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The present study examined review articles in medical sciences and analyzed their citations of retracted Iranian papers. This was a quantitative and applied study using scientometrics and descriptive cross-sectional approaches. Review articles' citation trends of retracted studies were investigated using the quantitative method, and the status of the mentioned citations was determined using the descriptive method. The study population comprised 53 review studies that cited 28 retracted Iranian articles. The current study on review articles citing retracted papers revealed that most citations in 2019 were in the form of systematic reviews and meta-analyses by Iranian authors. These articles were occasionally published in journals with a high credibility and impact factor. Although the most frequent reasons for article retraction in the present study were scientific misconduct, most of the citing review articles did not mention this issue. Further research is required to determine the impact of referencing retracted articles on the results of review articles, especially systematic reviews, meta-analyses, and randomized clinical trials (RCTs), regarding the reasons for retraction. [ABSTRACT FROM AUTHOR]

Conceptualizing tobacco dependence as a chronic relapsing condition suggests the need to use analytic strategies that reflect that premise. However, clinical trials for smoking cessation typically define the primary endpoint as a measure of abstinence at a single timepoint distal to the intervention, typically 3–12 months. This reinforces the concept of tobacco outcomes as a dichotomous state—one is, or is not, abstinent. Fortunately, there are several approaches available to handle longitudinal data that reflect the relapsing and remitting nature of tobacco use during treatment studies. In this paper, sponsored by the Society for Research on Nicotine and Tobacco's Treatment Research Network, we present an introductory overview of these techniques and their application in smoking cessation clinical trials. Topics discussed include models to examine abstinence outcomes (eg, trajectory models of abstinence, models for transitions in smoking behavior, models for time to event), models that examine reductions in tobacco use, and models to examine joint outcomes (eg, examining changes in the use of more than one tobacco product). Finally, we discuss three additional relevant topics (ie, heterogeneity of effects, handling missing data, and power and sample size) and provide summary information about the type of model that can be used based on the type of data collected and the focus of the study. We encourage investigators to familiarize themselves with these techniques and use them in the analysis of data from clinical trials of smoking cessation treatment. Implications Clinical trials of tobacco dependence treatment typically measure abstinence 3–12 months after participant enrollment. However, because smoking is a chronic relapsing condition, these measures of intervention success may not accurately reflect the common trajectories of tobacco abstinence and relapse. Several analytical techniques facilitate this type of outcome modeling. This paper is meant to be an introduction to these concepts and techniques to the global nicotine and tobacco research community including which techniques can be used for different research questions with visual summaries of which types of models can be used for different types of data and research questions. [ABSTRACT FROM AUTHOR]

Biostatistics plays a pivotal role in developing, interpreting and drawing conclusions from clinical, biological and epidemiological data. However, the improper application of statistical methods can lead to erroneous conclusions and misinterpretations. This paper provides a comprehensive examination of the most frequent mistakes encountered in the biostatistical analysis process. We identified and elucidated 10 common errors in biostatistical analysis. These include using the wrong metric to describe data, misinterpreting P -values, misinterpreting the 95% confidence interval, misinterpreting the hazard ratio as an index of prognostic accuracy, ignoring the sample size calculation, misinterpreting analysis by strata in randomized clinical trials, confusing correlation and causation, misunderstanding confounders and mediators, inadequately codifying variables during the data collection, and bias arising when group membership is attributed on the basis of future exposure in retrospective studies. We discuss the implications of these errors and propose some practical strategies to mitigate their impact. By raising awareness of these pitfalls, this paper aims to enhance the rigor and reproducibility of biostatistical analyses, thereby fostering more robust and reliable biomedical research findings. [ABSTRACT FROM AUTHOR]

Background: This study examines the effect of a Theory of Mind (ToM) intervention on ToM abilities and social–emotional functioning in adolescents with developmental language disorder (DLD) or who are deaf/hard of hearing (D/HH). It emphasizes the importance of self‐reflection and measurement for personal growth. The research design incorporates both subjective and objective measures to evaluate the intervention's efficacy. Aims: To investigate the impact of the ToM intervention on ToM abilities and social–emotional functioning in adolescents with DLD or who are D/HH. It hypothesizes that participants in the intervention groups will show improved ToM and social–emotional functioning compared with those in the control groups. Methods & Procedures: Adolescents with DLD or who are D/HH were recruited through collaboration with educational institutions. The study utilized a pre‐/post‐test design, assigning participants to either the intervention or the control group. The ToM intervention involved targeted activities to enhance ToM abilities. ToM abilities and social–emotional functioning were assessed using standardized tests and self‐report questionnaires. Statistical analyses compared outcomes between the intervention and no intervention groups. Outcomes & Results: The findings reveal subjective improvements in social–emotional functioning among the D/HH intervention group. However, no significant effects on objective ToM measures were observed. These results highlight the need for further investigation and refinement of interventions in these areas. Future research should focus on improving intervention strategies and exploring additional objective measures to gain a comprehensive understanding of the intervention's impact on ToM and social–emotional functioning in this population. Conclusions & Implications: The ToM intervention shows subjective benefits in improving social–emotional functioning among D/HH adolescents. However, it does not yield significant effects on objective ToM measures. These findings emphasize the ongoing need to refine interventions targeting ToM abilities and social–emotional functioning in this population. Future studies should explore alternative strategies and incorporate additional objective measures to enhance understanding and outcomes. WHAT THIS PAPER ADDS: What is already known on this subject: Before this study, it was known that ToM interventions have the potential to enhance ToM abilities. However, the specific effects of such interventions on subjective and objective measures for ToM and social–emotional functioning in adolescents with DLD or who are D/HH remained unclear, necessitating further research. What this paper adds to the existing knowledge: This study adds to the existing knowledge by demonstrating subjective improvements in social–emotional functioning among adolescents who are D/HH and underwent a ToM intervention. However, no significant effects on objective ToM measures were observed. These findings highlight the need for refining interventions and exploring additional measures to better understand the intervention's impact. What are the potential or actual clinical implications of this work?: The subjective improvements in social–emotional functioning observed in this study have important clinical implications. They suggest that ToM interventions can positively impact the social well‐being of adolescents who are D/HH. However, the lack of significant effects on objective ToM measures emphasizes the need for further research and intervention refinement to address specific areas of improvement in this population. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream and downstream manufacturing processes for EV large-scale production, also focusing on post-processing technologies such as surface bioengineering and uploading studies to yield novel EV-based diagnostics and advanced therapy medicinal products. This paper also focuses on the quality, safety, and efficacy issues of the bioengineered EV drug candidates before first-in-human studies. Because clinical trials involving extracellular vesicles are on the global rise, this paper encompasses different clinical studies registered on clinical-trial register platforms, with varying levels of advancement, highlighting the growing interest in EV-related clinical programs. Navigating the regulatory affairs of EVs poses real challenges, and obtaining marketing authorization for EV-based medicines remains complex due to the lack of specific regulatory guidelines for such novel products. This paper discusses the state-of-the-art regulatory knowledge to date on EV-based diagnostics and medicinal products, highlighting further research and global regulatory needs for the safe and reliable implementation of bioengineered EVs as diagnostic and therapeutic tools in clinical settings. Post-marketing pharmacovigilance for EV-based medicinal products is also presented, mainly addressing such topics as risk assessment and risk management. [ABSTRACT FROM AUTHOR]

