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Background: Research transparency is crucial for ensuring the relevance, integrity, and reliability of scientific findings. However, previous work indicates room for improvement across transparency practices. The primary objective of this study was to develop an extensible tool to provide individualized feedback and guidance for improved transparency across phases of a study. Our secondary objective was to assess the feasibility of implementing this tool to improve transparency in clinical trials. Methods: We developed study-level "report cards" that combine tailored feedback and guidance to investigators across several transparency practices, including prospective registration, availability of summary results, and open access publication. The report cards were generated through an automated pipeline for scalability. We also developed an infosheet to summarize relevant laws, guidelines, and resources relating to transparency. To assess the feasibility of using these tools to improve transparency, we conducted a single-arm intervention study at Berlin's university medical center, the Charité – Universitätsmedizin Berlin. Investigators (n = 92) of 155 clinical trials were sent individualized report cards and the infosheet, and surveyed to assess their perceived usefulness. We also evaluated included trials for improvements in transparency following the intervention. Results: Survey responses indicated general appreciation for the report cards and infosheet, with a majority of participants finding them helpful to build awareness of the transparency of their trial and transparency requirements. However, improvement on transparency practices was minimal and largely limited to linking publications in registries. Investigators also commented on various challenges associated with implementing transparency, including a lack of clarity around best practices and institutional hurdles. Conclusions: This study demonstrates the potential of developing and using tools, such as report cards, to provide individualized feedback at scale to investigators on the transparency of their study. While these tools were positively received by investigators, the limited improvement in transparency practices suggests that awareness alone is likely not sufficient to drive improvement. Future research and implementation efforts may adapt the tools to further practices or research areas, and explore integrated approaches that combine the report cards with incentives and institutional support to effectively strengthen transparency in research. [ABSTRACT FROM AUTHOR]

Background: Hospital Hyperglycemia (HH) is linked to poorer outcomes, including higher mortality rates, increased ICU admissions, and extended hospital stays, and occurs in both people living with diabetes or not. The prevalence of HH in non-critical patients ranges from 22 to 46%. This panel reviewed the evidence and made recommendations for the best care for hospitalized hyperglycemic patients, with or without diabetes mellitus. Methods: The methodology was published previously and was defined by the internal institutional steering committee. The SBD Acute and Hospital Complications Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to Hospital Hyperglycemia. Results and conclusions: The department members and external experts developed 23 recommendations for the management of patients with HH, including screening, initial interventions, treatment adjustments, and care for potential complications. Based on the best available evidence, our article provides safe and effective management strategies for both public and private healthcare settings. [ABSTRACT FROM AUTHOR]

Background & aims: Sarcopenia, characterized by the loss of muscle mass and strength, is a significant concern in cirrhotic patients. Nutritional interventions have been explored for its management, but the comparative efficacy of these interventions remains unclear. This study synthesizes current evidence to evaluate the effectiveness of nutritional interventions for sarcopenia in cirrhosis. Methods: Data sources included Scopus, PubMed, Web of Science Core Collection, and Cochrane Library up to Dec 2024. Eligible trials compared different nutritional interventions against control diets, placebos, or each other. A Bayesian network meta-analysis was performed to combine direct and indirect evidence. Effect sizes were calculated as mean differences (MD) with 95% confidence intervals (CIs). Intervention rankings were assessed using P-score, and evidence quality was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: A total of 14 randomized controlled trials (RCTs) involving 1,437 patients met the inclusion criteria. For improving muscle mass (MAMC), post-paracentesis intravenous nutritional support combined with an oral nutritional protocol (Treat A) showed the greatest effect compared to high-calorie, high-protein diets (HCHP) (MD: 2.78 cm, 95% CI: 1.15 to 4.40, low certainty), and oral nutritional protocol (Treat B) (MD of 3.41 cm, 95% CI: 2.12, 4.69). For muscle strength, the HINT diet (MD: 8.01 kg, 95% CI: 7.64 to 8.37, low certainty) and the HCHP (MD: 5 kg, 95% CI: 3.90 to 6.10, low certainty) were more effective than control diets. HCHP also demonstrated greater handgrip improvement than the HINT diet (MD: 3.00 kg, 95% CI: 1.84, 4.16; low certainty evidence). BCAA combined with vitamin D (2000 IU once a day) significantly improved skeletal muscle index (SMI) compared to both BCAA (MD: 0.72 kg/m2, 95% CI: 0.11 to 1.34; low certainty evidence) and placebo (MD: 0.25 kg/m2, 95% CI: -0.05 to 0.05; very low certainty evidence). BCAA supplementation effectively improved handgrip strength compared to placebo (MD: 2.36 kg, 95% CI: 1.85, 2.88; low certainty evidence). Conclusions: Post-paracentesis intravenous nutritional support combined with an oral nutritional protocol effectively improves muscle mass, while high-calorie, high-protein diets enhance handgrip strength. BCAA supplementation alone or with vitamin D has been shown to effectively enhance muscle strength and muscle mass. However, these findings should be interpreted cautiously due to low evidence certainty. [ABSTRACT FROM AUTHOR]

Adverse event (AE) collection is a key part of evidence generation in clinical trials and an integral element of safety reporting. AE assessment and documentation is particularly challenging in neonates who are a heterogeneous population with high rates of co-morbidities. Neonatal research is finally gaining the attention of regulators regarding drug development and the need for optimal dosing specific to this population. However, further efforts are necessary to ensure that adverse events (AEs) are adequately collected, allowing for the generation of essential safety data. It is also crucial that the methodology used aligns with the intended trial outcomes to minimise the burden on trial sites. In resource-constrained settings, where pharmacovigilance implementation can be particularly challenging, a pragmatic approach to safety reporting is even more important given the significant public health need for effective drugs. This commentary reflects on some of the challenges and potential areas of improvement in safety reporting that could be addressed in future neonatal-focused trials. [ABSTRACT FROM AUTHOR]

Background: Theoretical models of conduct disorder (CD) highlight that deficits in emotion recognition, learning, and regulation play a pivotal role in CD etiology. With CD being more prevalent in boys than girls, various theories aim to explain this sex difference. The "differential threshold" hypothesis suggests greater emotion dysfunction in conduct-disordered girls than boys, but previous research using conventional statistical analyses has failed to support this hypothesis. Here, we used novel analytic techniques such as machine learning (ML) to uncover potentially sex-specific differences in emotion dysfunction among girls and boys with CD compared to their neurotypical peers. Methods: Multi-site data from 542 youth with CD and 710 neurotypical controls (64% girls, 9–18 years) who completed emotion recognition, learning, and regulation tasks were analyzed using a multivariate ML classifier to distinguish between youth with CD and controls separately by sex. Results: Both female and male ML classifiers accurately predicted (above chance level) individual CD status based solely on the neurocognitive features of emotion dysfunction. Notably, the female classifier outperformed the male classifier in identifying individuals with CD. However, the classification and identification performance of both classifiers was below the clinically relevant 80% accuracy threshold (although they still provided relatively fair and realistic estimates of ~ 60% classification performance), probably due to the substantial neurocognitive heterogeneity within such a large and diverse, multi-site sample of youth with CD (and neurotypical controls). Conclusions: These findings confirm the close association between emotion dysfunction and CD in both sexes, with a stronger association observed in affected girls, which aligns with the "differential threshold" hypothesis. However, the data also underscore the heterogeneity of CD, namely that only a subset of those affected are likely to have emotion dysfunction and that other neurocognitive domains (not tested here) probably also contribute to CD etiology. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Purpose: An earlier multicenter phase III study demonstrated the safety and efficacy of mitoxantrone hydrochloride injection for tracing (MHI) for detecting sentinel lymph nodes (SLNs) in breast cancer patients. This ancillary study was conducted to further analyze and discover differences between the two tracers that had not been reported previously. Methods: This analysis used single-center data from a phase III trial. Patients with breast cancer were injected with both MHI and 99mTc as SLN tracers before surgery. To account for cluster effects of multiple SLNs from the same patient and further analyze the differences between the two methods and factors that could impact detection, Obuchowski's modified McNemar test, the GLIMMIX model, and univariate and multivariate analyses were used as appropriate. Results: In total, 463 SLNs from 109 patients were resected, 47 of which were pathologically positive. The SLN detection rate did not significantly differ between MHI and 99mTc. MHI blue staining was an independent predictor of pathological positivity (OR 3.58, 95% CI: 1.21–10.60, p = 0.02), while the 99mTc signal was not significant in the same model (p = 0.39). Conclusion: MHI was comparable to 99mTc in safety and SLN detection rates but differed in sensitivity on positive SLNs. [ABSTRACT FROM AUTHOR]

Background: Based on current guidelines, surgical treatment of hepatic oligometastases in patients with pancreatic ductal adenocarcinoma (PDAC) is not primarily recommended. Systematic chemotherapy is the therapy of choice for these patients. The relevance of subsequent surgical resection after chemotherapy remains unclear. This multicentre, randomized, controlled phase III trial is planned to evaluate whether resection of the primary tumor and liver metastases can improve overall survival in patients with PDAC with hepatic oligometastases in a multimodal treatment setting. Methods: After an induction therapy with eight cyles of mFOLFIRINOX and a response assessment after four and eight cycles, patients will be randomized to either Arm 1 (perioperative mFOFIRINOX plus resection of the primary tumor with resection or ablation of all hepatic metastases) or Arm 2 (continuation of 4 cycles of the standard-of-care mFOLFIRINOX chemotherapy). This clinical trial will focus on a well-defined patient group with metastatic disease limited to the liver as the target organ, with a maximum of three metastases. Discussion: METAPANC is the first international, randomized, controlled, open-label, multicentre, phase III clinical trial for curative intended surgical therapy of oligometastatic pancreatic cancer in Europe and America. The multimodal surgical treatment of patients with oligometastatic pancreatic cancer could significantly extend the overall survival of this patient group. A possible recommendation of this multimodal treatment regimen outside of clinical trials requires data from randomized controlled trials first. To identify patient subgroups that might benefit from multimodal surgical therapy, additional information on tumor genetics could supplement valid parameters. Trial registration: EU Clinical Trials No. 2023-503558-10-00. [ABSTRACT FROM AUTHOR]

