Reducing health inequalities through general practice: a realist review and action framework.

Background: Socio-economic inequalities in health have been in the public agenda for decades. General practice has an influential role to play in mitigating the impact of inequalities especially regarding chronic conditions. At the moment, general practice is dealing with serious challenges in relation to workforce shortages, increasing workload and the impact of the COVID-19 pandemic. It is important to identify effective ways so that general practice can play its role in reducing health inequalities. Objectives: We explored what types of interventions and aspects of routine care in general practice decrease or increase inequalities in health and care-related outcomes. We focused on cardiovascular disease, cancer, diabetes and/or chronic obstructive pulmonary disease. We explored for whom these interventions and aspects of care work best, why, and in what circumstances. Our main objective was to synthesise this evidence into specific guidance for healthcare professionals and decision-makers about how best to achieve equitable general practice. Design: Realist review. Main outcome measures: Clinical or care-related outcomes by socio-economic group, or other PROGRESS-Plus criteria. Review methods: Realist review based on Pawson's five steps: (1) locating existing theories, (2) searching for evidence, (3) selecting articles, (4) extracting and organising data and (5) synthesising the evidence. Results: Three hundred and twenty-five studies met the inclusion criteria and 159 of them were selected for the evidence synthesis. Evidence about the impact of general practice interventions on health inequalities is limited. To reduce health inequalities, general practice needs to be: • connected so that interventions are linked and coordinated across the sector; • intersectional to account for the fact that people's experience is affected by many of their characteristics; • flexible to meet patients' different needs and preferences; • inclusive so that it does not exclude people because of who they are; • community-centred so that people who receive care engage with its design and delivery. These qualities should inform action across four domains: structures like funding and workforce distribution, organisational culture, everyday regulated procedures involved in care delivery, interpersonal and community relationships. Limitations: The reviewed evidence offers limited detail about the ways and the extent to which specific interventions increase or decrease inequalities in general practice. Therefore, we focused on the underpinning principles that were common across interventions to produce higher-level, transferrable conclusions about ways to achieve equitable care. Conclusions: Inequalities in general practice result from complex processes across four different domains that include structures, ideas, regulated everyday procedures, and relationships among individuals and communities. To achieve equity, general practice needs to be connected, intersectional, flexible, inclusive and community-centred. Future work: Future work should focus on how these five essential qualities can be better used to shape the organisational development of future general practice. Study registration: This trial is registered as PROSPERO CRD42020217871. 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: NIHR130694) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information.

Health inequalities are unfair differences in health across different groups of the population. In the United Kingdom, the health inequality gap in life expectancy between the richest and poorest is increasing and is caused mostly by differences in long-term conditions like cancer and cardiovascular disease and respiratory conditions, such as chronic obstructive pulmonary disease. Partly National Health Service inequalities arise in delays in seeing a doctor and care provided through doctors' surgery, such as delays in getting tests. This study explored how general practice services can increase or decrease inequalities in cancer, cardiovascular disease, diabetes and chronic obstructive pulmonary disease, under what circumstances and for whom. It also produced guidance for general practice, both local general practices and the wider general practice system, to reduce inequalities. We reviewed existing studies using a realist methodology. This methodology helps us understand the different contexts in which interventions work or not. We found that inequalities in general practice result from complex processes across different areas. These include funding and workforce, perceptions about health and disease among patients and healthcare staff, everyday procedures involved in care delivery, and relationships among individuals and communities. To reduce inequalities in general practice, action should be taken in all these areas and services need to be connected (i.e. linked and coordinated across the sector), intersectional (i.e. accounting for the fact that people's experience is affected by many of their characteristics like their gender and socio-economic position), flexible (i.e. meeting patients' different needs and preferences), inclusive (i.e. not excluding people because of who they are) and community-centred (i.e. working with the people who will receive care when designing and providing it). There is no one single intervention that will make general practice more equitable, rather it requires long-term organisational change based on these principles.

Reducing health inequalities through general practice.

Although general practice can contribute to reducing health inequalities, existing evidence provides little guidance on how this reduction can be achieved. We reviewed interventions influencing health and care inequalities in general practice and developed an action framework for health professionals and decision makers. We conducted a realist review by searching MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and Cochrane Library for systematic reviews of interventions into health inequality in general practice. We then screened the studies in the included systematic reviews for those that reported their outcomes by socioeconomic status or other PROGRESS-Plus (Cochrane Equity Methods Group) categories. 159 studies were included in the evidence synthesis. Robust evidence on the effect of general practice on health inequalities is scarce. Focusing on common qualities of interventions, we found that to reduce health inequalities, general practice needs to be informed by five key principles: involving coordinated services across the system (ie, connected), accounting for differences within patient groups (ie, intersectional), making allowances for different patient needs and preferences (ie, flexible), integrating patient worldviews and cultural references (ie, inclusive), and engaging communities with service design and delivery (ie, community-centred). Future work should explore how these principles can inform the organisational development of general practice.

Reducing health inequalities through general practice: protocol for a realist review (EQUALISE).