The application of STEM (Science, Technology, Engineering, and Math) education in solving real-world problems is challenging. To tackle this challenge, a project-based learning approach that integrates robots with cost-effective self-made toys to problem-solving was adopted to assist rural primary school students to apply STEM skills. The purpose of this study was to evaluate the effects of the project-based learning approach which includes lecturing and hands-on activities on primary school students' STEM learning outcomes and attitudes. An experiment was conducted with 25 primary school students who voluntarily participated in a STEM summer-camp programme. Students were asked to assemble a paper house equipped with an IoT control module and LED light switches, and write and edit robot scripts to produce a robot-based storytelling narrative using the paper house they made as a context. The results show that the project-based learning approach was an effective approach for cultivating primary school students' STEM knowledge and skills as evidenced from the post-written test. The relationships between the students' STEM learning outcomes and attitudes were also confirmed by a clustering analysis. Students who had higher learning attitudes also achieved higher STEM learning outcomes; the findings are also supported by the feedback from the open-ended questionnaire items. This study suggests that integrating low-cost self-made toys and robots in project-based learning activities is an effective and practical approach to enhance primary school students' learning outcomes and learning attitudes in STEM education. [ABSTRACT FROM AUTHOR]

Clinical trials are very important for determining the safety and efficacy of medical trials, which is further critical to the progress of the various healthcare businesses. Conducting such studies requires substantial preparation and adherence to the various ethical norms; such norms which are especially crucial when dealing with medical emergencies like the COVID-19 outbreak. This paper discusses the Site Initiation Visit (SIV) and the development of Essential Document Files (EDF) for clinical research. Site initiation visit specifies fundamental tasks to ensure team preparedness, logistical planning, and regulatory compliance. Team training, investigational product (IP) storage, and post-SIV follow-up procedures are all valuable considerations. On the other hand, throughout the trial's lifecycle, the document files play a very vital role in ensuring a complete documentation process thereby promoting transparency and adherence to Good Clinical Practice (GCP) guidelines. The paper highlights the importance of established protocols and regulatory compliance, in safeguarding safety by outlining these procedures. [ABSTRACT FROM AUTHOR]

Complex and enduring mental health problems require greater treatment resources, usually in the form of multidisciplinary support, including providing psychological therapies. This paper reports on an NHS, tertiary-level specialist psychotherapy service offering Psychodynamic therapies with longer-term, exploratory transdiagnostic approaches to support complexity and sustained personality functioning. This paper adopts a naturalistic study design evaluating the effectiveness of Psychodynamic therapy using pre- and post-outcomes across a 10-year period. A total of n = 474 participants self-report pre- and post-outcome measures were used as the marker of effectiveness along with therapist assessments during intake and engagement. The findings showed that Psychodynamic therapy was effective in reducing psychological distress based on service-user self-report and therapist assessments. While intake scores varied by socio-demographic factors, the rate of change across most groups was similar. There were several limitations relating to data quality and completeness which reflect the naturalistic design. Despite the limits of a naturalistic design, this study provides evidence of support for the place of Psychodynamic therapies within NHS mental health care, catering to those with complex and enduring mental health problems. [ABSTRACT FROM AUTHOR]

Background: A skin tear is a traumatic wound that occurs in up to one in five hospitalized patients. Nursing care includes application of a dressing to create a moist wound healing environment. Aim: To compare the effectiveness of two standard dressings (adhesive silicone foam vs. meshed silicone interface) to heal hospital‐acquired skin tear. Methods: An intention‐to‐treat pilot study was designed using a randomized, non‐inferiority trial in an Australian tertiary hospital setting. Consenting participants (n = 52) had acquired a skin tear within the previous 24 h and had agreed to a 3‐week follow‐up. Data were collected between 2014 and 2020. The primary outcome measure was wound healing at 21 days. Results: Baseline characteristics were similar in both arms. Per protocol, 86% of skin tears were fully healed at 3 weeks in the adhesive silicone foam group, compared to 59% in the meshed silicone interface group. Greater healing was observed across all skin tear categories in the adhesive silicone foam dressing group. In the intention‐to‐treat sample, healing was 69% and 42%, respectively. Conclusions: Results suggest the adhesive silicone foam dressing may be superior, as it produced clinically significant healing of skin tears at 3 weeks compared to the meshed silicone interface dressing. Accounting for potential loss to follow‐up, a sample of at least 103 participants per arm would be required to power a definitive study. Summary statement: What is already known about this topic? A skin tear is a traumatic wound that is commonly acquired during hospitalization that affects older adults in particular. In hospital settings, it may occur in up to one in five patients.A variety of skin tear dressings have been used in previous studies, with healing rates ranging from 34% to 97% at 21 days; however, evidence for the most effective dressing type is inconclusive.If treated inappropriately, or left untreated, minor skin tears can become chronic or complicated wounds, yet prevalence and treatment of hospital‐acquired injuries are under‐reported. What this paper adds? Based on our per‐protocol results, an adhesive silicone foam dressing may be superior, as it produced clinically significant healing of 86% of skin tears at 3 weeks compared to 59% with the meshed silicone interface dressing.Based on the methods and results from this pilot study, a future definitive trial would be feasible but would need to account for a relatively large loss to follow‐up rate. The implications of this paper: Using our intention‐to‐treat results, a future study would need a sample size of 103 per arm to be sufficiently powered, which may be impractical to achieve within a single hospital setting; thus, a multi‐site study would be advisable. [ABSTRACT FROM AUTHOR]

Background: The prevalence of sexually transmitted diseases (STDs) remains high worldwide in today's society, especially among young people. Youth education on STDs could help to reduce the prevalence of the condition in society and prevent new cases. Aim: The aim of this study is to assess the effectiveness of peer‐based short‐form educational videos on youths' knowledge of STDs. Methods: This quasi‐experimental study was conducted in Turkey. The sample consisted of 121 students divided into experimental and control groups. Pre‐ and post‐test control group quasi‐experimental research design was employed in this study during the spring semester of the academic year 2021–2022. Peer‐based short‐form educational videos created by nursing students were used as an intervention. The survey form and Sexually Transmitted Disease Knowledge Questionnaire were used to collect data. Results: Participants with parental responsibilities and had previous STD experience had higher knowledge score than the other subgroups. There was a significant main effect of peer‐based short‐form educational video on participants overall knowledge score of STDs. Additionally, the effect of intervention continued at 12‐week follow‐up measurement. Conclusion: Peer‐based short‐form educational videos increase young people's knowledge of STD, and the impact of the intervention continued at 12‐week follow up. Summary statement: What is already known about this topic? Sexually transmitted diseases continue to be prevalent in society, particularly among young people.Sexually transmitted diseases can lead to serious health conditions and have a significant impact on sexual and reproductive health.The effectiveness of internet‐based education and lectures on sexually transmitted diseases has already been investigated.Little research has been addressed to determine the impact of educational materials, which are short videos on knowledge of sexually transmitted diseases created by utilizing nursing students' peer assessment. What this paper adds? Peer‐based short‐form educational videos increase young people's sexually transmitted disease knowledge.People with parental responsibilities and a previous sexually transmitted infections responded to interventions more favourably.The effects of peer‐based short‐form educational videos persisted 3 months afterwards. The implications for this paper: This cost‐free method has a potential to be widely used as a public health intervention to educate young people on sexually transmitted diseases.The peer‐based short‐form educational videos can be combined with other interventions to increase young people's knowledge of sexually transmitted diseases. [ABSTRACT FROM AUTHOR]

