User-friendly information at the point of care for health care professionals should be well structured, rapidly accessible, comprehensive, and trustworthy. The reliability of information and the associated methodological process must be clear. There is no standard tool to evaluate the trustworthiness of such point-of-care (POC) information.We aim to develop and validate a new tool for assessment of trustworthiness of evidence-based POC resources to enhance the quality of POC resources and facilitate evidence-based practice.We designed the Critical Appraisal of Point-of-Care Information (CAPOCI) tool based on the criteria important for assessment of trustworthiness of POC information, reported in a previously published review. A group of health care professionals and methodologists (the authors of this paper) defined criteria for the CAPOCI tool in an iterative process of discussion and pilot testing until consensus was reached. In the next step, all criteria were subject to content validation with a Delphi study. We invited an international panel of 10 experts to rate their agreement with the relevance and wording of the criteria and to give feedback. Consensus was reached when 70% of the experts agreed. When no consensus was reached, we reformulated the criteria based on the experts’ comments for a next round of the Delphi study. This process was repeated until consensus was reached for each criterion. In a last step, the interrater reliability of the CAPOCI tool was calculated with a 2-tailed Kendall tau correlation coefficient to quantify the agreement between 2 users who piloted the CAPOCI tool on 5 POC resources. Two scoring systems were tested: a 3-point ordinal scale and a 7-point Likert scale.P<.01) and scoring with the 7-point Likert scale .After validation, the CAPOCI tool was designed with 11 criteria that focused on methodological quality and author-related information. The criteria assess authorship, literature search, use of preappraised evidence, critical appraisal of evidence, expert opinions, peer review, timeliness and updating, conflict of interest, and commercial support. Interrater agreement showed substantial agreement between 2 users for scoring with the 3-point ordinal scale (τ=.621, The CAPOCI tool may support validation teams in the assessment of trustworthiness of POC resources. It may also provide guidance for producers of POC resources. Evidence-based medicine (EBM) aims to integrate the experience of the health care professional, the values of the patient, and the best available scientific information to guide clinical decision making. Back in 1996, Sackett defined EBM as “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.” The practice of EBM means integrating individual clinical expertise with the best available external clinical evidence from systematic research . HoweverTrustworthy POC information sources for health care professionals require a robust methodological process for searching, appraisal, and synthesis of the best available evidence in a reproducible way. Health information for professionals differs at this point from health information for the lay public, and consequently the initiatives to evaluate health information for patients  started from the results of the systematic review to derive relevant criteria for the CAPOCI tool. They related the relevance of criteria to frequency of occurrence in the existing tools and contribution of the criteria to the trustworthiness of POC information according to the reviewers. A working group of health care professionals and methodologists  then discussed the relevance, applicability, and accurate wording of the different criteria. The further refinement of the items for the CAPOCI tool was the result of an iterative process of discussion and pilot testing until consensus was reached for all criteria, resulting in a tool with 9 criteria.The content validity of the CAPOCI tool was tested on an international panel of experts  with theAll panel members received a study protocol and an electronic questionnaire. They were asked to rate the relevance and wording (accuracy and correctness) of the different CAPOCI criteria. The panel members rated their agreement with each item as strongly agree, agree, disagree, or strongly disagree. If the answer was disagree or strongly disagree, an explanation was required.The questionnaires were returned to the study coordinator. Consensus on a criterion was achieved when 70% of the panelists rated a criterion as strongly agree or agree. Based on the justification formulated in case of disagreement, the criterion was reformulated and again presented to all panel members in a next round. The process was repeated until consensus was reached for all criteria. The results of the systematic review did not identify the most appropriate scoring system for the CAPOCI tool. Therefore, we decided to test 2 scoring systems. The first scoring system rated each criterion on a 3-point ordinal scale with the following possible ratings: (1) fulfilled, (2) minor remark, and (3) major remark. The conditions for awarding one of the 3 ratings were discussed and defined by the authors of this paper. The second scoring system rated each criterion on a 7-point Likert scale, where a score of 1 indicated fully disagree and a score of 7 indicated fully agree.The CAPOCI tool was tested for interrater reliability. To this end, two methodologists (GB and GL) assessed 5 POC resources used in Belgian health care with the CAPOCI tool, using the 2 scoring systems described above.The statistical analyses were performed using SPSS . A 2-tailed Kendall tau correlation coefficient was calculated to quantify the agreement between the 2 reviewers for the entire CAPOCI tool per scoring system. Level of significance was set at .01. In addition, a descriptive analysis was performed for each criterion separately. We counted how often a criterion was scored differently by the 2 reviewers for the 5 evaluated POC resources. For scoring with the Likert scale, a difference in score of more than 1 was considered a different score. The reason for interrater disagreement was documented.Based on the results of the systematic review, the CAPOCI tool was initially defined with 9 criteria. These 9 criteria were then tested in the Delphi study. Ten experts from a diverse range of organizations and institutions reputable in EBM worldwide participated see . One expThe 9 criteria were assessed as relevant by all the experts after the first round, but refinement of the wording was needed. After 4 rounds of the Delphi study, a final version of the CAPOCI tool was developed including 11 criteria, where the criteria related to authorship and experience of authors, literature search and surveillance were split up. P<.01) for scoring with the 3-point ordinal scale and .677 (P<.01) for scoring with the 7-point Likert scale, as calculated by the Kendall tau correlation coefficient.Assessment of 5 POC resources with the CAPOCI tool  showed aThe descriptive analysis of agreement between the reviewers for each criterion separately showed that both scoring systems lead to similar results . There wWe developed a uniform, comprehensive, and validated tool specifically designed for the evaluation of POC information. The CAPOCI tool allows the systematic evaluation of the trustworthiness of POC resources, including the methodological process of searching, appraising, and synthesizing the best available evidence for a specific health topic.Our systematic review showed that items for assessing POC resources could be divided into 4 main domains: author-related information, criteria related to evidence-based methodology, criteria related to website quality, and criteria related to website design and usability . The rigThe rigorous reporting of author-related information is a first important point when we focus on trustworthiness of (web-based) POC information. In this internet era, where personal opinions are easily expressed, it is crucial to have one or more authors who take responsibility for the content of a POC resource. Clarity and transparency about authorship must always go hand in hand with transparent and consistent reporting of conflicts of interest. Users of EBP resources need to be sure that the provided information reflects the best evidence and potential influence by competing interests has been minimized. The disclosure of conflicts of interests in guideline development has received much attention after reports on undisclosed financial conflicts of interest in guideline panels . In respTo fulfill the claim of being evidence-based, a POC resource should be built on a robust methodological process. First, an explicit methodology for literature search and surveillance helps to avoid biases. A literature search should be systematic and well-documented for transparency and auditability. However, a systematic search with nonsystematic article selection can negate the effort for systematic search and surveillance. Therefore, a systematic strategy for article selection should be worked out as well, including a clear definition of inclusion and exclusion criteria for the selection of source information. These are basic principles of comprehensiveness in literature search that are important and widely adopted for guideline development , but comOnce the information is selected, it should be critically appraised to assess the validity of the evidence it provides and to prevent inclusion of biased results. Some sources such as Cochrane systematic reviews are conducted following a strict protocol, and therefore they can be considered as trustworthy. But there are an increasing number of systematic reviews available in which the quality is often suboptimal ,30. WhenWhen the criteria for literature and surveillance and critical appraisal of evidence are met, the criterion concerning the use of best available evidence will probably be fulfilled as well. We added this criterion to the tool to clarify that the content production process of a POC resource should be based preferentially on well-designed and conducted evidence synthesis documents rather than single studies. The best available evidence can be explained in different ways. The 6S pyramidal model of Haynes is often used as a conceptual framework for searching information resources for EBM , suggestFor some clinical questions concerning rare diseases, best practice guidance, or treatments that are strongly context-dependent , the evidence may be limited. In these situations, obtaining evidence from experts can be efficient, and experts may be the only or main source of evidence. However, the use of expert opinion should be clearly distinguished from empirical data in a POC resource . To thisPeer review, procedures for updating, and clear policies on conflict of interest and commercial support are basic principles for EBP that are present in all critical appraisal tools for clinical trials, systematic reviews, or guidelines ,14,36. BPOC resources are often web-based, which makes them very interesting for biomedical companies for online advertising. It is possible that a POC resource depends on commercial funding. In that case, a strict policy that ensures that the funder or advertiser has no influence on the content of the POC resource is mandatory. The distinction between content and advertising must always be very clear to the user.We tested 2 scoring systems for the CAPOCI tool, both showing good reliability. The purpose of the evaluation of a POC resource can be a determining factor in the choice of scoring system. The 7-point Likert scale allows more nuance. It is also used in the AGREE II instrument and therefore probably familiar for users. It allows for a quantitative comparison when rating and comparing different POC sources.The 3-point scale may be better suited when different reviewers must formulate a final judgement on a POC resource  in consensus. The predefined conditions for the 3 categories also allow structured feedback to developers for POC resources on the criteria where additional information is required.The CAPOCI tool is valid and reliable instrument that can be used by health care providers, researchers, and decision and policy makers for the evaluation of the trustworthiness of POC resources. Developers of POC resources can also use the tool as a guide in the development process.Although the results of the interrater variability tests showed substantial agreement between reviewers for the CAPOCI tool, the descriptive analysis showed a difference in rigor of application between reviewers for 8 of the 11 criteria. In addition, different reviewers might interpret information in the POC resource differently, and the necessary information for evaluation was sometimes not retrieved. Therefore, a robust use of the CAPOCI tool includes an evaluation by at least 2 independent reviewers who reach a joint final judgment after discussion in order to reduce subjectivity and inaccuracy in the evaluation. Furthermore, reviewers should have experience with EBP methodology or should be trained by an experienced methodologist. Pilot testing is recommended to mitigate differences in rigor of application between reviewers and can be part of training for the good use of the CAPOCI tool.The CAPOCI tool is based on a rigorous development process starting from a systematic review to consider and cover all possible criteria for the assessment of trustworthiness of POC information. The author group who defined the initial CAPOCI criteria consisted of methodologists and health care professionals, each with broad experience in guideline development and/or guideline validation.Of all POC tools that were previously analyzed in our systematic review, only 2 were validated and tested for reliability . HoweverReliability testing was performed by reviewers who were involved in the development of the tool, which might have influenced the results. We will use this tool among different methodologists at our institute. The criteria and scoring methods will be refined where needed based on the experience and feedback of the users. Adding examples to the different criteria may also contribute to a better understanding and ease of use for less experienced users. Furthermore, content validation was done with a panel of 10 experts and reliability testing with only 2 reviewers, which can be considered as a limitation of this study. Using more reviewers or a more extended expert panel would add to the quality of validity and reliability testing.With the development of the CAPOCI tool, we filled a gap in the evaluation of POC information. The CAPOCI tool facilitates the assessment of trustworthiness in POC resources. It may also provide guidance for producers of POC resources. Wide use of the CAPOCI tool may improve the quality and reliability of POC resources over time and may take EBP in daily practice to a higher level.