INTRODUCTION: Healthcare organisations recognise the moral imperative to address inequalities in health outcomes but often lack an understanding of which types of interventions are likely to reduce them. This realist review will examine the existing evidence on the types of interventions or aspects of routine care in general practice that are likely to decrease or increase health inequalities (ie, inequality-generating interventions) across cardiovascular disease, cancer, diabetes and chronic obstructive pulmonary disease. METHODS AND ANALYSIS: Our realist review will follow Pawson's five iterative stages. We will start by developing an initial programme theory based on existing theories and discussions with stakeholders. To navigate the large volume of literature, we will access the primary studies through the identification of published systematic reviews of interventions delivered in general practice across the four key conditions. We will examine the primary studies included within each systematic review to identify those reporting on inequalities across PROGRESS-Plus categories. We will collect data on a range of clinical outcomes including prevention, diagnosis, follow-up and treatment. The data will be synthesised using a realist logic of analysis. The findings will be a description and explanation of the general practice interventions which are likely to increase or decrease inequalities across the major conditions. ETHICS AND DISSEMINATION: Ethics approval is not required because this study does not include any primary research. The findings will be integrated into a series of guiding principles and a toolkit for healthcare organisations to reduce health inequalities. Findings will be disseminated through peer-reviewed publications, conference presentations and user-friendly summaries. PROSPERO REGISTRATION NUMBER: CRD42020217871.

Perspectives on involvement in the peer-review process: surveys of patient and public reviewers at two journals.

OBJECTIVE: In 2014/2015, The BMJ and Research Involvement and Engagement (RIE) became the first journals to routinely include patients and the public in the peer review process of journal articles. This survey explores the perspectives and early experiences of these reviewers. DESIGN: A cross-sectional survey. SETTING AND PARTICIPANTS: Patient and public reviewers for The BMJ and RIE who have been invited to review. RESULTS: The response rate was 69% (157/227) for those who had previously reviewed and 31% (67/217) for those who had not yet reviewed. Reviewers described being motivated to review by the opportunity to include the patient voice in the research process, influence the quality of the biomedical literature and ensure it meets the needs of patients. Of the 157 who had reviewed, 127 (81%) would recommend being a reviewer to other patients and carers. 144 (92%) thought more journals should adopt patient and public review. Few reviewers (16/224, 7%) reported concerns about doing open review. Annual acknowledgement on the journals' websites was welcomed as was free access to journal information. Participants were keen to have access to more online resources and training to improve their reviewing skills. Suggestions on how to improve the reviewing experience included: allowing more time to review; better and more frequent communication; a more user-friendly process; improving guidance on how to review including videos; improving the matching of papers to reviewers' experience; providing more varied sample reviews and brief feedback on the usefulness of reviews; developing a sense of community among reviewers; and publicising of the contribution that patient and public review brings. CONCLUSIONS: Patient and public reviewers shared practical ideas to improve the reviewing experience and these will be reviewed to enhance the guidance and support given to them.

Longitudinal qualitative evaluation of pharmacist integration into the urgent care setting.

PURPOSE: To describe the most effective model for managing, educating, and training pharmacist advanced clinical practitioners (ACPs) in the urgent care center (UCC) setting, role evolution and how to measure their effectiveness. PARTICIPANTS AND METHODS: Ethical approval was obtained to perform a qualitative longitudinal cohort study in three sites, with three pharmacists in each trained as ACPs from 2016 to 2017. ACP role, location, management, mentorship, and supervision were locally determined. ACPs attended focus groups (FGs) at 1 and 3 months (sites 1-3), 6 and 12 months (site 1 only), and the UCC staff were interviewed once with a topic guide regarding training, integration, role, and impact. Verbatim transcriptions were analyzed thematically. RESULTS: Eight ACP FGs and 24 stakeholder interviews produced major themes of communication, management, education and training, role, and outcomes. Effective education, training, and integration required communication of role to address concerns regarding salary differentials, supportive management structure, and multi-professional learning. ACPs reported that the model of workplace training, experiential learning, and university-based education was appropriate. Training was better located in the minor injuries and general practitioner areas. Recommended measures of effectiveness included patient satisfaction and workload transfer. CONCLUSION: The education and training model was appropriate. Communication and management require careful consideration to ensure effective integration and role development. Pharmacists were better located initially in the minor illness rather than major trauma areas. Quality of patient experience resulting from the new role was important in addition to reassurance that the role represented a positive contribution to workload.

Frequency of reporting on patient and public involvement (PPI) in research studies published in a general medical journal: a descriptive study.

