The Emergency Medicine Education and Research by Global Experts (EMERGE) network was formed to generate and translate evidence to improve global emergency care. We share the challenges faced and lessons learned in establishing a global research network.We describe the challenges encountered when EMERGE proposed the development of a global emergency department (ED) visit registry. The proposed registry was to be a six-month, retrospective, deidentified, minimal dataset of routinely collected variables, such as patient demographics, diagnosis, and disposition.Obtaining reliable, accurate, and pertinent data from participating EDs is challenging in a global context. Barriers experienced ranged from variable taxonomies, need for language translation, varying site processes for curation and transfer of deidentified data, navigating institution- and country-specific data protection regulations, and substantial variation in each participating institution’s research infrastructure including training in research-related activities. We have overcome many of these challenges by creating detailed data-sharing agreements with bilateral regulatory oversight agreements between EMERGE and participating EDs, developing relationships with and training health informaticians at each site to ensure secure transfer of deidentified data, and formalizing an electronic transfer process ensuring data privacy.We believe that networks like EMERGE are integral to providing the necessary platforms for education, training, and research collaborations for emergency care. We identified substantial challenges in data sharing and variation in local sites’ research infrastructure and propose potential approaches to address these challenges. Research in emergency medicine (EM) has increased in complexity and sophistication through collaborative efforts in the past two decades.3www.EMERGENetwork.org). Aggregating high quality data on a common platform regardless of geographic borders is critical for describing and comparing the basic epidemiology of emergency care globally; increasing numbers to power hypothesis-generating studies; and improving generalizability of research findings.The Emergency Medicine Education and Research by Global Experts (EMERGE) network was formed in June 2018, with the goals of generating evidence, translating knowledge to improve emergency care for patient populations, and strengthening EM research capacity globally.Operating on a carousel model,EMERGE experienced considerable barriers ranging from variable data taxonomies, need for language translation, varying processes for data cleaning and transfer of deidentified data, and navigating numerous data protection regulations . InstituWe have overcome many of these challenges through creating detailed data-sharing agreements with bilateral regulatory oversight, developing relationships with and training site health informaticians to ensure secure transfer of deidentified data, and formalizing a transfer process ensuring data privacy. Currently, 18/19 EMERGE sites in 13 countries have institutional review board approval, 13/18 have provided initial sample data while 8/13 have provided complete six-month data . In mostEMERGE encountered substantial challenges in obtaining high quality data across its participating sites in a timely manner, which is an inherent barrier toward generating evidence and improving emergency care globally. Barriers encountered ranged from restrictive regulatory data governance to lack of time and support for emergency clinicians to participate. Despite the barriers we identified in this article, EMERGE was able to quickly respond and conducted a pandemic preparedness study among 26 member and 103 non-member sites. By leveraging the EMERGE network, many more sites were recruited via referrals and direct solicitation, and all participants who were approached agreed to participate in the study.Because it is an unfunded network, such intense data efforts from EMERGE will require substantial resources and are unsustainable. We believe the future viability of international research networks will depend on developing a federated data model in which the data is collected using standardized definitions and processes, retained at the institution, analysed locally or using federated machine learning, and reported in an aggregated manner while preserving privacy and overcoming regulatory requirements.Another approach to enhancing site research capabilities is to enhance the research training and education of the personnel in each participating ED. We are currently collaborating with the Development Implementation, and Assessment of Novel Training in Domain-based competencies (DIAMOND), which is a web-based, curated research education platform, developed by the Clinical & Translational Awards (CTSA) mechanism in the United States.The barriers encountered and solutions proposed are based on our experience, and it is possible that research networks in other specialities or those that have more robust support may have different barriers and challenges. Our experience is that with limited resources, there is a risk of over-burdening the sites as well as the central data-coordinating center. Some of these barriers can be potentially circumvented by site commitment of time and resources to the network research goals and aligning priorities.11We identified challenges in data-sharing and variation in research infrastructure among sites. Immediate next steps include the need to create regulatory-compliant federated data models, enhance research education and training, develop relevant research priorities, and identify research questions that require global participation yet can be performed at sites with limited resources.


Neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Frontotemporal lobe degeneration (FTLD), Polyglutamine diseases such as Huntington's disease (HD), Spinocerebellar ataxias (SCAs) etc., are a group of debilitating disorders that affects millions of people worldwide and have no cure to-date. Despite the advancement in our understanding of molecular and genetic mechanisms underlying these NDs, only a limited symptom-based treatment options are available. As the life expectancy increases there is an increase in the number of ND patients, which will seriously challenge the availability of resources and will impact a nation's economy. There is an urgent need to develop an affordable healthcare system and find effective treatment options to provide better clinical regimens to cure these diseases. NDs affect neurons, neuronal connections associated with memory, cognition, thinking, strength, sensation, movements, learning, co-ordination, and other abilities. Although the causative factors of NDs varies from one to another and the differences in the disease symptoms could be many, these diseases share some common features. One of the common pathological hallmarks among the most NDs is aggregation or deposition of misfolded proteins. Compelling evidence from neuropathological, genetic, animal models studies, and other approaches have strongly supported the fact that accumulation of misfolded protein aggregates triggers a series of detrimental events, which results in synaptic alterations, neuronal cell loss, and significantly contributes toward disease pathogenesis.This Research Topic highlights the new approaches employed to develop therapeutics, which can effectively block or slow down the onset or progression of these fatal NDs. This manuscripts collection highlights the current advances in the field of neurodegenerative disorders, which may help in addressing some of the unanswered questions pertaining to this Research Topic. This collection of manuscripts is divided into three vital categories: (1) Disease mechanisms, (2) Therapeutic perspectives, and (3) Animal model(s). We hope that this topic may help discern the gaps, connect the missing links, improve our current understanding, knowledge related to this topic and open new avenues of research focuses to improve current treatments options against these deadly yet incurable disorders.Montalbano et al.). The study suggested that tau modulates the gene expression of the transcripts associated with chromatin remodeling and splicing complexes . The WT and mutant P301L tau were found to differentially regulate the transcription and alternative polyadenylation (APA) profiles; and P301L mutation was found to affect the transcription mediated by tau protein .Among the many fatal NDs, Alzheimer's Disease (AD) is the most prevalent neurological disorder that affects around 6.5 million Americans of age group 65 and older today . This nuFarrawell and Yerbury utilized NSC-34 cells and investigated this aspect. Based on the findings from their study, the group supported the notion that turnover of mutant SOD1 is faster in comparison to the wild-type SOD1 (Farrawell and Yerbury). However, the study also reported that the turnover and synthesis of SOD1 is impaired in the cells containing insoluble SOD1A4V aggregates following impairment of ubiquitin–proteasome system (UPS), and thereby highlighted the role of UPS dysfunction in ALS pathogenesis (Farrawell and Yerbury).Another age-associated protein misfolding disorder and a common motor neuron disease is the Amyotrophic Lateral Sclerosis (ALS). Dominant missense mutation in superoxide dismutase 1 (SOD1) and aggregation of misfolded mutant SOD1 has been associated with ALS pathogenesis  and mitochondrial UPR (UPRmt). The review discusses the crucial roles played by UPRER and UPRmt signaling and changes in context of aging and neurodegeneration . Furthermore, the review also highlights the therapeutic strategies targeting UPRER and UPRmt, that may help improve human health conditions .In this Research Topic, a review by de Mena et al. highlighted the complex interplay between TAR DNA binding protein-43  and endoplasmic reticulum (ER) stress. TDP-43 proteinopathy is a major pathological hallmark of ALS and FTLD . The review points out the underexplored research areas, highlights the key mechanistic and therapeutic questions which are worthy of investigation. Furthermore, the review also discusses the effect of ER stress and UPR activation in TDP-43 aggregation, post-translational modifications and its interest as potential therapeutic target .Another review in this Research Topic by Kaku et al. utilized a 179 amino acid long, 20-kDa, cytosolic, mammalian protein (highly conserved) known as Fas Apoptosis Inhibitory Molecule (FAIM)  using in vitro and cell free system. Results from their study showed that FAIM knockout (KO) cells accumulates the insoluble Aβ fibrils/aggregates . Their study also reported that recombinant human FAIM solubilizes the amyloid-β fibrils, generate monomers and suppresses the protein fibrillization/aggregation in a cell free system . The recombinant human FAIM was observed to prevent Aβ fibrils, as evidenced from Neuro 2A cells . Altogether, the study suggested that FAIM (a single and unique metazoan ATP independent protein) prevents aggregation, induces dissociation of aggregated proteins and is an attractive possibility for therapeutic intervention to treat AD or related dementias .A general notion in the field of AD is that the insoluble protein fibrils contribute toward AD etiology and pathophysiology. However, some studies have also suggested that the soluble oligomers or protofibrils can also be toxic, which makes them a target for future disease modifying therapies that can effectively treat AD .Another