Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.

Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.

Theorising Support for Interdisciplinary Early-Career Researchers Using Communicative Genre and 'Rules of the Game'.

Qualitative social scientists working in medical faculties have to meet multiple expectations. On the one hand, they are expected to comply with the philosophical and theoretical expectations of the social sciences. On the other hand, they may also be expected to produce publications which align with biomedical definitions and framings of quality. As interdisciplinary scholars, they must handle (at least) two sets of journal editors, peer reviewers, grant-awarding panels, and conference audiences. In this paper, we extend the current knowledge base on the 'dual expectations' challenge by drawing on Orlikowski and Yates' theoretical concept of communicative genres. A 'genre' in this context is a format of communication (e.g. letter, email, academic paper, and conference presentation) aimed at a particular audience, having a particular material form and socio-linguistic style, and governed by both formal requirements and unwritten social rules. Becoming a member of any community of practice involves becoming familiar with its accepted communicative genres and adept in using them. Academic writing, for example, is a craft that is learned through participation in the social process of communicating one's ideas to one's peers in journal articles and other formats. In this reflective paper, we show how the concept of a communicative genre can sensitise us to the conflicting and often dissonant expectations and rule systems governing different academic fields. We use this key concept to suggest ways in which the faculty can support early-career researchers to progress in careers which straddle qualitative social science and medical science.

Unravelling the potential of social prescribing in individual-level type 2 diabetes prevention: a mixed-methods realist evaluation.

BACKGROUND: Social prescribing (SP) usually involves linking patients in primary care with services provided by the voluntary and community sector. Preliminary evidence suggests that SP may offer a means of connecting patients with community-based health promotion activities, potentially contributing to the prevention of long-term conditions, such as type 2 diabetes (T2D). METHODS: Using mixed-methods realist evaluation, we explored the possible contribution of SP to individual-level prevention of T2D in a multi-ethnic, socio-economically deprived population in London, UK. We made comparisons with an existing prevention programme (NHS Diabetes Prevention Programme (NDPP)) where relevant and possible. Anonymised primary care electronic health record data of 447,360 people 18+ with an active GP registration between December 2016 and February 2022 were analysed using quantitative methods. Qualitative data (interviews with 11 primary care clinicians, 11 social prescribers, 13 community organisations and 8 SP users at high risk of T2D; 36 hours of ethnographic observations of SP and NDPP sessions; and relevant documents) were analysed thematically. Data were integrated using visual means and realist methods. RESULTS: People at high risk of T2D were four times more likely to be referred into SP than the eligible general population (RR 4.31 (95% CI 4.17-4.46)), with adjustment for socio-demographic variables resulting in attenuation (RR 1.33 (95% CI 1.27-1.39)). More people at risk of T2D were referred to SP than to NDPP, which could be explained by the broad referral criteria for SP and highly supportive (proactive, welcoming) environments. Holistic and sustained SP allowed acknowledgement of patients' wider socio-economic constraints and provision of long-term personalised care. The fact that SP was embedded within the local community and primary care infrastructure facilitated the timely exchange of information and cross-referrals across providers, resulting in enhanced service responsiveness. CONCLUSIONS: Our study suggests that SP may offer an opportunity for individual-level T2D prevention to shift away from standardised, targeted and short-term strategies to approaches that are increasingly personalised, inclusive and long-term. Primary care-based SP seems most ideally placed to deliver such approaches where practitioners, providers and commissioners work collectively to achieve holistic, accessible, sustained and integrated services.

Implementation and delivery of group consultations for young people with diabetes in socioeconomically deprived, ethnically diverse settings.