The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of ovarian tumours, including imaging techniques, biomarkers and prediction models.ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumours and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised.Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements.This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumours and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement. The accurate characterization of newly diagnosed adnexal lesions is of paramount importance to define appropriate treatment pathways. Patients with masses that are suspicious for malignancy should be referred to a gynaecological oncology centre, in order to receive specialist care, as per the definitions of the European Society of Gynaecological Oncology (ESGO)  and natiThe ESGO, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) have, jointly, developed clinically relevant and evidence- based statements on the preoperative diagnosis of ovarian tumours and assessment of disease spread, including imaging techniques, biomarkers and predictive models. Neither screening and follow-up modalities, nor economic analysis of the imaging techniques, biomarkers and prediction models addressed herein, are included within the remit of this Consensus Statement.The present series of statements form a consensus of the authors regarding their currently accepted approaches for the preoperative diagnosis of ovarian tumours and assessment of disease spread, based on the available literature and evidence. Any clinician applying or consulting these statements is expected to use independent medical judgment in the context of individual clinical circumstances to determine all patients’ care and treatment. These statements are presented without any warranty regarding their content, use or application and the authors disclaim any responsibility for their application or use in any way.This Consensus Statement on the preoperative diagnosis of ovarian tumours and assessment of disease spread was developed using an eight-step process, chaired by Professors Christina Fotopoulou and Dirk Timmerman . Aiming These experts included seven gynaecologists with special interest in ultrasonography, two radiologists and 10 gynaecological oncologists. They did not represent the societies from which they were selected, and were asked to base their decisions on their own experience and expertise. Also included in the group was a patient representative, who is Chair of the Clinical Trial Project of the European Network of Gynaecological Cancer Advocacy Groups, ENGAGe. An initial conference call, including the whole group, was held to facilitate introductions, as well as to review the purpose and scope of this Consensus Statement.To ensure that the statements were evidence- based, the current literature was reviewed and critically appraised. Thus, a systematic literature review of relevant studies published between 1 May 2015 and 1 May 2020 was carried out using the MEDLINE database . The litThe chairs were responsible for drafting preliminary statements based on the review of the relevant literature. These were then sent to the multidisciplinary international group prior to a second conference call. During this conference call, the whole group discussed each preliminary statement and a first round of binary voting (agree/disagree) was carried out for each potential statement. All 20 participants took part in each vote, but they were permitted to abstain from voting if they felt they had insufficient expertise to agree/disagree with the statement or if they had a conflict of interest that could be considered to influence their vote. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The chairs then discussed the results of this first round of voting and revised the statements if necessary. The voting results and the revised version of the statements were again sent to the whole group and another round of binary voting was organized, according to the same rules, to allow the whole group to evaluate the revised version of the statements. The statements were finalized based on the results of this second round of voting. The group achieved consensus on 18 statements. In this Consensus Statement, we present a summary of the supporting evidence, the finalised series of statements, and their levels of evidence and grades.Even though the test performance of any biochemical or radiological diagnostic test appears to increase after excluding borderline ovarian tumours and non-gynaecological primary tumours, such as of the gastrointestinal tract or breast, we included in our literature assessment studies addressing all types of adnexal tumour, as this is a better reflection of clinical reality.A transvaginal ultrasound examination is often regarded in clinical practice as the standard first- line imaging investigation for the assessment of adnexal pathology . The diaSubjective assessment by expert ultrasound examiners has excellent performance to distinguish between benign and malignant ovarian tumours . In manySeveral attempts have been made to develop more objective ultrasound-based approaches for discriminating between benign and malignant adnexal tumours. These include the risk of malignancy index (RMI), a scoring system based on menopausal status, a transvaginal ultrasound score and serum cancer antigen 125 (CA 125) level . Many stTo homogenize and standardize the quality, description and evaluation of ultrasonography across different centres, and thereby increase diagnostic accuracy, the IOTA group first published a consensus paper on terms and definitions to describe adnexal lesions in 20003 . Using tAs many ovarian masses can be recognized relatively easily, the IOTA group also proposed four ‘Simple Descriptors’ of the features typical of common benign lesions and two suggestive of malignancy, which can give an ‘instant diagnosis’ and reflect the pattern recognition that is a key part of ultrasonography. These are applicable to about 43% of adnexal masses . A threeA randomized controlled trial assessing surgical intervention rates and the oncologic safety of decision-making processes using on an RMI-based protocol developed by the British Royal College of Obstetricians and Gynaecologists (RCOG) vs triage using the IOTA Simple Rules  showed tThe IOTA group have also developed the Assessment of Different NEoplasias in the adneXa (ADNEX) model. This multiclass prediction model is the first risk model to differentiate between benign and malignant tumours, whilst also offering subclassification of any malignancy into borderline tumours, Stage-I and Stage-II– IV primary cancers and secondary metastatic tumours. The IOTA ADNEX model was developed and validated using parameters collected by experienced ultrasound examiners . SeveralThe Gynaecologic Imaging Reporting and Data System (GI-RADS) was first introduced by Amor et al. in 2009 and was validated prospectively by the same team in a multicentre study 2 years later . This reThe Ovarian-Adnexal Reporting and Data System (O-RADS) lexicon for ultrasound was published in 2018, providing a standardized glossary that includes all appropriate descriptors and definitions of the characteristic ultrasound appearance of normal ovaries and various adnexal lesions  ultrasound examiners has the best performance to distinguish between benign and malignant ovarian tumours.Level of evidence: 1aGrade of statement: AConsensus: yes, 95% (n = 19); no, 0% (n = 0); abstain, 5% (n = 1)If an expert ultrasound examiner is not available, the use of ultrasound-based diagnostic models can assist clinicians to distinguish between benign and malignant ovarian tumours.Level of evidence: 2aGrade of statement: BConsensus: yes, 90% (n = 18); no, 0% (n = 0); abstain, 10% (n = 2)Ultrasound-based diagnostic models (IOTA Simple Rules risk model or IOTA ADNEX model) are preferable to CA 125 level, HE4 level or ROMA as they are superior in distinguishing between benign and malignant ovarian tumours.Level of evidence: 2bGrade of statement: BConsensus: yes, 95% (n = 19); no, 0% (n = 0); abstain, 5% (n = 1)The IOTA ADNEX model and the IOTA Simple Rules risk model are recommended as they outperform existing morphological scoring systems, including the RMI.Level of evidence: 1bGrade of statement: AConsensus: yes, 95% (n = 19); no, 0% (n = 0); abstain, 5% (n = 1)The IOTA ADNEX model is a multiclass model and is helpful to differentiate between benign tumours, borderline tumours, early- or advanced- stage ovarian cancer and secondary metastatic tumours.Level of evidence: 3bGrade of statement: CConsensus: yes, 85% (n = 17); no, 0% (n = 0); abstain, 15% (n = 3)The threshold risk of there being a secondary metastatic tumour (as predicted by the IOTA ADNEX model), above which additional investigations to detect the primary organ of origin should be triggered, is 10%.Level of evidence: 5Grade of statement: DConsensus: 5% threshold, 10% (n = 2); 10% threshold, 75% (n = 15); 15% threshold, 0% (n = 0); 20% threshold, 0% (n = 0); abstain, 15% (n = 3)Levels of evidence and grades are described in According to a systematic quantitative review assessing the accuracy of CA 125 level in the diagnosis of benign, borderline and malignant ovarian tumours, CA 125 is the best available single-protein biomarker identified to date . AlthougMultiple studies, including meta-analyses, have highlighted the role of HE4 as a potential complement to CA 125, especially in differentiating benign endometriotic and inflammatory lesions in younger women . AdditioCA 125 is the best single-protein biomarker for the preoperative characterization of ovarian tumours. However, it is not useful as a screening test for ovarian cancer.Level of evidence: 2bGrade of statement: BConsensus: yes, 95% (n = 19); no, 0% (n = 0); abstain, 5% (n = 1)Neither HE4 nor ROMA improves the discrimination between benign and malignant masses compared with CA 125 alone.Level of evidence: 2bGrade of statement: BConsensus: yes, 70% (n = 14); no, 0% (n = 0); abstain, 30% (n = 6)CA 125 does not increase the performance of ultrasound-based risk models to distinguish between benign and malignant tumours.Level of evidence: 2bGrade of statement: BConsensus: yes, 60% (n = 12); no, 10% (n = 2); abstain, 30% (n = 6)CA 125 is helpful as a biomarker in cases of suspected malignancy and it helps to distinguish between subtypes of malignant tumours, such as borderline and early- and advanced-stage primary ovarian cancers and secondary metastatic tumours.Level of evidence: 2bGrade of statement: BConsensus: yes, 90% (n = 18); no, 5% (n = 1); abstain, 5% (n = 1)CEA may be useful in specific cases to