Background: Lack of sexual and reproductive health (SRH) knowledge among adolescents can lead to risky sexual behaviors and poor SRH outcomes. This study aimed to assess the difference in SRH knowledge between adolescents in schools that received SRH interventions and those in non-intervention schools in Ebonyi State, Southeast, Nigeria. Methods: This was an intervention study that employed an ex-post outcome design. Data were collected from 503 in-school adolescent boys and girls aged 13–18 who were randomly selected from the eligible schools. The data were collected through a structured interviewer-administered questionnaire Participants were randomly selected for technique. Bivariate and multivariate analyses were conducted. Results: A significantly higher proportion of respondents who participated in the intervention (94.16%) demonstrated good knowledge of SRH compared to those who did not participate (85.77%), with a p-value of 0.002. Senior secondary school students (92.31%) exhibited better SRH knowledge than junior secondary school students (86.39%) (p = 0.031). Female adolescents were 3.2 times less likely to have good SRH knowledge compared to male adolescents. Conclusions: Efforts to adopt and scale up SRH interventions should prioritize equal and full participation across all adolescent groups, especially girls, junior students, working adolescents, and urban residents. [ABSTRACT FROM AUTHOR]

Stem cell therapies have in many respects revolutionized the way we explore and treat neurological diseases. Characterizing past and ongoing clinical trials using stem cells for neurological diseases will provide important insights for academia, industry and government. Based on the Trialtrove database, we retrospectively analyzed 530 clinical trials initiated by the end of 2023. [ABSTRACT FROM AUTHOR]

As the fastest growing demographic worldwide, the elderly population is projected to reach nearly 1 billion by 2030 and double the 2022 number by 2050. Despite being the largest consumers of medications, they have been historically underrepresented in clinical trials. However, we are witnessing a promising shift as their participation in trials is on the rise. In fact, recent megatrials enrolling more than 30,000 elderly participants demonstrated the feasibility of large-scale clinical trials involving this very specific population. However, unique challenges, including multi-morbidities, frailty, and ethically sound informed consent in those with cognitive deficits, require continuous careful reassessments and flexibility. Creative and tailored strategies are of paramount importance to bolster elderly trial participation. This paper highlights challenges and shares our experiences on novel methods and success stories associated with the enrollment and retention of elderly individuals in clinical trials. Successful tactics to balance the burden of clinical trial participation with its benefits encompass regular contact, family and friends' engagement, making travel easier or unnecessary, use of digital tools, and building relationships with community organizations. Through innovative strategies that consider the unique needs and limitations of this population, we can achieve successful participation in clinical trials. This will lead to more effective treatments and interventions for our growing elderly population. [ABSTRACT FROM AUTHOR]

Background: The effects of tPBMT are from influencing compounds by triggering specific reactions, which stimulate Adenosine triphosphate biosynthesis and neurogenesis. According to these effects, tPBMT has been applied as a potential treatment for various neural-related diseases. The purpose of this study was to evaluate the impact of tPBMT on reducing anxiety, depression, and opioid craving in patients undergoing MMT. Methods: This randomized controlled clinical trial included two groups of substance-dependent patients undergoing MMT. They were randomly assigned to receive tPBMT or a sham tPBMT. The intervention group received PBM in the form of Light- Emitting Diodes (LEDs) for four minutes of light exposure at 810 nm wavelength producing 250 mW/cm2 when applied to 4 mm skin depth (totaling 60 J/cm2) in both forehead locations. The levels of anxiety, depression, and opioid craving were compared between the two groups before and after the intervention, as well as at one-month and three-month follow-up assessments. Results: Both groups consisted of 32 (91.4%) males and 3 (8.6%) females, with the mean age of patients in the intervention group being 37.97 ± 10.58 years, and 39.66 ± 9.94 years in the control group (P = 0.495). There were no significant differences between the two groups in terms of depression, anxiety, and opioid craving scale scores before the intervention (p>0.05). However, the tPBMT group had statistically significant reductions in their scores compared to the sham tPBMT group. (p<0.05). Conclusion: tPBMT led to significant improvements in anxiety, depression, and opioid craving among individuals in MMT, and these improvements were sustained at one month and three months after treatment, indicating a long-lasting positive effect. Trial registration: Trial registration: IRCT code: IRCT20210502051162N1, Approval ID: IR.SBMU.MSP.REC.1400.111, registered on 01.06.2021 [ABSTRACT FROM AUTHOR]

Objective: An important criterion for selecting clinical trials to be compared in systematic reviews and meta-analyses is that they measure the same outcomes. However, this represents a challenge as there is a wide variety of outcomes, and it is difficult to standardize them for comparing clinical trials containing them. To address this challenge, we utilized our annotated dataset, which includes 211 abstracts of clinical trials related to glaucoma and type 2 diabetes mellitus. We then developed a tool that provides an overview of the annotated clinical trial information and enables users to group them by outcomes. Results: Using our visualization tool, we formed groups of outcomes and their respective clinical trials. We were able to determine the most common outcomes in clinical trials for these diseases. As a case study on diabetes, we compared our outcomes with those consented by diabetes stakeholders and found that many of the grouped outcomes are aligned with the consented ones. This demonstrates that tools such as the one presented can help standardize clinical outcomes, which in turn help in the synthesis of clinical trials. Finally, we also offer some recommendations that could help in the automation of clinical trials based on outcome standardization. [ABSTRACT FROM AUTHOR]

Background: Increasing transparency in clinical research is crucial to avoid misleading conclusions. Registering clinical trials prior to participant enrolment is mandatory, and the publication of trial protocols could further enhance transparency. However, the impact of protocol publication on primary outcomes (PO) and sample sizes (SS) remains unclear. This study aimed to determine the rates of trial protocol publication and registration for a sample of randomized controlled trials (RCTs) and to compare the consistency of published and registered PO and SS. Methods: A search was conducted in MEDLINE via PubMed® for RCT reports indexed in May and June 2023 across various medical specialties, focusing on general and high-impact factor journals. Data were extracted regarding trial registration, protocol publication, and comparisons were made between PO and SS in articles, registries, and published protocols. Results: Out of 1119 references, 589 (52.6%) were RCTs. The corresponding protocol was published for 146 RCTs (24.8%) including 40 over 140 (28.6%) (6 without end date available) after the trial had ended. Sixty-two (42.4%) protocols were published before the trial conclusion, with no significant differences between PO and SS in published protocols and their corresponding articles. Five hundred and twenty-eight (89.6%) RCTs were registered, 225 over 510 (44%) were registered before the study start with no differences in PO and SS between article and registry. Articles published in generalist or high impact factor journals were associated with higher frequencies of published protocols and trial registration and a lower frequency of difference in PO and SS between articles, registries, and published protocols. Conclusions: While publishing trial protocols may enhance transparency in peer-review process, the initial registered protocol alone appears sufficient for ensuring consistency in primary outcomes and sample sizes. Protocol publication does not seem to provide additional significant benefits in terms of outcome reporting. [ABSTRACT FROM AUTHOR]

Background: The high incidence of recurrence and malignant transformation of colorectal adenoma (CRA) are current issues that need to be addressed in clinical practice. Canmei Formula (CMF) has shown promising results in the prevention and treatment, however, it lacks effective clinical data support and its mechanism of action is not fully elucidated. Objective: The aim of this study is to evaluate the clinical efficacy and safety of CMF in preventing and treating CRA, and to explore its effective chemical components and pharmacological mechanisms. Method: A randomized controlled clinical trial was conducted, with patients diagnosed with CRA within 6 months as the study subjects. After randomization, the patients were divided into a treatment group (receiving CMF granules) or a control group (receiving berberine hydrochloride tablets). The one-year recurrence rate of CRA was used as the key efficacy indicator to assess the effectiveness of CMF in preventing and treating CRA. The chemical components of CMF were identified using the UFLC-Q-TOF-MS/MS combined system. Data mining and the wSDTNBI algorithm were combined to construct a differential expression gene (DEG) - CMF prediction target interaction network for CRA. The core targets of CMF in CRA prevention and treatment were identified through topological analysis, and validated using molecular docking and in vitro experiments. Result: During the period from October 1 2021 to December 31 2023, a total of 228 participants were included in the study. After block randomization, 114 patients were assigned to each group. In the treatment group, 98 patients completed follow-up examinations, with 16 patients (14.0%) exhibiting shedding, Adenoma recurrence was identified in 24 (24.5%) patients through colonoscopy. In the control group, 99 cases completed the follow-up examination, while 15 cases (13.2%) were lost to follow-up. There were 45 cases (45.5%) experienced recurrence of adenomas. During the follow-up period, no cases of colorectal cancer or severe adverse reactions were reported. UFLC-QTOF-MS/MS identification was combined with traditional Chinese medicine database mining to obtain 192 active chemical components of Canmei Formula. Using the wSDTNBI algorithm, 1044 prediction targets were predicted, and 3308 differentially expressed genes of CRA were extracted from the TCGA database. Network topology analysis and bioinformatics analysis were performed on 164 intersecting core targets. Molecular docking and qPCR analysis revealed that CMF downregulates angiotensin II type 1 receptor (AT1R) and regulated interleukin-8 (CXCL8) and matrix metalloproteinase 13 (MMP13) within the REN/Ang II/AT1R axis of the renin-angiotensin signaling pathway, thereby preventing and treating CRA. Conclusion: This small-scale randomized controlled clinical trial showed that CMF granules can safely and effectively reduce the risk of CRA recurrence. CMF prevents and treats colorectal adenomas by modulating the renin-angiotensin signaling pathway and the inflammatory response. [ABSTRACT FROM AUTHOR]

