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Team-Based Learning and Threshold Concepts in Biological Security and Dual-Use: Toward a Transformative Biological Security Pedagogy—The Game Changing Implications of CRISPR/Cas and the Design of a Novel Methodology for Influencing the Culture of Life and Associated Science through Awareness Raising and EducationCRISPR (clustered regularly interspaced short palindromic repeats) gene editing technologies appear to be a game-changer and suggest great potential for genome manipulation and for developments in next-generation therapeutics. Ethical, legal and social concerns have been raised in light of recent applications in humans. Concern also arises in relation to the potential of such developments for misuse. In addressing the post-COVID19 challenges raised by responsible research innovation and in confronting what to do about the vexed question of “dual-use”, we contend that awareness-raising and education concerning the ethical, legal and social implications of scientific research innovation represents a welcome and empowering alternative to top down regulatory responses that may serve to stifle innovation. The design and subsequent implementation of a novel transformative pedagogy combining Team-Based Learning and Threshold Concepts yields both empirical evidence-based metrics for real-time learning. As well as generating novel empirical data-sets for the identification of subject-specific threshold concepts across discrete specialisms in the life sciences, we argue that this hybrid methodology can be used to engage science professionals and students alike in meaningful and much-needed dialogue about developments relating to genome manipulation. We demonstrate how evidence-based threshold concepts can inform the design of bespoke subject-specific training as we suggest was the case from our deployment of team-based learning and threshold concepts during our proof of concept application, prior to the pandemic, during the course of two European Union Human Brain Project training programmes undertaken in 2017 and 2018, with experts in neuroscience research at the Karonlinska Institutet, Stockholm, Sweden.
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A piriform jar from the cemetery at el-Dakka: contexts and contentsWhile stone vessels were sometimes included in ancient Egyptian elite burials of the New Kingdom, presumed to have been used as cosmetic vessels, we still know little about the contents they held. The situation is even more vague for jars in Nubia, where they occur less frequently. We report here on a study of a travertine jar from the Cemetery of el-Dakka in Lower Nubia, and the scientific analysis of its contents, comparing the jar with other known examples.
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"To make the unseen seen": Organic residue analysis of Late Roman grave depositsThe concept that invisible molecular traces may remain in grave deposits, the often discarded ‘dirt’ from substantial mortuary containers, is not widely appreciated. Organic residue analysis of samples from Late Roman (2nd–4th c. AD) burials in Britain has revealed their potential to retain diagnostic biomarkers. Alongside the analysis of visible residues from similar continental burials, these results confirm that resinous substances were employed in the treatment of the dead throughout the Roman Empire. Deposited in close proximity to the body, they masked the reality of decay, signified the status of the deceased and promoted memorialisation. These findings, in conjunction with the sampling approach and methodology detailed here, have important implications for future mortuary research in the late antique period and beyond.
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Development and optimisation of inhalable EGCG nano-liposomes as a potential treatment for pulmonary arterial hypertension by implementation of the design of experiments approachEpigallocatechin gallate (EGCG), the main ingredient in green tea, holds promise as a potential treatment for pulmonary arterial hypertension (PAH). However, EGCG has many drawbacks, including stability issues, low bioavailability, and a short half-life. Therefore, the purpose of this research was to develop and optimize an inhalable EGCG nano-liposome formulation aiming to overcome EGCG’s drawbacks by applying a design of experiments strategy. The aerodynamic behaviour of the optimum formulation was determined using the next-generation impactor (NGI), and its effects on the TGF-β pathway were determined using a cell-based reporter assay. The newly formulated inhalable EGCG liposome had an average liposome size of 105 nm, a polydispersity index (PDI) of 0.18, a zeta potential of −25.5 mV, an encapsulation efficiency of 90.5%, and a PDI after one month of 0.19. These results are in complete agreement with the predicted values of the model. Its aerodynamic properties were as follows: the mass median aerodynamic diameter (MMAD) was 4.41 µm, the fine particle fraction (FPF) was 53.46%, and the percentage of particles equal to or less than 3 µm was 34.3%. This demonstrates that the novel EGCG liposome has all the properties required to be inhalable, and it is expected to be deposited deeply in the lung. The TGFβ pathway is activated in PAH lungs, and the optimum EGCG nano-liposome inhibits TGFβ signalling in cell-based studies and thus holds promise as a potential treatment for PAH.
