Indigenous young people worldwide are at greater risk of developing mental health concerns due to ongoing inequity and disadvantage. Digital mental health (dMH) interventions are identified as a potential approach to improving access to mental health treatment for Indigenous youth. Although involvement in the development and evaluation of dMH resources is widely recommended, there is limited evidence to guide engagement of Indigenous young people in these processes. This scoping review aims to examine the methods used to involve Indigenous young people in the development or evaluation of dMH interventions.Articles published in English, involving Indigenous young people (aged 10–24 years) in the development or evaluation of dMH interventions, originating from Australia, New Zealand, Canada and the USA will be eligible for inclusion. PubMed, Scopus and EBSCOhost databases  will be searched to identify eligible articles (from January 1990 onwards). Infomit and Google Scholar (limited to 200 results) will be searched for grey literature. Two reviewers will independently screen citations, abstracts and full-text articles. Study methods, methodologies, dMH intervention details, participant information and engagement, and dissemination methods will be extracted, analysed , and qualitatively assessed for alignment with best practice ethical guidelines for undertaking Indigenous health research. A narrative summary of findings will be presented. Reporting will follow the Consolidated Criteria for Strengthening Reporting of Health Research involving Indigenous peoples (CONSIDER) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines.To date, there are no reviews which analyse engagement of Indigenous young people in the development and evaluation of dMH interventions. This review will appraise alignment of current practice with best practice guidelines to inform future research. It will highlight appropriate methods for the engagement of young people in study processes, providing guidance for health practitioners, policy makers, and researchers working in the field of Indigenous youth and dMH.osf.io/2nkc6).Open Science Framework (The online version contains supplementary material available at 10.1186/s13643-021-01685-7. The majority of Indigenous young people worldwide are resilient, proud of their culture, and possess social capital beyond any other recent generation –3. DespidMH is identified as “mental health, suicide prevention and alcohol and other drugs services delivered via a digital platform” . There rDespite widespread recognition of the importance of end-user involvement in the development and evaluation of dMH interventions , 20, 21,Furthermore, ethical guidelines on the conduct of research with Indigenous communities emphasise the importance of cultural considerations when engaging Indigenous people in research practices –29. MostInternational research has identified strengths unique to Indigenous young people which help build and maintain resilience , 35. StrScoping reviews are particularly useful in providing an overview of research on a given topic where evidence is emerging  and to rThis scoping review protocol is being reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement , observational studies , quasi-experimental studies and qualitative studies. Systematic reviews, meta-analyses, opinion pieces and narrative reviews will be excluded.Studies involving Indigenous young people, originating from Australia , New Zealand (Maori), Canada  and the USA (First Nations people) are eligible for inclusion. Indigenous people in these developed first world countries have experiences of colonisation, persistent health inequities and notable rural and remote residence. In addition, Indigenous people’s health worldviews, language and cultural needs differ from mainstream populations. Young people, for the purposes of this review, refer to those who are aged 10−24 years, representative of a broader definition of adolescence, as described by Sawyer et al. .dMH services are identified as “mental health, suicide prevention and alcohol and other drugs services delivered via a digital platform”, which include the “provision of information, digital counselling services, treatment services  and peer-to-peer support services” . Some exThere are two broad categories of outcomes that are of interest: (1) study methodology and methods and (2) alignment of methods with relevant ethical guidelines. Specifically, methods will be assessed in terms of accessible, clear and co-constructed benefits to the community or individual; meaningful relationships, consultation and participation of Indigenous people within all stages of research processes; respect and recognition of Indigenous knowledge and practices and Indigenous self-determination and governance –30.Following recommendations by Joanna Briggs Institute, a three-step search process will be used. First, two independent reviewers  will undertake a limited search of the databases (EBSCOhost and PubMed). Search terms for EBSCOhost database are included in supplementary file First, the titles and abstracts of articles returned from initial searches will be screened based on the eligibility criteria outlined above. Two reviewers  will independently review a 10−15% subset of the complete set of search results to establish a good inter-rating agreement (defined as kappa of 0.81 or above). Once good inter-rater reliability is established, one reviewer (JP) will then continue to screen the rest of the articles before proceeding to full-text review. The same procedure will be carried out for the second screening stage using full texts. In the third stage, references of all considered articles will be hand-searched to identify any relevant studies missed in the search strategy. Any disagreements will be resolved by discussion to meet a consensus, if necessary. If consensus is not reached throughout each stage of study selection, a third reviewer (MT) will review the articles in question. A flow chart showing details of studies included and excluded at each stage of the study selection process will be provided .Data extraction variables, outlined in Table Relevant references will be exported into Endnote X9, including full text. Endnote X9 allows reviewers to collaboratively manage duplicates, group and code references and add annotations and notes. Data will be grouped by dMH intervention attributes, study design and alignment with research best practice and synthesised in table format. Qualitative content analysis will be undertaken . RevisioEmerging themes will be documented and used to facilitate discussion with two Senior Indigenous Research Officers (PPJRM) on at least three occasions, and written notes will be taken during consultation meetings . DiscussThis scoping review aims to provide a comprehensive overview of current methods described in the literature regarding the involvement of Indigenous young people in development or evaluation of dMH interventions. The systematic nature of this review will ensure all relevant information on study methods is captured. Findings will provide insight into how methods align with best practice guidelines for the involvement of Indigenous people in ethical research and will inform recommendations for future projects aiming to develop or evaluate dMH interventions with Indigenous young people. As the design and use of dMH with Indigenous populations is an emerging field, potential limitations may be the small number of studies reported in the peer-reviewed literature as well as variations in study design and rigour. Therefore, broad definitions of inclusion terms will be used and the identification of relevant grey literature will expand data sources, allowing the identification of evidence gaps.The findings from this review will assist researchers, clinicians and technology developers through establishing best practice processes for engagement of Indigenous young people in dMH approaches as well as for health research more broadly. As no other review has previously examined processes of development or evaluation in depth, this review aims to assist researchers to determine the ‘how’ of research design and develop clear methodology for respectful and culturally safe engagement with Indigenous young people.Additional file 1. PRISMA-P 2015 Checklist.Additional file 2. Search terms.