common neurological disorder, Parkinson's Disease  was initially characterized by Dr. James Parkinson in the year 1817 , an invertebrate insect model, has proved to be an excellent model to study NDs. This versatility of Drosophila model is due to its fully sequenced genome, shorter life cycle, conservation of the basic genetic machinery, less genetic redundancy, presence of orthologs, or homologs of human disease genes etc. Drosophila has been used to model NDs like AD  neurons. The study also reported reduction in the synthesis of rate limiting enzyme: tyrosine hydroxylase (TH), alterations in the levels of dopamine (DA), as well as its metabolites in the brain . Overall, this study indicated that the PD-associated phenotypes validate the robustness of their fly model of PD and that this model would offer great help in discovering the life stage-specific genetic targets of small molecules that can offer DAergic neuroprotection . This may potentially help in the development of therapeutics that can effectively treat PD in future . Additionally, an another study conducted by Rai and Tapadia also utilized fruit fly model to establish the functional link between heat shock cognate (Hsc70), innate immune response (NF-kB) and neurodegeneration under polyQ conditions.Besides understanding the disease mechanisms, another arduous challenge for the researchers studying the human NDs is to recapitulate the exact life stage-matched animal models. Several excellent animal models have been developed and extensively utilized by the researchers to study NDs  model of PD that recapitulates the pathological features of PD and may offer great hope to the development of future therapeutics. This Research Topic in Frontiers in molecular neuroscience emphasizes the need of detailed understanding of protein aggregation biology required for the development of efficient therapeutics that may either cure or help slow down the onset or progression of NDs and may substantially contribute toward improving the quality life of ND patients.In conclusion, the research aimed at elucidating the cellular and molecular commonalities among the NDs and targeting them for therapeutics development, holds great potential. Being a common hallmark among the many NDs, it is important to deeply understand the complex biology behind protein misfolding and the cross talk between misfolded proteins, neurodegeneration, and NDs. The articles (including research and reviews) that build up this Research Topic provides deeper insights into the mechanisms that contribute toward NDs. Articles presented in the therapeutics section discusses the new, effective target(s), and compelling strategies for therapeutic intervention that may help in early diagnosis or treatment of diseases. Findings from these studies may potentially be extrapolated from laboratory setting to the translational or clinical research. Lastly, this Research Topic also covers an article pertaining to the use of an interesting Altogether, we strongly believe that this collection will help us appreciate and acknowledge the new developments in the field of NDs and how new strategies can help find the cure for these fatal diseases. We hope that the readers enjoy the broad spectrum of topics covered in this collection.NG and AS developed the concept and contributed to manuscript writing and editing. MT and RK were involved in reviewing, editing, and providing comments on the manuscript. All authors approved the final version of the manuscript for publication.


Empirical evidence suggests data and insights from the clinical practice guidelines and clinical quality registries are not being fully utilised, leaving health service managers, clinicians and providers without clear guidance on how best to improve healthcare delivery. This lack of uptake of existing research knowledge represents low value to the healthcare system and needs to change.Five electronic databases  were systematically searched. Included studies were published between 2000 and 2020 reporting on the attributes, evidence usage and impact of clinical practice guidelines and clinical quality registries on health service delivery.Twenty-six articles including one randomised controlled trial, eight before-and-after studies, eight case studies/reviews, five surveys and four interview studies, covering a wide range of medical conditions and conducted in the USA, Australia and Europe, were identified. Five complementary strategies were derived to maximise the likelihood of best practice health service delivery: (1) feedback and transparency, (2) intervention sustainability, (3) clinical practice guideline adherence, (4) productive partnerships and (5) whole-of-team approach.These five strategies, used in context-relevant combinations, are most likely to support the application of existing high-quality data, adding value to health service delivery. The review highlighted the limitations of study design in opportunistic registry studies that do not produce clear, usable evidence to guide changes to health service implementation practices. Recommendations include exploration of innovative methodologies, improved coordination of national registries and the use of incentives to encourage guideline adherence and wider dissemination of strategies used by successful registries.The online version contains supplementary material available at 10.1186/s13643-022-02104-1. Clinical practice guidelines (CPGs) have long been used to inform best clinical practice by compiling the latest, high-quality evidence on the diagnosis, treatment and management of serious acute and chronic illnesses. In Australia, CPGs are generally condition specific and written by clinicians and experts, including consumers.Clinical quality registries (CQRs) are a more recent advancement, systematically monitoring the quality of healthcare by using the collected data to identify benchmarks and variation in health outcomes. Variations are fed back to clinicians to inform clinical practice, thereby creating a feedback loop, as a mechanism for continuous quality improvement .The growth in the development and acceptability of CQRs was underpinned by the Learning Healthcare Systems (LHS) framework, first outlined by the former United States Institute of Medicine (IoM) in 2006 ; the CQRCQRs function to inform, monitor and report on the implementation of QI measures, aiming to reduce variation and extend best practice care to as many patients as possible, delivering more equitable outcomes . RegistrThe change management or implementation phase of the LHS is often less well managed , 9, meanDespite there being an abundance of CPGs and CQRs, empirical evidence suggests they are not being used to their full potential , 10. Quewhich strategies support the effective use of clinical practice guidelines and clinical quality registry data to identify gaps in best practice care and to inform and improve health service delivery? The deliberate framing of the research question in this way supports a more positive exploratory process, focusing on the benefits of utilising existing research knowledge to promote high value health services practices and policies.This systematic review addresses a broader research question: Five electronic bibliographic databases were systematically searched using two separate search processes, between 3 and 30 March 2020: MEDLINE, Embase, CINAHL, Cochrane Central and Cochrane Database of Systematic Reviews (the latter to identify other related reviews). The search strategies included studies published from 1 January 2000 to 30 March 2020 or later because the aim was to inform Australia’s developing health translation services with reference to the contemporary theories of learning healthcare systems. Detailed information on the search strategies is available in Additional file Publications were included if published in English, between January 2000 and March 2020, involving participants of any age, and with no restrictions on country of study or type of medical condition. Included publications presented original empirical research on the attributes and/or impact of CPGs/CQRs on health service delivery . All design types were eligible  providing they included specific information on how the evidence/data was used to inform health service delivery. The only exclusion criteria were particular publication types .KD worked with Mr. Roderick Dyson, a research librarian at The University of Sydney, to develop the search criteria for the bibliographic database searches. Initial search terms were based on the suggested key words and nominated databases proposed by The Australian Health Research Alliance (AHRA) Health System Improvement and Sustainability Working Group. Mr. Dyson and KD met on several occasions to refine the search criteria, and two separate searches were conducted to ensure as many relevant publications as possible were identified. The specific details of these searches are contained in Additional file All abstracts identified in the searches were exported to an EndNote version 9 library. KD and CF separately reviewed all abstracts . When exclusion criteria were applied and duplicates removed, this left a total of 231 abstracts for further review (as agreed by KD and CF). Of these, 48 underwent full-text review by both KD and CF via hard copy Microsoft Word documents, and an inter-rater reliability statistic was calculated  is shown in Tables KD undertook a simultaneous search of relevant grey literature using a list of suggested sources provided in the initial review template and expanded this list using a “snowballing” approach of checking relevant references and citations , a validated critical appraisal tool relevant for qualitative, quantitative RCTs, quantitative non-randomised, quantitative descriptive, and mixed methods study designs . Each stFour studies , 19, 27 Four articles could not be assessed for quality with existing tools as they documented processes and procedures of effective registries , 33, 35.n = 26).Figure The 11 CPG articles included only one randomised controlled trial (RCT) , four beEight of the 11 CPG articles mentioned registry data , 22, 23 The 15 CQR articles included the following: four before-and-after studies –28, 36; This review identified five strategies that strengthen adherence to CPGs and utilise CQRs for quality assurance and benchmarking to facilitate best practice health service delivery.One study evaluated the impact of surgeon-specific performance reports on adherence to treatment guidelines for older women with breast cancer . The autSustainability of QI is another important consideration. In a study of post-discharge stroke care, the authors noted the importance of measuring “long-term sustainability impact” . A compaA direct mechanism for sustainable CQRs is the legal mandate to report specific disease conditions, as noted in the USA in relation to cancer reporting  and in SGuaranteed funding is another major component of sustainability. In the USA, cardiovascular registries have found a variety of ways to maintain financial stability, including subsidies from pharmaceutical and device manufacturers, dues paid by participating providers and revenues from the sale of registry data and from grants/contracts for studies derived from those data . FundingIn Sweden, registry governance and funding are derived from its 21 regional counties and include financial levers, such as incentive payments to healthcare providers, to participate . While tWhile funding is crucial to provide long-term