Designing and implementing a research integrity promotion plan: Recommendations for research funders.

Various stakeholders in science have put research integrity high on their agenda. Among them, research funders are prominently placed to foster research integrity by requiring that the organizations and individual researchers they support make an explicit commitment to research integrity. Moreover, funders need to adopt appropriate research integrity practices themselves. To facilitate this, we recommend that funders develop and implement a Research Integrity Promotion Plan (RIPP). This Consensus View offers a range of examples of how funders are already promoting research integrity, distills 6 core topics that funders should cover in a RIPP, and provides guidelines on how to develop and implement a RIPP. We believe that the 6 core topics we put forward will guide funders towards strengthening research integrity policy in their organization and guide the researchers and research organizations they fund.

Similar Outcomes of Web-Based and Face-to-Face Training of the GRADE Approach for the Certainty of Evidence: Randomized Controlled Trial.

BACKGROUND: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach is a system for transparent evaluation of the certainty of evidence used in clinical practice guidelines and systematic reviews. GRADE is a key part of evidence-based medicine (EBM) training of health care professionals. OBJECTIVE: This study aimed to compare web-based and face-to-face methods of teaching the GRADE approach for evidence assessment. METHODS: A randomized controlled trial was conducted on 2 delivery modes of GRADE education integrated into a course on research methodology and EBM with third-year medical students. Education was based on the Cochrane Interactive Learning "Interpreting the findings" module, which had a duration of 90 minutes. The web-based group received the web-based asynchronous training, whereas the face-to-face group had an in-person seminar with a lecturer. The main outcome measure was the score on a 5-question test that assessed confidence interval interpretation and overall certainty of evidence, among others. Secondary outcomes included writing a recommendation for practice and course satisfaction. RESULTS: In all, 50 participants received the web-based intervention, and 47 participants received the face-to-face intervention. The groups did not differ in the overall scores for the Cochrane Interactive Learning test, with a median of 2 (95% CI 1.0-2.0) correct answers for the web-based group and 2 (95% CI 1.3-3.0) correct answers for the face-to-face group. Both groups gave the most correct answers to the question about rating a body of evidence (35/50, 70% and 24/47, 51% for the web-based and face-to-face group, respectively). The face-to-face group better answered the question about the overall certainty of evidence question. The understanding of the Summary of Findings table did not differ significantly between the groups, with a median of 3 correct answers to 4 questions for both groups (P=.352). The writing style for the recommendations for practice also did not differ between the 2 groups. Students' recommendations mostly reflected the strengths of the recommendations and focused on the target population, but they used passive words and rarely mentioned the setting for the recommendation. The language of the recommendations was mostly patient centered. Course satisfaction was high in both groups. CONCLUSIONS: Training in the GRADE approach could be equally effective when delivered asynchronously on the web or face-to-face. TRIAL REGISTRATION: Open Science Framework akpq7; https://osf.io/akpq7/.

Effectiveness of letters to patients with or without Cochrane blogshots on 10-year cardiovascular risk change among women in menopausal transition: 6-month three-arm randomized controlled trial.

BACKGROUND: Health information and patient education on lifestyle changes may have a positive effect on the prevention of many chronic conditions, especially cardiovascular diseases (CVDs). We performed a parallel, three-arm randomized controlled trial (RCT) of 6-month educational intervention in a form of letters containing a reminder of the participant's CVD risk with or without Cochrane blogshots to reduce CVD risk among women aged 45-65 with one or more known CVD risk factors. METHODS: The control group received a letter about their CVD risk at the beginning of the trial. The intervention groups received the initial letter about their CVD risk and remainder letters about their CVD risk every 2 months, with or without Cochrane blogshots: (1) effect of calcium in the prevention of high blood pressure, (2) effect of reducing saturated fat acids in eating habits, and (3) effects of green and black tea in CVD prevention. The primary outcome was CVD risk reduction calculated as the difference between the baseline and 6-month score for a 10-year risk of fatal CVD according to the ACC/AHA guidelines. RESULTS: After both interventions, CVD risk reduction was significantly higher compared to the control group (P < 0.001, Kruskal-Wallis H test). The number of participants who decreased their CV risk was 29% (20/70) in the control group, 69% (48/70) in the group receiving the reminder letters, and 70% (49/70) in the group receiving the reminder letters and blogshots. The number needed to treat to achieve risk reduction was 2.41 (95% CI = 1.77 to 3.78) for letters with a CVD risk reminder and 2.50 (1.81 to 4.03) for letters with a reminder and a blogshot. The group receiving reminder letters with Cochrane blogshots had a significant change in the category of CVD risk, mainly from high to moderate and from moderate to low CVD risk category. CONCLUSIONS: A simple and inexpensive intervention method in a form of letters reminding women about their CVD risk with or without providing additional health information in the form of Cochrane blogshots about interventions for important CVD risk factors may be effective in CVD management and could be considered by primary care providers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04601558. Retrospectively registered on October 19, 2020.

