Completeness of intervention description in invasive cardiology trials: an observational study of ClinicalTrials.gov registry and corresponding publications.

Introduction: Non-pharmacological invasive interventions in cardiology are complex and often inadequately reported. Template for Intervention Description and Replication (TIDieR) checklist and guide were developed to aid reporting and assessment of non-pharmacological interventions. The aim of our study was to assess the completeness of describing invasive cardiology interventions in clinical trials at the level of trial registration and corresponding journal article publication. Methodology: We searched for clinical trials in invasive cardiology registered in Clinicaltrials.gov and corresponding journal publications. We used the 10-item TIDieR checklist for registries and 12-item checklist for journal publications. Results: Out of 7,017 registry items retrieved by our search, 301 items were included in the analysis. The search for corresponding published articles yielded 192 journal publications. The majority of trials were funded by the industry and were medical device trials. The median number of reported TIDieR items was 4.5 (95% CI 4.49-4.51) out of 10, and while the corresponding journal articles reported 6.5 (95% CI 6.0-6.5) out of 12 TIDieR items. Conclusion: Registration and reporting of invasive cardiology trials is often incomplete and adequate detailed description of the interventions is not provided. TIDieR checklist is an important tool which should be used to ensure rigorous reporting of non-pharmacological interventions in cardiology.

Diplomatic response to global health challenges in recognizing patient needs: A qualitative interview study.

Background: Global health diplomacy is the applied practice of foreign affairs to further national goals that focus on health issues requiring international cooperation and collective action. We aimed to determine how international diplomats and health policy-related professionals in the EU understand the concept of health diplomacy, which impacts both diplomatic relations as well as patients' rights. Methods: In a qualitative interview study, we used a heterogeneous stratified purposeful sampling to reach participants from different countries and different practitioners from the Pyramid of Health Diplomacy: core, multi-stakeholder, and informal. Reflexive thematic analysis was used to identify the main themes. Findings: We contacted 131 practitioners of GHD, of which 37 responded, and nine agreed to be interviewed. From 11 interview questions, four main themes emerged from the analysis of the individual interview. The participants reported limited knowledge about the definition of GHD but also that they engaged in daily activities and decisions of inter-governmental bodies. They were not aware of existing special education and training for health attachés and made suggestions for improving the field and practice of GHD. They were not fully familiar with the European Charter of Patients' Rights. There was a consensus from all participants that patient rights need to improve as a fundamental right. They stressed the fact that the hospital lockdown and the right access to healthcare were impaired during the COVID pandemic. Interpretation: The role of health diplomacy in linking public health and foreign affairs is key to respecting patients' rights. Health over other interests is becoming an increasingly critical element in foreign policy. Establishing a clear career path for health attachés is necessary to foster effective global health agreements and coordination across countries.

Student Moral Foundations in the Context of Research Misbehavior: An Experimental Study.

The study aimed to examine whether the use of words related to different moral foundations can predict the perceived severity of research misconduct. We gave two groups of participants, undergraduate medical students, the same hypothetical scenarios of research misconduct cases containing words related to different aspects of morality, and asked them to assess how inappropriate the described behavior was. Students ranked the described behaviors differently by the inappropriateness of the behavior, but the group wording was not a significant predictor of appropriateness. The reasons for the ranking were not related to any standardized procedures for research integrity but were related to the moral assessment of the students, which was assessed using qualitative approach. The results of this study implicate that personal moral views are an important part in research integrity training.

Perception of organizational climate by university staff and students in medicine and humanities: A qualitative study.

Organizational climate and culture are important for research organizations because they foster research integrity and responsible conduct of research, reduce questionable research practices, and improve job satisfaction. The aim of our study was to explore how employees and students perceive organizational climate and its consequences in the university setting. We conducted semi-structured interviews with senior students and employees (teaching and non-teaching staff) from two different university schools: School of Medicine and Faculty of Humanities and Social Sciences. Participants were asked questions regarding perceived climate, working environment, and the role of the institution. The data were analyzed using reflexive thematic analysis approach. Three themes were identified. The first theme addressed the difference in the perception and understanding of organizational climate. The second theme dealt with institutional issues emanating from organizational climate. The third theme described the behavior of stakeholders in the formation of organizational climate. Organizational climate is important concept in academic organizations as it influences both employees, particularly early career researchers, and students. Institutional leadership can strongly influence organizational climate, which can in turn affect job and job satisfaction. Due to the importance of personal morality on everyday decision-making, virtue-based research integrity training could be useful in improving academic institutions' organizational climate.

