In-situ simulation is increasingly employed in healthcare settings to support learning and improve patient, staff and organisational outcomes. It can help participants to problem solve within real, dynamic and familiar clinical settings, develop effective multidisciplinary team working and facilitates learning into practice. There is nevertheless a reported lack of a standardised and cohesive approach across healthcare organisations. The aim of this systematic mapping review was to explore and map the current evidence base for in-situ interventions, identify gaps in the literature and inform future research and evaluation questions.A systematic mapping review of published in-situ simulation literature was conducted. Searches were conducted on MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, MIDIRS and ProQuest databases to identify all relevant literature from inception to October 2020. Relevant papers were retrieved, reviewed and extracted data were organised into broad themes.Sixty-nine papers were included in the mapping review. In-situ simulation is used 1) as an assessment tool; 2) to assess and promote system readiness and safety cultures; 3) to improve clinical skills and patient outcomes; 4) to improve non-technical skills (NTS), knowledge and confidence. Most studies included were observational and assessed individual, team or departmental performance against clinical standards. There was considerable variation in assessment methods, length of study and the frequency of interventions.This mapping highlights various in-situ simulation approaches designed to address a range of objectives in healthcare settings; most studies report in-situ simulation to be feasible and beneficial in addressing various learning and improvement objectives. There is a lack of consensus for implementing and evaluating in-situ simulation and further studies are required to identify potential benefits and impacts on patient outcomes. In-situ simulation studies need to include detailed demographic and contextual data to consider transferability across care settings and teams and to assess possible confounding factors. Valid and reliable data collection tools should be developed to capture the complexity of team and individual performance in real settings. Research should focus on identifying the optimal frequency and length of in-situ simulations to improve outcomes and maximize participant experience. In-situ simulation (ISS) training enables teams to practice and be assessed in their own, familiar clinical environments , 2. ISS ISS has been identified as a useful mechanism to explore and learn from adverse events –9. EmbedOrganisational resilience is focused on understanding how healthcare organisations can deliver standardised, replicable and predictable services while embracing inherent variations, disruptions and unexpected events . During ISS offers a feasible and acceptable approach through which individual and team competency can be assessed through simulated scenarios in controlled and standardised clinical settings . GriswolAlthough ISS has been identified as a promising approach in healthcare settings, ISS terms and concepts require standardisation and integrated models of learning are required to provide a more comprehensive and cohesive strategic approach , 31, 32.We chose to conduct a systematic mapping review to capture the wide evidence base on main uses of ISS in healthcare. Mapping reviews are specifically designed to describe the extent of research in a field, spanning broad topic areas and research objectives to identifying evidence gaps to be addressed by future research . The repThe search strategy was developed for MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, MIDIRS and ProQuest databases and completed the literature search in March 2019 and updated in October 2020. A summary of the search terms is included in Table Papers were included in the review if they met the following criteria: (i) published in English, (ii) based in an Organisation for Economic Co-operation and Development (OECD) member country , (iii) reporting quantitative primary research including randomised controlled trials, quasi-experimental studies, cohort studies, economic evaluation and observational quantitative studies (iv), included healthcare practitioners as participants  (v) reported simulation training or interventions conducted in any patient care settings (vi) reported quantitative measures of safety, governance, quality improvement, technical and non-technical skills performance, and educational or clinical outcomes. Exclusion criteria were (i) papers reporting simulation activities conducted in educational institutions and centres, simulation laboratories or training suites or non-patient areas (ii) qualitative studies, secondary data analysis and literature reviews. The timeframe for inclusion was from inception to October 2020.Papers retrieved from the literature databases were imported to an EndNote library, and duplicate records were identified. Two researchers independently screened the titles and abstracts against the review inclusion and exclusion criteria . Full text papers of the remaining citations were then retrieved and independently assessed by two researchers . A third researcher (BB) moderated any discrepancies until the final selection of papers was agreed upon.The quality of studies included in the review was evaluated using a range of established critical appraisal tools selected for the particular study design: Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group ; The CocData extraction forms were designed and piloted before beginning data extraction, completed by two independent researchers. Data extraction tables consisting of numerical and textual data presented the study characteristics, results and quality assessments.Synthesis of the extracted data were conducted in a descriptive and tabular way . Categorn = 1493). Papers were then screened  based on the information provided by the title and abstract. Potentially eligible papers (n = 258) were retrieved for full text assessment by two independent reviewers  and any disagreement resolved by discussion with a third reviewer (BB) until agreement was reached. The level of agreement between the two reviewers produced a kappa value of 0.9 which suggests a very good strength of agreement . Excluded papers (n = 189) a) did not include relevant outcome measures, b) did not report ISS activities or interventions c) were not conducted in OECD countries. The literature search and inclusion process are detailed in the PRISMA Flow diagram [The search identified 6,105 potentially eligible papers. Duplicate papers were removed n = 1493)Findings were organised into categories to reflect the aims and objectives of the included studies using ISS: 1) as an assessment tool; 2) to assess and promote system readiness and safety cultures; 3) to improve clinical skills and patient outcomes; 4) to improve NTS, knowledge and comfort and confidence. The themes presented are:n = 17), with one study reporting a quasi-experimental design to compare outcomes using different resuscitation equipment [Eighteen studies conducted ISS as a method of assessment Table . Studiesquipment . Samplesquipment , LSTs inquipment , paediatquipment , pediatrquipment , and bloquipment . Four stquipment , sepsis quipment , blood tquipment  and cardquipment . Four stquipment –59, withquipment –62. ISS quipment  and to aquipment . One stuquipment  conducteAuerbach et al.  and KessISS performance was assessed by direct observation and by accessing feedback from participants. Two studies used evidence based clinical standards to assess performance, quality and safety metrics , 54. OutAuthors reported positive benefits of conducting ISS to identify risks and hazards in clinical environments and improve the ability to detect errors. ISS was reported to help identify system susceptibilities, evaluate the effectiveness of training programmes and highlight variability in performance across different departments and systems. Overall, aauthors reported positive benefits of ISS as a method of assessment, providing useful information to inform future improvement initiatives.Nine studies conducted ISS interventions with the aim of improving system or departmental performance outcomes Table . StudiesData were mainly collected via pre and post participant self-assessment questionnaires, outcomes included identification of LSTs, assessment of departmental readiness scores, safety cultures and attitudes, orientation and team and departmental performance. Identification of LSTs was captured via observation and via participant during ISS debriefing.Ventre et al.  identifiThree studies conducted ISS to improve safety compliance, cultures and attitudes –75. AlthSeventeen studies conducted ISS interventions with the aim of improving clinical skills, performance and clinical management Table . StudiesSome studies which involved more complex practices and clinical outcomes implemented regular ISS interventions over longer time periods. Andreatta et al.  conducteStudies which included more easily defined or isolated tasks, reported one to three ISS sessions as effective in improving: infection control practices ; thoracoNon-technical Skills (NTS) are individual and team social and cognitive skills, hat support technical skills when performing complex tasks. NTS can include planning and preparation for complex tasks, situation awareness, perception of risk, decision-making, communication, teamwork and leadership . Twenty-Significant improvements in confidence scores were reported for single session , 114, thImprovements in participants’ performance scores were reported in six studies , 113, wiTwo studies reported significant improvements in participants management and leadership scores following a single session  and threTwo studies , 118 repTwo studies reported significant improvement in anxiety scores following a single ISS intervention , 111.Four studies reported a significant improvement in participants knowledge scores following a brief ISS intervention , 115.Outcome measures included self-reported confidence scores, performance scores, management and leadership scores, communication, and self-reported anxiety and knowledge. Outcome measures, ISS frequency and outcomes scores are presented in Table n = 12, 6 units in each group). The median technical score was significantly higher for the ISS groups compared to the control groups. In the