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The 1983 Orphan Drug Act in the United States (US) changed the landscape for development of therapeutics for rare or orphan diseases, which collectively affect approximately 300 million people worldwide, half of whom are children. The act has undoubtedly accelerated drug development for orphan diseases, with over 6,400 orphan drug applications submitted to the US Food and Drug Administration (FDA) from 1983 to 2023, including 350 drugs approved for over 420 indications. Drug development in this population is a global and collaborative endeavor. This position paper of the International Society for Central Nervous System Clinical Trials and Methodology (ISCTM) describes some potential best practices for the involvement of key stakeholder feedback in the drug development process. Stakeholders include advocacy groups, patients and caregivers with lived experience, public and private research institutions (including academia and pharmaceutical companies), treating clinicians, and funders (including the government and independent foundations). The authors articulate the challenges of drug development in orphan diseases and propose methods to address them. Challenges range from the poor understanding of disease history to development of endpoints, targets, and clinical trials designs, to finding solutions to competing research priorities by involved parties. [ABSTRACT FROM AUTHOR]

Many individuals with autism spectrum disorder (ASD) experience various degrees of impairment in social interaction and communication, restricted, repetitive behaviours, interests/activities. These impairments make a significant contribution to poorer everyday adaptive functioning. Yet, there are no pharmacological therapies to effectively treat the core symptoms of ASD. Since symptoms of ASD likely emerge from a complex interplay of vulnerabilities, environmental factors and compensatory mechanisms during the early developmental period, pharmacological interventions arguably would have the greatest impact to improve long-term outcomes when implemented at a young age. It is essential therefore, that clinical development programmes of investigational drugs in ASD include the paediatric population early on in clinical trials. Such trials need to offer the prospect of direct benefit (PDB) for participants. In most cases in drug development this prospect is supported by evidence of efficacy in adults. However, the effectiveness of treatment approaches may be age-dependent, so that clinical trials in adults may not provide sufficient evidence for a PDB in children. In this white paper, we consolidate recommendations from regulatory guidelines, as well as advice from the Food and Drug Administration, USA (FDA) and the Committee for Human Medicinal Products (CHMP) consultations on various development programmes on: 1) elements to support a PDB to participants in early paediatric clinical trials in ASD, including single-gene neurodevelopment disorders, 2) aspects of study design to allow for a PDB. This white paper is intended to be complementary to existing regulatory guidelines in guiding industry and academic sponsors in their conduct of early paediatric clinical trials in ASD. [ABSTRACT FROM AUTHOR]

Background: Unhealthy diet is a key risk factor for Non-Communicable Diseases (NCDs) that contribute to increased morbidity and premature mortality. With increased computer literacy and mobile phone penetration, there is a high opportunity for mobile application-based interventions. The current study was conducted to develop a mobile application to monitor dietary intake and to assess its acceptability and effectiveness in diet control compared to a similar paper-based intervention. A mobile application was developed based on research evidence and opinions of local experts. The mobile application was introduced to a selected group of office workers who were in preparation, action, and maintenance stages of the Trans Theoretical Model (TTM) and a paper-based intervention was used as the comparator. Socio-demographic data were collected through a self-administered questionnaire. Participants were followed up for three months for adherence. The effectiveness of interventions was assessed at the end of three months by comparing the progressive change in the stage of change and the change from unhealthy to healthy dietary intake between two groups as primary and secondary outcomes respectively. Results: Among 123 office workers who participated in the study, 19.5% preferred the mobile intervention over the paper-based intervention. Younger, unmarried office workers and those who do not have children, had a higher acceptance for the mobile intervention (p < 0.05). There was no difference in adherence (in all three months) or outcomes between the two groups of intervention. Conclusion and recommendations: Mobile application-based interventions are better accepted among the young age group and further studies are recommended to explore their applicability. Trial registration: The study was registered in the Sri Lankan Clinical Trial Registry (Registration No. SLCTR/2020/025; Date 15th December 2020). [ABSTRACT FROM AUTHOR]

Summary This Good Practice Paper provides recommendations for the diagnosis and initial management of transplant‐eligible high‐risk myeloma patients. It describes recent updates to the genetic diagnostics of high‐risk myeloma and provides recommendations for treatment on the basis of recent prospective clinical trial evidence. [ABSTRACT FROM AUTHOR]

The apps for drawing are present in our children's life. Nevertheless, little is known about the impact of mobile technology on the freehand drawing educational activity. There are few works which are contextualised within short periods of time, with teachers who are not theirs and, in some cases, outside the children's classroom. In this paper, we are focussed on the use of technology on freehand drawing activity. Thus, we have compared the graphics produced by 4- and 5-year-old children with paper&crayon in comparison with those with tablet-finger. Children made the drawings during a planned free-drawing activity, in their ordinary classrooms, with their teachers and during five sessions. Assessment of drawings has evidenced tablet feasibility for making graphics. Nevertheless, with the passing of time, quality of graphics (tablet-finger vs paper&crayons), are nearly matched, demonstrating the low impact level technology has on this activity. In addition, if drawings are analysed specifically according to ages, results have shown that both groups have to develop adaptation strategies of visual perceptual skills and fine motor skills for the touch screen in order to obtain the same quality in the drawings made on both support types. [ABSTRACT FROM AUTHOR]

