Evidence-based guideline implementation in low and middle income countries:Lessons for mental health care

Abstract Background There is a significant treatment gap in provision of effective treatment for people with mental disorders globally. In some Low and Middle Income Countries (LMICs) this gap is 90% or more in terms of untreated cases. Clinical practice guidelines (CPGs) are one tool to improve health care provision. The aim of this review is to examine studies of the effectiveness of evidence-based CPG implementation across physical and mental health care, to inform mental healthcare provision in low and middle income countries (LMICs), and to identify transferable lessons from other non-communicable diseases to mental health. Methods A systematic literature review employing narrative synthesis and utilising the tools developed by the Cochrane Effective Practice and Organisation of Care (EPOC) group was conducted. Experimental studies of CPG implementation relating to non-communicable diseases, including mental disorders, in LMICs were retrieved and synthesised. Results Few (six) studies were identified. Four cluster randomised controlled trials (RCTs) related to the introduction of CPGs for non-communicable diseases in physical health; one cluster-RCT included CPGs for both a non-communicable disease in physical health and mental health, and one uncontrolled before and after study described the introduction of a CPG for mental health. All of the included studies adopted multi-faceted CPG implementation strategies and used education as part of this strategy. Components of the multi-faceted strategies were sometimes poorly described. Results of the studies included generally show statistically significant improvement on some, but not all, outcomes. Conclusion Evidence for the effectiveness of interventions to improve uptake of, and compliance with, evidence-based CPGs in LMICs for mental disorders and for other non-communicable diseases is at present limited. The sparse literature does, however, suggest that multifaceted CPG implementation strategies that involve an educational component may be an effective way of improving guideline adherence and therefore of improving clinical outcomes. Further work is needed to examine cost-effectiveness of CPG implementation strategies in LMICs and to draw conclusions on the transferability of implementation experience in physical health care to mental health practice settings. Strategies to ensure that CPGs are developed with clear guidance for ..

Functional plasticity of antibacterial EndoU toxins.

Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CTSTECO31 from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CTSTECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNAGlu between nucleotides C37 and m2 A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems

Designing High-Quality Implementation Research: Development, Application, Feasibility and Preliminary Evaluation of the Implementation Science Research Development (Impres) Tool and Guide

BACKGROUND: Designing implementation research can be a complex and daunting task, especially for applied health researchers who have not received specialist training in implementation science. We developed the Implementation Science Research Development (ImpRes) tool and supplementary guide to address this challenge and provide researchers with a systematic approach to designing implementation research. METHODS: A multi-method and multi-stage approach was employed. An international, multidisciplinary expert panel engaged in an iterative brainstorming and consensus-building process to generate core domains of the ImpRes tool, representing core implementation science principles and concepts that researchers should consider when designing implementation research. Simultaneously, an iterative process of reviewing the literature and expert input informed the development and content of the tool. Once consensus had been reached, specialist expert input was sought on involving and engaging patients/service users; and economic evaluation. ImpRes was then applied to 15 implementation and improvement science projects across the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London, a research organisation in London, UK. Researchers who applied the ImpRes tool completed an 11-item questionnaire evaluating its structure, content and usefulness. RESULTS: Consensus was reached on ten implementation science domains to be considered when designing implementation research. These include implementation theories, frameworks and models, determinants of implementation, implementation strategies, implementation outcomes and unintended consequences. Researchers who used the ImpRes tool found it useful for identifying project areas where implementation science is lacking (median 5/5, IQR 4-5) and for improving the quality of implementation research (median 4/5, IQR 4-5) and agreed that it contained the key components that should be considered when designing implementation research (median 4/5, IQR 4-4). Qualitative feedback from researchers who applied the ImpRes tool indicated that a supplementary guide was needed to facilitate use of the tool. CONCLUSIONS: We have developed a feasible and acceptable tool, and supplementary guide, to facilitate consideration and incorporation of core principles and concepts of implementation science in applied health implementation research. Future research is needed to establish whether application of the tool and guide has an effect on the quality of implementation research

Developing Implementation Research Capacity: Longitudinal Evaluation of the King’s College London Implementation Science Masterclass, 2014-2019

