In 2018, the UK National Institute for Health and Care Excellence (NICE), in partnership with Public Health England, NHS England, NHS Improvement and others, developed an evidence standards framework (ESF) for digital health and care technologies (DHTs). The ESF was designed to provide a standardised approach to guide developers and commissioners on the levels of evidence needed for the clinical and economic evaluation of DHTs by health and care systems.The framework was developed using an agile and iterative methodology that included a literature review of existing initiatives and comparison of these against the requirements set by NHS England; iterative consultation with stakeholders through an expert working group and workshops; and questionnaire-based stakeholder input on a publicly available draft document.The evidence standards framework has been well-received and to date the ESF has been viewed online over 55,000 times and downloaded over 19,000 times.In April 2021 we published an update to the ESF. Here, we summarise the process through which the ESF was developed, reflect on its global impact to date, and describe NICE’s ongoing work to maintain and improve the framework in the context for a fast moving, innovative field. The pace of development in this field has meant that many DHTs are being introduced to the market with little evidence to show effectiveness, and no standardised evaluation by healthcare systems. Robust health technology assessment (HTA) is used to identify the most effective interventions and ensures the most efficient use of resources. However, traditional HTA relies on the appraisal of published evidence, which is time- and resource-intensive to generate and doesn’t fit the rapid development cycles of DHTs. Requirements for published clinical and economic studies are often described as a barrier to innovations that have the potential to drive service improvements, bring transformational change to health and care delivery, and offer wider economic benefits.25Digital health technologies (DHTs) comprise a wide range of products including apps, software and online platforms that are intended to benefit people or the wider health and care system. The rapid emergence of DHTs presents both opportunities and challenges to health systems seeking new ways to deliver effective, lower cost, patient-centred care at scale. A number of initiatives have attempted to create frameworks for evaluating DHTs. A review of evaluation frameworks for mobile medical applications by Moshi et al. identified 45 frameworks published between 2011 and 2016 which sought to guide health technology assessment of these tools.In light of this perceived conflict between traditional HTA methods and the rapid nature of DHT development, some have argued that the HTA of DHTs should use a different level and type of evidence to other interventions. The aim of the ESF is to provide NHS England health and care commissioners with a tool to understand what ‘good evidence’ looks like – what kind of evidence is needed to show that DHTs are likely to be clinically- and cost-effective. In addition, it can help developers to understand what kind of evidence they should develop for their DHT to be used in the UK health and care system.In this context, NHS England commissioned the UK National Institute for Health and Care Excellence (NICE) to develop a proportional evidence standards framework (ESF) for DHTs, to include both effectiveness and economic impact considerations. It complements other initiatives including NHSX’s Digital Technology Assessment Criteria (DTAC), which was launched in Spring 2021 to replace NHS Digital’s digital assessment questionnaire (DAQ). The DTAC covers 5 core areas: clinical safety, data protection, technical assurance, interoperability, and usability and accessibility.The ESF was created to underpin principle 8 of the Code of Conduct for Data-Driven Health and Care Technology published by the UK Department of Health and Social Care. The code of conduct outlines 10 principles to guide the development and implementation of DHTs in the UK health and care system.In this paper, we describe the agile policy research approach used to develop the ESF, outline how the ESF works, and describe its impact to date and ongoing work to ensure that the ESF remains up to date with the rapidly changing field of digital healthcare.A core working group was established to develop the NICE ESF. This included representatives from NICE, NHS England, Public Health England and the health and life science cluster organisation MedCity. Additional stakeholders included NHS Digital, the UK Office for Life Sciences, National Institute for Health Research, British Standards Institute, Innovate UK and Digital Health London.The ESF was not intended to be used for DHTs that incorporate artificial intelligence using adaptive algorithms (those which continuously evolve), although it would cover tools that use fixed algorithms .The ESF was not intended to cover safety issues nor to be a regulatory tool: in the UK, the regulation of DHTs that are categorised as medical devices is governed by the Medicines and Healthcare products Regulatory Agency (MHRA).be suitable for use by health and care commissioners and people who are not expert in HTA, clinical matters or digital information technologybe sufficiently comprehensive to cover the range of DHTs that are most often commissioned in the UK health and care systemtake account of the current evidence levels available for digital tools across the spectrum of DHT functionsinclude defined standards of evidence that must be met for commissioning in the UK health and care systemfit alongside other existing regulation in the UK without duplication or omission of factorsinclude some means to assess the economic and system-level impacts of DHTs.NHS England set the following requirements that the ESF should:NICE were given the following criteria for developing the ESF:The required timeline for the development of the framework necessitated an agile and iterative methodology. This involved: a literature review of existing initiatives and comparison of these against the requirements set by NHS England, iterative consultation with stakeholders through an expert working group and series of workshops, and questionnaire-based stakeholder input on a draft document which was made publicly available.Literature searches were carried out to identify published methods for classifying and evaluating DHTs. Database searches were conducted via the Ovid platform in MEDLINE, MEDLINE In-Process, MEDLINE ePub ahead of print, MEDLINE daily update, Embase and the Health Management Information Consortium (HMIC) database in May 2018, when the first version of the ESF was developed. MeSH terms in combination with free text searches for keywords in the title were used. In addition, website searches were conducted to identify grey literature in May 2018.Potentially relevant papers were reviewed to assess whether they presented a framework for the evaluation of DHTs, and in particular whether any frameworks met the 6 requirements which had been specified by NHS England.The ESF was drafted by the core working group based on the literature searches and using NICE’s experience of evaluating medical devices and DHTs. The draft ESF was then repeatedly iterated based on feedback received from a series of workshops.In total, 13 workshops were held between June and December 2018 with representatives of the medtech and DHT industry, health and care commissioners, academic HTA experts, clinicians and others. Over 150 people from 95 organisations, including universities, industry, National Institute for Health Research, NHS Trusts, National Associations, Royal Colleges, Department of Health and Social Care, NHS Digital, NHS Improvement, private health insurers, Office for Life Sciences and Public Health England, took part. In addition to the workshops, the draft ESF was shared directly with key stakeholder organisations, such as the MHRA, for comment.11 of the 13 workshops were held to develop the content of the ESF, and the final 2 were held to assess the usability of the final ESF. The usability workshops were attended by innovators and developers from 31 companies, 11 of which had been represented in the ESF development workshops.In December 2018, a beta version of the ESF was published on the NICE website. Scrutiny, comment and feedback on the beta version were invited from stakeholders and the public, via direct email to stakeholders who had expressed an interest during the workshops or were identified by the project team as having relevant experience and expertise. In addition, an extensive marketing, social media and communication campaign was coordinated by MedCity, who produced a video describing the ESF project. This approach was seen to be particularly relevant for small to innovators in medium enterprises (SMEs) and international stakeholders. NICE staff and other core working group members presented the ESF at over 20 relevant industry and healthcare events to gather verbal feedback and an online survey was used for written feedback. The survey included dichotomous, Likert scale and free text questions and was open for one month after the publication of the draft framework. Numerical responses were analysed using frequencies and free text responses were grouped thematically to identify common concerns.A user guide to explain the concepts and terms used in the ESFA budget