differentiate between primary ovarian cancer and secondary (ovarian) tumours.Level of evidence: 3bGrade of statement: CConsensus: yes, 90% (n = 18); no, 0% (n = 0); abstain, 10% (n = 2)CA 19-9 can help to differentiate secondary metastatic tumours in the ovary.Level of evidence: 3bGrade of statement: CConsensus: yes, 75% (n = 15); no, 5% (n = 1); abstain, 20% (n = 4)Levels of evidence and grades are described in Several reports have found that magnetic resonance imaging (MRI), alone or in combination with computed tomography (CT), predicts accurately the presence of peritoneal carcinomatosis in patients undergoing preoperative evaluation for cytoreductive surgery, particularly when the assessment is carried out by an experienced radiologist . RecentlDedicated multidetector CT protocols with standardized peritoneal carcinomatosis index forms are the most common diagnostic tool used in routine clinical practice to assess the extent of tumour dissemination and the presence of peritoneal carcinomatosis . A radioPositron emission tomography-computed tomography (PET-CT) may be useful in differentiating malignant from borderline or benign ovarian tumours, with the limitation that its diagnostic performance can be impacted negatively by certain tumour histological subtypes, due to the lower fluorodeoxyglucose uptake in clear-cell and mucinous invasive subtypes . PET-CT MRI with the inclusion of the functional sequences, dynamic contrast-enhanced and diffusion-weighted MRI, is not a first-line tool but may be used as a second-line tool after ultrasonography to further differentiate between benign, malignant and borderline masses.Level of evidence: 2aGrade of statement: BConsensus: yes, 100% (n = 20); no, 0% (n = 0); abstain, 0% (n = 0)PET-CT and whole-body diffusion MRI as a second step can help to detect non-ovarian origin of secondary metastatic tumours if suspicions are raised by the initial ultrasound examination.Level of evidence: 4Grade of statement: CConsensus: yes, 90% (n = 18); no, 0% (n = 0); abstain, 10% (n = 2)PET-CT cannot differentiate reliably between borderline and benign tumours.Level of evidence: 4Grade of statement: CConsensus: yes, 95% (n = 19); no, 0% (n = 0); abstain, 5% (n = 1)Imaging alone cannot detect reliably the entire extent of either peritoneal carcinomatosis  or mesenteric and bowel serosal involvement.Level of evidence: 3bGrade of statement: BConsensus: yes, 85% (n = 17); no, 5% (n = 1); abstain, 10% (n = 2)Imaging alone should not be used for surgical decision-making in terms of the prediction of peritoneal tumour resectability.Level of evidence: 3bGrade of statement: BConsensus: yes, 80% (n = 16); no, 15% (n = 3); abstain, 5% (n = 1)Levels of evidence and grades are described in Circulating cell-free DNA and circulating tumour cells as non-invasive cancer biomarkers and in non-invasive biopsy  have been investigated in multiple studies . DNA metOne meta-analysis suggested that quantitative analysis of cell-free DNA has unsatisfactory sensitivity but acceptable specificity for the diagnosis of ovarian cancer . In a moCirculating cell-free DNA and circulating tumour cells should not yet be used in routine clinical practice to differentiate between benign and malignant ovarian masses.Level of evidence: 4Grade of statement: CConsensus: yes, 85% (n = 17); no, 5% (n = 1); abstain, 10% (n = 2)Levels of evidence and grades are described in The experts also reached a consensus on a flowchart describing steps recommended to distinguish between benign and malignant tumours  and to dA consensus was also reached on further steps necessary to differentiate between subgroups of malignancy and extent of disease within gynaecological oncology centres . Ultraso


Hyperhidrosis is a chronic skin condition that impairs the patient’s quality of life (QoL). There are several patient-reported outcome measures (PROMs) for patients affected by hyperhidrosis available; however an evidence-based assessment of their quality has not been undertaken so far.In our systematic review, we aim to identify all existing PROMs that were developed and/or validated for measuring patient-reported outcomes in patients with hyperhidrosis and assess their measurement properties in a transparent and structured way to give a recommendation for future clinical research.Our systematic review aims to contain all PROMs developed and/or validated for patients with hyperhidrosis. We will perform a highly sensitive, systematic literature search including the databases MEDLINE (Ovid), EMBASE (Ovid), and Science Citation Index Expanded and Social Sciences Citation Index (Web of Science). Especially studies which evaluate, describe, or compare measurement properties of PROMs for patients with hyperhidrosis will be considered as eligible. Two independent reviewers will judge the eligibility of the studies found in the literature search. The study and PROM characteristics will be summarized in evidence tables. The methodological quality of each study will be assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist. We will apply predefined and consensus-based quality criteria for good measurement properties. Subsequently, the quality of the evidence will be graded. Furthermore, aspects on interpretability and feasibility will be described. A final recommendation will be given.In our systematic review, we aim to provide a comprehensive description of the quality of all existing PROMs for patients with hyperhidrosis. The assessment of measurement properties, interpretability, and feasibility will serve as a guidance regarding the selection of PROMs for future clinical hyperhidrosis trials.PROSPERO CRD42020170247The online version contains supplementary material available at 10.1186/s13643-021-01701-w. Hyperhidrosis is a term used to describe a skin condition which is characterized by excessive sweating beyond what is physiologically necessary . It can To foster involvement of patients in both clinical research as well as routine health care, the use of patient-reported outcome measures (PROMs) has steadily increased in the past decades. These instruments reflect the patient’s perspective of how they perceive their health status and whether health care interventions have been effective. PROMs are self-completed questionnaires measuring, e.g., health-related QoL or health status . In hypeIn a recent narrative review , 22 QoL https://www.cosmin.nl/) aims to improve the selection of the most suitable PROM and therefore, developed a methodology and practical tools for the assessment of the quality of single PROMs and their development and validation studies. This recent narrative review based their recommendation only on the judgement of a small group [However, it is important in clinical research to select measurement instruments which are reliable, valid, responsive, and feasible. The selection of instruments should be based on complete information regarding these measurement properties and the quality of the underlying research. The international COSMIN  initiative  statement  and the A.Target population: patients with hyperhidrosis. In order to reach maximal sensitivity a broad compilation of controlled vocabulary and free text terms will be used.B.Construct of interest: all patient-reported outcome measures regardless of the underlying construct. For optimal sensitivity the search strategy of this search element will be based on a combination of the PubMed filter “Quality of life (QoL)” of Vissers and de Vries , the PubC.Measurement properties: the validated and sensitive search filter (recommended by the COSMIN group ) for finD.Feasibility of PROMs: the search strategy for this element will be based on the search terms for the concept ‘feasibility’ of Heinl et al.  include.E.Individual PROMs: a list of known relevant PROMs in the context of hyperhidrosis . This liF.Exclusion filter: this will be the exclusion filter from Terwee et al.  for a nuG.Language filter: only reports in English, German, French, or Italian will be included.A systematic literature search will be performed in the bibliographic databases MEDLINE , EMBASE , Science Citation Index Expanded , and Social Sciences Citation Index . The search strategy will be comprised of the following search elements :A.TargeThe search elements will be combined as follows in order to identify all articles on the measurement properties or the feasibility of PROMs in the context of hyperhidrosis. From these records, the exclusion filter will remove irrelevant publication types as well as animal-only studies: (((A AND B AND (C OR D)) OR (C AND E)) NOT F) AND G, or in words: (((population AND construct AND (measurement properties OR feasibility)) OR ) NOT (exclusion filter)) AND language filter. A graphical overview of the search structure in form of a tree is given in Fig. https://eprovide.mapi-trust.org/about/about-proqolid), the COSMIN database of systematic reviews of outcome measurement instruments (http://www.cosmin.nl/database-of-systematic-reviews.html), the Test Archive of Leibniz Institute for Psychology Information (https://www.testarchiv.eu/) and the PubPsych search engine (https://pubpsych.zpid.de/pubpsych/). In addition to the electronic search, hand searching of the reference lists of the studies included and key articles on this topic will be searched.In addition, databases specific for PROMs will be searched for records relevant to the target population: PROQOLID  Risk of Bias checklist consisting of ten boxes: PROM development, content validity, structural validity, internal consistency, cross-cultural validity/measurement invariance, reliability, measurement error, criterion validity, hypotheses testing for construct validity, and responsiveness . Only thDefinitions of all included measurement properties are included in the paper of Mokkink et al. . ContentSecond, we will apply criteria for good measurement properties . The updated criteria for good measurement properties recommended by the COSMIN group  are presThird, we aim to summarize the evidence per measurement property per PROM, rate the overall result against criteria for good measurement properties, and grade the quality of the evidence by using the GRADE approach. Here, we focus on the PROM and not as in the previous steps on the single studies .The third sub step includes several further substeps.First, we will have to decide if the results of all studies per measurement property are consistent or not .If they are consistent, they can be pooled or summarized and an overall rating as either sufficient (+), insufficient (−), or indeterminate (?) can be provided after the comparison against the quality criteria. Finally, their quality