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Inhaled dry powder liposomal azithromycin for treatment of chronic lower respiratory tract infectionA dry powder inhaled liposomal azithromycin formulation was developed for the treatment of chronic respiratory diseases such as cystic fibrosis and bronchiectasis. Key properties including liposome size, charge and encapsulation efficiency powder size, shape, glass transition temperature (Tg), water content and in vitro respiratory deposition were determined. Antimicrobial activity against cystic fibrosis (CF) respiratory pathogens was determined by MIC, MBC and biofilm assays. Cytotoxicity and cellular uptake studies were performed using A549 cells. The average liposome size was 105 nm, charge was 55 mV and encapsulation efficiency was 75 %. The mean powder particle size d[v,50] of 4.54 µm and Mass Median Aerodynamic Diameter (MMAD) was 5.23 µm with a mean Tg of 76˚C and water content of 2.1 %. These excellent physicochemical characteristics were maintained over one year. Liposomal loaded azithromycin demonstrated enhanced activity against P. aeruginosa clinical isolates grown in biofilm. The formulation was rapidly delivered into bacterial cells with > 75 % uptake in 1 h. Rapid uptake into A549 cells via a cholesterol-dependent endocytosis pathway with no cytotoxic effects apparent. These data demonstrate that this formulation could offer benefits over current treatment regimens for people with chronic respiratory infection.
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The patient’s perspectives of safe and routine proactive deprescribing in primary care for older people living with polypharmacy: a qualitative studyBackground: The process of identifying and discontinuing medicines in instances in which harms outweigh benefits (deprescribing) can mitigate the negative consequences of problematic polypharmacy. This process should be conducted with a focus on the patient and involve collaborative decision-making. Evidence is needed regarding patients’ views on how deprescribing should be safely and routinely implemented in English primary care to improve its application. This study aimed to identify optimal methods of introducing and actioning deprescribing from the patient’s perspective. Methods: Participants in England aged 65 and above who were taking five or more medicines and residing in their own homes were recruited through social media and service user groups. An interview guide was created from deprescribing literature and input from patients and the public, guided by the Normalisation Process Theory (NPT). The interviews were held online using Microsoft Teams® or via phone, recorded, and then transcribed. The data was analysed using the Framework analysis. Results: Twenty patients (mean age of 74.5, SD = 6.93), with 75% being female, were enrolled in the study. Three main themes emerged: (1) ‘Why deprescribe now?’ emphasised the significance of explaining the reasons behind deprescribing; (2) ‘Monitoring and follow-up’ underscored the necessity of safety measures during deprescribing and patients’ willingness to self-monitor post-intervention; (3) ‘Roles and relationships’ explored patient perceptions of various healthcare professionals involved in deprescribing and the essential interpersonal skills for fostering therapeutic relationships. Conclusion: Optimal methods of introducing deprescribing included communicating a convincing rationale for stopping medicines and preparing patients for deprescribing conversations. Patients required support from a range of healthcare professionals with whom they had an existing therapeutic relationship. Whilst patients were motivated to self-monitor unwanted/unexpected effects post-deprescribing, timely support was required. The nature of such bolstered collective action and cognitive participation within NPT enhances the normalisation potential of deprescribing. These findings highlight the significance of considering the content and process of deprescribing consultations to enhance normalisation and tackle problematic polypharmacy. This provides a deeper understanding of patients’ needs for implementing safe and routine deprescribing in primary care, which should be considered when designing medication review and deprescribing services.