CQR viability, additional spending does not necessarily lead to improved outcomes. When a Swedish heart failure registry and osteoarthritis registry were compared, there was no difference in the number of sustained improvements of the chosen goal indicators despite substantial additional funding to the heart registry . TherefoOne way to improve the quality of care is by providing evidence-based care aligned with clinical guideline recommendations . ImproveModels of care associated with improved guideline adherence includes the Fox Chase Cancer Center partners community hospital/academic partnership model, which uses a tumour registry for disease-specific data and undertakes regular audits of participating hospitals for adherence to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology . The KaiTwo studies on guideline adherence stressed the importance of electronic data systems for decision support. The development of timed medical decision support systems can be used to manage new chronic patients, to audit the clinical actions performed in healthcare centres and to analyse the adherence of clinical actions to the standard procedures described in CPGs . A DutchSeveral National Cancer Institute (NCI)-designated Comprehensive Cancer Centers in the USA have established academic and clinical partnership models, including the Duke Cancer Network, MD Anderson Cancer Network, the Memorial Sloan Kettering (MSK) Cancer Centre Alliance  and Fox Productive partnerships between professional associations that address a specific health condition are illustrated by the leading cardiovascular societies in the USA. The American College of Cardiology, the STS and the American Heart Association share several collaborative registries in addition to individual registries . These rSeveral studies have reported the low levels and/or infrequent use of registry data to inform clinical practice or continuous QI activities , 29–33. A fourth solution centres on a supportive organisational culture. Findings from interviews with registry workers in England and Denmark noted that management support in the data collection and entry phase was crucial. Their findings showed that getting high-quality data into a registry requires a dedicated, sustained effort that involves not only staff but also all stakeholders . DevelopThe final solution highlights the importance of ongoing communication. In a large metropolitan hospital in Australia involved in 69 data registries, a range of communication strategies were tested to maintain engagement of clinicians in sharing CQR outcomes. Strategies included the establishment of a registry interest group, a calendar of clinical quality registry reports and a reporting guideline, template and dashboard. The reporting tool and dashboard have shown success at the pilot stage . CommuniThis comprehensive systematic review of CPGs and CQRs has identified five important strategies to facilitate the translation of research evidence and data into practice, across a range of health conditions and countries. This set of strategies, applied in context-relevant combinations, is likely to be the most successful tools for informing health services delivery options and facilitating those options that have the best chance of improving health outcomes across different health settings, conditions and systems.The defining feature of a CQR is the feedback loop to clinicians which transforms it from a data repository into the change management component of a LHS . TranspaSustainability strategies (strategy 2) are echoed in the 2017 Cochrane Effective Practice and Organisation of Care (EPOC) systematic review guidelines which specify a minimum of three data collection time points both before and after an intervention to be eligible for inclusion in a Cochrane EPOC systematic review .Adherence to CPGs (strategy 3) is one of two major ways of benchmarking health services around adherence to best evidence practice. Monitoring adherence with evidence-based CPGs is the primary purpose of some registries in the United States of America (USA). There are examples where even this basic use of registry data appears to have increased use of evidence-based therapy, more efficient patient care and shorter hospital stays . A seconEffective CQR outputs, capable of identifying gaps in services and providing reliable data for benchmarking, require sustained effort by the whole team including those involved in CQR design, management, data collection, data entry and data usage (strategy 5). LHSs aim to simplify the link between knowledge generation and evidence implementation and represent the perfect environment for maximising potential benefits from CQRs. In practice, however, there are few examples of where these systems work well .Overall, the quality of included studies was high. Twenty of the 26 publications were able to be assessed using quality criteria; of these, 15 could be considered high quality (eleven scored 4 or 5 out of 5 on one measure (Additional file More efficient usage of CPG evidence and CQR data would be facilitated by improved coordination of national registries and greater dissemination of information on how successful registries operate. For example, the authors and AHRA Working Group are aware of several high-impact registries that were not represented in the peer-reviewed literature. While some information about these registries is available through their respective websites (see Additional file Greater coordination of registries on a national basis would enable newer CQRs to benefit from the methods and models used by their more experienced counterparts. The Australian Commission on Safety and Quality in Health Care is well-placed to oversee the further development of CQRs and is currently working on a revised framework and the development of quality standards for CQR governance, reporting and technical infrastructure arrangements, to minimise duplication and maximise the use of health data for the community .Innovative methodologies such as implementation laboratories, which encourage the partitioning of major research projects into smaller, more manageable parcels and the sharing of knowledge between groups working in the same area, are one example of a promising approach . Rather There are several other areas of potentially useful research in this field. Quantitative surveys and qualitative studies that explore the reasons for non-publication of successful examples of best practice are needed to determine the extent of under-reporting and propose solutions. Such research could explore the potential role of positive or negative incentives to promote better coordination and publication of research and consider a greater role for patient views on what works best for the service users through the incorporation of patient-reported outcome and experience measures. The use of hybrid study designs that aim to simultaneously consider both the intervention and the implementation strategies used to promote uptake , 48 may This review was rigorously conducted and satisfied the PRISMA-S checklist criteria  see Add. It coveThis extensive review of CPG and CQR studies aimed at improving health service delivery identified a set of five key strategies that have been used to facilitate the translation of research evidence/data into practice across a range of health conditions and countries. The use of these strategies, in different combinations according to their potential utility to address issues in different contexts, may provide a helpful framework for considering options demonstrated to have worked in similar contexts. Greater coordination and knowledge sharing, in conjunction with higher-quality research methodology, are also required to improve evidence uptake, health service delivery and patient outcomes.Additional file 1. Literature search strategiesAdditional file 2. Grey literatureAdditional file 3. Critical appraisal using MMATAdditional file 4. Critical appraisal using QI-MCQSAdditional file 5. CPG results [Clinical Practice Guideline results]Additional file 6. CQR results [Clinical Quality Registry results]Additional file 7. PRISMA-S checklist


Nuts are nutrient-rich foods that contain many bioactive compounds that are beneficial for cardiovascular health. Higher consumption of nuts has been associated with a reduced risk of several cardiovascular diseases (CVD) in prospective cohort studies, including a 19% and 25% lower risk of CVD incidence and mortality, respectively, and a 24% and 27% lower risk of coronary heart disease incidence and mortality, respectively. An 18% lower risk of stroke mortality, a 15% lower risk of atrial fibrillation, and a 19% lower risk of total mortality have also been observed. The role of nuts in stroke incidence, stroke subtypes, peripheral arterial disease and heart failure has been less consistent. This narrative review summarizes recommendations for nuts by clinical practice guidelines and governmental organizations, epidemiological evidence for nuts and CVD outcomes, nut-containing dietary patterns, potential mechanisms of nuts and CVD risk reduction, and future research directions, such as the use of biomarkers to help better assess nut intake. Although there are still some uncertainties around nuts and CVD prevention which require further research, as summarized in this review, there is a substantial amount of evidence that supports that consuming nuts will have a positive impact on primary and secondary prevention of CVD. Cardiovascular diseases (CVD) are the leading cause of death worldwide and a major cause of premature mortality, causing an estimated 31% of all deaths globally . FurtherDespite a decline in CVD in several regions around the globe, it remains a major threat to public health as the absolute numbers continue to increase, with prevalent cases of total CVD nearly doubling from 1990 to 2019 . These nIn this narrative review, we describe the importance given to nuts in clinical practice guidelines, the evidence we have in relation to the beneficial effects of frequent consumption of nuts in the prevention of CVD, as well as the possible mechanisms involved. However, we also emphasize the gaps that exist in the literature and discuss the possible studies that we should develop in the future to increase the level of evidence and establish recommendations.Given their cardiovascular health-promoting properties, tree nuts and peanuts are recognized by several international health organizations for cardiovascular risk reduction for both primary and secondary prevention. To encourage the consumption of foods that may be beneficial for health, governmental agencies review the evidence and approve health claims that can provide consumers with reliable information about the relationship between the consumption of food and a specific health benefit. Several regulated disease risk reduction health claims have been approved for nuts and CVD by the U.S. Food and Drug Administration (FDA), the European Food Safety Authority (EFSA) and Food Standards Australia New Zealand (FSANZ), as shown in The scientific study of the role of nuts in preventing CVD started over 30 years ago, first with a discovery that individuals in the Adventist Health Study who consumed nuts more frequently (more than four times per week) had fewer coronary heart disease (CHD) events compared to those who consumed nuts less than once per week . InvestiTotal CVD is a composite outcome of CVD incidence  or may include CVD mortality outcomes only, which is a composite of different