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Abstract Background Following government calls for General Practices in England to work at scale, some practices have grown in size from traditionally small, General Practitioner (GP)-led organisations to large multidisciplinary enterprises. We assessed the effect of practice list size and workforce composition on practice performance in clinical outcomes and patient experience. Methods We linked five practice-level datasets in England to obtain a single dataset of practice workforce, list size, proportion of registered patients ≥ 65 years of age, female-male sex ratio, deprivation, rurality, GP contract type, patient experience of care, and Quality and Outcomes Framework (QOF) and non-QOF clinical processes and outcomes. Latent Profile Analysis (LPA) was used to cluster general practices into groups based on practice list size and workforce composition. Bayesian Information Criterion, Akaike Information Criterion and deliberation within the research team were used to determine the most informative number of groups. One-way ANOVA was used to assess how groups differed on indicator variables and other variables of interest. Linear regression was used to assess the association between practice group and practice performance. Results A total of 6024 practices were available for class assignment. We determined that a 3-class grouping provided the most meaningful interpretation; 4494 (74.6%) were classified as ‘Small GP-reliant practices’, 1400 (23.2%) were labelled ‘Medium-size GP-led practices with a multidisciplinary team (MDT) input’ and 131 (2.2%) practices were named ‘Large multidisciplinary practices’. Small GP-reliant practices outperformed larger multidisciplinary practices on all patient-reported indicators except on confidence and trust where medium-size GP-led practices with MDT input appeared to do better. There was no difference in performance between small GP-reliant practices and larger multidisciplinary practices on QOF incentivised indicators except on asthma reviews where medium-size GP-led practices with MDT input performed worse than smaller GP-reliant practices and immunisation coverage where the same group performed better than smaller GP-reliant practices. For non-incentivised indicators, larger multidisciplinary practices had higher cancer detection rates than small GP-reliant practices. Conclusion Small GP-reliant practices were found to provide better patient reported access, continuity of care, experience and satisfaction with care. Larger multidisciplinary practices appeared to have better cancer detection rates but had no effect on other clinical processes and outcomes. As England moves towards larger multidisciplinary practices efforts should be made to preserve good patient experience.

Objectives Increasingly, healthcare and public health strategists invite us to look at healthcare organisations as not just care providers but as anchor institutions (ie, large community-rooted organisations with significant impact in the local economy, social fabric and overall community well-being). In response, this study explores the mechanisms through which healthcare organisations can impact social determinants of health and communities in their local areas.Design We conducted case studies with interviews and synthesised the findings using a realist approach to produce a set of explanations (programme theory) of how healthcare organisations can have a positive impact on the overall well-being of local communities by operating as anchor institutions.Setting Secondary healthcare organisations in England, including mental health and community services.Participants Staff from case study sites which were directly employed or actively engaged in the organisation’s anchor institution strategy. Data collection took place from early June to the end of August 2023.Results We found four building blocks for effective anchor activity including employment, spending, estates and sustainability. Healthcare organisations—as anchor institutions—can improve the social determinants of health for their local communities through enabling accessible paths for local community recruitment and career progression; empowering local businesses to join supply chains boosting income and wealth; transforming organisational spaces into community assets; and supporting local innovation and technology to achieve their sustainability goals. These blocks need to be integrated across organisations on the basis of a population health approach promoted by supportive leadership, and in collaboration with a diverse range of local partners.Conclusions Healthcare organisations have the potential for a positive impact on the overall well-being of local communities. Policymakers should support healthcare organisations to leverage employment, spending, estates and sustainability to help address the unequal distribution of the social determinants of health.