Factors to Consider During Identification and Invitation of Individuals in a Multi-stakeholder Research Partnership.

BACKGROUND: Health research teams increasingly partner with stakeholders to produce research that is relevant, accessible, and widely used. Previous work has covered stakeholder group identification. OBJECTIVE: We aimed to develop factors for health research teams to consider during identification and invitation of individual representatives in a multi-stakeholder research partnership, with the aim of forming equitable and informed teams. DESIGN: Consensus development. PARTICIPANTS: We involved 16 stakeholders from the international Multi-Stakeholder Engagement (MuSE) Consortium, including patients and the public, providers, payers of health services/purchasers, policy makers, programme managers, peer review editors, and principal investigators. APPROACH: We engaged stakeholders in factor development and as co-authors of this manuscript. Using a modified Delphi approach, we gathered stakeholder views concerning a preliminary list of 18 factors. Over two feedback rounds, using qualitative and quantitative analysis, we concentrated these into ten factors. KEY RESULTS: We present seven highly desirable factors: 'expertise or experience', 'ability and willingness to represent the stakeholder group', 'inclusivity (equity, diversity and intersectionality)', 'communication skills', 'commitment and time capacity', 'financial and non-financial relationships and activities, and conflict of interest', 'training support and funding needs'. Additionally, three factors are desirable: 'influence', 'research relevant values', 'previous stakeholder engagement'. CONCLUSIONS: We present factors for research teams to consider during identification and invitation of individual representatives in a multi-stakeholder research partnership. Policy makers and guideline developers may benefit from considering the factors in stakeholder identification and invitation. Research funders may consider stipulating consideration of the factors in funding applications. We outline how these factors can be implemented and exemplify how their use has the potential to improve the quality and relevancy of health research.

Inadequate reporting quality of registered genome editing trials: an observational study.

BACKGROUND: To assess registration completeness and safety data of trials on human genome editing (HGE) reported in primary registries and published in journals, as HGE has safety and ethical problems, including the risk of undesirable and unpredictable outcomes. Registration transparency has not been evaluated for clinical trials using these novel and revolutionary techniques in human participants. METHODS: Observational study of trials involving engineered site-specific nucleases and long-term follow-up observations, identified from the WHO ICTRP HGE Registry in November 2020 and two comprehensive reviews published in the same year. Registration and adverse events (AEs) information were collected from public registries and matching publications. Published data were extracted in May 2021. RESULTS: Among 81 eligible trials, most were recruiting (51.9%) phase 1 trials (45.7%). Five trials were withdrawn. Most trials investigated CAR T cells therapies (45.7%) and used CRISPR/Cas9 (35.8%) ex vivo (88.9%). Among 12 trials with protocols both registered and published, eligibility criteria, sample size, and secondary outcome measures were consistently reported for less than a half. Three trials posted results in ClinicalTrials.gov, and one reported serious AEs. CONCLUSIONS: Incomplete registration and published data give emphasis to the need to increase the transparency of HGE trials. Further improvements in registration requirements, including phase 1 trials, and a more controlled publication procedure, are needed to augment the implementation of this promising technology.

Deidentification of facial photographs: a survey of editorial policies and practices.

