reference to a recombination system involving an attentuated laboratory strain A/PR8/34 (HoN1) and a recent isolate of the epidemic strain A/Hong Kong/68 (H3N2). A variety of properties of the viruses were shown to be segregated independently of one another during recombination. These properties included the envelope antigens (haemagglutinin and neuraminidase), growth capacity in the fertile egg and attenuation for man. Some of the recombinants were considered suitable for use in vaccines either inactivated (whole virus particles or subunits) or live. The application of this technique to future requirements for vaccine strains are discussed with particular reference to the safety aspect of using recombinants in live vaccines. [ABSTRACT FROM PUBLISHER]

Background: There has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking., Aim: To explore GP and pharmacist views and experiences of in-person, interprofessional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice., Design and Setting: A mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands, between February 2021 and September 2023., Method: Audio-recordings of IPCDs between GPs and pharmacists, along with individual semi-structured interviews to explore their reflections on these discussions, were used. All recordings were transcribed verbatim and analysed thematically., Results: A total of 14 practices took part in the process evaluation from February 2022 to September 2023; 17 IPCD meetings were audio-recorded, discussing 30 patients (range 1-6 patients per meeting). In all, six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits, including: strengthening their working relationship; gaining in confidence to manage more complex patients; and learning from each other. It was often challenging, however, to find time for the IPCDs., Conclusion: The model of IPCD used in this study provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for interprofessional liaison and collaboration, and structured interventions may facilitate improved patient care., (© The Authors.)

Background: Prescription medication sharing refers to the lending or borrowing of prescription medications where the recipient is someone other than the person for whom the prescription is intended. Sharing prescription medication can cause significant harm. Adverse consequences include an increased risk of side effects, delayed health seeking, and severity of disease. Prevalence estimates vary across different populations and people's reasons for, and perceptions of risks from, sharing are poorly understood., Aim: To better understand prescription medication-sharing behaviours and practices - specifically, the prevalence, types of medications, reasons, perceived benefits and risks, and factors associated with medication sharing., Design and Setting: This systematic review included primary studies in any setting, focusing on people who engage in medication sharing., Method: Electronic databases were searched from inception of databases to February 2023., Results: In total, 19 studies were included. Prevalence of lifetime sharing ranged from 13% to 78%. All 19 studies reported that analgesics were the most shared, followed by antibiotics ( n = 12) and allergy medication ( n = 9). Common reasons for sharing were running out of medication ( n = 7), cost ( n = 7), and emergency ( n = 6). Perceived benefits included resolution of the problem and convenience. Perceived risks included adverse drug reactions and misdiagnosis. Characteristics associated with sharing included age, female sex, having asthma, and unused medicines stored at home., Conclusion: Findings suggest that medication-sharing behaviour is common and involves a range of medicines for a variety of reasons. Data on the prevalence and predictors of prescription medication sharing are inconsistent. A better understanding of non-modifiable and potentially modifiable behavioural factors that contribute to sharing is needed to support development of effective interventions aimed at mitigating unsafe sharing practices., (© The Authors.)

Background: Clinical medication reviews are a recognised strategy to address polypharmacy, a key part of general practice and positively associated with patient safety and clinical effectiveness. To date there has been little investigation of the patient perspective of medication reviews., Objective: To explore patient experiences of medication review including the processes and activities that led up to and shaped the review., Methods: Qualitative interview study within 10 general practices in Bristol. Participants were adults with polypharmacy (≥ 4 medications) and ≥ 2 long-term conditions who had a record of medication review with either a GP or pharmacist. Interviews were transcribed verbatim and analysed thematically using a data driven approach. Co-design work was undertaken with four patient and public involvement advisers to design and develop resources to support patient preparation for medication review., Results: Twenty-one patients were interviewed (10 female, mean age 73 years, range 59-88 years). Medication review was viewed as an opportunity to assess the effectiveness and need for medications. Participants expected the review to focus upon medication related concerns, side-effects and symptoms. Those who were newer to review, were uncertain of the intended purpose, and described their review as a box-ticking exercise. Some participants were unfamiliar with the role of the pharmacist and expressed a lack of confidence in their clinical skills and knowledge. Face-to-face consultation and relationship continuity were considered important for efficient and effective medication review. Results informed co-production of a patient information leaflet to facilitate greater patient engagement and involvement in medication review., Conclusions: A lack of understanding of the rationale for medication review can limit the value patients attach to these healthcare encounters. Improved prior communication and information around the intended purpose and potential benefits of medication review may enhance patient engagement and improve patient experience and outcomes., (© 2022. The Author(s).)