fatal CVD endpoints. A recent systematic review and meta-analysis of prospective cohort studies that were commissioned to update the clinical practice guidelines for nutrition therapy for the European Association for the Study of Diabetes (EASD) found that in three cohort comparisons , high consumption of nuts was associated with a 15% lower risk of CVD incidence  compared to low consumption . In 15 cA more recent 2022 umbrella review assessing the role of nuts in preventing several chronic diseases found similar associations with CVD incidence and mortality . For CVDSimilar to total CVD, CHD incidence may include fatal and nonfatal events, whereas CHD mortality includes CHD mortality outcomes only. The systematic review and meta-analysis conducted to update the EASD nutrition therapy guidelines assessed 7 cohort comparisons  and found that high nut consumption was associated with an 18% lower risk of CHD incidence  compared to low consumption . For CHDStroke outcomes include stroke incidence and mortality, and the main stroke subtypes, ischemic and hemorrhagic stroke. The association between nut consumption and stroke risk has been less consistent than that observed for total CVD and CHD. For stroke incidence, the EASD systematic review and meta-analysis included 7 cohort comparisons  and found no associations when comparing high to low consumption  . In contAnother meta-analysis including 11 cohort studies (9272 stroke cases) and 396,768 participants also reported an inverse association in the high vs. low analysis , but not in the linear dose-response analysis ; however, there was some indication of a non-linear J-shaped association with a reduction in risk up to approximately 10–15 g/day, but a slight positive association at 30 g/day . There wFew prospective cohort studies have assessed the role of nut consumption in preventing one of the major complications of CVD, HF. The EASD systematic review and meta-analysis included two cohort studies with 53,877 participants and 4253 cases, and for high vs. low categories of nut consumption, the RR was 1.00 (CI: 0.86–1.16) . The cerSimilar to HF, fewer prospective cohort studies have examined the role of nuts in preventing this important risk factor for stroke and HF. The EASD systematic review and meta-analysis assessed two prospective cohort studies, including 53,965 participants and 10,867 cases . CompariFew studies have assessed the association between nut consumption and the risk of PAD . In the The 2022 umbrella review also assessed the association between nut consumption and overall total mortality. In 16 cohort comparisons , both high vs. low categories of nut consumption  and per serving  were associated with lower risk of total mortality . SimilarChanges in nut intake over time and the substitution of nuts for other dietary factors have also been associated with a lower risk of CVD. For instance, Liu et al. examined the association between 4-year changes in nut consumption and risk of CVD outcomes in the subsequent 4 years in the Health Professionals Follow-up Study (HPFS) and Nurses’ Health Study (NHS) I and II . They foSeveral healthy dietary patterns that are recommended in CVD clinical practice guidelines contain nuts as a key food component. These include dietary patterns such as the Mediterranean, Nordic, Dietary Approaches to Stop Hypertension (DASH), vegetarian and Portfolio diets. Each of these dietary patterns has been shown to lower important CVD risk factors in RCTs and is associated with a lower risk of CVD in prospective cohort studies ,36,37,38There are several mechanisms by which nuts can lower the risk of developing CVD, such as through positively impacting intermediate cardiovascular risk factors, including blood lipids, blood pressure, inflammation, and markers of glycemic control, among others. Nuts are rich in unsaturated fatty acids, plant protein, phytosterols, fiber, some minerals , vitamins (vitamin E and B6) and phenolic and bioactive compounds, all of which may contribute to their CV health-promoting benefits . A systeThe evidence for nut consumption and total CVD and CHD is more consistent in prospective cohort studies compared to other CVD outcomes, with low to moderate certainty of evidence using the GRADE criteria. The GRADE criteria, however, may not be the best grading system to use when evaluating the certainty of evidence from observational studies, particularly in the field of nutritional epidemiology . Future Using objective biomarkers of nut consumption alongside dietary intake assessment methods will additionally be important in the future, as they are less prone to measurement error from FFQs or 24-h recalls . For exaOther future directions include undertaking large CV outcome trials of nut-containing dietary patterns, as was previously done with PREDIMED  and the The overall findings and conclusions from this review are that nuts are a beneficial food for CVD risk reduction, with consistent findings for the benefit for total CVD and CHD in prospective cohort studies and likely benefits for stroke and AF, but additional research is needed for HF, AF, PAD and stroke subtypes. Considering all evidence from mechanistic studies, RCTs of intermediate risk factors and CV events, and prospective cohort studies, at least one serving per day of nuts should be considered for CV risk reduction, although further research on the optimal dose is needed. The type of nut may not be important, though more research is needed to confirm this finding. However, a general nut recommendation will provide more variety of options and be important for any availability and affordability concerns for consumers. In conclusion, future research is urgently needed as outlined above, particularly for stroke subtypes, PAD and HF, and include individual cohort pooled analyses, large RCTs of nut-containing dietary patterns and using -omics methodologies to better capture adherence and metabolic responses to diet, including the consumption of nuts.


Multicomponent interventions can reduce cardiometabolic disease (CMD) risk factors in childhood; however, little synthesis of the literature has taken place in the Pacific region. Pacific Islanders experience a disproportionately high prevalence of CMD risk factors, yet interventions have been slow to reach many communities. We present this protocol for a scoping review to identify and summarize existing multicomponent interventions to address CMD risk in Pacific Islander children.Eligible interventions will (1) address CMD risk factors  in 2-to-12-year-old Pacific Islander children, and (2) be multi-component (including at least two lifestyle/behavior change strategies to address CMD risk factors). To investigate existing interventions for adaptation and potential use in Pacific Islander communities, we will search Scopus, MEDLINE ALL (Ovid), EMBASE (Ovid), Yale-licensed Web of Science Core Collection, Cochrane Library, CINAHL (EBSCOhost), ProQuest Dissertations & Theses Global, Global Health (EBSCO), non-indexed Pacific journals, grey literature, government reports, and clinical trial registrations. The Joanna Briggs Institute Manual for Evidence Synthesis and the Preferred Reporting Items for Scoping Reviews will guide data extraction, evidence mapping, synthesis, and reporting of information including study population, intervention components, behavioral changes, health and implementation outcomes, theoretical frameworks, and evaluation measures.Formal ethical approval is not required. The dissemination strategy will include peer-reviewed journal publications and presentations. Synthesis of existing multicomponent interventions for Pacific Islander children will help to identify best practices that could be replicated, adapted, or combined. Multicomponent interventions that use a combination of evidence-based behavioral, psychosocial, and/or environmental change strategies have been developed and implemented to prevent and treat childhood obesity in different population settings , 2. SevePacific Islanders have among the highest risk of obesity and related cardiometabolic diseases (CMD), yet few interventions and innovations to address CMD risk factors have reached Pacific communities , 7, 9–12With this in mind, a scoping review is necessary to identify and summarize existing multi-component interventions for Pacific Islanders that could be potentially replicated or adapted for use in Pacific Islander communities in future research. Since our preliminary search of Scopus reported no published or ongoing reviews on this topic, we will review all published original studies, reports, and grey literature that discuss multicomponent interventions to address CMD risk among Pacific Islander children in the USA, the USAPIs, other countries with a large portion of residents who identify as Pacific Islander , and three Pacific zones .The scoping review questions include, but are not limited to:What are the existing multicomponent intervention designs in published original studies, reports, and grey literature?Were the methods developed within a Pacific-focused research framework and/or theoretical model for implementation science?How were CMD risk factors  measured and defined in multicomponent interventions for Pacific Islander children?What lifestyle/behavior changes did the multicomponent interventions focus on?What qualitative and quantitative measures of reported efficacy, feasibility, and acceptability were used? Were data disaggregated by subgroups of Pacific Islanders?What were the reported intervention and implementation outcomes?What knowledge gaps remain in the existing literature?The evidence synthesis from this scoping review will help to identify best practices from existing multicomponent interventions in Pacific communities that could be replicated or adapted to address CMD risk among Pacific Islander children.The protocol is based on the scoping review methods and reporting guidelines provided by the Joanna Briggs Institute Manual for Evidence Synthesis and the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) –20. The Studies will be included in the scoping review if they fulfill the following criteria:Studies will include Pacific Islander children (ranging in ages from 2 years up to 12 years old) living in the USA, the USAPIs, other countries with a large portion of residents who identify as Pacific Islander , or countries in three geographical zones in the Pacific: Polynesia, Micronesia, and Melanesia. The list of included countries or regions follows the WHO definition of Pacific Island Countries  and prevCMD risk factors are the primary outcomes of interest and will include combinations of clinical and behavioral measures as defined by the American Heart Association  and receWe will include studies published in the 10 years prior to search completion, because of advances in intervention research and implementation science during this period  and to mTo represent the most recent and important work in the field of multicomponent interventions, this scoping review will include original research studies and study protocols published in peer-reviewed journals, government reports, and other grey literature. There are Pacific Journals, for example, Pacific Health Dialog, Papua New Guinea Medical Journal, and Journal of Samoan Studies, that are not yet indexed in PubMed. Locally implemented programs may not be reported in academic journals, but rather in state or government reports. Clinical trial registrations , dissertations, conference abstracts, and masters’ theses will be eligible for inclusion.Studies published in English will be included. If a study is written in a language other than English, but the title and abstracts are in English, we will include the paper in the title abstract screening stage and attempt to obtain a translation of the full text should it be determined to be relevant to our outcomes of interest.Literature search strategies will be developed using three concepts: (1) CMD risk factors , (2) children, and (3) Pacific Islander populations. This search strategy can retrieve potentially-relevant papers even if the authors did not explicitly frame their work as “multicomponent interventions.” The search strategy was developed by the first author (CCC) in consultation with all co-authors, including a public health librarian (KN). The section of our search that retrieves papers about Pacific Islander populations in the world is based on the search strategy in a previous protocol . The seaWe will search the following eight databases: Scopus, MEDLINE ALL (Ovid), EMBASE (Ovid), Web of Science Core Collection as licensed at Yale, Cochrane Library, CINAHL (EBSCOhost), ProQuest Dissertations & Theses Global, and Global Health (EBSCO). Articles published in regional journals across the Pacific will be searched independently.We will conduct backward and forward citation chaining on papers that meet inclusion criteria and relevant reviews to identify additional studies that may have been missed in the initial search, using CitationChaser to query the bibliographic database Lens . The cita priori with authors, 2) add to a shared Zotero library documents of potential relevance based on screening questions (that are used for title/abstract screening of bibliographic results in databases), and 3) the full-text of all documents of potential relevance will be screened for eligibility . Similar to prior review studies in other settings [We will manually search reports from territorial, state, national, and international agencies, including, but not limited to the Government, Department of Health, Ministry of Health, Pacific Island Health Officers Association, the US Centers for Disease Control, and World Health Organization. This will be completed in the following steps: 1) go to the respective websites of the agencies based on a list developed settings , 29, we We will use Covidence to download and import all search results from databases to deduplicate, title-abstract screen, and full-text screen. We will add other relevant studies identified in hand-searching and citation chaining to the Covidence screening project. We will report the selection process using the PRISMA flowchart.We will pilot the inclusion and exclusion criteria before the main phase of the title-abstract screening process. For the pilot, at least two authors will review 10–50 records and make title-abstract screening decisions (yes/no). If there are disagreements between the authors, this will be discussed with a senior author to reach a consensus on the interpretation of the inclusion and exclusion criteria.Screening for each article will occur in two phases: 1) title and abstract screening, and 2) full-text screening. For each phase, at least two authors will review the publications independently. During the screening process, disagreements will be discussed by the first and senior authors to reach a consensus. We record the reason for exclusion during the full-text screening stage. As the review process proceeds, we may record additional exclusion criteria.Screening questions will include:Was the article or title-abstract published in the English language?Is the article a case report? (Exclude if yes)Does the article discuss an intervention with at least two components addressing lifestyle/behavior change ? (Exclude if no)Were children (including ages from 2 years up to 12 years old) the population of interest? (Exclude if no)Were participants included in the intervention identified as Pacific Islander children or children living in the USAPIs, other settings with a large portion of residents who identify as Pacific Islander, or countries in three geographical zones in the Pacific (see eligibility criteria)? (Exclude if no)Were one or more CMD risk factors in children the outcomes of the intervention ? (Exclude if no)We will use all articles that meet the eligibility criteria and pass the screening questions. The first author (CCC) will extract relevant data from the articles and compare their data by categories  are in progress. We expect to complete this scoping review by May 2023.We will provide a narrative summary of the included multicomponent interventions and discuss how our findings in this scoping review answer our research questions. This summary will highlight the advances and gaps in research, as well as existing methodologies in multicomponent behavioral/lifestyle interventions for CMD risk in children. We will organize extracted data by setting , distinct groups , intervention type , and quantitative and qualitative measures . Supporting figures and tables will be developed to map the evidence and draw implications for future intervention development and adaptation research.Ethical approval is not required, since we are not collecting primary data but rather analyzing published studies, grey literature, and reports. As part of our dissemination plan, we plan to further discuss the feasibility and fit of the identified, existing multicomponent interventions for continued use among Pacific Islanders. The findings will be disseminated through peer-reviewed publications and conferences, as well as in relevant meetings in local and international settings. If any amendments to the protocol are made following its publication, we will provide the date of each amendment, describe the change(s), and report the rationale for the change(s) in future publications arising from this protocol.This scoping review will synthesize and map existing multicomponent interventions to reduce CMD risk among children, with a particular focus on Pacific Islanders.The search strategy of this scoping review is designed to identify and summarize multicomponent interventions implemented over the past decade to address CMD risk during childhood among Pacific Islanders and across the Pacific region; this represents a period in which there has been great advancement in intervention research and implementation science , 2. It wWe anticipate that the scoping review data will guide future research to address gaps in the literature and to help build a stronger evidence basis for the adaptation, implementation, and evaluation of multicomponent interventions for Pacific Islander children. Interventions developed in the Pacific region, using a Pacific and/or implementation science framework will be prioritized for intervention development and adaptation because behavior change strategies may be better aligned with the cultural values of the Pacific community and implementation/evaluation plans may be easier to replicate.


External pressures, such as public reporting requirements, national ranking lists, and nonpayment for HAIs all carry an expectation of institutions to reduce HAI rates and slow the spread of MDROs. Similarly, value-based models of care expect healthcare systems to demonstrate improvement as evidence of care quality. However, many of these pressures have not yielded the desired outcome, and we remain far from goal achievement. One potential solution, improvement science  is a method growing in popularity for its ability to affect outcomes relatively quickly by influencing a system rather than targeting a single intervention or people. Improvement science is not a simple ‘let’s do something’ approach, and is not meant to bypass rigorous investigation and evaluation. Rather, improvement science possesses methodologies and principles that when followed can generate reproducible results that affect outcomes and enhance a broad range of practice. In this review, we intend to introduce the reader to the discipline of improvement science, providing examples of successful improvement science work in infection prevention and control (IPC) and antimicrobial stewardship in the United States and globally. It is our hope that Antimicrobial Stewardship and Healthcare Epidemiology (ASHE) will serve as a platform to report such work in the future, advancing knowledge and practice for the fields of IPC and antimicrobial stewardship.The goal of infection prevention and control (IPC) and antimicrobial stewardship programs is to prevent harm to patients and others from healthcare-acquired infection (HAI) and infection with multidrug-resistant organisms (MDROs). The harm caused by HAIs and MDROs is well documented, with cost estimates upward of $10 billion and deaths upward of 100,000 annually. Shared learning includes both successes and failures. A key tenet of improvement science is that failing is inevitable and acceptable and can lead to insights that contribute to success. This idea contrasts with more traditional research, in which negative results are omitted from reports or are not published at all.Improvement science is based on the belief that learning from one another in real time is important and an effective means to achieve goals. Solutions for Patient Safety, an engagement network of >145 North American children’s hospitals, has used this concept of ‘All Teach, All Learn’ to reduce harm to hospitalized children, including HAIs like catheter-associated bloodstream infections (CLABSIs), surgical site infections (SSIs), and catheter-associated urinary tract infections (CAUTIs). The importance of provider hand hygiene was first demonstrated by Schemmelweiss >170 years ago (and 14 years before germ theory was introduced), but investigators like Didier Pittet and others conducted the seminal work that led to the World Health Organization (WHO) Five Moments of Hand Hygiene and demonstrated how to measure and improve hand hygiene to impact HAI rates.Similarly, collaborative improvement science efforts have transformed adult care. The Comprehensive Unit-based Safety Program (CUSP) demonstrated the efficacy of care bundles to prevent CLABSIs, which have now become the standard of care. In these scenarios, adherence to improvement science methodology and purposeful design and interpretation of planned experimentation are essential to success. Methodologies developed in production industries have been applied in healthcare settings, and numerous frameworks and approaches have been published and publicized through organizations like the Institute for Healthcare Improvement (IHI). Institutions have developed internal educational collaboratives, some of which are open to nonemployees, to teach and disseminate improvement science.Improvement science has been used to implement published evidence, shorten the estimated 17-year gap between research publication and adoption, and generate evidence where none exists. It is essential to define scope and goals to explain why improvement is needed at a project’s outset. This emphasis is similar to the ‘What is the problem we are trying to solve?’ question that is an essential part of most basic or clinical research grant proposals. The method then provides a framework for (1) application of improvement fundamentals, including developing a change that will affect improvement (hypothesis or theory); (2) having a feedback mechanism to detect improvement (assay or measure); (3) testing a change before implementing (experimentation); and (4) knowing when to implement the change permanently (conclusion). A robust analysis methodology, statistical process control (SPC), is used to measure processes and outcomes to detect the true change  in a system. Interestingly, some seminal SPC papers were published in Infection Control and Hospital Epidemiology by Benneyan in 1998, foreshadowing the partnership between IPC, antimicrobial stewardship, and improvement science.Common to all methodologies is the requirement for planned experimentation and improvement driven by data. The Model for Improvement, based on the work of W.E. Deming and a core component of the IHI approach, begins with a seemingly simple question: What are we trying to accomplish? The guidelines include 18 items for authors to consider and address when publishing “reports that describe system level work to improve the quality, safety, and value of healthcare, and [use] methods to establish that observed outcomes were due to the intervention(s).” Authors are encouraged to adapt the guidelines and to exclude items irrelevant to their story to disseminate the knowledge gained in their work. Many journals, including Antimicrobial Stewardship and Hospital Epidemiology, require or encourage use of SQUIRE guidelines for submissions of improvement science manuscripts for publication, similar to the standard formats expected for other study types.A standard framework for publishing improvement science work already exists, termed the Standards for QUality Improvement Reporting Excellence (SQUIRE) guidelines. Initially proposed in 2005 and published in 2009, the guidelines have undergone modification, most recently in 2016, and they are available online along with explanations and resources to aid in their effective use. Studies evaluating the effectiveness of cleaning of high-touch surfaces after patient discharge have shown that only ∼50% of surfaces were cleaned. Application of improvement science principles has improved the consistency of cleaning of hospital-room surfaces and the efficiency of ultraviolet light disinfection.A key element of HAI reduction efforts over the past 20 years has been improving and ensuring environmental cleaning practices. Florence Nightingale’s demonstration of the importance of cleanliness within healthcare settings is >170 years old, but like hand hygiene, systematic efforts to improve hospital cleaning practices have been implemented more recently.The hand hygiene practices of healthcare personnel (HCP), considered the foundation of all efforts to reduce HAIs, has been a focus of many improvement efforts. Projects have focused on improving hand hygiene in intensive care units (ICUs), inpatient settings and emergency departments. They have addressed the behavior of nurses, physicians, and other HCP groups. Improvement efforts have also spanned the globe addressing infrastructure and societal challenges specific to improving hand hygiene in low- and middle-income countries (LMICs). Early projects were able to improve this to 66%–80% through promotion of alcohol-based hand rub use, education, and increased awareness. Subsequent projects have utilized different methods capable of achieving higher reliability, such as real-time feedback from peers or electronic reminders, that have resulted in sustained hand hygiene above 90%.Not long ago, poor hand hygiene behavior of HCWs was the norm, and device-associated infections were an expected complication of inpatient care. Thankfully, much has changed, improving in a stepwise fashion over time. Reports of HCP hand hygiene compliance was frequently very low, 40%–50%. Significant rate reduction in each HAI has been achieved through sharing of effective interventions from individual healthcare settings and multicenter collaborations that have utilized improvement science methodology to identify effective practices.Four HAIs are most commonly tracked, and these data are used to assess facilities’ patient safety and care quality: CLABSI, CAUTI, ventilator-associated pneumonia (VAP), and SSI. A common method to prevent these HAIs is control of a patient’s normal flora. Bacterial colonization on the skin of a patient may result in infection when allowed to colonize a catheter or contaminate a surgical wound. Likewise, excessive bacterial colonization of the mouth and oral secretions can increase the risk of VAP. Standardizing patient bathing, procedural skin preparation, and oral care have become important components of efforts to reduce device-associated infections and SSIs. Contrary to most research studies in which a single intervention is tested under very controlled circumstances, improvement science seeks to improve outcomes in real-world settings, often testing multiple interventions simultaneously. Implementing a group of interventions together, as a bundle, has become a global standard. The National Health and Safety Network reported mean ICU CLABSI rates during 2006–2008 of 1.3 to 5.5 per 1,000 line days. Development and implementation of insertion and maintenance bundles reduced rates to 1.4–2.3 CLABSIs per 1,000 line days in adults and children. Since that time, additional studies have refined these bundles and identified strategies to increase the reliability of bundle elements performance. Projects focusing on high-risk populations  have implemented interventions addressing population-specific risks to expand CLABSI reduction to these groups as well. Once thought to be unachievable, rates below 1 CLABSI per 1,000 line days have become more commonplace.Determinants of HAIs are typically complex and multifactorial, and multimodal changes are required to reduce infections sustainably. Other project designs utilizing control units or cross-over designs can also be employed to increase confidence that changes made result in improved outcomes. A hospital-based project to improve healthcare worker hand hygiene sequentially tested interventions, including real-time reminders of healthcare workers forgetting to perform hand hygiene, on 2 different units. Improvement on each unit occurred only after the interventions were introduced.The use of more rigorous designs such as factorial design, which utilizes subgroups to simultaneously test multiple variables, can determine the relative impact of different interventions or the interaction of variables on the desired outcome. A multicenter collaborative to reduce CLABSIs in pediatric intensive care units (PICUs) utilized a factorial design and determined that the addition of chlorhexidine scrub and chlorhexidine impregnated sponges were not associated with reduced CLABSIs. Rather, reliability, the consistency of performing the bundle components at each opportunity, has been found to be an important part of any bundle. Improvement science methodology provides for measurement of both reliability and effect on outcome, and applying improvement science principles can ensure a clear association between tested interventions and improvement.Although implementing evidence-based bundles can accelerate improvement, it can be difficult to determine which interventions are vital to improvement. From a practical standpoint, ensuring that each bundle component contributes directly to improved outcomes allows for efficient use of resources. However, retrospective studies of small and large databases have failed to identify which factors are necessary and sufficient to yield the desired outcome. For example, the Solutions for Patient Safety collaborative has reduced CLABSIs (13.7%), CAUTIs (56.6%) and SSIs (16.6%) since 2012. Another multicenter collaborative of 5 adult hospitals in Brazil reduced CLABSI, CAUTIs and VAPs. Regular communication and collaboration among collaborative members has been cited as a key factor for their success.The urgency to prevent patient harm necessitates coordinated improvement efforts to increase the speed of learning, implementation, and spread of interventions to reduce HAIs. Multicenter collaboratives are an excellent platform to accelerate improvement through shared resources, learning and accountability. As previously discussed, they can also incorporate methodologic designs capable of more in-depth understanding of the impact of various interventions on improvement and the interaction of local context and culture on the effectiveness of interventions at different sites. Multicenter collaboratives have led to improved healthcare worker hand hygiene and reduced device-associated infections in the intensive care unit.Even though reaching zero HAIs may not be achievable, continued efforts to identify novel risk factors and to implement interventions to address them as well as application of improvement science to sustain improvements will continue to push the boundaries of preventable harm. Many of the factors affecting antimicrobial use are system-based and suitable for experimentation and optimization using improvement science methodology. Normative beliefs, observational learning experience, and assumed or vocalized patient expectations may push providers to prescribe antimicrobials when they are not indicated. A recent analysis from the United Kingdom reported that patients formed expectations of expectations, trying to read the prescribers’ intentions and reflect on the dependency between what prescribers and patients want. Reciprocal determinism is a model composed of 3 factors that influence behavior; the individual (including how they think or feel), their environment, and the behavior itself. For example, a parent of a sick child not wanting to miss work or with a false belief in antimicrobial effectiveness for viral illness may drive a demand for antibiotics despite a lack of indication. However, surprisingly, few antimicrobial stewardship programs are developed utilizing these improvement science concepts; therefore, they may not be as effective as they could be. Additionally, reports in the literature tend to be single-site limited engagement reports that are difficult to replicate and generalize to other contexts.The threat of antimicrobial resistance, the need to limit unnecessary prescribing and the need for effective antimicrobial stewardship programs to improve clinical outcomes while reducing adverse effects is increasingly evident in inpatient, outpatient, and long-term care settings. The COM-B/BCW framework provides a systematic method for identifying and organizing potential behaviors to a behavior change, selecting the barriers that are most likely to lead to the behavior change in each context and choosing evidence-based behavior change techniques most likely to be effective in overcoming targeted barriers. Prochaska and DiClemente’s transtheoretical model (TTM) is another framework consisting of 5 stages that conceptualize how people change their health behavior. This model has been broadly applied to infection prevention and control demonstrating the value in understanding motives among clinicians to adhere to standard precautions and success with stage-matched interventions.To be effective, antimicrobial stewardship implementation requires not only rapid knowledge transfer to the provider community for adoption of best practices but also the involvement of nurses, patients and families to accelerate organizational, programmatic, and cultural change. Many existing improvement science tools could be utilized to assess and implement programs. For example, individual barriers can be assessed using a knowledge, attitudes, and perceptions (KAP) survey for stakeholders or via the COM-B/Behavior Change Wheel (BCW) framework