How to Conduct Clinical Research in Cardiovascular Imaging: A Primer for Clinical Cardiologists and Researchers. A Statement of the European Association of Cardiovascular Imaging (EACVI) of the ESC.

This statement from the European Association of Cardiovascular Imaging (EACVI) of the ESC aims to address the fundamental principles that guide clinical research in the field of cardiovascular imaging. It provides clinical researchers, cardiology fellows, and Ph.D. students with a condensed, updated, and practical reference document to support them in designing, implementing, and conducting imaging protocols for clinical trials. Although the present article cannot replace formal research training and mentoring, it is recommended reading for any professional interested in becoming acquainted with or participating in clinical trials involving cardiovascular imaging.

Multilevel Longitudinal Functional Principal Component Model.

Sensor devices, such as accelerometers, are widely used for measuring physical activity (PA). These devices provide outputs at fine granularity (e.g., 10-100 Hz or minute-level), which while providing rich data on activity patterns, also pose computational challenges with multilevel densely sampled data, resulting in PA records that are measured continuously across multiple days and visits. On the other hand, a scalar health outcome (e.g., BMI) is usually observed only at the individual or visit level. This leads to a discrepancy in numbers of nested levels between the predictors (PA) and outcomes, raising analytic challenges. To address this issue, we proposed a multilevel longitudinal functional principal component analysis (mLFPCA) model to directly model multilevel functional PA inputs in a longitudinal study, and then implemented a longitudinal functional principal component regression (FPCR) to explore the association between PA and obesity-related health outcomes. Additionally, we conducted a comprehensive simulation study to examine the impact of imbalanced multilevel data on both mLFPCA and FPCR performance and offer guidelines for selecting optimal methods.

Articles Published in Korean Journal of Family Medicine: Impact of COVID-19 on Study Trends.

Background: The Korean Journal of Family Medicine (KJFM), which is an official journal of the Korean Academy of Family Medicine, is an English-text medical journal published since 2009. Although nearly 15 years have passed since the journal was launched, to the best of our knowledge, no study has reviewed articles published in the KJFM. Accordingly, we analyzed articles published in the KJFM for the first time. Methods: Articles published in the KJFM between January 2018 and November 2023 were categorized according to article type. Information about author affiliations, study subjects, research methods, and modes of data collection was then scrutinized. Moreover, we compared the frequencies of subjects, research methods and modes of data collection before, during, and after the coronavirus disease 2019 pandemic. Results: Original article was the most common article type. Approximately 52% of the articles were published by authors affiliated with departments other than family medicine, and 40% were published by family medicine. Approximately 60% and 38% of the articles were published by Korean authors and authors of international affiliations, respectively. Throughout the pandemic periods, research subjects focusing on "diseases & symptoms" have diminished, while "principles of family medicine" have progressively increased. Additionally, the use of cross-sectional study methods has declined. In terms of data collection, the use of "big data," "medical records," and "questionnaires" has decreased, whereas the use of "study results" has increased. Conclusion: KJFM is journal with wide and international participation covering various research subjects and study methods. We believe that our study provides valuable data for the future direction and development of the KJFM.

Generating the Evidence Base for Convalescent Plasma Use for a New Infectious Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept across the world in the waning months of 2019 and emerged as the cause of the coronavirus disease 19 (COVID-19) pandemic in early 2020. The use of convalescent plasma (CP) for prior respiratory pandemics provided a strong biological rationale for the rapid deployment of COVID-19 convalescent plasma (CCP) in early 2020 when no validated treatments or prior immunity existed. CCP is an antiviral agent, with its activity against SARS-CoV-2 stemming from specific antibodies elicited by the virus. Early efforts to investigate the efficacy of CCP in randomized clinical trials (RCTs) that targeted hospitalized patients with COVID-19 did not demonstrate the overall efficacy of CCP despite signals of benefit in certain subgroups, such as those treated earlier in disease. In contrast, studies adhering to the principles of antibody therapy in their study design, choice of patient population, and product qualification, i.e., those that administered high levels of specific antibody during the viral phase of disease in immunocompromised or very early in immunocompetent individuals, demonstrated benefits. In this chapter, we leverage the knowledge gained from clinical studies of CCP for COVID-19 to propose a framework for future studies of CP for a new infectious disease. This framework includes obtaining high-quality CP and designing clinical studies that adhere to the principles of antibody therapy to generate a robust evidence base for using CP.

Building inclusive research cultures in nursing - getting ready for the Research Excellence Framework 2029.