impact template to help users to develop a budget impact modelA case studies document describing real DHTs that were already in use in the NHS, their functional classification and how they were already meeting the evidence standardsA functional classification document describing how over 90 real DHTs would be classified according to the ESF functional classification.After consideration of the feedback on the beta version, ESF version 1.0 was published in March 2019. Alongside the ESF document we published the following supporting materials that had been developed by the NICE team and academic collaborators:A second round of stakeholder feedback was sought in September 2019 to ascertain whether the ESF was meeting the needs of users, and to collect suggestions for improving the ESF and its supporting documents.An online survey was created and linked from the ESF pages of the NICE website. Key stakeholders were contacted by email to encourage participation in the survey. The survey included dichotomous, Likert scale and free text questions and was open for 6 weeks. Analysis of the survey responses was performed as before. In addition, interviews were held with key stakeholders to obtain their views on the ESF.1320 None of the 8 shortlisted systems met all 6 requirements.The search for existing frameworks yielded a total of 4877 hits when it was conducted in March 2018. An initial sift for relevant titles identified 299 potentially relevant articles, and from these we identified 8 published frameworks which at least partially met the requirements set by the policy commissioners for the evaluation of effectiveness see .13–20 NoThe review of the literature also identified 3 approaches to classifying DHTs based on their functionality. This classification is easy to understand but has multiple categories that were outside our remit. It also lacked granularity for DHTs which provide treatment or diagnosis. Secondly, the FDA used the International Medical Device Regulators Forum (IMDRF) principles to approach the clinical evaluation of DHTs. This model stratifies the level of independent review needed, according to the level of risk. Risk is based on the function of the software  and the severity of the healthcare situation or condition . We concluded that more than 3 functional groups would be needed to cover the breadth of DHTs included in our remit, and that the function of the DHT may be a more suitable driver for risk rather than the health condition. Finally, at the time of writing the UK MHRA classified digital and non-digital medical devices and diagnostics according to risk in line with the EU Medical Devices Directive CE marking system, in which higher-risk devices  had higher evidence requirements. However, CE marking is designed to regulate the safety of medical devices, whereas our framework is intended to demonstrate effectiveness. Also, the remit for the ESF includes many DHTs that fall outside the current CE marking classifications. Therefore, it was concluded that aligning the ESF to the CE marking classifications would not be useful in practice.Firstly, the World Health Organization (WHO) Classification of Digital Health Interventions uses 87 functional categories split into 4 end user groups.Based on the literature searches and feedback from stakeholder workshops, we developed a bespoke taxonomy with 10 functional categories that are expected to cover the functions of the majority of the DHTs most frequently commissioned in the UK health and care system . This apThe 10 functional categories are arranged into ‘tiers’ according to the level of potential risk associated with that function. We use the term ‘potential risk’ to describe level of harm to the user which could arise for example from unintended negative consequences for the user’s health and wellbeing from using the DHT. Some DHTs may fit into several functional categories and in this case the highest risk category should be used.Each tier within the functional classification is linked to a set of evidence standards that are designed to be appropriate to the risk and impact for that level of the classification to 5. ThThe evidence requirements were set according to key evidence areas identified by the NICE team, based on NICE’s experience of evaluating medical devices and DHTs. We took a pragmatic approach of identifying key issues that should be evidenced in order to inform any commissioning decision.At the most basic level, DHTs need to be based on plausible principles and to be useful in UK clinical and care pathways. People from the intended user groups should have been consulted or included in the development of the DHT, and any equalities issues should have been considered by the developer. Any health information included in the DHT must be accurate and up to date, and safeguarding measures must be in place for any DHTs that allow communication between users. We have asked that developers should collect data to show that the DHT is being used in line with the developer’s and commissioner’s expectations, and to show that it is offering good value to the health and care system. For higher-risk DHTs, we require evidence of effectiveness.During further testing and feedback, further refinements were made. We developed both minimum  and best practice (desirable) evidence standards for each tier, to allow flexibility for commissioners to stipulate higher evidence levels where specific risks were recognised. We developed a set of contextual questions  to identThe evidence standards are not designed to replace the requirements for regulatory approval, nor to measure compliance with relevant technical standards for information governance, security, resilience or interoperability.Our original intention was to integrate the effectiveness and economic impact standards within a single framework, but the resulting matrix was too complex and unclear to users. Instead we developed a separate brief framework for economic impact . This toThe evidence for economic impact standards provide information on the key considerations required for undertaking and reporting economic evaluations of DHTs, as well as categorising the level of financial ‘risk’ into 3 levels: basic, low and high. Typical examples of these 3 levels are, for basic: a pilot project at a local level; for low: a regional initiative or a potentially cost-saving national initiative; and for high: a national commissioning decision likely to be cost-incurring, for example, through service redesign. The type of economic analysis specified in the standards is related to the level of financial risk identified see .The ESF was initially published in beta version on the NICE website on the 10 December 2018. Alongside the ESF and supporting documents was an invitation to stakeholders to provide feedback, with a link to an online survey.46 complete responses to the feedback survey were received, along with 7 separate written responses. Responses were received from wide range of stakeholders including companies and industry associations, NHS clinicians and managers, digital health academics and national health and care system organisations. At least 80% of respondents who submitted a complete response said that they were clear what the standards were for (93%), who they were aimed at (83%) and how to use them (80%).the need for greater clarification of terms and definitions; more explanation of how the standards fit within the current regulatory compliance regime and their place in existing market access arrangementsinsufficient recognition of the widespread use of DHTs within social care; a lack of patient and public engagement; difficulties using the framework arising from the dynamic and rapidly evolving nature of digital tools and the likely crossover of technologies between evidence tiersa perceived lack of capacity and capability in the system for economic analysis; greater attention needed on the impact of real-world data and real-world evidencerefinement of the risk concepts and the approach to artificial intelligence. Following this feedback, minor changes were made to the framework to provide additional clarity and specificity.The framework was generally welcomed, and most respondents agreed with the content and methods used. The free text comments showed the following concerns:The post-launch feedback survey in September 2019 had 52 responses from stakeholders across industry, academia, patients and clinical experts. Most of the survey respondents had used the framework and overall user experience was positive. Additional feedback was obtained from interviews with a range of stakeholders including digital health specialists, service design consultants and collaborators from partner organisations.requesting additional resources to help users understand evidence generation and health economic analyses, a perceived lack of clarity about the remit of the ESF and how it fitted with other initiatives including the NHS Digital DAQ and 2017 EU Medical Device Regulation (MDR) for softwarethe need to engage further with commissioners and social care, the need for guidance on the use of real-world evidence in the ESFa need for greater clarity in the functional classification system and evidence requirements, requesting information on the role of users in testing and signing off new DHTsquestions about the process of how the ESF will be used in practice.The main themes of the feedback were:Tier A: System impactTier B: Understanding and