A systematic review of behaviour change interventions to improve maternal health outcomes in sub-Saharan Africa.

The rate of decline in the global burden of avoidable maternal deaths has stagnated and remains an issue of concern in many sub-Saharan Africa countries. As per the most recent evidence, an average maternal mortality ratio (MMR) of 223 deaths per 100,000 live births has been estimated globally, with sub-Saharan Africa's average MMR at 536 per 100,000 live births-more than twice the global average. Despite the high MMR, there is variation in MMR between and within sub-Saharan Africa countries. Differences in the behaviour of those accessing and/or delivering maternal healthcare may explain variations in outcomes and provide a basis for quality improvement in health systems. There is a gap in describing the landscape of interventions aimed at modifying the behaviours of those accessing and delivering maternal healthcare for improving maternal health outcomes in sub-Saharan Africa. Our objective was to extract and synthesise the target behaviours, component behaviour change strategies and outcomes of behaviour change interventions for improving maternal health outcomes in sub-Saharan Africa. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Our protocol was published a priori on PROSPERO (registration number CRD42022315130). We searched ten electronic databases (PsycINFO, Cochrane Database of Systematic Reviews, International Bibliography of Social Sciences, EMBASE, MEDLINE, Scopus, CINAHL PLUS, African Index Medicus, African Journals Online, and Web of Science) and included randomised trials and quasi-experimental studies. We extracted target behaviours and specified the behavioural interventions using the Action, Actor, Context, Time, and Target (AACTT) framework. We categorised the behaviour change strategies using the intervention functions described in the Behaviour Change Wheel (BCW). We reviewed 52 articles (26 randomized trials and 26 quasi-experimental studies). They had a mixed risk of bias. Out of these, 41 studies (78.8%) targeted behaviour change of those accessing maternal healthcare services, while seven studies (13.5%) focused on those delivering maternal healthcare. Four studies (7.7%) targeted mixed stakeholder groups. The studies employed a range of behaviour change strategies, including education 37 (33.3%), persuasion 20 (18%), training 19 (17.1%), enablement 16 (14.4%), environmental restructuring 8 (7.2%), modelling 6 (5.4%) and incentivisation 5 (4.5%). No studies used restriction or coercion strategies. Education was the most common strategy for changing the behaviour of those accessing maternal healthcare, while training was the most common strategy in studies targeting the behaviour of those delivering maternal healthcare. Of the 52 studies, 40 reported effective interventions, 7 were ineffective, and 5 were equivocal. A meta-analysis was not feasible due to methodological and clinical heterogeneity across the studies. In conclusion, there is evidence of effective behaviour change interventions targeted at those accessing and/or delivering maternal healthcare in sub-Saharan Africa. However, more focus should be placed on behaviour change by those delivering maternal healthcare within the health facilities to fast-track the reduction of the huge burden of avoidable maternal deaths in sub-Saharan Africa.

Exploration of the individual, social and environmental factors influencing dietary behaviour in shift workers with type 2 diabetes working in UK healthcare-The Shift-Diabetes Study: A qualitative study using the theoretical domains framework.

AIM: To identify factors influencing dietary behaviour in shift workers with type 2 diabetes (T2D) working in UK healthcare settings. METHODS: Semi-structured qualitative interviews based on the theoretical domains framework (TDF) were conducted with a convenience sample (n = 15) of shift workers (32-59 years) diagnosed with T2D who worked night shifts as part of a mixed shift schedule. The TDF was applied to analyse transcripts using a combined deductive framework and inductive thematic analysis approach. Identified influences were mapped to the behaviour change technique taxonomy to identify potential strategies to change dietary behaviour in this context. RESULTS: Key barriers to healthy dietary behaviours were access and cost of food available during night work (TDF domain: Environment Context and Resources). Factors identified as both enablers and barriers included: availability of staff facilities and time to take a break, (Environment Context and Resources), the physical impact of night work (Beliefs About Consequences), eating in response to stress or tiredness (Emotion), advance planning of meals/food and taking own food to work (Behavioural Regulation). Potential techniques to address these influences and improve dietary behaviour in this context include: meal planning templates, self-monitoring and biofeedback, and increasing accessibility and availability of healthier food choices during night shifts. CONCLUSIONS: The dietary behaviour of shift workers with T2D is influenced by interacting individual, socio-cultural and environmental factors. Intervention should focus on environmental restructuring and strategies that enable monitoring and meal planning.

Perceptions and experiences of the prevention, detection, and management of postpartum haemorrhage: a qualitative evidence synthesis.