ISS groups, the frequency of achieving a heart rate of 90 per minute at 3 min improved significantly and the number of hazardous events decreased significantly. Four studies which compared ISS groups with control or comparison groups reported no statistical significant difference in outcomes: Gundrosen et al. [Rubio-Gurung et al.  comparedn et al.  comparedn et al.  comparedn et al.  comparedn et al.  comparedStudies conducted ISS interventions in in-patient care settings, predominantly in adult and paediatric EDs, obstetric/maternity units, cardiac response teams, adult and paediatric ICUs, and operating rooms. Data collection methods included direct observation, video review and data collected from simulation or clinical equipment. Participants’ knowledge, anxiety, comfort and safety attitudes were exclusively measured by self-reported questionnaires. There was a range of methods between and within studies to measure task performance, clinical management, teamwork and communication (including assessment from direct or video observation), alongside participants’ self-reported outcomes and /or clinical outcomes data.Teamwork and non-technical skills: Simulation Team Assessment Tool STAT , NONTECHReadiness scores: TESTPILOT , EmergenClinical performance: Clinical performance during Paediatric Advanced Life Support simulation scenarios , Self-EfConfidence scale Communication and collaboration Studies used various tools to assess performance during ISS interventions including:The benefits and limitations of conducting ISS reported across all included studies are summarised in Table This systematic mapping review found that ISS is reported to be feasible and beneficial in a variety of inpatient clinical settings. It is used to assess a number of different domains of practice including adherence to clinical guidelines and standards, task completion times, team performance, non-technical skills, detection of errors and latent safety threats.Lamé and Dixon-Woods  make an ISS outcomes were used to highlight where additional or new methods of training might be required to improve the quality of care, to identify LSTs and explore the accuracy and efficiency of task completion over the period of a working shift. Exploring the factors that can affect variations in adherence to clinical procedures, outcomes and performance may help to uncover where and why errors occur. ISS has the potential to reveal the constraining and facilitating mechanisms which impact performance and to identify modifiable factors at the individual, departmental, institutional level or system level –54.Some multicentre studies were conducted to assess clinical performance used validated tools to assessed adherence to guidelines and departmental readiness scores. The ability to standardise simulation across participating sites can help isolate independent variables and to reduce the risk of bias introduced by variations in local contexts . DiffereThere were considerable variations in the frequency of ISS sessions, length of ISS sessions and use of announced and unannounced ISS. However the length and frequency of ISS were not always reported. Studies which are focused on relatively straightforward, easily defined or isolated tasks, see improved outcomes after one to three ISS sessions , 93, 94.Most of the studies included in the review used locally developed checklists, developed through previous pilot testing or amended from checklists developed for other clinical settings. In general, there was a paucity of reporting of the validity and reliability of assessment measures and tools. Studies which reported team and system level assessments adopted more established outcome measures , 123. MeGoldstein et al.  stated tUnannounced ISS (or mock drills) were mainly conducted where studies sought to carry out a system audit or to assess clinical performance against a benchmark. Whereas announced ISS, which gave participants varying levels of notice and access to supportive resources, were mainly conducted as part of improvement projects or as part of clinical training. Posner et al.  highlighCheng et al.  recommenISS to assist teams train, rehearse and practice for low frequency, high impact events were frequently reported simulation activities in the review. The theoretical base for ISS as a training intervention was not reported in many studies, however ISS as a training intervention maps to the concepts within cognitive learning approaches where participants preconceptions are explored, and new or unexpected events are presented via the simulation activity to challenge precognitions . ISS is This review should be viewed in light of several limitations. This review did not include grey literature, conference abstracts and academic theses. It is likely that grey literature may include ISS practice-based improvement and educational projects which further illustrate the current uses of ISS in healthcare settings. However, this review highlights the lack of rigorous intervention ISS research and the urgent need to increase research output and methodological quality. The mapping review aimed to provide an overview of the broad ISS published literature and did not conduct in-depth analysis of study outcomes to enable meaningful comparisons. The review has highlighted different categories and approaches to ISS, identifying common outcomes measures and measurement tools. Mapping reviews are distinguished by the presentation of the data in a digestible format and assessment of whether the total population of studies is similar enough to undertake a coherent synthesis of the current data . TherefoThis review presents an overview of the literature on ISS interventions by mapping the study objectives, methods, outcomes, barriers, and facilitators at work across different settings. The mapping review provides a useful summary for healthcare educators and researchers seeking to develop ISS strategies in healthcare settings. Additionally, it highlights important evidence gaps, including the need to (1) identify appropriate tasks capable of standardisation and reproducibility in ISS assessment scenarios (2) capture adequate demographic data from participants to assess the impact on outcomes  (3) explore different methodologies in an attempt to reduce bias and confounding factors (4) develop and validate sensitive data collection methods and tools to capture the complexity of team and individual performance in real settings (5) identify optimal frequency and length of time to complete ISS, considering feasibility and acceptability in the clinical setting. This systematic mapping review has provided a useful framework to navigate the expansive and diverse research literature on a relatively new and underdefined approach to ISS as a function to assess individual, team and departmental performance. There is currently a lack of consensus for the rationale for conducting ISS interventions and well-developed studies are required to identify the potential benefits of ISS and the impacts on patient outcomes. Overall, studies reported ISS to be feasible and beneficial to address various learning and improvement objectives. The components and mechanisms employed across the included studies which have been designed to address a range of objectives can inform future design of ISS interventions to meet specific objectives.


Physical literacy has quickly gained global attention as a holistic approach to combat physical inactivity and obesity. However, research silos may limit the growth and application of the physical literacy paradigm for effective physical activity promotion. The purpose of this study was to measure the underlying network structure of scholars publishing on physical literacy  through co-authorship analysis.Data collection resulted in 1,070 documents related to physical literacy retrieved. A total of 198 articles met inclusion criteria and were included in the full network, with authors operationalized as actors in the network. A total of 75 empirical studies were included in the sub-network for critical appraisal and further analysis. Social network analysis was then conducted at the macro- and component-level, using quantification and visualization techniques.Results revealed a collaborative, yet fragmented physical literacy network with sub-groups representing substantive and geographically diverse scholars. The majority of scholarship lacked empirical evidence, suggesting a research-practice gap.Recommendations for advancing physical literacy research and practice include strategic collaborations that transcend geographic and disciplinary boundaries, cooperative efforts across scholars and practitioners, and productive discourse through professional avenues to progress knowledge generation, dispersion, and application. Physical inactivity is considered one of the most significant public health issues of the twenty-first century based on its prevalence, global reach, and health effect Blair, . The WorFrom an ecological perspective, individual , interpersonal , and environmental  factors often impede physical activity engagement among underserved populations  can be employed to characterize and quantify the social structure and interaction among scholars contributing to the physical literacy idea space Freeman, . BroadlyScholars within the physical literacy scientific community have identified an absence of empirical research to support the operationalizing, theorizing, and measuring of physical literacy ?RQ2: What is the social network structure of the global sub-network of authors publishing empirical research on physical literacy .Social network studies seeking to evaluate the global network structure of a community of people require data on the presence—or absence—of social interactions among the members of the population studied  used as a guide  published in peer-reviewed journals; (2) written in English language; and (3) utilized the phrase “physical literacy” in the title or abstract. Technical reports, book chapters, abstracts, conference presentations, and community resources were excluded. Full-text digital copies for 11 articles could not be retrieved via any available sources  and were also excludedData collection resulted in a total of 1,070 records retrieved. A backward search of reference lists from the eligible records resulted in retrieving an additional 38 records. Preliminary screening identified 365 duplicate records, once removed a total of 743 records were screened for inclusion and