Background: The use of technology in medical education has been increasing with more students exposed to some form of online learning or tutorials, under the umbrella of virtual learning (VL). Many programmes, particularly those involving virtual reality, have centred on practical skills, such as surgical techniques or anatomical knowledge, rather than communication. The study presented here examined the feasibility and acceptability of a VL module developed to aid communication when handling angry patients and their relatives. Methods: Participants were 4th and 5th year medical students at the Brighton and Sussex Medical School. Students were randomly allocated to receive training about having angry conversations in a clinical setting via virtual reality headset or desktop application. Prior to the intervention, everyone completed the SE12 self-efficacy questionnaire, a 5-item confidence measure, and free-response study specific survey. Following the module, they completed another study specific survey, with fixed and free responses, the confidence measure, along with the UTAUT2 questionnaire on acceptance and use of technology. Quantitative data was analysed descriptively, conceptual content analysis was applied to free responses. Participants received a £25 voucher for their time. Results: Twenty students took part in the project. Scores on the SE12 did not differ significantly between intervention arms. Confidence improved across all five categories - recognising responses that diffuse or exacerbate anger, identifying anger signals, remaining calm in hostile situations, moving forward with empathy, and applying techniques to different situations. Responses to the UTAUT2 indicated acceptance of VL, including the psychological safety it provides. Nineteen categories for free text responses were developed via content analysis. Participants spoke frequently about the challenges of navigating anger. There was initial apprehension VL would not feel realistic, though this was largely reversed post-intervention. Students expressed preference for a combination of VL, whichever modality, and face-to-face teaching, recognising benefits of both. Conclusion: Students found the training to be acceptable, providing them with tangible skills. There should be a consideration as to how to incorporate VL, with a mix of face-to-face practice for added realism. Trial Registration: Clinical trial number not applicable. [ABSTRACT FROM AUTHOR]

Background: Linking registered clinical trials with their published results continues to be a challenge. A variety of natural language processing (NLP)-based and machine learning-based models have been developed to assist users in identifying these connections. To date, however, no system has attempted to detect mentions of registry numbers within the full-text of articles. Methods: Articles from the PubMed Central full-text Open Access dataset were scanned for mentions of ClinicalTrials.gov and international clinical trial registry identifiers. We analyzed the distribution of trial registry numbers within sections of the articles and characterized their publication type indexing and other metrics. Results: Registry numbers mentioned in article metadata (e.g., the abstract) or in the Methods section of full-text are highly predictive of clinical trial articles. When a clinical trial article mentioned ClinicalTrials.gov identifier numbers (NCT) only in the Methods section, in every case examined, it was reporting clinical outcomes from that registered trial, and thus can reliably be used to link that trial to that publication. Conversely, registry numbers mentioned in Tables arise almost entirely from reviews (including systematic reviews and meta-analyses). Registry numbers mentioned in other full-text sections have relatively little predictive value for linking trials to their publications. Clinical trial articles that mention CONSORT or SPIRIT guidelines have a higher rate of mentioning registry numbers in article metadata, and hence are more easily linked to their underlying trials, than articles overall. Conclusions: The appearance and location of trial registry numbers within the full-text of biomedical articles provide valuable features for connecting clinical trials to their publications. They also potentially provide information to assist automated tools in assigning publication types to articles. [ABSTRACT FROM AUTHOR]

Background: Phase-3 clinical trials provide the highest level of evidence on drug safety and effectiveness needed for market approval by implementing large randomized controlled trials (RCTs). However, 30–40% of these trials fail mainly because such studies have inadequate sample sizes, stemming from the inability to obtain accurate initial estimates of average treatment effect parameters. Methods: To remove this obstacle from the drug development cycle, we present a new algorithm called Trend-Adaptive Design with a Synthetic-Intervention-Based Estimator (TAD-SIE) that powers a parallel-group trial, a standard RCT design, by leveraging a state-of-the-art hypothesis testing strategy and a novel trend-adaptive design (TAD). Specifically, TAD-SIE uses synthetic intervention (SI) to estimate individual treatment effects and thereby simulate a cross-over design, which makes it easier for a trial to reach target power within trial constraints (e.g., sample size limits). To estimate sample sizes, TAD-SIE implements a new TAD tailored to SI given that using it violates assumptions under standard TADs. In addition, our TAD overcomes the ineffectiveness of standard TADs by allowing sample sizes to be increased across iterations without any condition while controlling significance level with futility stopping. Our TAD also introduces a hyperparameter that enables trial designers to trade off between accuracy and efficiency (sample size and number of iterations) of the solution. Results: On a real-world Phase-3 clinical RCT (i.e., a two-arm parallel-group superiority trial with an equal number of subjects per arm), TAD-SIE obtains operating points ranging between 63% to 84% power and 3% to 6% significance level in contrast to baseline algorithms that get at best 49% power and 6% significance level. Conclusion: TAD-SIE is a superior TAD that can be used to reach typical target operating points but only for trials with rapidly measurable primary outcomes due to its sequential nature. The framework is useful to practitioners interested in leveraging the SI algorithm for their study design. [ABSTRACT FROM AUTHOR]

Background & Aim: Metabolic and cardiovascular health outcomes are strongly influenced by diet. Dietary habits established in early childhood may persist into adulthood. This study aimed to examine the association between dietary patterns at both 2 and 8 years of age, explaining the maximum variability of high- and low-quality fats, sugars, and fibre, and cardiometabolic markers at age 8 years. Methods: This was a secondary analysis of the European Childhood Obesity Project, formerly a randomized clinical trial across five European countries performed in healthy term newborns. Children in the study were categorized at ages 2 and 8 years into two groups based on cluster analysis of dietary patterns (DP) derived from Reduction Rank Regression (RRR). A cross-sectional and prospective analysis was conducted to evaluate the associations between these DPs and cardiometabolic outcomes, including body mass index (BMI), blood pressure (BP), and biochemical markers. Triglycerides, HDL cholesterol and insulin resistance index (HOMA-IR) were also categorized as altered versus normal values. Asociations between dietary patterns and health outcomes were assessed using linear and logistic regression models, adjusting for covariates based on a step-wise approach. Results: A total of 336 children were classified based on quality of nutrient intakes into either a "Poor-Quality dietary pattern" (PQ-DP) (48% and 66% of infants at 2 and 8 years, respectively) or the "Health-Conscious dietary pattern" (HC-DP) (52% and 34% of infants at 2 and 8 years, respectively). Following a PQ-DP at both ages 2 and 8 was associated with higher triglycerides (β = 0.061, p = 0.049), systolic and diastolic BP (β = 13.019, p < 0.001 & β = 7.612, p = 0.014, respectively) and altered levels of HOMA-IR (OR = 3.1, p = 0.037, 95% CI = 1.1–9.1) at 8 years, compared to children with an HC-DP at both ages, after adjusting for confounders. Conclusion: Adherence to a dietary pattern with a poorer nutritional profile in early childhood and school age is associated with worse cardiometabolic risk markers at 8 years old. [ABSTRACT FROM AUTHOR]

Background and aim: Remimazolam has proved to be a very promising sedative drug in randomized clinical trials for usage in a wide spectrum of patients, including critically ill ones. The purpose of our study was to verify efficacy and safety of remimazolam for procedural sedation during diagnostic and first level operative endoscopy in a real-world setting. Methods: This single centre prospective study evaluated sedation regimen with remimazolam for EGDS and fentanyl and remimazolam for colonoscopy in consecutive ASA 1–3 patients. Results: Seventy-one patients underwent 73 procedures (25 EGDS, 48 colonoscopies) with a total amount of 13.2 ± 8.7 mg and 10.2 ± 6.2 mg of remimazolam administered respectively. In 6 EGDS, rescue sedation with propofol was needed. Transient hypotension was frequent (37%) and no cases of hypoxia occurred. One case of suspected allergy (erythema of the trunk) without anaphylaxis was reported. Conclusions: Procedural sedation can be applied with remimazolam without the use of propofol, obtaining effective sedation in colonoscopies while in EGDS remimazolam alone guarantees the result in a percentage of around 70–75% of cases. [ABSTRACT FROM AUTHOR]

Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorphism is inherently present in HIV-1 subtype C and conferred resistance to BVM. Second generation BVM analogs with modifications at C-28 position gained potent activity against HIV-1 subtype C. In this study, we have evaluated the efficacy of nine second-generation MIs (BVM analogs) with varying length of C28 carbon linker against HIV-1 subtype B and C. Increasing the length of carbon linker decreased their activity against both subtypes. These MIs were also active against integrase inhibitor-resistant viruses and protease inhibitor-resistant viruses. Our data has provided vital information that in addition to the nature of the functional group at C28 position of the MI, the length of linker contributes significantly to its activity. The shorter the length, the better the activity of MIs. These results will further pave way for design of novel and potent MIs. [ABSTRACT FROM AUTHOR]

