Final Evaluation Research Articles

Combined micro-needling with topical metformin versus micro-needling with topical placebo in the treatment of melasma: a concurrent split-face study.

Melasma is an acquired dysfunction of melanogenesis, that poses a major therapeutic challenge and tends to recur after therapy. Several combination therapies are being tested nowadays for the treatment of melasma, with promising results. Metformin, an anti-diabetic medication, seems to inhibit melanogenesis by different mechanisms. In addition, there has been a long-term improvement in melasma after microneedle therapy. To evaluate the potential therapeutic role of topical metformin combined with micro-needling for the treatment of melasma. Eighteen patients with melasma received treatment in split-face manner, right side with micro-needling and topical metformin, while the left side was treated with micro-needling and topical placebo for four sessions at 2-week intervals. Hemi-mMASI score was used for the final evaluation of results. ThevariabilitypatterninHemi-mMASI score between both sides revealed significant reduction in the right side (micro-needling + metformin), as compared to the left side (micro-needling + placebo) (2.39 ± 1.42 vs 4.72 ± 1.27, p = 0.001). The effectiveness of topical metformin in the management of melasma could be significantly improved by pretreatment with micro-needling as a combined therapy, without any apparent side effects.

Abstract 4144560: Phase 2 Open-label, Single-arm, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Camostat Mesylate in Patients with Protein-losing Enteropathy after Fontan Operation-Preliminary Outcome

Introduction: Protein-losing enteropathy (PLE) is a multifaceted condition that profoundly affects the systemic health and quality of life of Fontan patients. Despite medical progress, the treatment of PLE remains a significant challenge. This study investigates the efficacy and safety of Camostat Mesylate for managing PLE patients who have undergone the Fontan operation. Hypothesis: We hypothesize that Camostat Mesylate will enhance the gut environment, resulting in increase of serum albumin levels and decrease of stool alpha-1 antitrypsin levels in PLE patients following Fontan operation. Methods: This phase 2, multicenter, open-label, single-arm trial included patients over 4 years old diagnosed with PLE following Fontan operation. Camostat Mesylate was added to conventional treatments, with follow-up assessments at 1, 3, and 6 months, and a final evaluation one month after discontinuation. Efficacy was measured by changes in serum albumin, stool alpha-1 antitrypsin levels, and PLE symptoms such as diarrhea, edema, weight changes, and ascites. Results: Nineteen patients were enrolled in the study, of whom fifteen patients completed follow-up as per protocol. The median age was 15 years (interquartile range, 12.0-21.3). The median time between the Fontan operation and PLE diagnosis was 2.4 years. Serum albumin levels increased from 2.5 to 2.6 g/dL (p=0.504), and stool alpha-1 antitrypsin levels decreased significantly from 280.0 to 172.1 mg/dL (p=0.033). Notably, patients with diarrhea at baseline showed substantial improvement in both parameters, with increased serum albumin levels from 1.8 to 2.2 g/dL and decreased stool alpha-1 antitrypsin levels from 220.3 to 80.2 mg/dL. No serious adverse events were reported during study period. Conclusions: Camostat Mesylate demonstrated safety and efficacy, reducing stool alpha-1 antitrypsin in PLE patients after Fontan operation, especially those with diarrhea at baseline. Therefore, Camostat Mesylate could be considered as an additional treatment option for patients with PLE following Fontan operation. Key words: Camostat mesylate; protein-losing enteropathy; Fontan operation Source of Funding: This research was funded by SNUH Lee Kun-hee Child Cancer&Rare Disease Project, Republic of Korea.

Study on the Role and Effectiveness of Physiotherapy in Cervical Brachial Syndrome

Cervicobrachial syndrome is defined as a common condition characterized by pain in the cervical and shoulder region occurring in the C5-C8 cervical root distribution territory with the main symptom being pain. The present study focuses on the need for physical therapy in the management of the pain and functional disorders present in a 46-year-old female patient diagnosed with cervicobrachial syndrome. The research was carried out over a period of 3 months, during which time the patient underwent a complex treatment programme involving both kinetic and electrotherapy techniques and aids. The results obtained were highlighted by applying evaluation tests (muscle balance, joint balance and cervical disability index) in 3 successive stages: initial, intermediate and final evaluation. Analysis of the scores obtained in the 3 tests allowed us to identify an improvement in the patient's quality of life, sleep, concentration and daily activities not disturbed by the algesic phenomena and functional disorders generated by the cervicobrachial syndrome.