BACKGROUND: Postpartum haemorrhage (PPH), defined as blood loss of 500 mL or more after childbirth, is the leading cause of maternal mortality worldwide. It is possible to prevent complications of PPH with timely and appropriate detection and management. However, implementing the best methods of PPH prevention, detection and management can be challenging, particularly in low- and middle-income countries. OBJECTIVES: Our overall objective was to explore the perceptions and experiences of women, community members, lay health workers, and skilled healthcare providers who have experience with PPH or with preventing, detecting, and managing PPH, in community or health facility settings. SEARCH METHODS: We searched MEDLINE, CINAHL, Scopus, and grey literature on 13 November 2022 with no language restrictions. We then performed reference checking and forward citation searching of the included studies. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored perceptions and experiences of PPH prevention, detection, and management among women, community members, traditional birth attendants, healthcare providers, and managers. DATA COLLECTION AND ANALYSIS: We used three-stage maximum variation sampling to ensure diversity in terms of relevance of the study to the review objectives, richness of data, and coverage of critical contextual elements: setting (region, country income level), perspective (type of participant), and topic (prevention, detection, management). We extracted data using a data extraction form designed for this review. We used thematic synthesis to analyse and synthesise the evidence, and we used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. To identify factors that may influence intervention implementation, we mapped each review finding to the Theoretical Domains Framework (TDF) and the Capability, Motivation, and Opportunity model of Behaviour change (COM-B). We used the Behaviour Change Wheel to explore implications for practice. MAIN RESULTS: We included 67 studies and sampled 43 studies for our analysis. Most were from low- or middle-income countries (33 studies), and most included the perspectives of women and health workers. We downgraded our confidence in several findings from high confidence to moderate, low, or very-low confidence, mainly due to concerns about how the studies were conducted (methodological limitations) or concerns about missing important perspectives from some types of participants or in some settings (relevance). In many communities, bleeding during and after childbirth is considered "normal" and necessary to expel "impurities" and restore and cleanse the woman's body after pregnancy and birth (moderate confidence). In some communities, people have misconceptions about causes of PPH or believe that PPH is caused by supernatural powers or evil spirits that punish women for ignoring or disobeying social rules or for past mistakes (high confidence). For women who give birth at home or in the community, female family members or traditional birth attendants are the first to recognise excess bleeding after birth (high confidence). Family members typically take the decision of whether and when to seek care if PPH is suspected, and these family members are often influenced by trusted traditional birth attendants or community midwives (high confidence). If PPH is identified for women birthing at home or in the community, decision-making about the subsequent referral and care pathway can be multifaceted and complex (high confidence). First responders to PPH are not always skilled or trained healthcare providers (high confidence). In health facilities, midwives may consider it easy to implement visual estimation of blood loss with a kidney dish or under-pad, but difficult to accurately interpret the amount of blood loss (very low confidence). Quantifying (rather than estimating) blood loss may be a complex and contentious change of practice for health workers (low confidence). Women who gave birth in health facilities and experienced PPH described it as painful, embarrassing, and traumatic. Partners or other family members also found the experience stressful. While some women were dissatisfied with their level of involvement in decision-making for PPH management, others felt health workers were best placed to make decisions (moderate confidence). Inconsistent availability of resources (drugs, medical supplies, blood) causes delays in the timely management of PPH (high confidence). There is limited availability of misoprostol in the community owing to stockouts, poor supply systems, and the difficulty of navigating misoprostol procurement for community health workers (moderate confidence). Health workers described working on the maternity ward as stressful and intense due to short staffing, long shifts, and the unpredictability of emergencies. Exhausted and overwhelmed staff may be unable to appropriately monitor all women, particularly when multiple women are giving birth simultaneously or on the floor of the health facility; this could lead to delays in detecting PPH (moderate confidence). Inadequate staffing, high turnover of skilled health workers, and appointment of lower-level cadres of health workers are key challenges to the provision of quality PPH care (high confidence). Through team-based simulation training, health workers of different cadres (doctors, midwives, lay health workers) can develop a shared mental model to help them work quickly, efficiently, and amicably as a team when managing women with PPH (moderate confidence). AUTHORS' CONCLUSIONS: Our findings highlight how improving PPH prevention, detection, and management is underpinned by a complex system of interacting roles and behaviours (community, women, health workers of different types and with different experiences). Multiple individual, sociocultural, and environmental factors influence the decisions and behaviours of women, families, communities, health workers, and managers. It is crucial to consider the broader health and social systems when designing and implementing PPH interventions to change or influence these behaviours. We have developed a set of prompts that may help programme managers, policymakers, researchers, and other key stakeholders to identify and address factors that affect implementation and scale-up of interventions to improve PPH prevention, detection, and management.

Factors influencing staff attitudes to COVID-19 vaccination in care homes in England: a qualitative study.

