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Background Cardiovascular disease is the most common cause of death worldwide, highlighting the need for studies to determine options for palliative care within the management of patients with heart failure. Although there are promising examples of integrated palliative care and heart failure interventions, there is heterogeneity in terms of countries, healthcare settings, multidisciplinary team delivery, modes of delivery and intervention components. Hence, this review is vital to identify what works, for whom and in what circumstances when integrating palliative care and heart failure. Objectives To (1) develop a programme theory of why, for whom and in what contexts desired outcomes occur; and (2) use the programme theory to co-produce with stakeholders key implications to inform best practice and future research. Design A realist review of the literature underpinned by the Realist and Meta-narrative Evidence Syntheses: Evolving Standards quality and reporting standards. Data sources Searches of bibliographic databases were conducted in November 2021 using the following databases: EMBASE, MEDLINE, PsycInfo, AMED, HMIC and CINAHL. Further relevant documents were identified via alerts and the stakeholder group. Review methods Realist review is a theory-orientated and explanatory approach to the synthesis of evidence. A realist synthesis was used to synthesise the evidence as successful implementation of integrated palliative care and heart failure depends on the context and people involved. The realist synthesis followed Pawson’s five iterative stages: (1) locating existing theories; (2) searching for evidence; (3) document selection; (4) extracting and organising data; and (5) synthesising the evidence and drawing conclusions. We recruited an international stakeholder group (n = 32), including National Health Service management, healthcare professionals involved in the delivery of palliative care and heart failure, policy and community groups, plus members of the public and patients, to advise and give us feedback throughout the project, along with Health Education England to disseminate findings. Results In total, 1768 documents were identified, of which 1076 met the inclusion criteria. This was narrowed down to 130 included documents based on the programme theory and discussions with stakeholders. Our realist analysis developed and refined 6 overarching context–mechanism–outcome configurations and 30 sub context–mechanism–outcome configurations. The realist synthesis of the literature and stakeholder feedback helped uncover key intervention strategies most likely to support integration of palliative care into heart failure management. These included protected time for evidence-based palliative care education and choice of educational setting (e.g. online, face to face or hybrid), and the importance of increased awareness of the benefits of palliative care as key intervention strategies, the emotive and intellectual need for integrating palliative care and heart failure via credible champions, seeing direct patient benefit, and prioritising palliative care and heart failure guidelines in practice. The implications of our findings are further outlined in the capability, opportunity, motivation, behaviour model. Limitations The realist approach to analysis means that findings are based on our interpretation of the data. Future work Future work should use the implications to initiate and optimise palliative care in heart failure management. Conclusion Ongoing refinement of the programme theory at each stakeholder meeting allowed us to co-produce implications. These implications outline the required steps to ensure the core components and determinants of behaviour are in place so that all key players have the capacity, opportunity and motivation to integrate palliative care into heart failure management. Study registration This study is registered as PROSPERO CRD42021240185. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR131800) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 34. See the NIHR Funding and Awards website for further award information. Plain language summary People with heart failure can frequently become unwell with poor quality of life despite advanced medical therapies. Palliative care can do much to alleviate suffering for people with heart failure as it focuses on adding to patient care by treating the whole person – their physical, psychosocial and spiritual needs, which improves quality of life for both the patient and their loved ones. However, poor integration of palliative care into the management of heart failure is an ongoing problem. To understand why this is, we have undertaken a particular method of literature review called realist synthesis that looks at all types of literature to identify what works, for whom and in what circumstances. We have worked closely with our stakeholder group (including healthcare providers and patients who have heart failure and their carers) to advise and give us feedback throughout this review. We found the following: A review of education for health and social care professionals is needed to make sure that palliative care for patients with non-cancer conditions such as heart failure is adequately covered. Education is also needed for patients and those who care for them to help them understand what palliative care is (holistic care delivered alongside active heart failure management based on patient need) and what it is not (only for cancer patients and end-of-life care). All health and social care staff should work closely together when managing patients with heart failure to learn from each other. Policy, practice and service user champions must be identified and supported to share the benefits of integrated care. Visible guidelines should prioritise integrated palliative care and heart failure so they become part of everyday practice. Scientific summary Background Cardiovascular disease is the most common cause of death worldwide and the most frequent cause of hospitalisation among individuals aged > 65 years. In 2012, heart failure (HF) was estimated to account for £22.5B of health expenditure globally; between 2012 and 2030 it is estimated that total costs will increase by 127%. Integrating palliative care (PC) with routine management of HF has been shown to significantly reduce healthcare costs overall compared to usual care (without PC) and significantly reduces the number of hospital visits and duration of inpatient stays. There is evidence of improved patient and informal caregiver outcomes when PC is integrated in HF management. Integrated palliative and HF care aims to achieve continuity of care by integrating administrative, organisational, and clinical services that make up the patients care network. However, two decades have passed since the first publication on the benefits of PC for patients with HF. The scarcity of effective integration of PC into HF management can be explained by a number of factors, including uncertainty around the HF disease trajectory and complexities of communicating this uncertainty to the patient and family members. The 2021 European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of acute and chronic HF highlighted the need for studies to determine specific options for PC within the treatment of HF. Although we have some promising examples of integrated PC and HF interventions, there is heterogeneity in terms of countries, healthcare settings, delivery and intervention components. Hence, this review is vital for identifying what works best, for whom and in what circumstances. Aim and objectives To understand how integrated PC and HF interventions work in different healthcare settings for example inpatient/outpatient, and for which groups of people, so we can recommend strategies to maximise the potential for widespread implementation, reduce healthcare costs, and improve quality of life (QoL) for patients and informal carers. To conduct a realist synthesis (RS) to build an understanding of which integrated PC and HF interventions work best together, in which contexts and for which patients who have HF and informal carers. To co-produce implications with an expert stakeholder group, to maximise potential for widespread implementation through a user guide for healthcare providers and user-friendly summaries for patients and the public. Review questions What are the mechanisms by which integrated PC and HF interventions work to produce their intended outcomes? What are the contexts which determine whether integrated PC and HF interventions produce their intended or unintended outcomes? In what settings are integrated PC and HF interventions likely to be effective? Methods To understand and make sense of the complexity of integrating PC in HF management, we used a RS approach to examine what works for whom, in what circumstances, how and why. RS is a theory-driven approach for understanding existing diverse sources of evidence relating to complex interventions. It is theory driven because it uses evidence to iteratively develop and test structurally coherent explanations (i.e. theories) of complex interventions. The methodology followed Pawson’s five iterative stages for RS: (1) locating existing theories; (2) searching for evidence; (3) selecting documents; (4) extracting and organising data; and (5) synthesising the evidence and drawing conclusions. The review ran for 22 months, from September 2021 to June 2023. Data sources Searches of bibliographic databases were conducted in November 2021 using the following databases: EMBASE, MEDLINE, PsycInfo, AMED (via Ovid), HMIC (via Ovid) and CINAHL (via EBSCOhost). Further relevant documents were identified via alerts and through our stakeholder group. Study selection The initial inclusion and exclusion criteria for the review were deliberately broad as we aimed to identify all relevant quantitative, qualitative, mixed-methods and non-empirical documents relating to HF and PC. We applied the following inclusion criteria: Document types – All documents focused on PC for patients who have HF Study design – All study designs. Non-empirical data (e.g. from opinion/commentary pieces) which help direct/shape theory development Types of settings – All documents about inpatient or outpatient or home-based care settings Types of participants – All adult patients (18 years and over) Types of intervention – Any combination of PC strategies for the management of patients with HF Outcome measures – All integrated PC- and HF-related outcome measures Following the presentation of the preliminary initial programme theory to our stakeholder group, stakeholders focused on healthcare professionals’ perspectives for implementation of integrated PC in HF management. This iterative process of identifying the most pertinent explanatory theory allowed us to narrow the scope of the synthesis to focus on healthcare professionals’ perspectives on integrated PC into HF management. Data extraction Initial coding of the documents used both inductive (codes emerging through data analysis) and deductive methods (codes determined prior to analysis through initial programme theory and stakeholder discussions). The coding framework resulted from the analysis of the richest documents, which were documents with the most potential to inform the programme theory; within this review, these were mostly qualitative research papers. Examples of initial codes identified were ‘biomedical culture within cardiology’ and ‘terminology – understanding what PC is and is not’. We concurrently worked to identify ‘guiding principles’ and features underpinning the interventions, and relevant implications discussed mostly in policy documents, reviews and commentaries. The framework generated was applied to the remainder of the documents and refined as the analysis progressed. For example, we identified relevant contexts when mechanisms were likely to be ‘triggered’, such as a shared understanding (across patient, informal caregiver and healthcare professionals) that PC in HF management positively contributes to optimised QoL. Such contexts and mechanism became ‘codes’. Analysis and synthesis The analysis was driven by a realist logic. We sought to interpret and explain mechanisms, such as shared vision and provision of joint PC and HF education, in which integrated PC in HF management would occur (or not). We used the coding of the included documents within NVivo (QSR International, Warrington, UK) to draw relationships between contexts, mechanisms and outcomes, and to further develop our initial programme theory. In summarising, the evidence synthesis process was achieved using the below analytic processes: Juxtaposition of data sources: data reported in different documents were compared and contrasted. Reconciling ‘contradictory’ or disconfirming data: when outcomes differed in seemingly comparable circumstances, further investigation was undertaken to find explanations for why different outcomes happened. This involved looking closer at what made up the context for different kinds of ‘problems’, to understand how mechanisms triggered could explain different outcomes. Consolidation of sources of evidence: when findings from different documents had similarities, a judgement was made as to whether these similarities could adequately form patterns to inform the development of context–mechanism–outcome configurations (CMOcs) and programme theory, or whether there were nuances that required highlighting, and for what purpose. The aim of the analysis was to reach theoretical saturation, that sufficient information had been captured to portray and explain the processes leading to the implementation of integrated PC in HF management and the mechanisms that can aid this implementation. Consistency checks Consistency checks were carried out by a second reviewer Tracey McConnell (TM) on a 10% random sample of the screening (title, abstract and full text) and the coding process for the main search. Minimal inconsistencies were identified and, when identified, were resolved through discussion. Stakeholder group Our patient and public involvement (PPI) group members were involved throughout the planning and execution of this project. They sat on our stakeholder group made up of 32 stakeholder participants including specialist HF nurses, cardiology and PC consultants, people who had HF, an informal caregiver, and researchers. During the review, we asked PPI stakeholder group members: to help us develop our initial programme theory; for their advice and feedback on our programme theory as it evolved; to consider our findings and implications from their varied perspectives; to provide input and support into our dissemination strategy; and to review and contribute to our materials, to ensure they met the needs of patients and the wider public. Results (research findings) A total of 1768 documents were identified, of which 1076 met the inclusion criteria for further screening. Based on programme theory and discussions with stakeholders, it was decided to refine the inclusion criteria further to align with the focus of the review leading to 130 documents being included. Our realist analysis developed and refined 6 overarching context–mechanism–outcome configurations with 30 sub CMOcs. We used the capability, opportunity, motivation, behaviour (COM-B) model to help identify intervention strategies needed to produce desired behaviours and avoid undesired behaviours. Although the COM-B model relates to individual behaviour change, it also considers team and organisational behaviour. For example, an individual’s capacity to carry out a specific behaviour also depends on the organisational culture they work within, and the opportunities afforded to them within their team and organisation. Capacity According to the ‘capacity’ component of the COM-B model, individuals must believe they have the required knowledge and skills to carry out a behaviour. Unsurprisingly, education was a key intervention strategy for providing key individuals with the required knowledge and skills to overcome many of the key blockages identified in the literature, from a biomedical culture (CMOc 1–1.1), to misunderstandings around terminology which equate PC with end-of-life care only (CMOc 1.2–1.5), complexities of the HF illness trajectory (CMOc 1.6–1.7), to the challenges of integrating PC in the context of patients with HF who have life-prolonging devices (CMOc 1.8–1.8b). The realist analysis and synthesis of the literature helped uncover what ‘types’ of educational strategies are required to achieve integration of PC into HF management. These included shared education and experiential learning within and between disciplines across all care settings (CMOc 2.1), communication skills training (CMOc 2.8), public health approach/messaging (CMOc 2.9), evidence-based examples of good practice (CMOc 3) and guidelines embedded in undergraduate (UG) and postgraduate education (CMOc 6). Opportunity The opportunity component of the COM-B model proposes that individuals must have the required physical (time and resources) opportunities for behaviour change to occur. Therefore, providing evidence-based educational strategies is not enough to create behaviour change without due attention to the required opportunities. The literature and stakeholders stressed the importance of protected time for education and choice of educational setting (e.g. online, face to face or hybrid) (CMOc 2.7). The importance of having guidelines was highlighted by the review findings. This also showed that despite the availability of guidelines there is still a lack of clarity within HF management around who is responsible for initiating PC conversations, when this should happen, and how often. Therefore, guidelines for integrating PC and HF should be visible, easily accessible and their use prioritised, with clarity on expectations and roles, so patients receive the right care, from the right people, at the right time (CMOc 6). Motivation According to the COM-B model, motivation is a core component necessary for behaviour change, meaning that the behaviour must be more desirable and important than other competing priorities. CMOc 3 identified the importance of increased awareness and seeing benefits of PC in HF management (CMOc 3) as key intervention strategies. Stakeholders noted that evidence may win minds, but we also need to convince hearts, and so emphasised the importance of winning both hearts and minds. The synthesis of the international evidence also supported the importance of conveying the emotive and intellectual need for integrating PC and HF via credible champions, seeing direct patient benefit, and evidence-based education (CMOc 3.1). Conclusions and implications Ongoing refinement of the programme theory at each stakeholder meeting allowed us to co-produce implications. These implications outline the required steps to ensure the core components and determinants of behaviour are in place so that all key players have the capacity, opportunity and motivation to integrate PC into HF management. Integrated PC and HF services must be prioritised by senior decision-makers in the health and care system. Services must be adequately funded to ensure that staff are able to develop and run fully integrated PC and HF services. Service design should start with an assessment of the availability of PC and HF services in their locality (e.g. ‘postcode lottery’ issues) and find solutions. Services integrating PC into HF management must be provided which are reflective of the diversity of the whole population within the local healthcare context. Develop service delivery models that provide continuity of care for patients with HF including: reconfigured services to promote a multidisciplinary team (MDT) working between specialties and settings (including primary care) processes to monitor and address gaps in provision and caseloads processes to show the benefits (e.g. reduction in the need for inpatient care and cost-savings) of integrated PC and HF resources for all settings (e.g. primary and secondary care) and all audiences involved (e.g. patients, carers and clinicians) with clear and consistent messages about PC and HF. For example, develop a patient information leaflet, co-designed by PPI and engagement, to highlight what integrated PC in HF management is and when this might be suitable Develop guidelines for MDT meetings to identify who, when and how each of the below key decisions and action will be completed for each patient with HF: who is responsible for introducing PC to the patient and informal caregiver(s)? who will assess PC needs and how often (e.g. at every healthcare professional contact)? agreeing care plan (needs to be individualised to each patient) executing care plan reassessing care plan ensuring needs and care plans are communicated across settings and specialties ongoing evaluation including patient reported outcome measures, to enable refinement and benchmarking of guidelines/care pathway. Evaluate current PC education in UG and post-registration medical, nursing, allied health and social care (HSC) professional curriculum to identify deficits in the PC curriculum around caring for those with HF. Effective communications skills training is required across all levels of the curriculum in nursing, medicine and allied HSC professional education to ensure all have the means to communicate the value of PC and HF and provide ongoing care. Facilitate joint decision-making: Set up and run MDT meetings for those involved in PC and HF that enable members to develop trusting relationships, work collaboratively and learn from each other. Create active engagement by demonstrating the value of integrated PC in HF, for example, through the sharing of examples of good practice, for example through visits and placements. Develop effective patient PC education for individuals diagnosed with HF. Equip and enable all people involved with PC and HF (e.g. patients, consultants, nurses, informal carers) to champion the value and need for integrated PC and HF. Address public (mis)understanding of PC and HF through public health campaigns focused on raising awareness of PC as a holistic, wrap around care plan for improving QoL for those with HF. Study registration This study is registered as PROSPERO CRD42021240185. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR131800) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 34. See the NIHR Funding and Awards website for further award information.

