'I think we could probably do more': an interview study to explore community pharmacists' experiences and perspectives of frailty and optimising medicines use in frail older adults.

BACKGROUND: Community pharmacists potentially have an important role to play in identification of frailty and delivery of interventions to optimise medicines use for frail older adults. However, little is known about their knowledge or views about this role. AIM: To explore community pharmacists' knowledge of frailty and assessment, experiences and contact with frail older adults, and perceptions of their role in optimising medicines use for this population. METHODS: Semi-structured interviews conducted between March and December 2020 with 15 community pharmacists in Northern Ireland. Interviews were transcribed verbatim and analysed thematically. RESULTS: Three broad themes were generated from the data. The first, 'awareness and understanding of frailty', highlighted gaps in community pharmacists' knowledge regarding presentation and identification of frailty and their reluctance to broach potentially challenging conversations with frail older patients. Within the second theme, 'problem-solving and supporting medication use', community pharmacists felt a large part of their role was to resolve medicines-related issues for frail older adults through collaboration with other primary healthcare professionals but feedback on the outcome was often not provided upon issue resolution. The third theme, 'seizing opportunities in primary care to enhance pharmaceutical care provision for frail older adults', identified areas for further development of the community pharmacist role. CONCLUSIONS: This study has provided an understanding of the views and experiences of community pharmacists about frailty. Community pharmacists' knowledge deficits about frailty must be addressed and their communication skills enhanced so they may confidently initiate conversations about frailty and medicines use with older adults.

The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis.

INTRODUCTION: Colorectal cancer is the fourth most common cancer in the UK. There remains a need for improved risk stratification following curative resection. Circulating-tumour DNA (ctDNA) has gained particular interest as a cancer biomarker in recent years. We performed a systematic review to assess the utility of ctDNA in identifying minimal residual disease in colorectal cancer. METHODS: Studies were included if ctDNA was measured following curative surgery and long-term outcomes were assessed. Studies were excluded if the manuscript could not be obtained from the British Library or were not available in English. RESULTS: Thirty-seven studies met the inclusion criteria, involving 3002 patients. Hazard ratios (HRs) for progression-free survival (PFS) were available in 21 studies. A meta-analysis using a random effects model demonstrated poorer PFS associated with ctDNA detection at the first liquid biopsy post-surgery [HR: 6.92 CI: 4.49-10.64 p < 0.00001]. This effect was also seen in subgroup analysis by disease extent, adjuvant chemotherapy and assay type. DISCUSSION: Here we demonstrate that ctDNA detection post-surgery is associated with a greater propensity to disease relapse and is an independent indicator of poor prognosis. Prior to incorporation into clinical practice, consensus around timing of measurements and assay methodology are critical. PROTOCOL REGISTRATION: The protocol for this review is registered on PROSPERO (CRD42021261569).

Interventions to improve medicines optimisation in older people with frailty in primary care: a systematic review.

OBJECTIVES: To identify studies that delivered an intervention to frail older people to improve medicines optimisation; identify the outcomes reported in these studies; and assess the effectiveness of these interventions on chosen study outcomes. METHOD: Eight electronic databases and four trial registries were systematically searched from the date of inception to April 2020. Inclusion criteria were randomised controlled trials and non-randomised studies of interventions to improve medicines optimisation (including administration, adherence, deprescribing, prescribing and/or medication review) in community-dwelling older people (aged ≥65 years) with a frailty diagnosis. Only studies published in English were included. A narrative synthesis was conducted, and quality was assessed using an appropriate risk of bias tool. KEY FINDINGS: Searches identified 601 articles; one study met the criteria for inclusion. The single eligible study used a quasi-experimental pre-test-post-test study design to evaluate the impact of a pharmacist-led, team-based medication review for 54 frail older patients living in primary care. Improvements in the total number of medications and prescribing appropriateness were observed. The study was judged to be at an overall serious risk of bias. CONCLUSION: There is a dearth of high-quality evidence demonstrating the effectiveness of medicines optimisation interventions for older people with frailty within primary care. Due to the strong association between patients' level of frailty and adverse outcomes, it is important that future research focuses on proactive interventions which may be beneficial to this patient population.