BACKGROUND: Young people with diabetes experience poor clinical and psychosocial outcomes, and consider the health service ill-equipped in meeting their needs. Improvements, including alternative consulting approaches, are required to improve care quality and patient engagement. We examined how group-based, outpatient diabetes consultations might be delivered to support young people (16-25 years old) in socio-economically deprived, ethnically diverse settings. METHODS: This multi-method, comparative study recruited a total of 135 young people with diabetes across two implementation and two comparison sites (2017-2019). Informed by a 'researcher-in-residence' approach and complexity theory, we used a combination of methods: (a) 31 qualitative interviews with young people and staff and ethnographic observation in group and individual clinics, (b) quantitative analysis of sociodemographic, clinical, service use, and patient enablement data, and (c) micro-costing analysis. RESULTS: Implementation sites delivered 29 group consultations in total. Overall mean attendance per session was low, but a core group of young people attended repeatedly. They reported feeling better understood and supported, gaining new learning from peers and clinicians, and being better prepared to normalise diabetes self-care. Yet, there were also instances where peer comparison proved difficult to manage. Group consultations challenged deeply embedded ways of thinking about care provision and required staff to work flexibly to achieve local tailoring, sustain continuity, and safely manage complex interdependencies with other care processes. Set-up and delivery were time-consuming and required in-depth clinical and relational knowledge of patients. Facilitation by an experienced youth worker was instrumental. There was indication that economic value could derive from preventing at least one unscheduled consultation annually. CONCLUSIONS: Group consulting can provide added value when tailored to meet local needs rather than following standardised approaches. This study illustrates the importance of adaptive capability and self-organisation when integrating new models of care, with young people as active partners in shaping service provision. TRIAL REGISTRATION: ISRCTN reference 27989430.

What were the historical reasons for the resistance to recognizing airborne transmission during the COVID-19 pandemic?

The question of whether SARS-CoV-2 is mainly transmitted by droplets or aerosols has been highly controversial. We sought to explain this controversy through a historical analysis of transmission research in other diseases. For most of human history, the dominant paradigm was that many diseases were carried by the air, often over long distances and in a phantasmagorical way. This miasmatic paradigm was challenged in the mid to late 19th century with the rise of germ theory, and as diseases such as cholera, puerperal fever, and malaria were found to actually transmit in other ways. Motivated by his views on the importance of contact/droplet infection, and the resistance he encountered from the remaining influence of miasma theory, prominent public health official Charles Chapin in 1910 helped initiate a successful paradigm shift, deeming airborne transmission most unlikely. This new paradigm became dominant. However, the lack of understanding of aerosols led to systematic errors in the interpretation of research evidence on transmission pathways. For the next five decades, airborne transmission was considered of negligible or minor importance for all major respiratory diseases, until a demonstration of airborne transmission of tuberculosis (which had been mistakenly thought to be transmitted by droplets) in 1962. The contact/droplet paradigm remained dominant, and only a few diseases were widely accepted as airborne before COVID-19: those that were clearly transmitted to people not in the same room. The acceleration of interdisciplinary research inspired by the COVID-19 pandemic has shown that airborne transmission is a major mode of transmission for this disease, and is likely to be significant for many respiratory infectious diseases.

What does the literature mean by social prescribing? A critical review using discourse analysis.

Social prescribing (SP) seeks to enhance the role of the voluntary and community sector in addressing patients' complex needs in primary care. Using discourse analysis, this review investigates how SP is framed in the scientific literature and explores its consequences for service delivery. Theory driven searches identified 89 academic articles and grey literature that included both qualitative and quantitative evidence. Across the literature three main discourses were identified. The first one emphasised increasing social inequalities behind escalating health problems and presented SP as a response to the social determinants of health. The second one problematised people's increasing use of health services and depicted SP as a means of enhancing self-care. The third one stressed the dearth of human and relational dimensions in general practice and claimed that SP could restore personalised care. Discourses circulated unevenly in the scientific literature, conditioned by a wider political rationality which emphasised individual responsibility and framed SP as 'solution' to complex and contentious problems. Critically, this contributed to an oversimplification of the realities of the problems being addressed and the delivery of SP. We propose an alternative 'care-based' framing of SP which prioritises (and evaluates) holistic, sustained and accessible practices within strengthened primary care systems.

Case study research for better evaluations of complex interventions: rationale and challenges.