Background: An unequal distribution of the social determinants of health drives health inequalities. Existing training fails to communicate the impossible circumstances that disadvantaged groups face. Game-based learning is increasingly used as an innovative method with the potential to enhance health staff's ability to address health inequalities, but its effectiveness is unknown. Therefore, the aim of this systematic review was to evaluate the effectiveness of ‘equity-focused’ game-based learning in training health staff. Study design: Systematic Review. Methods: Three databases (Ovid Medline, Embase, Web of Science) and a citation search were systematically searched for articles from January 2010 to July 2023, reporting on effectiveness of ‘equity-focused’ game-based learning. Titles and abstracts were screened using eligibility criteria to identify relevant studies. Data was extracted and the ROBINS-I tool was used to assess quality. Results: The search identified 7615 articles, of which thirteen were included involving 2412 healthcare workers. A variety of game-based learning tools were found to have an overall positive effect on motivation, knowledge, attitudes, and engagement of health staff. However, the significance of the results varied depending on specific game context. All included studies were judged to have serious to critical risk of bias. Conclusions: Game-based learning has the potential to improve the effectiveness of ‘equity-focused’ training for health staff. Educators and researchers should further collaborate to expand the tools available and evaluate their effectiveness on long-term clinical practice.

Abstract Background Tobacco smoking remains a key cause of preventable illness and death globally. In response, many countries provide extensive services to help people to stop smoking by offering a variety of effective behavioural and pharmacological therapies. However, many people who wish to stop smoking do not have access to or use stop smoking supports, and new modes of support, including the use of financial incentives, are needed to address this issue. A realist review of published international literature was undertaken to understand how, why, for whom, and in which circumstances financial incentives contribute to success in stopping smoking for general population groups and among pregnant women. Methods Systematic searches were undertaken from inception to February 2022 of five academic databases: MEDLINE (ovid), Embase.com, CIHAHL, Scopus and PsycINFO. Study selection was inclusive of all study designs. Twenty-two studies were included. Using Pawson and Tilley’s iterative realist review approach, data collected were screened, selected, coded, analysed, and synthesised into a set of explanatory theoretical findings. Results Data were synthesised into six Context-Mechanism-Outcome Configurations and one overarching programme theory after iterative rounds of analysis, team discussion, and expert panel feedback. Our programme theory shows that financial incentives are particularly useful to help people stop smoking if they have a financial need, are pregnant or recently post-partum, have a high threshold for behaviour change, and/or respond well to external rewards. The incentives work through a number of mechanisms including the role their direct monetary value can play in a person’s life and through a process of reinforcement where they can help build confidence and self-esteem. Conclusion This is the first realist review to synthesise how, why, and for whom financial incentives work among those attempting to stop smoking, adding to the existing evidence demonstrating their efficacy. The findings will support the implementation of current knowledge into effective programmes which can enhance the impact of stop smoking care. PROSPERO registration number CRD42022298941.

Abstract Background People experiencing long-term homelessness face significant difficulties accessing appropriate healthcare at the right time and place. This study explores how and why healthcare performance management and funding arrangements contribute to healthcare accessibility or the lack thereof using long-term homeless adults as an example of a population experiencing social exclusion. Methods A realist evaluation was undertaken. Thirteen realist interviews were conducted after which data were transcribed, coded, and analysed. Results Fourteen CMOCs were created based on analysis of the data collected. These were then consolidated into four higher-level CMOCs. They show that health systems characterised by fragmentation are designed to meet their own needs above the needs of patients, and they rely on practitioners with a special interest and specialised services to fill the gaps in the system. Key contexts identified in the study include: health system fragmentation; health service fragmentation; bio-medical, one problem at a time model; responsive specialised services; unresponsive mainstream services; national strategy; short health system funding cycles; and short-term goals. Conclusion When health services are fragmented and complex, the needs of socially excluded populations such as those experiencing homelessness are not met. Health systems focus on their own metrics and rely on separate actors such as independent NGOs to fill gaps when certain people are not accommodated in the mainstream health system. As a result, health systems lack a comprehensive understanding of the needs of all population groups and fail to plan adequately, which maintains fragmentation. Policy makers must set policy and plan health services based on a full understanding of needs of all population groups.