To describe the quality and completeness of the description and reporting of physical activity and exercise interventions delivered to young people to promote mental health or treat mental illness.We conducted a series of scoping reviews identifying 64 controlled trials of physical activity and exercise interventions delivered to young people. We extracted: intervention characteristics, personnel and delivery format, the intensity, duration, frequency and type of physical activity or exercise.There was limited reporting of intervention details across studies; 52% did not provide information to confidently assess intervention intensity, 29% did not state who delivered the intervention, and 44% did not specify the intervention delivery format.We recommend that authors adhere to the CONSORT reporting requirements and its intervention reporting extensions, (a) the Template for Intervention Description and Replication, (b) Consensus for Exercise Reporting Template and (c) as part of this, detail the frequency, intensity, time and type of physical activity recommendations and prescriptions. Without this, future trials are unable to replicate and extend previous work to support or disconfirm existing knowledge, leading to research waste and diminishing translation and implementation potential. Title/abstract and then full text screening were independently undertaken by at least two authors. Data charting . Full texts were independently reviewed by two authors . There were no conflicts. Data charting  and subjective (ratings of perceived exertion) measures of exercise intensity, and classified intervention intensity for aerobic  and subjective (ratings of perceived exertion) measures of exercise intensity  did not state who delivered the intervention; 28 (44%) did not specify if the intervention was delivered in a group or individual format; 9 (14%) did not report the intervention dose as defined by both duration and frequency.4This report highlights an important limitation in the literature and a need for better specification and clearer reporting of physical activity interventions for mental health promotion and treatment for youth.Many existing studies have failed to specify intervention intensity and delivery format. This has limited the interpretation and application of the evidence base for physical activity/exercise as a treatment for mental illness or mental health promotion strategy. It is clear from our scoping reviews, and previous research, that a variety of modalities and intensities may produce positive effects, and that factors such as delivery in group or individual formats may potentially explain some of the positive effects seen in physical activity/exercise interventions. However, due to poor reporting, it remains unclear if the intensity and the type of activity are important for mental health benefits. Therefore, although different intensities and different physical activity/exercise modalities may produce different effects on mental health outcomes, current poor reporting likely hinders efforts to identify which of these components, if any, are driving change. Better reporting in future studies will shed light on the role each plays on mental health outcomes and facilitate implementation in practice.Whether the type and intensity of the physical activity engaged in is prescribed or self‐selected also should be specified. Autonomy is proposed as one of three basic psychological needs fundamental to positive mental health .Although this guidance is not new, poor intervention reporting has important implications for the field today and into the future (Glasziou et al., The method of delivery also needs to better reported, including detailed information regarding who delivered the intervention and their level of training, the environment in which the intervention was delivered, if the interventions were self‐selected based on preference or prescribed, and delivered individually or in groups. Improved reporting of physical activity/exercise interventions could shed light on whether minimum dosages are required to improve mental health outcomes in young people, or whether interventions promoting messaging such as ‘move more, sit less’ and ‘more is probably better’ are sufficient (Teychenne et al., Michaela Pascoe, Alex Parker, Melinda Craike conducted the literature search; Michaela Pascoe designed the figures and tables; all authors contributed to study design; Michaela Pascoe, Alex Parker, Alan Bailey, Nigel Stepto, Rhiannon Patten, Timothy Carter contributed to data collection; Michaela Pascoe, Alex Parker, Alan Bailey, Nigel Stepto, Rhiannon Patten, Timothy Carter contributed to data analysis and data interpretation; All authors contributed to writing and reviewing the manuscript.


To date, the mHealth Research Core has held seven seminars, completed 71 case consultations, assisted four COVID-related clinical studies, advised the IRB on shifting to remote research, and widely disseminated eConsent navigation tools. Although pre-pandemic stakeholder and investigator needs led to the creation of the mHealth Research Core, this institutional resource played a critical role in continuing clinical research during the pandemic by assisting investigators in rapidly shifting to remote study methodology.COVID-19 has forced medical research institutions to conduct clinical research remotely. Here, we describe how a university’s mHealth Research Core helped facilitate the shift to remote research during the COVID-19 pandemic. In 2019 (pre-pandemic), we conducted stakeholder interviews and leadership group sessions to identify, create, and implement resources and core functions to support investigator-initiated mHealth research. Between April 2019 and February 2020, we identified four investigator needs: 1) a  The emergence of the smartphone   was an iPrior to the SARS-CoV-2/COVID-19 pandemic, the National Institutes of Health and the National Science Foundation had both prioritized a shift towards digital methods for conducting clinical studies – to achieve efficiencies and reduce costs, as well as to improve participant access and experience ,7.As the world emerges from the pandemic, the scientific community finds itself in a similar situation: after witnessing transformational achievements in medical science – made possible in large part by technology – how do we continue to nurture science through innovation ,9? RecogHere, we chronicle the pre-pandemic development of a mobile health  research core (mHRC) at a large US academic medical center by leveraging existing research infrastructure. We also discuss the critical role the mHRC played in aiding individual investigators, institutional leaders, and regulatory groups to address system-wide scientific and operational challenges to continuing research in a remote capacity throughout the COVID-19 pandemic.The mHRC at Washington University in St. Louis (WU) was formed in April of 2019. Leaders of the CTSA-supported Washington University Institute of Clinical and Translational Sciences (ICTS) approached the authors, based on the increasing need to support mHealth investigators in navigating institutional regulatory processes, and our experience which included launching the first fully remote clinical trial at the institution . With inAgile project management accelerates innovation by prioritizing transparency and adaptability, favoring flexibility and iterative project execution over fixed, sequential steps. This approach has been used to promote innovation in research and healthcare through human-centered design, embracing new insights from key stakeholders with early and iterative adaptation. The mHRC adapted an agile project management approach See Fig.  for deveTo better understand implementation needs and barriers, we convened an Advisory Committee of investigators and institutional leaders representing clinical informatics, computer science and engineering, implementation science, public health, and clinical disciplines in May 2019. The group established a set of core mHRC offerings to assist investigators, including providing 1) a seminar series to learn about new resources and trends in mHealth research, 2) case consultation to champion peer support and review of ideas, aims pages, manuscripts, and grant proposal, 3) liaison services between groups and University Departments to promote collaborative projects, and 4) online navigation tools to offer guidance for eConsent, virtual sessions, 3rd Party technology partnerships, and computerized systems in FDA regulated trials.Case Consultations: Tailored scientific, strategic, technological, and regulatory resources and guidance for emerging researcher needs .Seminar Series: Regularly occurring seminars featuring virtual talks and panel discussions with leading mHealth research and industry experts.Liaison Services: Intermediating among Barnes Jewish Hospital (BJH) and WU departments, centers, and institutions to promote innovation, reduce barriers, improve communication, and streamline process across mHealth projects .Library of Navigation Tools: A library of online navigation tools  to promote consistency and to prevent future researchers from reinventing the wheel.The advisory committee met every 6 weeks throughout the remainder of 2019 to review and address barriers to progress, as well as to discuss new developments and changes. Priorities were focused on developing the four core mHRC service offerings, as follows:In late March 2020, clinical research was completely shut down due to COVID-19. Coincidentally, on the day prior to this announcement, the mHRC had prescheduled one of the regularly occurring seminar series events. As a result, the mHRC devoted a portion of the seminar to a discussion of the imminent shutdown and the need to rapidly shift to fully remote research. This discussion was shared with regulatory leadership, such as the Institutional Review Board (IRB) and Human Research Protection Office (HRPO). To ensure timely and safe