BACKGROUND: The need for better methods for evaluation in health research has been widely recognised. The 'complexity turn' has drawn attention to the limitations of relying on causal inference from randomised controlled trials alone for understanding whether, and under which conditions, interventions in complex systems improve health services or the public health, and what mechanisms might link interventions and outcomes. We argue that case study research-currently denigrated as poor evidence-is an under-utilised resource for not only providing evidence about context and transferability, but also for helping strengthen causal inferences when pathways between intervention and effects are likely to be non-linear. MAIN BODY: Case study research, as an overall approach, is based on in-depth explorations of complex phenomena in their natural, or real-life, settings. Empirical case studies typically enable dynamic understanding of complex challenges and provide evidence about causal mechanisms and the necessary and sufficient conditions (contexts) for intervention implementation and effects. This is essential evidence not just for researchers concerned about internal and external validity, but also research users in policy and practice who need to know what the likely effects of complex programmes or interventions will be in their settings. The health sciences have much to learn from scholarship on case study methodology in the social sciences. However, there are multiple challenges in fully exploiting the potential learning from case study research. First are misconceptions that case study research can only provide exploratory or descriptive evidence. Second, there is little consensus about what a case study is, and considerable diversity in how empirical case studies are conducted and reported. Finally, as case study researchers typically (and appropriately) focus on thick description (that captures contextual detail), it can be challenging to identify the key messages related to intervention evaluation from case study reports. CONCLUSION: Whilst the diversity of published case studies in health services and public health research is rich and productive, we recommend further clarity and specific methodological guidance for those reporting case study research for evaluation audiences.

RAMESES II reporting standards for realist evaluations.

BACKGROUND: Realist evaluation is increasingly used in health services and other fields of research and evaluation. No previous standards exist for reporting realist evaluations. This standard was developed as part of the RAMESES II project. The project's aim is to produce initial reporting standards for realist evaluations. METHODS: We purposively recruited a maximum variety sample of an international group of experts in realist evaluation to our online Delphi panel. Panel members came from a variety of disciplines, sectors and policy fields. We prepared the briefing materials for our Delphi panel by summarising the most recent literature on realist evaluations to identify how and why rigour had been demonstrated and where gaps in expertise and rigour were evident. We also drew on our collective experience as realist evaluators, in training and supporting realist evaluations, and on the RAMESES email list to help us develop the briefing materials. Through discussion within the project team, we developed a list of issues related to quality that needed to be addressed when carrying out realist evaluations. These were then shared with the panel members and their feedback was sought. Once the panel members had provided their feedback on our briefing materials, we constructed a set of items for potential inclusion in the reporting standards and circulated these online to panel members. Panel members were asked to rank each potential item twice on a 7-point Likert scale, once for relevance and once for validity. They were also encouraged to provide free text comments. RESULTS: We recruited 35 panel members from 27 organisations across six countries from nine different disciplines. Within three rounds our Delphi panel was able to reach consensus on 20 items that should be included in the reporting standards for realist evaluations. The overall response rates for all items for rounds 1, 2 and 3 were 94 %, 76 % and 80 %, respectively. CONCLUSION: These reporting standards for realist evaluations have been developed by drawing on a range of sources. We hope that these standards will lead to greater consistency and rigour of reporting and make realist evaluation reports more accessible, usable and helpful to different stakeholders.

Implementing supported self-management for asthma: a systematic review and suggested hierarchy of evidence of implementation studies.