communicatingTier C: Interventions. This upper tier had previously been split into 2 parts but is now merged into a single tier.The 3 evidence tiers were renamed in order to make them simpler to understand and to avoid any confusion with CE marking classes. The new tiers, from lowest evidence requirement to highest, are:The evidence requirements for each evidence tier remain the same but we have changed how they are presented: instead of describing the evidence tiers as ‘cumulative’, whereby the evidence levels for tier 3 included those in tiers 1 and 2, we’ve put all evidence requirements into a single table for each tier. The evidence requirements have not changed, but this change in presentation is intended to make the ESF easier to use.The functional category that was originally named ‘simple monitoring’ has been renamed ‘health diaries’, to make it easier to distinguish between the functional categories in Tier B: understanding and communicating.We have improved the explanations of which DHTs are likely to fit into which functional category , the budget impact template (over 1500 downloads) and the functional classification case studies (over 1400 downloads).Several healthcare systems, academic groups and commercial organisations outside of the UK have expressed interest in the NICE ESF. These include academic groups, national evaluators or governmental bodies from India, Norway, Indonesia, The Republic of Korea, Denmark, the Netherlands, and Sweden.The ESF has been cited in over 50 academic publications. has been cited 35 times.The descriptive paper explaining the purpose of the ESFThe accelerator groups that were involved in the co-design of the ESF use the standards routinely to advise innovators on evidence generation.The ESF is now being used as the standard by innovators seeking to access funding from the UK’s major research and development funders such as NIHR i4i and Innovate UK SME.Since its initial publication in December 2018 the NICE ESF has been widely viewed and discussed within the HTA and digital healthcare fields. Here we provide some illustrative examples of the global impact of the ESF.1324 MTEP was established in 2009 to evaluate medical devices, which similar to DHTs, frequently have low levels of evidence and this experience helped to inform the design of the functional categories. The NICE and NHSE IAPT assessment programme evaluated DHTs that provided therapist-guided psychological therapies. Work from this programme helped to inform the setting of evidence levels, and understanding the context of, and other requirements  for implementing DHTs within the health and care system.We have described the development and update of the NICE ESF, a framework to help guide DHT developers in planning their evidence base, and for commissioners to evaluate the evidence on DHTs. In doing so, we used experience and insights from stakeholders as well as from NICE’s medical technologies evaluation programme (MTEP), from the evaluation of digital mental health technologies for the NICE and NHSE IAPT assessment programme, and incorporated lessons learned from other work on the assessment of DHTs.It was clear from our workshop discussions that while stakeholders were well informed and encouraging about using new evaluation approaches for digital tools (such as those more familiar in the field of software development like A-B testing), the majority view was that the evidence standards should be grounded in ‘traditional’ approaches to health technology assessment, using a pragmatic evidence hierarchy that has randomised controlled trials at the top as the best practice standards for the most high risk tools, but allows for less rigorous study designs as minimum standards and in lower tiers. Both in the workshops and during the consultation phase, attention was given to the opportunities DHTs present to harness ‘real-world’ evidence for evaluation. The framework acknowledges that the value of new study designs should continue to be investigated as the potential for using real-world data increases.Despite the rapid development of the ESF within a short timescale we were able to review an extensive literature base and consult with over 100 stakeholders and their organisations to produce a pragmatic guide for the health and care system. There was limited time within the project to fully test the framework; however, we were encouraged by the supplementary case study work. As part of this, researchers who were not in the core project team were able to apply the functional classification and describe evidence on selected DHTs that was in line with that recommended by our standards. Similarly, there was not time to undertake a full systematic synthesis of all previous work, or to pause development of the framework at key stages and consult widely at each stage. Development required frequent minor modifications prior to a final consultation phase.The ESF is limited to some extent by the exclusion of DHTs that incorporate adaptive algorithms from the framework, and clearly this is an area for further development work. Here, we define ‘adaptive algorithms’ as those that constantly evolve over time, and so their effectiveness is not fixed at any time. This is in contrast to fixed algorithm DHTs, which are within the remit of the ESF. We define fixed algorithms as those that may have periodic updates but are not constantly changing. We would envision that at the point of commissioning a fixed-algorithm DHT, the commissioner and developer would agree processes for rolling out any such updates.26 NHSX’s AI lab has been created to address the challenges of safe and ethical adoption of AI-based DHTs within the healthcare system and has a number of workstreams to address these challenges. NHSX, NICE, CQC and MHRA will be jointly working on developing a ‘joined-up’ regulatory and approval system for AI-based DHTs in the health and care system. This work will be provide a useful means for pulling together the currently fragmented system for regulating and evaluating AI-based DHTs, into a coherent process for the UK health and care system.It is anticipated that as consensus develops on the HTA of DHTs that use adaptive AI, the ESF would be extended to include these. Recent work by the British Standards Institute (BSI) and the Association for the advancement of Medical Instrumentation (AAMI) has set out recommendations for AI in medical devices.Another limitation is that our main focus was on health settings but we recognise the extensive and increasing use of DHTs in social care.A further (and related) limitation of this work is that it conceptualises DHTs as standalone tools which provide specific functions, rather than as part of services or pathways. Future developments in this area are likely to see DHTs become harder to separate as single entities for evaluation, as they become more integrated within clinical pathways or more embedded within health consumer’s own digital ecosystems as providers such as Apple and Google incorporate health functions across a range of devices and consumer facing services. The ESF was designed to be used for appraising evidence for DHTs being commissioned in the UK health and care system and it is less relevant to technologies that are available directly to public users, such as through app stores. This programme allows a formalised evaluation setting for higher risk DHTs.Since its initial publication in December 2018, the NICE ESF has generated global interest and largely positive feedback from evaluators, DHT developers and academic groups. Positive feedback has been given by app evaluator organisations and governmental groups from several countries have shown an interest in the ESF. This indicates that the evaluation of DHTs has proven challenging to many organisations and that the NICE ESF fills a gap in providing an innovative HTA approach for DHTs. In 2019 NICE ran a pilot project to produce NICE guidance on DHTs, and in 2020 announced that the digital evaluation programme was now open to any DHT in evidence tier 3 of the ESF.In 2019 we sought and responded to feedback on the ESF and made minor amendments to the ESF in response. We acknowledge the need for continual surveillance of the digital healthcare field over time and anticipate further iterations of the ESF in coming years.The NICE evidence standards framework for digital health and care technologies demonstrates how a novel approach to HTA can be taken in a fast-moving field, whereby proportionality provides a pragmatic solution to the need for an agile approach. It requires higher levels of evidence for the functions that pose the highest risk to health, and more intensive health economic analysis when the financial risk to the health system is highest. This framework is designed to support local and national purchasing decisions around DHTs in England, and to help developers of DHTs to plan the generation of their evidence base.The ESF was developed in a dynamic way. It was informed by the existing literature but also through broad and iterative consultation with healthcare commissioners and healthcare innovators, creating a co-design approach. We have continued to closely monitor the digital healthcare environment in England and have used stakeholder feedback to ensure that the ESF is up to date and meets the needs of users. We believe that the ESF may also provide a useful template for other jurisdictions and health systems that are considering ways to evaluate DHTs.