of the evidence will be graded .If an explanation is found, the different results will be summarized  followed by an overall rating for the specific measurement property. It should be considered that high-quality studies provide more evidence than low quality studies when determining the overall rating .If no explanation for inconsistency is found, the overall rating could be either inconsistent (±) or based on the majority of the results and therefore downgraded for inconsistency (see GRADE approach explained below) .If the results are inconsistent, we will look for explanations for inconsistency.Second, we will pool the results quantitatively or summarize them qualitatively in Summary of Findings (SoF) Tables. Each measurement property per PROM in one table .Third, each pooled or summarized result will be again rated against the quality criteria Table  to obtaiFourth, the quality of the evidence will be graded to define whether the pooled or summarized result is trustworthy. It is important to consider the quality of evidence because insufficient attention to quality of evidence can lead to inappropriate recommendations that may have negative impacts for the patients. The recognition of the quality of evidence can help to prevent misguided recommendations . Using tInterpretability and feasibility which are also important for a recommendation will be described after the evaluation of the measurement properties. Interpretability means the degree to which qualitative meaning can be assigned to a PROM’s quantitative score. Feasibility contains aspects of the ease of application  .A.PROMs with evidence for sufficient content validity (any level) AND at least low-quality evidence for sufficient internal consistency: recommended for useB.PROMs categorized not in A or C: further validation neededC.PROMs with high-quality evidence for an insufficient measurement property: should not be recommended for useThe included PROMs will be classified into three categories :A.PROMsIf only PROMs of category B will be found, the PROM with the best evidence for content validity can be preliminarily recommended for use, until further evidence is given .A broad and accurate assessment of the measurement properties of existing PROMs for patients with hyperhidrosis has not been done so far and is planned for this systematic review. Our aim is to recommend the best PROM(s) for each of the constructs identified in the literature search. We will fully report each step of the systematic review in a transparent and structured way. Furthermore, we will involve at least two independent reviewers to assure quality and reduce variability in the assessments. The COSMIN Risk of Bias checklist is a recently developed and well-established method to assess the methodological quality of the studies. By using the GRADE approach, we ensure the certainty of the evidence. If concerns about the quality of the evidence are given , the quality of evidence will be downgraded to prevent errors in recommendation . InterprAdditional file 1:. PRISMA-P 2015 Checklist.Additional file 2:. MEDLINE search strategy.


Five BAs, including tryptamine, β-phenylethylamine, putrescine, histamine, and spermidine, were analysed by high-performance liquid chromatography with UV detection. The level of total BAs was higher in the mackerel fillet (108.14 µg/g) than the headed and gutted fish (91.58 µg/g). Roasted, fried, and stewed mackerel recorded total BA concentrations of 54.28, 82.25, and 163.05 µg/g, respectively. Stewed mackerel contained about 3-fold more BAs than roasted mackerel. The level of total BAs in mackerel increased significantly up to 190%, 236% and 152% as the roasting temperature increased, upon frying, and as stewing temperature increased, respectively ( Mackerel is one of the most popular fish consumed in Korea. Safety issues for fishery products are increasing every year. Safety investigations on radioactive, heavy metal, and pesticide residues have been conducted for fishery products ,2. HowevThe BAs that affect the human body are tryptamine (TRP), histamine (HIS), putrescine (PUT), spermidine (SPD), and β-phenylethylamine (PHE), which are derived from amino acid precursors . High leBAs are generally known to be heat-stable compounds. However, this is still controversial. Recent studies have indicated that the corresponding amino acid precursors can be formed by oxidative decarboxylation during the heating process . StudiesThere are several studies investigating concentrations of biogenic amines in raw mackerel ,15,16,17Scomber japonicus), five BAs, including TRP, PHE, PUT, HIS, and SPD, formed in mackerel were analyzed considering its origin (Korea and Norway), pre-treatment  and cooking method .In this study, to assess how various conditions can affect BAs in chub mackerel (S. japonicus from Korea and Norway) was purchased from Namyang Seafood Co. . Mackerel was purchased within a year of being caught and was kept at −18 °C until sample preparation. Canned tuna  was purchased in the general market in Seoul, Korea, and used to validate the five BAs.Mackerel . HPLC-grade water and acetonitrile were purchased from J.T. Baker . The dansyl chloride reagent used for derivatisation was purchased from Tokyo Chemical Industry Co., Ltd. .2 of the calibration curve), limit of detection (LOD), limit of quantitation (LOQ), recovery (%), and precision  were determined. The calibration curve of the five BAs in canned tuna was prepared by measuring seven concentrations of the BAs standard solution . LOD and LOQ were calculated by the respective equations, 3.14 × standard deviation (σ1)/slope factor and 10 × standard deviation (σ1)/slope factor of the BAs calibration curve derived from eight points . For accuracy (%) and precision, the level of BAs were determined in canned tuna samples without internal standards. The intra-day accuracy and precision were analysed on one day by performing five replicates at each level of the BAs . The inter-day accuracy and precision were tested once a day for 5 days at each level of the BAs .Canned tuna was used to validate the five BAs since it has a similar fatty acid composition to mackerel and has not been reported to have BAs. For method validation, linearity  and head removed. Mackerel fillets were cut along the entire side of the fish, removing the spine and most bones from the meat. The cooking method applied to mackerel was conducted with reference to the Korean Dietetic Association . Roasted mackerel was prepared by roasting 50 g of mackerel at 150, 200, and 250 °C for 15 min in an oven . For fried mackerel, 50 g of mackerel was fried in soybean oil  at 140, 170, and 200 °C for 10 min using a fryer . For stewed mackerel, 50 g of mackerel, 200 mL of soy sauce , and 200 mL of water were combined and boiled at 75, 85, and 95 °C for 15 min. A calibrated infrared thermometer  was used for temperature measurement in all cooking procedures. Prepared samples were stored at 4 °C for 3 h until analysis. The sample preparation of mackerel is described in The BAs analysis of mackerel was carried out according to the procedure proposed by Lee et al. . In a 50BAs were derivatised according to the previously published method . One milThe BAs were quantitated using an HPLC 1200 Series  equipped with a UV-Vis detector and Nova-Pack C18 column . The mobile phases were 0.1 M ammonium acetate (solvent A) and acetonitrile (solvent B) at the flow rate of 1 mL/min with gradient elution for 25 min. The injection volume was 20 μL. The sample was detected by UV at a wavelength of 254 nm. After 25 min, the gradient was re-adjusted to 50% solvent A and 50% solvent B.The results were expressed as mean ± standard deviation of three measurements. Triplicate analyses were performed for each mackerel sample. Data were evaluated for origin, cooking methods, and temperature by one-way analysis of variance (ANOVA) and Duncan’s multiple range test using IBM SPSS Statistics 23 . We ran a One-way ANOVA followed by Duncan’s multiple range test because we were interested in the effect of each independent variable  rather than the interaction between them. While it seems like temperature is nested in the cooking method, each variable was specifically selected for each cooking method; therefore, cooking method and temperature need to be treated independently. 2 of the calibration curve), limit of detection (LOD), limit of quantitation (LOQ), recovery (%), and precision  can be found in 2 > 0.99) The measured LOD and LOQ ranges of the five BAs were 0.78–1.45 and 1.65–4.40 µg/g, respectively. Recovery (%) and precision (%) were measured, respectively, using three concentrations  of the BAs standard solutions. The recovery rate ranged from 85.78% to 118.06%, the inter-day and intra-day precision values ranged from 0.95% to 9.68% and from 0.82% to 8.65%, respectively. The validation data of this study was similar to the previous reports [For method validation, the results of linearity  with 126.84–192.53 µg/g. Roasted mackerel had 34.6–93.32 µg/g (n = 12), and fried mackerel (n = 12) recorded 33.09–100.28 µg/g. By origin, the total BAs content was higher in pre-treated mackerel from Norway (51.81 ± 1.80µg/g) than Korea (45.09 ± 1.81 µg/g). The BA levels of fillet and H/G fish from Korea were lower than Norway by 14% and 15%, respectively.In the 40 mackerel samples, the concentration ranges of PUT, HIS, TRP, PHE, and SPD were 11.43–43.11, 6.34–84.2, 4.12–45.51, 4.01–42.87, and 2.13–10.09 µg/g, respectively. Among the cooking methods, the level of BAs was highest in stewed mackerel samples  than the H/G fish (46.9 ± 2.38 µg/g). In the previous study dealing with biogenic amines formation and its relation to microbiological and sensory attributes in ice-stored whole, gutted, and filleted Mediterranean Sea bass, the number of microorganisms in fillet was more than headed and gutted part . BAs areThe reason that stewed mackerel recorded the highest level of BAs (163.05 µg/g) by the cooking method can be explained by the presence of BAs in the soy sauce or soybean paste ,23. Accop < 0.05 for all). Since there has not been reports about the effect of cooking on the BA formation in fishery products it was hard to evaluate our results. However, in the roasting of cocoa beans, the highest temperature, and air humidity led to the greatest rise in BA due to precursor transformation at high heat treatment [In all cooking methods, the level of total BAs increased significantly as the temperature increased. Increases of up to 190%, 236%, and 152% were observed as roasting, frying and stewing temperature increased, respectively (reatment . Referrireatment .Additionally, recent studies have shown that BA can be formed during heat treatment by chemical decarboxylation of amino acids in the presence of lipid peroxides . TherefoIn this study, five BAs, including TRP, PHE, PUT, HIS, and SPD, formed in mackerel subjected to various cooking methods and conditions were analysed. In 40 mackerel samples, the detected concentration ranges of PUT, HIS, TRP, PHE, and SPD were 11.43–43.11, 6.34–84.2, 4.12–45.51, 4.01–42.87, and 2.13–10.09 µg/g, respectively. The total BAs formed during roasting, frying, and stewing were 42.01–93.32, 33.09–146.58, and 126.84–19.53 µg/g, respectively. The total level of BAs increased significantly with increasing temperature in all cooking methods. Compared to the control group, the total BAs for roasting, frying, and stewing increased up to 170%, 311%, and 398%, respectively, when cooking was completed.The results of this study indicate that a change of the cooking conditions such as temperature and time may contribute to the reduction of BA concentration in foods. Future studies should include a comprehensive analysis of the BA levels in foods using various western and eastern cooking recipes for controlling the formation and dietary exposure to BAs.