exclusion criteria. Upon screening, 545 records were excluded and 198 articles included in the full network see 2. Among The structure of relational webs is a central concept within global social networks  in this sub-network. The average number of authors per publication was 3.43. A total of 490 pairs of authors collaborated at least twice, 352 pairs three times, 296 pairs four times, 228 pairs five times, 120 pairs six times, 18 pairs seven times, 16 pairs eight times, six pairs 12 times, four pairs 13 times, and two pairs at least 14 times which was the maximum frequency of co-authorship.As indicated in As presented in Group 2 was composed of two researchers from Canada and one from Australia (associated with Group 5 in the full network). To frame the physical literacy construct, these authors synthesized the many definitions of physical literacy found in the literature. Research from Group 2 reflected an integration of health and education, with keywords including physical activity promotion, free play, sport, and youth development. Similar to the measurement contribution of Group 1, members of Group 2 were responsible for the development of the Physical Literacy Assessment for Youth (PLAY) tools. Members of Group 2 were also part of the Physical Literacy Research Group, responsible for the special issue on physical literacy in the Journal of Teaching in Physical Education.Group 3 included three researchers from the UK, one from Canada, and one from Australia (associated with Group 4 in the full network). Research from Group 3 seemed to focus on clarifying the definitions, foundations, and measures of physical literacy to inform policy and practice. This was illustrated by the authors' engagement with prominent groups working to promote and develop physical literacy, contribution of multiple systematic reviews of physical literacy literature, and use of keywords such as definition, policy, practice, and international. Further, members of Group 2 developed a new definition of physical literacy sensitive and appropriate to the Australian context, that can also contribute to productive scholarly debate and conceptual development of the physical literacy construct.The density of the network structure is based upon the degree of interconnectedness among all possible social ties within the social network Scott, . The denConsidering the “six degrees of separation”  and 28 components in the empirical sub-network (excluding isolates). For Newman's modularity, a relatively high value within a co-authorship network component indicates a network consists of authors that are more likely to publish papers together while a low value indicates authors are less likely to work together. The results show that scholars within the physical literacy co-authorship network were more likely to collaborate, having relatively high values of Newman's modularity for the full network (0.695) and empirical sub-network (0.630).Through SNA of the physical literacy scientific community, the network structure can reveal existing research silos and potential unifying pipelines to prompt cooperative efforts around a scientific paradigm necessary for physical literacy to be systematically leveraged for global application Crane, . To advaWhile Young et al.  identifiAs a whole, the co-authorship network tended to be geographically bound  and researchers from universities across Canada —Group 1—were identified as the most co-authored scholars  and most influential in disseminating information through the network. This finding suggests this particular collaboration may be uniquely positioned to serve as a scientific bridge within the physical literacy scholarly community. Within this cluster, Tremblay and Longmuir—the lead developers of the CAPL—were identified as the most well-connected scholars. However, the comparable closeness centrality within the full network and empirical sub-network suggests no singular leading actor in the physical literacy idea space, confirming the diversity of perspectives present.Of the 198 articles in the full network, <40% were classified as empirical studies. These results suggest a research-practice gap, aligning with Giblin et al.'s  findingsSince 2018, 47 empirical studies have been published—of which 14 came from BMC Public Health's special issue on the CAPL, contributing to Group 1's influence within the empirical sub-network. Further, seven studies came from the Journal of Teaching in Physical Education's special issue on physical literacy, contributing to Group 2's influence within the empirical sub-network. These findings demonstrate increasing interest in physical literacy evidence and intervention in the past several years. Physical literacy special issues in academic journals may foster exponential growth of the physical literacy idea space through scholars' cooperative efforts to advance physical literacy scholarship. However, these special issues may also perpetuate bias as the literature remains constrained to dominant fields , viewpoints , and measures , limiting scholars' exposure to alternative ideas necessary to re-examine and improve the physical literacy paradigm (Quatman and Chelladurai, Despite the surge in physical literacy scholarship, confusion around its conceptualization remains (Shearer et al., In reviewing consensus statements and frameworks from the countries represented in the empirical sub-network, there were subtle differences in the conceptualization of physical literacy. Canada's Physical Literacy Consensus Statement  identifiInconsistencies throughout the body of empirical literature were highlighted further in a second systematic review by Edwards et al.  from GroMuch of the available research thus far has focused on the physical education, public health, or sport/exercise science sectors within the youngest generations (Roetert et al., However, the current study demonstrates physical literacy scholarship is a fragmented network which might impede or slow down the advancement of physical literacy strategies to address physical inactivity and obesity Crane, . While tAligning with Whitehead's  holisticAn approach to building connections within the fragmented physical literacy network could be engaging in productive discourse and coordinating efforts through professional associations, conferences, workshops, meetings, as well as academic and practitioner journals. The study identified several professional avenues—such as the International Physical Literacy Association—that provide an opportunity for scholars and practitioners across disciplines to collaboratively advance physical literacy. Through innovative collaboration, the physical literacy scientific community can facilitate continued growth and application of a cumulative body of knowledge to mitigate physical inactivity among underserved populations through the promotion of physical literacy.physical literacy for a more complete picture of physical literacy scholarship. The systematic search and selection process was also limited to six major online research databases. Broadening the search to multidisciplinary databases, such as SCOPUS or Web of Science, might capture additional literature in other disciplines. Further, the current study's focus on empirical scholarship does not account for all actors engaged in the physical literacy idea space. Future research should consider examining the social network of physical literacy scholars engaged in non-empirical work that contributes to the advancement of the paradigm.While the current study extends our understanding of the physical literacy idea space, the results should be interpreted with several limitations in mind. Physical literacy literature retrieved was limited to the English language due to the authors' language barriers, which may result in bias toward the Anglo-Saxon research lens. Future scholars should consider inclusion of literature written in other languages and translated variations of the term The authors only used co-authorship to capture the individual and collaborative work of the physical literacy scientific community (Hazlett et al., The current study examined the social network of physical literacy scholars to advance the evolution, growth, research, and application of this paradigm for physical activity promotion. Study findings revealed a highly collaborative yet fragmented physical literacy network, with opportunity for greater social interactions among the scholars working in the physical literacy idea space. Of the 198 articles included in the full network, only 75 articles were classified as empirical studies. This gap between research and practice must be addressed for the physical literacy paradigm to effectively inform physical activity interventions for the goal of promoting healthy development of the whole person. Through SNA, diverse collaborative groups were identified, with implications for cooperative efforts to build a cumulative and coherent body of knowledge that enables physical literacy to be globally operationalized and leveraged for physical activity promotion. Ultimately, the physical literacy paradigm can provide a unifying framework for public health, recreation, sport, and education agencies to effectively promote physical activity among underserved populations in greatest need.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.SB, MP, and CZ collected the data and supported manuscript development. LL-H and AK analyzed the data and drafted the manuscript. LS and CQ-Y provided critical revisions of the manuscript. All authors made substantial contributions in drafting or revising the manuscript. All authors gave final approval of the version submitted.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.


The BLSA is an invaluable resource for the study of human aging with uniquely rich measures taken longitudinally on a continuous replenishment cohort since 1958. Tremendous interest has been expressed by the United States and international research communities in expanded access to and use of BLSA data to address emerging scientific questions. Here, we will describe recent study leadership initiatives into: (1) making the BLSA data more FAIR , (2) growing a BLSA data ecosystem that enables scalable sharing, and (3) leveraging and developing platforms for accessing the ecosystem. Lastly, we will demonstrate current platform functions that empower researchers to find and access BLSA data, metadata, protocols, code and supporting materials to make new discoveries.