This represents an extremely challenging issue for clinicians as sepsis is the leading cause of mortality in burn patients. Since hyperinflammation and immune dysfunction are a result of an immune imbalance, restoring these conditions seem to have promising benefits for burn patients. A key network that modulates the immune balance is the central nervous system (CNS)-spleen axis, which coordinates multiple signaling pathways, including sympathetic and parasympathetic pathways. Modulating inflammation is a key strategy that researchers use to understand neuroimmunomodulation in other hyperinflammatory disease models and modulating the CNS-spleen axis has led to improved clinical outcomes in patients. As the immune balance is paramount for recovery in burn-induced sepsis and patients with hyperinflammatory conditions, it appears that severe burn injuries substantially alter this CNS-spleen axis. Therefore, it is essential to address and discuss the potential therapeutic techniques that target the CNS-spleen axis that aim to restore homeostasis in burn patients. To understand this in detail, we have conducted a systematic review to explore the role of the CNS-spleen axis and its impact on immunomodulation concerning the burn-induced hypermetabolic response and associated sepsis complications. Furthermore, this thorough review explores the role of the spleen, CNS-spleen axis in the ebb and flow phases following a severe burn, how this axis induces metabolic factors and immune dysfunction, and therapeutic techniques and chemical interventions that restore the immune balance  Severe burns  are one of the most devastating traumas and are a global public health concern –3. The Whigh) that reside in the spleen and that are larger in number than their blood monocyte equivalents  and parasympathetic nervous system (PNS) pathways (2AR) on immune, vasculature, and connective tissue cells. This activates splenic cytokines such as Tumor necrosis factor α (TNFα), and Human mobility group B1 (HMGB1), which increases pro-inflammation in the body. In fact, not only does the SNS communicate with the spleen, but the cytokines released by the spleen also communicate with the SNS in a negative feedback loop  and cyclosporin A (unconditioned stimulus), the drink alone mimicked the effects of cyclosporin A and resulted in suppression of immune function, by way of the PNS, including impaired Tferation . Furtherferation .Staphylococcus aureus. The pathogen activates nociceptors by releasing N-formyl peptides and pore forming toxin α-hemolysin, inducing action potentials  critically analyze the potential contribution of the CNS-spleen axis in modulating the immune response in the severe burn patient population, and 2) discuss the therapeutic advances made thus far along with areas of improvement in targeting the CNS-spleen axis to treat the septic burn population.After a severe burn injury, patients undergo a biphasic metabolic response to burn injury. The acute response is known as to as the ebb (or shock) phase and the chronic response is referred to as the flow phase , 33. Thevia T-cell suppression  is important in the signaling performed by the vagus nerve to inhibit proinflammatory cytokines. ACh, released by the vagus nerve and immune cells, acts as a ligand for the CHRNA7 receptor and induces inhibition of proinflammatory cytokines in the spleen. Holmes et al. found a >70% reduction of protein levels of the CHRNA7 in burn patients despite significantly elevated ACh . AdditioAdditionally, extramedullary hematopoiesis occurs in the flow phase in which hematopoietic stresses mobilize hematopoietic stem cells from the bone marrow to the spleen . SplenicIt is important to note that much of the criteria for sepsis in the general population is already present in the burn patient population, however, without septic infection . TherefoThe post-recovery phases of burn injuries in patients who survive septic burns are not fully independent of post-septic symptoms. Post-sepsis syndrome is a condition that affects sepsis survivors, in which they have a range of physical, psychological, and emotional challenges while recovering. The categories of long-term effects of sepsis include immunometabolic, neurocognitive, psychiatric, and physical derangements . These evia norepinephrine to secrete more cytokines. Serum HMGB1 levels in septic mice were found to be significantly elevated for 4‐6 weeks, and administration of an anti‐HMGB1 monoclonal antibody significantly attenuated splenomegaly as well as splenocyte priming since the effects of cytokines produced via the SNS were inhibited  to determine the post-septic effects on the PNS response of the CNS-spleen axis. ACh KO mice with CLP-induced sepsis demonstrated a decreased CD8+ cytotoxic T cells and CD4+ Th and an increase in Th17 cells compared to the control . Th17 ceBurn survivors and post-septic deceased patients have multiple similarities in the bodily changes that have occurred because of septic burns. However, post-septic deceased patients have some distinguishing characteristics. Patients who die as a result of burn-induced systemic sepsis have a marked loss of noradrenergic nerves, which occurs due to the apoptosis of splenic cells . Nerve lThe CNS-spleen axis may be of great importance in combating burn-induced sepsis as it regulates systemic inflammation. Various novel therapies that target the CNS-spleen axis exist for the treatment of the general sepsis population. These therapies may be effective in the septic burn population too. Here, we will discuss the potential use of vagus nerve stimulation (VNS), agonists and antagonists of major molecules in the CNS-spleen axis, approaches targeting proinflammatory cytokines and approaches targeting catecholamines to mitigate burn-induced sepsis  and dopamine act as vital hormones that are produced, in part, by the adrenal medulla and secreted into the circulation in response to stress or injury. Catecholamines influence and modulate sympathetic neural modulation of immune responsiveness . SpecifiSepsis is a major concern, not only in the general patient population but aggressively so in burn patients. The CNS-spleen axis pathway may be a crucial aspect to consider when developing treatments for burn patients as this bidirectional pathway communication leads to hyperinflammation in the body in response to burns and sepsis. Specifically, the SNS has been shown to increase pro-inflammatory cytokines in patients using epinephrine/norepinephrine, and the PNS has been shown to decrease inflammation in the body using ACh and the vagus nerve. Since targeting this axis has demonstrated clinical efficacy in patients with many ongoing inflammatory conditions , 30, 31,The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.NK has done primary research and wrote major portions of the manuscript. SK and CK both wrote portions of the manuscript and proofread the manuscript. MJ conceptualized the idea, guided the research, and proofread the manuscript. All authors contributed to the article and approved the submitted version.The research work of this review article is supported by the national institute of health (NIH R01GM133961) grant.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.


Self-related processes (SRPs) have been theorized as key mechanisms of mindfulness-based interventions (MBIs), but the evidence supporting these theories is currently unclear. This evidence map introduces a comprehensive framework for different types of SRPs, and how they are theorized to function as mechanisms of MBIs (target identification). The evidence map then assesses SRP target engagement by mindfulness training and the relationship between target engagement and outcomes . Discussion of the measurement of SRPs is also included. The most common SRPs measured and engaged by standard MBIs represented valenced evaluations of self-concept, including rumination, self-compassion, self-efficacy, and self-esteem. Rumination showed the strongest evidence as a mechanism for depression, with other physical and mental health outcomes also supported. Self-compassion showed consistent target engagement but was inconsistently related to improved outcomes. Decentering and interoception are emerging potential mechanisms, but their construct validity and different subcomponents are still in development. While some embodied self-specifying processes are being measured in cross-sectional and meditation induction studies, very few have been assessed in MBIs. The SRPs with the strongest mechanistic support represent positive and negative evaluations of self-concept. In sum, few SRPs have been measured