Abstract Background A third of older people take five or more regular medications (polypharmacy). Conducting medication reviews in primary care is key to identify and reduce/ stop inappropriate medications (deprescribing). Recent recommendations for effective deprescribing include shared-decision making and a multidisciplinary approach. Our aim was to understand when, why, and how interventions for medication review and deprescribing in primary care involving multidisciplinary teams (MDTs) work (or do not work) for older people. Methods A realist synthesis following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards guidelines was completed. A scoping literature review informed the generation of an initial programme theory. Systematic searches of different databases were conducted, and documents screened for eligibility, with data extracted based on a Context, Mechanisms, Outcome (CMO) configuration to develop further our programme theory. Documents were appraised based on assessments of relevance and rigour. A Stakeholder consultation with 26 primary care health care professionals (HCPs), 10 patients and three informal carers was conducted to test and refine the programme theory. Data synthesis was underpinned by Normalisation Process Theory to identify key mechanisms to enhance the implementation of MDT medication review and deprescribing in primary care. Findings A total of 2821 abstracts and 175 full-text documents were assessed for eligibility, with 28 included. Analysis of documents alongside stakeholder consultation outlined 33 CMO configurations categorised under four themes: 1) HCPs roles, responsibilities and relationships; 2) HCPs training and education; 3) the format and process of the medication review 4) involvement and education of patients and informal carers. A number of key mechanisms were identified including clearly defined roles and good communication between MDT members, integration of pharmacists in the team, simulation-based training or team building training, targeting high-risk patients, using deprescribing tools and drawing on expertise of other HCPs (e.g., nurses and frailty practitioners), involving patents and carers in the process, starting with ‘quick wins’, offering deprescribing as ‘drug holidays’, and ensuring appropriate and tailored follow-up plans that allow continuity of care and management. Conclusion We identified key mechanisms that could inform the design of future interventions and services that successfully embed deprescribing in primary care.