developed through review and synthesis of 19 existing behaving change frameworks. A systematic review of antimicrobial stewardship in the ambulatory setting found that considering interactions between people and their workplace, the role of the physical environment and external pressures in antibiotic prescribing may be avenues for improvement.Organizational level strengths and barriers are also important to assess. Study outcomes can be evaluated using indicators to assess reach, effectiveness, adoption, implementation, and maintenance of the intervention (RE-AIM framework). demonstrated in a randomized controlled trial in 5 outpatient primary care clinics, displaying poster-sized commitment letters  in patient examination rooms decreased inappropriate antibiotic prescribing for acute respiratory infections (ARIs). Quintos-Alagheband et al described developing an antimicrobial stewardship program with sustained reduction in antibiotic prescribing using a multifaceted quality improvement methodology that included a key driver diagram and rapid Plan–Do–Study–Act (PDSA) cycles. Brink et al incorporated results of a pre-implementation provider survey to implement antimicrobial stewardship process measures in a step-wise fashion in a diverse group of South African urban and rural private hospitals.To our knowledge, few studies have utilized improvement science in the implementation of antimicrobial stewardship programs in any setting. Meeker et al incorporated improvement science to address unnecessary antibiotic use for ARIs by existing antimicrobial stewardship programs in emergency departments and urgent care centers at 3 tertiary-care centers. A dynamic adaptation process was utilized to redesign the antimicrobial stewardship programs and interventions tested using a cluster-randomized comparative effectiveness clinical trial. Investigators adapted the CDC Core Elements for Outpatient Antimicrobial Stewardship by incorporating stakeholder interviews, validated provider surveys, workflow analyses and key personnel engagement. Data were collected on implementation process outcomes such as acceptability, fidelity, adoption, adaptation, and appropriateness. Results demonstrated that adaptation of the intervention components to the local setting followed by an implementation phase led to high acceptability and adoption of the intervention.Yadav et alMore studies in antimicrobial stewardship program implementation and evaluation through the lens of improvement science are needed to help demonstrate the practical utility of applying these theories and tools to further evolve the field of antimicrobial stewardship and tailor these interventions to a breadth of settings.In conclusion, improvement science has been utilized to study and improve IP and antimicrobial stewardship efforts, but more work is necessary to control and eliminate HAIs and antimicrobial resistance. As healthcare contexts evolve, those involved in IP and antimicrobial stewardship efforts will be challenged to remain flexible and adaptive. Improvement science may be the answer for practitioners with limited resources and daunting challenges due to its framework and methodology that addresses systems, accounts for context, encourages rapid experimentation, and adjusts to achieve a goal. As the number and type of projects to reduce HAIs and promote antimicrobial stewardship expands, resources to support and coordinate this work will need to follow a similar trajectory. We encourage our colleagues conducting improvement science projects to share their experience, both positive and negative, with each other to promote common knowledge and collaboration to prevent harm. With the SQUIRE guidelines, precedent publications in both fields, and now the platform of ASHE, we look to move closer to our goals together.


Bipolar disorder (BD) is associated to high personal and social burden, impaired social functioning and high levels of disability. Recent studies have showed that relapse rates are significantly reduced in those patients whose families receive psychoeducational interventions. Even though most of available evidences are related to the short-term efficacy of psychoeducational family interventions (PFI). No evidence is available on medium and long-term efficacy.This study aims to assess the efficacy after one and five years of PFI in BD in terms of: 1) improvement of patients’ symptoms and global functioning; 2) improvement of relatives’ objective and subjective burden and coping strategies.A multicenter, controlled, outpatient trial has been conducted in BD patients and their key relatives, recruited in 11 Italian mental health centers. Patient’s clinical status, social and personal functioning, burden of illness, and relative’s burden and coping strategies were assessed with specific instruments at baseline, after 1 year and after 5 years.137 families were recruited, 70 allocated to the experimental intervention. After one year, an increasing positive effect on patients’ clinical status, global functioning and objective and subjective burden was found. Moreover, were observed a reduced number of relapses and of hospitalizations after five years, compared to the control group. A reduction in the levels of family burden and an improvement of their coping strategies were also observed.Positive effects of the experimental intervention persist over the mid and long-term period. PFI should be provided in mental health centres to patients with BD and their relatives.No significant relationships.


Cholera still affects millions of people worldwide, especially in lower- and middle-income countries (LMICs). The Global Task Force on Cholera Control (GTFCC) has identified surveillance and oral cholera vaccines as two critical interventions to actualise the global roadmap goals—reduction of cholera-related deaths by 90% and decreasing the number of cholera endemic countries by half by 2030. Therefore, this study aimed to identify facilitators and barriers to implementing these two cholera interventions in LMIC settings.A scoping review using the methods presented by Arksey and O’Malley. The search strategy involved using key search terms  in three databases  and reviewing the first ten pages of Google searches. The eligibility criteria of being conducted in LMICs, a timeline of 2011–2021 and documents only in English were applied. Thematic analysis was performed, and the findings were presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension.Thirty-six documents met the predefined inclusion criteria, covering 2011 to 2021. There were two themes identified regarding the implementation of surveillance: timeliness and reporting (1); and resources and laboratory capabilities (2). As for oral cholera vaccines, there were four themes identified: information and awareness (1); community acceptance and trusted community leaders (2); planning and coordination (3); and resources and logistics (4). Additionally, adequate resources, good planning and coordination were identified to be operating at the interface between surveillance and oral cholera vaccines.Findings suggest that adequate and sustainable resources are crucial for timely and accurate cholera surveillance and that oral cholera vaccine implementation would benefit from increased community awareness and engagement of community leaders.The online version contains supplementary material available at 10.1186/s12889-023-15326-2. The risk of adverse clinical outcomes, such as hospitalisation and death, following cholera infection, is higher in vulnerable or fragile settings where access to treatment, standard supplies of potable water and basic sanitation are sparse . CholeraThe relative ease with which the 2021 outbreak spread across Nigeria underlines the importance of meeting the World Health Organization (WHO) Global Task Force on Cholera Control (GTFCC) goals for cholera control. These goals include reducing cholera-related deaths by 90% and decreasing the number of cholera endemic countries by half by 2030. Moreover, cholera control is a core component of achieving the Sustainable Development Goals (SDGs), particularly Goal 3 - “ensuring healthy lives and wellbeing for all” – and Goal 6 - “access to clean water and sanitation for all” . In ordeSurveillance relates to early detection of cholera to guide timely outbreak response and routine collection of epidemiological data to assess disease burden and identify endemic areas and cholera hotspots . Timely The relationship between surveillance and OCV is important during outbreak management and informed our decision to explore these two interventions concurrently. Evidence on the facilitators and barriers to the implementation of both interventions would serve as a valuable and relevant tool for global, regional and local policymakers, as well as for the GTFCC in planning and implementation of said interventions. Our study aimed to identify the factors influencing the implementation of surveillance and OCV interventions for cholera control in LMICs.We conducted a scoping review, as per the guide presented by Arksey and O’Malley . The fivThe specific research questions for the present study were: (1) What are the facilitators that influence the implementation of surveillance and OCVs for cholera control in LMICs? (2) What are the barriers hindering the implementation of surveillance and OCVs for cholera control in LMICs?cholera, surveillance, epidemiology and vaccines . A systematic Google website search was also conducted, using the above mentioned key search terms and screening the first ten pages to find potential documents that may not have been indexed in the previous databases for inclusion. However, no data from the Google search was eventually included for analysis due to duplications. Database searches were conducted on 12 February 2021 and Google search was conducted on 2 and 5 of April 2021. Additional file 2 and 3 present the database and Google search respectively, along with their search terms and outputs.Identification of relevant documents for this scoping review relied on searching through three research databases  and Web of Science) and the Google website. A search strategy was developed through consultations with a Karolinska Institute librarian. Medical Subject Headings (MeSH) terms were used where possible and were otherwise modified to fit databases that do not use MeSH terms. Several combinations of the search terms were created and the key search terms were We used the following inclusion criteria: the study was conducted in an LMIC, as defined per the latest World Bank classification system . TimelinThe charting process consisted of structuring the collected data into a Microsoft Excel database, which acted as an extraction form where relevant variables from the selected documents addressing the research questions were charted. Descriptive and methodological indicators were used to categorise the data. There were separate columns for surveillance facilitators and barriers and columns for OCV facilitators and barriers. At this stage, we identified the facilitators and barriers from the included documents in their entirety.At this stage, the included data were collated, compared and summarised. Then thematic analysis was conducted using the methodology recommended by Braun and Clarke . An induFigure Timeliness and reporting are crucial to cholera surveillance and response. Timeliness is characterised by early detection, reporting and confirmation of cholera cases, and declaring and responding to cholera