in MBIs, and additional research using well-validated measures is needed to clarify their role as mechanisms. Mindfulness-based interventions (MBIs), the most common of which are Mindfulness-based Cognitive Therapy MBCT;  and MindThe primary goals of this evidence map are: (1) to identify which SRPs have been theorized to play a mediational role in MBIs; (2) to evaluate the extent to which these theories have been empirically investigated; and (3) to provide recommendations for future research. To do this, we first provide a conceptual framework in order to identify and differentiate the various types of SRPs that may be targeted through MBIs. We identify various SRPs and how they are theorized to operate as mechanisms in MBIs. For each theorized SRP, we evaluate the current state of evidence for MBI target engagement and assess to what extent SRP target engagement impacts outcomes . The review of the evidence provides commentary on the measurement of SRPs, highlights limitations in extant research, and identifies areas that require more clarification.Studying self-related processes is necessarily complex on account of involving the notion of self, which has long been recognized as a “mushy, muddle-headed construct without empirical referents” that encompasses multiple meanings  (p. 4). Perhaps the most fundamental aspect of the self-as-subject is the perspectival self, or the sense that our experience is situated from a specific, first-person perspective or vantage point , 2012. OIn contrast to the pre-reflective self-as-subject, the upper circle in Lastly, we identify SRPs that function as self-regulation skills, specifically decentering and self-efficacy. Self-efficacy, for example, is the perceived capability of an imagined future self to perform a target behavior  and is aMindfulness-based interventions operate at the confluence of multiple disciplines, including clinical, health, cognitive, and positive psychology, as well as Buddhist theories of mind. As products of clinical and health psychology, MBIs might be expected to promote any number of SRPs associated with self-concepts and self-regulation. However, in line with the Buddhist theories from which they are derived, many contemporary models for the mechanisms of mindfulness also propose that MBIs affect  many, if not most, dimensions of selfhood, not just conceptual ones . Indeed,Self-related processes are theorized as key mechanisms of MBIs. According to the experimental medicine approach, hypothesized intervention targets must meet several other basic criteria to qualify as a mechanism . In addiThe current paper is an evidence map that uses a multidimensional methodology to synthesize the evidence. An evidence map is generally a type of knowledge synthesis that maps key concepts, types of evidence, and gaps in knowledge. While unrestricted to a specific methodology, depending on goals and resources an evidence map typically includes: a review of key documents; consultation with stakeholders or experts; specific inclusion criteria and a systematic method of search; data extraction; and critical evaluation . Compareagency, body awareness, decentering, disidentification, ego, embodiment, experiential self, identity/identification, interoception, meta-awareness, narrative self, observing self, perceived control, reperceiving, self-awareness, self-compassion, self-criticism, self-distancing, self-efficacy, self-esteem, self-loathing, self-monitoring, self-praise, self-referential processing, self-regulation, self-related rumination, self-worth, sense of agency, sense of control, and sense of ownership.A detailed description of our methodology can be found in the Eligible studies were English-language RCTs of standard Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy (MBCT) with one or more active and/or inactive control condition(s), with adult participants (age 18 or older) from both clinical and non-clinical samples. Of the 10,802 studies identified, only 14 standard MBI RCTs assessed SRPs. In addition, only five of the 30 SRP constructs generated by the expert panel had been measured within an RCT of a standard MBI, namely: self-evaluation, self-compassion, rumination, self-esteem, and self-efficacy.interoception, decentering, selflessness and self-transcendence  SRP constructs that have been theorized as central or key mechanism of MBIs, specifically cendence . This alThus, using the experimental medicine framework  we creatThe review of each construct included four parts: (1) a definition and how it is theorized to function as a mechanism of MBIs (target identification); (2) description of target engagement by mindfulness meditation training according to a hierarchical levels of evidence ; (3) description of target validation, or the degree to which target engagement account for desired outcomes, using similar levels of evidence above, with Kazdin’s full mediation criteria at the top ; and (4)Conceptual SRPs constituted the highest level of evidence as mechanisms of MBIs. Five SRP constructs were organized under two types of self-evaluation: negative and positive. Specifically, rumination, dysfunctional attitudes and negative automatic thoughts were categorized under negative self-evaluation, while self-compassion and self-esteem were categorized under positive self-evaluation.Rumination could be described as a form of depressive negative automatic thinking . Howeverr = 0.31, p < 0.001) between MBIs and rumination in six studies of MBCT and MBSR. In another meta-analysis focused mainly on MBCT for depressed patients, pooled results showed significant reductions in rumination following MBCT compared to treatment-as-usual , a significant reduction in depression scores was facilitated by changes in rumination . In the subgroup of studies that found weak effects on rumination (k = 6), there was a reduced effect on depression . In a narrative review focused on mediation studies, results showed that rumination was successfully engaged in MBCT and MBSR and that this engagement led to improved health states . In another RCT among adults with Bipolar I disorder . A systematic review  examinedNegative automatic thoughts also come from Beck’s cognitive theory , 1976. TNo systematic reviews or meta-analyses have examined MBIs’ impact on negative automatic thoughts. MBIs led to reduced negative automatic thoughts in RCTs with college students , patientSelf-compassion is one of the mostly widely theorized and tested SRP mechanisms of change in MBIs . Self-cog = 0.60), but noted that the effect was not consistent across studies. In addition, increases in self-compassion are not unique to or superior in MBIs. Evidence from active controls suggests self-compassion may also improve with other behavioral interventions such as exercise, yoga or biofeedback , found significantly greater increases in self-esteem in the MBI than in the control group in 6 of the 12 studies rated strong for their study design , but between group results were non-significant. Although potentially engaged by MBIs, self-esteem has yet to be investigated as a mechanism of MBIs on any outcome.Self-esteem was assessed in only one study that we identified to be of the highest methodological quality, y design . A meta-Self-efficacy reflects confidence in one’s ability to exert control over one’s motivation, behavior, and social environment , 1997. GAccumulating reviews demonstrate that MBIs can engage self-efficacy. In a recent meta-analysis of controlled trials of 19 “mindfulness programs” for health profession students, two studies examined self-efficacy . MBIs siFurther evidence of target engagement comes from a variety of RCTs in clinical and non-clinical samples. For instance, in two studies that used variations of MBSR, results showed improved maternal self-efficacy among breastfeeding women when compared to a waitlist  and imprA construct called “decentering” has emerged as a central hypothesized mechanism of MBIs . Here weanatta), MBIs expand the disidentification process to include not just negative thoughts but all thoughts, and all internal experiences, including emotions and body sensations. According to the Handbook of Mindfulness, disidentification is “fundamental to the effects of [mindfulness training] on positive functioning” . When studies were examined separately by trial design, only RCT studies maintained a significant relationship, although effect sizes were similar in magnitude across all study designs. A further meta-analysis of only heartbeat-related interoceptive accuracy studies  than constructs with the same name   and the ame name . In addiame name .The Multidimensional Assessment of