Background: Interest in and use of electronic consent (e-consent) in the conduct of academic clinical trials has increased since the COVID-19 pandemic. E-consent offers advantages including increased efficiency and accessibility, and reduced burden on site staff, which can be appealing to academic trialists anticipating challenges in recruitment to complex trial designs or with limited funding. However, there are many options to consider when using e-consent in a study protocol. This paper presents five case studies from Norwich Clinical Trials Unit, demonstrating how e-consent models can be effectively tailored to the needs of different trials. These examples illustrate the options around and benefits of e-consent, the acceptability of e-consent by participants, and the design considerations that were made during the development of the trial protocols. Case studies: Five randomised trials are presented, selected from a range of different trial designs, disease areas, interventions, and patient populations. E-consent was either offered as an alternative to paper consent, according to participant preference, or as the sole method of consent. E-consent was generally used to facilitate remote consent in decentralised trials but was also chosen to increase efficiency and reduce burden in an emergency department setting. The technical implementation of e-consent and detailed participant procedures were tailored to the needs of the trial settings and patient populations. For example, accompanying participant information sheets were provided in paper or electronic form, and electronic signatures could be typed or drawn. Administrative data on uptake of e-consent is presented where available. Conclusion: This paper demonstrates that the operational and technical aspects of implementing e-consent in clinical trials can be influenced by the trial design, the needs and characteristics of the trial population, financial/efficiency considerations, and level of risk. E-consent is not a one-size-fits-all tool for trials, and its use should be carefully considered during the development of the trial protocol, in conjunction with patient and public involvement contributors, site staff and other trial stakeholders. [ABSTRACT FROM AUTHOR]

This document discusses the key concepts of translational research in the field of ophthalmology. Translational research aims to bridge the gap between existing knowledge and medical practice, with the goal of benefiting patients. It involves the transfer of diagnostic and therapeutic advances from the laboratory to clinical practice. The document explores the stakeholders of translational research, the scope of translational medicine, the components of translational research, barriers to its success, and future directions. It emphasizes the importance of collaboration and communication among different stakeholders to promote effective translational research. [Extracted from the article]

Background: There is an often-held assumption that the engagement of clinicians and healthcare organizations in research improves healthcare performance at various levels. Previous reviews found up to 28 studies suggesting a positive association between the engagement of individuals and healthcare organizations in research and improvements in healthcare performance. The current study sought to provide an update. Methods: We updated our existing published systematic review by again addressing the question: Does research engagement (by clinicians and organizations) improve healthcare performance? The search covered the period 1 January 2012 to March 2024, in two phases. First, the formal updated search ran from 1 January 2012 to 31 May 2020, in any healthcare setting or country and focussed on English language publications. In this phase two searches identified 66 901 records. Later, a further check of key journals and citations to identified papers ran from May 2020 to March 2024. In total, 168 papers progressed to full-text appraisal; 62 were identified for inclusion in the update. Then we combined papers from our original and updated reviews. Results: In the combined review, the literature is dominated by papers from the United States (50/95) and mostly drawn from the Global North. Papers cover various clinical fields, with more on cancer than any other field; 86 of the 95 papers report positive results, of which 70 are purely positive and 16 positive/mixed, meaning there are some negative elements (i.e. aspects where there is a lack of healthcare improvement) in their findings. Conclusions: The updated review collates a substantial pool of studies, especially when combined with our original review, which are largely positive in terms of the impact of research engagement on processes of care and patient outcomes. Of the potential engagement mechanisms, the review highlights the important role played by research networks. The review also identifies various papers which consider how far there is a "dose effect" from differing amounts of research engagement. Additional lessons come from analyses of equity issues and negative papers. This review provides further evidence of contributions played by systems level research investments such as research networks on processes of care and patient outcomes. [ABSTRACT FROM AUTHOR]

Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of zanubrutinib in approved indications may be challenging. This article presents the results of a group discussion among an ad hoc constituted panel of experts to identify and address unmet clinical needs (UCNs) in using zanubrutinib in patients with CLL. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. Panel members reviewed the results of first‐line and upstream controlled trials in which the efficacy and toxicity profile of zanubrutinib and other BTK inhibitors were investigated in patients with CLL. Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners. [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 Patient Cloud ePRO app was adopted by the National Cancer Institute National Clinical Trials Network (NCTN) to facilitate capturing electronic patient-reported (ePRO) outcome data, but use has been low. The study objectives were to test whether a patient-targeted ePRO educational resource (ePRO-E) would increase ePRO intent (number of users) and improve data quality (high quality: ≥80% of the required surveys submitted) within an ongoing NCTN study. Methods The ePRO-E intervention, a patient-targeted educational resource (written material and 6-minute animated YouTube video), was designed to address ePRO barriers. ePRO intent and data quality were compared between 2 groups (N  =   69): a historical control group and a prospectively recruited intervention group exposed to ePRO-E. Covariates included technology attitudes, age, sex, education, socioeconomic status, and comorbidity. Results Intervention group ePRO intent (78.8%) was statistically significantly higher than historical control group intent (47.1%) (P  =  .03). Patients choosing ePRO versus paper surveys had more positive and higher technology attitudes scores (P  =  .03). The odds of choosing ePRO were 4.7 times higher (95% Confidence Interval [CI] = 1.2 to 17.8) (P  =  .02) among intervention group patients and 5.2 times higher (95% CI = 1.3 to 21.6) (P = .02) among patients with high technology attitudes scores, after controlling for covariates. However, the 80% submission rate (percentage submitting ≥80% of required surveys) in the ePRO group (30.6%) was statistically significantly lower than in the paper group (57.9%) (P  =  .05). Conclusions ePRO-E exposure increased ePRO intent. High technology attitudes scores were associated with ePRO selection. Since the ePRO survey submission rate was low, additional strategies are needed to promote high-quality data submission. [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]