Behavioural interventions can support the adoption of healthier lifestyles and improve physical health outcomes, but it is unclear what factors might drive success of such interventions in people with serious mental illness (SMI). We systematically identified and reviewed evidence of the association between determinants of physical health self-management behaviours in adults with SMI. Data about American Association of Diabetes Educator's Self-Care Behaviours (AADE-7) were mapped against the novel Mechanisms of Action (MoA) framework. Twenty-eight studies were included in the review, reporting evidence on 104 determinant-behaviour links. Beliefs about capabilities and beliefs about consequences were the most important determinants of behaviour, especially for being physically active and healthy eating. There was some evidence that emotion and environmental context and resources played a role in determining reducing risks, being active, and taking medications. We found very limited evidence associated with problem solving, and no study assessed links between MoAs and healthy coping. Although the review predominantly identified evidence about associations from cross-sectional studies that lacked validated and objective measures of self-management behaviours, these findings can facilitate the identification of behaviour change techniques with hypothesised links to determinants to support self-management in people with SMI.Systematic Review Registration: PROSPERO, registration CRD42018099553. Adults with serious mental illness (SMI), such as schizophrenia or bipolar disorder, experience considerable inequalities in health outcomes compared with the general adult population. Life expectancy for individuals with SMI is 10–20 years shorter and the mortality rate 3.7 times higher than in the general population . FurtherSupported self-management is critical to prevention and improving outcomes of long-term physical conditions and there is robust evidence that behavioural interventions can effectively support people in the general population to self-manage their health . Self-maThe evidence for behavioural interventions to support self-management in people with SMI is limited. There is some evidence that prescribed and directly administered exercise interventions that include up to 90 min a week of moderate-to-vigorous exercise can improve physical fitness and cardiometabolic risk as well as reduce psychiatric symptoms in people with schizophrenia . HoweverLiving with SMI may pose significant barriers to engaging in self-management of physical health. Individuals with SMI spend less time being physically active , are lesOver and above individual level factors, social and community level factors also underscore health inequalities experienced by people with SMI. People with SMI are more likely to experience higher levels of deprivation than the general population  and SMI To maximise the chance that behavioural interventions to support physical health self-management in people with SMI are effective and sustainable, an approach that draws on the science of behaviour change is needed. Intervention development in such an approach proceeds by the description of behavioural targets that drive risk factors, identification of mechanisms of action through which behaviour change might occur, followed by the identification of specific techniques that might alter the target, and the formulation of process measures that can measure the extent to which the intervention was successful . Our appCapability relates to a person's psychological and physical capacity to undertake a behaviour, including know-how and skills to do so. Opportunity concerns all the available social and physical factors within a person's environment that make the behaviour possible, while Motivation is specified as both reflective processes associated with planning and automatic processes associated with emotional responses, reactions, and impulses. The COM-B model proposes that capability and opportunity can influence motivation, to bring about behaviour through both direct and indirect paths. There is emerging evidence that COM-B outperforms other more established models of behaviour such as the theory of planned behaviour, theory of reasoned action, and the health belief model, in explaining the variance in delivery of opportunistic behaviour change interventions and the variance in time spent delivering interventions  with expert rated links to 56 frequently used behaviour change techniques , 40. TheThis systematic review forms the first phase of work of the DIAMONDS research programme that is dedicated to developing, piloting, and then definitively testing a supported self-management intervention based on evidence based behaviour change techniques for people with SMI and diabetes . Our revWhat are the determinants of self-management behaviours that underpin physical health in adults with SMI?How do these determinants differ for people with SMI who have co-morbid long-term physical health conditions?Studies were eligible if they reported determinants of self-management of physical health in adults with SMI. In this review physical health relates to a dynamic state related to a person's ability to self-manage and restore functional capacity and well-being . DetermiIn keeping with previous systematic reviews where populations with mixed diagnoses and age groups might be identified  we excluBecause we wanted to use the findings from this systematic review to inform the development of behaviour change interventions for people with SMI and diabetes in a high-income health service context we restricted studies to those reported in English and conducted in high income countries according to 2018 OECD Country Classifications . There wWe searched the following databases:CINAHL (EBSCO) 1981- 25/07/2018Conference Proceedings Citation Index- Science  1990 - 25/07/2018Evidence Search (NICE), all available years - 25/07/2018HMIC Health Management Information Consortium (Ovid) 1983 - 25/07/2018Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily 1946 to August 26, 2020PsycINFO (Ovid) 1806 to August Week 3 2020We also checked relevant systematic reviews identified in the search for additional eligible primary studies.All databases were searched on 25th July 2018. Update searches were conducted on 21st November 2019 and 27th August 2020 in the two databases that generated the most eligible studies in the original searches (MEDLINE and PsycINFO). A comprehensive search was designed using textwords, synonyms and indexing-terms. The searches were peer-reviewed by a second information specialist. An example search strategy for Ovid MEDLINE is shown in Unique records identified by the search were imported into Covidence . Two revRelevant data were extracted by one reviewer into a table organised by determinants and behaviours. Using the MoA definitions , each deEach behaviour was then mapped to one AADE-7 category: healthy eating; being active; monitoring; taking medication; problem solving; reducing risks , and healthy coping. Once a data item was mapped as described, an MoA and AADE-7 determinant-behaviour link was formed.Quantitative findings describing determinants of self-management behaviours in individuals with SMI were the data of interest. Where studies included a non-SMI control group only the SMI group data were extracted.The methodological quality of the included studies was assessed by one reviewer using the NICE quality appraisal checklist for quantitative studies reporting correlations and associations , which pWe performed a narrative synthesis as data were too heterogenous to allow for meta-analysis of statistical tests of associations between determinants and behaviours. Studies reporting statistical tests of associations were prioritised in the synthesis. Where a study performed a multivariable analysis of determinants we opted to use the univariate associations to enhance comparability with other studies that did not include multivariate analyses. We mapped links between MoAs and AADE-7 self-management behaviours against the superordinate COM-B framework. This allowed for MoAs that derive from the TDF to be easily identifiable within the COM-B framework and offers the means to identify candidate intervention functions associated with MoAs using the behaviour change wheel . Links wA flowchart of study selection in the context of the overarching review is shown in Characteristics of the included studies are shown in Quality appraisal ratings are shown in Twenty-one MoAs were identified as determinants of self-management behaviours for people with SMI and people with SMI and diabetes. Nineteen tests of association between MoAs and self-management behaviours were identified in six studies that could be grouped under the Capability domain. There was only limited evidence from one cross-sectional study about barriers to effective diabetes management in people with SMI, which reported that knowledge was positively associated with the frequency of following a healthy eating plan . This saThere was mixed evidence that behavioural regulation was associated with monitoring, with one result showing a positive association with this behaviour , and anoBehavioural regulation was positively associated with being active in a cross-sectional study of predictors of physical activity in people with a wide range of SMI ; howeverCross-sectional data from a study about glycaemic control and diabetes self-care