Postoperative Karnofsky performance status prediction in patients with IDH wild-type glioblastoma: A multimodal approach integrating clinical and deep imaging features.

Glioblastoma is a highly aggressive brain tumor with limited survival that poses challenges in predicting patient outcomes. The Karnofsky Performance Status (KPS) score is a valuable tool for assessing patient functionality and contributes to the stratification of patients with poor prognoses. This study aimed to develop a 6-month postoperative KPS prediction model by combining clinical data with deep learning-based image features from pre- and postoperative MRI scans, offering enhanced personalized care for glioblastoma patients. Using 1,476 MRI datasets from the Brain Tumor Segmentation Challenge 2020 public database, we pretrained two variational autoencoders (VAEs). Imaging features from the latent spaces of the VAEs were used for KPS prediction. Neural network-based KPS prediction models were developed to predict scores below 70 at 6 months postoperatively. In this retrospective single-center analysis, we incorporated clinical parameters and pre- and postoperative MRI images from 150 newly diagnosed IDH wild-type glioblastoma, divided into training (100 patients) and test (50 patients) sets. In training set, the performance of these models was evaluated using the area under the curve (AUC), calculated through fivefold cross-validation repeated 10 times. The final evaluation of the developed models assessed in the test set. Among the 150 patients, 61 had 6-month postoperative KPS scores below 70 and 89 scored 70 or higher. We developed three models: a clinical-based model, an MRI-based model, and a multimodal model that incorporated both clinical parameters and MRI features. In the training set, the mean AUC was 0.785±0.051 for the multimodal model, which was significantly higher than the AUCs of the clinical-based model (0.716±0.059, P = 0.038) using only clinical parameters and the MRI-based model (0.651±0.028, P<0.001) using only MRI features. In the test set, the multimodal model achieved an AUC of 0.810, outperforming the clinical-based (0.670) and MRI-based (0.650) models. The integration of MRI features extracted from VAEs with clinical parameters in the multimodal model substantially enhanced KPS prediction performance. This approach has the potential to improve prognostic prediction, paving the way for more personalized and effective treatments for patients with glioblastoma.

Safety and Effectiveness of Vibegron in Japanese Patients With Overactive Bladder: A Japanese Postmarketing Survey.

To evaluate the safety and effectiveness of vibegron, a highly selective β3-adrenoceptor agonist, in Japanese patients with overactive bladder (OAB) in a real-world clinical setting. This prospective survey was conducted from August 2019 to July 2023 using a central registration method. Patients newly treated with vibegron for OAB were followed for 12 weeks, and those who continued treatment were observed for up to 52 weeks. Adverse drug reactions (ADRs) and the overall improvement level were assessed, and overactive bladder symptom score (OABSS) and International Prostate Symptom Score-Quality of Life (IPSS QOL) score were collected. Of the 1848 patients in the safety analysis set, 154 ADRs were reported in 141 patients (7.63%). Common ADRs were increased residual urine volume (1.30%), constipation (1.14%), dysuria and urinary retention (0.97% each), cystitis (0.65%), and dry mouth (0.32%). The incidence of urinary retention-related adverse events (AEs) was higher in male patients, patients ≥ 65 years old, and patients with benign prostatic hyperplasia. The effectiveness rate was 88.8% among the 1561 patients in the effectiveness analysis set. Significant improvement in both OABSS and IPSS QOL scores was observed at all observation periods. The rate of achieving the minimal clinically important change in OABSS total score at the final evaluation was 75.35%. OABSS scores were also significantly reduced in all subgroup analyses. This survey found no major concerns regarding the safety and effectiveness of vibegron in Japanese OAB patients, except for urinary retention-related AEs. Vibegron is considered to represent a useful drug for treating OAB symptoms in a real-world clinical setting.