Background: Inadequate medication knowledge and medication nonadherence by patients are considered an issue in healthcare, as they can lead to negative outcomes, such as therapeutic failures and hospitalization. Even though drug dispensing, which has pharmacist counseling as a core element, is a service traditionally performed by pharmacists, there is still no evidence about the influence of this service on these health outcomes. Objective: To evaluate the influence of drug dispensing on patients' medication knowledge and medication adherence. Methods: A systematic review was conducted in which a literature search was performed in the PubMed/Medline, Biblioteca Virtual da Saúde, Web of Science, and Embase databases, as well as in gray literature. Two reviewers read the titles, abstracts and complete texts according to the eligibility criteria and extracted the data from the included articles. Original studies—of any design—evaluating the influence of drug dispensing on patients' medication knowledge and/or adherence in community pharmacies were included. The methodological quality was assessed through the tools provided by the JBI Institute. The data was analyzed through qualitative synthesis and a meta-analysis was conducted for randomized controlled trials which used the outcome of medication adherence using the RStudio version 4.3.3 program. Results: A total of 7,590 studies were identified in the initial search, of which 11 articles met the eligibility criteria and were included in this systematic review. The studies were published in Africa, Latin America, Asia, Europe and Australia. Most of the studies were interventional (n = 7). Four studies evaluated the influence of drug dispensing on the patient's medication knowledge, and all showed that knowledge increased after dispensing. Eight studies evaluated the influence of dispensing on medication adherence. Three studies were included in the meta-analysis, which showed moderate heterogeneity (I2 = 44%, p = 0.17). The results indicated that there was no statistically significant difference in medication adherence post-dispensing (RR: 1.19; 95%CI 0.99 to 1.43, p = 0.07). Six studies met more than 70% of the quality assessment criteria. Conclusion: This systematic review demonstrated that patient's medication knowledge can be increased through drug dispensing. However, the meta-analysis indicated that drug dispensing does not have an impact on medication adherence. Our findings can support evidence-based decisions, guiding the planning and development of public policies and interventions which improve drug dispensing for patients, families, and communities. [ABSTRACT FROM AUTHOR]

Background: Even though major improvements have been made in the treatment of myeloma, the majority of patients eventually relapse or progress. Patients with multiple myeloma who relapse after initial high-dose chemotherapy with autologous stem cells have a median progression free survival up to 2–3 years, depending on risk factors such as previous remission duration. In recent years, growing evidence has suggested that allogeneic stem cell transplantation could be a promising treatment option for patients with relapsed or progressed multiple myeloma. However, prospective randomized trials including allogeneic stem cell transplantation as second-line therapy do not exist to date and therefore urgently needed to demonstrate the value of this therapy in the overall setting of patients with multiple myeloma. Methods: This clinical trial is a national, multicenter, randomized, open labeled phase III study conducted in 30 hospitals spread all over Germany. After study inclusion, all patients will receive 3 cycles of salvage therapy with one of the currently approved triplet regimens for first relapse. After 3 cycles of salvage therapy, remission status will be assessed. If the patient achieves at least stable disease, partial or complete remission and an HLA compatible stem cell donor could be identified, he/she will be randomized (1:1) to the control or interventional study arm. Approximately 400 patients will be enrolled to enable a randomization of 280 patients. The primary endpoint is overall survival at five years after randomization. The main secondary objectives and endpoints are progression-free survival rate, time-to first occurrence of an infection with CTCAE grade 3–5, non-relapse mortality rate and incidence of acute and chronic graft-versus-host disease after allogeneic stem cell transplantation. Discussion: The present clinical study is designed to evaluate the superiority of allogeneic stem cell transplantation compared to conventional therapy (triplet chemotherapy) for the difference in overall survival at 5 years, toxicity and quality of life in patients with multiple myeloma who have relapsed or progressed after first-line autologous stem cell therapy. Trial registration: ClinicalTrials.gov (NCT05675319) registered on January 9, 2023. [ABSTRACT FROM AUTHOR]

Background: Residual speech sound disorder (RSSD) is a high-prevalence condition that negatively impacts social and academic participation. Telepractice service delivery has the potential to expand access to technology-enhanced intervention methods that can help remediate RSSD, but it is not known whether remote service delivery is associated with a reduction in the efficacy of these methods. This project will systematically measure the outcomes of visual-acoustic biofeedback intervention when delivered in-person or online. Methods/design: This project, Visual-acoustic Intervention with Service delivery In-person and via Telepractice (VISIT), aims to treat 76 children in a parallel randomized controlled clinical trial in which children with RSSD will receive visual-acoustic biofeedback treatment either in person or via telepractice. Eligible children will be speakers of American English aged 9–17 years who exhibit RSSD affecting /ɹ/ but otherwise show cognitive-linguistic and hearing abilities within the typical range. All participants will receive twenty sessions of visual-acoustic biofeedback; they will be randomized, with stratification by pre-treatment speech production ability and site, to complete their treatment sessions either in the laboratory setting or at home via telepractice. For the primary outcome measure, blinded listeners will evaluate changes in the perceived accuracy of /ɹ/ production after the end of treatment. Discussion: By comparing outcomes in children randomized to receive a standard course of biofeedback treatment either via telepractice or in-person, this study will provide evidence-based guidance for clinicians seeking flexible service delivery options for a challenging and prevalent condition. Trial registration: ClinicalTrials.gov identifier NCT06517225, 07/23/2024. URL: https://clinicaltrials.gov/study/NCT06517225. [ABSTRACT FROM AUTHOR]

There has been a global increase in the use of cannabinoids as a treatment for mental health (MH) and substance use disorders (SUD). In 2016, an Australian government-funded review found that although medicinal cannabinoids accounted for a small reduction in MH symptoms, the results varied according to study design. There has since been a rise in randomised controlled trials (RCTs) aiming to examine the efficacy of cannabinoids for the treatment of MH and SUD. Therefore, the current systematic review will (a) identify all RCTs examining the efficacy of cannabinoids in treating MH and SUD, (b) provide a quantitative or narrative synthesis of the evidence examining efficacy, and (c) synthesise adverse event data to examine evidence of harm. Electronic databases (Ovid MEDLINE, PsychINFO, Cochrane Central Register of Controlled Clinical Trials, Cochrane Database of Systematic Reviews, and Embase) were searched from 1980 to 24 May 2023. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guidelines. Articles will be screened to capture peer-reviewed RCTs evaluating the efficacy of plant-based and pharmaceutical cannabinoids in reducing or treating MH and SUD among people of any age. The Cochrane risk of bias tool 2.0 will be used to assess bias, while the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) tool will be used to assess the quality of evidence for each outcome. Study findings will be disseminated through published manuscripts, conferences, and health policy guidelines. Systematic review registration PROSPERO CRD42023392718. [ABSTRACT FROM AUTHOR]

Background: Baseline systemic inflammation is associated with worse long-term outcomes after coronary artery bypass grafting [CABG], but the mechanisms of this association are unclear. This study aims to explore the association between pre-operative white blood cell [WBC] count and CABG graft failure. Methods: We pooled individual patient data from two randomized clinical trials with systematic CABG graft imaging. The primary analysis was the association between pre-operative WBC count and graft failure, as a continuous variable, at the time of imaging after CABG, using mixed-effects multivariable logistic regression models. Results: Overall, 910 patients and 2,036 grafts were included in the analysis [1,120 saphenous vein grafts, 828 left internal thoracic arteries, 76 right internal thoracic arteries, and 12 radial arteries]. The median time to imaging was 1.01 [interquartile range (IQR), 0.99;1.03] years and the median pre-operative WBC count was 7.1 [IQR, 6.0;8.4] x 109/L. There was no association between WBC count and graft failure at both the patient and the individual graft level [adjusted odds ratio (aOR) 1.07 (95% confidence interval (CI), 0.98;1.17), p = 0.11 and aOR 1.09 (95% CI, 0.91;1.30), p = 0.37], respectively. When evaluated as a dichotomous variable [≥ 11 vs. < 11 × 109/L] and by quartile, WBC count was not associated with graft failure at the patient and individual graft levels. Conclusion: In this pooled analysis of individual patient data from two randomized clinical trials, WBC count was not associated with graft failure after CABG. The reported association between inflammation and CABG is likely mediated through other mechanisms, such as native coronary artery disease progression. Impact on daily practice: The lack of a clear association between WBC count and graft failure suggests that pre-operative WBC count should not be routinely used as a predictor of graft failure after CABG. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of heart-collateral-based enlightenment words intervention on anxiety and depression in patients following percutaneous coronary intervention (PCI). Methods: In this class experimental study, one hundred patients who were hospitalized after PCI from May 2020 to October 2021, were included in this interventional study. They were divided into the test group (n = 50) and the control group (n = 50) based on the random number table. The heart-collateral-based enlightenment words intervention was used in the test group versus routine nursing in the control group. Data was collected using a self-rating anxiety scale (SAS), self-rating depression scale (SDS), and an independently developed satisfaction questionnaire. Psychological indicators and satisfaction were compared between the two groups before and after the intervention. Results: After 3 months of intervention, the test group scored significantly lower in SDS and SAS than the control group (SDS score: [55.06 ± 8.63] vs. [62.90 ± 9.52]; SAS score: [46.83 ± 10.24] vs. [56.02 ± 8.92]) (P < 0.05 for both SDS and SAS difference). The satisfaction rate of the test group vs. control group was 96% vs. 82% after the intervention, with a statistically significant difference (P < 0.05). Conclusion: Heart-collateral-based enlightenment words intervention can effectively alleviate anxiety and depression in patients after PCI and increase their satisfaction with nursing services. To develop the theory and guide clinical practice, future research in different treatment area with larger sample size should be conducted. [ABSTRACT FROM AUTHOR]