Objectives (1) Develop a programme theory of why, for whom and in what contexts integrated palliative care (PC) and heart failure (HF) services work/do not work; (2) use the programme theory to co-produce with stakeholders, intervention strategies to inform best practice and future research.Methods A systematic review of all published articles and grey literature using a realist logic of analysis. The search strategy combined terms significant to the review questions: HF, PC and end of life. Documents were included if they were in English and provided data relevant to integration of PC and HF services. Searches were conducted in November 2021 in EMBASE, MEDLINE, PsycINFO, AMED, HMIC and CINAHL. Further relevant documents were identified via monthly alerts (up until April 2023) and the project stakeholder group (patient/carers, content experts and multidisciplinary practitioners).Results 130 documents were included (86 research, 22 literature reviews, 22 grey literature). The programme theory identified intervention strategies most likely to support integration of PC and HF services. These included protected time for evidence-based PC and HF education from undergraduate/postgraduate level and continuing professional practice; choice of educational setting (eg, online, face-to-face or hybrid); increased awareness and seeing benefits of PC for HF management; conveying the emotive and intellectual need for integrating PC and HF via credible champions; and prioritising PC and HF guidelines in practice.Conclusions The review findings outline the required steps to take to increase the likelihood that all key players have the capacity, opportunity and motivation to integrate PC into HF management.PROSPERO registration number CRD42021240185.