Interoceptive Awareness MAIA; , 2018 isThree main validated measures have been developed for the assessment of self-transcendence in the context of meditation. The Non-dual Awareness Dimensional Assessment-Trait NADA-T;  is a welThe Perceived Body Boundaries Scale PBBS;  is a sinThis knowledge synthesis investigated the potential role of self-related processes (SRPs) as a mechanism of change in standard mindfulness-based interventions (MBIs). A change or attenuation in selfhood is frequently advanced as a mechanism of MBIs, a perspective that comes at least in part from the substantial influence of the theory and practice of Buddhism on MBIs. However, which SRPs should be considered the target is often un- or under-specified. Contemporary research across multiple fields has demonstrated that the sense of self is grounded in multiple processes, ranging from pre-reflective embodied “self-as-subject” processes to conceptual and often valenced evaluative “self-as-object” processes. This evidence map has attempted (1) to synthesize and clarify which and in what way these processes are theorized to be mechanisms of MBIs, (2) to evaluate the current degree of evidence across the full range of SRPs, and (3) to indicate where research into SRPs require additional clarification and precision in order to navigate the jingle-jangle fallacy.Based on the current review, extant data show that MBIs significantly engage some SRPs, regardless of MBI or population type, which confirms that some SRPs have a signal as potential mechanisms leading to beneficial health outcomes. Most of the SRPs that have been measured in MBI RCTs are conceptual senses of self or self-regulation skills. Specifically, the SRPs measured and engaged by MBIs include increased positive and decreased negative self-evaluation, as measured by rumination, negative thoughts and attitudes, self-compassion, self-esteem and self-efficacy. With support from multiple meta-analyses, rumination showed the strongest evidence as an MBI mechanism for depression, with other physical and mental health outcomes also supported. Self-compassion showed consistent target engagement but was inconsistently related to improved health outcomes. Self-efficacy and self-esteem were reliably engaged by MBIs but have not been evaluated as mechanisms. Evidence for decentering as a mechanism was mixed and undermined by inadequate construct validity and discrepancies between theory and assay. Across all RCTs, MBIs engaged SRPs more than passive, but not active controls, which suggests that engagement of SRPs is neither specific to nor greater in MBIs. Overall, positively and negatively valenced conceptual senses of self investigated through clinical and health psychology have received the most attention and have the larger evidence base for a mechanistic relationship with MBIs.In contrast, very few, embodied SRPs have been measured in an MBI or longitudinal intervention study. Interoceptive processes were the only process with enough studies of any kind to facilitate a meta-analysis. Evidence for interoceptive processes as mechanisms of MBIs was mixed, and dependent on type of interoceptive process and method of measurement. Aside from interoception, measurement of other embodied self-specifying processes were entirely absent from standard MBI trials, and with the exception of one non-standard MBI trial, came mostly from experimental induction studies in healthy samples or qualitative case reports. In addition to the lack of data from clinical trials, evidence for attenuations in self-specifying process as mechanisms of MBIs or meditation is limited by measurement issues and lack of assessment of enduring outcomes.While this evidence (gap) map is one of the first attempts to identify and evaluate a wide range of SRPs in MBIs, it also has many limitations. The current review may not be exhaustive, as SRPs are often measured as secondary outcomes and thus some important studies may not have been identified in this map. In addition, this review investigated the effects of meditation practice on SRPs without differentiating the types of meditation practices, which may impact target engagement and target validation . AdditioAs one of the first reviews to integrate and evaluate evidence for SRPs as mechanisms in MBIs, many other questions still remain to be explored. Importantly, this evidence map suggests that greater attention needs to be placed on identifying, delineating and measuring specific SRPs. Theoretical models proposing changes in sense of self have often insufficiently specified SRPs, leaving ambiguity as to whether those processes are conceptual and evaluative “self-as-object” SRPs, pre-reflective and embodied “self-as-subject” SRPs, or self-regulation skills. They have also insufficiently attended to whether increases or attenuations of SRPs is the proposed mechanism of change. This evidence (gap) map found evidence that mindfulness training leads to decreases in certain conceptual senses of self  and increases in others  suggesting an important and often underemphasized role of valence. Although preliminary, current research also suggests that mindfulness training may lead certain embodied processes  to decrease while others  increase, although how these changes are related to outcomes is still unknown. Attending to these differences remains crucial for both theoretical models and empirical research, as certain directions of change in specific SRPs have better evidence for target engagement and target validation than others, and researchers should not expect that a global attenuation of SRPs will be optimal in all circumstances .Given that different meditation practices are intended to target different forms of selfhood in different ways, more attention should be paid to practice-specific effects . FurtherThe findings of the current review has several implications for mindfulness-based interventions. The strongest evidence for an SRP-based mechanism of MBIs’ beneficial effects comes from increasing positively valenced and/or decreasing negatively valenced conceptual senses of self. Consistent with other studies, this suggests that mindfulness-related wellbeing is better explained and achieved by self-concept enhancement than Buddhist-derived ego-quieting or multi-level SRP reduction . In ordeMindfulness-based intervention research on embodied SRPs remain understudied, especially in relation to outcomes. However, there is reason to think that reductions in embodied SRPs or global reductions in all SRPs is not the primary mechanism of MBI benefits. In a recent MBI trial, “self-disturbances” were among meditation-related adverse effects associated with enduring impairment . In addiIn addition to mental health risks, medical ethicists have identified epistemic costs and raised ethical concerns that MBIs are “metaphysically loaded with philosophical claims about the self” that may create tension with people’s core beliefs  p, 567. Self-related processes are a promising area of research for investigating mechanisms of mindfulness-based interventions. However, senses of self are multiple, and many constructs remain poorly delineated or differentiated. Available assays often either assess multiple SRPs or have embedded within them additional features such as positive affect, which inflate their relationship with outcomes . Thus, rWB, GD, SP, DV, SL, ZS-O, RF, and EM conceptualized, designed, and developed the protocol for this study. SP, WB, and JRL wrote the initial drafts. TD, JL, HK, LS, HR, AC, PA, and JS conducted literature searches, compiled data, and aided writing efforts. WB, RA, JRL, NC, DV, and EM completed the final evidence map review and writing. All authors contributed to the article and approved the submitted version.WB is a MBSR and MBCT teacher and has received financial compensation for this role. WB is nominally affiliated with the Mindfulness Center at Brown University which generates income by offering mindfulness classes to the public. WB is the founder of Cheetah House, a RI non-profit organization that provides information about meditation-related difficulties, individual consultations, and support groups, as well as educational trainings to meditation teachers, clinicians, educators and mindfulness providers. JL’s spouse is the founder of Cheetah House. JL has also received compensation for providing educational trainings on meditation-related difficulties. These interests have been disclosed to and is being managed by Brown University, in accordance with its Conflict of Interest and Conflict of Commitment policies. The remaining 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.