Background: Despite an increasing number of training opportunities in implementation science becoming available, the demand for training amongst researchers and practitioners is unmet. To address this training shortfall, we developed the King\u27s College London \u27Implementation Science Masterclass\u27 (ISM), an innovative 2-day programme (and currently the largest of its kind in Europe), developed and delivered by an international faculty of implementation experts. Methods: This paper describes the ISM and provides delegates\u27 quantitative and qualitative evaluations (gathered through a survey at the end of the ISM) and faculty reflections over the period it has been running (2014-2019). Results: Across the 6-year evaluation, a total of 501 delegates have attended the ISM, with numbers increasing yearly from 40 (in 2014) to 147 (in 2019). Delegates represent a diversity of backgrounds and 29 countries from across the world. The overall response rate for the delegate survey was 64.5% (323/501). Annually, the ISM has been rated \u27highly\u27 in terms of delegates\u27 overall impression (92%), clear and relevant learning objectives (90% and 94%, respectively), the course duration (85%), pace (86%) and academic level 87%), and the support provided on the day (92%). Seventy-one percent of delegates reported the ISM would have an impact on how they approached their future work. Qualitative feedback revealed key strengths include the opportunities to meet with an international and diverse pool of experts and individuals working in the field, the interactive nature of the workshops and training sessions, and the breadth of topics and contexts covered. Conclusions: Yearly, the UK ISM has grown, both in size and in its international reach. Rated consistently favourably by delegates, the ISM helps to tackle current training demands from all those interested in learning and building their skills in implementation science. Evaluation of the ISM will continue to be an annual iterative process, reflective of changes in the evidence base and delegates changing needs as the field evolves

Development and psychometric evaluation of the Implementation Science Research Project Appraisal Criteria (ImpResPAC) tool: a study protocol

Introduction: The need for quantitative criteria to appraise the quality of implementation research has recently been highlighted to improve methodological rigour. The Implementation Science Research development (ImpRes) tool and supplementary guide provide methodological guidance and recommendations on how to design high-quality implementation research. This protocol reports on the development of the Implementation Science Research Project Appraisal Criteria (ImpResPAC) tool, a quantitative appraisal tool, developed based on the structure and content of the ImpRes tool and supplementary guide, to evaluate the conceptual and methodological quality of implementation research. Methods and analysis: This study employs a three-stage sequential mixed-methods design. During stage 1, the research team will map core domains of the ImpRes tool, guidance and recommendations contained in the supplementary guide and within the literature, to ImpResPAC. In stage 2, an international multidisciplinary expert group, recruited through purposive sampling, will inform the refinement of ImpResPAC, including content, scoring system and user instructions. In stage 3, an extensive psychometric evaluation of ImpResPAC, that was created in stage 1 and refined in stage 2, will be conducted. The scaling assumptions (inter-item and item-total correlations), reliability (internal consistency, inter-rater) and validity (construct and convergent validity) will be investigated by applying ImpResPAC to 50 protocols published in Implementation Science. We envisage developing ImpResPAC in this way will provide implementation research stakeholders, primarily grant reviewers and educators, a comprehensive, transparent and fair appraisal of the conceptual and methodological quality of implementation research, increasing the likelihood of funding research that will generate knowledge and contribute to the advancement of the field. Ethics and dissemination: This study will involve human participants. This study has been registered and minimal risk ethical clearance granted by The Research Ethics Office, King’s College London (reference number MRA-20/21-20807). Participants will receive written information on the study via email and will provide e-consent if they wish to participate. We will use traditional academic modalities of dissemination (eg, conferences and publications)

Metabolomics datasets in the Born in Bradford cohort [version 2; peer review: 1 approved, 1 approved with reservations].

Metabolomics is the quantification of small molecules, commonly known as metabolites. Collectively, these metabolites and their interactions within a biological system are known as the metabolome. The metabolome is a unique area of study, capturing influences from both genotype and environment. The availability of high-throughput technologies for quantifying large numbers of metabolites, as well as lipids and lipoprotein particles, has enabled detailed investigation of human metabolism in large-scale epidemiological studies. The Born in Bradford (BiB) cohort includes 12,453 women who experienced 13,776 pregnancies recruited between 2007-2011, their partners and their offspring. In this data note, we describe the metabolomic data available in BiB, profiled during pregnancy, in cord blood and during early life in the offspring. These include two platforms of metabolomic profiling: nuclear magnetic resonance and mass spectrometry. The maternal measures, taken at 26-28 weeks’ gestation, can provide insight into the metabolome during pregnancy and how it relates to maternal and offspring health. The offspring cord blood measurements provide information on the fetal metabolome. These measures, alongside maternal pregnancy measures, can be used to explore how they may influence outcomes. The infant measures (taken around ages 12 and 24 months) provide a snapshot of the early life metabolome during a key phase of nutrition, environmental exposures, growth, and development. These metabolomic data can be examined alongside the BiB cohorts’ extensive phenotype data from questionnaires, medical, educational and social record linkage, and other ‘omics data

Carboxyl Methyltransferase Catalysed Formation of Mono‐ and Dimethyl Esters under Aqueous Conditions: Application in Cascade Biocatalysis