A multimodal approach is developed in rats, which enables the interrogation of effects of temperature changes on neurovascular coupling.

Abstract Background Prostate cancer is the third most prevalent cancer in the American population. Furthermore, the prognosis is worse in African American as there is increased morbidity and mortality associated with it. Purpose The purpose of this study is to evaluate the effectiveness of a new online method to educate the patient population regarding prostate cancer risk, diagnosis, treatments, and their decisions about whether to be screened for the early detection of prostate cancer. Methods Two hundred Black male patients are recruited from different clinical sites and randomized to either the control arm (usual care) or the intervention arm (educational program). We will compare the effectiveness of the intervention to see if patients are discussing the need of getting a prostate-specific antigen (PSA) test, and the possible benefits and harms that may result of having or not having the test, with their primary care providers. Discussion Shared decision-making (SDM) is the current standard in most cancer-screening guidelines and also a standard of person-centered care. However, there is a lack of evidence-based approaches to improve decision quality in clinical settings and an increased ambiguity of applying SDM for PSA-based screening among Black men in primary care. Our proposal to evaluate a decisional-aid intervention and measure the actual application of SDM during clinical encounters has a high potential to advance the translation path of implementing shared decision-making in clinical settings and provide evidence of the applicability of the guideline in general. Innovation and overall impact Given the 2018 USPSTF updated guidelines recommending shared decision-making about PSA-based screening, the increased risk of prostate cancer mortality in Black men, the challenges of evidence-based decision-making due to the underrepresentation of Blacks in major randomized clinical trials, and implicit racial bias among primary care providers, the time is ripe for interventions to improve shared decision-making about prostate cancer screening in Black men. In this study, we address communication and knowledge gaps between Black men and their primary care providers. The intervention, if proven effective, can be readily scaled across primary care practices across the U.S. and may be adapted to other types of cancer where guidelines have included shared decision-making as well. Early detection of prostate cancer may decrease mortality and morbidity in the long term.

Abstract Investigating neurovascular coupling in awake rodents is becoming ever more popular due, in part, to our increasing knowledge of the profound impacts that anaesthesia can have upon brain physiology. Although awake imaging brings with it many advantages, we still do not fully understand how voluntary locomotion during imaging affects sensory-evoked haemodynamic responses. In this study we investigated how evoked haemodynamic responses can be affected by the amount and timing of locomotion. Using an awake imaging set up, we used 2D-Optical Imaging Spectroscopy (2D-OIS) to measure changes in cerebral haemodynamics within the sensory cortex of the brain during either 2 s whisker stimulation or spontaneous (no whisker stimulation) experiments, whilst animals could walk on a spherical treadmill. We show that locomotion alters haemodynamic responses. The amount and timing of locomotion relative to whisker stimulation is important, and can significantly impact sensory-evoked haemodynamic responses. If locomotion occurred before or during whisker stimulation, the amplitude of the stimulus-evoked haemodynamic response was significantly altered. Therefore, monitoring of locomotion during awake imaging is necessary to ensure that conclusions based on comparisons of evoked haemodynamic responses (e.g., between control and disease groups) are not confounded by the effects of locomotion.

BackgroundDespite the overall reduction in the HIV mother-to-child transmission (MTCT) rate in South Africa, poor adherence and retention in care during breastfeeding contribute to this period being a major driver of MTCT in South Africa. To improve this retention, postnatal clubs were created as an integrated, differentiated model of care providing psychosocial support and comprehensive care for the mother-infant pairs (MIP), including HIV and under-5-child services. We describe the implementation of these facility-based clubs and examine its health outcomes in a peri-urban primary health care setting in Cape Town, South Africa.MethodsIn this prospective cohort study, conducted between June 2016 and December 2019, MIPs were recruited into postnatal clubs between 6 weeks and 6 months of age and followed-up until 18 months of age. Outcomes including maternal Viral Load (VL), and children's HIV testing were compared to a historical control group. Children's immunizations and maternal sexual and reproductive health outcomes are also described.ResultsDuring the implementation of the postnatal club study period, 484 MIP were recruited with 84% overall attendance, 95% overall viral load suppression, and 98% overall uptake of HIV infant testing. Compared to historical controls, the club infant rapid test uptake was 1.6 times higher (95% CI: 1.4-1.9) at 9 months and 2.0 times higher at 18 months (95% CI: 1.6-2.6). Through 12 months and between 12-18 months, maternal VL monitoring was higher in the club group compared to the historical control by 1.5 times (95% CI: 1.3-1.6) and 2.6 times (95% CI: 2.1-3.2), respectively, with similar maternal VL suppression. Of 105 infants attending the 12 months visit, 99% were fully vaccinated by one year.ConclusionMIP in the postnatal clubs showed better PMTCT outcomes than historical controls with high levels of retention in care. Other outcomes such as immunisation results suggest that integration of services, such as in the postnatal club, is feasible and beneficial for MIPs.