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.

Standard of care for COVID-19 in randomized clinical trials registered in trial registries and published in preprint servers and scholarly journals: a cross-sectional study.

BACKGROUND: The concept of standard of care (SoC) treatment is commonly utilized in clinical trials. However, in a setting of an emergent disease, such as COVID-19, where there is no established effective treatment, it is unclear what the investigators considered as the SoC in early clinical trials. The aim of this study was to analyze and classify SoC reported in randomized controlled trial (RCT) registrations and RCTs published in scholarly journals and on preprint servers about treatment interventions for COVID-19. METHODS: We conducted a cross-sectional study. We included RCTs registered in a trial registry, and/or published in a scholarly journal, and/or published on preprint servers medRxiv and bioRxiv (any phase; any recruitment status; any language) that aim to compare treatment interventions related to COVID-19 and SoC, available from January 1, 2020, to October 8, 2020. Studies using "standard" treatment were eligible for inclusion if they reported they used standard, usual, conventional, or routine treatment. When we found such multiple reports of an RCT, we treated those multiple sources as one unit of analysis. RESULTS: Among 737 unique trials included in the analysis, 152 (21%) reported that SoC was proposed by the institutional or national authority. There were 129 (18%) trials that reported component(s) of SoC; the remaining trials simply reported that they used SoC, with no further detail. Among those 129 trials, the number of components of SoC ranged from 1 to 10. The most commonly used groups of interventions in the SoC were antiparasitics (62% of the trials), antivirals (57%), antibiotics (31%), oxygen (17%), antithrombotics/anticoagulants (14%), vitamins (13%), immunomodulatory agents (13%), corticosteroids (12%), analgesics/antipyretics (12%). Various combinations of those interventions were used in the SoC, with up to 7 different types of interventions combined. Posology, timing, and method of administration were frequently not reported for SoC components. CONCLUSION: Most RCTs (82%) about treatment for COVID-19 that were registered or published in the first 9 months of the pandemic did not describe the "standard of care" they used. Many of those interventions have, by now, been shown as ineffective or even detrimental.

Clinical use of ivabradine in the acute coronary syndrome: A systematic review and narrative synthesis of current evidence.

Heart rate (HR) lowering during acute coronary syndrome (ACS) is beneficial as it reduces myocardial oxygen consumption. However, the role of ivabradine as an HR-lowering agent in the setting of ACS is not clear. We aimed to systematically review and synthesize the current evidence on the role of ivabradine use in the ACS. A systematic review was conducted for eligible randomized clinical trials and quasi-experimental studies, between 2009 and 2020, that investigated the use of ivabradine in ACS. Various clinical endpoints were evaluated such as major adverse cardiovascular events, efficacy in HR control, impact on left ventricular (LV) dimensions and function, and overall safety. Eleven publications were included encompassing a total of 1833 patients. The mean age of the examined cohort was 57 ± 11 years and 80 % were men. Seven studies were in the setting of ST-segment elevation myocardial infarction (MI) while the remaining studies also included patients with unstable angina and non-ST-segment elevation MI. Ivabradine was administered as a peroral drug with dosing from 2.5 to 7.5 mg b.i.d. Overall, the addition of ivabradine was superior to the control arm concerning HR control with a good safety profile. Beneficial effects on LV function and potential impact on infarct size reduction were observed as well. The use of ivabradine appeared to not affect short-term mortality. In conclusion, the use of ivabradine for HR control is safe, feasible, and efficacious for HR control in the ACS. Further studies are required to elucidate other potentially beneficial effects of ivabradine.

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.

Antifragility of healthcare systems in Croatia and Bosnia and Herzegovina: Learning from man-made and natural crises.

Acute crises, such as a war or a pandemic, are the ultimate tests for health care systems' resilience (temporary response to stress with change and adaptation) and antifragility (permanent benefit from change in response to stress). In this Health Policy paper, we analyse and discuss how the healthcare systems of two European countries - Bosnia and Herzegovina and Croatia - adapted to war as a man-made disaster, and how they adapted to COVID-19 pandemic twenty-five years later. These countries experienced full scale wars in recent history, which significantly changed their political and healthcare systems. This experience prepared the countries for the response to the pandemic, which coincided with two earthquakes in Croatia. We argue that healthcare systems in Croatia and Bosnia and Herzegovina are not only resilient but antifragile, and that they benefited from stressors they were exposed to. The antifragility of the two systems were primarily based on human effort - the strength, adaptability and resilience of health care professionals. We will look at lessons from the wars that were applied to the pandemic and discuss newly recognized opportunities and improvements.