BACKGROUND: The research environment is a complex ecosystem but is vital for nurturing excellence, vitality and sustainability. The Research Excellence Framework (REF) applies to research in the four nations of the UK. The framework and principles for the next REF have been published, with submissions due in 2028 and the results to be published in 2029. The three elements of the REF have changed and new weightings applied, with 'People, Culture and Environment' forming 25% of the whole. AIM: To inform research leaders, investigators, clinical nurse researchers, and doctoral and postdoctoral students about how to prepare dynamic research strategies that prioritise inclusivity in talent management and succession. DISCUSSION: This article considers inclusivity in research cultures, what has been learned from the previous REF and what more needs to be done collectively across the sector and specifically in nursing. The discussion draws on the author's personal knowledge and experience as a research leader, senior manager and university governor. It is intended to be challenging and practically oriented. CONCLUSION: The article sets out provocations to shape an agenda for promoting inclusive research cultures to ensure organisational readiness for REF 2029. IMPLICATIONS FOR PRACTICE: The article provides pragmatic suggestions for moving forward at pace with making the culture in nursing research more open, transparent and fair.

Designing the first culturally-sensitive stigma survey tailored for adolescents: RN-CSS.

AIMS: The Red Noses Culturally-Sensitive Stigma Survey (RN-CSS) contributes to the underexplored research domain of adolescents' stigmatising attitudes and behaviours towards peers with mental health difficulties and mental healthcare services. It also addresses the need for comprehensive and culturally-sensitive tools to assess stigma in this context. METHODS: Drawing on insights from focus groups and building upon the existing Stigma in Global Context-Mental Health Study, we have successfully developed and implemented the first culturally-sensitive stigma survey tailored for school-aged adolescents of different migration/cultural backgrounds. The questionnaire includes an unlabelled case vignette depicting a peer with symptoms of depression and gathers data on various domains, including (1) sociodemographic variables; (2) education-related information; (3) COVID-19; (4) perceptions of mental health difficulties and mental healthcare services (i.e. severity assessment, causal attributions, care recommendations, personal stigma, perceived stigma, and service stigma); (5) subjective wellbeing and familiarity with mental health difficulties; (6) social support; (7) school context; (8) bullying; and (9) knowledge of anti-stigma campaigns. RESULTS: Our final sample comprises 5075 pupils from 38 secondary schools in Flanders, Belgium. CONCLUSIONS: In this article, we present the study's background and rationale, the development of the questionnaire, and the sampling and recruitment methods employed. Furthermore, we provide a summary of the sample characteristics and preliminary descriptive results of the RN-CSS. Subsequent empirical studies will address the research objectives outlined in this protocol paper. The research opportunities provided by the developed materials and dataset are being discussed.

Short-term learning effect of ChatGPT on pharmacy students' learning.

Introduction: Students in pharmacy are positive towards integrating artificial intelligence and ChatGPT into their practice. The aim of this study was to investigate the direct short-term learning effect of using Chat GPT by pharmacy students. Methods: This was an experimental randomized study. Students were allocated into two groups; the intervention group (n = 15) used all study tools and ChatGPT, while the control group (n = 16) used all study tools, except ChatGPT. Differences between groups was measured by how well they performed on a knowledge test before and after a short study period. Results: No significant difference was found between the intervention and control groups in level of competence in the pretest score (p = 0.28). There was also no significant effect of using ChatGPT, with a mean adjusted difference of 0.5 points on a 12-point scale. However there was a trend towards a higher proportion of ChatGPT participants having a large (at least four point) increase in score (4 out of 15) vs control group (1 out of 16). Conclusion: There is a potential for positive effects of ChatGPT on learning outcomes in pharmacy students, however the current study was underpowered to measure a statistically significant effect of ChatGPT on short term learning.

Reflections on the study of empathy in a sample of refugees and migrants from Arabic-speaking countries with diverse experiences of war-related trauma.

Empathic abilities are proposed to affect the trajectory from trauma exposure to psychopathology. Yet, studies addressing the role of empathy in refugees with diverse experiences of war-related trauma are lacking. This may relate to missing recommendations on aspects to consider in the planning and execution of such a study. In the present methodological paper, we hence share our experiences in designing and implementing a study on the interrelations of war-related trauma, post-traumatic stress disorder, and empathy in individuals from Arabic-speaking countries who had entered Germany as refugees or migrants. In specific, we reflect on decisions related to the choice of experimental groups and measures of empathy, and describe unanticipated problems encountered during recruitment, screening and testing. Overall, we recommend applying a multi-method approach (i.e., a combination of questionnaire, behavioral and biological measures) to gain a comprehensive picture of the different facets of empathy. Further, we stress the importance to consider that not only refugees, but also migrants may have experienced war-related trauma. Beyond that, we advise to consult individuals of the study population of interest for the translation of instruments, realization of effective recruitment strategies, and to ensure that the testing procedures are sensitive to participants' past experiences and current needs. We hope that sharing these insights will benefit researchers interested in conducting basic and intervention research aimed at improving the mental health of individuals exposed to war-related trauma.