We analysed all journals from two Journal Citation Reports (JCR) categories: 'Dentistry, Oral Surgery and Medicine' and 'Otorhinolaryngology' published in 2018 for their policies on publishing facial photographs and actual practices of publishing these photographs in articles. We extracted the following data for each journal: JCR category, impact factor, volume, issue, instructions for authors regarding ethical issues, instructions for photograph deidentification, journals' references to standard research and publishing policies, presence and type of published clinical images, separate informed consent for the publication of patient photograph and methods of deidentification. The sample included 103 journals, which published 568 articles with 1404 clinical images. Around a half of the journals (52%) had a policy on clinical images, however, the only predictor of having a journal policy on clinical images was reference in the policy to International Committee of Medical Journal Editors Recommendations (OR=3.00, 95% CI 1.26 to 7.14, p=0.013). Identifiable patient photographs were found in 13% (79/568) of the articles, constituting 9% (128/1404) of the total sample of images. Only 16% (13/79) of articles publishing recognisable patient facial images included a statement about consent for publication of the image. From the total sample of articles, 34% (27/79) contained deidentified but recognisable patient photographs and only 22% (6/27) of them had a statement about patient consent for photograph publication. The patients' consent was more likely stated in the article in cases of recognisable facial images (OR=2.81, 95% CI 1.41 to 5.63, p=0.004). Journals publishing clinical research involving the face and neck region need to establish and enforce policies on publishing clinical images.

Publishing Identifiable Patient Photographs in Scientific Journals: Scoping Review of Policies and Practices.

BACKGROUND: Publishing identifiable patient data in scientific journals may jeopardize patient privacy and confidentiality if best ethical practices are not followed. Current journal practices show considerable diversity in the publication of identifiable patient photographs, and different stakeholders may have different opinions of and practices in publishing patient photographs. OBJECTIVE: This scoping review aimed to identify existing evidence and map knowledge gaps in medical research on the policies and practices of publishing identifiable photographs in scientific articles. METHODS: We performed a comprehensive search of the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL with Full Text, Database of Abstracts of Reviews of Effects, Ovid MEDLINE, and Scopus. The Open Science Framework, PROSPERO, BASE, Google Scholar, OpenGrey, ClinicalTrials.gov, the Campbell Collaboration Library, and Science.gov were also searched. RESULTS: After screening the initial 15,949 titles and abstracts, 98 (0.61%) publications were assessed for eligibility at the full-text level, and 30 (0.19%) publications were included in this review. The studies were published between 1994 and 2020; most had a cross-sectional design and were published in journals covering different medical disciplines. We identified 3 main topics. The first included ethical aspects of the use of facial photographs in publications. In different clinical settings, the consent process was not conducted properly, and health professionals did not recognize the importance of obtaining written patient consent for taking and using patient medical photographs. They often considered verbal consent sufficient or even used the photographs without consent. The second topic included studies that investigated the practices and use of medical photography in publishing. Both patients and doctors asked for confidential storage and maintenance of medical photographs. Patients preferred to be photographed by their physicians using an institutional camera and preferred nonidentifiable medical photographs not only for publication but also in general. Conventional methods of deidentification of facial photographs concealing the eye area were recognized as unsuccessful in protecting patient privacy. The third topic emerged from studies investigating medical photography in journal articles. These studies showed great diversity in publishing practices regarding consent for publication of medical photographs. Journal policies regarding the consent process and consent forms were insufficient, and existing ethical professional guidelines were not fully implemented in actual practices. Patients' photographs from open-access medical journals were found on public web-based platforms. CONCLUSIONS: This scoping review showed a diversity of practices in publishing identifiable patient photographs and an unsatisfactory level of knowledge of this issue among different stakeholders despite existing standards. Emerging issues include the availability of patients' photographs from open-access journals or preprints in the digital environment. There is a need to improve standards and processes to obtain proper consent to fully protect the privacy of patients in published articles.

Web-Based Educational Intervention to Improve Knowledge of Systematic Reviews Among Health Science Professionals: Randomized Controlled Trial.