in people with schizophrenia did not show either a positive or negative relationship between skills and behaviours associated with reducing risks . Memory,The certainty of evidence for associations between MoAs and AADE-7 health behaviours within the Capability domain was rated as moderate across all studies. Only two studies reported positive associations: one for healthy eating (knowledge) and one for monitoring, problem solving, and being active . One study reported negative associations for healthy eating with memory, attention and decisional processes and behavioural regulation and also with monitoring for behavioural regulation. The majority of associations in this domain were inconclusive for five of the seven health behaviours.Eighteen tests of association between MoAs and self-management behaviours were identified in studies that could be grouped under the Opportunity domain. Cross-sectional data from one study showed that social influences and environmental context and resources were positively associated with healthy eating . EnvironThe certainty of evidence for associations between MoAs and AADE-7 health behaviours within the Opportunity domain was rated as moderate across all studies. There was more inconclusive evidence for the importance of social influences being associated with behaviours, with only one study showing a positive association for this MoA with healthy eating and being active. The role of environmental context and resources appears to be important with four studies reporting positive associations for four behaviours . Two studies reported negative associations with being active and environmental context and resources. There was little conclusive evidence about the role of behavioural cueing in prompting behaviours.Sixty-three tests of association between MoAs and self-management behaviours were identified in twelve studies that could be grouped under the Motivation domain. The most consistent evidence was observed between MoAs and healthy eating, with positive associations observed in one cross-sectional study for reinforcement, emotion, beliefs about capabilities, beliefs about consequences, intentions, goals, and optimism . This stEvidence about the links between MoAs and monitoring was also drawn from the same cross-sectional study, but findings were equivocal. A positive significant association was reported for the link between emotion and monitoring, but no significant associations were observed for reinforcement, beliefs about consequences, intentions, goals, optimism, and social/professional role identity with this behaviour .The most evidence was observed for determinants of being active. Eleven MoAs were positively associated with being active across ten studies , 78, 82.Two cross-sectional studies reported positive associations between emotion and reducing risks associated with smoking and diabetic foot problems , 71, andNo positive associations were reported for links between determinants of taking medications. All observations were drawn from one cross-sectional study . Goals wThere was no evidence found for links between AADE-7 self-management behaviours and these MoAs: norms, needs, social learning/imitation, feedback processes, and general attitudes/beliefs.The certainty of evidence for associations between MoAs and AADE-7 health behaviours within the Motivation domain was generally rated as moderate, but some evidence for positive associations was drawn from studies with low and very low ratings. The bulk of the evidence about determinants of behaviours was captured within this domain, with 44 links between four behaviours  and 11 MoAs being reported as positive. Results for being active and healthy eating clustered around beliefs about capabilities and beliefs about consequences. Goals and intentions were also linked three times with these behaviours. There was less inconclusive evidence within this domain with only four studies reporting no associations across four behaviours. Negative associations were reported for motivation (being active), goals , but these findings were reported in just two studies.Using the novel MoA framework that comprehensively captures processes known to be associated with behaviour change, this review aimed to identify the determinants of self-management behaviours that underpin physical health in adults with SMI. The bulk of the evidence for associations between MoAs and self-management behaviours clustered around the super-ordinate Motivation domain in the COM-B framework. This finding lends further empirical support to the proposition that Motivation (which includes reflective and automatic processes) sits at the centre of the COM-B model and mediates behaviour via Capability and Opportunity . In keepOutside of the capability and motivation constructs we also showed that environmental context and resources were important determinants of being active. Previous reviews have shown that lower self-efficacy and social isolation are correlated with lower physical activity participation in people with schizophrenia  and bipoThere was less evidence and less consistency across available evidence about determinants of other self-management behaviours. Ten MoAs were linked with healthy eating, but none were reported more than once. It is worth noting that memory, attention, and decision processes, and behavioural regulation were negatively associated with healthy eating in people with SMI and diabetes. Both these MoAs include higher level cognitive processing that some people with SMI might find challenging. Cognitive deficits associated with attention and working memory are considered a central feature of schizophrenia . These dReducing risks, monitoring, and taking medication are critical behaviours to self-managing long-term conditions, and this is especially the case in the context of SMI. We identified four studies of self-management in people with diabetes and SMI. Lower diabetes related distress was associated with less smoking and more frequent blood glucose monitoring among people with SMI and diabetes. People with SMI are three times as likely as the general population to smoke  and are We also did not identify much evidence about what determines medication taking, but there was some signal that environmental context in the form of access to health services might play an important role in driving this behaviour among people with SMI and diabetes. Adherence to oral hypoglycaemic medication is known to be higher among adults with diabetes who take three or more other medications and have more frequent physical health checks . In the Despite there being good evidence for how health behaviour models might explain physical activity in the general population, few behaviour change interventions used in people with SMI are underpinned by theory. Only nine out of 32 studies included in a systematic review of behaviour change interventions to promote physical activity in people with SMI were based on theory . Social A major strength of this systematic review is that it has operationalised the novel MoA framework using the COM-B model, possibly for the first time, to synthesise published evidence about links between determinants of self-management behaviours in people with SMI, including people with SMI and diabetes. The strengths of the MoA framework stem from the fact that it is based on the result of evidence synthesis and expert consensus, with a series of subsequent triangulation studies that sought to integrate the previous findings quantitatively and through expert consensus. This approach has resulted in evidence that builds upon the previous BCT Taxonomy V1  and provWe did not find studies of people with other long-term conditions so we cannot be sure this evidence extends beyond diabetes. Methodological strengths of the review include independent assessment of study eligibility by two reviewers and checking of data extraction and quality appraisal by a second reviewer. We conducted comprehensive searches but it is possible some evidence was missed through exclusion of conference abstracts and dissertations and a top-up search was conducted in only two databases.We did not rate quality of included studies based on sample size. Nor did we exclude studies that reported smaller sample sizes. There is little empirical evidence that sample size drives risk of bias and smaller studies can still make a significant contribution to innovative and translational research . Our revUsing the MoA framework can make it difficult to maintain specificity in how determinants are identified, especially among those existing within broader domains such as environmental context and resources, with implications for the appropriateness of subsequent selection of behaviour change techniques. More descriptive and nuanced data about whether determinants acted as barriers or motivators could also have been lost through the methods used, pointing to the need for qualitative studies about drivers of self-management behaviours in people with SMI. Additionally, the framework does not describe relationships between mechanisms established by social cognition models of behaviour and behaviour change . HypotheWe assessed the strength and direction of associations using conventional measures of statistical significance for univariate analyses that assessed the relationship between MoAs and self-management behaviours. This approach might limit the robustness of the synthesis as tests of significance and non-significance are dependent on a range of factors such as sample size or quality which is not captured using these methods. Furthermore, many of the included studies had small sample sizes that precluded the use of multivariate regression analyses that would offer adjusted and more accurate assessments of predictors of self-management behaviours.A further limitation of the review is that it included mainly moderate to low quality cross-sectional evidence that cannot attribute causality, but this was partly a result of excluding intervention studies to avoid including associations between determinants and behaviours that had been modified by behaviour change techniques. This approach effectively restricted the evidence base to single group cohort designs. Most of the included studies did not use valid measures of behaviour. This was especially true for physical activity. Only one study used an accelerometer to objectively measure activity but the small sample size precludes drawing firm conclusions. There were also studies which compared SMI groups to non-SMI control groups and only the SMI group data could be extracted from these studies. It was not always straightforward to