OBJECTIVES: While documented plans for patient and public involvement (PPI) in research are required in many grant applications, little is known about how frequently PPI occurs in practice. Low levels of reported PPI may mask actual activity due to limited PPI reporting requirements. This research analysed the frequency and types of reported PPI in the presence and absence of a journal requirement to include this information. DESIGN AND SETTING: A before and after comparison of PPI reported in research papers published in The BMJ before and 1 year after the introduction of a journal policy requiring authors to report if and how they involved patients and the public within their papers. RESULTS: Between 1 June 2013 and 31 May 2014, The BMJ published 189 research papers and 1 (0.5%) reported PPI activity. From 1 June 2015 to 31 May 2016, following the introduction of the policy, The BMJ published 152 research papers of which 16 (11%) reported PPI activity. Patients contributed to grant applications in addition to designing studies through to coauthorship and participation in study dissemination. Patient contributors were often not fully acknowledged; 6 of 17 (35%) papers acknowledged their contributions and 2 (12%) included them as coauthors. CONCLUSIONS: Infrequent reporting of PPI activity does not appear to be purely due to a failure of documentation. Reporting of PPI activity increased after the introduction of The BMJ's policy, but activity both before and after was low and reporting was inconsistent in quality. Journals, funders and research institutions should collaborate to move us from the current situation where PPI is an optional extra to one where PPI is fully embedded in practice throughout the research process.

Imaging sialylated tumor cell glycans in vivo.

Cell surface glycans are involved in numerous physiological processes that involve cell-cell interactions and migration, including lymphocyte trafficking and cancer metastasis. We have used a bioorthogonal metabolic labeling strategy to detect cell surface glycans and demonstrate, for the first time, fluorescence and radionuclide imaging of sialylated glycans in a murine tumor model in vivo. Peracetylated azido-labeled N-acetyl-mannosamine, injected intraperitoneally, was used as the metabolic precursor for the biosynthesis of 5-azidoneuraminic, or azidosialic acid. Azidosialic acid-labeled cell surface glycans were then reacted, by Staudinger ligation, with a biotinylated phosphine injected intraperitoneally, and the biotin was detected by subsequent intravenous injection of a fluorescent or radiolabeled avidin derivative. At 24 h after administration of NeutrAvidin, labeled with either a far-red fluorophore or (111)In, there was a significant azido-labeled N-acetyl-mannosamine-dependent increase in tumor-to-tissue contrast, which was detected using optical imaging or single-photon-emission computed tomography (SPECT), respectively. The technique has the potential to translate to the clinic, where, given the prognostic relevance of altered sialic acid expression in cancer, it could be used to monitor disease progression.

Evaluation of predicted network modules in yeast metabolism using NMR-based metabolite profiling.

Genome-scale metabolic models promise important insights into cell function. However, the definition of pathways and functional network modules within these models, and in the biochemical literature in general, is often based on intuitive reasoning. Although mathematical methods have been proposed to identify modules, which are defined as groups of reactions with correlated fluxes, there is a need for experimental verification. We show here that multivariate statistical analysis of the NMR-derived intra- and extracellular metabolite profiles of single-gene deletion mutants in specific metabolic pathways in the yeast Saccharomyces cerevisiae identified outliers whose profiles were markedly different from those of the other mutants in their respective pathways. Application of flux coupling analysis to a metabolic model of this yeast showed that the deleted gene in an outlying mutant encoded an enzyme that was not part of the same functional network module as the other enzymes in the pathway. We suggest that metabolomic methods such as this, which do not require any knowledge of how a gene deletion might perturb the metabolic network, provide an empirical method for validating and ultimately refining the predicted network structure.

A novel method for observing proteins in vivo using a small fluorescent label and multiphoton imaging.

A novel method for the fluorescence detection of proteins in cells is described in the present study. Proteins are labelled by the selective biosynthetic incorporation of 5-hydroxytryptophan and the label is detected via selective two-photon excitation of the hydroxyindole and detection of its fluorescence emission at 340 nm. The method is demonstrated in this paper with images of a labelled protein in yeast cells.

COI1 links jasmonate signalling and fertility to the SCF ubiquitin-ligase complex in Arabidopsis.

Jasmonates (JAs) regulate Arabidopsis thaliana wound and defence responses, pollen development, and stress-related growth inhibition. Significantly, each of these responses requires COI1, an F-box protein. Other F-box proteins interact with SKP1 and cullin proteins to form SCF complexes that selectively recruit regulatory proteins targeted for ubiquitination. To determine whether COI1 also functions in an SCF complex, we have characterized Arabidopsis proteins that bind to COI1. An Arabidopsis cDNA expression library was screened in yeast for clones that produce proteins which can bind to COI1. We recovered two SKP1 homologues and a histone deacetylase. The Arabidopsis F-box protein TIR1 interacted with SKP1 proteins, but not with the histone deacetylase. Mutant COI1 proteins revealed that the F-box is required for interaction with SKP1s, but that sequences in leucine-rich repeat domains are required for interaction with the histone deacetylase. Epitope-tagged COI1 was introduced into Arabidopsis plants and cell cultures. Co-immunoprecipitation experiments confirmed the interaction in planta of COI1 with SKP1-like proteins and histone deacetylase, and also indicated that COI1 interacted with cullin. These results suggest that COI1 forms an SCFCOI1 complex in vivo. COI1 is therefore expected to form a functional E3-type ubiquitin ligase in plants and to regulate expression of jasmonate responsive genes, possibly by targeted ubiquitination of a histone deacetylase.