Carboxyl methyltransferase (CMT) enzymes catalyse the biomethylation of carboxylic acids under aqueous conditions and have potential for use in synthetic enzyme cascades. Herein we report that the enzyme FtpM from Aspergillus fumigatus can methylate a broad range of aromatic mono- and dicarboxylic acids in good to excellent conversions. The enzyme shows high regioselectivity on its natural substrate fumaryl-l-tyrosine, trans, trans-muconic acid and a number of the dicarboxylic acids tested. Dicarboxylic acids are generally better substrates than monocarboxylic acids, although some substituents are able to compensate for the absence of a second acid group. For dicarboxylic acids, the second methylation shows strong pH dependency with an optimum at pH 5.5-6. Potential for application in industrial biotechnology was demonstrated in a cascade for the production of a bioplastics precursor (FDME) from bioderived 5-hydroxymethylfurfural (HMF)

The green valley is a red herring : Galaxy Zoo reveals two evolutionary pathways towards quenching of star formation in early-and late-type galaxies

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Monthly Notices of the Royal Astronomical Society following peer review. The version of record [Kevin Schawinski, et al, 'The green valley is a red herring: Galaxy Zoo reveals two evolutionary pathways towards quenching of star formation in early- and late-type galaxies' MNRAS, Vol. 440(1): 889-907, May 2014] is available online at: https://doi.org/10.1093/mnras/stu327.We use SDSS+GALEX+Galaxy Zoo data to study the quenching of star formation in lowredshift galaxies. We show that the green valley between the blue cloud of star-forming galaxies and the red sequence of quiescent galaxies in the colour-mass diagram is not a single transitional state through which most blue galaxies evolve into red galaxies. Rather, an analysis that takes morphology into account makes clear that only a small population of blue early-type galaxies move rapidly across the green valley after the morphologies are transformed from disc to spheroid and star formation is quenched rapidly. In contrast, the majority of blue star-forming galaxies have significant discs, and they retain their late-type morphologies as their star formation rates decline very slowly. We summarize a range of observations that lead to these conclusions, including UV-optical colours and halo masses, which both show a striking dependence on morphological type. We interpret these results in terms of the evolution of cosmic gas supply and gas reservoirs. We conclude that late-type galaxies are consistent with a scenario where the cosmic supply of gas is shut off, perhaps at a critical halo mass, followed by a slow exhaustion of the remaining gas over several Gyr, driven by secular and/or environmental processes. In contrast, early-type galaxies require a scenario where the gas supply and gas reservoir are destroyed virtually instantaneously, with rapid quenching accompanied by a morphological transformation from disc to spheroid. This gas reservoir destruction could be the consequence of a major merger, which in most cases transforms galaxies from disc to elliptical morphology, and mergers could play a role in inducing black hole accretion and possibly active galactic nuclei feedback.Peer reviewe

Discovery and characterisation of detached M-dwarf eclipsing binaries in the WFCAM Transit Survey

We report the discovery of 16 detached M-dwarf eclipsing binaries with J<16 mag and provide a detailed characterisation of three of them, using high-precision infrared light curves from the WFCAM Transit Survey (WTS). Such systems provide the most accurate and model-independent method for measuring the fundamental parameters of these poorly understood yet numerous stars, which currently lack sufficient observations to precisely calibrate stellar evolution models. We fully solve for the masses and radii of three of the systems, finding orbital periods in the range 1.5<P<4.9 days, with masses spanning 0.35-0.50 Msun and radii between 0.38-0.50 Rsun, with uncertainties of ~3.5-6.4% in mass and ~2.7-5.5% in radius. Close-companions in short-period binaries are expected to be tidally-locked into fast rotational velocities, resulting in high levels of magnetic activity. This is predicted to inflate their radii by inhibiting convective flow and increasing star spot coverage. The radii of the WTS systems are inflated above model predictions by ~3-12%, in agreement with the observed trend, despite an expected lower systematic contribution from star spots signals at infrared wavelengths. We searched for correlation between the orbital period and radius inflation by combining our results with all existing M-dwarf radius measurements of comparable precision, but we found no statistically significant evidence for a decrease in radius inflation for longer period, less active systems. Radius inflation continues to exists in non-synchronised systems indicating that the problem remains even for very low activity M-dwarfs. Resolving this issue is vital not only for understanding the most populous stars in the Universe, but also for characterising their planetary companions, which hold the best prospects for finding Earth-like planets in the traditional habitable zone.Comment: 30 pages, 14 figures, 16 tables, Accepted for publication in MNRA

Challenges, solutions and future directions in the evaluation of service innovations in health care and public health

HeadlineEvaluating service innovations in health care and public health requires flexibility, collaboration and pragmatism; this collection identifies robust, innovative and mixed methods to inform such evaluations.This is the final version of the article. It first appeared from the National Institute for Helath Research via http://dx.doi.org/10.3310/hsdr0416