The quality of the very early emotional experiences in a child's life are recognized today as foundational in the mental health of becoming an adult. Unsurprisingly, clinicians and health authorities agree on the importance of early detection and treatment of any mental health issues experienced by the preschool child. This is even more important and challenging as young children do not yet have the language skills necessary to express their distress. But do the caregivers in charge of these populations have the best tools at their disposal to carry out that important mission in an efficient and scientifically robust manner reflecting the latest research findings and scientific literature? This is the question we try to answer in this paper. We revisited the theoretical underpinnings behind the concept of mentalization as playing a key role in the ability to understand the other's inner reality. We then carried out an extensive review of scientific papers written over the past 30 years on the subject. We examined mental representations of the adult on the child and analyzed those mentalizations as key inputs. We focused on extracting cross analyses of the mentalizations of one child by several adults with different functions in the life of the child. In this process, we used the PRISMA methodology applied to large international medical databases. We found that the qualitative approach, usually associated with a lengthy process, has been overwhelmingly used in trying to assess patients' mental states and to analyze the mentalizations on the patient, adult or child. Furthermore, cross analyses of mentalizations from more than one adult on a given child were almost nonexistent, despite having high epistemic and clinical potential. There is a dearth of reliable quantitative tools, able to capture and analyze the mentalizations on a patient, that are scientifically robust, transposable, and easy to implement in a clinical setting. The absence of such tools for medical professionals in charge of assessing preschool children contributes, in our view, the low detection and poor treatment of mental disorders in that particularly vulnerable population. We believe there is here an urgent unmet need and that such tools should be designed, validated, and deployed into the target populations as early as possible. [ABSTRACT FROM AUTHOR]

Background: The lack of a clear answer regarding the efficacy of physiotherapy in the treatment of cubital tunnel syndrome (CuTS) has led to attempts to critically assess the scientific studies conducted to date. Materials and Methods: Two databases (MEDLINE via PubMed and PEDro) and Google Scholar were used to search for papers. The inclusion criteria were randomized controlled trials, case series, and case reports that evaluate the effects of physiotherapy in the treatment of patients with CuTS. Results: A total of 18 studies met the eligibility criteria, capturing a total of 425 participants. Seven papers were randomized controlled trials, three more described prospective studies without a control group, and eight papers contained case reports. An analysis of the literature evaluating the effectiveness of various forms of broadly defined physiotherapy indicates that their use can have a beneficial effect in reducing many subjective and objective symptoms and improving function. In the majority of papers included in this review, their authors indicated positive therapeutic effects. Only one randomized controlled trial reported no change following therapy. It can therefore be stated that the results of the research conducted so far are optimistic. However, only 7 of the 18 papers were randomized controlled trials, while 3 were prospective studies, and 8 papers were case studies, in which 23 people with CuTS were studied. Conclusions: The small number of randomized clinical trials and their considerable heterogeneity do not allow firm conclusions to be drawn about the effectiveness of physiotherapy in the conservative treatment of CuTS. [ABSTRACT FROM AUTHOR]

Background: The SAVVY project aims to improve the analyses of adverse events (AEs) in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). This paper summarizes key features and conclusions from the various SAVVY papers. Methods: Summarizing several papers reporting theoretical investigations using simulations and an empirical study including randomized clinical trials from several sponsor organizations, biases from ignoring varying follow-up times or CEs are investigated. The bias of commonly used estimators of the absolute (incidence proportion and one minus Kaplan-Meier) and relative (risk and hazard ratio) AE risk is quantified. Furthermore, we provide a cursory assessment of how pertinent guidelines for the analysis of safety data deal with the features of varying follow-up time and CEs. Results: SAVVY finds that for both, avoiding bias and categorization of evidence with respect to treatment effect on AE risk into categories, the choice of the estimator is key and more important than features of the underlying data such as percentage of censoring, CEs, amount of follow-up, or value of the gold-standard. Conclusions: The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. Whenever varying follow-up times and/or CEs are present in the assessment of AEs, SAVVY recommends using the Aalen-Johansen estimator (AJE) with an appropriate definition of CEs to quantify AE risk. There is an urgent need to improve pertinent clinical trial reporting guidelines for reporting AEs so that incidence proportions or one minus Kaplan-Meier estimators are finally replaced by the AJE with appropriate definition of CEs. [ABSTRACT FROM AUTHOR]

Background/aims: The value of using qualitative methods within clinical trials is widely recognised. How qualitative research is integrated within trials units to achieve this is less clear. This paper describes the process through which qualitative research has been integrated within Cardiff University's Centre for Trials Research (CTR) in Wales, UK. We highlight facilitators of, and challenges to, integration. Methods: We held group discussions on the work of the Qualitative Research Group (QRG) within CTR. The content of these discussions, materials for a presentation in CTR, and documents relating to the development of the QRG were interpreted at a workshop attended by group members. Normalisation Process Theory (NPT) was used to structure analysis. A writing group prepared a document for input from members of CTR, forming the basis of this paper. Results: Actions to integrate qualitative research comprised: its inclusion in Centre strategies; formation of a QRG with dedicated funding/roles; embedding of qualitative research within operating systems; capacity building/training; monitoring opportunities to include qualitative methods in studies; maximising the quality of qualitative research and developing methodological innovation. Facilitators of these actions included: the influence of the broader methodological landscape within trial/study design and its promotion of the value of qualitative research; and close physical proximity of CTR qualitative staff/students allowing sharing of methodological approaches. Introduction of innovative qualitative methods generated interest among other staff groups. Challenges included: pressure to under-resource qualitative components of research, preference for a statistical stance historically in some research areas and funding structures, and difficulties faced by qualitative researchers carving out individual academic profiles when working across trials/studies. Conclusions: Given that CTUs are pivotal to the design and conduct of RCTs and related study types across multiple disciplines, integrating qualitative research into trials units is crucial if its contribution is to be fully realised. We have made explicit one trials unit's experience of embedding qualitative research and present this to open dialogue on ways to operationalise and optimise qualitative research in trials. NPT provides a valuable framework with which to theorise these processes, including the importance of sense-making and legitimisation when introducing new practices within organisations. [ABSTRACT FROM AUTHOR]

JAMA: Journal of the American Medical Association has published a Special Communication titled "The Integration of Clinical Trials With the Practice of Medicine: Repairing a House Divided," which discusses the need to integrate clinical trials with clinical practice. The authors highlight the separate missions and infrastructures of clinical trialists and clinicians, leading to inefficiencies and limitations in trials. They propose solutions such as implementation science, novel statistical analysis approaches, and integration of trials with electronic health records. JAMA is launching a new series called "Integrating Clinical Trials and Practice" to explore innovations in trial design, funding, regulation, education, and application. The goal is to align clinical trials with clinical practice and improve patient care. [Extracted from the article]

Purpose: Advances in germline genetics, and related therapeutic opportunities, present new opportunities and challenges in prostate cancer. The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group was established to address genetic testing for men with prostate cancer, especially those with advanced disease undergoing testing for treatment-related objectives and clinical trials. Methods: The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group met monthly to discuss the current state of genetic testing of men with prostate cancer for therapeutic or clinical trial purposes. We assessed current institutional practices, developed a framework to address unique challenges in this population, and identified areas of future research. Results: Genetic testing practices in men with prostate cancer vary across institutions; however, there were several areas of agreement. The group recognized the clinical benefits of expanding germline genetic testing, beyond cancer risk assessment, for the goal of treatment selection or clinical trial eligibility determination. Genetic testing for treatment selection should ensure patients receive appropriate pretest education and consent and occur under auspices of a research study whenever feasible. Providers offering genetic testing should be able to interpret results and recommend post-test genetic counseling for patients. When performing tumor (somatic) genomic profiling, providers should discuss the potential for uncovering germline mutations and recommend appropriate genetic counseling. In addition, family members may benefit from cascade testing and early cancer screening and prevention strategies. Conclusion: As germline genetic testing is incorporated into practice, further development is needed in establishing prompt testing for time-sensitive treatment decisions, integrating cascade testing for family, ensuring equitable access to testing, and elucidating the role of less-characterized germline DNA damage repair genes, individual gene-level biologic consequences, and treatment response prediction in advanced disease. [ABSTRACT FROM AUTHOR]