Objectives Hospital-acquired pressure injuries (PIs) are a source of morbidity and mortality, and many are potentially preventable.Design This study prospectively evaluated the prevalence and the associated factors of PIs in adult critical care patients admitted to intensive care units (ICU) in the UK.Setting This service evaluation was part of a larger, international, single-day point prevalence study of PIs in adult ICU patients. Training was provided to healthcare givers using an electronic platform to ensure standardised recognition and staging of PIs across all sites.Participants The characteristics of the ICUs were recorded before the survey; deidentified patient data were collected using a case report form and uploaded onto a secure online platform.Primary and secondary outcome measures Factors associated with ICU-acquired PIs in the UK were analysed descriptively and using mixed multiple logistic regression analysis.Results Data from 1312 adult patients admitted to 94 UK ICUs were collected. The proportion of individuals with at least one PI was 16% (211 out of 1312 patients), of whom 8.8% (n=115/1312) acquired one or more PIs in the ICU and 7.3% (n=96/1312) prior to ICU admission. The total number of PIs was 311, of which 148 (47.6%) were acquired in the ICU. The location of majority of these PIs was the sacral area, followed by the heels. Braden score and prior length of ICU stay were associated with PI development.Conclusions The prevalence and the stage of severity of PIs were generally low in adult critically ill patients admitted to participating UK ICUs during the study period. However, PIs are a problem in an important minority of patients. Lower Braden score and longer length of ICU stay were associated with the development of injuries; most ICUs assess risk using tools which do not account for this.Trial registration number NCT03270345.

Plasmodium falciparum, the causative agent of malaria, remains a global health threat as parasites continue to develop resistance to antimalarial drugs used throughout the world. Accordingly, drugs with novel modes of action are desperately required to combat malaria. P. falciparum parasites infect human red blood cells where they digest the host’s main protein constituent, hemoglobin. Leucine aminopeptidase PfA-M17 is one of several aminopeptidases that have been implicated in the last step of this digestive pathway. Here, we use both reverse genetics and a compound specifically designed to inhibit the activity of PfA-M17 to show that PfA-M17 is essential for P. falciparum survival as it provides parasites with free amino acids for growth, many of which are highly likely to originate from hemoglobin. We further show that loss of PfA-M17 results in parasites exhibiting multiple digestive vacuoles at the trophozoite stage. In contrast to other hemoglobin-degrading proteases that have overlapping redundant functions, we validate PfA-M17 as a potential novel drug target.

Abstract Vaccines against SARS-CoV-2 are likely to be critical in the management of the ongoing pandemic. A number of candidates are in Phase III human clinical trials, including ChAdOx1 nCoV-19 (AZD1222), a replication-deficient chimpanzee adenovirus-vectored vaccine candidate. In preclinical trials, the efficacy of ChAdOx1 nCoV-19 against SARS-CoV-2 challenge was evaluated in a ferret model of infection. Groups of ferrets received either prime-only or prime-boost administration of ChAdOx1 nCoV-19 via the intramuscular or intranasal route. All ChAdOx1 nCoV-19 administration combinations resulted in significant reductions in viral loads in nasal-wash and oral swab samples. No vaccine-associated adverse events were observed associated with the ChAdOx1 nCoV-19 candidate, with the data from this study suggesting it could be an effective and safe vaccine against COVID-19. Our study also indicates the potential for intranasal administration as a way to further improve the efficacy of this leading vaccine candidate.

Despite numerous studies investigating responses to visual perception, there is limited research into how horses respond to different auditory stimuli. Although ‘noise-damping’ ear covers are frequently used on sport horses to minimise distraction from external auditory stimuli, the effectiveness of ear covers has not been established. This study aimed to (i) investigate the responses of horses to different sounds commonly present in a competition environment, and (ii) compare these responses in the presence and absence of ear covers. A total of 18 horses were presented with 5 sounds commonly heard in competition or stable environments both with and without ear covers, in a randomised order crossover design. Behavioural and heart rate responses were recorded. Responses were compared between sounds and with/without ear covers. Differences in physiological and behavioural responses to different complex auditory stimuli were shown. An overall difference in physiological and behavioural responses with and without ear covers was detected, although the only difference in heart rate between ear covers and no ear covers that individually achieved significance was the feed sound. These findings suggest that horses can discriminate sounds and alter their responses based on the individual stimulus, and these responses are reduced when wearing ear covers with varying effectiveness for different sounds.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. Aim: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. Design & setting: Retrospective 2-year closed-cohort study. Method: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. Results: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. Conclusion: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered.

Neurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. In this study, we examined cortical haemodynamics in mouse preparations that modelled Alzheimer’s disease (J20-AD) and atherosclerosis (PCSK9-ATH) between 9 and 12 m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume, altered levels of oxyhaemoglobin and deoxyhaemoglobin, in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a 3 x increase in hippocampal amyloid-beta plaques. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia. These findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer’s-related amyloid-plaques.