Best practices for recruitment in veterinary clinical trials.

A successful clinical trial requires participants, but many factors can impede effective study recruitment. To better recruit for quality veterinary clinical trials in client-owned animals that lead to improved evidence-based patient care and outcomes, there is a collective need to share and implement current best practices for recruitment strategies. These strategies should utilize a holistic view of recruitment, encompassing study design and logistics, representative participation, incentives, personnel resources, advertising, and participant retention. Although human clinical trial data and resources can provide guidance, effort also needs to be put into evaluating current practices and opportunities for process improvement that are specific to the conduct of veterinary clinical trials. Considering the power of pets as naturally occurring models of disease and as sentinels, improved conduct of veterinary clinical research has the potential to inform human health outcomes. Continued development of collaborations surrounding best practices and training opportunities in veterinary clinical research will improve the impact of veterinary clinical trials teams, while also promoting workforce development and alternate career paths for veterinary professionals.

Evidence of being cured for nasopharyngeal carcinoma: results of a multicenter patient-based study in China.

Background: The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape. Methods: This retrospective multicenter study enrolled 6315 patients with nonmetastatic NPC from nonendemic and endemic regions of China from 2007 to 2020. We applied mixture and nonmixture cure models to estimate the cure probabilities and cure times by incorporating background mortality for the general population, matching by gender, age, and diagnosed year. Findings: With death as the uncured event, the probability of patients with NPC achieving a life expectancy at par with the general population was 78.1%. Considering progression as the uncured event, the likelihood of patients attaining a life expectancy without progression equivalent to that of the general population was 72.4%. For individuals, the probabilities of achieving cure were conditional and time-dependent, requiring approximately 7.1 and 4.7 years with 95% certainty, respectively. The corresponding cure times for uncured patients were 8.9 and 6.8 years, respectively. The cure probability was correlated with age, Eastern Cooperative Oncology Group score, TNM staging, Epstein-Barr virus DNA copies, and lactate dehydrogenase. The correlation was excellent between 5-year overall survival/progression-free survival and cure fractions. Interpretation: Statistical cure is potentially achievable among patients with NPC undergoing contemporary treatment modalities. The results hold significant potential implications for both clinical practice and patient perspectives. Funding: National High Level Hospital Clinical Research Funding; Beijing Xisike Clinical Oncology Research Foundation; Beijing hope run fund.

A worked example of contextualising and using reflexive thematic analysis in nursing research.

BACKGROUND: A researcher must consider their research question within their world view before selecting a technique appropriate for analysing their data. This will affect their choices of methodology and methods for collecting and analysing data. Reflexive thematic analysis (RTA) has become a go-to technique for qualitative nurse researchers. However, the justifications for using it and its application in the context of a wider approach are under-discussed. AIM: To rationalise the use of RTA within a wider philosophical-methodological-methods-analysis approach and provide nurse researchers with practical guidance about how to apply it to qualitative data. DISCUSSION: This article conceptually grounds the seminal work of Braun and Clarke (2006 ) and provides a process for rigorously and systematically analysing qualitative data. Researchers undertaking qualitative research must use a rigorous philosophical-methodological-method-analysis approach. Before selecting a technique appropriate for analysing their data, they must consider their research question within their own world view. This has implications for their choice of methodology and consequently the data collection methods and analysis techniques they use. Researchers should be mindful of RTA's conceptual roots when applying it. CONCLUSION: Transparent and rigorous data analysis leads to credible findings, supports evidence-based practice and contributes to the growing body of nursing research. Within the context of the wider philosophical-methodological-methods-analysis approach, RTA produces high-quality, credible findings when applied well. IMPLICATIONS: for practice This article can guide nursing students and novice researchers in choosing and applying RTA to their research.

PATIENT RECRUITMENT USING ELECTRONIC HEALTH RECORDS UNDER SELECTION BIAS: A TWO-PHASE SAMPLING FRAMEWORK.