BACKGROUND: The COVID-19 pandemic disproportionately affected people living and working in UK care homes causing high mortality rates. Vaccinating staff members and residents is considered the most effective intervention to reduce infection and its transmission rates. However, uptake of the first dose of the COVID-19 vaccine in care homes was variable. We sought to investigate factors influencing uptake of COVID-19 vaccination in care home staff to inform strategies to increase vaccination uptake and inform future preparedness. METHODS: Twenty care home staff including managerial and administrative staff, nurses, healthcare practitioners and support staff from nine care homes across England participated in semi-structured telephone interviews (March-June 2021) exploring attitudes towards the COVID-19 vaccine and factors influencing uptake. We used thematic analysis to generate themes which were subsequently deductively mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. The Behavioural Change Wheel (BCW) was used to identify potential intervention strategies to address identified influences. RESULTS: Enablers to vaccine uptake included the willingness to protect care home residents, staff and family/friends from infection and the belief that vaccination provided a way back to normality (reflective motivation); convenience of vaccination and access to accurate information (physical opportunity); and a supporting social environment around them favouring vaccination (social opportunity). Barriers included fears about side-effects (automatic motivation); a lack of trust due to the quick release of the vaccine (reflective motivation); and feeling pressurised to accept vaccination if mandatory (automatic motivation). CONCLUSIONS: We identified influences on COVID-19 vaccine uptake by care home staff that can inform the implementation of future vaccination programmes. Strategies likely to support uptake include information campaigns and facilitating communication between staff and managers to openly discuss concerns regarding possible vaccination side effects. Freedom of choice played an important role in the decision to be vaccinated suggesting that the decision to mandate vaccination may have unintended behavioural consequences.

Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

The protein kinases of Dictyostelia and their incorporation into a signalome.

Protein kinases are major regulators of cellular processes, but the roles of most kinases remain unresolved. Dictyostelid social amoebas have been useful in identifying functions for 30% of its kinases in cell migration, cytokinesis, vesicle trafficking, gene regulation and other processes but their upstream regulators and downstream effectors are mostly unknown. Comparative genomics can assist to distinguish between genes involved in deeply conserved core processes and those involved in species-specific innovations, while co-expression of genes as evident from comparative transcriptomics can provide cues to the protein complement of regulatory networks. Genomes and developmental and cell-type specific transcriptomes are available for species that span the 0.5 billion years of evolution of Dictyostelia from their unicellular ancestors. In this work we analysed conservation and change in the abundance, functional domain architecture and developmental regulation of protein kinases across the 4 major taxon groups of Dictyostelia. All data are summarized in annotated phylogenetic trees of the kinase subtypes and accompanied by functional information of all kinases that were experimentally studied. We detected 393 different protein kinase domains across the five studied genomes, of which 212 were fully conserved. Conservation was highest (71%) in the previously defined AGC, CAMK, CK1, CMCG, STE and TKL groups and lowest (26%) in the "other" group of typical protein kinases. This was mostly due to species-specific single gene amplification of "other" kinases. Apart from the AFK and α-kinases, the atypical protein kinases, such as the PIKK and histidine kinases were also almost fully conserved. The phylogeny-wide developmental and cell-type specific expression profiles of the protein kinase genes were combined with profiles from the same transcriptomic experiments for the families of G-protein coupled receptors, small GTPases and their GEFs and GAPs, the transcription factors and for all genes that upon lesion generate a developmental defect. This dataset was subjected to hierarchical clustering to identify clusters of co-expressed genes that potentially act together in a signalling network. The work provides a valuable resource that allows researchers to identify protein kinases and other regulatory proteins that are likely to act as intermediates in a network of interest.

Factors influencing postpartum haemorrhage detection and management and the implementation of a new postpartum haemorrhage care bundle (E-MOTIVE) in Kenya, Nigeria, and South Africa.

BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of global maternal deaths, accounting for 30-50% of maternal deaths in sub-Saharan Africa. Most PPH-related deaths are preventable with timely detection and initiation of care, which may be facilitated by using a clinical care bundle. We explore influences on current PPH detection and management and on the future implementation of a new PPH bundle (E-MOTIVE) in low-resource, high-burden settings. METHODS: Semi-structured qualitative interviews based on the Theoretical Domains Framework were conducted with 45 healthcare providers across nine hospitals in Nigeria, Kenya and South Africa, to identify barriers and enablers to current PPH detection and management and future implementation of a new PPH care bundle. Data were analysed using thematic and framework analysis. The Behaviour Change Wheel was used to identify potential interventions to address identified barriers and enablers. RESULTS: Influences on current PPH detection and management fell under 12 domains: Environmental Context and Resources (drug and staff shortages), Skills (limited in-service training), Knowledge (variable understanding of the recommended practice), Behaviour Regulation (limited quality improvement culture), Beliefs about Consequences (drawbacks from inaccurate detection), Emotion (stress from the unpredictability of PPH), Social Influence (teamwork), Memory, Attention and Decision-making (limited guideline use), Social/Professional Role and Identity (role clarity), Beliefs about Capabilities (confidence in managing PPH), Reinforcement (disciplinary procedures) and Goals (PPH as a priority). Influences on bundle uptake included: Beliefs about Consequences (perceived benefits of new blood loss measurement tool), Environmental Context and Resources (high cost of drugs and new tools), Memory, Attention and Decision-making (concerns about whether bundle fits current practice), Knowledge (not understanding 'bundled' approach), Social Influence (acceptance by women and staff) and Intention (limited acceptance of 'bundled' approach over existing practice). These influences were consistent across countries. Proposed interventions included: Education, Training, Modelling (core and new skills), Enablement (monitoring uptake), Persuasion (leadership role) and Environmental Restructuring (PPH emergency trolley/kit). CONCLUSIONS: A wide range of individual, socio-cultural and environmental barriers and enablers to improving PPH detection and management exist in these settings. We identified a range of interventions that could improve PPH care and the implementation of new care bundles in this context. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04341662.