Nursing care is increasingly supported by computerized information systems and decision support aids. Since the advent of handheld computer devices (HCDs), there has been limited exploration of their use in nursing practice.The study aimed to understand the professional and clinical impacts of the use of mobile health apps in nursing to assist clinical decision-making in acute care settings. The study also aimed to explore the scope of published research and identify key nomenclature with respect to research in this emerging field within nursing practice.This scoping review involved a tripartite search of electronic databases  using preliminary, broad, and comprehensive search terms. The included studies were hand searched for additional citations. Two researchers independently screened the studies for inclusion and appraised quality using structured critical appraisal tools.Of the 2309 unique studies screened, 28 (1.21%) were included in the final analyses: randomized controlled trials  and quasi-experimental , observational , mixed methods , qualitative descriptive , and diagnostic accuracy  studies. Studies investigated the impact of HCDs on nursing decisions ; the effectiveness, safety, and quality of care ; and HCD usability, uptake, and acceptance  and were judged to contain moderate-to-high risk of bias. The terminology used to describe HCDs was heterogenous across studies, comprising 24 unique descriptors and 17 individual concepts that reflected 3 discrete technology platforms . Study findings varied, as did the range of decision-making modalities targeted by HCD interventions. Interventions varied according to the level of clinician versus algorithmic judgment: unstructured clinical judgment, structured clinical judgment, and computerized algorithmic judgment.The extant literature is varied but suggests that HCDs can be used effectively to support aspects of acute nursing care. However, there is a dearth of high-level evidence regarding this phenomenon and studies exploring the degree to which HCD implementation may affect acute nursing care delivery workflow. Additional targeted research using rigorous experimental designs is needed in this emerging field to determine the true potential of HCDs in optimizing acute nursing care. The commercial release of smartphones in 2007 initiated a revolution in handheld device ownership, facilitating multimodal instant communication options and the rapid evolution of mobile health apps that provide instantaneous access to web-based information and resources . HandhelHCDs provide nursing staff with a powerful and accessible mobile platform for a range of decision support applications. Tiffen et al  defined Reviews of the extant literature have typically explored HCD use by nonnurses ,17, did In this paper, we report the findings of a scoping review that sought to identify and evaluate the body of published empirical literature investigating the use and effectiveness of HCDs in supporting nurses’ clinical decision-making in the acute health care settings. This review aimed to summarize the extent, quality, characteristics, and scope of published research and identify key nomenclature with respect to this emerging field.To address the above aims, we undertook a scoping review involving both systematic electronic database searches and hand searches of the reference lists of the included studies. The PRISMA-ScR  checklist was used to guide review methodology and reporting .We operationally defined HCDs as any portable computer device that a person can hold in one hand and control using the other hand, including PDAs, smartphones, and tablet devices but excluding ubiquitous computing devices. Studies were screened against inclusion and exclusion criteria by one reviewer (DG). Ambiguous papers were subjected to full-text review. Two reviewers (DG and AH) independently performed full-text review of the screened papers, appraised the methodological quality of the included studies using Joanna Briggs Institute critical appraisal tools , and undKeywords denoting HCDs varied among studies. Consequently, we used a strategy involving 3 successive literature searches  to generate productive search terms and provide multiple patterns of literature coverage. All searches were limited to English language publications.We undertook a preliminary scoping of literature published between 2001 and 2021 in CINAHL Complete, MEDLINE Complete, Embase, and Scopus. MEDLINE and CINAHL were searched using a combination of medical subject headings, CINAHL subject headings, and the following keywords: “Nursing Staff, Hospital”; “Acute Care Nurse Practitioner”; nurs*; “Decision Making, Computer Assisted”; “Decision Making, Clinical”; “Decision Making”; “Decision Making, Patient”; “Nursing Care Plans, Computeri?ed”; “clinical judgement”; “mobile application”; and “mhealth.” Embase and Scopus searched with simple keywords: “nurs*”; “decision*”; and “handheld computer*.” Search terms were initially derived from the systematic literature review by Mickan et al  and are Results from the preliminary database search identified few studies on current generation HCDs such as smartphones, Android, iOS, and tablet devices. Therefore, a second search using a small number of broad search terms and limited to 2010 to 2021 was conducted to help identify additional keywords. We conducted this search in CINAHL Complete, MEDLINE Complete, Embase, and Google Scholar using the following keywords: “Decision Making, Computerised”; “nurs*”; “acute”; and “handheld” . It was A final, comprehensive search was conducted in MEDLINE, Embase, and CINAHL (2010 to 2021). This search was conducted to determine whether a more structured and detailed search strategy derived from the results of literature searches 1 and 2 would identify a more comprehensive list of relevant studies. Details of the search algorithm is provided in Studies were included according to the following criteria: (1) primary research study; (2) study that explored the effect, acceptability, or usability of HCDs with respect to nurses’ clinical decision-making; (3) study conducted in an acute care setting; and (4) peer-reviewed journal publication. Conference proceedings and dissertations, studies that did not include nurses in the evaluation, studies not conducted at the point of patient care, and studies that explored the effect of HCD devices on nurse education or professional development were excluded from the review. As this was a scoping review, studies were not excluded on the basis of study design or methodological quality.Management of scoping review citations and study data was undertaken in the Covidence reference management platform . To cateStudy data were extracted and recorded on a spreadsheet, capturing study characteristics—design, methodology, sample size context, type of computer technology used, information delivery mode, decision support information provided—and study outcomes—outcome measures and findings.A total of 3108 records were identified from the 3 literature searches and hand searches of reference lists. After removing duplicate records, 74.29% (2309/3108) of studies were screened based on title and abstract, and 24.17% (558/2309) underwent full-text review. A total of 98.79% (2281/2309) of studies failed to meet the inclusion criteria and were excluded from the review. In total, 28 studies were included in the final analysis. These comprised randomized controlled trials  ; quasi-eOverall, 3 thematic areas of inquiry emerged from the included studies : impact The characteristics and outcomes of the 12 studies that investigated HCDs as clinical decision-making supports are summarized in Research investigating the impact of HCDs on the quality of clinical decisions or processes 10/28, 36%) found significantly greater rates of diagnosis when using an HCD system for the assessment and management of obesity, tobacco use, and depression , 36% fou and clinResearch  examining the degree to which handheld technology may enhance nurses’ self-rated decision-making capacity reported no significant impact from HCDs. Specifically, Sedgwick et al  found thThe characteristics and outcomes of the 32% (9/28) of studies that investigated the effect of HCD decision support systems on the efficiency, quality and safety of care delivery are summarized in Most  published research that examined the flow of nursing activities reported a positive association between the use of HCDs in the clinical setting and nursing efficiency. Research that found a positive clinical impact of HCDs in this respect comprised 50% (2/4) of studies of an HCD-based medical dosing support system, which resulted in significantly reduced drug preparation time, time to drug delivery, and medication errors compared with usual care ,30 and 5The literature suggested that HCD interventions enhanced team communication and were safe, but the number of relevant studies was less. Authors reporting on postimplementation focus groups  and quesThe final study within the theme of efficiency, safety, and quality of care explored perceptions of HCD-facilitated care quality in 10 nurses . InterviStudies that evaluated the usability, uptake, and acceptance of HCDs among clinical end users are detailed in Studies that explored HCD usability, uptake, and acceptance varied by technology platform. Except for 21% (3/14) of PDA studies ,47,53 anThe reviewed findings consistently suggested that HCD devices may facilitate improved processes for clinical data entry and retrieval at the point of care . For example, recording children’s physiological data was found to be faster and more accurate when using a handheld device compared with traditional written medical records , and a fStudies of the usability of HCD interventions with respect to heuristics, human factors, or ergonomics 5/14, 36%) reported varied findings. Cognitive work analysis interviews undertaken with cardiac nurse coordinators  suggested that the PDA-based decision support aids were easier to use and yielded clearer and more consistent data collection by nursing staff than their paper-based equivalents . In anot% reporteDescriptive research on nurses’ patterns of HCD use  reported on the frequency of self-initiated access of mobile phones and PDAs in the clinical space ,48 and iThe social pervasiveness of HCD technology, coupled with its low cost, provides nurses with access to a set of tools capable of optimizing patient care at the bedside. Despite the slow initial adoption of this technology , this syThis review identified that the literature investigating nurses’ use of HCDs at the point of care has targeted a variety of decision-making modalities ranging from the use of static guides supporting unstructured clinical judgments to fully algorithmic decisions based upon the computation of patient