Cross-cultural generalizability of suicide first aid actions: an analysis of agreement across expert consensus studies from a range of countries and cultures

Background A number of Delphi expert consensus studies have been carried out with different countries and cultural groups to develop guidelines on how a member of the public should provide assistance to a person who is suicidal. The present study aimed to determine whether cross-culturally generalizable suicide first aid actions are possible by comparing agreement across these Delphi studies. Methods Data on endorsement rates for items were compared across six Delphi studies. These studies involved panels of professionals and consumer advocates from English-speaking countries, professionals from Sri Lanka, professionals from Japan, professionals from India, professionals from the Philippines, and professionals and consumer advocates in refugee and immigrant mental health. Correlations were calculated between item endorsement rates across panels. Results There were 18 items that were highly endorsed across all eight of the Delphi panels and an additional 15 items highly endorsed across the panels from the three lower middle-income countries (India, Philippines and Sri Lanka). Correlations across panels in item endorsement rates were all 0.60 or above, but were higher between panels from countries that are socioeconomically similar. Conclusions There is broad agreement across the diverse expert panels about what are appropriate suicide first aid actions for members of the public, indicating that cross-cultural generalizability is possible. However, there is also some cultural specificity, indicating the need for local tailoring

Exploring the genetics of irritable bowel syndrome: A GWA study in the general population and replication in multinational case-control cohorts

OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11\u2005326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31 710(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Analytical development to support manufacturing of a sustainable vaccine against Invasive Nontyphoidal Salmonellosis

GVGH is developing a candidate trivalent Salmonella vaccine to fight invasive nontyphoidal Salmonellosis (iNTS) and typhoid fever, especially aimed for sub-Saharan Africa to impact disease burden and to reduce anti-microbial resistance spread. This trivalent vaccine may be the only viable option for a sustainable iNTS vaccine in sub-Saharan Africa over the separate administration of Typhoid Conjugate Vaccines (TCV) and a vaccine against iNTS. GVGH generated the iNTS-TCV formulation by combining the GMMA technology for the iNTS components, S. Typhimurium (STm) and S. Enteritidis (SEn) GMMA adsorbed on Alhydrogel, and the Vi-CRM197 glycoconjugate, originally developed by GVGH and recently WHO prequalified as TCV TYPHIBEV by Biological E Ltd (Hyderabad, India). A set of analytical methods to support the vaccine lot release and characterization have been developed by GVGH. In particular, to quantify the key active ingredients of iNTS components a competitive ELISA-based method (FAcE, Formulated Alhydrogel competitive ELISA assay) has been setup and characterized in terms of specificity, accuracy and precision. Vi component is instead characterized by means of HPAEC-PAD method, able to specifically identify and quantify the total polysaccharide in the final drug product. With regard to safety assessment, a Monocyte Activation Test (MAT) has been developed as to monitor the intrinsic pyrogenicity of GMMA-based vaccines and applied as surveillance test for the Phase 1 clinical lot, with the plan to set release criteria based on clinical experience. In vivo potency assay has been set to characterize the immunogenicity of vaccine lots in comparison to freshly formulated material at the time of release and during real-time stability. A significant antibody response to each of the active ingredients of the trivalent vaccine is raised in mice and assessed by Parallel Line Assay. Overall, the applied analytical panel and the results support the development of an iNTS-TCV vaccine as a viable option for a sustainable iNTS vaccine in sub-Saharan Africa

Exploring the potential of civic engagement to strengthen mental health systems in Indonesia (IGNITE) : a study protocol

Background Indonesia has the highest rate of years of life lost to disability or early death from Schizophrenia than any other country in the world. More than 90% of people with mental illness do not get any treatment and tens of thousands of people with psychosis are illegally detained ('pasung') in the family home. Civic engagement, a core part of the recent World Health Organisation global strategy, has the potential to address some of these challenges through the development of person-centered models of care. The aim of the study is to develop a testable systems level, culturally appropriate, civic engagement framework for use in Jakarta and Bogor, Indonesia to strengthen local mental health services. Methods A mixed methods study underpinned by a realist approach will be undertaken across four phases in two study sites in Indonesia (Jakarta and Bogor). Phase 1 will explore the use of civic engagement across South East Asia by conducting a systematic review of existing evidence. By surveying 300 mental health professionals, phase 2 will identify the stakeholders, the sources of collaboration and the evidence used by professionals in decision making within local mental health systems and identify potential opportunities for civic engagement within the system. In order to explore the potential use of civic engagement within Indonesian mental health services and identify priorities for a culturally appropriate framework, phase 3 will undertake two focus groups with participants with experience of psychosis or caring for someone with psychosis (n = 20–30). Professionals and other key decision makers in a range of roles across the system at a national (n = 5) and local level (n = 10–15/site) will also take part in semi-structured interviews. Phase 4 will co-produce a civic engagement framework for use in Indonesia by synthesising evidence from phases 1–3 collaboratively with key stakeholders. Discussion Civic engagement is a potential way in which health services in low and middle income countries can address the burden of mental health conditions through the development of person-centred models of care. However, such approaches are underexplored in Indonesia. This study will work with local stakeholders to design a testable civic engagement framework for use in mental health services in Indonesia

High Yield Production Process for Shigella Outer Membrane Particles

Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, outer membrane proteins, and soluble periplasmic components. These particles have been proposed for use as vaccines but the yield has been problematic. We developed a high yielding production process of genetically derived outer membrane particles from the human pathogen Shigella sonnei. Yields of approximately 100 milligrams of membrane-associated proteins per liter of fermentation were obtained from cultures of S. sonnei ΔtolR ΔgalU at optical densities of 30–45 in a 5 L fermenter. Proteomic analysis of the purified particles showed the preparation to primarily contain predicted outer membrane and periplasmic proteins. These were highly immunogenic in mice. The production of these outer membrane particles from high density cultivation of bacteria supports the feasibility of scaling up this approach as an affordable manufacturing process. Furthermore, we demonstrate the feasibility of using this process with other genetic manipulations e.g. abolition of O antigen synthesis and modification of the lipopolysaccharide structure in order to modify the immunogenicity or reactogenicity of the particles. This work provides the basis for a large scale manufacturing process of Generalized Modules of Membrane Antigens (GMMA) for production of vaccines from Gram-negative bacteria

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries