Reviews on recent clinical trials最新文献

Background: Huntington's disease (HD) is a neurodegenerative disorder due to a CAG trinucleotide repeat expansion in the HD gene. Animal models have been instrumental in revealing the genetic and molecular bases of HD. While animal models cannot exactly model the human disease because of anatomical and lifespan differences, they are essential in revealing HD pathology and possible treatments.

Objective: This review aimed to highlight the significance of animal models, particularly rodents, in deepening our knowledge of Huntington's disease. It underlines how non-genetic and genetic models have aided research and therapy innovation as well as their limitations.

Methods: This review addresses the use of different models of animals, including genetic models, such as transgenic mice and non-genetic models, for example, invertebrates and non-human primates. It addresses the creation of these models through methods, such as gene transfer techniques and transgenic manipulation, to simulate the genetic defects that occur in humans. The applicability of model choice based on validity criteria, including symptom manifestation and treatment effectiveness, is also discussed.

Results: This study underscores the effectiveness of the R6/2 mouse model, characterized by accelerated symptom onset and HD pathology. Progress in genetic engineering has also boosted the construction of murine and rat models that reproduce the hereditary aspects of HD, providing significant platforms for experimental investigation.

Conclusion: Even with their limitations, animal models, especially rodents, continue to play a vital role in the study of HD pathogenesis and therapeutic intervention. These models still shed light on the disease and direct towards the identification of effective treatments.

Introduction: Pressure injuries (PIs) pose a significant threat to the safety of hospitalized, mobility-compromised patients globally. Olive oil has shown promising results in preventing PIs due to its high concentrations of monounsaturated fatty acids and phenol antioxidants, known for their anti-inflammatory and cell-protective properties. This study aimed to evaluate the effectiveness of topical olive oil combined with routine preventive interventions in reducing PI incidence.

Methods: A single-blinded, cluster-randomized study was conducted among 80 hospitalized patients at risk of developing PIs. Participants were randomized into two clusters: the intervention group (IVG, n=40) received standard PI preventive care (skin assessment, repositioning, support surfaces) plus topical olive oil application for 7 consecutive days; the control group (CG, n=40) received only standard care. PI prevalence and Braden Scale scores were assessed at baseline and post-intervention (days 3-8). Data were analyzed using descriptive statistics and paired sample ttests.

Results: At baseline, both groups had a PI prevalence of 52.5% (n=21). After the intervention, prevalence reduced to 5% (n=2) in IVG and 22.5% (n=9) in CG. The Braden Scale score in the IVG declined from 12.45±0.50 to 11.75±1.13. Statistically significant improvements were observed in Braden scores between day 1 and day 3 (IVG: x̄= -0.28±0.55, t= -3.14, p <0.05; CG: x̄= -0.58±4.69, t= -4.66, p <0.05) and between day 1 and day 8 (IVG: x̄= -0.70±1.07, t= -4.15, p <0.05; CG: x̄= 1.38±1.58, t= -5.50, p <0.05).

Discussion: The findings underscore the clinical benefit of incorporating topical olive oil into standard PI preventive care. The significant reduction in PI prevalence and improved Braden Scale scores suggest olive oil's potential role as a protective agent due to its anti-inflammatory and antioxidant properties. These results align with existing literature on natural oil-based interventions for skin integrity. However, limitations include the small sample size and short duration, warranting further large-scale studies.

Conclusion: Topical olive oil, when used alongside standard care practices, significantly reduced the incidence of pressure injuries in hospitalized, at risk patients. This approach could serve as a cost-effective, natural adjunct to PI prevention protocols, particularly in resource-limited healthcare settings.

Background: Colonoscopy is a critical tool for the management of Ulcerative Colitis (UC). In this study, we aim to explore the accuracy of Virtual Chromoendoscopy (VCE) using Narrow Banding Imaging (NBI), and magnification using Near Focus (NF) for a better definition of endoscopic inflammation grade in UC patients compared to standard white light (WL) endoscopy alone.

Methods: This is a non-randomized prospective study including all the patients who underwent a colonoscopy (for any reason) between April and September 2023 (with protocol number n. 60/2019.20). During the endoscopic evaluation, at least one image with white light - evaluated using the Mayo Endoscopic Score (MES), one image with NBI, one image with NBI plus NF, and a biopsy were obtained in each colonic tract (cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum). All the stored images were evaluated by three endoscopists separately and compared with the results of the histological evaluation.

Results: A total of 31 UC patients were included. The inter-rater reliability concerning the different scores used (MES, NBI score, and NBI plus NF score), which was evaluated with Cohen's kappa coefficient, was good for the MES, good to excellent for the NBI score, and good for the NBI plus NF score. The concordance between histological evaluation (using the Nancy Index) and the MES was unsatisfactory for all the endoscopists, while the concordance between the NBI evaluation score and the Nancy Index was good to excellent.

Conclusion: The results in the present study suggest that the new endoscopic technologies could be useful to better define disease activity in IBD patients driving better therapeutic strategy.

Introduction: Lifestyle interventions have been increasingly studied for their potential to improve health outcomes in breast cancer survivors. However, the relative effectiveness of these interventions remains unclear. This study aimed to evaluate the impact of various lifestyle changes on the health outcomes of breast cancer survivors.

Methods: A comprehensive analysis of randomized controlled trials (RCTs) involving breastcancer survivors was conducted across major databases, including PubMed, Scopus, Embase,CINAHL, Cochrane Library, and ClinicalTrials.gov. Studies were selected based on theirevaluation of lifestyle interventions aimed at reducing breast cancer risk and its recurrence and orimproving survival. Non-RCTs and studies focusing solely on pharmacological or geneticinterventions were excluded. The risk of bias in included randomized controlled trials wasassessed using the Cochrane Risk of Bias 2 (RoB 2). The results of the included studies werepresented in tabulated form.

Results: Physical activity emerged as the most effective intervention, significantly enhancingmetabolic health, body composition, and cardiorespiratory fitness. Dietary changes and weightmanagement programs provided secondary health benefits, such as modest improvements in dietquality, metabolic markers, and quality of life. The combined intervention of diet and exercisefurther improved these outcomes although it did not significantly reduce cancer recurrence. Thedigital support system (EMPOWER-SMS) was feasible and acceptable, offering minorimprovements in medication adherence and self-efficacy, though its effects on BMI and qualityof life were less pronounced.

Discussion: Among the various lifestyle interventions explored for breast cancer survivors,physical activity consistently emerged as the most effective in improving health outcomes. Whiledietary changes, weight management, and combined interventions also offered health benefits,their direct impact on key outcomes like cancer recurrence and survival was less clear. However,when integrated with regular exercise, these interventions contributed to holistic improvementsin quality of life, making a combined approach potentially the most comprehensive forsupporting breast cancer survivors. This systematic review's limitations include interventionheterogeneity, varied follow-up durations, inconsistent outcome measures, small sample sizes,lack of control over confounding variables, limited participant diversity, potential publicationbias, and a focus on short-term outcomes.

Conclusion: Physical activity emerged as the most beneficial lifestyle intervention for breastcancer survivors, particularly when combined with dietary modifications and weightmanagement. A holistic approach that integrates physical activity, dietary changes, and digitalsupport may provide the most comprehensiv

Hutchinson-Gilford Progeria Syndrome (HGPS), or progeria, is an exceptionally rare disorder characterized by premature aging. It is primarily caused by a c.1824C>T point mutation in exon 11 of the LMNA gene, though other rare pathogenic variants have also been reported. This mutation leads to aberrant splicing, producing a farnesylated mutant form of lamin A known as progerin. Progerin accumulates abnormally in the nuclear lamina, triggering numerous cellular dysfunctions, including nuclear deformation, disrupted proteostasis, endoplasmic reticulum (ER) stress, replicative stress, increased reactive oxygen species (ROS) production, impaired DNA endjoining repair, mitochondrial dysfunction, and cellular senescence. These disruptions collectively manifest as a multisystem disorder characterized by failure to thrive, accelerated atherosclerosis, and severe complications such as myocardial infarction, heart failure, stroke, and risks associated with head trauma or surgical interventions. Farnesyltransferase inhibitors (FTIs) have shown potential in mitigating disease phenotypes in preclinical models, with lonafarnib achieving FDA approval in 2020 as the first-and currently only-drug for progeria treatment. This review focuses on the clinical trial outcomes of small-molecule therapeutics for progeria, with particular emphasis on emerging small molecules from recent research. These novel compounds, with their unique mechanisms of action, hold promise not only for improving disease management but potentially offering a cure for this devastating condition.

Background: Accurate mortality prediction in intensive care units (ICUs) is essential for enhancing patient outcomes and optimizing healthcare resource allocation. Traditional scoring systems, such as APACHE, APACHE II, and SAPS, have limitations in handling complex, high- -dimensional ICU data. In this study, multiple machine learning models were compared to establish an efficacious predictive model for mortality tailored explicitly to the Jordanian population and to explicate factors strongly associated with mortality.

Methods: This study was conducted as a single-center, retrospective cohort investigation, and the XGBoost machine learning algorithm was used to develop a novel ICU mortality prediction model. The model aimed to achieve superior prediction accuracy using a diverse set of readily available clinical data, including demographics, comorbidities, laboratory results, and medication groups. Model performance was evaluated against alternative machine learning algorithms, including logistic regression, conventionally employed in traditional scoring systems.

Results: Comparative analysis revealed that the XGBoost model performed better than other scoring systems, manifesting heightened accuracy (87.91%), sensitivity (92.88%), and Area Under the Receiver-Operating Characteristic Curve (AUC-ROC) Score/Curve (94.29%). Notably, the patient's length of hospital stays, albumin levels, and urea levels emerged as the most substantial predictors for ICU mortality, each exhibiting respective SHAP values of 0.5, 0.41, and 0.37.

Conclusion: A locally adapted ICU mortality prediction model was developed, underscoring the pivotal role of predictors such as hospital stay duration, albumin, and urea levels in predicting patient outcomes. The heightened accuracy and sensitivity of the XGBoost model signify its potential as an invaluable tool in the critical task of mortality prediction within the Jordanian ICU context.

Introduction: Brexit has significantly altered the regulatory landscape for pharmaceuticals, with the UK no longer under the European Medicines Agency (EMA). The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has since developed independent regulatory frameworks, introducing challenges for companies operating in both regions.

Methods: A qualitative approach was used, drawing on secondary data from peer-reviewed literature, official EMA and MHRA documents, and government publications. Sources were selected based on relevance to post-Brexit regulatory changes in drug approval, clinical trials, and pharmacovigilance.

Results: The MHRA has implemented distinct procedures, including the UK Conformity Assessed (UKCA) mark, new marketing authorization pathways, and accelerated drug review routes. Regulatory divergence has necessitated dual submissions, separate clinical trial approvals, and independent safety reporting systems, increasing costs and complexity.

Discussion: Despite shared safety objectives, the absence of harmonized processes complicates regulatory operations for pharmaceutical companies. The separation limits efficiency and may delay market access. However, international collaboration and the development of mutual recognition agreements offer potential pathways to reduce duplication and maintain alignment.

Conclusion: Brexit has created a fragmented regulatory environment for pharmaceuticals in the UK and the EU. Companies must adopt flexible compliance strategies to manage dual frameworks. Continued dialogue and cooperation between regulatory bodies will be essential to safeguard patient access and support innovation across both jurisdictions.

Introduction/objective: Clinical trial regulations (CTR) are essential for ensuring the safety, efficacy, and ethical conduct of drug development. However, the regulatory frameworks governing these trials vary significantly across different countries, affecting approval processes, trial conduct, and drug development timelines. This review examines the differences in clinical trial regulations in the USA, EU, Australia, and India between 2016 and 2024. The focus is on key regulatory aspects, such as the adoption of Good Clinical Practices (GCP), patient safety measures, and policies fostering innovation. By comparing drug regulations and trial management practices, it aims to identify regulatory challenges and propose improvements to enhance global harmonization.

Methods: A detailed review of drug regulations, acts, rules, and trial processes across different countries was conducted. The review compared global standards for clinical trials, focusing on costs, safety reporting, and trial management, and identifying key areas for improvement.