Impact of the first COVID-19 lockdown on study satisfaction and burnout in medical students in Split, Croatia: a cross-sectional presurvey and postsurvey.

OBJECTIVES: To evaluate the impact of the first COVID-19 lockdown in 2020 on the burnout and study satisfaction of medical students. DESIGN: A cross-sectional study with a presurvey and postsurvey. SETTING: University of Split School of Medicine (USSM), Split, Croatia. The lockdown in the COVID-19 pandemic lasted from late March to mid-May 2020. There was a full switch to e-learning at the USSM during this period, and all clinical teaching was stopped. PARTICIPANTS: Students enrolled in the 2019/2020 academic year. Data were collected before lockdown in December 2019 and January 2020 and again after the end of lockdown in June 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Study satisfaction was assessed using the study satisfaction survey. Burnout was assessed using two instruments: Oldenburg Burnout Inventory and Copenhagen Burnout Inventory. We used Bayesian statistics to compare before-and-after differences. RESULTS: 437 independent responses (77.2% response rate) were collected before and 235 after lockdown (41.5% response rate). 160 participant responses were eligible for pairing. There was no significant difference for both paired and unpaired participants in study satisfaction before (3.38 on a 1-5 scale; 95% credible interval (95% CrI) 3.32 to 3.44) and after (3.49, 95% CrI 3.41 to 3.57) lockdown. We found no evidence (Bayes factor (BF10) >3.00 as a cut-off value) for an increase in the level of burnout before and after lockdown, both in independent and paired samples. CONCLUSIONS: It seems that the first pandemic-related lockdown and a switch to e-learning did not affect burnout levels among medical students or their perception of their study programme. More insight is needed on the short-term and long-term effects of the COVID-19 pandemic on medical students and their education. Well-structured longitudinal studies on medical student burnout during the COVID-19 pandemic are needed.

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 .

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.

Perception of Organizational Ethical Climate by University Staff and Students in Medicine and Humanities: A Cross Sectional Study.

We assessed students' and employees' perception of ethical climate at a university school of medicine compared to that of social sciences and humanities, as well as temporal changes in the employees' perception of ethical climate. We also explored potential predictors of ethical climate, including moral foundations. This cross-sectional questionnaire study was conducted at the University of Split School of Medicine and the Faculty of Humanities and Social Sciences, in Croatia, from April to September 2019. We used 36-item Ethical Climate Questionnaire and 22-item Moral Foundation Questionnaire to survey employees, senior and doctoral students. We collected responses using ballot boxes as well as online survey. We collected 449 complete responses (response rate 36.8%). The dominant ethical climates at two schools were "Company rules and procedures" and "Laws and professional codes". We compared our results with a study conducted in 2012 and found that the perception of ethical climate had not changed dramatically in last 8 years. Ethical climate, or shared social and work-related behaviours, does not seem to change in these institutions even when students and staff are included with faculty in surveys. We provide further discussion of why this seems to be the case.

Assessments of attrition bias in Cochrane systematic reviews are highly inconsistent and thus hindering trial comparability.

BACKGROUND: An important part of the systematic review methodology is appraisal of the risk of bias in included studies. Cochrane systematic reviews are considered golden standard regarding systematic review methodology, but Cochrane's instructions for assessing risk of attrition bias are vague, which may lead to inconsistencies in authors' assessments. The aim of this study was to analyze consistency of judgments and support for judgments of attrition bias in Cochrane reviews of interventions published in the Cochrane Database of Systematic Reviews (CDSR). METHODS: We analyzed Cochrane reviews published from July 2015 to June 2016 in the CDSR. We extracted data on number of included trials, judgment of attrition risk of bias for each included trial (low, unclear or high) and accompanying support for the judgment (supporting explanation). We also assessed how many Cochrane reviews had different judgments for the same supporting explanations. RESULTS: In the main analysis we included 10,292 judgments and supporting explanations for attrition bias from 729 Cochrane reviews. We categorized supporting explanations for those judgments into four categories and we found that most of the supporting explanations were unclear. Numerical indicators for percent of attrition, as well as statistics related to attrition were judged very differently. One third of Cochrane review authors had more than one category of supporting explanation; some had up to four different categories. Inconsistencies were found even with the number of judgments, names of risk of bias domains and different judgments for the same supporting explanations in the same Cochrane review. CONCLUSION: We found very high inconsistency in methods of appraising risk of attrition bias in recent Cochrane reviews. Systematic review authors need clear guidance about different categories they should assess and judgments for those explanations. Clear instructions about appraising risk of attrition bias will improve reliability of the Cochrane's risk of bias tool, help authors in making decisions about risk of bias and help in making reliable decisions in healthcare.

