The competency index for clinical research professionals: a potential tool for competency-based clinical research academic program evaluation.

Background: Accreditation of graduate academic programs in clinical research requires demonstration of program achievement of Joint Task Force for Clinical Trial Competence-based standards. Evaluation of graduate programs include enrollment, student grades, skills-based outcomes, and completion rates, in addition to other measures. Standardized measures of competence would be useful. Methods: We used the Competency Index for Clinical Research Professionals (CICRP), in a separate-sample pretest-posttest study to measure self-confidence or self-efficacy in clinical research competency comparing cohorts of students entering and completing a master's degree program in clinical research across three semesters (summer 2021 - spring 2022). CICRP is a 20-item Likert scale questionnaire (0 = Not at all confident; 10 = extremely confident). Results: The study sample of 110 students (54 in the entry course, 56 in the exit course) showed overall 80.9% entered the program with only a baccalaureate degree and 55.5% had no prior experience in managing clinical trial research. Cronbach alpha for the instrument showed a high level of content validity (range 0.93-0.98). Median CICRP item rating range at entry was [1, 6] and at exit [7, 10]. Mean CICRP total score (sum of 20 items) at entry was 72.7 (SD 41.9) vs. 167.0 (SD 21.1) at exit (p < 0.001). Mean total score at program entry increased with increasing years of clinical trial management experience but attenuated at program exit. Conclusion: This is the first use of the CICRP for academic program evaluation. The CICRP may be a useful tool for competency-based academic program evaluation, in addition to other measures of program excellence.

ECLIM-SEHOP: how to develop a platform to conduct academic trials for childhood cancer.

INTRODUCTION: ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation. METHODS: The platform's database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted. RESULTS: ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months. DISCUSSION: ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.

Eye on the Prize: Patient Outcomes Research in Medical Education.

The overarching goal of medical education is to train clinicians who achieve and maintain competence in patient care. Although the field of medical education research has acknowledged the importance of education on clinical practices and outcomes, most research endeavors continue to focus on learner-centered outcomes, such as knowledge and attitudes. The absence of clinical and patient-centered outcomes in pulmonary and critical care medicine medical education research has been attributed to barriers at multiple levels, including financial, methodological, and practical considerations. This Perspective explores clinical outcomes relevant to pulmonary and critical care medicine educational research and offers strategies and solutions that educators can use to accomplish what many consider the "prize" of medical education research: an understanding of how our educational initiatives impact the health of patients.

Implementing Strategies to Recruit and Retain a Diverse Sample of Heart Failure Patients.

Introduction: The increased prevalence, severity, and mortality of heart disease and specifically heart failure among Hispanic and Black populations are a concern for clinicians and researchers. Additionally, patients of poor socioeconomic status also have worse outcomes for cardiovascular disease. To address disparities, it is necessary to address the persistent lack of representation in clinical research of diverse populations, including the Hispanic and Black populations and individuals who are of low socioeconomic status. Method: This study was a pilot randomized trial of a medication adherence intervention for heart failure patients conducted at a safety net hospital and affiliated pharmacy with a diverse patient population. Using an evidence-based multifactorial approach, this investigation implemented and adapted best practices to support the inclusion of Hispanic, Black, and socioeconomically diverse participants. Results: A total of 40 participants were recruited, 58% were Hispanic, 38% Black, and 5% White. A total of 40% reported the need for socioeconomic assistance. At 30 days after discharge, follow-up data were obtained for 37 of 40 (93%) of participants either by interview, electronic record, or both. Conclusion: Findings suggest that a combination of strategies used in this trial can be applied to recruit and retain ethnically and socioeconomically diverse participants.

A whole blood-based functional assay to characterize immunoglobulin A effector functions.