For the 40 years after the end of commercial whaling in 1976, humpback whale populations in the North Pacific Ocean exhibited a prolonged period of recovery. Using mark–recapture methods on the largest individual photo-identification dataset ever assembled for a cetacean, we estimated annual ocean-basin-wide abundance for the species from 2002 through 2021. Trends in annual estimates describe strong post-whaling era population recovery from 16 875 (± 5955) in 2002 to a peak abundance estimate of 33 488 (± 4455) in 2012. An apparent 20% decline from 2012 to 2021, 33 488 (± 4455) to 26 662 (± 4192), suggests the population abruptly reached carrying capacity due to loss of prey resources. This was particularly evident for humpback whales wintering in Hawai‘i, where, by 2021, estimated abundance had declined by 34% from a peak in 2013, down to abundance levels previously seen in 2006, and contrasted to an absence of decline in Mainland Mexico breeding humpbacks. The strongest marine heatwave recorded globally to date during the 2014–2016 period appeared to have altered the course of species recovery, with enduring effects. Extending this time series will allow humpback whales to serve as an indicator species for the ecosystem in the face of a changing climate.

Background Social exclusion is a process whereby certain individuals are born into or pushed to the margins of society and prevented from participating in social, cultural, economic, and political life. People who experience social exclusion are not afforded the same rights and privileges as other population groups. Socially excluded people often experience poorer outcomes in a variety of domains including health, education, employment, and housing than people with socio-economic privilege. People experiencing social exclusion frequently have higher and more complex health needs and poorer access to healthcare than the general population. The aim of this study is to better understand and explain how social exclusion occurs and how it impacts health over the life course. Methods A realist review will be undertaken. Data will be collected via a systematic search of databases of peer-reviewed literature and further iterative searches of peer-reviewed and other literatures as needed. The following data bases will be searched: MEDLINE, Embase, CINAHL, and ASSIA, using both indexed subject headings in each database and relevant key words. Grey literature will be searched via Google Scholar and relevant websites of organisations that work with populations affected by social exclusion. Conclusion A realist review will be conducted to explain the underlying societal mechanisms which produce social exclusion and related health outcomes in particular contexts affecting excluded population groups across the life course. The study has the potential to inform policy makers and service managers of how and why social exclusion occurs and potential key intervention points to prevent exclusion from happening.

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Objectives: The COVID-19 pandemic rapidly exacerbated health inequalities in England. Policy makers sought to ameliorate its impact. This paper aims to identify how health inequalities were framed in national policy documents published in England during the pandemic and how this impacts the framing of policy solutions. Study design: Discourse analysis of selected national policy documents. Methods: First, we identified relevant national policy documents through a broad search and eligibility criteria to identify illustrative policy documents. Second, we undertook a discourse analysis to understand the framing and constitution of health inequalities and consequent solutions within them. Third, we used existing health inequalities literature to critique the findings. Results: Based on analysis of six documents, we found evidence of the idea of lifestyle drift with a marked disjunction between the acknowledgement of the wider determinants of heath and the policy solutions advocated. The target population for interventions is predominantly the worst off, rather than the whole social gradient. Repeated appeals to behaviour change indicate an inherent individualist epistemology. Responsibility and accountability for health inequalities appears delegated locally without the power and resource required to deliver. Conclusion: Policy solutions are unlikely to address health inequalities. This could be done though through (i) shifting interventions towards structural factors and wider determinants of health, (ii) a positive vision of a health equitable society, (iii) a proportional universalism in approach and (iv) a delegation of power and resource alongside responsibility for delivering on health inequalities. These possibilities currently remain outside of the policy language of health inequalities.