BACKGROUND: Asthma self-management remains poorly implemented in clinical practice despite overwhelming evidence of improved healthcare outcomes, reflected in guideline recommendations over three decades. To inform delivery in routine care, we synthesised evidence from implementation studies of self-management support interventions. METHODS: We systematically searched eight electronic databases (1980 to 2012) and research registers, and performed snowball and manual searches for studies evaluating implementation of asthma self-management in routine practice. We included, and adapted systematic review methodology to reflect, a broad range of implementation study designs. We extracted data on study characteristics, process measures (for example, action plan ownership), asthma control (for example, patient reported control questionnaires, days off school/work, symptom-free days) and use of health services (for example, admissions, emergency department attendances, unscheduled consultations). We assessed quality using the validated Downs and Black checklist, and conducted a narrative synthesis informed by Kennedy's whole systems theoretical approach (considering patient, practitioner and organisational components and the interaction between these). RESULTS: We included 18 studies (6 randomised trials, 2 quasi-experimental studies, 8 with historical controls and 3 with retrospective comparators) from primary, secondary, community and managed care settings serving a total estimated asthma population of 800,000 people in six countries. In these studies, targeting professionals (n = 2) improved process, but had no clinically significant effect on clinical outcomes. Targeting patients (n = 6) improved some process measures, but had an inconsistent impact on clinical outcomes. Targeting the organisation (n = 3) improved process measures, but had little/no effect on clinical outcomes. Interventions that explicitly addressed patient, professional and organisational factors (n = 7) showed the most consistent improvement in both process and clinical outcomes. Authors highlighted the importance of health system commitment, skills training for professionals, patient education programmes supported by regular reviews, and on-going evaluation of implementation effectiveness. CONCLUSIONS: Our methodology offers an exemplar of reviews synthesising the heterogeneous implementation literature. Effective interventions combined active engagement of patients, with training and motivation of professionals embedded within an organisation in which self-management is valued. Healthcare managers should consider how they can promote a culture of actively supporting self-management as a normal, expected, monitored and remunerated aspect of the provision of care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (registration number: CRD42012002898 ) Accessed 24 May 2015.

Food supplementation for improving the physical and psychosocial health of socio-economically disadvantaged children aged three months to five years.

BACKGROUND: Undernutrition contributes to five million deaths of children under five each year. Furthermore, throughout the life cycle, undernutrition contributes to increased risk of infection, poor cognitive functioning, chronic disease, and mortality. It is thus important for decision-makers to have evidence about the effectiveness of nutrition interventions for young children. OBJECTIVES: Primary objective1. To assess the effectiveness of supplementary feeding interventions, alone or with co-intervention, for improving the physical and psychosocial health of disadvantaged children aged three months to five years.Secondary objectives1. To assess the potential of such programmes to reduce socio-economic inequalities in undernutrition.2. To evaluate implementation and to understand how this may impact on outcomes.3. To determine whether there are any adverse effects of supplementary feeding. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, PsycINFO, and seven other databases for all available years up to January 2014. We also searched ClinicalTrials.gov and several sources of grey literature. In addition, we searched the reference lists of relevant articles and reviews, and asked experts in the area about ongoing and unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster-RCTs, controlled clinical trials (CCTs), controlled before-and-after studies (CBAs), and interrupted time series (ITS) that provided supplementary food (with or without co-intervention) to children aged three months to five years, from all countries. Adjunctive treatments, such as nutrition education, were allowed. Controls had to be untreated. DATA COLLECTION AND ANALYSIS: Two or more review authors independently reviewed searches, selected studies for inclusion or exclusion, extracted data, and assessed risk of bias. We conducted meta-analyses for continuous data using the mean difference (MD) or the standardised mean difference (SMD) with a 95% confidence interval (CI), correcting for clustering if necessary. We analysed studies from low- and middle-income countries and from high-income countries separately, and RCTs separately from CBAs. We conducted a process evaluation to understand which factors impact on effectiveness. MAIN RESULTS: We included 32 studies (21 RCTs and 11 CBAs); 26 of these (16 RCTs and 10 CBAs) were in meta-analyses. More than 50% of the RCTs were judged to have low risk of bias for random selection and incomplete outcome assessment. We judged most RCTS to be unclear for allocation concealment, blinding of outcome assessment, and selective outcome reporting. Because children and parents knew that they were given food, we judged blinding of participants and personnel to be at high risk for all studies.Growth. Supplementary feeding had positive effects on growth in low- and middle-income countries. Meta-analysis of the RCTs showed that supplemented children gained an average of 0.12 kg more than controls over six months (95% confidence interval (CI) 0.05 to 0.18, 9 trials, 1057 participants, moderate quality evidence). In the CBAs, the effect was similar; 0.24 kg over a year (95% CI 0.09 to 0.39, 1784 participants, very low quality evidence). In high-income countries, one RCT found no difference in weight, but in a CBA with 116 Aboriginal children in Australia, the effect on weight was 0.95 kg (95% CI 0.58 to 1.33). For height, meta-analysis of nine RCTs revealed that supplemented children grew an average of 0.27 cm more over six months than those who were not supplemented (95% CI 0.07 to 0.48, 1463 participants, moderate quality evidence). Meta-analysis of seven CBAs showed no evidence of an effect (mean difference (MD) 0.52 cm, 95% CI -0.07 to 1.10, 7 trials, 1782 participants, very low quality evidence). Meta-analyses of the RCTs demonstrated benefits for weight-for-age z-scores (WAZ) (MD 0.15, 95% CI 0.05 to 0.24, 8 trials, 1565 participants, moderate quality evidence), and height-for-age z-scores (HAZ) (MD 0.15, 95% CI 0.06 to 0.24, 9 trials, 4638 participants, moderate quality evidence), but not for weight-for-height z-scores MD 0.10 (95% CI -0.02 to 0.22, 7 trials, 4176 participants, moderate quality evidence). Meta-analyses of the CBAs showed no effects on WAZ, HAZ, or WHZ (very low quality evidence). We found moderate positive effects for haemoglobin (SMD 0.49, 95% CI 0.07 to 0.91, 5 trials, 300 participants) in a meta-analysis of the RCTs.Psychosocial outcomes. Eight RCTs in low- and middle-income countries assessed psychosocial outcomes. Our meta-analysis of two studies showed moderate positive effects of feeding on psychomotor development (SMD 0.41, 95% CI 0.10 to 0.72, 178 participants). The evidence of effects on cognitive development was sparse and mixed.We found evidence of substantial leakage. When feeding was given at home, children benefited from only 36% of the energy in the supplement. However, when the supplementary food was given in day cares or feeding centres, there was less leakage; children took in 85% of the energy provided in the supplement. Supplementary food was generally more effective for younger children (less than two years of age) and for those who were poorer/ less well-nourished. Results for sex were equivocal. Our results also suggested that feeding programmes which were given in day-care/feeding centres and those which provided a moderate-to-high proportion of the recommended daily intake (% RDI) for energy were more effective. AUTHORS' CONCLUSIONS: Feeding programmes for young children in low- and middle-income countries can work, but good implementation is key.