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]

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]

In silico clinical trials (ISCTs) are an emerging method in modeling and simulation where medical interventions are evaluated using computational models of patients. ISCTs have the potential to provide cost-effective, time-efficient, and ethically favorable alternatives for evaluating the safety and effectiveness of medical devices. However, ensuring the credibility of ISCT results is a significant challenge. This paper aims to identify unique considerations for assessing the credibility of ISCTs and proposes an ISCT credibility assessment workflow based on recently published model assessment frameworks. First, we review various ISCTs described in the literature, carefully selected to showcase the range of methodological options available. These studies cover a wide variety of devices, reasons for conducting ISCTs, patient model generation approaches including subject-specific versus 'synthetic' virtual patients, complexity levels of devices and patient models, incorporation of clinician or clinical outcome models, and methods for integrating ISCT results with real-world clinical trials. We next discuss how verification, validation, and uncertainty quantification apply to ISCTs, considering the range of ISCT approaches identified. Based on our analysis, we then present a hierarchical workflow for assessing ISCT credibility, using a general credibility assessment framework recently published by the FDA's Center for Devices and Radiological Health. Overall, this work aims to promote standardization in ISCTs and contribute to the wider adoption and acceptance of ISCTs as a reliable tool for evaluating medical devices. Author summary: A new method for evaluating a medical device is an in silico clinical trial, where the device performance is tested using computational models representing a cohort of patients. Demonstrating that in silico clinical trials are reliable is clearly of paramount importance. However, little information is available on how to ensure this. In this paper we present a workflow for evaluating an in silico clinical trial. This workflow was developed by considering a wide-ranging sample of previously published in silico clinical trials, together with a detailed assessment of how specific model evaluation activities apply to in silico clinical trials. [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]

Background: Poor representation of pregnant and lactating women and people in clinical trials has marginalised their health concerns and denied the maternal–fetal/infant dyad benefits of innovation in therapeutic research and development. This mixed-methods systematic review synthesised factors affecting the participation of pregnant and lactating women in clinical trials, across all levels of the research ecosystem. Methods and findings: We searched 8 databases from inception to 14 February 2024 to identify qualitative, quantitative, and mixed-methods studies that described factors affecting participation of pregnant and lactating women in vaccine and therapeutic clinical trials in any setting. We used thematic synthesis to analyse the qualitative literature and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. We compared quantitative data against the thematic synthesis findings to assess areas of convergence or divergence. We mapped review findings to the Theoretical Domains Framework (TDF) and Capability, Opportunity, and Motivation Model of Behaviour (COM-B) to inform future development of behaviour change strategies. We included 60 papers from 27 countries. We grouped 24 review findings under 5 overarching themes: (a) interplay between perceived risks and benefits of participation in women's decision-making; (b) engagement between women and the medical and research ecosystems; (c) gender norms and decision-making autonomy; (d) factors affecting clinical trial recruitment; and (e) upstream factors in the research ecosystem. Women's willingness to participate in trials was affected by: perceived risk of the health condition weighed against an intervention's risks and benefits, therapeutic optimism, intervention acceptability, expectations of receiving higher quality care in a trial, altruistic motivations, intimate relationship dynamics, and power and trust in medicine and research. Health workers supported women's participation in trials when they perceived clinical equipoise, had hope for novel therapeutic applications, and were convinced an intervention was safe. For research staff, developing reciprocal relationships with health workers, having access to resources for trial implementation, ensuring the trial was visible to potential participants and health workers, implementing a woman-centred approach when communicating with potential participants, and emotional orientations towards the trial were factors perceived to affect recruitment. For study investigators and ethics committees, the complexities and subjectivities in risk assessments and trial design, and limited funding of such trials contributed to their reluctance in leading and approving such trials. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people. Conclusions: This systematic review highlights diverse factors across multiple levels and stakeholders affecting the participation of pregnant and lactating women in clinical trials. By linking identified factors to frameworks of behaviour change, we have developed theoretically informed strategies that can help optimise pregnant and lactating women's engagement, participation, and trust in such trials. Using a mixed-methods approach, Mridula Shankar and colleagues investigate the reasons why those who are pregnant and breastfeeding are under-represented in clinical trials. Author summary: Why was this study done?: Pregnant and lactating women and people are routinely excluded from participating in drug and vaccine clinical trials, resulting in limited options for prevention and treatment of medical conditions. Challenges to including pregnant and lactating women and people in clinical research have been identified at multiple levels of the research and health systems, but the full range of barriers and facilitators to participation are not well known. What did the researchers do and find?: We conducted a mixed-methods systematic review and identified 60 research articles from 27 countries on the views and experiences of pregnant and lactating women's participation in clinical research, from the perspectives of cisgender women, family and community members, health workers, and people involved in the conduct of clinical research. Using a thematic synthesis approach, we identified barriers affecting participation including women having a limited appetite for risk during pregnancy and lactation, concerns about women's bodily autonomy during pregnancy, and challenges in obtaining ethical approval for clinical research with pregnant women. We also identified facilitators of participation including the potential for personal health benefits, expectations of higher quality care, trust in the medical and research systems, and strong teamwork between researchers and health workers. What do these findings mean?: Our findings demonstrate the need for multipronged strategies to address barriers and reinforce facilitators across the various levels of the research and health systems. The actions that are needed to overcome these barriers and reinforce facilitators must be discussed, prioritised, and adapted to specific contexts. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people. [ABSTRACT FROM AUTHOR]