Background: The mind-body therapies of traditional Chinese medicine include several intervention types and combine physical poses with conscious relaxation and breathing techniques. The purpose of this Evidence Map is to describe these different interventions and report related health outcomes.Methods: This evidence map is based on the 3iE Evidence Gap Map methodology. We searched seven electronic databases  from inception to November 2019 and included systematic reviews only. Systematic reviews were analyzed based on AMSTAR 2. We used Tableau to graphically display quality assessment, the number of reviews, outcomes, and effects.Results: The map is based on 116 systematic reviews and 44 meta-analyses. Most of the reviews were published in the last 5 years. The most researched interventions were Tai Chi and Qi Gong. The reviews presented the following quality assessment: 80 high, 43 moderate, 23 low, and 14 critically low. Every 680 distinct outcome effect was classified: 421 as potential positive; 237 as positive; 21 as inconclusive/mixed; one potential negative and none no effect. Positive effects were related to chronic diseases; mental indicators and disorders; vitality, well-being, and quality of life. Potential positive effects were related to balance, mobility, Parkinson's disease, hypertension, joint pain, cognitive performance, and sleep quality. Inconclusive/mixed-effects justify further research, especially in the following areas: Acupressure as Shiatsu and Tuiná for nausea and vomiting; Tai Chi and Qi Gong for acute diseases, prevention of stroke, stroke risk factors, and schizophrenia.Conclusions: The mind-body therapies from traditional Chinese medicine have been applied in different areas and this Evidence Map provides a visualization of valuable information for patients, professionals, and policymakers, to promote evidence-based complementary therapies. MBT incQi Gong covers several practices and it is important to describe their meaning. The “Qi” means the energy that gives rise to activities of human life and “Gong” concerns the regulation of Qi through practice. Qi Gong practices consist of two forms: Qi Gong dynamic  or Qi Gong meditative . Qi Gong external involves movements of the whole body or limbs , while Qigong internal requires the maintenance of posture with subtle body movements when performing exercises involving breathing and the mind  .Acupressure Shiatsu and Tuiná hold the same principles as Acupuncture, but are non-invasive and do not need sophisticated equipment, as they are technics that use pressure through the body itself, such as through fingers, at the Acupuncture meridians points, to activate the body's internal energy flow (Qi), contributing to the restoration of its internal balance . These pSince 2006, Mind-Body Therapies from Traditional Chinese Medicine (MBTTCM) are some of the 29 complementary therapies included in the Brazilian National Health System. MBTTCM are ancient and consist of skills used in mind-body exercises integrating controlled breathing, body posture, gentle, and synergistic movements with mind adjustments .Therefore, these practices may contribute to the psychological component of quality of life , self-caThe methodological steps of the evidence map are parallel to those involved in the initial stages of a systematic review. Although, systematic reviews look to collate a limited subset of the evidence base to answer a specific research question. However, the evidence map does not attempt to answer a specific research question instead guided by broader research objectives .The Campbell Collaboration  suggestsThis Evidence Map summarizes the interventions and health outcomes related to MBTTCM. These evidence maps considered six steps, each with a set of activities: (1) Search, (2) Selection, (3) Categorization, (4) Informetric, (5) Evidence map, and (6) Gaps . The metOur search was conducted in several databases , from each database inception to November 2019, looking for systematic reviews in English, Spanish, and Portuguese. The review question to guide the database search considered the following: (P) general population, (I) MBTTCM as intervention, (C) no comparator, and (O) health-related outcomes. We consulted topic experts and developed the search strategy together with Latin American and Caribbean Center on Health Sciences Information (BIREME), then entered the following expressions as shown in Systematic reviews about MBTTCM interventions and adequate descriptions of health outcomes were eligible for inclusion. We defined systematic reviews studies that self-identified as such. All participants of all ages, regardless of health status, were eligible for inclusion in the review. We excluded systematic reviews that did not focus on MBTTCM health outcomes. We included interventions on Tai Chi, Qi Gong, Traditional Chinese Exercise, Baduanjin, Acupressure techniques Shiatsu, and Tuiná of any duration and follow up.Two blinded independent literature reviewers screened the systematic review search output through the Rayyan software. Citations deemed potentially relevant by at least one reviewer and unclear citations were obtained as full text. The full-text publications were screened against the specified inclusion criteria by two independent reviewers; disagreements were resolved through discussion. This process is displayed at the PRISMA Flow Diagram  Figure .Assessing the Methodological Quality of Systematic Review (AMSTAR 2) was applied to analyze the quality  of the included systematic reviews. The AMSTAR 2 by 16 item quality assessment analysis indicates confidence in the results of each review and describes the sources of bias: selection, measurement, and confounding ; Database ID; Focus Country; Publication Country; Publication Year; Type of Review; Review Design; Study Design; Quality Assessment. The systematic review outcomes were drafted by one reviewer and discussed by the review team, and the matrix was discussed in two workshops organized by BIREME. We organized the Evidence Map considering the outcomes, effects, and quality assessment of the included systematic reviews. We use the interactive Tableau platform to graphically display all this information.We identified 299 citations in the database search, 113 studies were excluded for not being systematic reviews, 172 were eligible for eligibility, 12 were excluded for being protocols, and 160 unique systematic reviews met the criteria for inclusion in the Evidence Map. Most of the reviews were published in 2017 and 2019. Tai Chi and Qi Gong were the most researched interventions.The results found in the 160 systematic reviews were divided into eight major outcomes groups: cancer; acute diseases; chronic diseases; physiological and metabolic indicators and nutritional and metabolic diseases; pain; patient safety; mental indicators and mental disorders; vitality, well-being, and quality of life. This evidence map spanned wide health outcomes, effects, and populations. The outcome group, quality assessment, and effect by interventions are presented in The interventions were divided into two groups: Chinese bodily practices as Tai Chi, Qi Gong, Baduanjin, and Traditional Chinese Exercises; and manual stimulation of Acupuncture points (Acupressure) as Shiatsu and Tuiná. The Chinese bodily practices form was the most found in the reviews, highlighting the 313 Tai Chi and 107 Qi Gong interventions to distinct outcomes.This evidence map analyzed data from the following populations: people with chronic disease (38), older adults (38), people in general (18), people with heart disease (16), people with cancer (12), women (11). and diabetics (8). In addition, smaller representations with adults (5), people with hypertension (3), patients with stroke (3), and people with osteopenia (2). Patients with schizophrenia, graduation students, children with autism, and women with cancer, each with only one study. Two reviews had mixed populations of adults, women, and older adults.The systematic reviews included analyzed data from the following countries: United States of America (50.3%), United Kingdom (23.7%), China (5.9%), Switzerland (5.1%), Singapore (2%), Germany (1.6%), Australia (1.4%), and England (1.25%).Mind-Body Therapies from Traditional Chinese Medicine (MBTTCM) was evaluated as an intervention for 109 distinct health outcomes. Every outcome effect was classified as 421 positives; 237 potential positives; 21 inconclusive/mixed; one potentially negative, and none no effect, several reviews had more than one effect. Chronic diseases highlight positive effects for rheumatoid arthritis, hypertension, diabetes mellitus, coronary diseases, osteopenia, and rates of glycemia and high-density lipoprotein (HDL). Mental disorders target depression, anxiety, cognitive performance, humor, well-being, and dementia. Vitality, well-being and, quality of life outcomes emphasize results as balance, physical function, mobility, exercise capacity, quality of life and, risk of falling.The cancer group results in the included systematic reviews were breast cancer, general cancer symptoms, cancer pain, fatigue, nausea, and vomiting. Among these, the MBTTCM showed positive effects for breast cancer, fatigue, and general cancer symptoms –23. The The acute disease group results represent Tai Chi and Qi Gong interventions for stroke prevention. However, the effect of the single survey that related the results for stroke were inconclusive and mixed .The chronic diseases group results were rheumatoid arthritis, coronary disease, Parkinson's disease, hypertension, diabetes, osteopenia, osteoporosis, fibromyalgia, osteoarthritis, chronic obstructive pulmonary disease (COPD), asthma, multiple sclerosis, and vestibulopathy. The effects of MBTTCM were positive for osteoarthritis –35, coroMind-Body Therapies from Traditional Chinese Medicine (MBTTCM), as interventions for metabolic and physiological indicators and nutritional and metabolic diseases, showed positive effects for cholesterol, glycemia, and triglycerides , 60. DesMind-Body Therapies from Traditional Chinese Medicine (MBTTCM), as interventions for pain conditions, showed positive effects for headache, joint pain, chronic pain, and low back pain –67 Also,Mind-Body Therapies from Traditional Chinese Medicine (MBTTCM), as interventions—for patient safety, showed positive effects