Most investigations on the immune cell-activating potency of IgA used purified total IgA and/or specific isolated cell populations. As IgA2 has been reported to be more pro-inflammatory than IgA1, we aimed to employ a fast and convenient whole blood-based assay to individually probe the capacity of the two IgA subclasses to activate immune cells in close physiological conditions. To this end, whole blood from healthy donors (n = 10) was stimulated with immobilized IgA1, IgA2m1 or IgA2m2 (the two main allotypic variants of IgA2). Activation of major leukocyte subsets was measured using a 10-color flow cytometry panel providing access to the expression of 5 activation markers on 6 different immune cell subsets. While capturing some heterogeneity of responses among donors, IgA2m1 and IgA2m2 systematically showed a stronger activation profile compared to IgA1 in a variety of dimensions. For example, both IgA2 allotypes led to stronger modulations of CD54, CD11b, CD62L, CD66b or CD69, on both or either monocytes or neutrophils, indicating a more pronounced pro-inflammatory effect for this subclass than IgA1. By taking into account donor-specific soluble and cellular components this whole blood-based functional approach provides new perspectives to further investigate IgA effector functions in mechanistic studies and/or translational research.

Pathological claustrum activity drives aberrant cognitive network processing in human chronic pain.

Aberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants. Moreover, we discover pathological activity of the claustrum and a region near the posterior inferior frontal sulcus of the right dorsolateral prefrontal cortex (piDLPFC) in migraine patients during acute pain and cognitive task performance. Dynamic causal modeling suggests a directional influence of the claustrum on activity in this piDLPFC region, and diffusion weighted imaging verifies their structural connectivity. These findings advance understanding of claustrum function during acute pain and provide evidence of a possible circuit mechanism driving cognitive impairments in chronic pain.

Progression-free survival is a weakly predictive surrogate end-point for overall survival in follicular lymphoma: A systematic review and meta-analysis.

Although progression-free survival (PFS) is a commonly used surrogate end-point for clinical trials of follicular lymphoma (FL), no analyses have evaluated the strength of surrogacy for PFS with overall survival (OS). A systematic review was performed and 20 studies (total participants, 10 724) met final inclusion criteria. PFS was weakly associated with OS (correlation coefficient; 0.383, p < 0.001). The coefficient of determination was 0.15 (95% CI: 0.002-0.35) suggesting 15% of OS variance could be explained by changes in PFS. This challenges the role for PFS as a surrogate end-point for clinical trials and drug approvals.

Clinical Evidence, Triangulation of Perspectives and Contextualization. Part 1: The Beginning of Carla's Treatment.

We propose to critically evaluate and strengthen the level of clinical evidence in psychoanalysis, using a strategy of triangulating clinical phenomena from different perspectives and increasing contextual knowledge. Insufficient discussion of alternative hypotheses and limited contextual information are two Achilles heels of psychoanalytic case presentations. We examine the concept and quality standards of clinical evidence in psychoanalysis and related disciplines, with particular attention to the contribution of the three-level model (3-LM). We analyze the case of a patient treated with transference-focused psychotherapy (TFP), making explicit the theoretical-clinical agreements and disagreements of the authors. We discuss the strengths and limitations of triangulation and contextualization, concluding that they make clinical work and psychoanalytic writing more reliable, transparent, auditable, and replicable.

Secondary Data Analysis: Using existing data to answer new questions.

INTRODUCTION: Secondary data analysis is a cost-effective, accessible, and efficient means of utilizing existing data to answer new research questions. METHOD: The manuscript provides an overview of the secondary data analysis process, as well as benefits and limitations inherent in the research method. RESULTS: An exemplar of pediatric focused research using a publicly available dataset is presented to facilitate understanding of the process. DISCUSSION: Novice and experienced researchers benefit from exploring the quantitative and qualitative secondary data analysis options available.

Wuhu decoction combined with azithromycin for treatment of Mycoplasma pneumoniae pneumonia in Asian children: a systematic review and meta analysis of randomized controlled trials.