Background: Use of electronic methods to support informed consent ('eConsent') is increasingly popular in clinical research. This commentary reports the approach taken to implement electronic consent methods and subsequent experiences from a range of studies at the Leeds Clinical Trials Research Unit (CTRU), a large clinical trials unit in the UK. Main text: We implemented a remote eConsent process using the REDCap platform. The process can be used in trials of investigational medicinal products and other intervention types or research designs. Our standard eConsent system focuses on documenting informed consent, with other aspects of consent (e.g. providing information to potential participants and a recruiter discussing the study with each potential participant) occurring outside the system, though trial teams can use electronic methods for these activities where they have ethical approval. Our overall process includes a verbal consent step prior to confidential information being entered onto REDCap and an identity verification step in line with regulator guidance. We considered the regulatory requirements around the system's generation of source documents, how to ensure data protection standards were upheld and how to monitor informed consent within the system. We present four eConsent case studies from the CTRU: two randomised clinical trials and two other health research studies. These illustrate the ways eConsent can be implemented, and lessons learned, including about differences in uptake. Conclusions: We successfully implemented a remote eConsent process at the CTRU across multiple studies. Our case studies highlight benefits of study participants being able to give consent without having to be present at the study site. This may better align with patient preferences and trial site needs and therefore improve recruitment and resilience against external shocks (such as pandemics). Variation in uptake of eConsent may be influenced more by site-level factors than patient preferences, which may not align well with the aspiration towards patient-centred research. Our current process has some limitations, including the provision of all consent-related text in more than one language, and scalability of implementing more than one consent form version at a time. We consider how enhancements in CTRU processes, or external developments, might affect our approach. [ABSTRACT FROM AUTHOR]

Background and Objectives: Chloroquine and its analog hydroxychloroquine are derivatives of 4-aminoquinoline and are regularly used in the treatment of malaria and autoimmune diseases. Among the side effects of these drugs, alterations associated with the auditory system are frequently mentioned. Thus, the aim of this systematic review is to systematically review publications on hearing disorders and chloroquine or hydroxychloroquine use. Materials and Methods: Inclusion criteria were observational or interventional studies on audiological assessment in participants who were using chloroquine or hydroxychloroquine. The methodological quality was independently assessed by two reviewers using the Meta-Analysis of Statistics: assessment and review Instrument. The certainty of the evidence was assessed using the GRADE tool. Results: A total of 1,372 non-duplicate papers were screened, out of which 17 were included in the final qualitative synthesis, and 5 studies in the meta-analysis. The odds ratio for the two subgroups evaluated did not show significance with no heterogeneity between the effects observed between the different diseases (I²=0%) and obtaining the global estimate of 0.76 (95% confidence interval [CI]=0.41-1.39; p>0.05). Despite the inclusion of papers with different disease samples, the heterogeneity observed in the analysis was low (I²= 0%) and prediction interval (95% PI=0.32-1.80; p>0.05) remained close to that estimated by the CI (95% CI=0.41-1.39; p>0.05). The certainty of the evidence assessed by the GRADE tool was considered very low due to the risk of bias, indirect evidence, and imprecision. Conclusions: The findings of this study suggest that the use of chloroquine/hydroxychloroquine is not associated with hearing disorders. [ABSTRACT FROM AUTHOR]

This document is a response to a letter regarding a paper titled "Real-World Effectiveness of First-Line Lenvatinib Therapy in Advanced Hepatocellular Carcinoma: Current Insights." The authors address concerns raised by the correspondents and clarify that their paper focused on scenarios where immunotherapy is not a viable option for treating hepatocellular carcinoma (HCC). They acknowledge the toxicity related to lenvatinib but highlight the positive results from the REFLECT trial, which showed non-inferior overall survival and significant improvements in secondary efficacy endpoints compared to sorafenib. The authors also mention that their paper focused on scenarios with contraindications to immunotherapy or as a second-line treatment following immunotherapy. They disagree with the suggestion that non-preplanned analysis or retrospective studies should determine the use of lenvatinib or sorafenib, and they favor lenvatinib based on the REFLECT data. The authors disclose their conflicts of interest. [Extracted from the article]