There are substantial inequalities in health across society which have been exacerbated by the COVID-19 pandemic. The UK government have committed to a programme of levelling-up to address geographical inequalities. Here we undertake rapid review of the evidence base on interventions to reduce such health inequalities and developed a practical, evidence-based framework to ‘level up’ health across the country.This paper overviews a rapid review undertaken to develop a framework of guiding principles to guide policy. To that end and based on an initial theory, we searched one electrotonic database (MEDLINE) from 2007 to July 2021 to identify published umbrella reviews and undertook an internet search to identify relevant systematic reviews, primary studies, and grey literature. Titles and abstracts were screened according to the eligibility criteria. Key themes were extracted from the included studies and synthesised into an overarching framework of guiding principles in consultation with an expert panel. Included studies were cross checked with the initial theoretical domains and further searching undertaken to fill any gaps.We identified 16 published umbrella reviews (covering 667 individual studies), 19 grey literature publications, and 15 key systematic reviews or primary studies. Based on these studies, we develop a framework applicable at national, regional and local level which consisted of five principles - 1) healthy-by-default and easy to use initiatives; 2) long-term, multi-sector action; 3) locally designed focus; 4) targeting disadvantaged communities; and 5) matching of resources to need.Decision-makers working on policies to level up health should be guided by these five principles.

Here we study how the structure and growth of a cellular population vary with the distribution of maturation times from each stage. We consider two cell cycle stages. The first represents early G1. The second includes late G1, S, G2, and mitosis. Passage between the two reflects passage of an important cell cycle checkpoint known as the restriction point. We model the population as a system of partial differential equations. After establishing the existence of solutions, we characterize the maturation rates and derive the steady-state age and stage distributions as well as the asymptotic growth rates for models with exponential and inverse Gaussian maturation time distributions. We find that the stable age and stage distributions, transient dynamics, and asymptotic growth rates are substantially different for these two maturation models. We conclude that researchers modeling cellular populations should take care when choosing a maturation time distribution, as the population growth rate and stage structure can be heavily impacted by this choice. Furthermore, differences in the models' transient dynamics constitute testable predictions that can help further our understanding of the fundamental process of cellular proliferation. We hope that our numerical methods and programs will provide a scaffold for future research on cellular proliferation.

Background: In England, demand for primary care services is increasing and GP shortages are widespread. Recently introduced primary care networks (PCNs) aim to expand the use of additional practice-based roles such as physician associates (PAs), pharmacists, paramedics, and others through financial incentives for recruitment of these roles. Inequalities in general practice, including additional roles, have not been examined in recent years, which is a meaningful gap in the literature. Previous research has found that workforce inequalities are associated with health outcome inequalities. Aim: To examine recent trends in general practice workforce inequalities. Design & setting: A longitudinal study using quarterly General Practice Workforce datasets from 2015–2020 in England. Method: The slope indices of inequality (SIIs) for GPs, nurses, total direct patient care (DPC) staff, PAs, pharmacists, and paramedics per 10 000 patients were calculated quarterly, and plotted over time, with and without adjustment for patient need. Results: Fewer GPs, total DPC staff, and paramedics per 10 000 patients were employed in more deprived areas. Conversely, more PAs and pharmacists per 10 000 patients were employed in more deprived areas. With the exception of total DPC staff, these observed inequalities widened over time. The unadjusted analysis showed more nurses per 10 000 patients employed in more deprived areas. These values were not significant after adjustment but approached a more equal or pro-poor distribution over time. Conclusion: Significant workforce inequalities exist and are even increasing for several key general practice roles, with workforce shortages disproportionately affecting more deprived areas. Policy solutions are urgently needed to ensure an equitably distributed workforce and reduce health inequities.

Regenerative medicine requires better pre-clinical tools in order to increase the efficiency of novel therapies transitioning to the clinic. Current monolayer cell culture methods are suboptimal for effectively testing new therapies and live mouse models are expensive, time consuming and require invasive procedures. Fetal organ culture, organoids, microfluidics and culture of thick sections of adult organs all aim to fill the knowledge gap between monolayer culture and live mouse studies. Here we report on an ex vivo organ perfusion system that can support whole adult mouse organs. Ex vivo perfusion of healthy and diseased mouse organs allows for real-time analysis that provides immediate feedback and accurate data collection throughout the experiment. Having a suitable normothermic ex vivo perfusion system for mouse organs provides a tool that will help contribute to our understanding of kidney physiology and disease and can take advantage of the many mouse models of human disease that already exist. Furthermore, an ex vivo kidney perfusion system can be used for testing novel cell therapies, drug screening, drug validation and for the detection of nephrotoxic substances. Critical to the success of mouse ex vivo organ perfusion is having a suitable bioreactor to maintain the organ. Here we have focused on the mouse kidney and mathematically modeled, built and validated a bioreactor that can maintain a kidney for 7 days. The long duration of the ex vivo perfusion will help to advance studies on kidney disease and can rapidly test for new regenerative medicine therapies compared to whole animal studies.