A realist evaluation of community-based participatory research: partnership synergy, trust building and related ripple effects.

BACKGROUND: Community-Based Participatory Research (CBPR) is an approach in which researchers and community stakeholders form equitable partnerships to tackle issues related to community health improvement and knowledge production. Our 2012 realist review of CBPR outcomes reported long-term effects that were touched upon but not fully explained in the retained literature. To further explore such effects, interviews were conducted with academic and community partners of partnerships retained in the review. Realist methodology was used to increase the understanding of what supports partnership synergy in successful long-term CBPR partnerships, and to further document how equitable partnerships can result in numerous benefits including the sustainability of relationships, research and solutions. METHODS: Building on our previous realist review of CBPR, we contacted the authors of longitudinal studies of academic-community partnerships retained in the review. Twenty-four participants (community members and researchers) from 11 partnerships were interviewed. Realist logic of analysis was used, involving middle-range theory, context-mechanism-outcome configuration (CMOcs) and the concept of the 'ripple effect'. RESULTS: The analysis supports the central importance of developing and strengthening partnership synergy through trust. The ripple effect concept in conjunction with CMOcs showed that a sense of trust amongst CBPR members was a prominent mechanism leading to partnership sustainability. This in turn resulted in population-level outcomes including: (a) sustaining collaborative efforts toward health improvement; (b) generating spin-off projects; and (c) achieving systemic transformations. CONCLUSION: These results add to other studies on improving the science of CBPR in partnerships with a high level of power-sharing and co-governance. Our results suggest sustaining CBPR and achieving unanticipated benefits likely depend on trust-related mechanisms and a continuing commitment to power-sharing. These findings have implications for building successful CBPR partnerships to address challenging public health problems and the complex assessment of outcomes.