Background: In the U.S. there are significant racial and gender disparities in the uptake of pre-exposure prophylaxis (PrEP). Black Americans represented 14% of PrEP users in 2022, but accounted for 42% of new HIV diagnoses in 2021 and in the South, Black people represented 48% of new HIV diagnoses in 2021 but only 21% of PrEP users in 2022. Women who use drugs may be even less likely than women who do not use drugs have initiated PrEP. Moreover, women involved in community supervision programs (CSP) are less likely to initiate or use PrEP, More PrEP interventions that focus on Black women with recent history of drug use in CSPs are needed to reduce inequities in PrEP uptake. Methods: We conducted a secondary analysis from a randomized clinical trial with a sub-sample (n = 336) of the total (N = 352) participants from the parent study (E-WORTH), who tested HIV negative at baseline were considered PrEP-eligible. Black women were recruited from CSPs in New York City (NYC), with recent substance use. Participants were randomized to either E-WORTH (n = 172) an HIV testing plus, receive a 5-session, culturally-tailored, group-based HIV prevention intervention, versus an HIV testing control group (n = 180). The 5 sessions included an introduction to PrEP and access. This paper reports outcomes on improved awareness of PrEP, willingness to use PrEP, and PrEP uptake over the 12-month follow-up period. HIV outcomes are reported in a previous paper. Results: Compared to control participants, participants in this study assigned to E-WORTH had significantly greater odds of being aware of PrEP as a biomedical HIV prevention strategy (OR = 3.25, 95% CI = 1.64–6.46, p = 0.001), and indicated a greater willingness to use PrEP as an HIV prevention method (b = 0.19, 95% CI = 0.06–0.32, p = 0.004) over the entire 12-month follow-up period. Conclusions: These findings underscore the effectiveness of a culturally-tailored intervention for Black women in CSP settings in increasing awareness, and intention to initiate PrEP. Low uptake of PrEP in both arms highlight the need for providing more robust PrEP-on-demand strategies that are integrated into other services such as substance abuse treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02391233. [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: In light of the FDA's Project Optimus initiative, there is fresh interest in leveraging Patient-reported Outcome (PRO) data to enhance the assessment of tolerability for investigational therapies within early phase dose-finding oncology trials. Typically, dose escalation in most trial designs is solely reliant on clinician assessed adverse events. Research has shown a disparity between patients and clinicians when assessing whether an investigational therapy is tolerable, leading to the recommendation of potentially intolerable doses for further investigation in subsequent trials. It is also increasingly recognized that patient and public involvement and engagement (PPIE) plays a pivotal role in enriching trial design and conduct. However, to our knowledge, no PPIE has explored the optimal integration of PROs in the development of advanced statistical trial designs within early phase dose-finding oncology trials. Methods: A virtual PPIE session was held with nine participants on 18th October 2023 to discuss the incorporation of PROs within a dose-finding trial design. This cross disciplinary session was developed and led by a team of statisticians, clinical specialists, qualitative experts, and trial methodologists. Following the session, in-depth perspectives were provided by two patient advocates who actively engaged in the PPIE session. We discuss the importance of PPIE in shaping advanced dose-finding trial designs, share insights from patients on integrating PROs to inform treatment tolerability, and present a template for meaningful patient involvement in trial design development. Results: Participants generally supported the introduction of PROs within dose-finding trials but showed some apprehensiveness as to how PROs may reduce the size of the recommended dose (and potentially efficacious effect). Some participants shared that they may be reluctant to record the real severity of their symptoms via PROs if it would mean that they would have to discontinue treatment. They discussed that PROs could be used to assess tolerability rather than toxicity of a dose. Conclusions: Amplifying patient voice in the development of patient-centric dose-finding trial designs is now essential. This paper offers an exemplary illustration of how trialists and methodologists can effectively incorporate patient voice in the future development of advanced dose-finding trial designs. Plain English summary: The aim of dose-finding oncology trials is to make sure a treatment is safe, understand its side effects, and recommend the right dose (or doses) for future clinical trials. Traditionally, a patient's tolerance to treatment is assessed by doctors who evaluate toxicities (side-effects) using established grading guidelines. Research has shown that doctors might not identify all the side effects that patients actually experience during a trial. There is growing interest in the introduction of patient-reported outcomes (PROs) within dose-finding trials. PROs are reports of a patient's health and well-being experiences which come directly from the patient themselves, usually assessed using a questionnaire. In a dose-finding trial, we start with a low dose of a drug and increase it until too many patients have severe side effects. The highest safe dose is then investigated in a later phase trial. We are suggesting a new way to do these trials. We want to look at both what doctors see as severe side effects and what patients say. This enables us to recommend a dose that balances both perspectives. We would also like to ask patients what level of risk they are comfortable with regarding severe side effects. In this paper, we highlight the importance of involving patients in creating advanced dose-finding trial designs, particularly with PROs to help decide whether a dose is tolerable for patients. We also share findings of a patient and public involvement and engagement session and provide a guide for meaningful patient involvement in developing trial designs. [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]

Effective clinical trials are necessary for understanding medical advances but early termination of trials can result in unnecessary waste of resources. Survival models can be used to predict survival probabilities in such trials. However, survival data from clinical trials are sparse, and DeepSurv cannot accurately capture their effective features, making the models weak in generalization and decreasing their prediction accuracy. In this paper, we propose a survival prediction model for clinical trial completion based on the combination of denoising autoencoder (DAE) and DeepSurv models. The DAE is used to obtain a robust representation of features by breaking the loop of raw features after autoencoder training, and then the robust features are provided to DeepSurv as input for training. The clinical trial dataset for training the model was obtained from the ClinicalTrials.gov dataset. A study of clinical trial completion in pregnant women was conducted in response to the fact that many current clinical trials exclude pregnant women. The experimental results showed that the denoising autoencoder and deep survival regression (DAE‐DSR) model was able to extract meaningful and robust features for survival analysis; the C‐index of the training and test datasets were 0.74 and 0.75 respectively. Compared with the Cox proportional hazards model and DeepSurv model, the survival analysis curves obtained by using DAE‐DSR model had more prominent features, and the model was more robust and performed better in actual prediction. [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]

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]

Healthcare is a critical area where blockchain technology (BT) is being heralded as a potential game-changer for facilitating secure and efficient data sharing. The purpose of this review is to examine BT applications, performance challenges, and solutions in healthcare. To begin, This review paper explores popular blockchain networks for data exchange, encompassing both public and permissioned platforms, such as Ethereum and Hyperledger Fabric. This paper analyzes the potential applications of BT's decentralized, immutable, and smart contract capabilities in healthcare settings, including secure and interoperable health data exchange, patient consent management, drug supply chain oversight, and clinical trial management. The healthcare industry might greatly benefit from the increased privacy, transparency, and accessibility that these technologies provide. Despite BT's promising medical uses, the technology is not without its drawbacks. High energy consumption, throughput, and scalability are all concerns. We wrapped up by discussing the solutions that have been implemented, including consensus processes, scalability measures like sharding, and off-chain transactions that are designed to mitigate the drawbacks. [ABSTRACT FROM AUTHOR]