Progress toward improvement in cancer therapy relies on clinical trials. Yet, only a minority of eligible patients with cancer enroll as a result of multiple barriers at the patient, investigator, center, and national level. However, the rise of the Internet and mobile technology has created a slew of tools with medical applications, from Web sites to apps to social media platforms, all of which may aide clinicians in our quest to improve the clinical research enterprise. SWOG is one of five members in the National Cancer Institute's National Clinical Trials Network--the nation's oldest and largest publicly funded cancer research network--and is taking a leadership role in exploring and testing the promise of digital engagement through the empaneling of the Digital Engagement Committee. This article outlines the mission, principles, and priorities of the Digital Engagement Committee and proposes how this work may inform the use of digital tools for the cancer research community and, hopefully, translate to improved outcomes for our patients. [ABSTRACT FROM AUTHOR]

Progress toward improvement in cancer therapy relies on clinical trials. Yet, only a minority of eligible patients with cancer enroll as a result of multiple barriers at the patient, investigator, center, and national level. However, the rise of the Internet and mobile technology has created a slew of tools with medical applications, from Web sites to apps to social media platforms, all of which may aide clinicians in our quest to improve the clinical research enterprise. SWOG is one of five members in the National Cancer Institute’s National Clinical Trials Network—the nation’s oldest and largest publicly funded cancer research network—and is taking a leadership role in exploring and testing the promise of digital engagement through the empaneling of the Digital Engagement Committee. This article outlines the mission, principles, and priorities of the Digital Engagement Committee and proposes how this work may inform the use of digital tools for the cancer research community and, hopefully, translate to improved outcomes for our patients. [ABSTRACT FROM AUTHOR]

Background Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato . The most frequent clinical manifestations are erythema migrans and Lyme neuroborreliosis. Currently, a large volume of diagnostic testing for LB is reported, whereas the incidence of clinically relevant disease manifestations is low. This indicates overuse of diagnostic testing for LB with implications for patient care and cost-effective health management. Aim The recommendations provided in this review are intended to support both the clinical diagnosis and initiatives for a more rational use of laboratory testing in patients with clinically suspected LB. Sources This is a narrative review combining various aspects of the clinical and laboratory diagnosis with an educational purpose. The literature search was based on existing systematic reviews, national and international guidelines and supplemented with specific citations. Implications The main recommendations according to current European case definitions for LB are as follows. Typical erythema migrans should be diagnosed clinically and does not require laboratory testing. The diagnosis of Lyme neuroborreliosis requires laboratory investigation of the spinal fluid including intrathecal antibody production, and the remaining disease manifestations require testing for serum antibodies to B. burgdorferi . Testing individuals with non-specific subjective symptoms is not recommended, because of a low positive predictive value. [ABSTRACT FROM AUTHOR]

Background Allergen exposure chambers ( AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. Methods For this task force initiative of the European Academy of Allergy and Clinical Immunology ( EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. Results The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. Conclusion This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future. [ABSTRACT FROM AUTHOR]

The lack of ideal measurement of treatment efficacy is a well acknowledged problem in the epilepsy community, both in clinical care and clinical trials. Whilst still the current gold-standard, self-reported seizure frequency significantly underestimates the true number of seizures and does not account for any other at least equally important outcome parameters, such as neurodevelopment and cognition. With the rise of disease modifying treatments, the need for more reliable endpoints in practice and clinical trials becomes more pressing. In this paper we assembled an expert panel to discuss the nature of these needs, current limitations, and obstacles based on a survey amongst these experts who were queried about the most important issues regarding the use of electroencephalography (EEG) parameters as endpoints in clinical drug and device development. A structured survey was sent to a group of experts in the design and conduct of epilepsy trials in adults and children. This was followed by a virtual in-person meeting discussing the results of the trial and identifying a list of most important issues. Six clinical trialists and 5 individuals from pharmaceutical companies returned the survey containing 14 questions, and 8 clinical trialists and 10 pharma-representatives attended the meeting. Three main issues were identified (1) lack of accuracy of seizure diaries due to nocturnal seizures, subtle motor seizures, impairment of consciousness and lack of awareness of the seizure by the patient (2) inter-rater variability of EEG assessment (3) lack of standardization regarding definition(s) of seizures (clinical and electrographic), EEG recording methods and EEG data management. Recommended solutions included (1) validation of EEG parameters as biomarkers and use of wearables (2) development of a manual that describes EEG rating criteria, protocol for validation by > 1 central reader and use of a resolution of disagreements reporting template (3) standardization of EEG recording, data management and reporting. Current developments in research and technology seem promising to advance the use of EEG parameters as potential endpoints and offer partial solutions to the current needs. However, continuous, focused and collaborative efforts of all stakeholders (academia, industry and regulatory agencies) are needed to formulate guidelines, validate emerging technologies and approve them for use in trials. It is the intent of this opinion "position paper" to stimulate those efforts. • Multiple potential EEG are parameters known and some already used. • EEG parameters must be selected to address a specific question. • Due to significant heterogeneity of seizure types, syndromes, the use of EEG will vary according to purpose. • Evidence is required to "validate" the utility of a specific measure to a specific question before use in a trial. [ABSTRACT FROM AUTHOR]

ABSTRACT In covariate‐adaptive or response‐adaptive randomization, the treatment assignment and outcome can be correlated. Under this situation, the re‐randomization test is a straightforward and attractive method to provide valid statistical inferences. In this paper, we investigate the number of repetitions in tests. This is motivated by a group sequential design in clinical trials, where the nominal significance bound can be very small at an interim analysis. Accordingly, re‐randomization tests lead to a very large number of required repetitions, which may be computationally intractable. To reduce the number of repetitions, we propose an adaptive procedure and compare it with multiple approaches under predefined criteria. Monte Carlo simulations are conducted to show the performance of different approaches in a limited sample size. We also suggest strategies to reduce total computation time and provide practical guidance in preparing, executing, and reporting before and after data are unblinded at an interim analysis, so one can complete the computation within a reasonable time frame. [ABSTRACT FROM AUTHOR]

Purpose: This paper reports a systematic review and meta-analysis protocol that will be used to evaluate the efficacy and safety of pembrolizumab, alone or combined with bevacizumab and other therapies, in adult women with cervical carcinoma from stage IB2 onwards. Methods: The protocol follows PRISMA-P recommendations and was registered on PROSPERO (CRD42024531233). The search will be conducted without restrictions on language and year of publication in the following databases: Pubmed, Embase, Scopus, Web of Science, Cancerlit, The World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) and Clinical Trials Registry Platform. Grey literature will be searched using the following sources: Clinicaltrials.gov, Google Scholar and Opengrey. Manual search will be carried out for the reference lists of eligible studies. The studies will be selected independently by two reviewers and all completed or ongoing randomized clinical trials that evaluated the efficacy and safety of pembrolizumab, used alone or combined with chemotherapy, radiotherapy, bevacizumab or surgery, in adult women diagnosed with cervical cancer, will be included. The data extraction will include population characteristics, type of treatment and main outcomes of studies. The methodological quality of the studies will be assessed using the Cochrane Risk of Bias 2.0. The certainty of the evidence will be rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Conclusions: The findings will be presented in narrative summary tables and a quantitative synthesis will be conducted using the 'meta' package of R software, version 4.3.1. This future systematic review may contribute with quality evidence for clinical decision-making on the use of pembrolizumab in women with cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Africa, specifically the Sub-Saharan region, has had numerous medical technology clinical trials to address the various healthcare challenges around infectious diseases, non-communicable diseases, and nutritional disorders it is facing. Medical device clinical trials provide performance data in terms of safety, efficacy, and efficiency, which is a requirement before commercialization. Key players such as academicians, governments, international organizations, and funders collaborate to drive these trials, but their growth in Africa remains slower compared to other parts of the globe. This paper aims to evaluate the number of medical device clinical trials conducted in different African countries that are registered on the clinicaltrials.gov website. Methods: Data on medical device clinical trials was mined from clinicaltrials.gov website accessed on 22nd September, 2022. The data extracted was analyzed and cleaned in Microsoft Excel and R. Countries were grouped into regions and descriptive statistical analyses for each region were done. Additionally, frequency distributions were also generated and no inferential statistical tests were performed, as the primary focus of this analysis was to describe the distribution of medical conditions across regions. Results: Thirty-one African countries had registered medical device clinical trials on the website with the majority taking place in Egypt and South Africa. Medical device trials for heart related issues took longer to complete compared to other conditions. Malaria, HIV, and male circumcision related device trials were mainly conducted in Eastern and Southern Africa while trials related to dental, fertility, and obesity were concentrated in Northern Africa. Female reproductive health issues were studied equally across all regions. Some African countries did not have any trials registered on clinicaltrials.gov website. Conclusion: Findings from this study clearly show the disparity in the number, status, and duration of medical device clinical trials across various African countries. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, the race to find an effective vaccine or treatment saw an 'extraordinary number' of clinical trials being conducted. While there were some key success stories, not all trials produced results that informed patient care. There was a significant amount of waste in clinical research during the pandemic which is said to have hampered an evidence-based response. Conducting trials which could have been predicted to fail to answer the research question (e.g. because they are not large enough to provide a definitive result) is not only a waste of resources but also a breach of research participants' trust and a violation of research ethics. The issues seen in COVID-19 clinical trials are symptomatic of a wider trial design crisis where many trials do not provide informative results. This paper examines the roles of key stakeholders in delivering ethical and informative trials and whether guidance published by 'The Good Clinical Trials Collaborative' could be used to align key stakeholder groups and enable a joined-up approach to improve clinical trial design. [ABSTRACT FROM AUTHOR]