Objective: This study constitutes a pioneering systematic review and meta analysis delving into the clinical efficacy and safety of the combined therapy involving Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. Methods: This study conducted a comprehensive computerized search, covering 6 Chinese databases and 6 English databases, to collect randomized controlled trials related to the combined use of Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. The search was extended until August 2023. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. Meta-analysis was performed using Stata 14.0 and RevMan 5.4 software. Additionally, meta-regression analysis and subgroup analysis were carried out on primary outcomes to identify potential sources of heterogeneity and confounding factors. Results: A total of 22 randomized controlled trials involving 2,026 patients were included in this study. The combined therapy of Wuhu Decoction and azithromycin demonstrated superior efficacy compared to azithromycin alone (RR = 1.17, 95% CI [1.13, 1.21], p < 0.00001; low certainty of evidence). Additionally, patients receiving the combination therapy experienced significantly reduced the disappearance time of fever (MD = -1.42, 95% CI [-1.84, -1.00], p < 0.00001; very low certainty of evidence), disappearance time of cough (MD = -2.08, 95% CI [-2.44, -1.71], p < 0.00001; very low certainty of evidence), disappearance of pulmonary rales (MD = -1.97, 95% CI [-2.31, -1.63], p < 0.00001; very low certainty of evidence), and disappearance time of wheezing (MD = -1.47, 95% CI [-1.72, -1.22], p < 0.00001; very low certainty of evidence). Meta-regression analysis suggested that course of disease, sample size, and age might be sources of heterogeneity. Subgroup and sensitivity analyses reaffirmed the stability of these results. Furthermore, analyses of secondary outcomes such as T lymphocytes, serum inflammatory factors, and the incidence rate of adverse reactions consistently favored the combination therapy of WHD and azithromycin over azithromycin alone, with statistically significant differences. Conclusion: Based on our meta-analysis findings, the combined therapy of Wuhu Decoction and azithromycin for treating pediatric Mycoplasma pneumoniae pneumonia exhibited superior overall efficacy in comparison to azithromycin monotherapy. However, in the included 22 studies, the majority of evaluated factors showed unclear bias risks, and a persistent bias risk was consistently present within one category. Moreover, due to the low quality of evidence, interpreting these results should be approached with caution. Hence, we emphasize the necessity for future high-quality, multicenter, and large-sample clinical randomized controlled trials. These trials are essential to provide more robust data for evidence-based research and to establish higher-quality evidence support. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023465606.

Rurality, Cardiovascular Risk Factors, and Early Cardiovascular Disease among Childhood, Adolescent, and Young Adult Cancer Survivors.

Background and Aims: Cardiovascular risk factors (CVRFs) later in life potentiate risk for late cardiovascular disease (CVD) from cardiotoxic treatment among survivors. This study evaluated the association of baseline CVRFs and CVD in the early survivorship period. Methods: This analysis included patients ages 0-29 at initial diagnosis and reported in the institutional cancer registry between 2010 and 2017 (n = 1228). Patients who died within five years (n = 168), those not seen in the oncology clinic (n = 312), and those with CVD within one year of diagnosis (n = 17) were excluded. CVRFs (hypertension, diabetes, dyslipidemia, and obesity) within one year of initial diagnosis, were constructed and extracted from the electronic health record based on discrete observations, ICD9/10 codes, and RxNorm codes for antihypertensives. Results: Among survivors (n = 731), 10 incident cases (1.4%) of CVD were observed between one year and five years after the initial diagnosis. Public health insurance (p = 0.04) and late effects risk strata (p = 0.01) were positively associated with CVD. Among survivors with public insurance(n = 495), two additional cases of CVD were identified from claims data with an incidence of 2.4%. Survivors from rural areas had a 4.1 times greater risk of CVD compared with survivors from urban areas (95% CI: 1.1-15.3), despite adjustment for late effects risk strata. Conclusions: Clinically computable phenotypes for CVRFs among survivors through informatics methods were feasible. Although CVRFs were not associated with CVD in the early survivorship period, survivors from rural areas were more likely to develop CVD. Implications for Survivors: Survivors from non-urban areas and those with public insurance may be particularly vulnerable to CVD.

Digital Health Technology (DHT) in European Clinical Trials, How to Improve the Status-Quo of the Regulatory Landscape?

Digital health technology (DHT) is increasingly used to facilitate the conduct of clinical drug trials. The European regulatory environment would benefit from some adjustments to realize the full potential of DHTs. Considering current discussions such as the European Accelerating Clinical Trial Initiative (ACT EU), we propose four concrete adjustments to this regulatory landscape to introduce risk-based qualification approaches for DHTs. In our view, these changes would have the potential to facilitate the use of DHT in clinical research and thus provide access to innovative therapies in Europe.

Novel agents and regimens in relapsed or refractory peripheral T-cell lymphoma: latest updates from 2023 ASH annual meeting.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological malignancies with poor survival, while treatment options for relapsed or refractory (R/R) disease remain quite limited, with a median progression-free survival of only 3-4 months. Notably, the emergence of innovative therapeutic agents and regimens holds promise for durable responses and improved survival for patients with R/R PTCL. We summarize recent advances in the treatment of R/R PTCL from the 2023 ASH Annual Meeting, highlighting novel agents targeting EZH1/2, JAK1, PI3K, KIR3DL2, CD38/CD3xCD28, or CDK9, as well as therapeutic regimens in combination with stem cell transplantation, immunomodulators, epigenetic modifying agents, or CD30/CD16A bispecific antibodies.

Across Time: A Chronological Progression of Clinical Trials in India.

The journey of clinical research in India spans centuries, marked by significant milestones and advancements in scientific, ethical, and regulatory domains. From early trials conducted by pioneers like James Lind to modern standards shaped by landmark events such as the Nuremberg Code and the adoption of Good Clinical Practice guidelines, India's progression reflects a commitment to ethical conduct and patient welfare. The Indian Council of Medical Research (ICMR) has played a pivotal role in this evolution, establishing national research centers and ethical committees to oversee biomedical research. Regulatory frameworks, exemplified by Schedule Y of the Drugs and Cosmetics Act, have adapted over time to align with global standards, facilitating India's integration into the international clinical development landscape. Despite challenges and setbacks, including misconceptions surrounding regulatory reforms, India's clinical trial ecosystem continues to evolve, driven by a dedication to ethical research practices and excellence in healthcare.

Integration of a deep learning basal cell carcinoma detection and tumor mapping algorithm into the Mohs micrographic surgery workflow and effects on clinical staffing: A simulated, retrospective study.

Background: Artificial intelligence (AI) enabled tools have been proposed as 1 solution to improve health care delivery. However, research on downstream effects of AI integration into the clinical workflow is lacking. Objective: We aim to analyze how integration of an automated basal cell carcinoma detection and tumor mapping algorithm in a Mohs micrographic surgery unit impacts the work efficiency of clinical and laboratory staff. Methods: Slide, staff, and histotechnician waiting times were analyzed over a 20-day period in a Mohs micrographic surgery unit. A simulated AI workflow was created and the time differences between the real and simulated workflows were compared. Results: Simulated nonautonomous algorithm integration led to savings of 35.6% of slide waiting time, 18.4% of staff waiting time, and 18.6% of histotechnician waiting time per day. Algorithm integration on days with increased reconstruction complexity resulted in the greatest time savings. Limitations: One Mohs micrographic surgery unit was analyzed and simulated AI integration was performed retrospectively. Conclusions: AI integration results in reduced staff waiting times, enabling increased productivity and a streamlined clinical workflow. Schedules containing surgical cases with either increased repair complexity or numerous tumor removal stages stand to benefit most. However, significant logistical challenges must be addressed before broad adoption into clinical practice is realistic.

Enhancing competency of clinical research nurses: A comprehensive training and evaluation framework.

The Sun et al's training program for clinical research nurses (CRNs) in the World Journal of Clinical Cases is a comprehensive and scientific approach. It includes structured frameworks for CRN training, aiming to improve CRN competency. This program emphasizes practical abilities, updates training content, and improves evaluation methods. The cultivation of CRN talents focuses on enhancing the training system, establishing a multifaceted evaluation framework, and continuously refining the training programs. Regular feedback and evaluation are essential to improve CRNs' competency in practical settings.