BACKGROUND: Lack of knowledge of systematic reviews (SRs) could prevent individual health care professionals from using SRs as a source of information in their clinical practice or discourage them from participating in such research. OBJECTIVE: In this randomized controlled trial, we evaluated the effect of a short web-based educational intervention on short-term knowledge of SRs. METHODS: Eligible participants were 871 Master's students of university health sciences studies in Croatia; 589 (67.6%) students who agreed to participate in the trial were randomized using a computer program into 2 groups. Intervention group A (294/589, 49.9%) received a short web-based educational intervention about SR methodology, and intervention group B (295/589, 50.1%) was presented with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. The participants' knowledge of SRs was assessed before and after the intervention. The participants could not be blinded because of the nature of the intervention. The primary outcome was the difference in the percentage of correct answers about SR methodology per participant between the groups after the intervention, expressed as relative risk and 95% CI. RESULTS: Results from 162 and 165 participants in the educational intervention and PRISMA checklist groups, respectively, were available for analysis. Most of them (educational intervention group: 130/162, 80.2%; PRISMA checklist group: 131/165, 79.4%) were employed as health care professionals in addition to being health sciences students. After the intervention, the educational intervention group had 23% (relative risk percentage) more correct answers in the postintervention questionnaire than the PRISMA checklist group (relative risk=1.23, 95% CI 1.17-1.29). CONCLUSIONS: A short web-based educational intervention about SRs is an effective tool for short-term improvement of knowledge of SRs among health care studies students, most of whom were also employed as health care professionals. Further studies are needed to explore the long-term effects of the tested education. TRIAL REGISTRATION: OSF Registries 10.17605/OSF.IO/RYMVC; https://osf.io/rymvc.

Creating an online educational intervention to improve knowledge about systematic reviews among healthcare workers: mixed-methods pilot study.

BACKGROUND: Lack of knowledge about systematic reviews (SRs) could prevent individual healthcare workers (HCWs) from using SRs as a source of information in their clinical practice or discourage them from participating in such research. In this study, we aimed to explore in-depth the opinion of a sample of HCWs about the newly created online educational intervention designed to improve knowledge about SRs. METHODS: We created a brief online educational intervention on SRs, consisting of 11 textual modules. We evaluated it among practicing HCWs who graduated from a university-level health sciences program using a mixed-methods pilot study that consisted of pre- and post-intervention questionnaires and qualitative evaluation via semi-structured interviews. We assessed participants' knowledge about SR methodology before and after the intervention, and compared the responses. We sought their opinions about the characteristics of SRs. Also, the participants were presented with four scientific abstracts, where they were asked to distinguish whether those abstracts presented summaries of a systematic or a non-systematic review. RESULTS: Twelve participants took part in the study. In the pilot study, the participants' knowledge about SRs was improved after the intervention compared to the baseline. Participants provided positive feedback regarding the educational intervention. Suggestions to improve the educational intervention were to provide more details about the forest plot, add more digital content or images, provide more details about the methodological steps of an SR, add descriptions about practical applications of SRs and provide links to additional educational materials. The participants suggested that HCWs could be motivated to take part in such an education if it is offered as continuing medical education (CME) course or credit for academic/career advancement. CONCLUSION: HCWs provided positive feedback about the newly designed online educational intervention on SRs; they considered it an appropriate tool for learning about SRs and resulted in increased knowledge about SRs. In addition, participants gave suggestions for improving education, which can be used to tailor the education for end-users. In future studies, it would be useful to examine the effectiveness of the modified educational intervention on increasing knowledge in a larger sample and in the form of a randomized controlled trial.

Stakeholders' Experiences of Research Integrity Support in Universities: A Qualitative Study in Three European Countries.

Fostering research integrity (RI) increasingly focuses on normative guidance and supportive measures within institutions. To be successful, the implementation of support should be informed by stakeholders' experiences of RI support. This study aims to explore experiences of RI support in Dutch, Spanish and Croatian universities. In total, 59 stakeholders (Netherlands n = 25, Spain n = 17, Croatia n = 17) participated in 16 focus groups in three European countries. Global themes on RI support experiences were identified by thematic analysis. Themes identified were: 'RI governance and institutional implementation', 'RI roles and structures', 'RI education and supervision', and 'Infrastructure, technology and tools supporting daily practice'. Experiences of support differed between countries in relation to: the efforts to translate norms into practice; the extent to which RI oversight was a responsibility of RE structures, or separate RI structures; and the availability of support close to research practice, such as training, responsible supervision, and adequate tools and infrastructure. The study reinforces the importance of a whole institutional approach to RI, embedded within local jurisdictions, rules, and practices. A whole institutional approach puts the emphasis of responsibility on institutions rather than individual researchers. When such an approach is lacking, some stakeholders look for intervention by authorities, such as funders, outside of the university.

Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews.

BACKGROUND: Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging, and ongoing critical appraisal of this output is essential. We aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic. METHODS: Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO's Global Research, LILACS, and Epistemonikos) were searched from December 1, 2019, to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory, and radiological findings), and quality assessment (AMSTAR 2). A meta-analysis was performed of the prevalence of clinical outcomes. RESULTS: Eighteen systematic reviews were included; one was empty (did not identify any relevant study). Using AMSTAR 2, confidence in the results of all 18 reviews was rated as "critically low". Identified symptoms of COVID-19 were (range values of point estimates): fever (82-95%), cough with or without sputum (58-72%), dyspnea (26-59%), myalgia or muscle fatigue (29-51%), sore throat (10-13%), headache (8-12%) and gastrointestinal complaints (5-9%). Severe symptoms were more common in men. Elevated C-reactive protein and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. A frequent finding on chest imaging was uni- or bilateral multilobar ground-glass opacity. A single review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3 to 13.9%. CONCLUSIONS: In this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all reviews was "critically low". Thus, systematic reviews that were published early on in the pandemic were of questionable usefulness. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards.

Reporting violations of European Charter of Patients' Rights: analysis of patient complaints in Croatia.

BACKGROUND: The European Charter of Patients' Rights (ECPR) presents basic patients' rights in health care. We analysed the characteristics of patients' complaints about their rights submitted through the official complaints system and to a non-governmental organization in Croatia. METHODS: The official system for patients'complaints in Croatia does not have a common pathway but offers different modes for addressing patient complaints. In this cross-sectional study, we analysed the reports about patients' complaints from the official regional committees sent to the Ministry of Health. We also analysed the complaints received by the Croatian Association for the Protection of Patient's Rights (CAPR) and mapped them to the ECPR. RESULTS: The aggregated official data from the Ministry of Health in 2017 and 2018 covered only 289 individual complaints from 10 out of 21 counties. Complaints were most frequently related to secondary and tertiary healthcare institutions and details were not provided. CAPR received a total of 440 letters, out of which 207 contained 301 complaints about violations of patients' rights in 2017-2018. The most common complaint was the Right of Access to health care (35.3%) from the ECPR, followed by the Right to Information (29.9%) and the Right to Safety (21.7%). The fewest complaints were about the Right to Complain (1.9%), Right to Innovation (1.4%), Right to Compensation (1.4%), and Right to Preventive Measures (1.0%). CONCLUSIONS: Reporting and dealing with patients' complaints about violations of their patients' rights does not appear to be effective in a system with parallel but uncoordinated complaints pathways. Mapping patient's complaints to the ECPR is a useful tool to assess the perception of patients' rights and to plan actions to improve the complaints system for effective health care.

Cognitive levels in testing knowledge in evidence-based medicine: a cross sectional study.