outbreaks , 20. StuWeak community-based surveillance contributed to the late reporting of cholera cases in Ghana . AdditioA variety of resources, including human resources (e.g. well-trained staff) , 27, finHowever, limited resources as identified above, the absence of an electronic system for reporting, as well as inadequate staff training acted as barriers to cholera surveillance , 24–26. A recurring facilitator of implementing OCV interventions was pre-existing knowledge of cholera as a disease in the community. Community members’ awareness of the seriousness and symptoms of cholera contributed to their motivation to receive OCV during OCV campaigns –32. SeveLack of knowledge of OCV however acted as a barrier to its implementation, an issue that was often characterised by misconceptions, vaccine hesitancy and refusal , 33, 41.In a study of attitudes toward OCV in Dhaka, Bangladesh, it was reported that only 16% of 2,830 participating families had heard of OCV . Lack ofIn several study contexts, a high level of acceptance of OCV was mediated by pre-existing positive attitudes towards and willingness to receive the vaccine by community members , 48–50. Another facilitator of OCV campaigns was having well-trained community leaders  and haviThe most common OCV information sources were messages through megaphones, local criers, healthcare workers, family and friends, community sensitisation in school, church, home visits, social networks, word of mouth from neighbours, trusted healthcare organisations and announcements inside Internally displaced persons (IDP) camps , 52, 53.However, a reported unpleasant taste and/or smell of the OCV was an often observed barrier , 51, 52,A core facilitator for OCV campaigns was adaptive planning and coordination of the actual campaign. Adapting to local contexts included conducting vaccination on weekends, mobile vaccination teams, door-to-door vaccination, using fixed sites, starting vaccination early and finishing late in the evening , 49, 53 One of the most prominent barriers in several studies was locating eligible recipients of the vaccines during OCV campaigns, as they were often absent from their home, busy, working, travelling or having other commitments , 52, 53.A variety of resources facilitated successful implementation of OCV campaigns: use of affordable and easy-to-use vaccines ; the exiAnother facilitator often observed was functioning logistics for proper OCV distribution, such as logistical vaccine management and a functioning cold chain system , 48, 55.A recurring barrier to OCV was the lack of OCV doses and stockpile shortages , 44, 48.Poor implementation of vaccination cards appeared with challenges in South Sudan  and in BFurther resource barriers were complicated OCV vial packaging , 47, 49,The main logistical barriers to OCV implementation are unmet cold chain requirements. For example, in humanitarian settings, the need for large storage of single-dose OCV while maintaining the cold chain was difficult to fulfil. Cold chain ruptures further hindered vaccine administration, resulting in loss of vials due to freezing , 49, 52.Having proper cholera surveillance is a facilitator to evaluate OCV campaigns . Using sThis scoping review of 36 documents has identified several facilitators and barriers influencing the implementation of surveillance and OCV for cholera control in LMICs. The themes identified under surveillance were timeliness and reporting, and resources and laboratory capabilities. For OCV, information and awareness, community acceptance and trusted community leaders, planning and coordination, and resources and logistics were identified.A key finding of this review is the importance of accurate and timely information on cholera and OCV delivery from a trusted information source to the community. If potential vaccine recipients do not receive adequate information, it could lead to misinformation and distrust of vaccines, thus hindering the implementation of OCV interventions. A study on possible OCV implementation in Haiti  discusseWhen there is delay of reporting of suspected and/or confirmed cholera cases from a lower to a higher surveillance level, there is a risk of outbreaks spiraling out of control. There may be a host of reasons for cholera cases not being reported. A country’s export interests and dependence on tourism have previously been perceived as possible reasons for not reporting cholera, with underreporting or no reporting as a consequence .A finding of importance in several studies was the frequent absence of persons eligible for vaccination during OCV campaigns. To avoid this, OCV campaigns should be adapted to local contexts and involve flexible delivery strategies involving generous vaccination hours. Such planning was documented in a study on the implementation of an OCV campaign in South Sudan. Organisers adapted the vaccination delivery strategy to the local context, using a mixed approach of fixed sites and mobile door-to-door vaccination teams resulting in improved vaccination coverage .The results of this article also show the crucial need of having laboratory capacity as close as possible to where cases occur, as a major facilitator for surveillance in many different settings and countries. A country may have a surveillance system in place, but without well-trained staff who are skilled in laboratory testing and diagnosis for confirmation of cholera cases, cholera surveillance cannot function properly. If there is an additional lack of sufficient laboratory resources and capabilities this will further hinder important surveillance activities. For instance, lacking diagnostic and laboratory capabilities hindered complete surveillance data on cholera in Nepal . SpecifiShortage of global OCV stockpiles also hinder interventions for cholera control, as OCV campaigns cannot be fully implemented when vaccine supply does not meet vaccine demand . This isAlthough the included journal articles on surveillance discussed the detection of cholera cases, there was little mentioning of hotspot mapping as an important part of surveillance activities. Hotspot mapping means identifying places where the likelihood of contracting cholera is elevated. Such mapping facilitates targeted OCV campaigns where there is a higher risk of an outbreak . There iThe results presented on the importance of clearly communicating OCV information to communities can inform future research on how to develop and adapt specific cholera and OCV information campaigns tailored to local contexts. There is a need for further studies on what information should be provided and how to get messages across to populations affected by cholera. The scoping review also supports the need for research on vaccine hesitancy, further supported by findings from the COVID-19 pandemic in reports of vaccine hesitancy from many developing countries . TogetheRecommendations for the betterment of cholera surveillance efforts, based on the results of this article, include detailed and structured record-keeping and reporting, having proper tools and know-how to analyse surveillance data, potential use of GPS to pin-point accurate locations of cholera cases as well as showing flexibility and providing generous hours for vaccine campaigns in order to reach populations during more hours of the week. This could further chances of reaching people who are away for work during the day and are not available during regular vaccination hours. There is also room for improving communication between neighbouring communities in order to strenghten local-level collaboration. In order to increase communication there could be a focus on low-cost mHealth interventions, such as using designated cholera mobile phones in order to communicate new cases between neighbouring communities and sharing and providing assitance and information.Cholera often appears in already vulnerable contexts, in places of conflict or crisis, increasing the burden of the disease. African and Asian countries are particularly affected by cholera and its consequences. Many of the issues relating to COVID-19 such as tracking cases and distributing vaccines while preventing vaccine hesitancy, mirror the issues faced by cholera control. Furthermore, cholera control activities are hampered due to limited focus and resources during the COVID-19 pandemic, increasing the risk of cholera transmission in vulnerable regions . It is pConcerning the concept of vaccine information, COVID-19 and cholera prevention efforts may benefit from each other, or risk exacerbating vaccine hesitancy. It is crucial to inform people about vaccine function, importance, benefits, risks, safety and explain, in the case of OCV, that the vaccine is aimed at adults as well as children. The issue of vaccine hesitancy has become clear during the COVID-19 pandemic, with a study on vaccine acceptability in LMIC settings showing that 50% of LMIC residents were willing to accept the vaccine against COVID-19 . The stuAs demonstrated by the results of this article, collaboration between community members, cholera stakeholders and representatives from government bodies and NGOs is crucial for furthering surveillance and OCV campaign activities. Being a conglomerate of various stakeholders including cholera endemic countries and the WHO, the GTFCC is representing and striving for cooperation in the quest to eliminate cholera. Going forward, the GTFCC is bringing surveillance, OCV and cooperation to the forefront of their policymaking: strengthening proper surveillance as the key to early detection of outbreaks; using OCV to show that cholera is not an inevitable disease and presenting solutions to cholera hotspots and outbreaks; implementing Water, Sanitation and Hygiene (WASH) programmes; and providing support and resources for national stakeholders working to prevent cholera in their own local contexts . AdditioMaintaining wide research questions facilitated the inclusion of a broad range of data and lessened the risk of overlooking relevant information. Furthermore, this scoping review covered a broad timeline, while capturing both historical and contemporary narratives of cholera surveillance and OCV. However, the review has some limitations that are worth noting. First, the use of three databases for the review of documents and restriction of searches to only documents written in English might have biased the findings if the omitted documents were systematically different from those included for the review. However, the duplications observed following Google search suggest this may not be a significant issue. Moreover, these databases were chosen in consultation with a librarian with extensive experience in conducting systematic reviews. The scoping review process does not necessarily put as much focus on the assessment of quality of included journal articles as a systematic review would . By not Resources are crucial for timely and accurate cholera surveillance systems. OCV interventions could be more successful if knowledge of cholera and its vaccines are prioritised in communities, along with effective community engagement where people getting vaccinated can be reassured of vaccine safety by people they trust. Having proper resources and good planning and coordination, are important for linking surveillance to OCV interventions. Combining the GTFCC’s efforts with knowledge provided by active researchers will further move towards global elimination of cholera.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3Supplementary Material 4