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A needle in a haystack: Landscape survey and archaeological detection experiments in Apalachee BayThis paper presents the results of a pilot landscape-scale seismic survey undertaken in Apalachee Bay, Florida, across a submerged landscape that contains dozens of Pre-Contact sites. In addition to the goals of improving the geophysical and remote sensing ground model for this submerged landscape, the survey also sought to undertake the first independent scientific test of the contentious ‘HALD’ methodology, an acoustic resonance method that it is claimed to identify knapped lithic artefacts at and/ or below the seabed through the identification of distinct ‘haystack’ responses. The results of this work indicate that the HALD method, as currently described, produces results that could not be scientifically replicated in this survey. We conclude that any HALD ‘haystack’ signal should therefore not be considered as an example of detection of human-modified lithic material but rather as a geophysical anomaly that requires additional constraints before it can be used to reliably identify human-modified lithic materials. Thus, although the authors note that laboratory studies have successfully produced an acoustic signal in human-modified lithics, the field-based methods remain yet to be reliably determined. In addition to these results, the landscape mapping survey also recorded valuable information on buried and previously unrecorded landscape features that have archaeological significance and that may guide future site prospection. We therefore conclude that despite the results of the HALD test, the well-preserved submerged landscape of Apalachee Bay region provides a highly useful testing ground for methods that can be deployed elsewhere globally.
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Design and modelling of an induction heating coil to investigate the thermal response of magnetic nanoparticles for hyperthermia applicationsMagnetic Field Hyperthermia is a technique where tumours are treated through an increase in local temperature upon exposure to alternating magnetic fields (AMFs) that are mediated by magnetic nano-particles (MNPs). In an AMF, these particles heat-up and kill the cells. The relationship between an AMF and the heating-rate is complex, leading to confusion when comparing data for different MNP and AMF conditions. This work allows for the thermal-response to be monitored at multiple AMF amplitudes while keeping other parameters constant. An induction-heating coil was designed based on a Zero-Voltage-Zero-Current (ZVZC) resonant circuit. The coil operates at 93 kHz with a variable DC drive-voltage (12–30 V). NEC4 software was used to model the magnetic field distribution, and MNPs were synthesised by the coprecipitation method. The magnetic field was found to be uniform at the centre of the coil and ranged from 1 kAm−1 to 12 kAm−1, depending on the DC drive-voltage. The MNPs were found to have a specific absorption rate (SAR) of 1.37 Wg−1[Fe] and 6.13 Wg−1[Fe] at 93 kHz and 2.1 kAm−1 and 12.6 kAm−1, respectively. The measured SAR value was found to be directly proportional to the product of the frequency and field-strength (SARα f Ho). This leads to the recommendation that, when comparing data from various groups, the SAR value should be normalized following this relationship and not using the more common relationship based on the square of the field intensity (SARα f Ho2).
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Normalising the Implementation of Pharmacogenomic (PGx) Testing in Adult Mental Health Settings: A Theory-Based Systematic ReviewPharmacogenomic (PGx) testing can help personalise psychiatric prescribing and improve on the currently adopted trial-and-error prescribing approach. However, widespread implementation is yet to occur. Understanding factors influencing implementation is pertinent to the psychiatric PGx field. Normalisation Process Theory (NPT) seeks to understand the work involved during intervention implementation and is used by this review (PROSPERO: CRD42023399926) to explore factors influencing PGx implementation in psychiatry. Four databases were systematically searched for relevant records and assessed for eligibility following PRISMA guidance. The QuADS tool was applied during quality assessment of included records. Using an abductive approach to codebook thematic analysis, barrier and facilitator themes were developed using NPT as a theoretical framework. Twenty-nine records were included in the data synthesis. Key barrier themes included a PGx knowledge gap, a lack of consensus in policy and guidance, and uncertainty towards the use of PGx. Facilitator themes included an interest in PGx use as a new and improved approach to prescribing, a desire for a multidisciplinary approach to PGx implementation, and the importance of fostering a climate for PGx implementation. Using NPT, this novel review systematically summarises the literature in the psychiatric PGx implementation field. The findings highlight a need to develop national policies on using PGx, and an education and training workforce plan for mental health professionals. By understanding factors influencing implementation, the findings help to address the psychiatric PGx implementation gap. This helps move clinical practice closer towards a personalised psychotropic prescribing approach and associated improvements in patient outcomes. Future policy and research should focus on the appraisal of PGx implementation in psychiatry and the role of pharmacists in PGx service design, implementation, and delivery.