mHealth modifications related to COVID-19, the mHRC leadership worked jointly with the Office of Information Security and the IRB to standardize methods for implementing econsent. This collaboration resulted in the mHRC developing online navigation tools for a) creating IRB-approved electronic informed consent using Research Electronic Data Capture (REDCap) and b) conducting study visits using virtual and telehealth technologies. These navigation tools were shared widely in the Institution’s research community. By April 2020, the mHRC added consultation-based services to provide support for investigators transitioning to remote functions.In mid-March 2020, at the beginning of the pandemic, the mHRC anticipated likely “lockdowns” and research shutdowns based on the experience of University of Toronto during the 2003 SARS outbreak in that city . The mHRC recommendations to the university’s IRB included (1) more widespread acceptance of eConsent; (2) rapid turnaround of modifications for remote/contactless research methods; (3) acceptance of protocol deviations for shifts to remote methodology, including investigator reporting of these deviations as a brief statement at the time of renewal . One week after the research shutdown occurred, the IRB swiftly instituted all recommendations. Research involving human contact was paused, except essential services within certain clinical research. The rapid shift of both COVID-19 and non-COVID-19 research to remote “contactless” methods allowed for continuing existing studies during the pandemic ,18. At tIn March 2020, the first project to receive mHRC econsent consultation services swiftly launched a COVID-19 research study and biospecimen bank. The project went from the idea phase to study implementation within 2.5 weeks [A primary goal of this project was to embed the eConsent process into the study site  workflow while also reducing participant burden and establishing minimal risk of exposure for patients, frontline healthcare workers, and staff engaged in the eConsent process. mHRC consulting services helped achieve this by recommending a verbal (waiver of written) eConsent process, that could be implemented in an efficient and contactless way. During the eConsent process, participants could review and retain a paper copy or be emailed a link to the eConsent for review on their own device or a study-designated tablet in the clinical setting. The person obtaining consent would use the phone to implement the verbal consent process and answer participant questions using REDCap to capture the participant’s response to eConsent. This touchless consent method was approved for this minimal risk study by the IRB and set a precedent for future minimal risk COVID-19 studies using a verbal consent process. The mHRC replicated efforts across 4 additional COVID-19 studies – using either verbal eConsent or eSignature eConsent methods – within 2 months.Upon the successful launch of eConsent for COVID-19 clinical research, and due to the technical skill required in implementing eSignature eConsent using REDCap, the mHRC assisted research teams in building their eConsent data dictionary using the REDCap online designer tool  product, costs would be invested in licensing the product for use. SaaS products may be a reasonable option for many investigators with the goal of implementing research using technology.Third-party SaaS vendors may offer a variety of options from highly configurable platforms to more “off the shelf” (static) platforms. The mHRC developed the Technology Partnerships Navigation Tool to help investigators navigate conversations with 3rd party vendors to determine a partnership of good fit, including but not limited to intellectual property rights, regulatory compliance, and cost considerations.Healthy Bodies Healthy Minds (HBHM) is a multisite pilot clinical trial utilizing an adapted Interactive Obesity Treatment Approach (iOTA) ,27 for ord Party Technology vendor and utilized an adapted agile project management approach to help the study successfully launch and continue operations uninterrupted during the pandemic  product, making use of existing digital resources for eConsent (see Case 1), secure virtual video study visits and remotely training study interventionists.The initial mHRC core offerings were designed to achieve critical impacts for WU research, including but not limited to the following: (1) educate investigators on how to best implement mHealth tools and concepts in their research, (2) help research studies and research teams operate in a remote capacity, and (3) promote an infrastructure of support for investigators employing mHealth tools or testing mHealth interventions in their research. These critical impacts were achieved by the mHRC through the implementation of the mHRC core offerings, and implementation of an adapted agile project management approach to ensure investigators could rapidly shift to fully remote study operations, continue ongoing studies and start newly funded studies during the pandemic.Reflecting the academic nature of the work, we published preliminary observations and recommendations from the mHRC’s work, including continuing and even expanding clinical research via mHealth during the COVID-19 pandemic ,32. ThesThe mHRC will continue facilitating and accelerating new and ongoing research across clinical areas and departments at WU. To foster inter-institutional collaboration among mHealth researchers at CTSA institutions, a future direction of the mHRC is to generate a resource page on our website that lists mHealth researchers and their associated area of research and institution. Even as the pandemic recedes in the USA, remote research methodology is here to stay. We hope this description of the mHRC experience can serve as a roadmap for institutions facing what are likely to be universal needs at academic medical institutions: go-to resources for researchers across clinical areas looking to utilize digital tools in remote study methodology, the reduction of technical and regulatory delays, and the sharing of accumulating knowledge and experience within and between CTSA-supported academic institutions to achieve research aims and collaboration among mHealth researchers.


Clinical practice guidelines (CPGs) are key instruments to implement the practice of evidence-based medicine. We aimed to evaluate the methodological quality and variations in CPGs recommendations on the diagnosis and management of polycystic ovary syndrome (PCOS).We searched MEDLINE, EMBASE, and CENTRAL until December 2020 for all evidence-based CPGs and consensus statements on PCOS. We extracted data in duplicate to map clinical recommendations across prespecified disease domains and assessed CPGs methodological quality of using the Appraisal of Guidelines, Research & Evaluation II tool.We included 13 PCOS CPGs published between 2007 and 2018. CPGs recommendations were mostly focused on screening for and managing metabolic disease , followed by cardiovascular risk assessment . Mental health  and diagnosis in adolescents  were the least reported domains. Most CPGs had a high quality for scope and purpose description  while stakeholder’s involvement and applicability of recommendations to clinical practice were appropriate in only 2 CPGs . We identified inconsistency in recommendations on PCOS diagnosis in adolescents, optimal lifestyle interventions, hirsutism and acne treatments, interventions to reduce the risk of ovarian hyperstimulation syndrome, the frequency and screening criteria for metabolic and cardiovascular disease, and optimal screening tools for mental health illness in women with PCOS.Current CPGs on the diagnosis and management of PCOS vary in their scope and methodological quality, which may hinder evidence translation into clinical practice. We identified disease domains with existing evidence gap to guide future research and guideline updates. Polycystic ovary syndrome (PCOS) is the most common endocrine condition affecting women of reproductive age worldwide . It signAdopting the principles of evidence-based medicine (EBM) has stimulated research conduct and evidence synthesis on the diagnosis and management of PCOS over the past few decades . Still, Clinical practice guidelines (CPGs) and consensus statements are now primary tools to enable the practice of EBM and facilitate the implementation of evidence in everyday clinical practice . TraditiWe undertook a systematic review using a prospectively registered protocol (CRD42018116809) and reported in line with the PRISMA CPGs .We searched MEDLINE, EMBASE, and Cochrane CENTRAL databases within the NICE Healthcare Database Advanced Search platform (hdas.nice.org.uk) using the following search terms to identify eligible CPGs on PCOS from inception until December 2020: clinical, CPGs, consensus statement, position statement, recommendation?, polycystic ovary, polycystic ovary syndrome, hyperandrogen*, anovulation, *menorrhea, wom?n, female, pregnan*. Complementary searches were conducted in Google Scholar, Tripdatabase, and Scopus. We searched the websites of established regulatory bodies on the topic of care for women with PCOS to identify relevant CPGs. We did not apply any search filters or language limitations.Two independent reviewers (BHA and MF) completed the study selection and inclusion process in 2 stages. Discrepancies were resolved in consensus with a third reviewer (LB). We included all purpose-developed evidence-based clinical CPGs and consensus statements addressing the diagnosis and/or management of PCOS across different clinical disciplines and populations. We excluded position or opinion statements that did not make direct recommendations linked to specific evidence and systematic reviews from scientific societies. All other designs of primary or secondary studies evaluating a particular scientific question were excluded.Two independent reviewers (LB and MF) extracted data in duplicate into an electronic