characteristics. Presently, the prevailing models of the psychology of decision-making identify 2 qualitatively distinct types of mental processing for decision-making: type 1, “autonomous processing,” reflecting automatic, rapid, intuitive, or associative judgments; and type 2, “effortful processing,” reflecting conscious or slow processing  ,57. StruAlthough the current trend of implementing HCD support for more structured nursing applications may better leverage the available mobile computing capabilities, many nursing tasks require rapid clinical judgments based on clinical experience . ClinicaThis review found that the most frequently undertaken domain of study on the bedside use of HCDs concerned device usability, uptake, and acceptance. However, these issues have not been explored in depth, or study outcomes were specific to individual interventions with unclear generalizability to external health settings. There was a high degree of reliance upon subjective outcomes such as staff self-reports, which may result in biased outcomes because of perceived pressures to respond positively. Although user uptake was a key component of several individual intervention studies, to date, the published research has not identified principle-based barriers and facilitators capable of guiding future HCD interventions. Furthermore, a serious gap in the existing research was the absence of detailed investigation into the degree to which HCD implementation may disrupt the existing workflows. Additional work in this area is critical to developing a more holistic understanding of the clinical value of HCD interventions to nursing care delivery in the acute health care setting.within these overarching labels, demonstrating a lack of standardized terminology. To assist future discovery and categorization of studies in this field, efforts to standardize the language may prove fruitful. Initially, we recommend that future researchers include clear terms such as “smartphone” and “tablet” that readily communicate the technology platform being used.Finally, this review identified significant heterogeneity in the descriptors used within the published literature to denote HCDs. Individual descriptors (n=24) could be subsumed under 3 discrete labels with respect to the type and degree of technological development . Despite this, there was limited uniformity between the descriptors The finding that the level of evidence within the body of empirical literature was insufficient to support meta-analyses indicates the critical need for additional research to investigate the impact of HCDs on clinical nursing care in the acute practice setting. Notably, the preponderance of small-scale studies using observational designs highlighted the need for large, well-designed experimental trials using randomization or cluster randomization, where possible. Furthermore, as much of the extant literature has evaluated the impact of HCDs in pooled samples of multidisciplinary health care cohorts, there is a need to measure nurse-specific outcomes via nursing-specific studies or multidisciplinary studies using stratified analyses. Finally, as the use of HCDs in nursing practice implicitly lends itself to data capture via large-scale digital connectivity, future investigations in this field should attempt to leverage the potential of “big data” involving sizable data sets from multiple users across multiple domains . DespiteMany of the retrieved studies measured the nursing and patient impacts of digital tools focused on multidisciplinary health assessment, diagnosis, and treatment modalities. However, this highlighted gaps in HCD-–based applications designed to support decision-making for other nurse-sensitive outcomes, including the assessment of clinical deterioration, patient comfort, functional status, and predischarge self-efficacy. Moreover, given the dynamic, treatment-based focus of care delivery in the acute health care environment, there is also a need to develop digital tools that support decisions for nursing care organization, including patient care prioritization, workflow, and safety. Other aspects of clinical handheld device use also need further exploration, including the potential benefits to patient care quality and safety resulting from productivity gains and the point-of-care use of specific computerized resources. Research should also systematically test the utility of various handheld programs’ user interface and interactivity designs to ensure that they assist rather than impede the flow of care delivery. Research should be undertaken to guide the future development of context-specific clinical HCD applications to improve the utility, safety, and value of such assistive devices in terms of the particular requirements and demands of acute nursing care delivery.This scoping review had several limitations. First, as the primary focus was on published peer-reviewed literature, the gray literature was not comprehensively searched, and this may be an area of inquiry for future research. This would assist in determining the degree of positive publication bias present in the peer-reviewed literature. Second, this review was limited to studies undertaken in acute settings. Future research should investigate the degree to which impacts measured in nonacute settings may be generalizable and applicable across a range of health care settings. Third, this review was undertaken in the context of research for a minor thesis, without the resource to translate and include non-English publications.This paper has described the complexities involved in conducting a systematic scoping review and the dearth of quality research on the use of HCDs to support acute clinical nursing practice, highlighting the need for more targeted and rigorous research on this phenomenon. It is suggested that future research adopts a recognized nurse- and patient-sensitive outcome framework and focuses explicitly on the integration of mobile computing technology into the existing workflows and investigation of the impact of HCDs on patient care outcomes.


Rates of unplanned pregnancies are high and stagnant globally, burdening women, families and the environment. Local limitations placed upon contraceptive access and abortion services exacerbate global disparities for women. Despite survey data suggesting men and their partners are eager for expanded male contraceptive options, efforts to develop such agents have been stymied by a paucity of monetary investment. Modern male hormonal contraception, like female hormonal methods, relies upon exogenous progestins to suppress the hypothalamic-pituitary-gonadal axis, in turn suppressing testicular testosterone production and sperm maturation. Addition of an androgen augments gonadotropin suppression, more effectively suppressing spermatogenesis in men, and provides androgenic support for male physiology. Previous contraceptive efficacy studies in couples have shown that hormonal male methods are effective and reversible. Recent efforts have been directed at addressing potential user and regulatory concerns by utilizing novel steroids and varied routes of hormone delivery. Provision of effective contraceptive options for men and women is an urgent public health need. Recognizing and addressing the gaps in our contraceptive options and engaging men in family planning will help reduce rates of unplanned pregnancies in the coming decades. Globally, unplanned pregnancy rates have remained high over the last three decades, a time that has coincided with global warming, population growth and increasing calls for policies that decrease greenhouse gas emissions . Limitedth century when academia, non-governmental organizations, pharmaceutical entities, and governmental agencies were investors. In the last decade, pharmaceutical companies have largely abandoned their male contraceptive development programs. Can this trend be reversed? We believe we are at a turning point with new male contraceptive methodologies showing promise and strongly positive receptivity from both men and their partners  committed to helping develop male contraceptives has recently conducted consumer market research among men in the United States. Their findings echo earlier enthusiasm; approximately 50% of US men, ages 18-49 who have sex with women and do not wish to father a pregnancy express a high level of interest in novel male contraceptives . Data haFor effective uptake, novel contraceptives must be cost-effective for users and for public health programs aimed to assist family planning. In this context, it is noteworthy that in the United States, long-acting reversible contraceptives (LARCs) female intrauterine devices and implants, are the most cost-effective contraceptive methods, despite high up-front costs . ModelliLike hormonal female methods, hormonal male contraceptives utilize exogenous steroids to interrupt physiologic hypothalamic-pituitary-gonadal pathways. Exogenous steroids suppress secretion of gonadotropins, LH and FSH; lack of gonadotropins impairs testosterone production and sperm maturation in the testes, resulting in profound reductions in sperm output 4-12 weeks following initiation of the method. Proof-of-principle studies in the 1980s performed by the World Health Organization (WHO) demonstrated that exogenous high-dose androgens given to healthy men markedly, and reversibly, suppressed spermatogenesis and provided effective contraception for couples –19. The To date, a total of eight hormonal male contraceptive efficacy studies have been conducted, five utilized only testosterone derivatives and three administered a progestin plus testosterone , 21–26. Eunice Shriver Kennedy National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, has evaluated transdermal gels delivering a novel progestin, segesterone acetate  and testosterone to inhibit sperm production. This transdermal NES/T gel has the potential to provide more independence and less discomfort for users than injections and implants and has few side effects whilst delivering physiologic doses of androgens . With the approval of transdermal formulations of testosterone, research supported by the ndrogens –31.We are conducting a Phase 2b contraceptive efficacy study of NES/T transdermal gel. This multi-national study enrolling 400 couples is the first to evaluate contraceptive efficacy of a daily, self-delivered male contraceptive agent. Importantly, with sites in the United States, Europe, South America and Africa, it will provide information from a diverse group of potential users and is the first male contraceptive efficacy study to include a site in Sub-Saharan Africa. Early clinical studies of NES/T gel demonstrated high effectiveness at suppressing gonadotropins and sperm production –31, and A notable deficiency in hormonal male contraceptive