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Frequency-of-seeing curves (psychometric functions) for perimetric stimuli in age-related macular degenerationPurpose: Frequency-of-seeing (FoS) curves (psychometric functions) for perimetric stimuli have been widely used in computer simulations of new visual field test procedures. FoS curves for age-related macular degeneration (AMD) are not available in the literature and are needed for the development of improved microperimetry test procedures, which are of particular interest for use as clinical trial endpoints. Methods: Data were refitted from a previous study to generate FoS curves for 20 participants with AMD, each tested at nine locations within the central 10°. Stimulus parameters, background luminance and dB scale were matched to the MAIA-2 microperimeter, and stimuli were presented in a method of constant stimuli to build up FoS curves over multiple runs. FoS curves were fitted with a modified cumulative Gaussian function. The relationship between sensitivity and slope of fitted FoS curves was modelled by robust linear regression, producing models both with and without an eccentricity parameter. Results: FoS curves were satisfactorily fitted to data from 174 visual field locations in 20 participants (age 65–83 years, 11 female). Each curve was made up of a median of 243 (range 177–297) stimulus presentations over a median of 12 (range 9–32) levels. Median sensitivity was 25.5dB (range 3.8–31.4dB). The median slope (SD of fitted function) was 1.6dB (range 0.5–8.5dB). As in previous studies of other conditions, the slope of fitted FoS curves increased as sensitivity decreased (p<0.001). Conclusions: FoS are provided for participants with AMD, as well as models of the relationship between sensitivity and slope. These fitted models and data may be useful for computer simulation studies of microperimetry procedures. Full details of the fitted curves are provided as supporting information.
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Genetic networks suggest Asperger’s syndrome as a distinct subtype of autism spectrum disordersBackground: The Diagnostic and Statistical Manual of Mental Disorders (DSM-V) issued new diagnostic criteria for autism spectrum disorders (ASD) which resulted in missing the diagnosis of some cases of Asperger’s syndrome (AS). This negatively affected the support received by those affected. In this study, we explored if AS could be biologically stratified from the broader spectrum through a gene co-expression network preservation analysis. Methods: We analysed the GEO microarray data of 24 individuals with Asperger’s syndrome and 72 individuals with autism. Then, we used a weighted gene co-expression network (WGCNA) pipeline to construct gene co-expression networks. We explored whether these modules share the same co-expression patterns between autism and Asperger’s syndrome using network preservation analysis. Results: Our results showed that all co-expression modules of autism are preserved into the Asperger’s syndrome. However, three modules of Asperger’s syndrome out of 30 modules were not preserved in autism. Gene enrichment analysis revealed that these modules were involved in chromatin remodelling, immune and neuroinflammatory response, synaptic and neuronal development. Brain enrichment analysis showed significant downregulation of neurodevelopment genes in different brain regions associated with impaired social recognition in Asperger’s syndrome. Conclusions: The identified genetic and molecular profiles suggest that Asperger’s syndrome, despite sharing numerous similarities with autism, possesses a distinct genetic profile that makes it a distinct subtype of autism. This distinction could have significant implications for the management and treatment strategies tailored to individuals with Asperger’s syndrome.
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Sidechain structure-activity relationships of cyclobutane-based small molecule αvβ3 antagonistsThe integrin family of cell surface extracellular matrix binding proteins are key to several physiological processes involved in tissue development, as well as cancer proliferation and dissemination. They are therefore attractive targets for drug discovery with cancer and non-cancer applications. We have developed a new integrin antagonist chemotype incorporating a functionalised cyclobutane ring as the central scaffold in an arginine–glycine–aspartic acid mimetic structure. Here, we report the synthesis of cyclobutanecarboxylic acids and cyclobutylamines with tetrahydronaphthyridine and aminopyridine arginine mimetic sidechains and masked carboxylic acid aspartic acid mimetic sidechains of varying length. Effective αvβ3 antagonists and new aspartic acid mimetics were identified in cell-based adhesion and invasion assays. A lead compound selected based on in vitro activity (IC50 < 1 μM), stability (t1/2 > 80 minutes) and synthetic tractability was well-tolerated in vivo. These results show the promise of this synthetic approach for developing αvβ3 antagonists and provide a firm foundation to progress into advanced preclinical evaluation prior to progression towards the clinic. Additionally, they highlight the use of functionalised cyclobutanes as metabolically stable core structures and a straightforward and robust method for their synthesis. This important contribution to the medicinal chemists' toolbox paves the way for increased use of cyclobutanes in drug discovery.