Throughout the COVID-19 pandemic, underserved populations, such as racial and ethnic minority communities, were disproportionately impacted by illness and death. Ensuring people from diverse backgrounds have the ability to participate in clinical trials is key to advancing health equity. We sought to analyze the spatial variability in locations of COVID-19 trials sites and to test associations with demographic correlates. All available and searchable COVID-19 studies listed on ClinicalTrials.gov until 04/04/2022 and conducted in the United States were extracted at the trial-level, and locations were geocoded using the Microsoft Bing API. Publicly available demographic data were available at the county level for national analysis and the census tract level for local analysis. Independent variables included eight racial and ethnic covariates, both sexes, and twelve age categories, all of which were population-normalized. The county-level, population-normalized count of study site locations, by type, was used as the outcome for national analysis, thereby enabling the determination of demographic associations with geospatial availability to enroll as a participant in a COVID-19 study. Z-scores of the Getis-Ord Gi statistic were used as the outcome for local analysis in order to account for areas close to those with clinical study sites. For both national (p < 0.001) and local analysis (p = 0.006 for Los Angeles, p = 0.030 for New York), areas with greater proportions of men had significantly fewer studies. Sites were more likely to be found in counties with higher proportions of Asian (p < 0.001) and American Indian or Alaska Native residents (p < 0.001). Areas with greater concentrations of Black or African American residents had significantly lower concentrations of observational (p < 0.001) and government-sponsored COVID-19 studies (p = 0.003) in national analysis and significantly fewer concentrations of study sites in both Los Angeles (p < 0.001) and New York (p = 0.007). Though there appear to be a large number of COVID-19 studies that commenced in the US, they are distributed unevenly, both nationally and locally. [ABSTRACT FROM AUTHOR]

Background: The influence of femoroacetabular (FA) impingement has been implied in early hip osteoarthritis, particularly in young patients who enjoy athletics. The purpose of this meta-analysis is to assess the effectiveness and safety of hip arthroscopy compared to open surgical dislocation for the treatment of femoroacetabular impingement (FAI), based on clinical trials that have been published. Methods: A comprehensive literature search was conducted through PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials for studies evaluating coxoscopy and open surgical dislocation as treatment modalities for femoroacetabular impingement syndrome (FAI). Results: Ultimately 9 studies were added in this meta-analysis. 9 studies reported the Improvement of alpha angle of the Hip Arthroscopy treatment group and the surgical treatment group, which was no remarkable statistical significance(SMD: -5.54; 95% Cl: -12.45,1.38; P = 0.117) compared to the surgical treatment group, Modified Harris Hip Score (mHHS) after 12 months of follow-up(SMD: 0.94; 95% Cl: -2.87,4.75; P = 0.629), Nonarthritic Hip Score (NAHS) after 12 months of follow-up (SMD:6.31; 95% Cl: 0.53,12.09; P = 0.032), rate of recurrence (OR: 0.48; 95% Cl: 0.29,0.82; P < 0.01), and rate of Complication (OR: 0.66; 95% Cl: 0.26,1.65; P = 0.372). Conclusion: Alpha angle improvement, mHHS, NAHS after 12 months of follow-up, rate of recurrence, and rate of Complication are some of the indicators of the study's results point to the possibility that hip arthroscopy may be effective for patients with FA impingement; hence, these conclusions required to be corroborated by additional superior-quality studies. [ABSTRACT FROM AUTHOR]

Background: Clinical competence and emotional intelligence are both essential factors for the success of nursing students in their profession. Due to the inconsistent findings regarding the relationship between clinical competence and emotional intelligence in nursing students, this study aims to investigate this relationship among nursing students at Alborz University of Medical Sciences, Iran. Methods: In this descriptive, correlational, cross-sectional study, 220 nursing students from the 2nd to the 8th semester were included in the study by census method. The data were collected using a questionnaire comprising three sections: demographic information, clinical competence assessment, and emotional intelligence assessment. Data analysis was performed using descriptive and inferential statistics with SPSS software version 22, at a significance level of P ≤ 0.05. Results: Out of 220 nursing students, 176 completed the questionnaires. The mean score of participants' clinical competence was 102.58 ± 19.94, indicating a moderate level. The emotional intelligence of the students also showed a moderate level, with a mean score of 81.16 ± 7.04. A significant positive correlation was observed between clinical competence and emotional intelligence (P < 0.001). The predictive role of three dimensions of emotional intelligence (self-awareness, self-management, and relationship management) was confirmed (P < 0.05). Conclusion: In this study, a positive and significant correlation was observed between clinical competence and emotional intelligence, indicating that higher emotional intelligence is associated with greater clinical competence. Accordingly, it is recommended to design and implement interventional studies aimed at enhancing students' emotional intelligence and evaluating the effectiveness of such interventions on their emotional intelligence and clinical competence. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit. Methods: Patients with laPDAC will receive at least six cycles of GEM-NABP with 1:1 randomisation to receive this with or without ATRA to assess response, until progression or intolerance. Those with stable/responding disease may undergo surgical resection. Primary endpoint is progression free survival (PFS) defined as the time from the date of randomisation to the date of first documented tumour progression (response evaluation criteria in solid tumours [RECIST] v1.1) or death from any cause, whichever occurs first. Secondary endpoints include objective response rate (ORR), overall survival (OS), safety and tolerability, surgical resection rate, R0 surgical resection rate and patient reported outcome measures (PROMS) as measured by questionnaire EQ-5D-5L. Exploratory endpoints include a decrease or increase in CA19-9 and serum Vitamin A over time correlated with ORR, PFS, and OS. Discussion: STARPAC2 aims to assess the role of stromal targeting in laPDAC. Trial registration: EudraCT: 2019–004231-23; NCT04241276; ISRCTN11503604. [ABSTRACT FROM AUTHOR]

Background: Africa's involvement in clinical trials remains very low. Although the crucial role of training initiatives in building clinical trial capacity in Africa has been documented, current efforts fall short as they lack alignment with local contexts. This study aimed to design, develop, implement, and evaluate an innovative clinical trial operations training program for Africa. Methods: We developed ClinOps, a novel 10-week clinical trial operations training program for study coordinators in Africa to enhance their expertise in four fundamental areas: designing, conducting, managing, and reporting clinical trials. To streamline the learning process, we used cloud-based applications that minimize the need for software installations while maximizing student engagement. VoiceThread facilitated interactive content that could be accessed offline. Moodle, an open-source learning management system, offered a platform for sharing learning tools, mentorship, and rubric-driven competency assessments, including quizzes, forums, tutorials, and group assignments. We utilized Zoom for live tutorials and mentoring as required. Effectiveness of the program was evaluated through quantitative pre- and post-surveys, qualitative end-course evaluations, and a comprehensive monitoring and evaluation framework. The pre- and post-surveys measured changes in trainees' confidence in clinical trial domains and leadership and coordination skills. End-course evaluations gathered feedback on the course content, organization, technology, and instructional methods. We used Wilcoxon rank test to analyze pre- and post-survey scores and thematic analysis to analyze the qualitative data. Results: In the initial cohort, 88 study coordinators from 19 countries participated, including 56 (64%) females, with 57 (65%) actively employed as study coordinators during the training, and 85 (97%) possessing prior experience in clinical trial roles. Among these, 71 (81%) successfully completed the course, with 69 (97%) also completing the post-course assessment. Post-training scores demonstrated substantial improvement compared to pre-training scores in each competency area, including in designing (pre-post training median score = 3.6 vs. 4.6, median difference = 1.0, 95% CI 0.8–1.1, p < 0.001), managing (pre-posttest median score = 3.4 vs. 4.2, median difference = 0.6, 95% CI 0.4–0.8, p < 0.001), conducting (pre-post training median score = 3.9 vs. 4.7, median difference = 0.9, 95% CI 0.6-1.0, p < 0.001), and reporting (pre-posttest median score = 3.0 vs. 4.5, median difference = 1.0, 95% CI 0.9–1.5, p < 0.001) clinical trials. The monitoring and evaluation data confirm the program's adherence to training best practices, including alignment with local priorities, country ownership, pedagogic innovation, institutional capacity building, sustainability, and ongoing partnerships. The end-course evaluation reflects participants' positive feedback on the program's structure, content, relevance to their current roles, and overall delivery methods. Conclusion: The ClinOps program, designed by experts from academia and product development partners, enhanced participants' clinical trial competencies. To effectively build clinical trials capacity on the continent, training programs should provide thorough competency development in designing, conducting, managing, and reporting trials. [ABSTRACT FROM AUTHOR]

Background: The PALLAS trial investigated the addition of palbociclib to standard adjuvant endocrine therapy to reduce breast cancer recurrence. This pre-specified analysis was conducted to determine whether adjuvant palbociclib benefited patients diagnosed with lower risk stage IIA disease compared to those with higher stage disease. Methods: PALLAS was an international, multicenter, randomized, open-label, phase III trial, representing a public–private partnership between Pfizer, the Austrian Breast Cancer Study Group, and the U.S. ALLIANCE Foundation. Patients diagnosed with stage II–III, hormone-receptor-positive, HER2/neu negative breast cancer within 12 months of diagnosis had completed all definitive therapy aside from endocrine therapy (started within 6 months prior to study entry) were eligible. All patients were required to submit a formalin-fixed paraffin-embedded (FFPE) tumor block. Patients were randomly assigned 1:1 to receive standard adjuvant endocrine therapy (of physicians' choice) for at least 5 years with or without 2 years of palbociclib, administered orally at a starting dose of 125 mg daily, given for 21 days followed by a 7-day break. Results: A total of 5,796 patients with HR + /HER2- early breast cancer (including 1,010 with stage IIA) were enrolled. Median follow-up was 50 months for stage IIA patients and 43.1 months overall. In the stage IIA cohort, 4-year iDFS in the palbociclib arm was 92.9% versus 92.1% for ET alone (HR 0.75, 95%CI 0.48–1.19, p = 0.23). There was no differential benefit by histologic grade, chemotherapy receipt, age, or anatomic/clinical risk. Additionally, no benefit to palbociclib was seen in this cohort in invasive breast cancer-free survival (iBCFS), locoregional relapse-free survival (LRFS), distant relapse-free survival (DRFS), or overall survival (OS). For the stage IIB/III patients, 4-year iDFS was 85.3% for palbociclib + ET versus 83.6% for ET alone (HR 0.91, 95% CI 0.77–1.07, p = 0.24). Conclusions and relevance: While there were substantial differences in outcome for stage IIA versus IIB/III patients at 4 years of follow-up, the addition of 2 years of palbociclib did not improve outcomes for patients, regardless of stage. Trial Registration: ClinicalTrials.gov number NCT02513394 Registered 30 Jul 2015. [ABSTRACT FROM AUTHOR]