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Background: While acupuncture treatment has gained extensive usage in addressing headaches, there remains a notable gap in the literature analysis for this field. Therefore, this study aims to conduct a literature review using Citespace, VOSviewer, and Bibliometrix, aiming to examine the current status, strengths, and potential future directions in the utilization of acupuncture for headache treatment. Methods: Relevant literature on acupuncture treatment for headaches between 2003 and 2023 was retrieved from the Web of Science (WoS) core database. Utilizing CiteSpace 6.1.R6, VOSviewer 1.6.18, and Bibliometrix 4.1.4, we conducted bibliometric analyses across various categories, including countries/regions, institutions, authors, journals, references, and keywords. Results: A total of 808 research reports were included. China and the United States have significantly contributed to this field. Chengdu University of Chinese Medicine holds the record for the highest number of published papers. Liu Lu has the highest publication output, while Linde K has the highest citation rate. MEDICINE leads in publication frequency, while CEPHALALGIA holds the highest citation rate. The Long-term Effect of Acupuncture for Migraine Prophylaxis a Randomized Clinical Trial is the most cited reference. Migraine was the most researched type. Filiform needle acupuncture was the most widely used stimulation method. The safety and efficacy of acupuncture have received significant attention. Modern mechanism research shows that depression, brain functional connectivity, and neuroimaging technology have become research hotspots in the acupuncture treatment of headaches. Conclusion: Acupuncture treatment for headaches has established a stable trend with a promising developmental trajectory. Research in this field mainly focuses on different acupuncture prevention and treatment for various types of headaches, the safety and efficacy of acupuncture, etc. Research on the mechanism of action mainly focuses on interpreting bidirectional and holistic regulation between pain and emotion by acupuncture and the regulation of brain function connection and neuroimaging technology by acupuncture. Future research should expand on the advantages and indications of acupuncture treatment for different headaches and their modern mechanisms. [ABSTRACT FROM AUTHOR]

Simple Summary: Metformin is one of the most widely used drugs in the world, since its first use in the second part of the 1950s in France (Aron, 1957) and in the United Kingdom (Rona, 1958), and is on the World Health Organization's List of Essential Medicines. Traditionally, metformin is used in diabetes mellitus, mainly in overweight and obese subjects, but also in other conditions of impaired glucose metabolism, such as insulin resistance. In recent years, in vitro and in vivo data on this molecule as an antiproliferative modulator have suggested a series of clinical trials in several tumors that—at the moment—have not confirmed the expected positive results. The aim of this paper is to offer a double vision of this molecule, with a very light side about the metabolic aspects and a darker side concerning its antineoplastic activity, focusing on molecular and subcellular pathways involved in both fields and discussing the contrast between preliminary cellular data and real clinical outcomes in different neoplasms. The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open? [ABSTRACT FROM AUTHOR]

According to an article in Pulse International, China is expected to become the world leader in research and clinical trials by 2025. Currently, the United States and China publish the most research papers, but China's progress in various fields, including clinical trials, is rapidly increasing. Other countries such as Japan, South Korea, Brazil, and India are also making significant advancements in clinical trials. The article emphasizes the importance of collaboration between academia and the pharmaceutical industry for successful clinical trials and the need for biotechnology plants in Pakistan. The author also discusses the different phases of clinical trials and the challenges faced in conducting research. The article concludes by highlighting the importance of integrity, ethics, and transparency in research, as well as the potential economic benefits of clinical research organizations. [Extracted from the article]

Purpose: Family-based treatment (FBT) has contributed significantly to the treatment of anorexia nervosa (AN) in young people (YP). However, parents are concerned that FBT and the active role of parents in the task of refeeding may have a negative impact on family relations. The aim of the review is to assess whether families engaged in FBT for AN are more or less impacted in their family wellbeing and caregiver burden, compared to families with a YP diagnosed with AN, who are not undergoing treatment with FBT. Method: Computerized searches across six databases complemented by a manual search resulted in 30 papers being included in the scoping review. Results: The review identified 19 longitudinal studies on change in family wellbeing in families in FBT-like treatments, and 11 longitudinal studies on change in family wellbeing in treatment where parents are not in charge of refeeding. Only three randomized controlled studies directly compare FBT to treatment without parent-led refeeding. Conclusion: The available research suggests no difference between intervention types regarding impact on family wellbeing. Approximately half of the studies find improvements in family wellbeing in both treatment with and without parent-led refeeding, while the same proportion find neither improvement nor deterioration. As parents play a pivotal role in FBT, there is a need for good quality studies to elucidate the impact of FBT on family wellbeing. Level of evidenceLevel V: Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees. [ABSTRACT FROM AUTHOR]

According to Prof. Javed Akram, President of the Pakistan Society of Internal Medicine, China is expected to become the world leader in research and clinical trials by 2025. Currently, the United States and China publish the most research papers, but China's progress in these fields is significant. Other countries, such as Japan, South Korea, Brazil, and India, are also prioritizing clinical trials. Prof. Akram emphasized the importance of collaboration between academia and the pharmaceutical industry for successful clinical trials and research publications. He also discussed various clinical trials conducted in Pakistan, including those related to COVID-19 and the need for biotechnology plants. Prof. Akram highlighted the phases of clinical trials, the challenges faced, and the importance of integrity, ethics, and transparency in research. [Extracted from the article]