What does social prescribing look like in practice? A qualitative case study informed by practice theory.

Social prescribing (SP) typically involves linking patients in primary care with a range of local, community-based, non-clinical services. While there is a growing body of literature investigating the effectiveness of SP in improving healthcare outcomes, questions remain about how such outcomes are achieved within the everyday complexity of community health systems. This qualitative case study, informed by practice theory, aimed to investigate how SP practices relevant to people at high risk of type 2 diabetes (T2D) were enacted in a primary care and community setting serving a multi-ethnic, socioeconomically deprived population. We collected different types of qualitative data, including 35 semi-structured interviews with primary care clinicians, link workers and SP organisations; 30 hours of ethnographic observations of community-based SP activities and meetings; and relevant documents. Data analysis drew on theories of social practice, including Feldman's (2000) notion of the organisational routine, which emphasises the creative and emergent nature of routines in practice. We identified different, overlapping ways of practising SP: from highly creative, reflective and adaptive ('I do what it takes'), to more constrained ('I do what I can') or compliant ('I do as I'm told') approaches. Different types of practices were in tension and showed varying degrees of potential to support patients at high risk of T2D. Opportunities to adapt, try, negotiate, and ultimately reinvent SP to suit patients' own needs facilitated successful SP adoption and implementation, but required specific individual, relational, organisational, and institutional resources and conditions. Feldman, M.S., 2000. Organizational Routines as a Source of Continuous Change. Organ. Sci. 11, 611-629.

Mandating indoor air quality for public buildings.

If some countries lead by example, standards may increasingly become normalized.

RAMESES publication standards: meta-narrative reviews.

BACKGROUND: Meta-narrative review is one of an emerging menu of new approaches to qualitative and mixed-method systematic review. A meta-narrative review seeks to illuminate a heterogeneous topic area by highlighting the contrasting and complementary ways in which researchers have studied the same or a similar topic. No previous publication standards exist for the reporting of meta-narrative reviews. This publication standard was developed as part of the RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) project. The project's aim is to produce preliminary publication standards for meta-narrative reviews. METHODS: We (a) collated and summarized existing literature on the principles of good practice in meta-narrative reviews; (b) considered the extent to which these principles had been followed by published reviews, thereby identifying how rigor may be lost and how existing methods could be improved; (c) used a three-round online Delphi method with an interdisciplinary panel of national and international experts in evidence synthesis, meta-narrative reviews, policy and/or publishing to produce and iteratively refine a draft set of methodological steps and publication standards; (d) provided real-time support to ongoing meta-narrative reviews and the open-access RAMESES online discussion list so as to capture problems and questions as they arose; and (e) synthesized expert input, evidence review and real-time problem analysis into a definitive set of standards. RESULTS: We identified nine published meta-narrative reviews, provided real-time support to four ongoing reviews and captured questions raised in the RAMESES discussion list. Through analysis and discussion within the project team, we summarized the published literature, and common questions and challenges into briefing materials for the Delphi panel, comprising 33 members. Within three rounds this panel had reached consensus on 20 key publication standards, with an overall response rate of 90%. CONCLUSION: This project used multiple sources to draw together evidence and expertise in meta-narrative reviews. For each item we have included an explanation for why it is important and guidance on how it might be reported. Meta-narrative review is a relatively new method for evidence synthesis and as experience and methodological developments occur, we anticipate that these standards will evolve to reflect further theoretical and methodological developments. We hope that these standards will act as a resource that will contribute to improving the reporting of meta-narrative reviews.

RAMESES publication standards: realist syntheses.