development and clinical testing has been candidate oral formulations. Many men report they would prefer an oral agent to other modes of contraceptive delivery . Until rin vivo, by endogenous esterases. DMA and 11β-MNT activate both androgen and progesterone receptors ) and 11-beta-methyl-19-Nortestosterone 17-beta-dodecylcarbonate (11β-MNTDC), are synthetic pro-drugs under investigation as both oral and injectable contraceptive agents. DMAU is converted to the active drug, DMA, and 11β-MNTDC to 11β-MNT, eceptors . These peceptors  to exerteceptors . In vitractivity , 38; thuin vivo demonstration of the androgenic activity of DMA previously observed in vitro  and acne  will be identified, similar to benefits of some female hormonal methods. While men do not experience medical risks of pregnancy, exploring the mental and economic costs and benefits men erlooked .A major impediment to moving male contraceptive development forward is a lack of regulatory guidance, inhibiting both scientific and financial investment. While work is ongoing to develop effective and well-tolerated products, it is not known what regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) will find permissible for initial approval of the first hormonal male contraceptive. Consensus recommendations from the research community have been published  but whetAlong with scientific and clinical investment and innovation, behavioral studies to understand and address the impact of user variables, including product preferences, compliance, barriers to uptake, social biases, and access to contraceptives are critical to advancing the field of male contraception. Male-directed contraception is not new, but the last novel method, the condom, was introduced to the marketplace over 200 years ago. Novel male contraceptive methodologies demonstrate strongly positive receptivity from both men and their partners. Innovative experimental designs are needed to understand behavioral aspects of modern male contraceptive use. In parallel, engaging reproductive-age male and female advocacy groups will be critical to disseminating accurate information regarding novel male contraceptive methods, helping to reduce misinformation and disparities in access to products. Engaging pharmaceutical companies to co-develop products and initiate new pathways to product development is critical to moving the field forward. Lastly, fair pricing, prescribing practices and health care coverage will be necessary to ensure male contraceptives impact unplanned pregnancies and the global health of future generations of men and women.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.All authors  contributed to the concept, writing and editing of this manuscript. All authors read and approved the final manuscript.Eunice Kennedy Shriver National Institute of Child Health and Human Development for Clinical Evaluation of Male Contraceptives (Contract number: HHSN275201300025I). SP is also supported by the Robert McMillen Professorship in Lipid Research. CW receives funding form the Eunice Kennedy Shriver National Institute of Child Health and Human Development for Clinical Evaluation of Male Contraceptives: Contract number HHSN275220130024I and 75N94020D0007 and P50 HD098593 National Male Reprodutive Epigenomics Center and the National Center for Advancing Translational Sciences UL1TR 001881 UCLA Clinical and Translational Science Institute.SP receives funding from the National Institutes of Health through the 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.


Due to the high availability and use of digital media, health-related information is increasingly shifting into the digital space. While there are increasing empirical findings on general health literacy (HL), there is a lack of evidence on digital HL in adolescence and its association with health behavior.A cross-sectional study of 490 secondary school students (grades eight and nine) from the federal state of Hesse was conducted from October 2019 to February 2020. Digital HL was assessed using five subscales of the Digital Health Literacy Instrument (DHLI), while consumption of fruits, vegetables, soft drinks, and weekly physical activity were used as indicators of health behavior. In addition to gender and grade level, subjective social status (SSS) was used as a social characteristic. Univariate, bivariate, and multivariate analyses were performed, with binary-logistic regression adjusted for gender and SSS.Across all items, the percentage of adolescents reporting difficulties in acquiring and dealing with digital health information ranges from 15.3 % to 37.5 %. Stratified by social characteristics, gender and socioeconomic differences were found with girls and respondents reporting a lower SSS more often showing a limited digital HL. Adolescents with moderate and low digital HL report higher levels of low physical activity, non-daily fruit and daily soft drink consumption. Depending on the health behavior, different relationship patterns can be observed for the dimensions of digital HL.The findings suggest a need for interventions to promote digital HL among adolescents, particularly for those of low SSS. In this context, the differential relationship patterns with health behaviors provide an avenue for the development of specific interventions.


Mycobacterium tuberculosis (Mtb) to establish infection. Alcohol misuse impairs the immune functions of the alveolar macrophage, the resident innate immune effector in the lung and the first line of defense against Mtb in the lower respiratory tract. Chronic alcohol ingestion also increases oxidative stress in the alveolar space, which could in turn facilitate Mtb growth. In this manuscript, we review the epidemiologic data that links AUD to TB. We discuss the existing literature on the potential mechanisms by which alcohol increases the risk of TB and review the known effects of alcohol ingestion on lung immunity to elucidate other mechanisms that Mtb may exploit. A more in-depth understanding of the link between AUD and TB will facilitate the development of dual-disease interventions and host-directed therapies to improve lung health and long-term outcomes of TB.Globally, an estimated 107 million people have an alcohol use disorder (AUD) leading to 2.8 million premature deaths each year. Tuberculosis (TB) is one of the leading causes of death globally and over 8% of global TB cases are estimated to be attributable to AUD. Social determinants of health such as poverty and undernutrition are often shared among those with AUD and TB and could explain the epidemiologic association between them. However, recent studies suggest that these shared risk factors do not fully account for the increased risk of TB in people with AUD. In fact, AUD has been shown to be an independent risk factor for TB, with a linear increase in the risk for TB with increasing alcohol consumption. While few studies have focused on potential biological mechanisms underlying the link between AUD and TB, substantial overlap exists between the effects of alcohol on lung immunity and the mechanisms exploited by  While tth century, physicians noted the increased incidence of infections, like TB and other causes of pneumonia, among patients that consumed alcohol  and active TB disease is higher among persons with alcohol use disorders (AUD) than those without AUD . For exaWhile improvements in diagnostics and broader access to treatment have led to global declines in TB incidence since 2000 , cases oAlthough the interactions between poverty, social marginalization, alcohol misuse, and TB remain complicated and difficult to disentangle, their overlap does not fully explain the increased risk of TB with AUD. Studies examining the relationship between AUD and TB have shown that AUD remains a significant independent risk factor for TB, with a relative risk of 2.9, even after controlling for confounders such as comorbidities, lifestyle, or social determinants of health , 26–28.Mtb bacterial load compared to TB without an AUD association  and reactive nitrogen species (RNS), that are released into the alveolar environment. In the lungs, there are efficient antioxidant defense systems, including antioxidant enzymes and antioxidant stores, that defend against oxidants and other reactive species , 64. MaiAUD increases pulmonary oxidative stress and induces an oxidized microenvironment within the lung through a variety of mechanisms. AUD depletes antioxidant stores, including GSH, within the pulmonary environment . GSH serThere are a number of mechanisms through which alcohol depletes pulmonary GSH stores. First, alcohol induces mitochondrial dysfunction which decreases ATP generation and, in turn, may decrease GSH synthesis , 71. GSHAUD further increases alveolar oxidative stress by enhancing the expression and activity of NADPH oxidases (Nox). Nox proteins are membrane-associated enzymes that catalyze the reduction of molecular oxygen to superoxide and hydrogen peroxide, thus serving as major sources of ROS in the lungs. In alcohol-fed mice and rats, increased Nox expression increases alveolar oxidative stress , 73, 75.The increased oxidative stress within the alveolar microenvironment of individuals with AUD has important implications for pulmonary innate immunity. GSH deficiency increases alveolar epithelial intercellular permeability and diminishes surfactant synthesis , 79, 80.Mtb has also been shown to increase oxidative stress and deplete antioxidant levels in the lungs. People with active TB disease had lower circulating levels of serum thiol and increased levels of its oxidized product serum disulfide (Mtb and Mycobacterium abscessus (a rapid growing mycobacterium), have been associated with increased oxidative stress, as shown by decreases in total serum antioxidant capacity, total GSH, and increased lipid peroxidation  infection , damage-associated molecular patterns (DAMPs), and pattern recognition receptors. They have robust phagocytic and killing abilities and act as initiators of the inflammatory response. They function as antigen presenting cells that assist in the activation of the adaptive immune system. Further, macrophages participate in tissue repair, tissue remodeling, and maintain homeostasis , and interferon gamma (IFNγ). It produces proinflammatory cytokines and chemokines like interleukin (IL)-12 and tumor necrosis factor alpha (TNFα), induces further inflammation and IFNγ release, and attracts neutrophils, natural killer (NK) cells, and lymphocytes to the site of infection . It reli1 production, both associated with suppression of inflammation, as well as decreased phagocytic ability  and IFNγ, ultimately promoting Mtb’s intracellular survival  , and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) .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.