Introduction: Considering the importance of sleep disorders in children with attention-deficit/hyperactivity disorder (ADHD) and effective therapeutic strategies, the present study aimed to investigate the effects of auriculotherapy on sleep quality in children with ADHD. Materials and methods: This clinical trial was conducted in children with ADHD in Kashan, Iran, 2021–2022. Fifty-two eligible samples were selected using convenience sampling and randomly assigned to intervention and sham groups. The intervention group used Vacaria seeds to apply ear acupressure to Shenmen, Sympathetic, Subcortex, Heart, and Endocrine points for four weeks, while the sham group received adhesives without seeds and pressure. Sleep quality was assessed using children's sleep habits questionnaire at the beginning (T0), at the end of the intervention (T1), and one month later (T2). Data from 45 children (23 and 22 children in the intervention and sham groups, respectively) were analyzed using the per-protocol and intention-to-treat designs using repeated measures analysis of variance. Results: The background variables did not significantly differ between two groups. The between-group analysis revealed a significant interaction effect of time and intervention on sleep quality (Effect Size = 0.545, p < 0.0001). The sleep quality score in the intervention group was significantly greater than in the sham group at T1 and T2 (p < 0.0001). The within-group analysis of the intervention group revealed a significant difference in sleep quality scores at three time points (Effect Size = 0.672, p < 0.05). In the sham group, sleep quality score increased significantly over time (Effect Size = 0.511, p < 0.05). Conclusions: The findings suggest that auriculotherapy may be a beneficial complementary treatment for improving sleep quality in children with ADHD. [ABSTRACT FROM AUTHOR]

Background: Pleural diseases is a common respiratory disorder, mainly characterized as pleural effusion and patients with pleural effusion caused by pneumonia and empyema constituted 29% of the cohort, which suggests pleural infection as the predominant etiology of pleural effusion in China. Medical thoracoscopy (MT) combined with intrapleural injection of Urokinase holds significant therapeutic value for patients with early to moderate-stage empyema. However, there remains a lack of high-quality evidence regarding the efficacy and safety of combining MT with intrapleural injection of Urokinase administration in patients with pleural infections. Methods: This study is a prospective, multicenter, randomized controlled clinical trial involving patients with pleural infections. The intervention involves medical thoracoscopy. The control group receives conventional treatment involving intrapleural urokinase injection followed by chest tube placement for drainage. The study outcomes include efficacy and health economic benefits. The estimated minimum sample size for each group is 64 cases, totaling 128 cases. The study groups are delineated as follows: patients in group A receives intrapleural urokinase injection followed by chest tube placement for drainage, while patients in group B undergoes MT to remove multiple septa and necrotic tissue followed by chest tube placement for drainage, and then intrapleural urokinase injection the day after MT. It is recommended that the diameter of the chest tube be 12–14 F, with three daily flushes of 30 ml normal saline to ensure optimal drainage. Subsequently, comprehensive statistical analyses will be conducted to compare treatment effects and complications across all groups, ultimately leading to conclusive findings. Discussion: The study is the first prospective, multicenter clinical trial on the efficacy and safety of medical thoracoscopy combined with intrapleural urokinase injection for the treatment of pleural infection. This study aims to offer clinical guidance for the management of pleural infection. Registration number: ChiCTR2300078352 (Registration Date: 2023/12/06). [ABSTRACT FROM AUTHOR]

Background: The incidence of acute cardiac arrest is increasing and is directly linked to patient survival, highlighting the critical role of nurses. Advanced nursing skills for cardiac arrest patients, such as self-directed pre-learning applied to various clinical situations, require a systematic blended learning approach to integrate knowledge and enhance clinical performance through face-to-face practice. The purpose of this study is to evaluate the effectiveness of a blended simulation education program for Advanced Cardiac Life Support (ACLS) using the PARTNER model. Methods: A nonequivalent control group pretest-posttest design with a time-lagged approach was used to collect data from 34 third-year nursing students. The experimental group(n = 17) received a 480-minute blended simulation education program based on the PARTNER model and flipped learning, while the control group(n = 17) participated in a 480-minute traditional simulation education program. Results: The study found that knowledge, confidence, performance in advanced cardiac life support, and clinical performance ability were effectively enhanced, although no significant effect was observed in learning satisfaction. Conclusions: The program provides a new direction in applying blended simulation using the PARTNER model for advanced cardiac life support nursing education, ultimately contributing to the training of nurses competent in advanced cardiac life support. [ABSTRACT FROM AUTHOR]

Background: Diabetic myocardial disorder (DbMD, evidenced by abnormal echocardiography or cardiac biomarkers) is a form of stage B heart failure (SBHF) at high risk for progression to overt HF. SBHF is defined by abnormal LV morphology and function and/or abnormal cardiac biomarker concentrations. Objective: To compare the evolution of four DbMD groups based on biomarkers alone, systolic and diastolic dysfunction alone, or their combination. Methods: The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial was a Phase 3 randomised trial of an aldose reductase inhibitor in patients with well-controlled type 2 diabetes mellitus (T2DM). The 1858 potential participants (age 67 ± 7 years; 50% women) were screened for SBHF based on abnormal echocardiography or biomarkers (N-terminal pro-B-type natriuretic peptide ≥ 40 ng/L or high sensitivity cardiac troponin T ≥ 10 ng/L [women] and ≥ 16 ng/L [men]). Exercise capacity (peak VO2) was reduced in 669 with DbMD (age 68 ± 7, 50% women), and peak VO2 was reassessed at 15 months. Results: The 1463 (79%) participants with DbMD were allocated to four clusters; 907 (49%) showed isolated elevation of cardiac biomarkers, 301 (16%) with systolic dysfunction/hypertrophy, 162 (9%) with diastolic dysfunction and 93 (5%) comprised an overlap cluster (combined diastolic, systolic or LV geometric abnormalities). Reduced VO2 (< 75% predicted) was present in 669 (46%); 72% of those with both systolic and diastolic dysfunction, 56% of those with systolic dysfunction and LVH, 53% of those with diastolic dysfunction and 38% with biomarkers alone (p < 0.0001). In 669 patients followed over 15 months, there was a similar small decrement in VO2 in all groups. Conclusions: Among individuals with T2DM and SBHF, reduced functional capacity is most prevalent in those with multiple physiological disturbances. However, there was no difference between phenogroups in the evolution of exercise intolerance. Trial Registration: ARISE-HF, NCT04083339. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the efficacy and safety of diacylglycerol (DAG) edible oil intervention in patients with chronic metabolic syndrome complicated by asymptomatic hyperuricemia through a multicenter, prospective, double-blind, randomized controlled clinical trial. Methods: A multicenter, double-blind, and randomized controlled trial involving 176 patients was designed. All patients with chronic metabolic syndrome complicated by asymptomatic hyperuricemia who meet inclusion and exclusion criteria will be included in the study and will be randomized to either group A or group B. Group A will receive DAG-rich oil (≥ 80%) and group B will receive conventional cooking oil (triacylglycerol (TAG)-rich oil) for 12 weeks. Serum uric acid level is the primary outcome. Fasting blood glucose, 2 h postprandial blood glucose, fasting insulin, glycated hemoglobin, lipid profile, and average carotid intima-media thickness will be evaluated as the secondary outcomes. Blood routine, urine routine, liver enzymes, and electrocardiogram will be tested to assess the safety. The sample size for each group was calculated to be 88 cases. Discussion: We will evaluate the efficacy and safety of DAG oil compared with conventional TAG oil in patients with chronic metabolic syndrome with asymptomatic hyperuricemia. The dietary oil with superior efficacy and better safety will be recommended for reference use. Trial registration: Chinese Clinical Trial Registry ChiCTR2400085336. Registered on June 5, 2024. [ABSTRACT FROM AUTHOR]

Background: Prescribing physical exercise as part of the clinical treatment of cancer patients has become an important strategy in the therapeutic arsenal available in the main health centers specialized in neoplastic diseases, but there is still uncertainty regarding the role of regular physical activity in modifying oxidative stress markers and antioxidants, as high levels of oxidative stress can lead to the development of carcinogens. Therefore, we assessed the effect of physical activity versus absence of physical activity on markers of oxidative stress and antioxidants in cancer patients. Methods: We looked for randomized controlled trials that included adult with any type of cancer performing some physical activity and compared them to a control group of cancer patients with no physical activity. The outcomes of interest collected were markers of oxidative stress and antioxidants. Six databases were used for the search (EMBASE, The Cochrane Library (CENTRAL), US National Library of Medicine (PubMed), Physiotherapy Evidence Database (PEDro), Cumulative Index of Nursing and Allied Health (CINAHL) and SPORTDiscus via EBSCO) until January 31st, 2024. Results: In the end, 7 randomized controlled clinical trials were included, totaling 573 participants. It was possible to conduct a meta-analysis with demonstrated that physical activity potentially increases the antioxidant marker Trolox, Taoc, Gpx, (SMD = 1.23, CI: 0.13 to 2.34). However, these findings were classified as having very low to moderate GRADE evidence. Conclusion: Cancer patients who participated in physical activity programs may have exhibited an increased concentration of antioxidants. Although the overall quality of the evidence in the studies was very low, these findings represent an important field of research that should be guided by studies with more participants and homogeneous methods of analysis of oxidant stress and antioxidant markers. Trial registration: PROSPERO CRD42021257815. [ABSTRACT FROM AUTHOR]