Conclusion: The findings reveal that while the studied countries have established strict regulatory frameworks, still there are specific areas for improvement. A key recommendation is to formally authorize Clinical Research Organizations (CROs) to enhance the quality and oversight of clinical trials. Additionally, specific regulations for herbal medicine trials are urgently needed to ensure safety and efficacy. Ethical concerns, especially regarding pediatric and orphan drug products, require more robust oversight. Integrating blockchain technology is also recommended to improve transparency and traceability in drug development. Finally, promoting global regulatory harmonization is crucial to minimize delays in patient access to essential therapies. These insights aim to guide policymakers, researchers, and stakeholders in enhancing the quality, safety, and accessibility of medicines.

An essential tool for assessing the efficacy and safety of novel therapies and interventions is the clinical trial. They are crucial for understanding disease causes, treatment effectiveness, and patient care processes. However, traditional clinical trials often suffer from inefficiencies, high costs, and extended timelines. This review explores how artificial intelligence can revolutionize clinical trials by addressing these inefficiencies in trial design, patient recruitment, and data analysis. It also discusses the challenges and solutions for incorporating AI within existing regulatory frameworks. This review is based on a comprehensive analysis of the existing literature on artificial intelligence applications in clinical trials. It includes an evaluation of studies that assess the role of artificial intelligence in enhancing trial efficiency, optimizing patient recruitment, and improving data analysis. Special attention is given to regulatory considerations, with a focus on Food and Drug Administration (FDA) guidelines and their impact on artificial intelligence integration in clinical research. The successful integration of artificial intelligence into clinical trials has the potential to optimize procedures, enhance clinical judgment, and improve patient outcomes. Artificial intelligence can streamline patient stratification, accelerate trial timelines, and enhance data analysis accuracy. However, overcoming challenges related to interpretability, data privacy, and regulatory compliance is crucial. Collaboration between researchers, artificial intelligence developers, and regulatory bodies is essential to establish guidelines ensuring artificial intelligence innovations are safe and effective. Ultimately, artificial intelligence could transform clinical research and pave the way for more personalized healthcare solutions.

Background: Among premenopausal women, polycystic ovarian syndrome (PCOS) is one of the most ubiquitous endocrine and metabolic conditions. Abdominal adiposity, insulin resistance, obesity, metabolic diseases, and cardiovascular hazards are often associated with PCOS. This investigation aims to decipher the influence of oral Vitamin D3 supplementation (2000 IU/day for three months) on glucose metabolism in PCOS women.

Methods: 123 subjects (females 16 to 40 years of age) were arbitrarily allocated to three cohorts (n = 41 in each cohort) Each participant received two tablets daily and a sachet every month for three months (Group I: Vitamin D3 Tablets + placebo sachets; Group II: Placebo Tablets + Vitamin D3 sachets; Group III: Tablets + Placebo sachets).

Results: Among 123 PCOS subjects, 93.4% exhibited hypovitaminosis D. The baseline 25- hydroxyvitamin D (25(OH)D) concentration of 13.76 (SD ± 10.61) ng/ml increased by 86.84% post-intervention. Groups I and II (active group) depicted substantial diminution in pre-treatment fasting and 2-h blood glucose, with no substantial change in the HOMA-IR. Group III (placebo) showed no improvement in vitamin D status or HOMA-IR. Overall, we observed no substantial HOMA-IR improvement with vitamin D subjunction. However, subgroup analysis revealed a statistically significant enhancement in HOMA-IR for subjects achieving a two-fold upsurge in post-supplementation 25(OH)D levels (≥ 20 ng/ml) compared to those without this increase (p = 0.025).

Conclusion: Vitamin D3 supplementation improves glucose metabolism, as demonstrated by lower fasting and 2-hour blood glucose levels, but overall has no substantial repercussion on measures of insulin sensitivity like HOMA-IR. A larger vitamin D3 dose and an extended follow-up study are essential to comprehend the complex physiology of vitamin D and glucose homeostasis. The cohort's mean blood 25-hydroxyvitamin D concentrations were successfully boosted by 84% by Vitamin D3 dosage; yet, the influence on insulin resistance markers displayed a subtle complexity. A relationship was found amid the absolute variation in HOMA-IR and the percentage variation in Vitamin D. Nevertheless, there was no substantial general alteration in the mean HOMA-IR across different subgroups.