Background: Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. Methods: A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. Results: An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The 'ALABAMA unit' within SystmOne was also created and provided a secure efficient environment to access participants' EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. Conclusions: ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. Trial registration: ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216. [ABSTRACT FROM AUTHOR]

Premature ventricular contractions (PVCs) are a common finding in clinical practice, requiring a full diagnostic work-up in order to exclude an underlying cardiomyopathy. Still, in a substantial proportion of patients, these investigations do not identify any substrate, and the PVCs are labelled as idiopathic. Cardiac magnetic resonance (CMR) has proven in the last decades as the method of choice for the exploration of patients with cardiomyopathies, since it can identify subtle changes in the myocardial tissue and help with risk stratification. In patients with idiopathic PVCs and a high PVC burden, several studies report the presence of late gadolinium enhancement (LGE) at CMR, which can offer additional diagnostic and prognostic benefits, as well as assistance in catheter ablation procedures, as the risk for adverse cardiac and risk for arrhythmic events events is higher compared to patients without scar. This paper focuses on the impact of the presence of LGE in patients with idiopathic PVCs, reviewing all the relevant studies published so far, including randomized controlled clinical trials, prospective or retrospective cohort studies, case series and case reports as well as systematic reviews. [ABSTRACT FROM AUTHOR]

In 2021, the US Congress passed the Accelerating Access to Critical Therapies for Amyotrophic Lateral Sclerosis Act. The law encourages development of "tools, methods, and processes" to improve clinical trial efficiency for neurodegenerative diseases. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an outcome measure administered during in-person clinic visits and used to support investigational studies for persons living with amyotrophic lateral sclerosis. Availability of a standardized, remote-use version of the ALSFRS-R may promote more inclusive, decentralized clinical trials. A scoping literature review was conducted to identify existing remote-use ALSFRS-R tools, synthesize feasibility and comparability of administration modes, and summarize barriers and facilitators to inform development of a standardized remote-use ALSFRS-R tool. Included studies reported comparisons between remote and in-person, clinician-reported, ALSFRS-R administration and were published in English (2002-2022). References were identified by searching peer-reviewed and gray literature. Twelve studies met the inclusion criteria and were analyzed to compare findings within and across modes of administration. Remote modes of ALSFRS-R administration were categorized into 4 nonmutually exclusive categories: telephone (n = 6), videoconferencing (n = 3), computer or online platforms (n = 3), mobile applications and wearables (n = 2), and 1 unspecified telemedicine modality (n = 1). Studies comparing in-person to telephone or videoconferencing administration reported high ALSFRS-R rating correlations and nonsignificant between-mode differences. There is insufficient information in the ALSFRS-R literature to support remote clinician administration for collecting high quality data. Future research should engage persons living with amyotrophic lateral sclerosis, care partners, and providers to develop a standardized remote-use ALSFRS-R version. • Telephone and videoconferencing modalities have shown promise as platforms for conducting clinical outcome assessments remotely. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is a commonly used clinical outcome assessments tool in investigative clinical trials for ALS, but no single, standardized, remote administration of the paper ALSFRS-R was identified in this review. • Limited psychometric data in support of remote modalities are reported in the evaluated literature including some indications of moderate reliability between modalites. Additionally, the ALSFRS-R was administered in non-English languages in almost half of the articles. The strength of the cultural adaptations is unknown making it challenging to determine if the results are fit for regulatory decision-making purposes. • Our review suggests a need for further research on the feasibility (including cross-cultural aspects), comparability, and psychometric performance of implementing standardized remote-use ALSFRS-R modalities. [ABSTRACT FROM AUTHOR]

Rationale and Aim: Testing of new drugs through clinical trials is essential in efforts to increase generalizable knowledge. Little is known about the medical students' perception of their participation as research subjects in clinical trials. The aim of this study was to examine the willingness and attitudes of medical students towards participation as volunteer subjects in clinical trials. Methods: A cross‐sectional study was conducted among 297 medical students in years 4, 5 and 6 at the University of Belgrade, from October to December 2023. Participants completed a pen‐and‐paper questionnaire including demographic characteristics, opinions on their participation in clinical trials, and attitudes towards clinical trials in general. The validity of the attitude scale was verified. Results: One in five medical students expressed a positive opinion about their participation in clinical trials, with the majority (about one‐half) remaining undecided. General attitudes of students about research and their participation were positive. Students with prior blood donation experience were more willing to participate. Lower socioeconomic status and volunteering experience were also associated with stronger positive attitudes towards clinical trials in general. Conclusion: Most students were undecided about their participation, but their attitudes towards clinical trials in general were positive. Positive attitudes towards clinical trials did not uniformly translate to the willingness for personal participation. Promotion of blood donation and volunteering at universities could help to increase the interest in clinical trials as volunteer subjects. [ABSTRACT FROM AUTHOR]

Introduction: Numerous treatment modalities have been suggested for managing tinnitus. Tailor-Made Notched Music Training (TMNMT) is a viable strategy in music therapy for tinnitus management. Many research studies have examined the effectiveness and potential benefits of this intervention. This study aims to assess the effectiveness of TMNMT in treating chronic tinnitus. Methods: This systematic review and meta-analysis study used a research methodology that covered up until February 2023. The search was conducted across academic databases including Google Scholar, PubMed, Scopus, and Web of Science. A total of 234 papers were evaluated, and seven relevant clinical trials were included. Results: The meta-analysis, which included five studies using the tinnitus handicap inventory (THI), showed no statistically significant effect of TMNMT on tinnitus handicap after 3 and 6 months of intervention (dppc2: − 0.99, 95%CI − 2.94 to 0.96; I2 = 79.96%, p = 0.00), (dppc2 − 1.81, 95%CI − 5.63 to 2.01; I2 = 79.96%, p = 0.00). However, four out of five studies using the total Visual Analogue Scale (VAS) or its subscale showed positive effects of TMNMT on chronic tinnitus. Unfortunately, there were not enough articles to conduct a meta-analysis on this outcome. Conclusion: Although the meta-analysis did not show a statistically significant effect of TMNMT on tinnitus handicap, the large effect size observed after at least 3 months of intervention suggests that this method may potentially decrease tinnitus handicap if more studies are conducted. Due to the limited number of studies, subgroup analysis could not be performed to analyze potential causes of heterogeneity. Therefore, further high-quality clinical trials are necessary to draw a definitive conclusion and evaluate the impact of different variables, techniques, and outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking. Materials and methods: A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment. Results: 15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic. Conclusion: Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered. [ABSTRACT FROM AUTHOR]