Introduction: Polypharmacy is increasingly common, and associated with undesirable consequences. Polypharmacy management necessitates balancing therapeutic benefits and risks, and varying clinical and patient priorities. Current guidance for managing polypharmacy is not supported by high quality evidence. The aim of the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial is to evaluate the effectiveness of an intervention to optimise medication use for patients with polypharmacy in a general practice setting., Methods: This trial will use a multicentre, open-label, cluster-randomised controlled approach, with two parallel groups. Practices will be randomised to a complex intervention comprising structured medication review (including interprofessional GP/pharmacist treatment planning and patient-facing review) supported by performance feedback, financial incentivisation, clinician training and clinical informatics (intervention), or usual care (control). Patients with polypharmacy and triggering potentially inappropriate prescribing (PIP) indicators will be recruited in each practice using a computerised search of health records. 37 practices will recruit 50 patients, and review them over a 26-week intervention delivery period. The primary outcome is the mean number of PIP indicators triggered per patient at 26 weeks follow-up, determined objectively from coded GP electronic health records. Secondary outcomes will include patient reported outcome measures, and health and care service use. The main intention-to-treat analysis will use linear mixed effects regression to compare number of PIP indicators triggered at 26 weeks post-review between groups, adjusted for baseline (pre-randomisation) values. A nested process evaluation will explore implementation of the intervention in primary care., Ethics and Dissemination: The protocol and associated study materials have been approved by the Wales REC 6, NHS Research Ethics Committee (REC reference 19/WA/0090), host institution and Health Research Authority. Research outputs will be published in peer-reviewed journals and relevant conferences, and additionally disseminated to patients and the public, clinicians, commissioners and policy makers., Isrctn Registration: 90146150 (28/03/2019)., Competing Interests: Competing interests: RAP, CCG and CS are in receipt of other funding from NIHR. CS is a NIHR Senior Investigator., (Copyright: © 2022 Payne RA et al.)

Background: Up to 50% of medicines are not used as intended, resulting in poor health and economic outcomes. Medicines optimisation is 'a person-centred approach to safe and effective medicines use, to ensure people obtain the best possible outcomes from their medicines'. The purpose of this exercise was to co-produce a prioritised research agenda for medicines optimisation using a multi-stakeholder (patient, researcher, public and health professionals) approach., Methods: A three-stage, multiple method process was used including: generation of preliminary research questions (Stage 1) using a modified Nominal Group Technique; electronic consultation and ranking with a wider multi-stakeholder group (Stage 2); a face-to-face, one-day consensus meeting involving representatives from all stakeholder groups (Stage 3)., Results: In total, 92 research questions were identified during Stages 1 and 2 and ranked in order of priority during stage 3. Questions were categorised into four areas: 'Patient Concerns' [e.g. is there a shared decision (with patients) about using each medicine?], 'Polypharmacy' [e.g. how to design health services to cope with the challenge of multiple medicines use?], 'Non-Medical Prescribing' [e.g. how can the contribution of non-medical prescribers be optimised in primary care?], and 'Deprescribing' [e.g. what support is needed by prescribers to deprescribe?]. A significant number of the 92 questions were generated by Patient and Public Involvement representatives, which demonstrates the importance of including this stakeholder group when identifying research priorities., Conclusions: A wide range of research questions was generated reflecting concerns which affect patients, practitioners, the health service, as well the ethical and philosophical aspects of the prescribing and deprescribing of medicines. These questions should be used to set future research agendas and funding commissions.