Electronic health records (EHRs) are increasingly recognized as a cost-effective resource for patient recruitment in clinical research. However, how to optimally select a cohort from millions of individuals to answer a scientific question of interest remains unclear. Consider a study to estimate the mean or mean difference of an expensive outcome. Inexpensive auxiliary covariates predictive of the outcome may often be available in patients' health records, presenting an opportunity to recruit patients selectively, which may improve efficiency in downstream analyses. In this paper we propose a two-phase sampling design that leverages available information on auxiliary covariates in EHR data. A key challenge in using EHR data for multiphase sampling is the potential selection bias, because EHR data are not necessarily representative of the target population. Extending existing literature on two-phase sampling design, we derive an optimal two-phase sampling method that improves efficiency over random sampling while accounting for the potential selection bias in EHR data. We demonstrate the efficiency gain from our sampling design via simulation studies and an application evaluating the prevalence of hypertension among U.S. adults leveraging data from the Michigan Genomics Initiative, a longitudinal biorepository in Michigan Medicine.

Effect of tirzepatide on the progression of coronary atherosclerosis using MDCT: Rationale and design of the Tirzepatide treatment on coronary atherosclerosis progression: The (T-PLAQUE) randomized-controlled trial design: tirzepatide and plaque.

INTRODUCTION: Tirzepatide is a novel once-week dual GIP/GLP-1 RA agonist approved for T2DM and its role to reduce cardiovascular events remains to be elucidated. The goal of this trial is to assess how tirzepatide affects the progression of atherosclerotic plaque as determined by multidetector computed tomography angiography (MDCTA). METHODS: This trial is a double blind, randomized, prospective, placebo-controlled multi-center phase IV trial. Participant eligible for the study will be adults with T2DM between 40 and 80 years of age who have HbA1c ≥7.0% to ≤10.5% and at least 20% stenosis in major epicardial vessel on CCTA. Baseline examination will include the results of their demographics, lab tests, coronary calcium, as well as coronary plaque volume/composition. Following randomization, tirzepatide or placebo will be given at a weekly dose of 2.5 mg, and a fixed dose-escalation strategy will be followed. Patients will undergo quarterly visits for safety assessments and labs, and follow up with repeat CCTA at 1 year. DISCUSSION: This study evaluates the anti-atherogenic potential of tirzepatide, providing a mechanism of potential CV benefit. This is crucial to our understanding of T2DM treatment and CVD since plaque progression portends worse outcomes in these populations. MDCTA is a noninvasive method that assesses the volume, composition, and degree of coronary vessel stenosis. CONCLUSION: This study will be the first study to assess the effects of tirzepatide on atherosclerotic plaque progression measured by MDCTA in participants with T2DM.

Ethnic-specific characteristics associated with longitudinal response patterns from prebirth to 12 years: evidence from Growing Up in New Zealand.

BACKGROUND: Longitudinal studies can generate valuable scientific knowledge, but can be compromised by systematic attrition. Previous research shows that sociodemographic characteristics (eg, ethnicity, age, educational level, socioeconomic circumstances) are associated with attrition rates. However, little is known about whether these characteristics differ by ethnicity, and how this impacts cohort retention strategies. METHODS: Using antenatal to 12-year data from the Growing Up in New Zealand birth cohort study (N=6743), we examined transversal response rates by ethnicity (Maori, Pacific, Asian, European), used sequence analysis and cluster analysis to identify unique longitudinal response patterns, and binary logistic regression to examine ethnic-specific sociodemographic characteristics associated with these response patterns. RESULTS: The overall response rate at 12 years was 71.0%, with ethnic differences in response rates widening over the six data collection waves. Three longitudinal response patterns were identified: frequent responders (65.2%), intermittent non-responders (29.6%) and frequent non-responders (5.2%). Sociodemographic characteristics such as younger maternal age and lower maternal education were associated with a higher likelihood of membership in the non-response clusters across all ethnic groups. However, there were also important nuances by ethnicity. Individual level factors (eg, household material deprivation and maternal general health) tended to be associated with non-response for Europeans, whereas structural level factors (eg, area-level deprivation and racial discrimination) tended to be associated with non-response for Maori, Pacific and Asian peoples. CONCLUSION: Ethnic differences in longitudinal response patterns are due to multiple factors of disadvantage, and therefore require targeted retention strategies. Stratifying analyses by ethnicity is important for revealing nuanced insights.

Long-term retention and positive deviant practices in Uganda's community client-led antiretroviral distribution groups (CCLADs): a mixed-methods study.