This paper aims to contribute fresh insights into youth participatory action research (YPAR) by using bell hooks' engaged pedagogy to illuminate the process of co-designing a program for transition beyond secondary school. Engaged pedagogy is a critical pedagogy that combines critical consciousness and radical wholeness and seeks to foster a learning community. The 10-week YPAR included six staff collaborators (SCs) and five youth collaborators (YCs). Data comprised recordings of weekly collaborative group meetings; group interviews with SCs and YCs; and reflections and artefacts such as planning documents, graphic organisers and photographs. Informed by engaged pedagogy, findings are represented in two themes. First, YCs and SCs raised critical consciousness by collectively unpacking and critiquing the concept of transition. Critical consciousness allowed YCs to share their lived experiences and critique the dominant deficit discourse that represents transition as a linear process that needs to be smoothed by expert adults. Second, YCs and SCs demonstrated what hooks describes as radical wholeness, by bringing their whole selves to the YPAR. While some SCs and YCs struggled with the messiness of co-design as they negotiated expectations and roles, they learned to be honest and share their emotions, becoming what hooks describes as a learning community. Using an engaged pedagogy lens, we conclude by advocating for a holistic approach for YPAR in which educators take the risk of being vulnerable, sharing uncertainty and discomfort while encouraging youth to also take risks by bringing their whole selves to the process. [ABSTRACT FROM AUTHOR]

Diabetic wounds, a prevalent diabetes complication, pose significant challenges in treatment. MicroRNA-engineered exosomes (miR-exo) are a promising new treatment for diabetic wounds; however, their mechanism remains to be completely understood. Therefore, we aimed to conduct a meta-analysis to evaluate the efficacy of miR-exo treatment in the management of diabetic wounds. To achieve this aim, academic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, were searched for papers published before July 4, 2023. Outcome indicators (e.g., rate of wound healing, neovascular count, rate of re-epithelialization, deposition of collagen, breadth of scar, and inflammatory factors) were assessed. Six studies (total of 72 animals) met inclusion criteria and were analyzed. The amalgamated data revealed that miR-exo treatment exhibited superior results compared to those of control therapy. miR-exo treatment significantly enhanced the rate of wound healing, increased the number of neovascular formations, accelerated the rate of re-epithelialization, increased collagen deposition, reduced scar width, while significantly downregulating the expression of inflammatory factors. Our findings indicate that miR-exo treatment augments overall diabetic wound healing, especially when administered in conjunction with innovative dressings. To ascertain the optimal parameters for miR-exo treatment in managing diabetic wounds, future studies must encompass rigorous, large-scale, double-blinded clinical trials while incorporating long-term follow-up assessments for enhanced reliability and accuracy. [ABSTRACT FROM AUTHOR]

AbstractThe efficacy of probiotics, prebiotics, or synbiotics in children and adolescents with overweight or obesity remains uncertain. This systematic review evaluates their intervention effects through a network meta-analysis of randomized clinical trials (RCTs). Searches of 4 electronic databases until January 7, 2024, yielded 17 papers reporting on 15 RCTs involving 820 participants. Multiple-strain probiotics (MSP) showed significant efficacy in reducing BMI (Mean Difference (MD) −2.13 kg/m2, 95% credible interval (CrI) [−2.7, −1.57]), waist circumference (MD −1.34 cm, 95% CrI [−2.33, −0.35]), total cholesterol (MD −6.55 mg/dL, 95% CrI [−10.61, −2.45]), triglycerides (MD −3.71 mg/dL, 95% CrI [−5.76, −1.67]), leptin (MD −3.99 ng/mL, 95% CrI [−4.68, −3.3]), and hypersensitive C-reactive protein (Hs-CRP) (MD −1.21 mg/L, 95% CrI [−1.45, −0.97]). Synbiotics were effective in reducing BMI-z score (MD −0.07, 95% CrI [−0.10, −0.04]) and LDL-C (MD −1.54 mg/dL, 95% CrI [−1.98, −1.09]) but led to a slight increase in fasting glucose (MD 1.12 mg/dL, 95% CrI [0.75, 1.49]). Single-ingredient prebiotics and single-strain probiotics also had some beneficial effects on BMI and Hs-CRP, respectively. Moderate to low evidence suggests MSP may be a potential choice for improving BMI and reducing lipids, leptin, and Hs-CRP levels, implying that MSP could aid in managing pediatric obesity and related metabolic issues by modulating the gut microbiota. Although synbiotics show their favorable effects on body metrics and lipid control, their potential impact on blood glucose currently prevents them from being an alternative to MSP for treating pediatric obesity. Further large-scale, well-designed studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Fibroblast cells have the ability to improve skin conditions through regenerative medicine and cell-based therapies. The purpose of this scoping review is to assess the contribution of fibroblast cells to skin homeostasis and extracellular matrix deposition in clinical trials involving skin disorders and cosmetic applications. Methods: Using targeted search terms, published publications from January 2000 to August 2023 that addressed fibroblast uses in clinical trials of skin conditions were obtained from bibliographic databases like PubMed, Scopus, and Web of Science (WoS). Precise inclusion and exclusion criteria were used during the screening process. The potential benefits of induction treatment with fibroblasts lead to the choosing of clinical trials for this kind of treatment. Results: Out of the 820 published ppapers initially identified, only 35 studies fulfilled our meticulous eligibility criteria after careful screening. To ensure clarity, we methodically eliminated any duplicate or irrelevant published papers, thereby offering a transparent account of our selection process. Conclusion: This study highlights the advantages of fibroblast therapy in treating skin conditions such as diabetic foot, venous leg ulcers, and cosmetic reasons. Fibroblasts possess remarkable regenerating capabilities, making dermal fibroblast therapy crucial in cell-based and skin regenerative treatments. Nevertheless, additional research is required for more disorders and cosmetic applications. [ABSTRACT FROM AUTHOR]

AbstractA dose-response curve is essential for determining the safe dosage of a drug and is widely used in bioassay and in phase 1 clinical trials. It is generally accepted that the probability of death or the probability of dose-limiting toxicity is a non-decreasing function of the dose. This paper proposes and develops an effective point-wise confidence interval for an isotonic dose-response curve, a problem without a satisfactory solution so far. We show that one subset of the observations informs the lower limit while the other subset informs the upper limit. A partial likelihood ratio test using these subsets of observations is fully investigated. The resulting confidence interval is compared to three existing methods (Morris, Meyer, and Oron) in an extensive simulation study. The new method produces tight intervals while maintaining coverage. It is therefore preferred when maintaining an actual coverage probability is crucial as often in a regulatory environment. The new method extends to one-way ANOVA of a continuous response variable in a straightforward way. An R function is provided. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment options for patients with advanced renal cancer are limited, as one of the main methods, chemotherapy, is prone to drug resistance in the course of treatment. There have been numerous studies confirming that ferroptosis is involved in the development of renal cancer and drug resistance during treatment. In this review, we provide new insights into the resistance of classical chemotherapy drugs sorafenib and sunitinib in renal cancer and explore the mechanism of different types of ferroptosis-related drugs to treat renal cancer, such as herb extract medicine, ferroptosis inducers, natural compounds, nanomaterials, etc. We have also conducted an in-depth discussion on the application of ferroptosis-related drugs in the clinical treatment of renal cancer. Renal cancer is a common and serious malignant tumor of the urinary system. While surgery effectively treats early-stage renal cancer, advanced cases pose a significant challenge due to poor treatment outcomes and chemotherapy resistance. Therefore, there is an urgent need to develop alternative therapeutic strategies. Ferroptosis is a newly defined form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which plays a critical role in tumor progression and drug resistance. Recent studies have shown that ferroptosis is involved in the occurrence and development of renal cancer, and ferroptosis-related genes can induce cell apoptosis and can be used as potential biomarkers for early diagnosis of renal cancer and participate in drug resistance of renal cancer chemotherapy. With the continuous improvement of the mechanism of ferroptosis, drugs targeting ferroptosis for the treatment of renal cancer are emerging in an endless stream. Based on the theoretical basis of the occurrence of ferroptosis, this paper reviewed drug-induced ferroptosis in renal cancer cells from the aspects of herbal medicine, natural compounds, drug resistance mechanisms, and nanomaterials, and delves into the clinical application potential of ferroptosis-related drugs in the treatment of renal cancer. [ABSTRACT FROM AUTHOR]