Miller-Fisher syndrome associated with SARS-CoV-2: a case report.

SARS-CoV-2 infections are increasingly associated with neurological complications, including immune-mediated neuropathies. Miller-Fisher syndrome is a rare variant of Guillain-Barré syndrome characterised by the triad of ataxia, ophthalmoplegia and areflexia. Here we present a case of Miller-Fisher syndrome following COVID-19 infection. The clinical presentation was a short history of a rapidly-progressive peripheral sensorimotor neuropathy with bulbar dysfunction and facial weakness following mild COVID infection. Examination revealed global areflexia and a broad-based ataxic gait. CSF analysis revealed albuminocytological dissociation and neurophysiological testing later supported the diagnosis. The patient required high flow nasal oxygen therapy for respiratory dysfunction in a level 2 care setting and received immunological treatment with intravenous immunoglobulins. We conclude that Miller-Fisher syndrome needs to be considered in patients presenting with new sensorimotor dysfunction following SARS-COV-2 infection. Early recognition is key given the propensity to cause life-threatening respiratory failure, and early administration of immunological treatment is associated with improved prognosis.

Isolated tumour microparticles induce endothelial microparticle release in vitro.

: Cancer induces a hypercoagulable state, resulting in an increased risk of venous thromboembolism. One of the mechanisms driving this is tissue factor (TF) production by the tumour, released in small lipid bound microparticles. We have previously demonstrated that tumour cell line media-induced procoagulant changes in HUVEC. The aim of this study was to investigate the effect of tumour microparticles and recombinant human TF (rhTF) on the endothelium. Procoagulant microparticles from the PANC-1 cell line were harvested by ultrafiltration. HUVEC were then incubated with these procoagulant microparticles or rhTF. Flow cytometry was used to investigate the effect of endothelial cell surface protein expression and microparticle release. Microparticles but not soluble TF was responsible for the procoagulant activity of cell-free tumour media. We also demonstrated an increase in endothelial microparticle release with exposure to tumour microparticles, with a positive linear relationship observed (R = 0.6630 P ≤ 0.0001). rhTF did not induce any of the changes observed with microparticles. Here we demonstrate that procoagulant activity of tumour cell line media is dependent on microparticles, and that exposure of endothelial cells to these microparticles results in an increase in microparticle release from HUVEC. This suggests a mechanism of transfer of procoagulant potential from the cancer to the remote endothelium.

Redefining community based on place attachment in a connected world.

The concept of community is often used in environmental policy to foster environmental stewardship and public participation, crucial prerequisites of effective management. However, prevailing conceptualizations of community based on residential location or resource use are limited with respect to their utility as surrogates for communities of shared environment-related interests, and because of the localist perspective they entail. Thus, addressing contemporary sustainability challenges, which tend to involve transnational social and environmental interactions, urgently requires additional approaches to conceptualizing community that are compatible with current globalization. We propose a framing for redefining community based on place attachment (i.e., the bonds people form with places) in the context of Australia's Great Barrier Reef, a World Heritage Area threatened by drivers requiring management and political action at scales beyond the local. Using data on place attachment from 5,403 respondents residing locally, nationally, and internationally, we identified four communities that each shared a type of attachment to the reef and that spanned conventional location and use communities. We suggest that as human-environment interactions change with increasing mobility (both corporeal and that mediated by communication and information technology), new types of people-place relations that transcend geographic and social boundaries and do not require ongoing direct experience to form are emerging. We propose that adopting a place attachment framing to community provides a means to capture the neglected nonmaterial bonds people form with the environment, and could be leveraged to foster transnational environmental stewardship, critical to advancing global sustainability in our increasingly connected world.