BACKGROUND: HIV testing and starting antiretroviral therapy (ART) are pivotal in treating people living with HIV (PLHIV) but sustaining PLHIV on treatment remains challenging. We assessed retention and attrition in community client-led antiretroviral distribution groups (CCLADs) in Uganda and identified positive deviant practices that foster long-term retention. METHODS: Using explanatory mixed methods, we collected longitudinal medical data from 65 health facilities across 12 districts in East Central Uganda. Quantitative phase, from 18 April 2021 to 30 May 2021, employed survival analysis and Cox regression to assess retention and identify attrition risk factors. Qualitative inquiry focused on four districts with high attrition from 11 August 2021 to 20 September 2021, where we identified nine health facilities exhibiting high retention in CCLADs. We purposively selected 50 clients for in-depth interviews (n=22) or focus group discussions (n=28). Using thematic analysis, we identified positive deviant practices. We integrated quantitative and qualitative findings into joint displays. RESULTS: Involving 3055 PLHIV, the study showed retention rates of 97.5% at 6 months, declining to 89.7% at 96 months. Attrition risk factors were lower levels of care (health centre three (adjusted HR (aHR) 2.80, 95% CI 2.00 to 3.65) and health centre four (aHR 3.61, 95% CI 2.35 to 5.54)); being unemployed (aHR 2.21, 95% CI 1.00 to 4.84); enrolment year into CCLAD (aHR 23.93, 95% CI 4.66 to 123.05) and virological failure (aHR 3.41, 95% CI 2.51 to 4.63). Of 22 clients interviewed, 8 were positive deviants. Positive deviants were characterised by prolonged retention in CCLADs, improved clinical outcomes and practised uncommon behaviours that enabled them to find better solutions than their peers. Positive deviant practices included fostering family-like settings, offering financial or self-development advice, and promoting healthy lifestyles. CONCLUSIONS: Findings underscore the importance of addressing factors contributing to attrition and leveraging positive deviant practices to optimise retention and long-term engagement in HIV care.

Quantifying the Impact of Co-Housing on Murine Aging Studies.

Analysis of preclinical lifespan studies often assume that outcome data from co-housed animals are independent. In practice, treatments, such as controlled feeding or putative life-extending compounds, are applied to whole housing units, and as a result the outcomes are potentially correlated within housing units. We consider intra-class (here, intra-cage) correlation in three published and two unpublished lifespan studies of aged mice encompassing more than 20 thousand observations. We show that the independence assumption underlying common analytic techniques does not hold in these data, particularly for traits associated with frailty. We describe and demonstrate various analytical tools available to accommodate this study design and highlight a limitation of standard variance components models (i.e., linear mixed models) which are the usual statistical tool for handling correlated errors. Through simulations, we examine the statistical biases resulting from intra-cage correlations with similar magnitudes as observed in these case studies and discuss implications for power and reproducibility.

Integrating gene expression and imaging data across Visium capture areas with visiumStitched.

Background: Visium is a widely-used spatially-resolved transcriptomics assay available from 10x Genomics. Standard Visium capture areas (6.5mm by 6.5mm) limit the survey of larger tissue structures, but combining overlapping images and associated gene expression data allow for more complex study designs. Current software can handle nested or partial image overlaps, but is designed for merging up to two capture areas, and cannot account for some technical scenarios related to capture area alignment. Results: We generated Visium data from a postmortem human tissue sample such that two capture areas were partially overlapping and a third one was adjacent. We developed the R/Bioconductor package visiumStitched, which facilitates stitching the images together with Fiji (ImageJ), and constructing SpatialExperiment R objects with the stitched images and gene expression data. visiumStitched constructs an artificial hexagonal array grid which allows seamless downstream analyses such as spatially-aware clustering without discarding data from overlapping spots. Data stitched with visiumStitched can then be interactively visualized with spatialLIBD. Conclusions: visiumStitched provides a simple, but flexible framework to handle various multi-capture area study design scenarios. Specifically, it resolves a data processing step without disrupting analysis workflows and without discarding data from overlapping spots. visiumStiched relies on affine transformations by Fiji, which have limitations and are less accurate when aligning against an atlas or other situations. visiumStiched provides an easy-to-use solution which expands possibilities for designing multi-capture area study designs.

Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study.

INTRODUCTION: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs. METHODS: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. REGISTRATION: https://www.comet-initiative.org/Studies/Details/1580. RESULTS: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life. CONCLUSION: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs. PROSPERO REGISTRATION NUMBER: CRD42020197293.