Detection and management of postpartum haemorrhage: Qualitative evidence on healthcare providers' knowledge and practices in Kenya, Nigeria, and South Africa.

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal death globally. Most PPH deaths can be avoided with timely detection and management; however, critical challenges persist. A multi-country cluster-randomised trial (E-MOTIVE) will introduce a clinical care bundle for early detection and first-response PPH management in hospital settings. This formative qualitative study aimed to explore healthcare providers' knowledge and practices of PPH detection and management after vaginal birth, to inform design and implementation of E-MOTIVE. Methods: Between July 2020-June 2021, semi-structured qualitative interviews were conducted with 45 maternity healthcare providers (midwives, nurses, doctors, managers) of nine hospitals in Kenya, Nigeria, and South Africa. A thematic analysis approach was used. Results: Four key themes were identified, which varied across contexts: in-service training on emergency obstetric care; limited knowledge about PPH; current approaches to PPH detection; and current PPH management and associated challenges. PPH was recognised as an emergency but understanding of PPH varied. Early PPH detection was limited by the subjective nature of visual estimation of blood loss. Lack of expertise on PPH detection and using visual estimation can result in delays in initiation of PPH management. Shortages of trained staff and essential resources, and late inter-hospital referrals were common barriers to PPH management. Conclusion: There are critical needs to address context-specific barriers to early and timely detection and management of PPH in hospital settings. These findings will be used to develop evidence-informed implementation strategies, such as improved in-service training, and objective measurement of blood loss, which are key components of the E-MOTIVE trial (Trial registration: ClinicalTrials.gov: NCT04341662).

Novel RNAseq-Informed Cell-type Markers and Their Regulation Alter Paradigms of Dictyostelium Developmental Control.

Cell differentiation is traditionally monitored with a few marker genes, which may bias results. To understand the evolution and regulation of the spore, stalk, cup and basal disc cells in Dictyostelia, we previously performed RNAseq on purified cell-types of taxon-group representative dictyostelids. Using promoter-lacZ constructs in D. discoideum, we here investigate the spatio-temporal expression pattern of 29 cell-type specific genes. Genes selected for spore- or cup-specificity in RNAseq were validated as such by lacZ expression, but genes selected for stalk-specificity showed variable additional expression in basal disc, early cup or prestalk populations. We measured responses of 25 genes to 15 single or combined regimes of induction by stimuli known to regulate cell differentiation. The outcomes of these experiments were subjected to hierarchical clustering to identify whether common modes of regulation were correlated with specific expression patterns. The analysis identified a cluster combining the spore and cup genes, which shared upregulation by 8-bromo cyclic AMP and down-regulation by Differentiation Inducing Factor 1 (DIF-1). Most stalk-expressed genes combined into a single cluster and shared strong upregulation by cyclic di-guanylate (c-di-GMP), and synergistic upregulation by combined DIF-1 and c-di-GMP. There was no clustering of genes expressed in other soma besides the stalk, but two genes that were only expressed in the stalk did not respond to any stimuli. In contrast to current models, the study indicates the existence of a stem-cell like soma population in slugs, whose members only acquire ultimate cell fate after progressing to their terminal location during fruiting body morphogenesis.

A dentist's dilemma: sharing wellbeing concerns to safeguard Scotland's children.

Introduction Over a decade ago, Getting it right for every child (GIRFEC) introduced the 'Named Person' as a central contact with whom professionals could share 'wellbeing' concerns in Scotland, aiming to promote inter-agency working to avoid potential child protection issues. The mandatory 'Named Person' scheme has since been repealed but the professional's responsibility to share concerns at wellbeing level remains.Aims To explore general dental practitioners' (GDPs') understanding of a child's 'wellbeing', along with the investigation of influencing factors on behaviour when sharing concerns at wellbeing level.Methods Qualitative one-to-one semi-structured telephone interviews with GDPs. Themes arising from transcriptions were organised into the Theoretical Domains Framework.Results In total, 11 dentists (five men and six women) participated. Risks to wellbeing included only attending in pain and dental neglect. There was good awareness of the 'Named Person' and triggers to sharing suspicions were identified, which were concern severity, multiple concerns and own intuition. Multiple barriers (eg poor knowledge, fear of consequences, environment) and enablers (eg professional responsibility and influences, positive consequences) influenced decisions to refer. GDPs struggled to differentiate between wellbeing and child protection.Conclusion Barriers and facilitators to sharing wellbeing suspicions are similar to child protection. GDPs may benefit from further training when safeguarding at a wellbeing level.