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A qualitative analysis of the role of the diagnostic radiographer in child safeguardingBackground: The role of medical imaging in the investigation of suspected child abuse is well documented. However, the role of the radiographer as an instigator of such concerns is less well understood. The fast-paced development of related technology and the evolution of the profession into new areas of work is argued to have impacted upon the traditional interaction between patient and professional; thus requiring a contemporary analysis of current practice. Objective: As part of a wider multimethod thesis, this qualitative study sought to fill a gap in the literature with regard the role of the radiographer in child safeguarding by exploring their knowledge of, attitude towards and practical experience of the phenomenon. Participants and setting: Online, semi-structured interviews were conducted with n=12 radiographers from across England between 2020 and 2021. Recruitment occurred via an initial survey and interviews were conducted online. Methods: Verbatim transcripts were analysed using a framework analysis approach to create initial codes which led to themes for discussion. Results: The framework analysis approach resulted in the identification of three constituent themes: (1) Patient, (2) Examination and (3) Radiographer. Each constituent themes were built from a comprehensive coding of the data. Analysis of these themes are presented in terms of quotes and diagrammatic depiction. Conclusion: For radiographers to be able to identify child safeguarding concerns, alignment of these constituent themes is necessary with the radiographer being the theme that can be greater controlled in terms of knowledge and attitude. Conceptually, this analysis could be extended to other professionals. Contemporary practice within medical imaging has made it more challenging to assess some physical and social signs of child safeguarding concern, and thus for the alignment to occur, as compared with previous generations. To maximise the contribution, education needs to account for wider paediatric practice and the imaging modality utilised by the radiographer. A case study approach demonstrating the potential that exists for the profession to contribute would be beneficial. Interprofessionally, greater involvement of radiographers in the assessment and escalation of any concerns could provide benefit to the patient.
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An analysis of pharmacogenomic-guided pathways and their effect on medication changes and hospital admissions: A systematic review and meta-analysisNinety-five percent of the population are estimated to carry at least one genetic variant that is discordant with at least one medication. Pharmacogenomic (PGx) testing has the potential to identify patients with genetic variants that puts them at risk of adverse drug reactions and sub-optimal therapy. Predicting a patient's response to medications could support the safe management of medications and reduce hospitalization. These benefits can only be realized if prescribing clinicians make the medication changes prompted by PGx test results. This review examines the current evidence on the impact PGx testing has on hospital admissions and whether it prompts medication changes. A systematic search was performed in three databases (Medline, CINAHL and EMBASE) to search all the relevant studies published up to the year 2020, comparing hospitalization rates and medication changes amongst PGx tested patients with patients receiving treatment-as-usual (TAU). Data extracted from full texts were narratively synthesized using a process model developed from the included studies, to derive themes associated to a suggested workflow for PGx-guided care and its expected benefit for medications optimization and hospitalization. A meta-analysis was undertaken on all the studies that report the number of PGx tested patients that had medication change(s) and the number of PGx tested patients that were hospitalized, compared to participants that received TAU. The search strategy identified 5 hospitalization themed studies and 5 medication change themed studies for analysis. The meta-analysis showed that medication changes occurred significantly more frequently in the PGx tested arm across 4 of 5 studies. Meta-analysis showed that all-cause hospitalization occurred significantly less frequently in the PGx tested arm than the TAU. The results show proof of concept for the use of PGx in prescribing that produces patient benefit. However, the review also highlights the opportunities and evidence gaps that are important when considering the introduction of PGx into health systems; namely patient involvement in PGx prescribing decisions, thus a better understanding of the perspective of patients and prescribers. We highlight the opportunities and evidence gaps that are important when considering the introduction of PGx into health systems.