Persistence of Labral Tears and Resolution of Paralabral Cysts with 2-year MRI analysis after Periacetabular Osteotomy (PAO) for Hip Dysplasia

To evaluate the labrum status and paralabral cysts on preoperative and postoperative magnetic resonance imaging (MRI) in patients with developmental dysplasia of the hip (DDH) who underwent periacetabular osteotomy (PAO). A retrospective review was conducted using prospectively collected data from patients who had undergone primary PAO between June 1, 2021 and May 30, 2022. Inclusion criteria were an age range of 16 to 55 years and a minimum follow-up of two years. MRI was utilized to evaluate the preoperative and postoperative conditions of the labrum and the presence of paralabral cysts. Furthermore, the correlations between the presence of paralabral cysts and demographic and radiographic variables were investigated. Additionally, patient-reported outcomes (PROs), minimal clinically important difference (MCID), and complications were reported during the final follow-up evaluation. A total of 23 patients were included in the final analysis, with an average follow-up of 26.6 ± 3.4 months (range, 24-32 months). All patients diagnosed with symptomatic DDH exhibited labrum tears. MRI scans revealed paralabral cysts in ten out of twenty-four (41.6%) patients, with a significant correlation noted between the presence of cysts and preoperative LCEA (ρ=-0.649; P=0.001), ACEA (ρ=-0.637; P=0.001), Tönnis angle (ρ=0.593; P=0.002) and age (ρ=-0.444; P=0.034). Postoperative MRI scans at one year showed resolution of all paralabral cysts, while labral tears were found to persist. At the end of the follow-up period, most patients improved considerably in PROs compared to preoperative values. The probabilities of achieving the MCID were 91.3% on the HOS-ADL, 78.2% on the HOS-SSS, 91.3% on the mHHS, 73.9% on the iHOT-12, and 69.6% on the VAS pain scale. All symptomatic patients with DDH had labral tears and a high prevalence of paralabral cysts, which were corrected with reduced acetabular coverage. After PAO surgery, patients experienced notable enhancements in PROs, with resolution of paralabral cysts but persistence of labral tears.

A protocol for trustworthy EEG decoding with neural networks

Deep learning solutions have rapidly emerged for EEG decoding, achieving state-of-the-art performance on a variety of decoding tasks. Despite their high performance, existing solutions do not fully address the challenge posed by the introduction of many hyperparameters, defining data pre-processing, network architecture, network training, and data augmentation. Automatic hyperparameter search is rarely performed and limited to network-related hyperparameters. Moreover, pipelines are highly sensitive to performance fluctuations due to random initialization, hindering their reliability. Here, we design a comprehensive protocol for EEG decoding that explores the hyperparameters characterizing the entire pipeline and that includes multi-seed initialization for providing robust performance estimates. Our protocol is validated on 9 datasets about motor imagery, P300, SSVEP, including 204 participants and 26 recording sessions, and on different deep learning models. We accompany our protocol with extensive experiments on the main aspects influencing it, such as the number of participants used for hyperparameter search, the split into sequential simpler searches (multi-step search), the use of informed vs. non-informed search algorithms, and the number of random seeds for obtaining stable performance. The best protocol included 2-step hyperparameter search via an informed search algorithm, with the final training and evaluation performed using 10 random initializations. The optimal trade-off between performance and computational time was achieved by using a subset of 3-5 participants for hyperparameter search. Our protocol consistently outperformed baseline state-of-the-art pipelines, widely across datasets and models, and could represent a standard approach for neuroscientists for decoding EEG in a trustworthy and reliable way.

Deep Learning and Handcrafted Features for Thyroid Nodule Classification

ABSTRACTIn this research, we present a refined image‐based computer‐aided diagnosis (CAD) system for thyroid cancer detection using ultrasound imagery. This system integrates a specialized convolutional neural network (CNN) architecture designed to address the unique aspects of thyroid image datasets. Additionally, it incorporates a novel statistical model that utilizes a two‐dimensional random coefficient autoregressive (2D‐RCA) method to precisely analyze the textural characteristics of thyroid images, thereby capturing essential texture‐related information. The classification framework relies on a composite feature vector that combines deep learning features from the CNN and handcrafted features from the 2D‐RCA model, processed through a support vector machine (SVM) algorithm. Our evaluation methodology is structured in three phases: initial assessment of the 2D‐RCA features, analysis of the CNN‐derived features, and a final evaluation of their combined effect on classification performance. Comparative analyses with well‐known networks such as VGG16, VGG19, ResNet50, and AlexNet highlight the superior performance of our approach. The outcomes indicate a significant enhancement in diagnostic accuracy, achieving a classification accuracy of 97.2%, a sensitivity of 84.42%, and a specificity of 95.23%. These results not only demonstrate a notable advancement in the classification of thyroid nodules but also establish a new standard in the efficiency of CAD systems.

Kinetic changes of gait initiation in individuals with chronic ankle instability: A systematic review.

Gait initiation (GI) in individuals with chronic ankle instability (CAI) has shown differences in the center of pressure (COP) and muscular measures compared to healthy controls. Some studies reported that these alterations appeared when GI was with the affected leg, while others indicated that they occurred when GI was with the non-affected leg. This systematic review aimed to understand kinetic and muscular differences between individuals with CAI, healthy controls, and the affected and non-affected legs of individuals with CAI. PubMed, Science Direct, Web of Science, Google Scholar, and Scopus databases (1990-2023) were searched using the Population, Exposure, Comparator, and Outcome measure. The PRISMA guidelines were followed. The outcome measures were the peak and rate of COP displacement in the medial-lateral and anterior-posterior directions, and resultant plane during phases 1, 2, and 3 of COP trace during GI and the duration of each phase. The other measures included the onset time of the tibialis anterior and soleus muscle activity between individuals with CAI, healthy controls, and the affected and non-affected legs of the individuals with CAI. The studies' quality assessment was conducted based on the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Five studies were included in the final evaluation. The results of included studies showed, individuals with CAI spent less time during phases 1 and 2, as well as a shorter peak of COP displacement in the lateral direction during phase 1 compared to healthy controls, regardless of whether the GI was with the affected or non-affected leg. Individuals with CAI have probably adopted a strategy involving adjusting the peak of COP displacement to manage internal sway while in a single-leg stance. Overall, there was no comprehensive conclusion about differences between the two legs in individuals with CAI.

Construction of a Competency Evaluation Indicator System for Specialist Nurses in Liver Transplantation: A Delphi Study.

Liver transplantation specialist nurses provide comprehensive and safe care for liver transplant patients, which requires them to have a wide range of competencies. However, at present, there is no comprehensive understanding of the competency of liver transplantation specialist nurses in China, and there is a lack of comprehensive evaluation indicators. The purpose of this study was to construct a competency evaluation indicator system for specialist nurses in liver transplantation. Utilizing the "Iceberg model" of competency, the indicator system for evaluating the competency of liver transplant specialist nurses was developed through literature review, semi-structured interviews, and two rounds of Delphi expert consultation. Twenty nursing and medical experts in liver transplantation were consulted over two rounds. The effective response rates for the expert consultation questionnaires were 90.91% and 100.00% for the first and second rounds, respectively. The coefficient of expert judgment was 0.920, the coefficient of familiarity was 0.880, and the authority coefficient was 0.900. The value range of the coefficient of variation in the second round was 0.00-0.16, both <0.25, indicating that the degree of coordination of expert opinions was high. The final competency evaluation index system for liver transplant specialist nurses encompassed 6 primary indicators, 17 secondary indicators, and 59 tertiary indicators, including professional knowledge, professional skills, social role, self-concept, personality quality, and motivation. The developed competency evaluation indicator system for liver transplant specialist nurses possesses scientific validity and reliability, offering a reference for the training and assessment of liver transplant specialist nurses.

Long-term follow-up after infective endocarditis: comparison of patients who have undergone cardiac surgery versus a conservative therapy with and without an indication for cardiac surgery

Abstract Background Infective endocarditis (IE) is still a serious disease, with a high mortality despite cardiac surgery and modern conservative therapy. However, data on long-term follow-up are sparse. Methods Retrospective single centre registry on the hospital course and long-term follow-up of patients with IE who have undergone cardiac surgery or a conservative therapy with and without an indication for cardiac surgery. Results Between 1/2013 and 12/2016, 171 IE patients were treated at our hospital. A follow-up with either patient contact, review of hospital charts or physician contact was performed in 2022. Due to lost to follow-up (n=4) or refusal to participate after discharge (n=1), the final evaluation was performed with 166 patients (97.1%). They were followed-up for a median 2385.0 (between 2156 and 2773) days. 139 (81.3%) of the patients were operated (surgery) and 32 (18.7%) were treated conservatively. Amongst the conservatively treated group, 34.4% (11/32) of the patients had an indication for surgery, but it was decided not to perform it (cons-with) and 65.6% (21/32) had no indication for surgery (cons-without). Operated patients were younger compared to cons treated patients (65.1 ± 13.0 vs 72.8 ± 15.7, p = 0.00016). Whereas hospital mortality was not different between both groups (21.6 % vs 21.9 %, p = 0.97112), calculated 5y mortality was higher in der cons treated group (71.0 % vs 49.6 %, p=0.03168). Conclusions These data on long-term follow-up after IE show a high total mortality amongst all patients regardless of type of therapy, but higher mortality rate after 5 years amongst conservative treated patients (71%) compared toa surgical treated (49.6% p= 0.03168). The highest mortality rate after 5 years (100%) was detected in the cons-with compared to 55% in the cons-without group. More than 2/3 of deaths were due to IE. However, operated patients were younger and had less co-morbidities. Furthermore, rehospitalisation rate for recurrent IE was also high.

Stereological study of organelle distribution in human mature oocytes

The ultrastructure of human oocytes has been described only qualitatively. To offer a precise organelle spatial distribution and organelle volume during the main maturation stages, we previously conducted stereological studies on prophase-I (GV) and metaphase-I (MI) oocytes, and here we present results on metaphase-II (MII) oocytes. Five donor oocytes from different donors were processed for transmission electron microscopy, and quantification of organelle distribution was performed using point-counting stereology. Statistical tests compared the means of the relative volumes occupied by organelles among oocyte regions. The most abundant organelles were elements of the smooth endoplasmic reticulum (SER), such as SER small vesicles, SER medium vesicles, SER large vesicles and SER isolated tubules, along with mitochondria, followed by SER tubular aggregates, cortical vesicles and lysosomes. Significant differences between oocyte regions were found for lysosomes, cortical vesicles and SER large vesicles. Comparisons of MII oocytes to previous findings in GV and MI oocytes evidenced specific patterns of organelle distribution and relative volumes. This final evaluation thus enables to track organelle spatial reorganization across oocyte stages, which, in addition to gathered knowledge, may be useful to assist in improvements of stimulation protocols, in-vitro maturation media and cryopreservation techniques.

Evaluation and Improvement of Oncologists' Adherence to NCCN Guideline for Prevent and Treatment of Cancer Associated Venous Thromboembolism

Objective: the aim of this study is asses the adherence of physician to NCCN guideline recommended anticoagulant therapy in patient with cancer associated venous thromboembolism. Method: study was designed with two phases an observational phase and an interventional prospective phase with the educational program, was conducted at Middle Euphrates cancer center /An-Najaf governorate/Iraq. Ten oncologists who agreed to participate in the study. Used validated questionnaire include (25 items) where distributed to 10 oncologists who were working at the Middle Euphrates cancer center then all questionnaires were collected from participated oncologists over two months. Subsequently, an educational part including a lecture and posters was submitted in cancer center to in raising awareness of seriousness of this disease and how prevention and treatment. Results: The overall mean total score of oncologists for prevention and management of cancer associated VTE (out of 25 items) of all questionnaire parts was remarkably increased from (0.54) to (0.72) after the intervention therefore the level of oncologist's adherence to NCCN guideline improved to 70% with large effect size (1.04). Conclusion: According to the final evaluation of responses of oncologists showed improvement in adherence toward the NCCN guideline. In addition, there were several barriers that mainly reduce the adherence like sever side effect, increase cost and Lack of awareness of guidelines.

Cobalt and Tungsten Extraction from Diamond Core Drilling Crowns by Aqua Regia Leaching.

In this work, a hydrometallurgical process for the recycling of diamond core drilling crowns by means of aqua regia leaching and subsequent alkali leaching was investigated. This investigation continues a previous study in which nitric acid was used for the acid leaching phase. In the current study, higher tungsten recovery was achieved, reaching 98.2%, which is an improvement of about 1.5%. Another advancement of this study was the high Co recovery (97.21%) and the high purity of the tungsten trioxide obtained, comparable to the previously proposed technological process. Furthermore, a novel laboratory method for testing recycled diamond drilling crowns based on infrared thermography was introduced. Although this innovative approach is not the most accurate, it is fast and cost-effective and provides valuable results before the actual field test is conducted as a final evaluation. In addition, the infrared thermography method offers the advantage of non-destructive testing, ensuring that the diamond drilling crowns can be assessed without compromising their structural integrity. Other instrumental methods used to characterize the products and intermediates were X-ray diffraction (XRD), scanning electron microscope with energy dispersive X-ray spectroscopy (SEM-EDS), and laser desorption ionization mass spectrometry (LDI-MS). The analytical method for the concentrations in all working solutions was ICP-AES.

AOP report: Development of an adverse outcome pathway for deposition of energy leading to abnormal vascular remodeling.

Cardiovascular diseases (CVDs) are complex, encompassing many types of heart pathophysiologies and associated etiologies. Radiotherapy studieshave shown that fractionated radiation exposure at high doses (3-17 Gy) to the heart increases the incidence of CVD. However, the effects of low doses of radiation on the cardiovascular system or the effects from space travel, where radiation and microgravity are important contributors to damage, are not clearly understood. Herein, the adverse outcome pathway (AOP) framework was applied to develop an AOP to abnormal vascular remodeling from the deposition of energy. Following the creation of a preliminary pathway with the guidance of field experts and authoritative reviews, a scoping review was conducted that informed final key event (KE) selection and evaluation of the Bradford Hill criteria for the KE relationships (KERs). The AOP begins with a molecular initiating event of deposition of energy; ionization events increase oxidative stress, which when persistent concurrently causes the release of pro-inflammatory mediators, suppresses anti-inflammatory mechanisms and alters stress response signaling pathways. These KEs alter nitric oxide levels leading to endothelial dysfunction, and subsequent abnormal vascular remodeling (the adverse outcome). The work identifies evidence needed to strengthen understanding of the causal associations for the KERs, emphasizing where there are knowledge gaps and uncertainties in both qualitative and quantitative understanding. The AOP is anticipated to direct future research to better understand the effects of space on the human body and potentially develop countermeasures to better protect future space travelers.

A comparative analysis of game-based learning and conventional learning in dental education.

To evaluate the efficacy of traditional teaching versus traditional teaching supplemented by serious gaming in imparting knowledge of periodontal indices among dentistry students. Additionally, the study seeks to measure the level of satisfaction among students engaging with the assessed teaching method. This comparative study was approved by the ethics committee of the University of Valencia with file number: 2479311. A sample of 61 subjects was divided randomly into two groups: the test group (n=36) and the control group (n=25). Baseline knowledge of community index of periodontal treatment need was assessed through a questionnaire completed by both groups before receiving a comprehensive explanation of the topic. The test group, in addition to the conventional explanation, received supplementary training via an educational gaming experience. Both groups underwent a final evaluation and, subsequently, a satisfaction survey was completed by the test group. Descriptive and inferential analyses were performed using a non-parametric Brunner-Langer model. The relationship between scores was examined using Mann-Whitney and Wilcoxon tests, with a significance level set at α=0.05. The training, in general, was effective as both the test group (p=0.003) and the control group (p=0.015) demonstrated an increase in scores with both teaching modalities, but no significant difference was observed between the groups. The test group expressed a high level of satisfaction with the instructional approach. No statistically significant difference in learning outcomes was identified between the traditional lecture teaching method and the approach supplemented by gaming. There was an elevated level of student satisfaction with the gaming method.