Evolution of a novel cell type in Dictyostelia required gene duplication of a cudA-like transcription factor.

The evolution of novel cell types has been proposed to result from duplication of gene regulatory networks, but proven examples are rare. In addition to stalk cells and spores that make up the fruiting bodies of three major groups of Dictyostelia, those in group 4 additionally evolved basal disc and cup cells that respectively anchor the stalk to the substratum and the spore mass to the stalk. We noted a putative group-4-specific duplication of a cudA-like transcription factor (TF) in a comparative analysis of group-representative genomes. Using increased taxon sampling, we here confirmed that this TF, cdl1, duplicated into cdl1a and cdl1b in the common ancestor to group 4. cdl1a, but not cdl1b, showed signatures of positive selection, indicative of functional innovation. Deletion of cdl1a in Dictyostelium discoideum resulted in fruiting bodies with sagging spore heads that lacked the supporting cup cells and expression of cup-specific genes. Deletion of cdl1b resulted in thinner fruiting body stalks, while a cdl1b-cdl1a- double knockout showed more severe stalk defects, suggesting an ancestral role of cdl1 in stalk formation. This was confirmed in a closely related non-group 4 species, Polysphondylium violaceum, where cdl1 knockout caused defective stalk formation. These data indicate that the group-specific duplication of cdl1 and subsequent diversification of cdl1a played a pivotal role in the evolution of a novel somatic cell type in group 4 Dictyostelia.

Interactome and evolutionary conservation of Dictyostelid small GTPases and their direct regulators.

GTP binding proteins known as small GTPases make up one of the largest groups of regulatory proteins and control almost all functions of living cells. Their activity is under, respectively, positive and negative regulation by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), which together with their upstream regulators and the downstream targets of the small GTPases form formidable signalling networks. While genomics has revealed the large size of the GTPase, GEF and GAP repertoires, only a small fraction of their interactions and functions have yet been experimentally explored. Dictyostelid social amoebas have been particularly useful in unravelling the roles of many proteins in the Rac-Rho and Ras-Rap families of GTPases in directional cell migration and regulation of the actin cytoskeleton. Genomes and cell-type specific and developmental transcriptomes are available for Dictyostelium species that span the 0.5 billion years of evolution of the group from their unicellular ancestors. In this work, we identified all GTPases, GEFs and GAPs from genomes representative of the four major taxon groups and investigated their phylogenetic relationships and evolutionary conservation and changes in their functional domain architecture and in their developmental and cell-type specific expression. We performed a hierarchical cluster analysis of the expression profiles of the ~2000 analysed genes to identify putative interacting sets of GTPases, GEFs and GAPs, which highlight sets known to interact experimentally and many novel combinations. This work represents a valuable resource for research into all fields of cellular regulation.

Loss of PIKfyve Causes Transdifferentiation of Dictyostelium Spores Into Basal Disc Cells.

The 1-phosphatidylinositol-3-phosphate 5-kinase PIKfyve generates PtdIns3,5P2 on late phagolysosomes, which by recruiting the scission protein Atg18, results in their fragmentation in the normal course of endosome processing. Loss of PIKfyve function causes cellular hypervacuolization in eukaryotes and organ failure in humans. We identified pikfyve as the defective gene in a Dictyostelium mutant that failed to form spores. The amoebas normally differentiated into prespore cells and initiated spore coat protein synthesis in Golgi-derived prespore vesicles. However, instead of exocytosing, the prespore vesicles fused into the single vacuole that typifies the stalk and basal disc cells that support the spores. This process was accompanied by stalk wall biosynthesis, loss of spore gene expression and overexpression of ecmB, a basal disc and stalk-specific gene, but not of the stalk-specific genes DDB_G0278745 and DDB_G0277757. Transdifferentiation of prespore into stalk-like cells was previously observed in mutants that lack early autophagy genes, like atg5, atg7, and atg9. However, while autophagy mutants specifically lacked cAMP induction of prespore gene expression, pikfyve - showed normal early autophagy and prespore induction, but increased in vitro induction of ecmB. Combined, the data suggest that the Dictyostelium endosomal system influences cell fate by acting on cell type specific gene expression.