BACKGROUND: Knowledge assessment in evidence-based medicine (EBM) is usually performed by the measurement of memorised facts, understanding of EBM concepts and application of learned knowledge in familiar situations, all of which are considered lower-level educational objectives. The aim of this study was to assess EBM knowledge both on higher and lower cognitive levels across EBM topics. METHODS: In order to assess knowledge on different EBM topics across learning levels, we created a knowledge test (Six Progressive Levels in Testing - SPLIT instrument), which consists of 36 multiple choice items and measures knowledge in EBM at six cognitive levels (Remembering, Understanding, Applying, Analysing, Evaluating and Creating) and addresses six EBM topics (Evidence-based practice, Internal validity, Clinical importance, Study design, Sources of evidence, Diagnostic studies). Three independent assessors defined the minimum passing score (MPS) for the overall test, based on the first-year course content and educational objectives. The instrument was assessed in a sample of first- (n = 119) and third-year medical students (n = 70) and EBM experts (n = 14). RESULTS: The MPS was 16 correct answers out of total 36 questions, and was achieved by 21 out of 119 first-year students, 14 out of 70 third-year students and 9 out of 14 EBM experts (χ2 = 13.3; P < 0.001, with significantly higher proportion of experts passing compared to students). Although experts had the highest scores overall, none of the groups outperformed others on individual cognitive levels, but the experts outperformed students in EBM topics of Study design and Sources of evidence (P = 0.002 and 0.004, respectively, Kruskal-Wallis test). First- and third-year students performed better on specific course topics taught in that study year (Diagnostic studies and Clinical relevance, respectively). CONCLUSION: EBM knowledge of students and experts differ according to the specificities of their education/expertise, but neither group had excellent knowledge in all areas. It may be difficult to develop a knowledge test that includes different EBM topics at different cognitive levels to follow the development of specific and general aspects of EBM knowledge.

Practices for Research Integrity Promotion in Research Performing Organisations and Research Funding Organisations: A Scoping Review.

Research integrity (RI) is a continuously developing concept, and increasing emphasis is put on creating RI promotion practices. This study aimed to map the existing RI guidance documents at research performing organisations (RPOs) and research funding organisations (RFOs). A search of bibliographic databases and grey literature sources was performed, and retrieved documents were screened for eligibility. The search of bibliographical databases and reference lists of selected articles identified a total of 92 documents while the search of grey literature sources identified 118 documents for analysis. The retrieved documents were analysed based on their geographical origin, research field and organisational origin (RPO or RFO) of RI practices, types of guidance presented in them, and target groups to which RI practices are directed. Most of the identified practices were developed for research in general, and are applicable to all research fields (n = 117) and medical sciences (n = 78). They were mostly written in the form of guidelines (n = 136) and targeted researchers (n = 167). A comprehensive search of the existing RI promotion practices showed that initiatives mostly come from RPOs while only a few RI practices originate from RFOs. This study showed that more RI guidance documents are needed for natural sciences, social sciences, and humanities since only a small number of documents was developed specifically for these research fields. The explored documents and the gaps in knowledge identified in this study can be used for further development of RI promotion practices in RPOs and RFOs.

Interventions for Organizational Climate and Culture in Academia: A Scoping Review.

Organizational climate and culture may influence different work-related outcomes, including responsible conduct of research and research misconduct in academic or research organizations. In this scoping review we collected evidence on outcomes of interventions to change organizational climate or culture in academic or research settings. Out of 32,093 documents retrieved by the search, we analysed 207 documents in full text, out of which 7 met the eligibility criteria and were included in the final analysis. The included studies measured organizational climate (2 studies), organizational culture (4 studies), or both (1 study) at biomedical faculties (4 studies) or non-academic university departments (3 studies). Four studies had post-test, and three before-and-after study designs. The majority of interventions were face-to-face activities (meetings, different teambuilding activities), and two were based on organizational change. Six studies reported positive changes in organizational climate/culture after the intervention. These positive changes were measured as improvements in score on different questionnaire survey or were described through authors' or external evaluator's narrative reports. However, the methodological quality of the studies was low, both for qualitative and quantitative study designs. Replicable studies, using rigorous methods and clearly defined outcomes are urgently needed if organizations want to achieve a real change in organizational climate or culture for responsible research. The protocol for this scoping review was registered at https://osf.io/7zjqb .

Important Topics for Fostering Research Integrity by Research Performing and Research Funding Organizations: A Delphi Consensus Study.