Background: The insertion of a tracheostomy is an established technique used to wean patients off ventilatory support, manage secretions in complex conditions, and as a potentially life-saving procedure to bypass upper airway obstruction. Life-threatening complications during aftercare are not uncommon and may be influenced by a lack of education of carers or healthcare providers of children and young people living with a tracheostomy. Education programmes designed and supported by the National Tracheostomy Safety Project are effective, but resources are not available to educate the workforce at scale. With the overarching aim of widening access to paediatric tracheostomy skills training, we present the protocol for the development and evaluation of a novel virtual reality (VR) training tool designed to simulate the emergency management of paediatric tracheostomy complications. Methods and discussion: A multi-centre, non-inferiority educational interventional study with historical controls will be used to evaluate the novel VR training package. A group of 69 healthcare staff and students will have one week to use the educational intervention as often as necessary to learn paediatric emergency tracheostomy skills. The primary outcome measure is skill performance in simulation in a pre- and post-intervention structure within subjects. Participant performance will also be assessed using non-inferiority metrics against historical traditional educational control data. Secondary outcomes include knowledge gain, knowledge retention, usability, side effects, and participant satisfaction. To minimise the risk of cybersickness, teleportation was the preferred locomotion method for the user navigation within the VR environment. Trial registration: Full registration of this study was completed at ClinicalTrials.gov. The registration number is NCT06350708 and was accepted on the 4th April 2024. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the predictive accuracy of 11 intraocular lens (IOL) calculation formulas in eyes with an axial length (AL) less than 22.00 mm. Methods: New-generation formulas (Barrett Universal II [BUII], Emmetropia Verifying Optical [EVO] 2.0, Hill-Radial Basis Function [Hill-RBF] 3.0, Hoffer QST, K6, Kane, Pearl-DGS) and traditional formulas (Haigis, Hoffer Q, Holladay 1 and SRK/T) were evaluated for predictive accuracy. Subgroup analyses were performed based on AL and anterior chamber depth (ACD). Results: The study enrolled a total of 184 eyes from 184 patients. The BUII, Hoffer QST, Hoffer Q, Holladay 1, and SRK/T showed myopic shifts (-0.49 to -0.18 diopters [D], P < 0.05), whereas K6 displayed a hyperopic shift (0.11 D, P = 0.03). The Kane exhibited no systematic bias (-0.07 D), and yielded lower mean absolute error (MAE) (0.48 D, P < 0.05) and root mean square absolute error (RMSAE) (0.65 D, P < 0.01). For eyes with an AL ≤ 21.5 mm and an ACD > 2.5 mm, the Pearl-DGS displayed the smallest MAE (0.43 D) and lowest RMSAE (0.57 D), while other new-generation formulas showed relatively worse performance (MAE: 0.46 to 0.67 D; RMSAE: 0.60 to 0.84 D). Conclusion: The Kane formula showed the highest accuracy in short eyes, whereas the Pearl-DGS had superior performance in eyes with a relatively shorter AL and deeper ACD. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Research into cancer treatment has been mainly focused on developing therapies to directly target cancer cells. Over the past decade, extensive studies have revealed critical roles of the tumour microenvironment (TME) in cancer initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) have emerged as one of the primary contributors in shaping TME, creating a favourable environment for cancer development. Many preclinical studies have identified promising targets on CAFs, demonstrating remarkable efficacy of some CAF-targeted treatments in preclinical models. Encouraged by these compelling findings, therapeutic strategies have now advanced into clinical evaluation. We aim to provide a comprehensive review of relevant subjects on CAFs, including CAF-related markers and targets, their multifaceted roles, and current landscape of ongoing clinical trials. This knowledge can guide future research on CAFs and advocate for clinical investigations targeting CAFs. [ABSTRACT FROM AUTHOR]

Background and methods: E-health solutions are a promising tool to assist patients in self-managing symptoms for various diseases. This study aimed to assess the feasibility, reliability, usability, and satisfaction of a digital medical device (ZEMY) for patients' self-monitoring of symptoms commonly experienced during breast cancer treatment and to enhance interaction with healthcare professionals. In this open-label, interventional, multicentre, single-arm clinical trial (NCT03558490), patients at all stages of breast cancer initiating oral and/or parenteral treatment were recruited at initiation of therapy and followed for 3 months. During treatment, the patients reported 9 symptoms (diarrhoea, nausea/vomiting, fever/febrile neutropenia, fatigue, pain, cutaneous and mucosal toxicities, hypertension, anxiety/depression) through the ZEMY application, which provided self-management recommendations and sent message alerts to healthcare professionals. To reach the primary feasibility endpoint, more than 50% of patients with one-sided 95% confidence interval (exact CI computed using Clopper-Pearson method) had to complete at least 3 symptoms entries, of which more than 60% complete until receiving a recommendation. Results: Out of the 56 screened patients, 54 were included in the analysis between June 12th 2018 and January 11th 2019, and 52 completed the study. Over half of patients (31/54 [57.4%]) were feasibility responders, but this percentage was not significantly higher than the predefined minimum feasibility cut-off of 50%, as the lower limit of the one-sided 95% exact CI was 45.3%. Nonetheless, 87.0% of patients reported at least 3 symptoms with ZEMY and 66.0% had an entry completion rate ≥ 60%. Six of the 9 symptoms were reported at least once by more than 30% of the patients. The recommendations were considered relevant at least once for more than 80% of cases for each symptom. Patients were more satisfied (mean 10-point visual analogue scale score: 6.3 ± 2.9) with ZEMY than healthcare professionals (4.4 ± 1.5). The global patients' quality of life remained stable during the study. Conclusions: ZEMY provided satisfactory recommendations for the self-management of selected symptoms occurring during anti-cancer treatment and demonstrated good usability, but its feasibility was indemonstrable. Trail registration: The trial was registered on June 14th 2018 at ClinicalTrails.gov (Trial Registration Number: NCT03558490). [ABSTRACT FROM AUTHOR]

Background: Virtual surgical planning for orthognathic surgery typically relies on two methods for intraoperative plan transfer: CAD/CAM occlusal splints and patient-specific implants (PSI). While CAD/CAM splints may offer limited accuracy, particularly in the vertical dimension, PSIs are constrained by higher costs and extended preparation times. Surgical navigation has emerged as a potential alternative, but existing protocols often involve invasive registration or lack transparent evaluation. This study introduces a novel protocol for point-based optical navigation using modified CAD/CAM splints for non-invasive registration and transparent intraoperative evaluation, assessing its effectiveness in maxillary positioning. Methods: This prospective case-control study included 20 patients undergoing bimaxillary orthognathic surgery. The experimental group employed surgical navigation with modified CAD/CAM splints, while the control group used standard CAD/CAM splints. Surgical accuracy was evaluated by measuring translational and rotational discrepancies between the planned and achieved maxillary positions. A mixed ANOVA was conducted to assess other factors, aside from surgical navigation, that might influence surgical accuracy. Results: Surgical navigation significantly improved accuracy in translational movements along the x-axis (right-left: -0.81 mm; p = 0.021) and z-axis (down-up: -0.82 mm; p = 0.014), as well as in yaw rotation (-0.45°; p = 0.045). Other movements also showed improved precision in the navigated group, though not statistically significant; y-axis (back-front): -0.60 mm (p = 0.094); pitch rotation: -0.70° (p = 0.071); roll rotation: -0.04° (p = 0.428). Besides the use of surgical navigation, the amount of planned movement significantly impacted surgical accuracy, although no specific factors could be identified to predict which cases would particularly benefit from surgical navigation. Conclusions: Surgical navigation with modified CAD/CAM splints enhances surgical accuracy without requiring invasive procedures, offering a straightforward and transparent protocol suitable for routine clinical practice that allows intraoperative evaluation of maxillary positioning. However, the clinical significance and cost-effectiveness compared to PSI need further investigation. These findings suggest new directions for future developments, especially with advancements in mixed reality technologies, which could broaden the application of surgical navigation. Trial registration: Retrospectively registered with the German Clinical Trials Register (DRKS00034795). [ABSTRACT FROM AUTHOR]

Background: A key challenge for many critical care clinical trials is that some patients will die before their outcome is fully measured. This is referred to as "truncation due to death" and must be accounted for in both the treatment effect definition (i.e. the estimand), as well as the statistical analysis approach. It is unknown which analytic approaches to this challenge are most relevant to stakeholders. Methods: Using a modified Delphi process, we sought to identify critical attributes of analytic methods used to account for truncation due to death in critical care clinical trials. The Delphi panel included stakeholders with diverse professional or personal experience in critical care-focused clinical trials. The research team generated an initial list of attributes and associated definitions. The attribute list and definitions were refined through two Delphi rounds. Panelists ranked and scored attributes and provided open-ended rationales for responses. A consensus threshold was set as ≥ 70% of respondents rating an attribute as "Critical" (i.e., score ≥ 7 on a 9-point Likert scale) and ≤ 15% of respondents rating the measure as "Not Important" (i.e., a score of ≤ 3). Results: Thirty-one (91%) of 34 invited individuals participated in one or both rounds. The response rate was 82% in Round 1 and 85% in Round 2. Participants included eight (26%) personal experience experts and 26 (84%) professional experience experts. After two Delphi rounds, four attributes met the criteria for consensus: accuracy (the approach will identify effects if they exist, but will not if they do not), interpretability (the approach enables a straightforward interpretation of the intervention's effect), clinical relevance (the approach can directly inform patient care), and patient-centeredness (the approach is relevant to patients and/or their families). Attributes that did not meet the consensus threshold included sensitivity, comparability, familiarity, mechanistic plausibility, and statistical simplicity. Conclusions: We found that methods used to account for truncation due to death in the treatment effect definition and statistical approach in critical care trials should meet at least four defined criteria: accuracy, interpretability, clinical relevance, and patient-centeredness. Future work is needed to derive objective criteria to quantify how well existing estimands and analytic approaches encompass these attributes. [ABSTRACT FROM AUTHOR]