This paper will discuss the European funded iToBoS project, tasked by the European Commission to develop an AI diagnostic platform for the early detection of skin melanoma. The paper will outline the project, provide an overview of the data being processed, describe the impact assessment processes, and explain the AI privacy risk mitigation methods being deployed. Following this, the paper will offer a brief discussion of some of the more complex aspects: (1) the relatively low population clinical trial study cohort, which poses risks associated with data distinguishability and the masking ability of the applied anonymisation tools, (2) the project's ability to obtain informed consent from the study cohort given the complexity of the technologies, (3) the project's commitment to an open research data strategy and the additional privacy risk mitigations required to protect the multi-modal study data, and (4) the ability of the project to adequately explain the outputs of the algorithmic components to a broad range of stakeholders. The paper will discuss how the complexities have caused tension which are reflective of wider tensions in the health domain. A project level solution includes collaboration with a melanoma patient network, as an avenue for fair and representative qualification of risks and benefits with the patient stakeholder group. However, it is unclear how scalable this process is given the relentless pursuit of innovation within the health domain, accentuated by the continued proliferation of artificial intelligence, open data strategies, and the integration of multi-modal data sets inclusive of genomics. [ABSTRACT FROM AUTHOR]

Background and Aims: Overweight and obesity have become global health challenges with increasing prevalence. Several drugs have received Food and Drug Administration approval for nonsyndromic obesity treatment, but most have limitations, including gastrointestinal side effects and limited weight loss efficacy. Body: Retatrutide, a novel incretin mimetic agent, has shown promise in clinical trials for significant weight reduction. It has demonstrated dosage‐dependent pharmacokinetics with favorable safety profiles. The primary focus of this paper is to explore retatrutide and critically assess its clinical trials to justify its use and feasibility while highlighting its shortcomings. This paper also delves into the subject of obesity and its health manifestations. Conclusion: It is expected that the use of retatrutide, a triple agonist, will result in significant weight loss among individuals who are obese or overweight. [ABSTRACT FROM AUTHOR]

Introduction and aim: Blue light is part of the natural light spectrum and plays a role in regulating the circadian rhythm. However, with the increasing use of electronic devices and energy-efficient lighting emitting high levels of artificial blue light, concerns are raised regarding its potential effect on human health. Blue-blocking filters have been developed and are advertised as a solution to be used in spectacles or intraocular lenses. This review aims to provide an in-depth analysis of the use of blue-blocking filters based on the results of clinical trials. Material and methods: This review included relevant original papers reporting on clinical trial results from PubMed, Science Direct, and Google Scholar databases using specified keywords. Analysis of the literature. Trials conducted with patients reveal mixed results, with some showing no significant changes in vision and reading abilities, while others indicating potential limitations such as reduced contrast vision. However, blue-blocking filters have demonstrated potential benefits in improving sleep quality and mood, particularly in patients with sleep disturbances or psychiatric disorders. The efficacy of blue-blocking filters in mitigating symptoms of digital eye strain remains inconclusive. Concusion: Overall, this paper provides a comprehensive assessment of the benefits and limitations associated with the use of blue-blocking filters, highlighting the need for further investigation in certain areas. [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]

A new form of volunteer-based intervention is mushrooming across Europe: social mentoring. Such programmes turn 'ordinary' citizens into mentors for individuals from disadvantaged groups. Related initiatives are becoming more institutionalised and social mentoring has gained popularity as a social policy measure, especially in the face of crises. However, the social work discussion has taken little notice of this burgeoning phenomenon adjoining our professional field. There is a lack of concepts and data that could fuel a debate at the intersection of mentoring for social inclusion, human services, and welfare policies. This paper presents a first attempt to outline what social mentoring means, why social work should engage with it and how we can research into it. It offers theoretical reflection on ongoing developments in the EU, based on observation of the literature and field. To expand the available knowledge, it is suggested that research should pay equal attention to all three constituent elements of the topic: personal relationships, programmes, and policies. In line with critical traditions, this paper suggests a holistic, multi-scalar perspective that is sensitive to social inequalities and power imbalances, while also embracing innovative and transformative aspects of social mentoring as a 'popular' form of social problems work. [ABSTRACT FROM AUTHOR]

Background: The Stop Cancer PAIN Trial was a phase III pragmatic stepped wedge cluster randomised controlled trial which compared effectiveness of screening and guidelines with or without implementation strategies for improving pain in adults with cancer attending six Australian outpatient comprehensive cancer centres (n = 688). A system for pain screening was introduced before observation of a 'control' phase. Implementation strategies introduced in the 'intervention' phase included: (1) audit of adherence to guideline recommendations, with feedback to clinical teams; (2) health professional education via an email-administered 'spaced education' module; and (3) a patient education booklet and self-management resource. Selection of strategies was informed by the Capability, Opportunity and Motivation Behaviour (COM-B) Model (Michie et al., 2011) and evidence for each strategy's stand-alone effectiveness. A consultant physician at each centre supported the intervention as a 'clinical champion'. However, fidelity to the intervention was limited, and the Trial did not demonstrate effectiveness. This paper reports a sub-study of the Trial which aimed to identify factors inhibiting or enabling fidelity to inform future guideline implementation initiatives. Methods: The qualitative sub-study enabled in-depth exploration of factors from the perspectives of personnel at each centre. Clinical champions, clinicians and clinic receptionists were invited to participate in semi-structured interviews. Analysis used a framework method and a largely deductive approach based on the COM-B Model. Results: Twenty-four people participated, including 15 physicians, 8 nurses and 1 clinic receptionist. Coding against the COM-B Model identified 'capability' to be the most influential component, with 'opportunity' and 'motivation' playing largely subsidiary roles. Findings suggest that fidelity could have been improved by: considering the readiness for change of each clinical setting; better articulating the intervention's value proposition; defining clinician roles and responsibilities, addressing perceptions that pain care falls beyond oncology clinicians' scopes of practice; integrating the intervention within existing systems and processes; promoting patient-clinician partnerships; investing in clinical champions among senior nursing and junior medical personnel, supported by medical leaders; and planning for slow incremental change rather than rapid uptake. Conclusions: Future guideline implementation interventions may require a 'meta-implementation' approach based on complex systems theory to successfully integrate multiple strategies. Trial registration: Registry: Australian New Zealand Clinical Trials Registry; number: ACTRN 12615000064505; data: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspxid=367236&isReview=true. [ABSTRACT FROM AUTHOR]