Excel sheet, which was piloted for its face validity. Data integrity was double-checked by a third reviewer (BHA). We extracted data on the following guideline characteristics: producing authority, named authors, country of origin, year of publication, consensus method, stakeholders involved, disease domain addressed in the CPG, description of the search strategy to identify evidence, inclusion/exclusion criteria of evidence, quality assessment instruments used, and grading system used. We mapped out the clinical recommendations in each guideline and tabulated them into the following prespecified domains: diagnosis in adolescents and adults; lifestyle interventions; management of menstrual irregularity, hirsutism, acne, and infertility; and risk assessment for metabolic disease, cardiovascular disease, mental health, and cancer.We used the AGREE II instrument  to assesWe calculated a total quality score for each guideline by adding the scores of the evaluated quality domains and standardizing them using a prescribed equation . We repoOur electronic search identified 575 titles and abstracts of which we screened 26 articles in full against our inclusion criteria and included a total of 5 national and 8 international PCOS CPGs (n = 13) .The majority of included CPGs were published within the last 10 years (range 2007-2018) and all but 1  were repThe median number of recommendations made per guideline was 26 (range 6-90). Screening for and managing metabolic disease was the most commonly covered disease domain in 12 CPGs  followed by recommendations on cardiovascular risk assessment . In contrast, management of mental health  and diagnosis in adolescents  were the least commonly addressed disease domains across the included CPGs .Our evaluation of CPGs’ quality using the AGREE II tool showed variations across the assessed domains with most CPGs offering high-quality scope and purpose description  as well as clarity in presentation . Stakeholder involvement and applicability of recommendation to clinical practice were poorly addressed by most CPGs with only 2 showing good quality for these domains  . There wMajority of CPGs focused on the different treatments of PCOS , risk assessment , and only 9 made recommendations on the diagnosis of PCOS  .For the diagnosis of PCOS in adults, 7 CPGs supported the use of the Rotterdam criteria  or its mTwo CPGs were particularly focused on the diagnosis and management of PCOS in adolescents ,19, and Nine CPGs recommended lifestyle treatments (LSTs) as first-line intervention in adolescents and adult women with PCOS ,25,27,28Six CPGs recommended the use of hormonal contraceptives as first-line of treatment for managing menstrual irregularity in adult women with PCOS ,19,21,25Only 5 CPGs made direct recommendations on treatments for hirsutism and acne with 3 CPGs recommending photoepilation and topical eflornithine as the first line of treatment ,19,25. B2) with PCOS  in overweight/obese women to optimize weight management, reduce insulin resistance, and minimize hyperandrogenism ,27,29,302 or in Asians > 23 kg/m2, central adiposity, substantial weight gain, increased waist circumference, symptoms of diabetes, family history of impaired glucose intolerance, type 2 diabetes, chronic hypertension or high-risk ethnicity, age > 40 years, personal history of gestational diabetes or high blood glucose level, use of antihypertensive medications, smoking, and physical inactivity (An oral glucose tolerance test was considered the gold standard to screen for impaired glucose intolerance and type 2 diabetes although there were variations on the recommended frequency of screening . More fractivity ,17,18,28activity ,21,25.Two CPGs recommended screening for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in women with insulin resistance and metabolic syndrome suggesting vitamin E as preferred treatment with specialist multidisciplinary team input ,25.Routine assessment for mental health and quality of life was supported in seven CPGs ,21,28 alAssessment of cardiovascular risk factors in women with PCOS was recommended in 8 CPGs using an array of risk factors including obesity especially increased abdominal adiposity, smoking, hypertension, dyslipidemia, subclinical vascular disease, impaired glucose tolerance, family history of premature cardiovascular disease, lack of physical activity, metabolic syndrome and type 2 diabetes, obstructive sleep apnea, high levels of CRP, and homocysteine ,21,28. OFive CPGs recommended routine screening for obstructive sleep apnea in women with PCOS by checking associated symptoms such as snoring, waking unrefreshed from sleep, and daytime sleepiness. All these CPGs considered a polysomnography test as the gold standard diagnostic test for obstructive sleep apnea ,19,21,28Routine screening for endometrial cancer was not recommended in women with PCOS in 3 CPGs ,21,25. TWe captured a high number of evidence-based CPGs produced over the last decade covering varied disease domains with a consistently increasing number of recommendations. Guideline quality was varied with poor stakeholders involvement and a substantial lack of clear implementation pathways.Reassuringly, most of the included CPGs recommended the use of homogenous PCOS diagnostic criteria. Still, there were variations in the recommended diagnostic reference ranges for biochemical hyperandrogenism and on the diagnostic value of anti-Müllerian hormone in adolescents with PCOS.Most CPGs recommended routine screening for cardiovascular and metabolic diseases in affected women; however, the recommended frequency of screening, measurement tools, and associated risk factors varied substantially . Mental Most of the included CPGs emphasized the importance of LST as the first-line treatment strategy for PCOS, although details on specific dietary regimes were lacking. Similarly, the role of anti-obesity medications and insulin sensitizers was varied across included CPGs. Few CPGs recommended particular treatments for hyperandrogenism that could be linked to the limitations of available evidence on this domain. Lastly, with a growing body of evidence on fertility treatments for women with PCOS, there were clearer recommendations on the treatment pathways for anovulation and subfertility. Variations existed on the role of letrozole as the primary ovulation induction agent; however, this is unsurprising giving the evolution of evidence on its effectiveness and safety over the last decade. There was limited guidance about the optimal ovarian stimulation protocols and adjuvant treatments to reduce the risk of ovarian hyperstimulation syndrome in women with PCOS.To our knowledge, our review is the first to evaluate the quality of all available evidence-based CPGs and consensus statements regarding the diagnosis and management of PCOS. We followed an established methodology to systematically review the literature and applied the AGREE II tool to assess guideline quality. Lastly, we mapped out CPGs recommendations to identify underrepresented disease domains and topics of uncertainty to aid future research conduct.Our analysis has a few limitations. The use of the AGREE II tool is relatively recent and older CPGs may not have adopted recently developed standards, which may skew our findings. Specifically, the practice of involving stakeholders, including lay consumers, in CPGs development as well as active guideline implementation in clinical practice is relatively new and usually absent in older CPGs. We aimed to provide a systematic assessment of current literature to illustrate the improvement in guideline quality over time. Interestingly, we did not detect a correlation between guideline quality and year of publication.We were unable to assess the quality and confidence in linked evidence to guideline recommendations as different evidence grading systems were used. This limited our ability to provide an in-depth analysis of the current evidence gap. The poor quality of available primary studies on PCOS is often reported as a source of heterogeneity and imprecision in published CPGs . RecogniPCOS is uniquely expressed as a multisystemic condition often with varied phenotypes across affected women . To addrAs more treatment options become available to address the different aspects of PCOS, there is a need to continuously update available CPGs as well as efficient data collection to enable large scale evidence synthesis and optimize the practice of EBM. This was particularly evident in this review with the limited scope of recommendations made on certain treatments such as the use of different contraceptives for the management of hirsutism and acne in PCOS . SimilarCurrent CPGs on the diagnosis and management of PCOS vary in their scope and methodological quality which may hinder evidence translation into clinical practice. We identified disease domains with existing evidence gap to guide future research and guideline updates.


Certified nursing assistants (CNAs) who care for vulnerable nursing home residents faced unprecedented circumstances due to the COVID-19 pandemic. While staff and PPE shortages were ubiquitous and widely known, the focus of this qualitative work was to gain a broader understanding of the numerous challenges they faced. We conducted 10 remote focus groups with CNAs at 5 nursing homes (N=56) in downstate New York. Content analysis was conducted, and emerging themes identified. Results showed a myriad of emotional challenges including helplessness, fear and anxiety. Operational challenges focused on lack of COVID testing capacity, information, and consistent guidance and support, in addition to staff and equipment. Individual challenges included personal experience of COVID illness and that of colleagues, and balancing high concurrent demands of work and family. These results are discussed in the context of developing recommendations to promote future safety, skill refinement and enhanced resilience in the workforce moving forward.