Background: Myelofibrosis (MF) is a clonal haematopoietic disease, with median overall survival for patients with primary MF only 6.5 years. The most frequent gene mutation found in patients is JAK2V617F, causing constitutive activation of the kinase and activation of downstream signalling. Fedratinib is an oral selective JAK2 inhibitor. It has shown activity in MF and is well-tolerated, but combination with other therapies is likely needed to achieve clonal remission. Combining a JAK2 inhibitor with an interferon may be synergistic, as haematopoietic cells are activated from quiescence (a typical kinase resistance mechanism) rendering them more sensitive to inhibition. Ropeginterferon alfa-2b is a next generation pegylated interferon-α-2b with high tolerability and clinical activity in patients with MF, however, evidence of tolerability and activity in combination with fedratinib is lacking in this setting. The aim of the FEDORA trial is to assess tolerability, safety, and activity of fedratinib with ropeginterferon alfa-2b in patients with MF who require treatment to justify further investigation in a phase III trial. Methods: FEDORA is a single arm, multicentre, open-label, Bayesian phase II trial to assess tolerability, safety, and activity of fedratinib with ropeginterferon alfa-2b aiming to recruit 30 patients. Patients with JAK2V617F positive primary or secondary MF, who are aged ≥ 18 years, have intermediate-1 with palpable splenomegaly of > 5cm, intermediate-2, or high-risk disease according to the Dynamic International Prognostic Scoring System (DIPSS), and who require treatment are eligible. The primary outcome is tolerability, whereby the combination is deemed intolerable in a patient if drug-related toxicities in the first four months of treatment lead to: either drug being discontinued; delays in treatment exceeding 28 consecutive days; or death. FEDORA uses a within-patient dose escalation regimen to ensure each patient reaches a personalised dose combination that is acceptable. Discussion: FEDORA is using a Bayesian trial design and aims to provide evidence of the tolerability, safety, and activity of combining fedratinib with ropeginterferon alfa-2b upon which the decision as to whether a phase III trial is warranted will be based. Trial registration: EudraCT number: 2021–004056-42. ISRCTN: 88,102,629. [ABSTRACT FROM AUTHOR]

Background: Diabetes with its highly prevalence has become a major contributor to the burden of health care costs worldwide. Recent unequivocal evidence has revealed a bidirectional link between oral health and diabetes. In this study, the effects of the Oral Health Promotion Program (OHPP) on oral hygiene, oral health-related quality of life and glycated haemoglobin (HbA1c) levels in diabetic elderly were examined. Moreover, microbial changes in the saliva microbiota community were also emphatically investigated. Methods: A quasi-experiment was conducted in regionally representative communities to assess oral health and oral microbiota of the elderly diabetic participants. The participants in the intervention group (n = 26) received OHPP including three phases of cognition, intensification and consolidation during the program, when those in the control group (n = 26) received routine oral care. Clinical parameters were recorded at two different time points as before the study (T0), and 3 months after intervention onset (T1). Oral health was measured via the oral health impact profile (OHIP-14) questionnaire, dental plaque index, HbA1c and mastery of oral health knowledge, and sequencing of the 16S rRNA gene from saliva samples was used to analyze the oral microbiota. Results: The average age of the final sample was 71.77 years (SD = 6.06), 53.8% (28/52) of whom were male. A reduction in the plaque index and improvements in oral health-related quality of life and mastery of oral health knowledge were observed in the intervention group. Meanwhile, the α-diversity of the microbiota increased in both groups, but more significant in the intervention group. PCoA analyses showed significant differences in microbial community structure in both groups, and LEfSe analyses revealed a decrease of g_Streptococcus and g_Rothia after the implementation of OHPP and a decrease of g_Streptococcusa, g_Porphyromonas, g_Gemella after the routine oral care. There was no statistically significant difference in the HbA1c level between two groups. Conclusions: OHPP superiorly contributes to the improvement of oral health and oral microbiota in elderly diabetic patients. The overarching goal is to introduce attention to the importance of good oral health as a crucial point in preventing and managing diabetes mellitus and thereby make it a meaningful contribution to public health and geriatric care. Trial registration: This study was retrospectively registered in Chinese Clinical Trial on October 9, 2022 (ID ChiCTR2200064453). [ABSTRACT FROM AUTHOR]

Background: In India, approximately 3.5 million children are affected by Developmental Delay (DD), often stemming from preterm births. These delays contribute to neurological and motor development delays, placing a significant financial burden on families. Maternal unemployment rates are also elevated in such cases. Delayed Developmental Milestones identification, often due to a lack of parental awareness, further compounds these challenges. This study introduces a multiphasic approach aimed at educating antenatal women on monitoring neurological maturation, with the overarching objective of assessing the effectiveness of a targeted multi-method parental education intervention in improving parents' knowledge and early detection of developmental disorders in early childhood. Methods: Antenatal women will be assigned to intervention or control groups. The intervention group will undergo specialized training in a multiphasic study, while the control group will receive routine care. A meticulously developed intervention module for early detection of neurodevelopmental disorders will empower mothers to monitor their newborns for potential deficits. Outcomes will be assessed through questionnaires, analyzing knowledge improvement and early identification of DD using statistical methods such as chi-square tests. The study involves three phases: preparatory, implementation, and evaluation, aiming to empower mothers to detect developmental concerns early and improve maternal awareness of child development. The study was approved by the SRM Institutional Ethical Committee with the reference number 8688/IEC/2023. Discussion: This study will identify DD and improve parental awareness by providing tools for early detection thereby empowers parents to identify developmental concerns early. The study supports policy goals to reduce the burden of DD, enhance early intervention, and improve long-term outcomes for children. It is anticipated that this intervention will complement existing health policies, contributing to better child health and developmental outcomes in India. Trial registration: Trail is registered under Clinical Trails Registry - India (CTRI/2024/04/065008) registered on 01 April 2024. [ABSTRACT FROM AUTHOR]

Background: Natural language processing (NLP) enables the extraction of information embedded within unstructured texts, such as clinical case reports and trial eligibility criteria. By identifying relevant medical concepts, NLP facilitates the generation of structured and actionable data, supporting complex tasks like cohort identification and the analysis of clinical records. To accomplish those tasks, we introduce a deep learning-based and lexicon-based named entity recognition (NER) tool for texts in Spanish. It performs medical NER and normalization, medication information extraction and detection of temporal entities, negation and speculation, and temporality or experiencer attributes (Age, Contraindicated, Negated, Speculated, Hypothetical, Future, Family_member, Patient and Other). We built the tool with a dedicated lexicon and rules adapted from NegEx and HeidelTime. Using these resources, we annotated a corpus of 1200 texts, with high inter-annotator agreement (average F1 = 0.841% ± 0.045 for entities, and average F1 = 0.881% ± 0.032 for attributes). We used this corpus to train Transformer-based models (RoBERTa-based models, mBERT and mDeBERTa). We integrated them with the dictionary-based system in a hybrid tool, and distribute the models via the Hugging Face hub. For an internal validation, we used a held-out test set and conducted an error analysis. For an external validation, eight medical professionals evaluated the system by revising the annotation of 200 new texts not used in development. Results: In the internal validation, the models yielded F1 values up to 0.915. In the external validation with 100 clinical trials, the tool achieved an average F1 score of 0.858 (± 0.032); and in 100 anonymized clinical cases, it achieved an average F1 score of 0.910 (± 0.019). Conclusions: The tool is available at https://claramed.csic.es/medspaner. We also release the code (https://github.com/lcampillos/medspaner) and the annotated corpus to train the models. [ABSTRACT FROM AUTHOR]

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes. Large randomized controlled trials are needed to assess the efficacy and safety of semaglutide in early-stage symptomatic AD. Methods: evoke and evoke+ are randomized, double-blind, placebo-controlled phase 3 trials investigating the efficacy, safety, and tolerability of once-daily oral semaglutide versus placebo in early-stage symptomatic AD. Eligible participants were men or women aged 55–85 years with mild cognitive impairment or mild dementia due to AD with confirmed amyloid abnormalities (assessed by positron emission tomography or cerebrospinal fluid [CSF] analysis). After a maximum 12-week screening phase, an anticipated 1840 patients in each trial are randomized (1:1) to semaglutide or placebo for 156 weeks (104-week main treatment phase and 52-week extension). Randomized participants follow an 8-week dose escalation regimen (3 mg [weeks 0–4], 7 mg [weeks 4–8], and 14 mg [weeks 8–156]). The primary endpoint is the semaglutide–placebo difference on change from baseline to week 104 in the Clinical Dementia Rating – Sum of Boxes score. Analyses of plasma biomarkers, collected from all participants, and a CSF sub-study (planned n = 210) will explore semaglutide effects on AD biomarkers and neuroinflammation. Results: Enrollment was undertaken between May 18, 2021, and September 8, 2023. Completion of the trials' main phase is expected in September 2025, and the 52-week extension (in which participants and investigators remain blinded to treatment assignment) will continue to October 2026. Conclusion: evoke and evoke+ are the first large-scale trials to investigate the disease-modifying potential of semaglutide in participants with early-stage symptomatic AD, including exploration of effects on AD biomarkers and neuroinflammation. The trials will provide data on the potential disease-modifying effects of semaglutide and will be important in evaluating its utility in the treatment of early-stage symptomatic AD. Trial registration: Clinicaltrials.gov, NCT04777396 and NCT04777409. Date: 02/03/2021 [ABSTRACT FROM AUTHOR]