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A rapid review of interventions to improve medicine self-management for older people living at homeBackground: As people age, they are more likely to develop multiple long-term conditions that require complicated medicine regimens. Safely self-managing multiple medicines at home is challenging and how older people can be better supported to do so has not been fully explored. Aim: This study aimed to identify interventions to improve medicine self-management for older people living at home and the aspects of medicine self-management that they address. Design: A rapid review was undertaken of publications up to April 2022. Eight databases were searched. Inclusion criteria were as follows: interventions aimed at people 65 years of age or older and their informal carers, living at home. Interventions needed to include at least one component of medicine self-management. Study protocols, conference papers, literature reviews and articles not in the English language were not included. The results from the review were reported through narrative synthesis, underpinned by the Resilient Healthcare theory. Results: Database searches returned 14,353 results. One hundred and sixty-seven articles were individually appraised (full-text screening) and 33 were included in the review. The majority of interventions identified were educational. In most cases, they aimed to improve older people's adherence and increase their knowledge of medicines. Only very few interventions addressed potential issues with medicine supply. Only a minority of interventions specifically targeted older people with either polypharmacy, multimorbidities or frailty. Conclusion: To date, the emphasis in supporting older people to manage their medicines has been on the ability to adhere to medicine regimens. Most interventions identify and target deficiencies within the patient, rather than preparing patients for problems inherent in the medicine management system. Medicine self-management requires a much wider range of skills than taking medicines as prescribed. Interventions supporting older people to anticipate and respond to problems with their medicines may reduce the risk of harm associated with polypharmacy and may contribute to increased resilience in the system. Patient or Public Contribution: A patient with lived experience of medicine self-management in older age contributed towards shaping the research question as well as the inclusion and exclusion criteria for this review. She is also the coauthor of this article. A patient advisory group oversaw the study.
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Patient and public co-creation of healthcare safety and healthcare system resilience: The case of COVID-19Healthcare system resilience is a conceptual approach that seeks to explore how health services adapt and respond to variability in demand and resources. As has been witnessed since the beginning of the COVID-19 pandemic, healthcare services have undergone many reconfigurations. One understudied aspect of how the 'system' is able to adapt and respond is the contribution of key stakeholders-patients and families, and in the context of the pandemic, the general public as a whole. This study aimed to understand what people were doing during the first wave of the pandemic to protect the safety of their health, and the health of others from COVID-19, and the resilience of the healthcare system. Social media (Twitter) was used as a method of recruitment due to its ability for social reach. Twenty-one participants took part in 57 semistructured interviews over three time points from June to September 2020. The included an initial interview and invitation to two follow-up interviews after 3 and 6 weeks. Interviews were conducted virtually using Zoom-an encrypted secure video conferencing software. A reflexive thematic analysis approach to analysis was used. Three themes, each with its own subthemes were identified in the analysis: (1) A 'new safety normal'; (2) Existing vulnerabilities and heightened safety and (3) Are we all in this together? This study found that the public had a role in supporting the resilience of healthcare services and systems during the first wave of the pandemic by adapting their behaviour to protect themselves and others, and to avoid overwhelming the National Health Service. People who had existing vulnerabilities were more likely to experience safety gaps in their care, and be required to step in to support their safety, despite it being more difficult for them to do so. It may be that the most vulnerable were previously required to do this extra work to support the safety of their care and that the pandemic has just illuminated this issue. Future research should explore existing vulnerabilities and inequalities, and the heightened safety consequences created by the pandemic. The National Institute for Health Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR Yorkshire and Humber PSTRC), Patient and Public Involvement and Engagement Research Fellow and NIHR Yorkshire and Humber PSTRC Patient Involvement in Patient Safety theme lay leader are involved in the preparation of a lay version of the findings within this manuscript.