Group care models, in which patients with similar health conditions receive medical services in a shared appointment, have increasingly been adopted in a variety of health care settings. Applying the Triple Aim framework, we examined the potential of group medical care to optimize health system performance through improved patient experience, better health outcomes, and the reduced cost of health care. A systematic review of English language articles was conducted using the Cochrane Controlled Trials Register (CENTRAL), MEDLINE/PubMed, Scopus, and Embase. Studies based on data from randomized control trials (RCTs) conducted in the US and analyzed using an intent-to-treat approach to test the effect of group visits versus standard individual care on at least one Triple Aim domain were included. Thirty-one studies met the inclusion criteria. These studies focused on pregnancy (n = 9), diabetes (n = 15), and other chronic health conditions (n = 7). Compared with individual care, group visits have the potential to improve patient experience, health outcomes, and costs for a diversity of health conditions. Although findings varied between studies, no adverse effects were associated with group health care delivery in these randomized controlled trials. Group care models may contribute to quality improvements, better health outcomes, and lower costs for select health conditions. Group care models, in which patients with similar health conditions receive medical services in a shared appointment, have increasingly been adopted in a variety of health care settings in the United States (US) due to their potential to enhance health care value . While aDesignated as a way to reinvent health care service delivery , this paSystematic reviews have demonstrated group visits to be as good as standard individual care, and in some cases, better at improving health outcomes for specific conditions such as diabetes , cardiacFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol , we condThe included studies used data from RCTs conducted in the US, were analyzed with an intent-to-treat approach to test the effect of group visits versus standard individual care, and included outcome variables related to at least one of the following Triple Aim dimensions: (1) patient experience, measured by patient satisfaction, adequacy and comprehensiveness of care, and perceived health status and quality of life; (2) health outcomes, measured by clinical outcomes and health behaviors; and (3) cost, measured by health care expenditures and additional service utilization  . No restThree authors independently screened citation titles, index terms, and abstracts to identify relevant articles for full-text review. Differences in assessment were resolved by discussion and reexamination until a consensus was achieved.We initially identified 1749 articles of interest and reviewed the full text of 114 articles. Thirty-one were included in the final review . These sThe two studies that assessed patient experience among pregnant women documented increased satisfaction with care among group visit patients compared to those in individual care. Kennedy et al. additionally found the women in group care were almost six times more likely to receive adequate prenatal care, based on the Adequacy of Prenatal Care Utilization Index , and felSome studies of patients with chronic health conditions also document higher levels of satisfaction with group versus individual care ,22. BeckSeveral studies suggest group visit patients may receive more comprehensive care. Compared to individual care, patients in group care were more likely to have had referrals for American Diabetes Association (ADA) process-of-care indicators . VaughanPerceived health status and quality of life are important aspects of patient experience. Berry et al. reported that group visit patients felt their health improved more than individual care patients , whereasCompared to standard individual care, group visits have been associated with reduced rates of preterm birth , low birNotably, Ickovics et al. documented a 33% risk reduction in preterm birth among adolescents in group care compared to those in individual care, and a 41% reduction among African American women, but found no differences for birth weight . The resSix studies found significant decreases in HbA1c levels and guideline concordance for target HbA1C for group visit patients compared to those randomized to individual care ,38,39,40Four studies examined blood glucose monitoring: two reported improvements among group visit patients compared to those in individual care ,39 and tThe findings from RCTs suggest the health outcomes and behaviors for individual and group care patients with chronic health conditions other than diabetes are largely equivocal. Beck et al. found no difference between the study arms for depressive symptoms, mobility, or functional status . LikewisOnly one study compared the costs associated with group prenatal care and standard individual care, finding no differences . Three sCompared to individual care, cost savings have been associated with group visits for the management of chronic health conditions ,30,48. CFive RCTs documented reduced emergency department utilization for patients randomized to group versus individual care ,23,42,49The findings from this systematic review of randomized controlled trials from 1974 to January 2021 contribute to the growing evidence base justifying investments in the scaling-up of group care models. Compared with individual care, group visits have the potential to improve patient experience, outcomes, and costs for a diverse range of health conditions. Although the findings between the studies varied regarding the extent to which group care leads to improvements in each Triple Aim domain, it is important to note that there were no adverse effects associated with group care.The implementation of group care models is not without challenges. The reasons that patients may not elect to participate in group care include scheduling conflicts, childcare issues, lack of transportation, privacy concerns, and a strong personal relationship with a specific non-participating provider . PrepariThis review has limitations. We limited this review to results from randomized controlled trials. Some inconsistent findings may be attributable to the heterogeneity between the studies. Those with small sample sizes may not have had sufficient power to detect differences between the study arms. Some studies were conducted in specific populations or sub-populations, thus may have limited generalizability. Moreover, some clinical outcomes may require a longer follow-up to document improvements. We also acknowledge that studies with no significant differences between conditions are less likely to have been published. Future reviews should report outcomes with more rigorous criteria, using tools such as the STROBE checklist and the procedure for the meta-aggregation of data in the Joanna Briggs Institute guidelines for systematic reviews of qualitative studies ,52. NoneThe US spends significantly more on health care than other high-income countries yet experiences worse population health outcomes. Group care models may contribute to meeting the Triple Aim for select health conditions. Health systems and payors should consider ways to incentivize the transformation of care to enable further exploration of group care models, as these often require some level of system redesign to implement successfully. Unlike those in many other countries, the US health care system is largely structured such that health care delivery and financing are entirely separate. New levels of cooperation are needed to incentivize innovations that will meet all three dimensions of the Triple Aim. Future research should further explore the characteristics of effective models of group care and how to address the adoption barriers among patients, providers, and health systems.


PathMaker is a regional, competitive pipeline program that nurtures high school or undergraduate trainees from historically underrepresented backgrounds towards a career in cancer research. Our faculty and staff team collaboratively developed a cohort model curriculum that increased student awareness of research career options; provided academic and professional development, cultural and social support, evolutionary success strategies, active mentorship, and leadership skill development; and fostered an environment of continuous evaluation and improvement. Since pilot program initiation in May 2016, the PathMaker Research Program (PathMaker) has engaged a total of 44 underrepresented trainees in cancer research labs at Huntsman Cancer Institute, the majority still in college. Eleven trainees graduated college: five employed in STEM, one pursuing a PhD in STEM; two in medical school, and three are lost to follow-up. Alumni report high levels of satisfaction with PathMaker and will be followed and supported for academic success. PathMaker is a replicable model to increase diversity and inclusion in the biomedical cancer research workforce.Given the well-documented inequities in health care outcomes by race, ethnicity, and gender, many health career pipeline programs have focused on supporting the development of a diverse and inclusive workforce. The State of Utah, is vast, but sparsely populated outside the Salt Lake City metropolitan area. More than 96% of our nearly 85,000 square miles is designated rural (<100 people/square mile) or frontier (<7 people/square mile). The Salt Lake City area is home to the Hunsman Cancer Institute, the only NCI-designated Comprehensive Cancer Center in the region, also noted the limited diversity in the biomedical cancer research workforce. Our primary objective was to increase the number of underrepresented trainees who pursue higher education with the goal of a career in cancer research.  