Reporting quality of European and Croatian health practice guidelines according to the RIGHT reporting checklist.

BACKGROUND: Health practice guidelines (HPGs) are important tools for the translation of evidence into practice. Reporting Items for Practice Guidelines in HealThcare (RIGHT) checklist provides guidance on reporting health practice guidelines (HPGs). We assessed the reporting completeness and quality of a set of national (Croatian) and relevant transnational (European) HPGs. METHODS: The national sample included all HPGs published in the official journal of the Croatian Medical Association in 2014-2016. We searched PubMed to identify relevant European guidelines (n = 24). Two independent reviewers assessed the adherence with the items on the RIGHT checklist. Kappa score was used to measure the level of agreement. Frequentist and Bayes statistics Bayes factor (BF10) was used to evaluate the differences between the national and transnational HPGs. RESULTS: Overall, Croatian and European HPGs adhered to less than 50% of RIGHT checklist items. Croatian HPGs reported a median of 14.0 (95% CI 13.0-15.0) RIGHT reporting items, and European counterparts reported a median of 16.0 (95% CI 14.0-17.2) out of the total of 35 checklist items (Mann Whitney U test, P = 0.048; BF10 = 1.543). European HPGs were better than Croatian HPGs in reporting stakeholder involvement and values and preferences (BF10 = 80.63), as well as describing the implications of costs and resources (BF10 = 55.15). Croatian HPGs better reported HPGs specified aims (BF10 = 16.90), primary intended users (BF10 = 8.70), and sources of funding (BF10 = 122.90). Most insufficiently reported items for both HPG sets were defining the guideline questions and clear outcomes, quality assurance, management of funding and conflicts of interest, and guideline limitations. CONCLUSIONS: Important methodological details are missing from most published HPGs at national and transnational levels. To ensure better quality and adequate use of HPGs, reporting guidelines should be endorsed and used by developers and users alike.

Improving completion rates of students in biomedical PhD programs: an interventional study.

BACKGROUND: Analysis of graduation success at the University of Split School of Medicine PhD programs conducted in 2011 revealed that only 11% of students who enrolled and completed their graduate coursework between 1999 and 2011 earned a doctoral degree. In this prospective cohort study we evaluated and compared three PhD programs within the same medical school, where the newest program, called Translational Research in Biomedicine (TRIBE), established in the academic year 2010/11, aimed to increase the graduation rate through an innovative approach. METHODS: The intervention in the new program was related to three domains: redefined recruitment strategy, strict study regulations, and changes to the curriculum. We compared performance of PhD students between the new and existing programs and analyzed their current status, time to obtain a degree (from enrolment to doctorate), age at doctorate, number of publications on which the thesis was based and the impact factor of journals in which these were published. RESULTS: These improvement strategies were associated with higher thesis completion rate and reduced time to degree for students enrolled in the TRIBE program. There was no change in the impact factor or number of publications that were the basis for the doctoral theses. CONCLUSION: Our study describes good practices which proved useful in the design or reform of the PhD training program.

Changes in epidermal thickness and cutaneous innervation during maturation in long-term diabetes.

AIM: Peripheral nerve fiber depletion in patients with chronic diabetes mellitus (DM) was linked to neuropathic symptoms, development of pain, foot ulcerations and lower extremity amputation. The aim of this study was to analyze cutaneous changes, including paw epidermal thickness and intraepidermal nerve fiber (IENF) density in long-term diabetes, in rats 6 months and 12 months after induction of diabetes. MATERIALS AND METHODS: Epidermal thickness and IENF density were studied in Sprague-Dawley diabetic rats 6 months and 12 months after diabetes induction with streptozotocin. Epidermal thickness was evaluated using hematoxylin and eosin staining. Peripheral nerve fibers were stained with polyclonal antiserum against protein gene product 9.5 (PGP 9.5). Successful diabetes induction was validated by measuring plasma glucose and body mass regularly throughout the experiment. RESULTS: This study showed that long-term diabetes, induced in Sprague-Dawley rats with streptozotocin, is characterized with significant epidermal thinning and reduction of intraepidermal nerve fibers, 6 months and 12 months after induction of diabetes. CONCLUSION: Long-term studies of streptozotocin models of diabetes could be used for making normative IENF densities that can be later used as age-dependent normative values for studying new treatment modalities.