Epidemiological studies have demonstrated an association between the degree of food processing in our diet and the risk of various chronic diseases. Much of this evidence is based on the international Nova classification system, which classifies food into four groups based on the type of processing: (1) Unprocessed and minimally processed foods, (2) Processed culinary ingredients, (3) Processed foods, and (4) “Ultra-processed” foods (UPF). The ability of the Nova classification to accurately characterise the degree of food processing across consumption patterns in various European populations has not been investigated so far. Therefore, we applied the Nova coding to data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in order to characterize the degree of food processing in our diet across European populations with diverse cultural and socio-economic backgrounds and to validate this Nova classification through comparison with objective biomarker measurements.-methyl syringol sulfate (an indicator for the consumption of smoked food and a component of liquid smoke used in UPF).After grouping foods in the EPIC dataset according to the Nova classification, a total of 476,768 participants in the EPIC cohort  9.93]; median age 52 [percentile (p)25–p75: 58–66] years) were included in the cross-sectional analysis that characterised consumption patterns based on the Nova classification. The consumption of food products classified as different Nova categories were compared to relevant circulating biomarkers denoting food processing, measured in various subsamples  within the EPIC cohort via  correlation analyses . These biomarkers included an industrial transfatty acid (ITFA) isomer  and urinary 4r = 0.54) and 4-methyl syringol sulfate (r = 0.43). Associations for the other 3 Nova groups with these food processing biomarkers were either inverse or non-significant .Contributions of UPF intake to the overall diet in % grams/day varied across countries from 7% (France) to 23% (Norway) and their contributions to overall % energy intake from 16%  to >45% (in the UK and Norway). Differences were also found between sociodemographic groups; participants in the highest fourth of UPF consumption tended to be younger, taller, less educated, current smokers, more physically active, have a higher reported intake of energy and lower reported intake of alcohol. The UPF pattern as defined based on the Nova classification  was positively associated with blood levels of industrial elaidic acid (These results, based on a large pan-European cohort, demonstrate sociodemographic and geographical differences in the consumption of UPF. Furthermore, these results suggest that the Nova classification can accurately capture consumption of UPF, reflected by stronger correlations with circulating levels of industrial elaidic acid and a syringol metabolite compared to diets high in minimally processed foods. Worldwide there has been a dramatic increase in the production of industrially processed foods which has coincided with a growing prevalence of obesity, metabolic disorders and multiple chronic diseases –16. GlobThe Nova classification system was developed in response to the increased recognition of the importance of classifying foods according to their degree and purpose of processing  rather than in terms of nutrients , 34, 35.The European Prospective Investigation into Cancer and Nutrition (EPIC) study offers an appropriate framework to investigate the validity of the Nova classification through comparison with food processing biomarkers already available, namely industrial trans-fatty acids (ITFA) measured in blood  and a meThe consumption of products from the different Nova categories in relation to relevant biomarkers that are related to food processing such as circulating ITFA has not been evaluated so far , 41. To EPIC is a multi-center prospective cohort study, designed to investigate the relationship between nutrition and cancer, among other diseases. A detailed description of the EPIC cohort, including study populations and data collection, has been previously described elsewhere . BrieflyAt baseline, information on lifestyle, dietary intake and medical information as well as sociodemographic and anthropometric data were collected. Lifestyle and medical history questionnaires were used to obtain information on education, smoking status and intensity, alcohol consumption, diabetes and women’s health . Physical activity levels were estimated using a questionnaire focused on past-year physical activity in occupational, leisure and household domains and classified according to the validated Cambridge physical activity index .2).Body weight and height were measured in all centers, except for Oxford (UK), France and Norway where these were self-reported. Anthropometric characteristics were measured by trained observers using standardized methods , 45. WeiDiet was assessed at study baseline using validated country/center-specific methods, including dietary questionnaires (DQs) spanning the previous 12 months . In mostn = 6,837), Greek participants  due to data access issues, and 9,684 participants in the top or bottom 1% of the ratio of energy intake to energy requirement, leaving a final sample of 476,768 adults.From the initial pool of 521,323 EPIC participants, we excluded subjects with missing dietary and/or lifestyle information Group 1: unprocessed or minimally processed foods, which are natural foods  and natural foods altered by methods such as freezing, pasteurization, fermentation, grinding, and other methods that do not include the addition of substances such as salt, sugar and/or oils or fats ;(2)Group 2: processed culinary ingredients are extractions of fresh foods or elements of nature, including substances obtained directly from group 1 foods or from nature by processes that include pressing, refining, grinding, milling, and drying, and consumed in combination with group 1 foods in freshly prepared dishes ;(3)Group 3: processed foods, which are products manufactured industrially with the addition of culinary ingredients  to unprocessed or minimally processed foods. Examples of Nova group 3 include canned vegetables; traditional cheese; traditional bread; smoked fish; plain sweetened yogurt;(4)Group 4: ultra-processed foods, which are commercial food and drink formulations containing besides salt, sugar or fats other substances derived from foods but not domestically used as culinary ingredients , flavors or additives designed to make the final product palatable or more appealing, such as colors, sweeteners, and emulsifiers. Examples of Nova group 4 include industrially produced bread, poultry and fish nuggets and sticks and other reconstituted meat products transformed with addition of preservatives other than salt; instant noodles and dehydrated soups; carbonated diet and regular sodas; chocolate with emulsifiers, chewing gums and candies with dyes (confectionery); margarine; instant desserts; most breakfast “cereals,” “energy” bars; “energy” drinks; flavored milk drinks/yogurts; sweet desserts made from fruit with added sugars, artificial flavors and texturizing agents; cooked seasoned vegetables with ready-made sauces; vegetable patties (meat substitutes) containing food additives; “health” and “slimming” products such as powdered or “fortified” meal and dish substitutes see .1 were also considered as sources of information on the degree of processing in the different EPIC countries . For breads, data from the Low Energy Ovens Project  were useountries .Changes in the practice of food processing over the past decades require the use of different scenarios when classifying foods according to the Nova classification in a long-term follow-up cohort like EPIC. Dietary intakes were collected at baseline, while the food environment has changed in the intervening years, exposing the EPIC participants to potentially different degrees of food processing over the course of their follow-up . As such, a particular food item can potentially be classified in different Nova groups depending on the time period. Therefore, we created three possible scenarios. The “most likely scenario,” in food safety terminology often called the middle bound scenario (MB), which is the scenario considering the most common food processing environment around the baseline period, was used as the main scenario (as agreed upon between the USP team and the IARC team). However, as we were unsure about the level of processing for some of the food items  for the period 1990–2020, we decided to introduce two alternative scenarios, namely a lower bound (LB) scenario reflecting the lowest degree of processing, and a more processed or upper bound (UB) scenario. For the lower bound scenario, some foods were classified in a less processed Nova group compared to the middle bound scenario when the food item may also have been prepared at home or in an artisanal setting instead of being industrially produced. For the upper bound scenario, some food items were classified in a more processed Nova group compared to the middle bound scenario when it was possible that the food item could be more processed than the most likely option assigned in the middle bound scenario. An example of these three scenarios used for the Nova classification is given in The coding of the Nova classification has been evaluated and checked via different quality controls . One of the quality controls was the comparison with an independent coding performed by the Spanish team in Barcelona on their food list from the Spanish EPIC cohort. The Nova coding performed by the international team was compared with the coding