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Developing a research community within an online healthcare feedback platformCare Opinion is an online feedback platform supporting patients to author stories about their care. It is not known whether authors would be willing to be involved in improving care through research. The aims of this study were to explore the views and preferences of Care Opinion authors about joining an online research community and to pilot new research community functionality. Five hundred and nine Care Opinion authors were invited to take part in an online survey in June 2019. Survey items included questions about participants' willingness to take part in research and their preferences for supporting processes. Data were analysed descriptively. Authors were invited to consent to join a research community and were asked to participate in three pilot studies. One hundred and sixty-three people consented to take part in the survey (32%). Participants indicated they would like to know the time commitment to the project (146, 90%), details about the organization carrying out the research (124, 76%) and safeguarding information (124, 76%). Over half indicated that they did not know how to get involved in healthcare research (87, 53%). Subsequently, 667 authors were invited to join the research community, 183 (27%) accepted, and three studies were matched to their expressed preferences for project attributes or organization type. Many people who leave online feedback about their experiences of healthcare are also willing to join a research community via that platform. They have strong preferences for supporting University and NHS research. Eligibility and acceptance rates to join pilot research studies varied. Further work is needed to grow the research community, increase its diversity, and create relevant and varied opportunities to support research. Four members of the Safety In Numbers patient and public involvement and engagement (PPIE) group advised about survey development.
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Barriers and facilitators of implementing proactive deprescribing within primary care: a systematic reviewProactive deprescribing - identifying and discontinuing medicines where harms outweigh benefits - can minimise problematic polypharmacy, but has yet to be implemented into routine practice. Normalisation process theory (NPT) can provide a theory-informed understanding of the evidence base on what impedes or facilitates the normalisation of routine and safe deprescribing in primary care. This study systematically reviews the literature to identify barriers and facilitators to implementing routine safe deprescribing in primary care and their effect on normalisation potential using NPT.PubMed, MEDLINE, Embase, Web of Science, International Pharmaceutical Abstracts, CINAHL, PsycINFO and The Cochrane Library were searched (1996-2022). Studies of any design investigating the implementation of deprescribing in primary care were included. The Mixed Methods Appraisal Tool and the Quality Improvement Minimum Quality Criteria Set were used to appraise quality. Barriers and facilitators from included studies were extracted and mapped to the constructs of NPT. A total of 12,027 articles were identified, 56 articles included. In total, 178 barriers and 178 facilitators were extracted and condensed into 14 barriers and 16 facilitators. Common barriers were negative deprescribing perceptions and suboptimal deprescribing environments, while common facilitators were structured education and training on proactive deprescribing and utilising patient-centred approaches. Very few barriers and facilitators were associated with reflexive monitoring, highlighting a paucity of evidence on how deprescribing interventions are appraised. Through NPT, multiple barriers and facilitators were identified that impede or facilitate the implementation and normalisation of deprescribing in primary care. However, more research is needed into the appraisal of deprescribing post-implementation.
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Incivility experiences of racially minoritised hospital staff, consequences for them and implications for patient care: An international scoping reviewWorkplace incivility is a pervasive complex problem within health care. Incivility manifests as subtle disrespectful behaviours, which seem inconsequential. However, evidence demonstrates that incivility can be harmful to targets and witnesses through negative emotions, poorer mental health, reduced job satisfaction, diminished performance and compromised patient care. It is unclear to what extent existing research critically explores how ethnicity, culture and racism influence how hospital staff experience incivility. This global scoping review systematically analysed existing research exploring the specific ways incivility manifests and impacts racially minoritised hospital workers. Of 2636 academic and 101 grey literature articles, 32 were included. Incivility experiences were categorised into four themes: (1) Cultural control, (2) Rejection of work contributions, (3) Disempowerment at work and (4) Managerial indifference. The included articles highlighted detrimental consequences, such as negative emotions, silencing, withdrawal and reduced support-seeking behaviours. Few studies presented evidence regarding the negative impacts of incivility on patient care. Racialisation and racial dynamics are a significant factor for hospital-based incivility. Currently we do not know the extent to which racialised incivility is associated directly or, perhaps either via burnout or disengagement, indirectly with poorer care. This knowledge can inform the creation of comprehensive, evidence-based interventions to address this important issue.