BACKGROUND: There is growing interest in realist synthesis as an alternative systematic review method. This approach offers the potential to expand the knowledge base in policy-relevant areas - for example, by explaining the success, failure or mixed fortunes of complex interventions. No previous publication standards exist for reporting realist syntheses. This standard was developed as part of the RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) project. The project's aim is to produce preliminary publication standards for realist systematic reviews. METHODS: We (a) collated and summarized existing literature on the principles of good practice in realist syntheses; (b) considered the extent to which these principles had been followed by published syntheses, thereby identifying how rigor may be lost and how existing methods could be improved; (c) used a three-round online Delphi method with an interdisciplinary panel of national and international experts in evidence synthesis, realist research, policy and/or publishing to produce and iteratively refine a draft set of methodological steps and publication standards; (d) provided real-time support to ongoing realist syntheses and the open-access RAMESES online discussion list so as to capture problems and questions as they arose; and (e) synthesized expert input, evidence syntheses and real-time problem analysis into a definitive set of standards. RESULTS: We identified 35 published realist syntheses, provided real-time support to 9 on-going syntheses and captured questions raised in the RAMESES discussion list. Through analysis and discussion within the project team, we summarized the published literature and common questions and challenges into briefing materials for the Delphi panel, comprising 37 members. Within three rounds this panel had reached consensus on 19 key publication standards, with an overall response rate of 91%. CONCLUSION: This project used multiple sources to develop and draw together evidence and expertise in realist synthesis. For each item we have included an explanation for why it is important and guidance on how it might be reported. Realist synthesis is a relatively new method for evidence synthesis and as experience and methodological developments occur, we anticipate that these standards will evolve to reflect further methodological developments. We hope that these standards will act as a resource that will contribute to improving the reporting of realist syntheses.

RAMESES publication standards: meta-narrative reviews.

BACKGROUND: Meta-narrative review is one of an emerging menu of new approaches to qualitative and mixed-method systematic review. A meta-narrative review seeks to illuminate a heterogeneous topic area by highlighting the contrasting and complementary ways researchers have studied the same or a similar topic. No previous publication standards exist for the reporting of meta-narrative reviews. This publication standard was developed as part of the RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) project. The project's aim is to produce preliminary publication standards for meta-narrative reviews. DESIGN: A mixed method study synthesising data between 2011 to 2012 from a literature review, online Delphi panel and feedback from training, workshops and email list. METHODS: We: (a) collated and summarized existing literature on the principles of good practice in meta-narrative reviews; (b) considered the extent to which these principles had been followed by published reviews, thereby identifying how rigor may be lost and how existing methods could be improved; (c) used a three-round online Delphi method with an interdisciplinary panel of national and international experts in evidence synthesis, meta-narrative reviews, policy, and/or publishing to produce and iteratively refine a draft set of methodological steps, and publication standards; (d) provided real-time support to ongoing meta-narrative reviews and the open-access RAMESES online discussion list so as to capture problems and questions as they arose; and (e) synthesized expert input, evidence review, and real-time problem analysis into a definitive set of standards. RESULTS: We identified nine published meta-narrative reviews, provided real-time support to four ongoing reviews, and captured questions raised in the RAMESES discussion list. Through analysis and discussion within the project team, we summarized the published literature, and common questions and challenges into briefing materials for the Delphi panel, comprising 33 members. Within three rounds this panel had reached consensus on 20 key publication standards, with an overall response rate of 90%. CONCLUSIONS: This project used multiple sources to draw together evidence and expertise in meta-narrative reviews. For each item we have included an explanation for why it is important and guidance on how it might be reported. Meta-narrative review is a relatively new method for evidence synthesis and as experience and methodological developments occur, we anticipate that these standards will evolve to reflect further theoretical and methodological developments. We hope that these standards will act as a resource that will contribute to improving the reporting of meta-narrative reviews.

RAMESES publication standards: realist syntheses.