applied in Spain for the Spanish food list. Differences between these two classifications have been discussed between the two teams and few corrections to the three scenarios were made based upon this quality control.n = 9,460). Elaidic acid was the only ITFA measured in EPIC and as such used as a biomarker for industrially produced foods in these validation analyses.To evaluate the validity of the Nova classification in EPIC, we investigated correlations between the different Nova categories and food processing biomarkers available in subsets of EPIC participants  analysed in biospecimens collected around the time that the baseline questionnaires were collected. ITFA (elaidic acid levels) measured in plasma phospholipids  have bee4-Methyl syringol sulfate which has recently been proposed as a biomarker of smoked meat intake (n = 417) from the EPIC calibration study that included samples from Italy, France and Germany. Sample preparation, laboratory measurement and data processing is described elsewhere . Baseline characteristics were examined for the total population and by sex-specific quartiles of each Nova food group. The potential differences between participants were assessed using analysis of variance or χ2 tests when appropriate. Descriptive analyses were performed for each Nova food group considering their daily actual and relative intake in grams and kcal.Pearson correlations were used to evaluate the association between the Energy % from UPF obtained via the Nova coding performed by the Spanish team (considered as the middle bound scenario) versus those obtained via the three codings performed by the international team for the Spanish food list. In addition, weighted kappa statistics were used to investigate agreement between these two independent codings of the Spanish food list.Pearson and Spearman correlations were used to investigate associations of levels of biomarkers with % grams and % energy derived from the four Nova groups. Sensitivity analyses were run using partial correlations adjusted for sex, age, BMI and country.In addition, we also ran sensitivity analyses for the Nova 3 and Nova 4 groups while excluding the alcoholic beverages from these two Nova groups in order to investigate associations between the Nova group intakes and the food processing biomarkers while eliminating the effect of alcohol.epic@iarc.fr. The request will then be passed to members of the EPIC Steering Committee for deliberation.EPIC data and biospecimens are available for investigators who seek to answer important questions on health and disease in the context of research projects that are consistent with the legal and ethical standard practices of IARC/WHO and the EPIC centres. The primary responsibility for accessing the data, including the Nova categories obtained in the frame of the present publication, belongs to the EPIC centres that provided them. The use of a random sample of anonymised data from the EPIC study can be requested by contacting 25–75: 58–66) years, respectively  investigating characteristics of the degree of food processing in EPIC. The mean and median age of participants at recruitment were 51 (SD 9.93) years and 52  performed by the international team (USP and IARC) for the Spanish food list were compared with the coding (most likely scenario) applied in Spain to the Spanish food list as one of the quality controls. This demonstrated good comparability (Spearman correlation for % energy derived from UPF = 0.78) between the codes independently assigned by the two teams for the middle bound/most likely scenario . The lowN = 9,460) and are presented in r for middle bound scenario = 0.37 and 0.54, respectively), while inverse or lower positive correlations were found with any other Nova group (see r for middle bound scenario = 0.17) but an inverse association when considering % kcal/day (Spearman r for middle bound scenario =−0.07). Overall, the correlations of the middle bound scenario (the most likely scenario) were most in line with our hypotheses that higher intakes of UPF would lead to higher plasma ITFA levels compared to the lower and upper bound scenario; this suggests better performance of this most likely scenario.Associations were investigated between the consumption of the 4 Nova groups and objective biomarkers related to food processing. Associations of industrial ITFA plasma levels (elaidic acid) with intakes of the different Nova groups in g/day, kcal/day, % of g/day and % of kcal/day were investigated in a subset of subjects from the nested case-control studies embedded in EPIC (roup see . Nova grN = 417) and are presented in Associations of urinary methyl syringol sulfate with intakes of the different Nova groups  were similarly investigated in another subset of subjects, derived from the EPIC calibration study  using partial correlations adjusted for sex, age and BMI which gave very similar results as for the unadjusted analyses, while additionally adjusting for country attenuated the correlations see , 10.The results from this multicenter European study, demonstrate sociodemographic and geographical differences in the consumption of UPF. Furthermore, the comparison with the objective biomarkers, i.e., plasma ITFA and a urinary methylsyringol metabolite showed fair to moderate correlations with the % energy derived from UPF further supporting that the Nova classification is generally suitable for the evaluation of food according to the degree of processing among European populations. The broad variety of foods included in the UPF (Nova 4) group may partially explain the fair to moderate correlations found in relation to the food processing biomarkers. The higher correlations found when considering energy intakes instead of grams of UPF in relation to the food processing biomarkers may be due to the higher energy content of foods high in trans-fat and smoked meat.The correlation with the food processing biomarkers was slightly higher for the middle bound scenario than for the lower and upper bound scenarios, which suggests better performance of this most likely scenario. Hence, future analyses investigating disease outcomes in relation to the consumption of UPF using the Nova classification are advised to predominantly use the middle bound scenario.Adjusting the analyses for sex, age and BMI had overall little impact on the correlations with the food processing biomarkers. However, adjustment for country attenuated the correlations , 10. TheCharacterisation of the degree of food processing in EPIC demonstrated differences between countries, with contributions of UPF intake to the overall diet in grams/day varying from 7% (France) to 23% (Norway) and their contributions to overall energy intake varying from 16%  to 46% (the Norway). In addition, differences were also found between sociodemographic groups in the consumption of ultra-processed and minimally processed foods. Indeed, participants in the highest fourth of UPF consumption tended to be younger, taller, more often current smokers, more physically active, have a lower level of attained education, have a higher reported intake of energy and lower reported intake of alcohol. These results on the characterisation of the degree of food processing in EPIC are in line with the findings from the NutriNet-Santé Cohort  . HoweverOur study is the largest ongoing multicentre cohort study conducted in Europe with a large battery of detailed participant information. Except for a study investigating associations between UPF consumption and urinary concentrations of phthalates and bisphenol  in a nationally representative sample of the US population , and twoIn conclusion, our analyses on the characterisation of the degree of food processing among various participating countries in the EPIC cohort demonstrated a pronounced gradient between and within countries, with higher consumption of UPF in individuals who were younger, taller, current smokers, more physically active, and with lower level of attained education, higher reported intake of energy and lower reported intake of alcohol. In addition, the comparison with the objective biomarkers, i.e., plasma ITFA and urinary syringol metabolites showed fair to moderate correlations with the % energy derived from UPF, supporting that the Nova classification is generally suitable for the evaluation of UPF among European populations.epic@iarc.fr. The request will then be passed to members of the EPIC Steering Committee for deliberation. Requests to access these datasets should be directed to epic@iarc.fr.The data analyzed in this study is subject to the following licenses/restrictions: EPIC data and biospecimens are available for investigators who seek to answer important questions on health and disease in the context of research projects that are consistent with the legal and ethical standard practices of IARC/WHO and the EPIC centres. The primary responsibility for accessing the data, including the NOVA categories obtained in the frame of the present publication, belongs to the EPIC centres that provided them. The use of a random sample of anonymised data from the EPIC study can be requested by contacting The studies involving human participants were reviewed and approved by IARC Ethics Committee (IEC). The patients/participants provided their written informed consent to participate in this study.IH: conceptualization and writing – original draft. IH, CB, CC, and GN: data curation. NK, RW, CB, and CC: formal analysis. IH and CM: funding acquisition. IH, FR, GN, CC, NK, RW, CB, CM, and RL: investigation. MG, CM, and RL: supervision. All authors: writing – review and editing and approved the submitted version.