Formative research to design an implementation strategy for a postpartum hemorrhage initial response treatment bundle (E-MOTIVE): study protocol.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. When PPH occurs, early identification of bleeding and prompt management using evidence-based guidelines, can avert most PPH-related severe morbidities and deaths. However, adherence to the World Health Organization recommended practices remains a critical challenge. A potential solution to inefficient and inconsistent implementation of evidence-based practices is the application of a 'clinical care bundle' for PPH management. A clinical care bundle is a set of discrete, evidence-based interventions, administered concurrently, or in rapid succession, to every eligible person, along with teamwork, communication, and cooperation. Once triggered, all bundle components must be delivered. The E-MOTIVE project aims to improve the detection and first response management of PPH through the implementation of the "E-MOTIVE" bundle, which consists of (1) Early PPH detection using a calibrated drape, (2) uterine Massage, (3) Oxytocic drugs, (4) Tranexamic acid, (5) Intra Venous fluids, and (6) genital tract Examination and escalation when necessary. The objective of this paper is to describe the protocol for the formative phase of the E-MOTIVE project, which aims to design an implementation strategy to support the uptake of this bundle into practice. METHODS: We will use behavior change and implementation science frameworks [e.g. capability, opportunity, motivation and behavior (COM-B) and theoretical domains framework (TDF)] to guide data collection and analysis, in Kenya, Nigeria, South Africa, Sri Lanka, and Tanzania. There are four methodological components: qualitative interviews; surveys; systematic reviews; and design workshops. We will triangulate findings across data sources, participant groups, and countries to explore factors influencing current PPH detection and management, and potentially influencing E-MOTIVE bundle implementation. We will use these findings to develop potential strategies to improve implementation, which will be discussed and agreed with key stakeholders from each country in intervention design workshops. DISCUSSION: This formative protocol outlines our strategy for the systematic development of the E-MOTIVE implementation strategy. This focus on implementation considers what it would take to support roll-out and implementation of the E-MOTIVE bundle. Our approach therefore aims to maximize internal validity in the trial alongside future scalability, and implementation of the E-MOTIVE bundle in routine practice, if proven to be effective. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04341662.

Excessive bleeding after birth is the leading cause of maternal death globally. The World Health Organization (WHO) has recommended several treatment options for bleeding after birth. However, these treatments are not used regularly, or consistently for all women. A key underlying issue is that it is challenging for health workers to identify when women are bleeding too much, because measuring the amount of blood loss is difficult.Maternal health experts have proposed a new clinical 'care bundle' for caring for women with excessive bleeding after birth. A care bundle is a way to group together multiple treatments (e.g. 3­5 treatments). These treatments are then given to the woman at the same time, or one after another in quick succession, and supported by strategies to improve teamwork, communication, and cooperation.This is a research protocol for the preliminary phase of our study ("E-MOTIVE"), which means that it is a description of what we plan to do and how we plan to do it. The aim of our study is to develop a strategy for how we will test whether the E-MOTIVE bundle works through collaborative activities with midwives and doctors in five countries (Kenya, Nigeria, South Africa, Sri Lanka, and Tanzania) to develop a strategy for how we will test whether the E-MOTIVE bundle works. We plan to do this by conducting interviews and surveys with midwives and doctors, and reviewing other research conducted on PPH to understand what works in different settings. We will discuss our research findings in a workshop, with midwives and doctors in the study countries to co-create a strategy that will work for them, based on their needs and preferences.

Feasibility study of hospital antimicrobial stewardship analytics using electronic health records.

BACKGROUND: Hospital antimicrobial stewardship (AMS) programmes are multidisciplinary initiatives to optimize antimicrobial use. Most hospitals depend on time-consuming manual audits to monitor clinicians' prescribing. But much of the information needed could be sourced from electronic health records (EHRs). OBJECTIVES: To develop an informatics methodology to analyse characteristics of hospital AMS practice using routine electronic prescribing and laboratory records. METHODS: Feasibility study using electronic prescribing, laboratory and clinical coding records from adult patients admitted to six specialities at Queen Elizabeth Hospital, Birmingham, UK (September 2017-August 2018). The study involved: (i) a review of AMS standards of care; (ii) their translation into concepts measurable from commonly available EHRs; and (iii) a pilot application in an EHR cohort study (n = 61679 admissions). RESULTS: We developed data modelling methods to characterize antimicrobial use (antimicrobial therapy episode linkage methods, therapy table, therapy changes). Prescriptions were linked into antimicrobial therapy episodes (mean 2.4 prescriptions/episode; mean length of therapy 5.8 days), enabling several actionable findings. For example, 22% of therapy episodes for low-severity community-acquired pneumonia were congruent with prescribing guidelines, with a tendency to use broader-spectrum antibiotics. Analysis of therapy changes revealed IV to oral therapy switching was delayed by an average 3.6 days (95% CI: 3.4-3.7). Microbial cultures were performed prior to treatment initiation in just 22% of antibacterial prescriptions. The proposed methods enabled fine-grained monitoring of AMS practice down to specialities, wards and individual clinical teams by case mix, enabling more meaningful peer comparison. CONCLUSIONS: It is feasible to use hospital EHRs to construct rapid, meaningful measures of prescribing quality with potential to support quality improvement interventions (audit/feedback to prescribers), engagement with front-line clinicians on optimizing prescribing, and AMS impact evaluation studies.