BACKGROUND: There is growing interest in realist synthesis as an alternative systematic review method. This approach offers the potential to expand the knowledge base in policy-relevant areas - for example, by explaining the success, failure or mixed fortunes of complex interventions. No previous publication standards exist for reporting realist syntheses. This standard was developed as part of the RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) project. The project's aim is to produce preliminary publication standards for realist systematic reviews. DESIGN: A mixed method study synthesising data between 2011-2012 from a literature review, online Delphi panel and feedback from training, workshops and email list. METHODS: We: (a) collated and summarized existing literature on the principles of good practice in realist syntheses; (b) considered the extent to which these principles had been followed by published syntheses, thereby identifying how rigour may be lost and how existing methods could be improved; (c) used a three-round online Delphi method with an interdisciplinary panel of national and international experts in evidence synthesis, realist research, policy and/or publishing to produce and iteratively refine a draft set of methodological steps and publication standards; (d) provided real-time support to ongoing realist syntheses and the open-access RAMESES online discussion list to capture problems and questions as they arose; and (e) synthesized expert input, evidence syntheses and real-time problem analysis into a definitive set of standards. RESULTS: We identified 35 published realist syntheses, provided real-time support to 9 ongoing syntheses and captured questions raised in the RAMESES discussion list. Through analysis and discussion within the project team, we summarized the published literature and common questions and challenges into briefing materials for the Delphi panel, comprising 37 members. Within 3 rounds this panel had reached consensus on 19 key publication standards, with an overall response rate of 91%. CONCLUSIONS: This project used multiple sources to develop and draw together evidence and expertise in realist synthesis. For each item we have included an explanation for why it is important and guidance on how it might be reported. Realist synthesis is a relatively new method for evidence synthesis and as experience and methodological developments occur, we anticipate that these standards will evolve to reflect further methodological developments. We hope that these standards will act as a resource that will contribute to improving the reporting of realist syntheses.

Improved endotoxin removal using ecofriendly detergents for intensified plasmid capture.

Increasing plasmid demand for both production of viral and gene therapies as well as nucleic acid based vaccines has highlighted bottlenecks in production. One bottleneck is traditional bead-based chromatography as a capture step. To meet the needs of fast-growing markets, new production solutions are needed. These solutions must enable efficient capture of a diverse range of plasmid types and excellent clearance of bacterial host impurities, such as endotoxin. Enhanced endotoxin clearance during chromatographic purification has previously been demonstrated with detergents such as Triton™ X-100. However, degradation products of Triton™ X-100 are known to have a negative environmental impact, and more sustainable, environmentally benign alternatives have been identified. This work establishes an efficient, intensified plasmid capture using convective anion exchange (AEX) chromatography. The feasibility of the intensified capture approach was assessed with different membrane and a monolith AEX supports. Various detergents from different physico-chemical classes were evaluated with different AEX technologies. Purification efficiency evaluated endotoxin and host cell protein (HCP) clearance, plasmid yield, potential interference of the detergents with analytical in-process control assays, and overall process compatibility. This comprehensive screening approach provides valuable insights to intensified plasmid production.

The impact of remote care approaches on continuity in primary care: a mixed-studies systematic review.

BACKGROUND: The value of continuity in primary care has been demonstrated for multiple positive outcomes. However, little is known about how the expansion of remote and digital care models in primary care have impacted continuity. AIM: To explore the impact of the expansion of remote and digital care models on continuity in primary care. DESIGN AND SETTING: A systematic review of continuity in primary care. METHOD: A keyword search of Embase, MEDLINE, and CINAHL databases was used along with snowball sampling to identify relevant English-language qualitative and quantitative studies from any country between 2000 and 2022, which explored remote or digital approaches in primary care and continuity. Relevant data were extracted, analysed using GRADE-CERQual, and narratively synthesised. RESULTS: Fifteen studies were included in the review. The specific impact of remote approaches on continuity was rarely overtly addressed. Some patients expressed a preference for relational continuity depending on circumstance, problem, and context; others prioritised access. Clinicians valued continuity, with some viewing remote consultations more suitable where there was high episodic or relational continuity. With lower continuity, patients and clinicians considered remote consultations harder, higher risk, and poorer quality. Some evidence suggested that remote approaches and/or their implementation risked worsening inequalities and causing harm by reducing continuity where it was valuable. However, if deployed strategically and flexibly, remote approaches could improve continuity. CONCLUSION: While the value of continuity in primary care has previously been well demonstrated, the dearth of evidence around continuity in a remote and digital context is troubling. Further research is, therefore, needed to explore the links between the shift to remote care, continuity and equity, using real-world evaluation frameworks to ascertain when and for whom continuity adds most value, and how this can be enabled or maintained.