The use of companion diagnostics has become a standard in precision oncology in the context of ongoing therapeutic innovation. However, certain limitations make their application imperfect in current practice. This position paper underscores the need to broaden the notion of companion testing, considering the potential of emerging technologies, including computational biology, to overcome these limitations. This wave of progress should impact not only our representation of the analytical tool itself but also the nature of the tumoral sample under analysis (liquid biopsies). The complex inter-relationship between companion test guided-personalized therapy, and health agency policies for new drug agreements will also be discussed. [ABSTRACT FROM AUTHOR]

In recent years, several strategies have been developed for the treatment of transthyretin-related amyloidosis, whose complex clinical manifestations involve cardiomyopathy and polyneuropathy. In view of this, transthyretin stabilizers represent a major cornerstone in treatment thanks to the introduction of tafamidis into therapy and the entry of acoramidis into clinical trials. However, the clinical treatment of transthyretin-related amyloidosis still presents several challenges, urging the development of new and improved therapeutics. Bearing this in mind, in this paper, the most promising among the recently published transthyretin stabilizers were reviewed. Their activity was described to provide some insights into their clinical potential, and crystallographic data were provided to explain their modes of action. Finally, structure–activity relationship studies were performed to give some guidance to future researchers aiming to synthesize new transthyretin stabilizers. Interestingly, some new details emerged with respect to the previously known general rules that guided the design of new compounds. [ABSTRACT FROM AUTHOR]

In this pilot study we investigated whether metalinguistic explanations (ME) could help young learners (YL) boost their metalinguistic awareness (MA) and, in turn, improve their accuracy at the time of using two grammatical features. Although previous research has established a positive correlation between MA, metalinguistic knowledge (MK) and better learning outcomes in a foreign language (FL), few interventional studies have been conducted in this regard. Using a pretest/post-test design, an intact classroom (N = 20) of L1 Spanish 10-year-old students of English as a FL (EFL) was divided into an experimental and a control group. First, both groups completed an individual pen-and-paper MA test. Then, they were paired up according to their proficiency level and asked to carry out a dictogloss task, in which they had to negotiate their final written output. Before the post-test phase, the experimental group was asked to engage with a learning sequence of ME concerning two problematic English grammatical features: third person –s and his/her. These explanations also included the definitions of metalinguistic terminology. Additionally, an individual three-step verbal protocol was carried out after the post-tests to triangulate collaborative data. The results showed a moderate effect of the treatment in MA scores. Likewise, ME had a large effect on the use of third person –s during the interaction, as well as a moderate effect on the accurate use of his/her. Also, the treatment group dyads produced significantly more episodes of noticing during the post-test task and at a higher resolution rate than during the pretest stage. These findings support the use of explicit learning devices such as ME with YL of EFL, as they seem to promote MA and increase their accuracy even in input-limited learning conditions. [ABSTRACT FROM AUTHOR]

Background: Despite Africa's significant infectious disease burden, it is underrepresented in global vaccine clinical trials. While this trend is slowly reversing, it is important to recognize and mitigate the challenges that arise when conducting vaccine clinical trials in this environment. These challenges stem from a variety of factors peculiar to the population and may negatively impact adverse event collection and reporting if not properly addressed. Methods: As a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), we have conducted 12 phase 1 to 3 vaccine trials over the past 10 years. In this article, we discuss the challenges we face and the strategies we have developed to improve the collection and reporting of adverse events in low-income settings. Outcome. Healthcare-seeking behaviors in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox healthcare; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. Instead, round-the-clock care is provided to trial participants, facilitating safety follow-up. Constraints in the healthcare system in the Gambia such as limitations in diagnostic tools limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the Medical Research Council Unit maintains a Clinical Services Department, offering medical care and diagnostic services to study participants. Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. Solicited adverse events are collected during home visits on paper-based or electronic report forms. Community engagement meetings are held before each study starts to inform community stakeholders about the study and answer any questions they may have. These meetings ensure that influential members of the community understand the purpose of the study and the risks and benefits of participating in the trial. This understanding makes them more likely to support participation within their communities. Conclusion: Conducting ethical vaccine clinical trials in resource-limited settings requires strategies to accurately collect and report adverse events. Our experiences from the Gambia offer insights into adverse event collection in these settings. [ABSTRACT FROM AUTHOR]

It is becoming increasingly popular to elicit informative priors on the basis of historical data. Popular existing priors, including the power prior, commensurate prior, and robust meta-analytic predictive prior, provide blanket discounting. Thus, if only a subset of participants in the historical data are exchangeable with the current data, these priors may not be appropriate. In order to combat this issue, propensity score approaches have been proposed. However, these approaches are only concerned with the covariate distribution, whereas exchangeability is typically assessed with parameters pertaining to the outcome. In this paper, we introduce the latent exchangeability prior (LEAP), where observations in the historical data are classified into exchangeable and non-exchangeable groups. The LEAP discounts the historical data by identifying the most relevant subjects from the historical data. We compare our proposed approach against alternative approaches in simulations and present a case study using our proposed prior to augment a control arm in a phase 3 clinical trial in plaque psoriasis with an unbalanced randomization scheme. [ABSTRACT FROM AUTHOR]

Whilst adolescence is often discussed as a challenging time, it is also a stage of life with tremendous potential for building positive skills that will support current and future mental health. This paper presents results from a pilot study of a mental health and stigma reduction program called The Inquiring Mind Youth, which is based on a series of programs that have previously demonstrated effectiveness in adult and workplace samples. The program was developed in collaboration with experts and youth and piloted in nine secondary schools across Canada (Calgary area and Eastern Coast). Data from 293 adolescent participants were collected using a pre-post-follow-up design. An overall medium effect size was found for both improved resilience skills (SMD = 0.49) and decreased stigmatizing attitudes (SMD = 0.38) pre-post program. An additional multi-level modelling analysis also showed improved resilience skills and decreased stigmatizing attitudes pre-post program, with more robust shifts in one geographic region (Calgary area). Further analysis showed that resilience improvements were retained at follow-up, with smaller effects. The results of this pilot study support ongoing work and development of programming that aims to foster resilience and reduce stigmatizing attitudes in young people. Highlights: A novel mental health promotion and stigma reduction program (The Inquiring Mind Youth) was developed and piloted in Canadian schools. Participants showed increased resilience skills, decreased stigmatizing attitudes, and increased willingness to seek help after participating in the program. Males saw more improvements than females on resilience, while the opposite was found with stigmatizing attitudes, with females decreasing significantly more. Results support efforts in program development aimed at fostering resilience and reducing stigmatizing attitudes in youth. [ABSTRACT FROM AUTHOR]

Clinical trial transparency is beneficial for patients, researchers, and the general public. However, rapidly evolving regulatory requirements for transparency have increased the information that will be published. Medical writers can play a key role in driving compliance with applicable regulations. This paper provides an overview of transparency regulations and provides some points for medical writers to consider in this rapidly evolving area. [ABSTRACT FROM AUTHOR]