The drop in historically underrepresented students (HUS) on the path towards becoming independent scientists has been well-documented ,2. In 20The Mountain West region, the catchment area for Huntsman Cancer Institute (HCI), encompasses the five-state area of Utah, Wyoming, Montana, Idaho, and Nevada and includes federally recognized American Indian Nations, rural and frontier populations, and an increasingly diverse population. For exaPrograms to enhance the diversity of the clinical health care and research workforce  may begiPathMaker Research Program (PathMaker) seeks to increase the number HUS pursuing biomedical cancer research. It was our hypothesis that a residential research experience in a supportive environment that included co-curricular experiences and ongoing engagement and support would be most likely to yield success. Co-curricular experiences included cultural and social support, mentorship, and leadership skill development. Our collaboratively developed multi-faceted cohort curriculum (Please see PathMaker is funded by a Supplement to the Cancer Center Support Grant (3P30CA042014-27S6) and receives the highest level of support from HCI. PathMaker leadership includes a senior HCI faculty leader as Program Director, a Program Coordinator, and a broad-based advisory committee that supports Cancer Training and Career Enhancement programs at HCI. The success of the PathMaker experience has resulted in a successful R25 application (1R25CA240171-01).The This paper outlines the program components, presents five-year outcomes and lessons learned, and addresses future considerations to support the success of HUS entering careers in biomedical cancer research.PathMaker is a residential summer program based at HCI, University of Utah Health (UUH). Initially funded as a one-year pilot program through the Office of Health Equity and Inclusion (UUH), extramural competitive funding was successfully achieved for the subsequent years through the National Cancer Institute’s Continuing Umbrella of Research Experiences (CURE) Supplement. PathMaker focuses on the transition between high school and college and provides incoming HUS (high school seniors and undergraduates) with an enriching cancer research experience; academic, professional, cultural, and social support; mentorship; and leadership skill development. Social support includes extensive peer networking and family engagement.Recruitment: PathMaker uses email, web, social media (Facebook and Twitter), and engagement with diversity-focused organizations to recruit trainees from high schools and colleges in the Mountain West. Word of mouth referrals by prior participants and community partners has also contributed to successful recruitment. Regional recruitment includes outreach through an existing extramurally funded regional partnership, the Geographic Management of Cancer Health Disparities Program . PathMaker also partners with diversity focused organizations that support HUS’s success in higher education. These included regional university organizations: TRiO and Upward Bound Programs, Latinos in Action, and the Black Student Union; university chapters of the Society for the Advancement of Chicanos and American Indians in Science (SACNAS); and the Utah State Board of Education Title VI: American Indian Education Program. High school outreach engaged high school advisors, educators, and every high school principal in the state.Application and selection process: Applicants must have completed their junior year of high school prior to participating in the program and must demonstrate an interest in health sciences. Completed applications include demographic factors: race/ethnicity, self-identified gender, age, current school, home zip code, and parents’ educational attainment. Applicants submit a 1–2 page personal statement, copy of their most recent transcript, and two letters of recommendation. Letters of recommendations may be from an employer, tribal leader, or mentor, and from a teacher. A copy of the most recent tax return is required if the student seeks consideration based on economic disadvantage. All application materials are submitted electronically to the PathMaker Program Coordinator. Incomplete applications are not reviewed.PathMaker Selection Committee. The PathMaker Selection Committee is diverse and inclusive of Black, Latinx, American Indian, Pacific Islander, LGBTQIA+, Asian, and non-Latinx, white members and represent multiple stakeholders across UUH. Members review and score each application using a standard scoring sheet. Review criteria include academic accomplishments; HUS identity; economic, social, or educational disadvantage; personal statement; and letters of recommendation. After all scores are entered, compiled and averaged, the selection committee meets to discuss and review the top-ranking applicants. In general, eight trainees are selected with three alternates.All applications are reviewed by the Student Peer Mentors: The Selection Committee also reviews applications for Student Peer Mentors (SPMs). Two SPMs are hired each year. The SPMs live with the PathMaker trainees in residential housing on-campus. As SPMs they serve as residential advisors, facilitators, and overall guides to the undergraduate experience. SPMs are generally senior level undergraduate students at the UU who have previously lived on campus as a residential advisor. SPMs complete the UU Youth Protection Training course prior to the PathMaker trainees’ arrival on campus. The SPMs work closely with the PathMaker Program Coordinator to manage all day-to-day aspects of the experience. They attend all educational activities with the cohort.Mentors: PathMaker mentors are HCI investigators whose research focuses on cancer aspects related to the basic, clinical, or population sciences. HCI principal investigators (PIs) are invited to participate as a mentor for PathMaker. Mentors are invited to a Mentor Orientation prior to the start of the PathMaker residential experience. Throughout the program, there is close communication between the Program Director, the Program Coordinator, the Student Peer Mentor, and the mentor. Formal, face-to-face student evaluation takes place at week 4 and upon program completion. In total, 27 HCI investigators have participated in PathMaker: 11 (40%) have participated with more than one cohort of trainees; 16 (59%) female, 11 (41%) male; 20 white, non-Latinx (74%), 3 Latinx (11%), and 4 Asian (15%).The Summer Experience: Upon enrollment, trainees receive a UU identification card which welcomes them and facilitates access to UU resources. The trainees, SPMs, and Program Coordinator communicate regularly using a mobile application called GroupMe, which allows for real-time group or individual conversations.PathMaker residential start date. At that time, the trainees meet the PathMaker Program team and participating mentoring research labs. After the welcome reception, trainees submit their top three lab choices to the PathMaker Program Coordinator.Upon acceptance, trainees receive a booklet of the HCI research labs with information about the participating research teams. All trainees and their families are invited to a welcome reception held the week prior to the PathMaker trainee to lab safety, basic lab techniques, and population research tools that they are likely to encounter during their research experience. The training is experiential in nature. All trainees complete HIPAA and CITI training. Additional trainings may also be offered depending on the work in the lab.The lab-intensive training course orients the Trainees participate in weekly educational and social activities which are intended to bring the cohort together, expose them to various career paths and resources, and develop their professional skills and resiliency see .Table 2.PathMaker is well integrated with other residential summer programs, e.g., Native American Research Internship (NARI), the Genomics Summer Research Internship for Minorities (GSRM), and Summer Program for Undergraduate Research (SPUR). Both NARI and GSRM focus on providing research experiences for trainees traditionally underepresesented in biomedical research. PathMaker, NARI, GSRM and SPUR collaborate on weekly events in order to build a larger community for the summer research trainees.PathMaker cohort meets weekly to reflect, debrief, and share successes and setbacks. These sessions are facilitated by the SPMs who offer reflective and motivational listening, share experiences, and offer the trainees support and guidance.The PathMaker trainees presenting their research posters at the annual Summer Symposium for Undergraduate Research sponsored by the UU Office of Undergraduate Research. The Symposium provides the trainees with the opportunity to engage with all UU PIs, trainees, and trainees engaged in summer research experiences and generally hosts more than 100 posters. The poster presentations are followed by an Honoring Ceremony for trainees, families, and friends. The ceremony includes a ‘graduation’ with certificate presentation, reception, group photo, and delivery of a digital Yearbook that includes a record of their experiences along with an individual research page with their poster.The summer experience concludes with Impact Assessment: PathMaker outcomes include program satisfaction; undergraduate retention and completion; academic accomplishments including scholarship awards; and progress on the path to pursue a biomedical cancer research career. For high school trainees, additional outcomes include high school completion and undergraduate acceptance. Our program outcomes assessment was reviewed by the UU Institutional Review Board and was deemed to be exempt.PathMaker changed or shaped your career or educational path. NVivo software was used to code open-ended responses. An inductive thematic analysis process of open coding, axial coding, and selective coding was used to identify themes in the responses[Participants completed ongoing concurrent programmatic assessments during the experience. They also received a follow-up survey. This survey asked a single question: How has responses. EmerginPathMaker data are entered into a de-identified database. PathMaker staff maintain ongoing engagement with the trainees through email correspondence, social media , and monthly newsletters. This post-experience engagement allows for ongoing support, opportunities for future work , reunion experiences, and informal mentorship opportunities across cohorts. These interactions maintain current contact information; educational progress, recommendation requests; accomplishments and honors; and current research activities. These outcomes may be correlated with demographics; cohort year and program dates; mentor name (grant title and number); high school; and college. University acceptance status – including multiple acceptances, scholarship award data, and post-graduation activities were obtained by a post-summer experience completion survey through email, LinkedIn profile, or follow-up text to individual