Venous thromboembolism (VTE) is prevalent and impactful, with a risk of death, morbidity and recurrence. Post-thrombotic syndrome (PTS) is a common consequence and associated with impaired quality of life (QoL). The ExACT study was a non-blinded, prospective, multicentred randomised controlled trial comparing extended versus limited duration anticoagulation following a first unprovoked VTE (proximal deep vein thrombosis or pulmonary embolism). Adults were eligible if they had completed ≥3 months anticoagulation (remaining anticoagulated). The primary outcome was time to first recurrent VTE from randomisation. The secondary outcomes included PTS severity, bleeding, QoL and D-dimers. Two-hundred and eighty-one patients were recruited, randomised and followed up for 24 months (mean age 63, male:female 2:1). There was a significant reduction in recurrent VTE for patients receiving extended anticoagulation [2·75 vs. 13·54 events/100 patient years, adjusted hazard ratio (aHR) 0·20 (95% confidence interval (CI): 0·09 to 0·46, P < 0·001)] with a non-significant increase in major bleeding [3·54 vs. 1·18 events/100 patient years, aHR 2·99 (95% CI: 0·81-11·05, P = 0·10)]. Outcomes of PTS and QoL were no different between groups. D-dimer results (on anticoagulation) did not predict VTE recurrence. In conclusion, extended anticoagulation reduced VTE recurrence but did not reduce PTS or improve QoL and was associated with a non-significant increase in bleeding. Results also suggest very limited clinical utility of D-dimer testing on anticoagulated patients., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Subclinical thyroid dysfunction - abnormal serum thyrotrophin (thyroid-stimulating hormone; TSH) concentrations with normal free thyroxine (FT4) is common in older people. It remains unclear whether individuals with subclinical serum status experience an increased symptom profile., Aim: To compare the prevalence of those symptoms typically associated with overt thyroid dysfunction in older individuals with a subclinical and euthyroid serum profile., Design and Setting: Cross-sectional study, nested within the Birmingham Elderly Thyroid Study (BETS); from 19 UK general practices., Method: Adults living in a community setting (aged ≥65 years), without overt thyroid dysfunction or associated treatment, self-reported the presence or absence of 18 symptoms (while serum result naïve). Serum concentrations of TSH and FT4 were measured to establish thyroid status., Results: A total of 2870 individuals were screened: 2703 (94%) were categorised as euthyroid (normal), 29 (1%) subclinically hyperthyroid, and 138 (5%) subclinically hypothyroid. Symptoms were common in all groups. No significant differences in the prevalence of individual symptoms were observed between the euthyroid and subclinically hypothyroid groups nor in comparison with the subclinically hyperthyroid group. Multivariate logistic regression analysis failed to reveal an association between individual or multiple symptoms and subclinical status., Conclusion: Findings suggest that subclinical thyroid dysfunction does not confer a symptom burden in older individuals and support adherence to guidelines in the non-treatment of subclinical thyroid dysfunction. GPs may use the findings to reassure older people presenting with symptoms that subclinical thyroid dysfunction is an unlikely explanation. The presence of persistently abnormal TSH concentrations may be linked to long-term risks of cardiovascular disease, especially atrial fibrillation, but whether this should prompt treatment and whether such treatment alters vascular outcomes is unknown., (© British Journal of General Practice 2020.)

Background: Many UK GP practices now employ a practice pharmacist, but little is known about how GPs and pharmacists work together to optimise medications for complex patients with multimorbidity., Aim: To explore GP and pharmacist perspectives on collaborative working within the context of optimising medications for patients with multimorbidity., Design and Setting: A qualitative analysis of semi-structured interviews with GPs and pharmacists working in the West of England, Northern England, and Scotland., Method: Thirteen GPs and 10 pharmacists were sampled from practices enrolled in the 3D trial (a complex intervention for people with multimorbidity). Participants' views on collaborative working were explored with interviews that were audiorecorded, transcribed, and analysed thematically. Saturation of data was achieved with no new insights arising from later interviews., Results: GPs from surgeries that employed a pharmacist tended to value their expertise more than GPs who had not worked with one. Three key themes were identified: resources and competing priorities; responsibility; and professional boundaries. GPs valued pharmacist recommendations that were perceived to improve patient safety, as opposed to those that were technical and unlikely to benefit the patient. Pharmacists who were not known to GPs felt undervalued and wanted feedback from the GPs about their recommendations, particularly those that were not actioned., Conclusion: A good working relationship between the GP and pharmacist, where each profession understood the other's skills and expertise, was key. The importance of face-to-face meetings and feedback should be considered in future studies of interdisciplinary interventions, and by GP practices that employ pharmacists and other allied health professionals., (© British Journal of General Practice 2020.)

Background: Medication reviews may improve the safety of prescribing and the National Institute for Health and Care Excellence (NICE) highlights the importance of involving patients in this process., Aim: To explore GP and pharmacist perspectives on how medication reviews were conducted in general practice in the UK., Design and Setting: Analysis of semi-structured interviews with GPs and pharmacists working in the South West of England, Northern England, and Scotland, sampled for heterogeneity. Interviews took place between January and October 2017., Method: Interviews focused on experience of medication review. Data saturation was achieved when no new insights arose from later interviews. Interviews were analysed thematically., Results: In total, 13 GPs and 10 pharmacists were interviewed. GPs and pharmacists perceived medication review as an opportunity to improve prescribing safety. Although interviewees thought patients should be involved in decisions about their medicines, high workload pressures meant that most medication reviews were conducted with limited or no patient input. For some GPs, a medication review was done 'in the quickest way possible to say that it was done' . Pharmacists were perceived by both professions as being more thorough but less time efficient than GPs, and few pharmacists were routinely involved in medication reviews even in practices employing a pharmacist. Interviewees argued that it was easier to continue medicines than it was to stop them, particularly because stopping medicines required involving the patient and this generated extra work., Conclusion: Practices tended to prioritise being efficient (getting the work done) rather than being thorough (doing it well), so that most medication reviews were carried out with little or no patient involvement, and medicines were rarely stopped or reduced. Time and resource constraints are an important barrier to implementing NICE guidance., (© British Journal of General Practice 2019.)