Wound care is an integral part of effective recovery. However, its associated financial burden on national health services globally is significant enough to warrant further research and development in this field. In this study, multifunctional polymer wafers were prepared, which provide antibacterial activity, high cell viability, high swelling capacity and a thermally stable medium which can be used to facilitate the delivery of therapeutic agents. The purpose of this polymer wafer is to facilitate wound healing, by creating nanosilver particles within the polymer matrix itself via a one-pot synthesis method. This study compares the use of two synthetic agents in tandem, detailing the effects on the morphology and size of nanosilver particles. Two synthetic methods with varying parameters were tested, with one method using silver nitrate, calcium chloride and sodium alginate, whilst the other included aloe vera gel as an extra component, which serves as another reductant for nanosilver synthesis. Both methods generated thermally stable alginate matrices with high degrees of swelling capacities (400–900%) coupled with interstitially formed nanosilver of varying shapes and sizes. These matrices exhibited controlled nanosilver release rates which were able to elicit antibacterial activity against MRSA, whilst maintaining an average cell viability value of above 90%. Based on the results of this study, the multifunctional polymer wafers that were created set the standard for future polymeric devices for wound healing. These polymer wafers can then be further modified to suit specific types of wounds, thereby allowing this multifunctional polymer wafer to be applied to different wounding scenarios.

Abstract Background During the twentieth century, hip replacement became one of the most popular and successful operations. In the 1990s, a new type of hip replacement namely the metal‐on‐metal hip resurfacing was developed. This paper draws on one of the available implants, namely the DePuy Orthopaedics’ Articular Surface Replacement (ASR) hip system which was withdrawn from the market because of higher than expected rates of failure. It examines media representations on the failure of the ASR metal‐on‐metal hip replacement device and its subsequent withdrawal from the market. Methods Drawing on content analysis this paper explores how systemic failure of the medical implant was framed and performed by press media in the UK. Results Two narratives were particularly important in framing press media coverage of the ASR case: the role of patients as passive recipients of care and a distinction between health and disability identities as related to how individuals’ narratives about the past shaped their sense of present and future. In all cases, the voice of the orthopaedic surgeons responsible for the selection and implantation of the ASR devices remains silent. Conclusions Press media coverage of medically induced harm in the UK is significantly less common than coverage of any other patient safety issues and public health debates. This study aims to contribute to the evidence base on how public discourse on medically induced harm becomes framed through the reported experiences of individuals in press media and also how this process influences the legitimacy of various solutions to medical errors or unanticipated outcomes.

The present study explores barriers and facilitators experienced by public health nurses introducing a mobile health technology platform (Goal Mama) to the Nurse-Family Partnership home-visiting program. Goal Mama is a HIPAA-compliant goal-coaching and visit preparation platform that clients and nurses use together to set and track goals. Forty-two nurses across five sites, including urban, suburban, and rural communities, piloted the platform with clients for 6 months. The mixed method, QUAL+quan pilot evaluation focused on deeply understanding the implementation process. Data were analyzed via iterative content analysis and multivariate regression analysis, and triangulated to identify salient findings. Over 6 months of use participants identified critical areas for product and implementation improvement, but still viewed the platform favorably. Key opportunities for improving sustained use revolved around supporting the technological and programmatic integration needed to lower key barriers and further facilitate implementation.

Antimicrobial resistant (AMR) bacteria can be shared between humans and animals, through food, water, and the environment. Wild animals are not only potential reservoirs of AMR, but are also sentinels mirroring the presence of AMR zoonotic bacteria in the environment. In Northern Ireland, little is known about levels of AMR in bacteria in wildlife, thus the current study aimed to estimate the prevalence of AMR bacteria in wildlife using wildlife species from two ongoing surveys as a proxy. Nasopharyngeal swabs and faecal samples from European badgers (Meles meles) (146 faecal samples; 118 nasal samples) and red foxes (Vulpes vulpes) (321 faecal samples; 279 nasal samples) were collected throughout Northern Ireland and were used to survey for the presence of extended spectrum beta lactamase resistant and AmpC-type beta lactamases Escherichia coli (ESBL/AmpC), Salmonella spp. (only in badgers) and methicillin resistant Staphylococcus aureus (MRSA). ESBLs were detected in 13 out of 146 badger faecal samples (8.90%) and 37 out of 321 of fox faecal samples (11.53%), all of them presenting multi-drug resistance (MDR). Fourteen out of 146 (9.59%) badger faecal samples carried Salmonella spp. [S. Agama (n = 9), S. Newport (n = 4) and S. enterica subsp. arizonae (n = 1)]. Overall, AMR was found only in the S. enterica subsp. arizonae isolate (1/14, 7.14%). No MRSA were detected in nasopharyngeal swabs from badgers (n = 118) and foxes (n = 279). This is the first attempt to explore the prevalence of AMR in the two common wildlife species in Northern Ireland. These findings are important as they can be used as a base line for further research exploring the origin of the found resistance. These results should encourage similar surveys where environmental samples are included to bring better understanding of AMR dynamics, and the impact on wildlife, domestic livestock and humans.

A fast and high throughput screening method for the determination of amantadine (ADA) in chicken muscle is presented. After acidic extraction and extractive derivatization with pentafluorobenzoyl chloride, ADA was analyzed directly without any preconcentration by GC/negative ion chemical ionization-tandem MS/MS. With the selective MS/MS detection, ADA in chicken muscle can be detected at concentrations well below 1 µg/kg. Quantification of ADA in chicken muscle was accomplished by using matrix-matched calibration with memantine as an internal standard. The method was validated with ADA fortified chicken muscle at 1, 2, and 5 µg/kg. The recoveries ranged from 89 to 95%, and RSDs were ≤10% in all cases. The estimated LOD and LOQ in chicken muscle were 0.020 and 0.054 µg/kg, respectively. This method is rapid, robust, and suitable for routine monitoring of ADA residues in chicken muscle samples. [ABSTRACT FROM AUTHOR]