extract and map behavioural determinants but mapping to MoAs was performed by researchers with past experience of applying the framework to evidence of behavioural determinants in SMI groups. We enhanced the internal validity of this process by consulting linked evidence, such as qualitative studies, to help pinpoint the most appropriate MoA, with a second reviewer checking all allocation of evidence to MoAs.Our heat-map matrix of MoAs and self-management behaviours, organised under the broader COM-B model of behaviour change, allows for easier identification and possible adaptation of candidate behaviour change techniques using existing resources such as the online theory and techniques tool . Using tFeedback and monitoring are among the BCTs linked to the MoAs that we identified as being associated with health behaviours under the Motivation domain of the COM-B. This finding tallies with the results of the STEPWISE process evaluation which showed that participants who wanted to lose weight wanted closer monitoring and healthcare professionals wanted to monitor weight outcomes too, but such a focus on monitoring lay outside the scope of the intervention. Going forwards, the advent of wearable technology to objectively measure physical activity, behaviour change applications for smartphones, and devices that allow continuous glucose monitoring are likely to transform the capacity of behaviour change interventions to facilitate monitoring. There is evidence that the use of wearable technology and digital applications are acceptable among adults who take part in facilitated and remotely delivered behaviour change interventions to reduce the risk of long-term conditions . The relThis review provides an evidential basis for the development of appropriate and theory-based behaviour change interventions for managing physical health in adults with SMI. We synthesised evidence about 21 determinants of physical health self-management behaviours known to be important in people with SMI and people with SMI and a long-term condition. Organisation of evidence within the MoA framework facilitates the identification of behaviour change techniques with hypothesised links to determinants. Many of these determinants overlap and stem from reflective and automatic motivational processes. Critical determinants for being active and healthy eating were beliefs about capabilities and beliefs about consequences. There was less evidence about what determines other self-management behaviours but emotion and environmental context and resources appear to be important determinants of reducing risks and taking medications. The next phase of research and development should involve drawing up a shortlist of candidate BCTs and the involvement of healthcare professionals and people with lived experience of SMI to support decisions about how they are delivered using methods such as expert consensus and co-design.The original contributions presented in the study are included in the article/NS, JT, PC, EP, IK, CK, SA, JW, and JL wrote the protocol. CK, JT, PC, SA, EP, JL, AB-K, BY, JBr, CC, and IK screened titles and abstracts. BY, AB-K, JBr, and CC screened full text records. CC, JBr, PC, AB-K, BY, and JT assessed quality of included studies. PC wrote the first complete draft of the manuscript. All authors edited the manuscript for substantive intellectual content.The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NHS, NIHR, or the Department of Health and Social Care. URKI does not necessarily endorse the views expressed by the authors.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 long-term care setting poses unique challenges and opportunities for effective knowledge translation. The objectives of this review are to (1) synthesize barriers and facilitators to implementing evidence-based guidelines in long-term care, as defined as a home where residents require 24-h nursing care, and 50% of the population is over the age of 65 years; and (2) map barriers and facilitators to the Behaviour Change Wheel framework to inform theory-guided knowledge translation strategies.Following the guidance of the Cochrane Qualitative and Implementation Methods Group Guidance Series and the ENTREQ reporting guidelines, we systematically reviewed the reported experiences of long-term care staff on implementing evidence-based guidelines into practice. MEDLINE Pubmed, EMBASE Ovid, and CINAHL were searched from the earliest date available until May 2021. Two independent reviewers selected primary studies for inclusion if they were conducted in long-term care and reported the perspective or experiences of long-term care staff with implementing an evidence-based practice guideline about health conditions. Appraisal of the included studies was conducted using the Critical Appraisal Skills Programme Checklist and confidence in the findings with the GRADE-CERQual approach.After screening 2680 abstracts, we retrieved 115 full-text articles; 33 of these articles met the inclusion criteria. Barriers included time constraints and inadequate staffing, cost and lack of resources, and lack of teamwork and organizational support. Facilitators included leadership and champions, well-designed strategies, protocols, and resources, and adequate services, resources, and time. The most frequent Behaviour Change Wheel components were physical and social opportunity and psychological capability. We concluded moderate or high confidence in all but one of our review findings.Future knowledge translation strategies to implement guidelines in long-term care should target physical and social opportunity and psychological capability, and include interventions such as environmental restructuring, training, and education.The online version contains supplementary material available at 10.1186/s13012-021-01140-0. Contributions to the literatureEvidence-based guidelines enhance the provision of care. However, trial-and-error-based approaches to implementation are costly and ineffective.This review summarizes knowledge on contextual factors in the long-term care setting that influence implementation of evidence-based guidelines to facilitate more effective and sustainable uptake in practice.By placing the findings of our qualitative evidence synthesis within the context of a behaviour change framework, our work provides theory-guided strategies to inform future translation of evidence into practice in long-term care homes.Evidence-based guidelines summarize the best available research on health care practices to enhance the provision of consistent and appropriate care . HoweverCapability, Opportunity, and Motivation as sources of Behaviour. Users can determine what needs to change for the desired behaviour  to occur by identifying barriers and facilitators and mapping them onto the COM-B system. The Behaviour Change Wheel then guides users to select potential knowledge translation interventions based on their COM-B analysis [Many existing knowledge translation frameworks guide researchers to consider complex factors that influence the success of guideline uptake prior to the implementation process –8. The Banalysis . TherefoThe need to effectively translate evidence-based guidelines into practice is especially pressing for older adults  as the pThe findings of our study will synthesize barriers and facilitators to evidence-based guideline implementation across health conditions in LTC and mapped onto the COM-B components. Our identified barriers and facilitators and suggested knowledge translation strategies based on the COM-B mapping can be used to design theory-guided knowledge translation interventions in LTC. This will save time, effort, and resources in identifying barriers and facilitators so that planners can design interventions more quickly and efficiently. Further, our review will identify gaps in research related to evidence-based guideline implementation in LTC and make suggestions for future work.The objectives of this qualitative evidence synthesis are to (1) synthesize barriers and facilitators that LTC staff experience during the implementation of evidence-based guidelines and (2) map the identified barriers and facilitators to the central component of the Behaviour Change Wheel framework to inform future theory-guided knowledge translation intervention development in the LTC setting. Our research question is “What are the barriers and facilitators to implementing evidence-based health care guidelines in LTC homes from the perspectives of staff ?” The phenomena of interest is implementation of health care guidelines into practice and the factors that hinder or facilitate implementation. The context is LTC homes who provide 24-h nursing care for mostly frail, medically complex older adults across the world in the 21st century.We conducted a qualitative evidence synthesis following the guidance of the Cochrane Qualitative and Implementation Methods Group Guidance Series  and the We included primary studies that use qualitative study designs such as ethnography, phenomenology, case studies, grounded theory studies, and qualitative process evaluations. We included studies that use both qualitative methods for data collection  and qualitative methods for data analysis . We included studies that collect data using qualitative methods but do not analyse these data using qualitative analysis methods  as long as the results or findings identify barriers and facilitators as described below. We only included published studies written in English. We did not exclude studies based on our assessment of methodological limitations. We used this information about methodological limitations to assess our confidence in the review findings.The target behaviour was implementing evidence-based guidelines into practice . Barriers were defined as any factors that obstruct the capacity for LTC staff and homes to implement guidelines, while facilitators were any factors that enable implementation.The group required to perform the target behaviour was LTC staff which included personal support workers, clinicians , and home administration .Studies were included if they were conducted in LTC, defined as a home where residents require 24-h nursing care, and 50% of the population is over the age of 65 years.Relevant articles were identified through a pre-planned literature search in MEDLINE Pubmed (1946 to present), EMBASE Ovid (1974 to present), and CINAHL (1981 to present) in July 2019 and updated in 2021. The key concepts used in the searches were “long-term care”, “guidelines”, “implementation”, “barriers”, and “facilitators”. The key concepts were combined with the Boolean operator AND, and the search words within