• Minimal clinically important difference (MCID) is crucial in interpreting results in clinical trials that use patient reported outcome measures (PROMs). • We used two distribution-based approaches to determine the MCIDs for the patient assessment of constipation symptoms (PAC-SYM), patient assessment of upper gastrointestinal symptoms (PAGI-SYM), patient assessment of constipation-quality of life (PAC-QOL) and their subscales. • The two distribution-based approaches, multiplications of the standard deviation (SD) or standard error of the mean (SEM), produced similar results. Minimal clinically important difference (MCID) is important to establish as a meaningful outcome in research when using patient reported outcome measures (PROMs). We determined the MCID using the distribution-based approach for three measurements used as part of the GALAXY study, which is an observational prospective study on gastrointestinal (GI) symptoms in cystic fibrosis (CF). Four hundred and two persons with cystic fibrosis (PwCF) participated in the GALAXY study, all with baseline values available for all questionnaires. Mean age was 20.9 years (2.1- 61.1) with 75 females and 94 males under the age of 18 (42.04 %) and 118 females and 115 males aged 18 or older (57.99 %). MCID was measured for Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL) and their subscales. Two distribution-based approaches, defined as multiplications of the standard deviation (SD) or standard error of the mean (SEM), were used to approximate the MCID. The two distribution-based approaches for determining the MCID estimates produced comparable results in trends in MCIDs across the subscales and total scores. In general, MCID estimates of subscales for all three measurements were higher than their total score MCIDs. The one-half SD- and SEM-based MCID estimates for total scores of each questionnaire are as follows: PAC-SYM: 0.26 and 0.14; PAGI-SYM: 0.32 and 0.15; PAC-QOL: 0.27 and 0.18, respectively. This paper establishes initial MCIDs estimated by the distribution-based approach for the PAC-SYM, PAGI-SYM and PAC-QOL that can now be used to evaluate interventional studies that may impact gastrointestinal symptoms in PwCF. [ABSTRACT FROM AUTHOR]

Purpose: Cricopharyngeus muscle dysfunction (CPMD) is a common clinical occurrence with very few clear diagnostic criteria and multiple pathways for treatment. Incidence of CPMD is not known, but some data suggest around 25% of people with dysphagia experience some degree of CPMD, which negatively impacts swallowing safety and efficiency. Workup and treatment of CPMD can require multidisciplinary collaboration across laryngologists, speech-language pathologists with training in dysphagia management, and gastroenterologists. The purpose of this paper is to review what is known about CPMD and identify areas of future research in CPMD diagnosis and treatment. Methods: An overview of CPMD, relative treatments and disorders, and a discussion of future areas of research needed to improve clinical care of CPMD. Results: Details regarding historical background, pathophysiology and treatment practiced for CPMD are included. Conclusion: In summary, CPMD is a poorly defined disease due to a lack of understanding of its pathophysiology and the lack of consensus diagnostic criteria. Well-designed, prospective clinical trials are necessary to develop a better understanding of clinical incidence of CPMD, impact of the disorder on oropharyngeal swallowing, and how to approach treatment of the disorder surgically or in conjunction with therapy directed by a specialized speech-language pathologist. [ABSTRACT FROM AUTHOR]

In this paper, we discuss the Bile Acid Comparison and Harmonisation project, a sub-study of the Trial of URsodeoxycholic acid vs RIFampicin in early-onset severe Intrahepatic Cholestasis of pregnancy, giving an overview of the current state of affairs for total bile acid measurements. [ABSTRACT FROM AUTHOR]

The International Union of Basic and Clinical Pharmacology (IUPHAR) Geriatric Committee aims to improve the use of drugs in older adults and develop new therapeutic approaches for the syndromes and diseases of old age through advocacy, education, and research. In the present paper, we propose strategies relevant to drug development and evaluation, spanning preclinical and the full range of clinical studies. Drugs for older adults need to consider not only age, but also other characteristics common in geriatric patients, such as multimorbidity, polypharmacy, falls, cognitive impairment, and frailty. The IUPHAR Geriatric Committee's position statement on 'Measurement of Frailty in Drug Development and Evaluation' is included, highlighting 12 key principles that cover the spectrum of translational research. We propose that where older adults are likely to be major users of a drug, that frailty is measured at baseline and as an outcome. Preclinical models that replicate the age, frailty, duration of exposure, comorbidities, and co‐medications of the proposed patients may improve translation. We highlight the potential application of recent technologies, such as physiologically based pharmacokinetic–pharmacodynamic modeling informed by frailty biology, and Artificial Intelligence, to inform personalized medicine for older patients. Considerations for the rapidly aging populations in low‐ and middle‐income countries related to health‐care and clinical trials are outlined. Involving older adults, their caregivers and health‐care providers in all phases of research should improve drug development, evaluation, and outcomes for older adults internationally. [ABSTRACT FROM AUTHOR]

The validity of driving simulators is a topic that has been addressed ever since their first use. In practice, a comparison of field data and simulator data is often used for validation purposes. A systematic literature search was conducted which identified large heterogeneity in both study designs and statistical methods used in research on simulator validity. Most of the included studies concluded simulator validity (thus equivalence of field data and simulator data) from non-significant results in Null-Hypothesis Significance Testing (NHST), which is a well-known yet somewhat controversial practice. In this work, the consequences of both study design choice and the choice of the statistical method are outlined and alternatives such as using Bayes factor hypothesis testing and equivalence tests are discussed and applied to a real data example. The present paper is intended to shed light on the influence of the statistical method on conclusions drawn from experimental data. For research on driving simulator validity, we highly encourage the use of equivalence tests or Bayes factor hypothesis tests, in particular when evidence of the data suggests that an effect might be absent. [ABSTRACT FROM AUTHOR]

Introduction: Currently, there is no consensus regarding the management of intermittent exotropia (IXT), which includes both surgical and non-surgical treatment options. Nonsurgical management of IXT has been suggested and includes watchful observation, patching, overminus lenses, prism, and vision therapy/orthoptics. While a significant portion of IXT patients are treated by surgery, it is reported that there is a substantial tendency for reoperation or recurrence of IXT. This paper provides a comprehensive review of non-surgical and surgical treatment options for the IXT. Methods: Search strategies involving combination of keywords including intermittent exotropia, divergence excess, basic exotropia, refractive error, glasses, spectacles, natural history, untreated, observe, occlusion, patch, overminus, overcorrecting minus, prism, vision therapy, orthoptic, anti-suppression, fusion exercise, and surgery were used in Medline. All English articles from 01/01/1900 to 01/09/2020 were reviewed. The reference list of the identified articles was also checked for additional relevant articles. Studies focused on animal models or strabismus associated with neurologic disorders or injury were excluded. The following filters were used for surgical management due to the abundance of reports: full text, randomized controlled trial, review, in the last 5 years. Results: Appropriate optical correction of refractive error is generally the starting point for all management approaches, but there is a lack of randomized clinical trial data regarding this treatment modality. Randomized clinical trial data indicate that both observation and occlusion are reasonable management options for children 3–10 years old, and there were insufficient data to recommend occlusion for children 12–35 months old. While overminus lenses were found to improve the control of IXT when assessed wearing overminus spectacles, this improvement did not persist after the treatment ended. The result of the only randomized clinical trial on the effectiveness of base-in prism indicated that this treatment is no more effective than nonprism spectacles for improving control. A recent randomized clinical trial showed that vision therapy/orthoptics is effective in improving the control of IXT when compared to observation alone. Surgery was found to alter a number of clinical characteristics of IXT, including reducing the distance and near angle of deviation, reducing photophobia, improving health-related quality of life, stereopsis, and the Newcastle Control Score. However, there are no randomized clinical trial data comparing surgery with a control group such as placebo or a no treatment observation group. Discussion: Rigorously designed clinical trials to investigate the effectiveness of non-surgical and surgical treatments for intermittent exotropia are needed. [ABSTRACT FROM AUTHOR]