Objectives: This study reviews qualitative research into the sociocultural meanings and subjective experiences that midlife men in the United Kingdom (UK) associate with their drinking. In the UK, average weekly alcohol consumption is highest among midlife men, and they are disproportionately affected by alcohol harm. There is increasing recognition that public health messages to support behaviour change must be based on an in-depth understanding of drinking motivations and experiences. Study design and methods: Systematic literature review of studies exploring motivations for and experiences of drinking among UK men aged 45–60 using qualitative methodology. Medline, PsycINFO and the Social Science Citation Index were used, along with manual searches of key journals, Google searches and a call for evidence. The Critical Appraisal Skills Programme tool was used to quality-assess papers. Thematic synthesis was used to combine and analyse the data. Results: From 5172 titles and abstracts (1995–2018), 11 publications were included, representing 6 unique studies. Five themes were identified: ‘Drinking Motivations’; ‘Drinking Justifications’; ‘Drinking Strategies and Control’; ‘Social Norms and Identity’ and ‘Harm’. Motivations for drinking among midlife men were associated with relaxation, socialising and maintenance of male friendships. They justified drinking as a choice and emphasised their ability to meet responsibilities, which they contrasted with ‘problem drinkers’. Social norms governed drinking behaviours as an expression of masculinity. Conclusion: This review highlights the significance of the meanings and social importance of alcohol consumption among midlife men. Interventions using information and guidance should consider these when aiming to effectively influence the way this group drinks. Keywords: United Kingdom, Systematic review, Thematic synthesis, Alcohol, Midlife men, Experience, Sociocultural meaning

Background: Treatment related toxicity is common after chemotherapy and radiotherapy. Our group has developed and validated an electronic Patient Reported Outcome questionnaire (ePRO) to assess symptoms and toxicity in lung cancer patients receiving (chemo)radiotherapy treatment. We assessed the need for volunteer support in clinics to assist patients in completing ePROs. Methods: Lung Cancer patients attending outpatient or radiotherapy clinics at The Christie NHS Foundation Trust, Manchester were consented and asked to complete a Patient Reported Outcomes questionnaire using an electronic device (a touchscreen). Trained volunteers were available if patients required help such as verbal or physical assistance. The primary objective was to determine the need for volunteers to assist lung cancer patients in completing ePROs. Results: 27/86 (31.4%) of patients who consented to this study required assistance to complete the ePRO. After questioning, we found that only 7/86 (8.1%) would have relied on volunteers for assistance as the majority of patients had a companion that could have provided help. 81/86 (94.2%) of patients were satisfied with the use of a touchscreen tablet to complete the ePRO. Conclusion: Our results demonstrate that the introduction of ePROs in lung cancer outpatient clinics is feasible, even without the use of volunteers for the majority of patients. The implementation of ePROs would allow large volumes of high quality (chemo)radiotherapy toxicity data to be collected accurately and quickly. This is essential for the development of predictive models of outcome using population-based data, which could allow the personalisation of (chemo)radiotherapy treatment for lung cancer patients. Keywords: Chemotherapy, Radiotherapy, Toxicity, Patient reported outcomes

Breast cancer is one of the most prevalent causes of cancer mortality in women. In order to increase patient prognosis and survival rates, new technologies are urgently required to deliver therapeutics in a more effective and efficient manner. Niosome nanoparticles have been recently employed as therapeutic platforms capable of loading and carrying drugs within their core for both mono and combination therapy. Here, niosome-based nanoscale carriers were investigated as a targeted delivery system for breast cancer therapy. The platform developed consists of niosomes loaded with letrozole and cyclophosphamide (NLC) and surface-functionalized with a folic-acid-targeting moiety (NLCPFA). Drug release from the formulated particles exhibited pH-sensitive properties in which the niosome showed low and high release in physiological and cancerous conditions, respectively. The results revealed a synergic effect in cytotoxicity by co-loading letrozole and cyclophosphamide with an efficacy increment in NLCPFA use in comparison with NLC. The NLCPFA resulted in the greatest drug internalization compared to the non-targeted formulation and the free drug. Additionally, downregulation of cyclin-D, cyclin-E, MMP-2, and MMP-9 and upregulating the expression of caspase-3 and caspase-9 genes were observed more prominently in the nanoformulation (particularly for NLCPFA) compared to the free drug. This exciting data indicated that niosome-based nanocarriers containing letrozole and cyclophosphamide with controlled release could be a promising platform for drug delivery with potential in breast cancer therapy.

Hybrid iron oxide-gold nanoparticles are of increasing interest for applications in nanomedicine, photonics, energy storage, etc. However, they are often difficult to synthesise without experience or ‘know-how’. Additionally, standard protocols do not allow for scale up, and this is significantly hindering their future potential. In this study, we seek to determine whether microfluidics could be used as a new manufacturing process to reliably produce hybrid nanoparticles with the line of sight to their continuous manufacture and scaleup. Using a Precision Nano NanoAssemblr Benchtop® system, we were able to perform the intermediate coating steps required in order to construct hybrid nanoparticles around 60 nm in size with similar chemical and physical properties to those synthesised in the laboratory using standard processes, with Fe/Au ratios of 1:0.6 (standard) and 1:0.7 (microfluidics), indicating that the process was suitable for their manufacture with optimisation required in order to configure a continuous manufacturing plant.

Liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) was applied to the determination of residual bacitracin A, colistin A, and colistin B in milk and animal tissue samples. Prior to instrumental analysis, samples were subjected to acid extraction followed by solid-phase cleanup using Strata-X cartridges. Mass spectral acquisitions were performed under selective multiple reaction monitoring (MRM) mode at m/ z 199 and 670 from triply charged precursors of bacitracin A ( m/ z 475); m/ z 385 and 379 from triply charged precursors of colistin A ( m/ z 391); and m/ z 380 and 374 from triply charged precursors of colistin B ( m/ z 386). Method precision was evaluated from spike recovery of samples fortified at concentrations corresponding to 2/5 of the maximum residue limits (MRLs) for each of the analytes under study. Intra-day and inter-day variations were found to range from 90.9 to 104% with relative standard deviation (RSD) <6.5%, and from 90.1 to 106% with RSD <9.1%, respectively. Limits of quantification (LOQs) were defined as the spiking concentrations at 2/5 MRL, and limits of detection (LODs) were 10–47 μg kg−1 for bacitracin A, 1–16 μg kg−1 for colistin A, and 6–14 μg kg−1 for colistin B in milk and animal tissues. The presented method has good precision and high sensitivity and was applied as a fast screening protocol and a quantitative tool for monitoring of the concerned polypeptides in foods as part of a surveillance program. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract Pre-clinical and retrospective studies of patients using statins to reduce plasma cholesterol have suggested that statins may be useful to treat cancer. However, prospective clinical trials have yet to demonstrate significant efficacy. We have previously shown that this is in part because a hydrophobic statin with a long half-life is necessary. Pitavastatin, the only statin with this profile, has not undergone clinical evaluation in oncology. The target of pitavastatin, hydroxymethylglutarate coenzyme-A reductase (HMGCR), was found to be over-expressed in all ovarian cancer cell lines examined and upregulated by mutated TP53, a gene commonly altered in ovarian cancer. Pitavastatin-induced apoptosis was blocked by geranylgeraniol and mevalonate, products of the HMGCR pathway, confirming that pitavastatin causes cell death through inhibition of HMGCR. Solvent extracts of human and mouse food were also able to block pitavastatin-induced apoptosis, suggesting diet might influence the outcome of clinical trials. When nude mice were maintained on a diet lacking geranylgeraniol, oral pitavastatin caused regression of Ovcar-4 tumour xenografts. However, when the animal diet was supplemented with geranylgeraniol, pitavastatin failed to prevent tumour growth. This suggests that a diet containing geranylgeraniol can limit the anti-tumour activity of pitavastatin and diet should be controlled in clinical trials of statins.