Interventions to improve appropriate antibiotic prescribing in long-term care facilities: a systematic review.

BACKGROUND: Overuse of antibiotics has contributed to antimicrobial resistance; a growing public health threat. In long-term care facilities, levels of inappropriate prescribing are as high as 75%. Numerous interventions targeting long-term care facilities' antimicrobial stewardship have been reported with varying, and largely unexplained, effects. Therefore, this review aimed to apply behavioural science frameworks to specify the component behaviour change techniques of stewardship interventions in long-term care facilities and identify those components associated with improved outcomes. METHOD: A systematic review (CRD42018103803) was conducted through electronic database searches. Two behavioural science frameworks, the Behaviour Change Wheel and Behaviour Change Technique Taxonomy were used to classify intervention descriptions into intervention types and component behaviour change techniques used. Study design and outcome heterogeneity prevented meta-analysis and meta-regression. Interventions were categorised as 'very promising' (all outcomes statistically significant), 'quite promising' (some outcomes statistically significant), or 'not promising' (no outcomes statistically significant). 'Promise ratios' (PR) were calculated for identified intervention types and behaviour change techniques by dividing the number of (very or quite) promising interventions featuring the intervention type or behaviour change technique by the number of interventions featuring the intervention type or behaviour change technique that were not promising. Promising intervention types and behaviour change techniques were defined as those with a PR ≥ 2. RESULTS: Twenty studies (of19 interventions) were included. Seven interventions (37%) were 'very promising', eight 'quite promising' (42%) and four 'not promising' (21%). Most promising intervention types were 'persuasion' (n = 12; promise ratio (PR) = 5.0), 'enablement' (n = 16; PR = 4.33) and 'education' (n = 19; PR = 3.75). Most promising behaviour change techniques were 'feedback on behaviour' (n = 9; PR = 8.0) and 'restructuring the social environment' (e.g. staff role changes; n = 8; PR = 7.0). CONCLUSION: Systematic identification of the active ingredients of antimicrobial stewardship in long-term care facilities was facilitated through the application of behavioural science frameworks. Incorporating environmental restructuring and performance feedback may be promising intervention strategies for antimicrobial stewardship interventions within long-term care facilities.

An interdisciplinary mixed-methods approach to developing antimicrobial stewardship interventions: Protocol for the Preserving Antibiotics through Safe Stewardship (PASS) Research Programme.

Behaviour change is key to combating antimicrobial resistance. Antimicrobial stewardship (AMS) programmes promote and monitor judicious antibiotic use, but there is little consideration of behavioural and social influences when designing interventions.  We outline a programme of research which aims to co-design AMS interventions across healthcare settings, by integrating data-science, evidence- synthesis, behavioural-science and user-centred design. The project includes three work-packages (WP): WP1 (Identifying patterns of prescribing):  analysis of electronic health-records to identify prescribing patterns in care-homes, primary-care, and secondary-care. An online survey will investigate consulting/antibiotic-seeking behaviours in members of the public. WP2 (Barriers and enablers to prescribing in practice): Semi-structured interviews and observations of practice to identify barriers/enablers to prescribing, influences on antibiotic-seeking behaviour and the social/contextual factors underpinning prescribing. Systematic reviews of AMS interventions to identify the components of existing interventions associated with effectiveness. Design workshops to identify constraints influencing the form of the intervention. Interviews conducted with healthcare-professionals in community pharmacies, care-homes, primary-, and secondary-care and with members of the public. Topic guides and analysis based on the Theoretical Domains Framework.  Observations conducted in care-homes, primary and secondary-care with analysis drawing on grounded theory.  Systematic reviews of interventions in each setting will be conducted, and interventions described using the Behaviour Change Technique taxonomy v1. Design workshops in care-homes, primary-, and secondary care. WP3 (Co-production of interventions and dissemination). Findings will be integrated to identify opportunities for interventions, and assess whether existing interventions target influences on antibiotic use. Stakeholder panels will be assembled to co-design and refine interventions in each setting, applying the Affordability, Practicability, Effectiveness, Acceptability, Side-effects and Equity (APEASE) criteria to prioritise candidate interventions.  Outputs will inform development of new AMS interventions and/or optimisation of existing interventions.  We will also develop web-resources for stakeholders providing analyses of antibiotic prescribing patterns, prescribing behaviours, and evidence reviews.