To foster research integrity (RI), it is necessary to address the institutional and system-of-science factors that influence researchers' behavior. Consequently, research performing and research funding organizations (RPOs and RFOs) could develop comprehensive RI policies outlining the concrete steps they will take to foster RI. So far, there is no consensus on which topics are important to address in RI policies. Therefore, we conducted a three round Delphi survey study to explore which RI topics to address in institutional RI policies by seeking consensus from research policy experts and institutional leaders. A total of 68 RPO and 52 RFO experts, representing different disciplines, countries and genders, completed one, two or all rounds of the study. There was consensus among the experts on the importance of 12 RI topics for RPOs and 11 for RFOs. The topics that ranked highest for RPOs concerned education and training, supervision and mentoring, dealing with RI breaches, and supporting a responsible research process (e.g. through quality assurance). The highest ranked RFO topics concerned dealing with breaches of RI, conflicts of interest, and setting expectations on RPOs (e.g. about educating researchers about RI). Together with the research policy experts and institutional leaders, we developed a comprehensive overview of topics important for inclusion in the RI policies of RPOs and RFOs. The topics reflect preference for a preventative approach to RI, coupled with procedures for dealing with RI breaches. RPOs and RFOs should address each of these topics in order to support researchers in conducting responsible research.

Fas receptor induces apoptosis of synovial bone and cartilage progenitor populations and promotes bone loss in antigen-induced arthritis.

Rheumatoid arthritis (RA) is an inflammatory joint disease that eventually leads to permanent bone and cartilage destruction. Fas has already been established as the regulator of inflammation in RA, but its role in bone formation under arthritic conditions is not completely defined. The aim of this study was to assess the effect of Fas inactivation on the bone damage during murine antigen-induced arthritis. Subchondral bone of wild-type (WT) and Fas-knockout (Fas-/-) mice was evaluated by histomorphometry and microcomputerized tomography. Proportions of synovial bone and cartilage progenitors were assessed by flow cytometry. Synovial bone and cartilage progenitors were purified by fluorescence-activated cell sorting and expression of Fas and Fas-induced apoptosis were analyzed in vitro. Results showed that Fas-/- mice developed attenuated arthritis characterized by preserved epiphyseal bone and cartilage. A proportion of the earliest CD200+ bone and cartilage progenitors was reduced in WT mice with arthritis and was unaltered in Fas-/- mice. During osteoblastic differentiation in vitro, CD200+ cells express the highest levels of Fas and are removed by Fas ligation. These results suggest that Fas-induced apoptosis of early CD200+ osteoprogenitor population represents potential mechanism underlying the impaired bone formation in arthritis, so their preservation may represent the bone-protective mechanism during arthritis.-Lazic Mosler, E., Lukac, N., Flegar, D., Fadljevic, M., Radanovic, I., Cvija, H., Kelava, T., Ivcevic, S., Sucur, A., Markotic, A., Katavic, V., Marusic, A., Grcevic, D., Kovacic, N. Fas receptor induces apoptosis of synovial bone and cartilage progenitor populations and promotes bone loss in antigen-induced arthritis.

Framing the numerical findings of Cochrane plain language summaries: two randomized controlled trials.

BACKGROUND: Cochrane systematic review Plain language Summaries (CSR PLSs should serve as a tool for the evidence translation to non-medical population. However, the evidence of optimal type of numerical presentation in CSR PLSs is still scarce. The aim of this study was to investigate readers' comprehension and preferences for different presentation of findings, including framing and numerical data, in Cochrane systematic review Plain Language Summaries (CSR PLSs). METHODS: We conducted a parallel randomized trial and a crossover randomized trial at the School of Medicine and family practice offices in Split, Croatia. The participants were students and consumers. We assessed possible differences in comprehension, measured by four questions on PLS content, of CSR PLSs depending on the positive or negative framing of results (n = 91) (Trial 1) or using percentages or frequencies for the presentation of results (n = 245) (Trial 2). The outcome measures were comprehension of PLS content, perceived effectiveness of the treatment and readiness to use the treatment (all on 1-10 scales). RESULTS: In Trial 1 we found no difference in readers' perception of the effectiveness of the described treatment, desire that the treatment be offered by their family doctor, readiness to use the treatment, or comprehension when CSR PLS results were presented positively or negatively. In Trial 2 we found no difference in CSR PLS comprehension when results were presented as natural frequencies or percentages (BF10 = 0.62, Bayesian t-test for independent samples). CONCLUSIONS: Numerical presentation and framing direction of results appear to have no significant impact on understanding of messages in CSR PLSs. TRIAL REGISTRATION: The trials were registered in ClinicalTrials.gov. Protocol registration numbers: Trial 1: NCT03442387; Trial 2: NCT03554252.