Diabetes is associated with dysfunction of the neurovascular unit, although the mechanisms of this are incompletely understood and currently no treatment exists to prevent these negative effects. We previously found that the nitric oxide (NO) donor sodium nitroprusside (SNP) prevents the detrimental effect of glucose on neurovascular coupling in zebrafish. We therefore sought to establish the wider effects of glucose exposure on both the neurovascular unit and on behaviour in zebrafish, and the ability of SNP to prevent these. We incubated 4-days post-fertilisation (dpf) zebrafish embryos in 20 mM glucose or mannitol for 5 days until 9 dpf, with or without 0.1 mM SNP co-treatment for 24 h (8-9 dpf), and quantified vascular NO reactivity, vascular mural cell number, expression of a klf2a reporter, glial fibrillary acidic protein (GFAP) and transient receptor potential cation channel subfamily V member 4 (TRPV4), as well as spontaneous neuronal activation at 9 dpf, all in the optic tectum. We also assessed the effect on light/dark preference and locomotory characteristics during free-swimming studies. We find that glucose exposure significantly reduced NO reactivity, klf2a reporter expression, vascular mural cell number and TRPV4 expression, while significantly increasing spontaneous neuronal activation and GFAP expression (all in the optic tectum). Furthermore, when we examined larval behaviour, we found that glucose exposure significantly altered light/dark preference and high and low speed locomotion while in light. Co-treatment with SNP reversed all these molecular and behavioural effects of glucose exposure. Our findings comprehensively describe the negative effects of glucose exposure on the vascular anatomy, molecular phenotype and function of the optic tectum, and on whole-organism behaviour. We also show that SNP or other NO donors may represent a therapeutic strategy to ameliorate the complications of diabetes on the neurovascular unit. This article has an associated First Person interview with the first author of the paper.

Background: Changes in prostate cancer apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) provide a noninvasive method for assessing radiotherapy response. This may be attenuated by neoadjuvant hormone therapy (NA-HT). We investigate ADC values measured before, during and after external beam radiotherapy (EBRT) following NA-HT. Methods: Patients with ⩾T2c biopsy-proven prostate cancer receiving 3 months of NA-HT plus definitive radiotherapy were prospectively identified. All underwent ADC-MRI scans in the week before EBRT, in the third week of EBRT and 8 weeks after its completion. Imaging was performed at 1.5 T. The tumour, peripheral zone (PZ) and central zone (CZ) of the prostate gland were identified and median ADC calculated for each region and time point. Results: Between September and December 2014, 15 patients were enrolled (median age 68.3, range 57–78) with a median Gleason score of 7 (6–9) and prostate-specific antigen (PSA) at diagnosis 14 (3–197) ng/ml. Median period of NA-HT prior to first imaging was 96 days (69–115). All patients completed treatment. Median follow up was 25 months (7–34), with one patient relapsing in this time. Thirteen patients completed all imaging as intended, one withdrew after one scan and another missed the final imaging. PZ and CZ could not be identified in one patient. Median tumour ADC before, during and post radiotherapy was 1.24 × 10 −3 mm 2 /s (interquartile range 0.16 × 10 −3 mm 2 /s), 1.31 × 10 −3 mm 2 /s (0.22 × 10 −3 mm 2 /s), then 1.32 × 10 −3 mm 2 /s (0.13 × 10 −3 mm 2 /s) respectively ( p > 0.05). There was no significant difference between median tumour and PZ or CZ ADC at any point. Gleason score did not correlate with ADC values. Conclusions: Differences in ADC parameters of normal and malignant tissue during EBRT appear attenuated by prior NA-HT. The use of changes in ADC as a predictive tool in this group may have limited utility.

Cases of vomiting and diarrhoea were reported in racing pigeons in Western Australia in May, 2016. Morbidity and mortality rates were high. Similar clinical disease was seen in Victoria in December and by early 2017 had been reported in all states except the Northern Territory, in different classes of domestic pigeon-racing, fancy and meat bird-and in a flock of feral pigeons. Autopsy findings were frequently unremarkable; histological examination demonstrated significant hepatic necrosis as the major and consistent lesion, often with minimal inflammatory infiltration. Negative contrast tissue suspension and thin section transmission electron microscopy of liver demonstrated virus particles consistent with a member of the Reoviridae. Inoculation of trypsin-treated Vero, MDBK and MA-104 cell lines resulted in cytopathic changes at two days after infection. Next generation sequencing was undertaken using fresh liver samples and a previously undescribed group A rotavirus (genotype G18P[17]) of avian origin was identified and the virus was isolated in several cell lines. A q-RT-PCR assay was developed and used to screen a wider range of samples, including recovered birds. Episodes of disease have continued to occur and to reoccur in previously recovered lofts, with variable virulence reported. This is the first report of a rotavirus associated with hepatic necrosis in any avian species.