such as Tai Chi on the quality of life of patients with chronic disease, self-efficacy, psychological health conditions, and to prevent and manage cardiovascular disease , 75–79.In the mental indicators and mental disorders group, Mind-Body Therapies from Traditional Chinese Medicine  had positive effects for cognitive performance, memory, physical and psychological well-being, depression, anxiety, dementia, stress , 80–83, Mind-Body Therapies from Traditional Chinese Medicine (MBTTCM) , as interventions in the vitality, well-being, and quality of life group, showed positive effects for balance, physical function, mobility , 85–101,The systematic reviews included were analyzed based on AMSTAR 2, resulting in the following quality assessment: 80 High, 43 Moderate, 23 Low, and 14 critically low. The systematic review's authors indicated some methodological flaws, highlighting population heterogeneity in the practice groups, period, and time of intervention.Even though Evidence Maps have several limitations, like the fact that we used only published reviews to provide an overview on the research on MBTTCM, more evidence, including qualitative studies, were not included. We did not calculate the effect sizes in a meta-analysis, nor provide the risk of bias assessments, but we tried to overcome these limitations by applying AMSTAR 2 to the quality assessment of the included systematic reviews.In addition, the grouping of outcomes was review-content driven. Even though individual primary research studies would have more contributions to add to the analysis, this was not the focus of the Map. Besides, we were unable to avoid overlapping the included studies across reviews, but we did not repeat the results from updated reviews. We relied on the review author's skills in conducting systematic reviews, evaluation of primary studies quality, choice of outcomes, analysis of effects, susceptibility to publication, and outcome reporting bias.Evidence maps are not designed to provide detailed and definitive information on the effectiveness of interventions. The implementation of the reviewed interventions in practice will require additional steps . Generally, evidence maps are a very broad overview of the evidence base, indicating areas in which research has been conducted, to help stakeholders interpret the state of the evidence to inform policy and clinical decision making.Therefore, this evidence gap map can only provide a broad research overview, the findings showed more positive effects than potential negative or negative ones, including reviews of high, moderate, low, and critically low-quality assessments. The duration, period, and frequency of MBTTCM have not been analyzed and need more research.The creation and publication of this evidence map consist in graphically representing the best evidence found, analyzed, and categorized, in addition to linking with the bibliographic records and full texts (when available) of the studies to facilitate access to information for all those interested.The systematic reviews included did not clearly report the time of practices, frequency, more details of each practice, and duration of interventions. Therefore, the heterogeneity of the studies regarding the included participants, intervention characteristics, durations, and control groups may also limit the validity of the results. Furthermore, there have been no studies with pregnant women.This Evidence Map will also not be able to answer more specific questions, such as the most appropriate method of applying Traditional Chinese Medicine Mind-Body Therapies, the difference between health services, adequate training of professionals, patient access, and self-application effects.Future research, such as qualitative review surveys and evidence maps that only include systematic reviews of randomized clinical trials, are needed to answer refined questions, which are extremely important for the development of Traditional Chinese Medicine Mind-Body Therapies.This evidence map for MBTTCM is based on 160 published systematic reviews and provides an available evidence broad overview of these interventions, related outcomes, and effects. It shows the volume of available research and highlights areas where the interventions showed positive effects.The characteristics of the MBTTCM  include low cost, moderate intensity, low technology, and low impact, and the possibility of practice by adults and older adults with chronic diseases . The movMind-Body Therapies from Traditional Chinese Medicine (MBTTCM) have been evaluated in different health conditions, including chronic diseases and mental disorders, and in vitality, well-being, and quality of life, assessed in a very broad population, from patients with chronic diseases to older adults.This evidence map demonstrates that Tai Chi can significantly benefit adults and older adults with chronic diseases related to rheumatoid arthritis, hypertension, diabetes mellitus, coronary diseases, and osteopenia. Furthermore, significant improvements emphasize the results such as balance, physical function, mobility, exercise capacity, quality of life, and risk of falling. Highlighting beneficial effects for reductions in depression, disability falls, pain, and stiffness.Tai Chi included significant improvements in cancers, chronic obstructive pulmonary disease, coronary heart disease, heart failure, hypertension, low back pain, osteoarthritis, osteoporosis, Parkinson's Disease, and stroke  as well The inconclusive/mixed-effects related to Tai Chi such as schizophrenia, aerobic exercise, visuospatial capacity, fatigue-reducing, and cardiovascular disease need more research.The evidence map outcomes related Qi Gong to mental disorders scoped depression, anxiety, cognitive performance, mood, and feeling of well-being as well as chronic diseases such as diabetes, hypertension, metabolic syndrome, and cancer. Also, beneficial effects for reductions blood pressure, rates of glycemia, and HDL, pain, and improving risk factors metabolic syndrome were associated with Qi Gong.Qi Gong may serve as a promising opportunity to improve psychological health domains such as the quality of life, depressive symptoms, fear of falling, and sleep quality in older adults , potentiAlthough this evidence map found positive effects of Qi Gong for diabetes, further research is suggested to debate these results. Also, Qi Gong applied to children with autism.This evidence map involves 10 reviews of the Traditional Chinese Exercise (TCE) and only three reviews to present the Baduanjin results. The health outcomes for these interventions report positive and potentially positive effects related to chronic diseases such as diabetes, hypertension, coronary disease, osteoarthritis, and Parkinson's disease and the improvements emphasize results of fatigue, low back pain, neck pain, cognitive performance, psychological well-being and quality of sleep. The Baduanjin to osteoarthritis demonstrated a statistically significant improvement in pain, stiffness, and physical function , effectiAlthough these studies include both high and moderate-quality assessments and could be considered for healthcare applications in these areas, further research with TCE and Baduanjin is needed.Acupressure techniques such as Shiatsu and Tuiná are variants of Acupuncture and use hands and fingers to rub, knead or strike soft tissues and joints of the Acupuncture point regions in the body. They are non-invasive body practices and can be administered by the patients themselves .This evidence map related to acupressure interventions showed potential positive effects involving dysmenorrhea, labor pain, nausea and vomit, low back pain, premenstrual syndrome, and pain relief. These effects appear in only seven reviews with high and moderate-quality assessment highlighting dysmenorrhea, nausea and vomit, and pain relief.The Cochrane review demonstrates that acupressure probably has efficacy in reducing nausea and vomiting in women in labor, however, the stand-out evidence was generally low warranting further research . AcupresThis Evidence Map demonstrated that acupressure could be considered for healthcare applications in these areas, nonetheless, further research is required.Our map showed more positive effects and only one potential negative effect from a moderate quality review related to adverse effects and sense of well-being . The mixThe outcomes and effects information of MBTTCM showed in these Maps will further advance our evidence-based knowledge of complementary therapies, such as that proposed by the complementary therapies policy in Brazil and promoted by the WHO MTCI 2014-2024 agenda.Mind-Body Therapies from Traditional Chinese Medicine (MBTTCM) have been applied in different areas and this map indicates 421 positive and promising health outcomes that need further research. Despite the outlined limitations, this evidence map provides a visualization of valuable information for patients, health practitioners, and policymakers, in order to promote evidence-based complementary therapies.The original contributions presented in the study are included in the article/LF and MS drafted the manuscript. LF, MS, RG, CA, and CP designed the study and were involved in data acquisition and analysis. CA, MS, and LF designed and executed the search strategy. All authors were involved in the interpretation of the data, contributed to the final manuscript, read, and approved the final manuscript.The study is part of a project funded by the Brazilian Ministry of Health in partnership with the Latin American and Caribbean Center on Health Sciences Information (BIREME - PAHO - WHO) and the Brazilian Academic Consortium for Integrative Health (CABSIN) to develop complementary therapies Evidence Gap Maps, including Mind-Body Therapies of Traditional Chinese Medicine. The Brazilian Ministry of Health funded the project and BIREME-research partners conducted the study; collection; management; analysis; interpretation of the data; preparation, review, and decision to submit the manuscript for publication. The findings and conclusions in this publication are those of the authors who are responsible for its contents; the findings and conclusions do not necessarily represent the views of the Brazilian Ministry of Health and BIREME-PAHO-WHO.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.