Phylogeny-wide conservation and change in developmental expression, cell-type specificity and functional domains of the transcriptional regulators of social amoebas.

BACKGROUND: Dictyostelid social amoebas self-organize into fruiting bodies, consisting of spores and up to four supporting cell types in the phenotypically most complex taxon group 4. High quality genomes and stage- and cell-type specific transcriptomes are available for representative species of each of the four taxon groups. To understand how evolution of gene regulation in Dictyostelia contributed to evolution of phenotypic complexity, we analysed conservation and change in abundance, functional domain architecture and developmental regulation of their transcription factors (TFs). RESULTS: We detected 440 sequence-specific TFs across 33 families, of which 68% were upregulated in multicellular development and about half conserved throughout Dictyostelia. Prespore cells expressed two times more TFs than prestalk cells, but stalk cells expressed more TFs than spores, suggesting that gene expression events that define spores occur earlier than those that define stalk cells. Changes in TF developmental expression, but not in TF abundance or functional domains occurred more frequently between group 4 and groups 1-3, than between the more distant branches formed by groups 1 + 2 and 3 + 4. CONCLUSIONS: Phenotypic innovation is correlated with changes in TF regulation, rather than functional domain- or TF acquisition. The function of only 34 TFs is known. Of 12 TFs essential for cell differentiation, 9 are expressed in the cell type for which they are required. The information acquired here on conserved cell type specifity of 120 additional TFs can effectively guide further functional analysis, while observed evolutionary change in TF developmental expression may highlight how genotypic change caused phenotypic innovation.

Barriers and enablers to the implementation of perioperative hypothermia prevention practices from the perspectives of the multidisciplinary team: a qualitative study using the Theoretical Domains Framework.

Purpose: Inadvertent perioperative hypothermia is a significant problem for surgical patients globally, and is associated with many detrimental side-effects. Despite the availability of rigorously developed international evidence-based guidelines for prevention, a high incidence of this complication persists. This qualitative study aims to identify and examine the domains which act as barriers and enablers to perioperative hypothermia prevention practices, from the perspectives of the key healthcare professionals involved with perioperative temperature management. Methods: A qualitative study employing semi-structured interviews was utilized. A purposive sample of key stakeholders involved in perioperative temperature management, including perioperative nurses, anesthetists, surgeons, and perioperative managers, were recruited via email. The interview guide was developed in reference to the Theoretical Domains Framework. All interviews were recorded, de-identified, transcribed, and coded. Belief statements were generated within each domain, and a frequency score generated for each belief. Finally, the domains were mapped to the COM-B model of the Behavior Change Wheel to develop recommendations for future interventions. Results: Twelve participants were included including eight nurses, two surgeons, and two anesthetists. Eleven key theoretical domains that influence the uptake of perioperative hypothermia practices were identified: knowledge; skills; social/professional role and identity; beliefs about capabilities; optimism; beliefs about consequences; reinforcement; goals; memory, attention, and decision processes; environmental context and resources; social influence. Suggested intervention strategies include training, reminder systems, audit, and feedback, organizational support to resolve lack of control of ambient temperature, as well as provision of accurate temperature measurement devices. Conclusion: Future interventions to address the key behavioral domains and improve perioperative hypothermia prevention need to be evaluated in the context of feasibility, effectiveness, safety, acceptability, and cost by the target users. All suggested intervention strategies need to take a team-based, multi-modal approach, as this is most likely to facilitate improvements in perioperative hypothermia prevention.

Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells.

BACKGROUND: A major hallmark of multicellular evolution is increasing complexity by the evolution of new specialized cell types. During Dictyostelid evolution novel specialization occurred within taxon group 4. We here aim to retrace the nature and ancestry of the novel "cup" cells by comparing their transcriptome to that of other cell types. RESULTS: RNA-Seq was performed on purified mature spore, stalk and cup cells and on vegetative amoebas. Clustering and phylogenetic analyses showed that cup cells were most similar to stalk cells, suggesting that they share a common ancestor. The affinity between cup and stalk cells was also evident from promoter-reporter studies of newly identified cell-type genes, which revealed late expression in cups of many stalk genes. However, GO enrichment analysis reveal the unexpected prominence of GTPase mediated signalling in cup cells, in contrast to enrichment of autophagy and cell wall synthesis related transcripts in stalk cells. Combining the cell type RNA-Seq data with developmental expression profiles revealed complex expression dynamics in each cell type as well as genes exclusively expressed during terminal differentiation. Most notable were nine related hssA-like genes that were highly and exclusively expressed in cup cells. CONCLUSIONS: This study reveals the unique transcriptomes of the mature cup, stalk and spore cells of D. discoideum and provides insight into the ancestry of cup cells and roles in signalling that were not previously realized. The data presented in this study will serve as an important resource for future studies into the regulation and evolution of cell type specialization.