PathMaker participants. All trainees set up an eRA Commons ID and are added to the NIH CareerTrac System where trainee outcomes are supported throughout their career.All Matriculation: PathMaker admission is competitive. PathMaker trainees are more diverse than the overall UU student population (Most trainees enrolled at the UU (31 of 43). pulation : Black  though Harvard and MIT. The BSRP is a highly competitive research program designed for trainees to pursue genomics-based research. After graduating, one trainee accepted a full-time research positon at the Broad Institute. Trainees have successfully obtained scholarships and have demonstrated that they are competitive applicants to nationally recognized colleges.Of the 43 alumni (1 trainee left the program within days of starting and has been lost to follow-up), 32 are enrolled an undergraduate program: 1 community college, 23 UU, 8 other undergraduate program (3 in programs ranked in the top 15 in the US). Eleven have completed their undergraduate degrees: five are employed in STEM; one is pursuing a PhD in STEM; two are in medical school, and three have been lost to follow-up.PathMaker trainees are contributing to the diversity of the biomedical workforce as they uniformly identify as HUS in the biomedical sciences as outlined above. All accepted incoming high school seniors have completed high school and are enrolled in college. Of those who have declared a major, 77% are pursuing a STEM major. Of those who have graduated college, all, with known current status, are engaged in a career in science or are pursuing ongoing education towards a career in science.PathMaker research experience within a supportive environment, one with the opportunity to build confidence, connect with mentors, and identify the intersection of interests with career opportunities, may bolster outcomes. The value of mentoring and an authentic research experience is a common theme in the undergraduate research literature[Qualitative data support our hypothesis that embedding the iterature. Findingiterature.Making Connections as a thread that spanned all themes. Linn et al. (2015) contend that STEM trainees need to have an authentic research experience but also experience the context of research and practice[PathMaker trainees had a research experience within a rich contextual environment that facilitated their ability to make explicit the connections between their new knowledge, their research experience, and their future career aspirations. PathMaker is an example of a high impact intervention that engages trainees in the act of learning and helps them make connections[Our data demonstrate the theme of  practice. Mentorinnections.PathMaker’s success has fueled the development of new opportunities to support the development of HUS in biomedical cancer research. HCI launched a two-week summer research program in Summer 2019 for rural high school trainees who had not completed their junior year. This residential program allowed the partnering of a younger student with a PathMaker trainee for a peer mentoring experience. The experience took place during the last two weeks of the PathMaker program. The rural high school student shadowed their partner PathMaker trainee in the research lab, attended the educational sessions, and supported the PathMaker trainee at the final poster symposium. We anticipate that this program will create a natural entry point for the rural trainees to enter the PathMaker program and expect several applications for the subsequent summer PathMaker program.PathMaker served as the cornerstone for our successful PathMaker Programs for Cancer Research application funded through the National Cancer Institute (NCI) Youth Enjoy Science Research Education Program (YES R25) (1R25CA240171-01) to HCI in September 2019. This award will fund 14 PathMaker Scholar trainees for two consecutive summers, a teacher education component, PathMaker Bridge, and a middle school educational outreach component, PathMaker Connect.Our experience with PathMaker has served as a formative experience for its alumni. We do not contend that PathMaker is the one experience that is singularly responsible for a student’s success nor that there is only road to success. It is not our goal to demonstrate causality. We consider success to be the result of multiple, and likely, a matrix of factors. Our goal is to provide students interested in science with experiences within a supportive environment where they can continue to grow and thrive towards their stated goal. PathMaker is early in its history. It has demonstrated success. We share our approach as it is replicable and can be tailored to your own community. Our trainees have found it valuable, and it has served as a foundation for additional funded interventions to support the diversity of the biomedical research workforce. We will continue to follow our cohorts. We will continue to support our mentees, and we look forward to learning and sharing their ongoing path making success in future reports.


The Acute Respiratory Distress Syndrome (ARDS) has caused innumerable deaths worldwide since its initial description over five decades ago. Population-based estimates of ARDS vary from 1 to 86 cases per 100,000, with the highest rates reported in Australia and the United States. This syndrome is characterised by a breakdown of the pulmonary alveolo-epithelial barrier with subsequent severe hypoxaemia and disturbances in pulmonary mechanics. The underlying pathophysiology of this syndrome is a severe inflammatory reaction and associated local and systemic coagulation dysfunction that leads to pulmonary and systemic damage, ultimately causing death in up to 40% of patients. Since inflammation and coagulation are inextricably linked throughout evolution, it is biological folly to assess the two systems in isolation when investigating the underlying molecular mechanisms of coagulation dysfunction in ARDS. Although the body possesses potent endogenous systems to regulate coagulation, these become dysregulated and no longer optimally functional during the acute phase of ARDS, further perpetuating coagulation, inflammation and cell damage. The inflammatory ARDS subphenotypes address inflammatory differences but neglect the equally important coagulation pathway. A holistic understanding of this syndrome and its subphenotypes will improve our understanding of underlying mechanisms that then drive translation into diagnostic testing, treatments, and improve patient outcomes. Acute Respiratory Distress Syndrome (ARDS) is a critical respiratory syndrome plagued by severe hypoxaemia and loss of pulmonary function . Five deARDS pathophysiology is characterised by dysregulated inflammation and associated coagulation dysfunction which can result in multisystem organ failure. In particular, ARDS severely affects the lungs leading to severe tissue damage, flooding of alveoli with proteinaceous fluid, decreased pulmonary function , and ultIn recent years, several retrospective landmark analyses have proven the presence of two inflammatory ARDS subphenotypes, differentiated by inflammatory markers, and biological and physiological parameters –11. Thus2/FiO2 ratio (PF ratio) which correlates closely with mortality , thrombomodulin (TM) and antithrombin (AT)] are designed to regulate the balance between coagulation and anti- coagulation within the body and its detrimental effects . ConsequAn important regulator of endogenous anticoagulant function and a mediator between inflammation and coagulation comes from a family of G-coupled protein receptors known as Protease Activated Receptors (PARs) , 30. WheThere are three main potent endogenous anticoagulant systems that occur to prevent unregulated coagulation and, to some degree, inflammation in patients . The mulPC circulates in healthy individuals as an inactive zymogen and is modified to Activated Protein C (APC) in the presence of TM and Thrombin. APC has potent anticoagulant effects as a result of proteolytic degradation of fV and fVIII . In addiTM, a transmembrane endothelial protein, is a potent anticoagulant that binds and alters thrombin's function from procoagulant and pro-inflammatory to an anticoagulant and anti-inflammatory state , 48, actA small portion of TM exists in a soluble form (sTM) in plasma, around 3–50 ng/mL under normal conditions . sTM is The human recombinant soluble form of TM (rTM), comprising of the ectodomain of TM has been shown to improve the PF ratio, and reduce ICU stays, as well as the in-hospital and 90-day mortality rates  in ARDS 2 formation leading to impairment of cytokine production, activation of leukocytes, and contributes to inhibition of platelet aggregation  indicate that biological patterns arise within the diverse ARDS population. These retrospective analyses have identified two distinct subgroups, named the hypoinflammatory (P1) and the hyperinflammatory subphenotype (P2), according to distinct functional and biological parameters , 18, 19.When examining the limited coagulation parameters available for these subphenotypes, analysis shows that PAI-1 and von Willebrand Factor (vWF) are consistently elevated in P2 patients, while PC and platelets are decreased in P2 patients as compared to P1 patients –10. The The impact of reduced levels of circulating endogenous anticoagulants  in ARDS patients appears to have a significant impact in the pathophysiology of this syndrome , 67, 68.The consistent identification of differentially expressed parameters of coagulation between the P2 and P1 among the 6 cohorts and the known close relationship between inflammation and coagulation leads to the assumption that the coagulation profiles are indeed different between the ARDS subphenotypes. Further research into classifying the differences in coagulation profiles of these two inflammatory subphenotypes holds potential to show a deeper understanding of the underlying mechanisms driving the subphenotypes, but also may lead to biomarkers for diagnostics and monitoring, as well as targeted anticoagulant treatment tailored to each patient. The treatment of phenotypes of diseases has been an emerging and promising field in cancer, asthma and sepsis to name a few . Rather ARDS is a critical and debilitating disease, plagued by dysregulated inflammation and coagulation. These abnormalities drive the formation of vascular thrombi and subsequent organ damage, contributing to the high mortality rates of ARDS. Having a greater understanding of how coagulation dysfunction varies in the two ARDS subphenotypes, and how this can be targeted is of great value in creating a holistic understanding and pinpointing therapeutic targets. Future directions should focus on phenotypical subpopulations of ARDS and reducing heterogeneity within patient cohorts which will help increase the likelihood of successful outcomes in treatment trials.SL and KW wrote and prepared the manuscript for publication. AU, HD, GL, JS, JF, KK, and MP assisted in reviewing and preparing the manuscript for publication. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Understanding Society databases. In unadjusted models testing the likelihood of reporting psychological distress (i) comparing against a white (British) reference population Indian, Pakistani, Bangladeshi and mixed ethnic minority groups recorded excess levels of distress; and (ii) increasing levels of social capital recorded a strong protective effect . In a subsequent series of gender-specific incremental logistic models-after adjustment for sociodemographic and socioeconomic factors Pakistani  and Indian females recorded higher likelihoods of psychological distress, and the further inclusion of social capital in these models did not materially alter these results. More research on the definition, measurement and distribution of social capital as applies to ethnic minority groups in Great Britain, and how it influences mental wellbeing is needed.Black and minority ethnic communities are at higher risk of mental health problems. We explore differences in mental health and the influence of social capital among ethnic minority groups in Great Britain. Cross-sectional linear and logistic regression analysis of data from Wave 6 (2014–2016) of the  Black and minority ethnic (BME) communities appear to be at a greater risk of psychosis compared to the white UK-born population –3 and raSocial capital refers to those potentially positive aspects of social life and is constructed through shared networks, norms, and trust. It enables a more effective pursuit of shared objectives  and is cWhile there is no real consensus on the relationship between social capital and mental wellbeing  some eviUnderstanding Society database, which contains representative samples of BME and white populations in the UK [We used a cross-sectional analysis of data drawn from Wave 6 (2014–2016) of the n the UK . Understn the UK .A detailed description of Understanding Society, sample design and the ethnic minority and migrant population sample structure has been published previously , 24. Comnatural attrition from Wave 1 to Wave 6 had been 35.4%, reducing the initial sample from 40,634 observations; and a small number of observations containing either missing values for the variables used in the analysis or where information had been gathered via proxies (less than 1%) were also excluded from analysis. Because of the relatively small amount of missing data, and large sample size it was thought unnecessary to impute this information.We extracted data from Wave 6 only. The final dataset used in analysis comprised 25,921 observations—a total arrived at as follows: a boosted sample (n = 4656) of ethnic minority participants in Wave 6 was excluded because they were not asked some detailed questions we relied on in this analysis; the ethnicity groups were identified: white (British); white (Irish); white (other); mixed ethnicity; Indian; Pakistani; Bangladeshi; Caribbean, African, with a residual other category comprising minorities deemed too small to justify separate categories for analysis. The mixed group represents a growing group of UK citizens whose parents are each from different ethnic groups, primarily partnerships between white British and people from ethnic minority groups [Ten y groups . The whiThe GHQ12 is a self-administered screening test used among respondents in community and non-psychiatric clinical settings to assess psychological distress. It has reliability coefficients ranging from 0.78 to 0.95 and good sensitivity and specificity among BME groups –31. FromThe Individual components of social capital—each with responses ranging from one (strong disagreement) to five (strong agreement)—have been found to be valid elsewhere –35. We sborn in UK (Yes/No). Acculturation and sense of assimilation was assessed via a continuous variable, British Identity measuring how individuals perceived the importance of being British, with responses on a scale from zero  to ten (extremely important).From country of birth we derived These include: age (continuous); gender; marital status ; family structure; and locale of residence—summarised as urban or rural . Family structure comprised four categories—single (no children), in a couple (no children), in a couple (with a child), or single (with a child). Proxy indicators of socioeconomic circumstance included home ownership , economic activity  and educational level. Education was classified as: primary (no GCSEs); secondary  or tertiary (degree level).Analysis utilized SPSS Version 25 software . Descriptive statistics for continuous variables included means, standard deviation and range, with percentages presented for categorical variables. All findings are presented for males and females separately. Independent sample T-tests for continuous variables, and Pearson’s chi-square for categorical variables determined gender differences in the population. We calculated mean differences in social capital across ethnic groups with a one-way ANOVA, and used linear regression to explore the relationship between ethnicity and social capital. Binary logistic regression examined determinants of psychological distress for the total sample and for men and women separately. Fully adjusted odds ratios (ORs) and 95% Confidence Intervals were derived. For all analyses, p-values of less than 0.05 were considered significant.This study was completed in keeping with the relevant ethical and legal obligations of data usage from the UK Longitudinal Household Study: as this information is publicly available ethical approval was not sought.More than 20% of the sample were psychologically distressed Table . Eighty ). Generally males recorded stronger effect sizes than women over the range of minority groups. Compared to the white British group, white (other), mixed, Caribbean, African and other ethnic groups reported lower social capital, while white (Irish) and Pakistani groups reported higher social capital. In the stratified analyses males recorded stronger effect sizes of white (Other), mixed, Caribbean, African and other ethnicities were more likely to report lower social capital whereas white (Irish), Pakistani and Bangladeshi groups reported higher social capital levels than the white British group. Similarly, for women, low social capital was reported by mixed, Caribbean, African and other ethnic groups .Social capital varied significantly across ethnic groups Table . Generalother—recorded excess likelihoods, highest  amongst Pakistanis. Females were more likely than males to report distress ; as were those not employed when compared to their employed peers ; those living in urban areas when compared to their rural peers ; and those not born in the UK . Those with higher education levels were somewhat protected, as was being currently married . Finally, the factors tested as continuous variables all show protective effects in their respective models: psychological distress declines by 1% with increasing age ; and 6%  and 4%  for increasing levels of social capital and increasing strength of feelings of Britishness respectively.Table Table To our knowledge this is the first study to examine the influence of social capital on the mental health of a wide range of ethnic groups in the UK. Our findings suggest that, compared to their white British peers, psychological distress may be more prevalent in some  BME communities. This corroborates other studies , 5, 36. In this study, while unemployment is a more specific determinant of psychological distress among males, for women  more personal, culturally significant factors exert particular pressures: for example, low educational attainment, marriage (but without children), and being born outside the UK. Previous research suggests specific socio-cultural factors—influence of extended family, single women not chosen for marriage, infertility, gender of offspring and social isolation—that may be relevant to psychological distress in Pakistani women . In thisThese findings underscore the different experiences and concerns of women and men in minority ethnic communities, with consequences that are differentially distributed across minority ethnic groups and which could be determined by the length of settlement and the resilience of their respective communities in coping with socioeconomic adversity , 45. ThuIn this study, for men and women separately and for ethnic groups, levels of social capital appear significantly associated with mental ill-health, corroborating current evidence of associations between social capital and CMDs . The proThis study suggests that in the UK certain BME groups—especially Indian, Pakistani and Bangladeshi groups—are at an increased risk of psychological distress. Levels of social capital are high in Pakistani and Bangladeshi men, but low for Caribbean and African women. While determinants for psychological distress may differ considerably among men and women, and social capital appears to be an important determinant of mental health for both men and women and for specific ethnic groups, its effect is diluted when examined against socioeconomic and sociodemographic considerations. These findings indicate possible need for investment in community-specific public health interventions to improve sense of security and belonging particularly among minority ethnic groups.Understanding Society contains a representative sample of minority ethnic populations in the UK. The inclusive and broad conceptualisation of ethnicity and self-reporting eliminates researcher bias. Using a large representative sample aids reliability. While the GHQ12 is not a diagnostic tool, it is well validated for use with ethnic minority groups. The analysis is cross-sectional, and as such no causality can be implied. Another limitation relates to the  measure of social capital used—however, items used in its construction relate to a number of the constructs of social capital. Further validation is warranted.