Background: Over the last several years, homelessness has increased in Ireland and across Europe. Rates have recently declined since the coronavirus disease 2019 (COVID-19) pandemic, but it is unclear whether emergency housing measures will remain in place permanently. Populations experiencing long-term homelessness face a higher burden of multi-morbidity at an earlier age than housed populations and have poorer health outcomes. However, this population also has more difficulty accessing appropriate health services. A realist review by the authors found that important health system contexts which impact access are resourcing, training, funding cycles, health system fragmentation, health system goals, how care is organised, culture, leadership and flexibility of care delivery. Using a realist evaluation approach, this research will explore and refine key system-level factors, highlighted in our realist review, in a local health care system. Aim: The aim of this study is to understand how funding procedures and health system performance management impact service settings, staff, providers and their ability to make services accessible to populations experiencing homelessness. Methods: A realist evaluation will be undertaken to explain how funding and health system performance management impact healthcare accessibility for populations experiencing homelessness. Data will be collected using qualitative and realist interview techniques and focus group methodology. Secondary data such as policy documents and budgets will utilised. The analysis will follow Pawson and Tilley’s iterative phases starting with building an Initial programme theory, then data collection, data analysis, synthesis and finally building a refined programme theory. Conclusion: Building on a realist review conducted by the same research team, this study will further test and refine findings that explain how health system factors impact healthcare accessibility for populations experiencing homelessness. The study has the potential to inform policy makers, health planners and managers of contextual factors that can be modified to increase healthcare accessibility.

ABSTRACT Following inhalation, Yersinia pestis rapidly colonizes the lung to establish infection during primary pneumonic plague. Although several adhesins have been identified in Yersinia spp., the factors mediating early Y. pestis adherence in the lung remain unknown. To identify genes important for Y. pestis adherence during primary pneumonic plague, we used transposon insertion sequencing (Tn-seq). Wild-type and capsule mutant (Δcaf1) Y. pestis transposon mutant libraries were serially passaged in vivo to enrich for nonadherent mutants in the lung using a mouse model of primary pneumonic plague. Sequencing of the passaged libraries revealed six mutants that were significantly enriched in both the wild-type and Δcaf1 Y. pestis backgrounds. The enriched mutants had insertions in genes that encode transcriptional regulators, chaperones, an endoribonuclease, and YPO3903, a hypothetical protein. Using single-strain infections and a transcriptional analysis, we identified a significant role for YPO3903 in Y. pestis adherence in the lung and showed that YPO3903 regulated transcript levels of psaA, which encodes a fimbria previously implicated in Y. pestis adherence in vitro. Deletion of psaA had a minor effect on Y. pestis adherence in the lung, suggesting that YPO3903 regulates other adhesins in addition to psaA. By enriching for mutations in genes that regulate the expression or assembly of multiple genes or proteins, we obtained screen results indicating that there may be not just one dominant adhesin but rather several factors that contribute to early Y. pestis adherence during primary pneumonic plague. IMPORTANCE Colonization of the lung by Yersinia pestis is a critical first step in establishing infection during primary pneumonic plague, a disease characterized by high lethality. However, the mechanisms by which Y. pestis adheres in the lung after inhalation remain elusive. Here, we used Tn-seq to identify Y. pestis genes important for adherence early during primary pneumonic plague. Our mutant enrichment strategy resulted in the identification of genes important for regulation and assembly of genes and proteins rather than adhesin genes themselves. These results reveal that there may be multiple Y. pestis adhesins or redundancy among adhesins. Identifying the adhesins regulated by the genes identified in our enrichment screen may reveal novel therapeutic targets for preventing Y. pestis adherence and the subsequent development of pneumonic plague.