Dissolving microneedles (DMNs) represent an innovative advancement in drug delivery and skincare technologies, offering significant advantages compared to traditional needles. This paper presents an overview of the historical evolution of microneedles and the rise of dissolving types, exploring their definition, concept, and diverse clinical applications such as vaccinations, drug delivery, and skincare treatments. Design and manufacturing considerations cover the materials employed, fabrication techniques, and methods for characterizing DMNs, focusing on aspects like mechanical strength, dissolution rate, and delivery efficiency. The mechanism of action section examines skin penetration mechanics, the process of microneedle dissolution, controlled release of active compounds, and considerations of biocompatibility and safety. Recent developments in DMNs encompass technological advancements, improved delivery systems, and updates on clinical trials and studies. Challenges and opportunities in scaling up production, overcoming market adoption barriers, and future research directions are discussed, aiming to address unmet medical needs and expand applications. In summary, DMNs have the potential to transform drug delivery and skincare treatments, with ongoing advancements aimed at tackling current challenges and unlocking new opportunities for enhanced healthcare outcomes. [ABSTRACT FROM AUTHOR]

Background Aims Methods Main Contribution Conclusions WHAT THIS PAPER ADDS What is already known on the subject What this paper adds to existing knowledge What are the clinical implications of this work? Communication impairments are a leading concern for parent caregivers of individuals with rare neurodevelopmental disorders (RNDDs). Clinical trials of disease modifying therapies require valid and responsive outcome measures that are relevant to individuals with RNDDs. Identifying and evaluating current psychometric properties for communication measures is a critical step towards the selection and use of appropriate instruments.This systematic review offers (1) a description of parent‐reported communication measures and (2) evidence for their psychometric properties, in RNDDs.The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022334649). MEDLINE (Ovid), Embase, PsychINFO, Web of Science, CINAHL Plus, Cochrane Library, ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry were searched from inception to August 2023. Methodological assessment of quality was completed using the COnsensus‐based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Parent‐reported measures used in observational studies and clinical trials were identified. Data on utility, reliability and validity for RNDDs were extracted.Sixteen parent‐reported communication measures were used in RNDD research, the Vineland Adaptive Behavior Scales being most commonly used. Validation data in RNDDs were identified for six of these measures. Limitations related to sample size or the scope of psychometric testing.Many communication measures have been used for RNDDs but there are few data validating their use. Valid and reliable methods of measuring communication in persons with RNDDs is a priority for future high‐quality clinical trials. Communication is a critical domain for families with a child with a rare neurodevelopmental disorder (RNDD). Validated outcome measures are essential for accurate evaluation and interpretation of responses to treatments in clinical trials. We identified 16 parent‐reported communication measures that have been used with RNDDs, but only six measures had validation data for at least one RNDD. High quality evidence is accumulating, with all validation studies in this review published between 2020 to 2023. Modifications of existing measures may be required to assess communication for RNDDs. This systematic review catalogues the available psychometric data for communication measures and indicates an ongoing need for new validation studies to ensure they are fit‐for‐purpose for upcoming clinical trials in RNDDs. This review will inform the selection of communication measures for clinical trials and research studies. [ABSTRACT FROM AUTHOR]

Management of chronic myeloid leukemia (CML) has been transformed by the use of tyrosine kinase inhibitors (TKIs). Presently in India, five TKIs are approved for the management of CML with distinct safety profiles. The selection of TKIs for chronic phase (CP)-CML patients is based on treatment goals, underlying comorbidities, and specific TKI toxicity profiles. Bosutinib is one of five TKIs indicated for the first-line treatment of CP-CML and patients with intolerance or resistance to prior TKI therapy. It possesses a distinct safety profile among other TKIs, with less cardiovascular adverse events (AEs), albeit the liver-related and gastrointestinal AEs have higher occurrence. The safety and efficacy of bosutinib have been examined in clinical trials; however, there is a paucity of data from Asia. A virtual expert panel meeting was convened to gather expert opinion from India on the selection of bosutinib as a treatment choice for patients with CP-CML. This is a white paper document drafted with the help of an expert panel of 14 oncologists and hematooncologists from India on bosutinib use in CP-CML. The experts concurred that bosutinib has proven efficacy for CP-CML in global randomized clinical trials and is well suited for CP-CML patients with existing cardiovascular comorbidities. However, it was not recommended for patients with gastrointestinal, pancreatic, or renal abnormalities. This review aims to put forth expert opinion and guidance document on key considerations for CP-CML clinical decision-making in India. [ABSTRACT FROM AUTHOR]