each concept were combined with OR. The full search strategy can be found in Additional file All titles and abstracts were screened by two team members (CM and YB) using a pilot-tested form and were included if they met our inclusion criteria as described above. We excluded articles that were not written in English, reported on implementation of guidelines that were not evidence-based , clinical commentaries, editorials, legal cases, letters, newspaper articles, abstracts, or unpublished literature. After title and abstract screening, the full texts of relevant articles were screened independently by the same two reviewers using a pilot-tested form. Disagreements were arbitrated by a third party.Two team members (CM and YB) independently extracted and charted the following data in duplicate using a pilot-tested data extraction form: study description , individual participant description (profession(s), number, mean age, sex, sampling technique, response rate), LTC home description , and results/findings (identified barriers and facilitators). Data for the study results were extracted verbatim from the text under the heading “results” or “findings” where authors identified barriers and facilitators  to implementation of the guidelines examined.The validity, robustness, and applicability of each included study was appraised by two team members (CM and PH) independently and in duplicate using the Critical Appraisal Skills Programme (CASP) Checklist . ConsensOur synthesis follows the three-stage Thomas and Harden approach to inductive thematic synthesis . We compTwo review authors (CM and PH) assessed the level of confidence for each finding using the GRADE-CERQual . GRADE-CWe present summaries of the findings and our assessments of confidence in these findings in the Summary of qualitative findings table Table . We presThe authors of this article are a multidisciplinary group of researchers and clinicians focused on geriatrics and improving care provision in LTC. They have engaged in several research studies in LTC including assessment of barriers and facilitators to implementation of practices, development of guidelines, knowledge translation, and randomized controlled trials. Since we have prior experience assessing barriers and facilitators in the LTC setting, some biases may exist as we may have preconceived ideas of what barriers and facilitators exist. Included studies that were conducted by one of the authors of the current paper were analyzed by two team members who were not authors of the included studies.After screening 2680 articles, 33 that were published between 2004 and 2020 were included in the analyses Fig. .Fig. 1FMost studies were conducted in Canada and Australia, with much fewer in the Netherlands, the USA, England, Sweden, Germany, South Korea, and Belgium Table . A wide Included studies recruited 12 to 500 LTC home staff from a variety of professions including nursing, medicine, management, rehabilitation , pharmacy, and food services Table . Many stMost studies had a clear research aim which was appropriately addressed through a qualitative research design. Likewise, most studies employed appropriate recruitment strategies and data were collected in a way that addressed the research question. In some studies, the description of data analysis techniques was limited. Overall, we found poor reporting of research reflexivity across most of the included studies. Details of the assessments of methodological limitations for individual studies are found in Additional file We had moderate or high confidence in all but one of our review findings. Confidence was most often downgraded due to concerns with methodological limitations including a lack of discussion about credibility of qualitative findings and a lack of reflexivity. The data was almost always relevant as most studies examined our phenomena and population of interest. The full CERQual evidence profile can be found in Additional file The line-by-line thematic analysis of barriers and facilitators is found in Additional file Physical and social opportunity were the COM-B components that the identified barriers and facilitators mapped onto most frequently Table . Within We previously described our initial positioning earlier (see review author reflexivity above). Throughout the review, our positioning remained the same. During analysis and writing of the discussion, we felt our findings confirmed our initial ideas about the most frequent barriers and facilitators.We systematically identified barriers and facilitators to implementing evidence-based guidelines in LTC and used behaviour change theory to link them to candidate knowledge translation functions. Across several guideline topics, time constraints and inadequate staffing, cost and lack of resources, knowledge gaps, and lack of teamwork and organizational support were frequently identified barriers. In contrast, leadership and champions, well-designed strategies, protocols, and resources, and adequate services, resources and time were frequently identified as facilitators. Linking to the central components of the Behaviour Change Wheel suggests physical and social opportunities and psychological capability are common targets for change to overcome barriers and leverage facilitators. While the most frequently identified barriers and facilitators appear to be universal regardless of guideline topics , some guidelines may have nuanced actions that have unique barriers and facilitators. We suggest that future knowledge translation and implementation science researchers assume the most frequently identified barriers and facilitators in our review are present and that they design strategies targeted at physical and social opportunity and psychological capability. A further analysis of barriers and facilitators may be necessary if the actions outlined by the guideline have unique features that could create additional barriers and facilitators.The reported barriers and facilitators in our qualitative systematic review most frequently mapped onto the central Behaviour Change Wheel components physical and social opportunity: the opportunities afforded by the environment  and interpersonal influences . The findings that environmental opportunities  are significant barriers to implementing evidence-based guidelines echo recent concerns surrounding quality of care provided in LTC highlighted by the COVID-19 pandemic  and is cGiven the recent international interest in improving LTC during and after the COVID-19 pandemic and the subsequent impetus to support significant changes to the sector , 25, sevKnowledge gaps pertaining to the information within guidelines, change fatigue, and lack of interest in work were frequently identified barriers and facilitators in our systematic review, which mapped onto the COM-B domains of psychological capability and reflective and automatic motivation. In many countries, most direct care within LTC homes is provided by care aides  , 28 who This is the first study to synthesize barriers and facilitators to guideline implementation in LTC from the perspectives of staff across healthcare conditions. Barriers and facilitators to guideline implementation have been systematically reviewed in other healthcare settings, but until now, no syntheses have been developed for the LTC context. Further, we not only identified the barriers and facilitators but also mapped them onto the central constructs of the Behaviour Change Wheel. This helps us explore the reasons why the factors identified are barriers and facilitators and the findings can be used to inform the development of future theory-guided knowledge translation intervention development.From a methodological point of view, the studies included in our review had several limitations. First, studies often did not report important information about the LTC home(s) which provides context from which the results were derived, such as the size, ownership, and rurality of the LTC home. The context of the LTC home including number of residents in a home, funding structure, and access to resources has been previously shown to affect implementation of best practice guidelines in LTC . Future A strength of our study is that we synthesized information across different health conditions within the LTC sector. Given that there are likely many similarities among barriers and facilitators across guidelines for different conditions in the LTC setting, the findings of this qualitative evidence synthesis can help inform the implementation of any evidence-based guideline in LTC homes. However, a limitation of our study is that we did not assess the strength of the barriers and facilitators identified in this review. A frequently identified barrier may not hinder implementation as much as one that is less frequently reported. We argue that frequently reported barriers across several guideline topics are nonetheless important to identify as they can inform design of knowledge translation strategies regardless of topic. Future work should examine the strength of barriers and facilitators in LTC for implementing evidence-based guidelines and determine which barriers significantly limit implementation to add to our work. Another limitation is that we did not complete the third stage of the Thomas and Harden approach to thematic synthesis  to develWe suggest that people designing LTC interventions to support guideline implementation assume the most frequently identified barriers  and facilitators  in our review are present and design strategies targeted at physical and social opportunity and psychological capability. Further analysis of barriers and facilitators specific to the guideline they are implementing may be necessary if the actions outlined by the guideline have unique features that could cause additional barriers and facilitators.Implications for research have been developed based on the findings of our study and our GRADE-CERQual assessment of findings. Future qualitative work in this area should transparently report researcher reflexivity including a reflection of the researchers’ roles and the influence this may have on the findings of the study. Additionally, researchers must fully describe the context of their LTC setting to ensure readers can determine whether the findings apply to their local LTC context. A full description of context would include the care philosophy of the home, staffing levels, and health system influences  among other factors.Additional file 1. ENTREQ Checklist.Additional file 2. Search Strategy.Additional file 3. Evidence Profile.Additional file 4. CASP Checklist.Additional file 5. Barriers and Facilitators Analysis.