Background: Guidelines recommend drug treatment for patients with heart failure with a reduced ejection fraction (HFrEF), however the evidence for benefit in patients with mild disease, such as most in primary care, is uncertain. Importantly, drugs commonly used in heart failure account for one in seven of emergency admissions for adverse drug reactions. Aim: To determine to what extent patients included in studies of heart failure treatment with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and aldosterone antagonists were representative of a typical primary care population with HFrEF in England. Design & setting: Systematic review of randomised controlled trials (RCTs) of drug treatment in patients with HFrEF. Method: MEDLINE, MEDLINE In-Process, EMBASE, and CENTRAL were searched from inception to March 2015. The characteristics of the patient’s New York Heart Association (NYHA) classification were compared with a primary care reference population with HFrEF. Results: Of the 30 studies included, two had incomplete data. None had a close match (defined as ≤10% deviation from reference study) for NYHA class I disease; 5/28 were a close match for NYHA class II; 5/28 for NYHA class III; and 18/28 for NYHA class IV. In general, pre-existing cardiovascular conditions, risk factors, and comorbidities were representative of the reference population. Conclusion: Patients recruited to studies typically had more severe heart failure than the reference primary care population. When evidence from sicker patients is generalised to less sick people, there is increased uncertainty about benefit and also a risk of harm from overtreatment. More evidence is needed on the effectiveness of treatment of heart failure in asymptomatic patients with NYHA class I.

We review the status of marine shellfish ecosystems formed primarily by bivalves in Australia, including: identifying ecosystem-forming species, assessing their historical and current extent, causes for decline and past and present management. Fourteen species of bivalves were identified as developing complex, three-dimensional reef or bed ecosystems in intertidal and subtidal areas across tropical, subtropical and temperate Australia. A dramatic decline in the extent and condition of Australia's two most common shellfish ecosystems, developed by Saccostrea glomerata and Ostrea angasi oysters, occurred during the mid-1800s to early 1900s in concurrence with extensive harvesting for food and lime production, ecosystem modification, disease outbreaks and a decline in water quality. Out of 118 historical locations containing O. angasi-developed ecosystems, only one location still contains the ecosystem whilst only six locations are known to still contain S. glomerata-developed ecosystems out of 60 historical locations. Ecosystems developed by the introduced oyster Crasostrea gigas are likely to be increasing in extent, whilst data on the remaining 11 ecosystem-forming species are limited, preventing a detailed assessment of their current ecosystem-forming status. Our analysis identifies that current knowledge on extent, physical characteristics, biodiversity and ecosystem services of Australian shellfish ecosystems is extremely limited. Despite the limited information on shellfish ecosystems, a number of restoration projects have recently been initiated across Australia and we propose a number of existing government policies and conservation mechanisms, if enacted, would readily serve to support the future conservation and recovery of Australia's shellfish ecosystems.

This article examines the somewhat perplexing pride that can be shown in the antebellum and Confederate history of the Old South on the one hand, and the celebration of African-American heritage and pride in an integrated New South on the other. It examines how each is celebrated in Atlanta, Georgia, focusing on the way in which the Old South was remembered from the end of the Civil War until the Civil Rights movement a century later – the «Old New South» – and how it has been re-remembered in the period since the Civil Rights movement – the «new New South». While today there is a vibrant pride in the city’s African-American culture, there also remains a healthy degree of pride in the Old South, and most of its adherents do not consider the two movements to be antagonistic. This paper seeks to examine how such a paradox could come about. It also posits reasons for the way in which Old South heritage was intentionally changed to make it acceptable when changing times made it questionable.