A computer-based evaluation system: Its design, implementation and results obtained on a general chemistry course

Using multiple evaluation methods and systems give a comprehensive assessment. A computer-based multiple-choice assessment system was designed, implemented, posted online, and used to assess students as part of their final evaluation marks for a discipline. The online system of evaluation was intended to be used multiple times for evaluating the assimilation degree of a specific course at the end of the course. The data recorded for the period 2017–2023 with about 1400 distinct users were used to analyze the performance of the evaluation system. The system worked fine and a slight modification of it served well on remote evaluation during COVID-19 period. However, the upturn of mobile phone applications requires the creation of a system adapted to the new virtual reality.

The decriminalization of illicit drugs in British Columbia: a national evaluation protocol

BackgroundOn January 31st, 2023, the province of British Columbia (BC), Canada, was granted a federal exemption allowing adults (aged 18 +) to possess up to 2.5 g of select illicit drugs. The exemption will be in place for three years (2023–2026), marking the first formal decriminalization of illicit drug policy reform in Canada. BC’s decriminalization initiative is premised on several goals. This project seeks to evaluate each of these goals and their individual and combined contributions to determine the overall success of this policy.MethodsThe following protocol paper provides a detailed outline of a five-year (2022-2027) national evaluation of BC’s decriminalization initiative, as well as the specific objectives, methodologies, and planned analyses for eight interrelated sub-studies that comprise the evaluation. These sub-studies fall under the following five topical areas of research: 1) people who use drugs (PWUD), 2) the police and the criminal justice system, 3) the general public, 4) the health services system, and 5) an economic analysis. Additional research activities may also be explored.ResultsThe overall evaluation and specific sub-study designs were informed by intensive stakeholder engagement. The evaluation was developed in collaboration with an international expert committee who came together to undertake a nominal group technique to decide on the final evaluation design and corresponding logic model. The evaluation will also employ an advisory board and individual sub-study working groups comprised of experts and PWUD who will oversee the development and implementation of the overall evaluation as well as each sub-study.DiscussionThis evaluation will draw on implementation science research practices to evaluate and understand the full impacts of this novel drug policy experiment. Results will be widely disseminated through manuscripts, reports, presentations, and infographics, which will be adapted and tailored for specific audiences. The protocol identifies several anticipated challenges and limitations. This evaluation’s evidence-based findings will be poised to offer pivotal insights that can shape and refine the discourse on drug policy and will serve as a critical resource for understanding the multifaceted impacts of decriminalization.

Real-World Safety and Effectiveness of Infliximab in 255 Patients with Intestinal, Neurological, and Vascular Behçet's Disease: A Post-Marketing Surveillance.

Behçet's disease (BD) with intestinal, neurological (NBD), and vascular (VBD) manifestations often leads to poor outcomes. Infliximab is approved for the treatment of intestinal BD, NBD, and VBD in Japan; however, evidence regarding its safety and effectiveness in these patients is limited. We conducted a 2-year post-marketing surveillance to evaluate the safety and effectiveness of infliximab in patients with intestinal BD, NBD, and VBD in Japan. This 2-year, multicenter, prospective, observational study included all patients with intestinal BD, NBD, or VBD, who had experiencedan insufficient response to conventional therapies (e.g., glucocorticoids and immunosuppressants/immunomodulators), and initiated infliximab for the first time at participating medical institutions. The safety endpoints included adverse events and adverse drug reactions (ADRs), and the effectiveness endpoints included global improvement, and for patients with acute NBD, acute attacks. Between October 2015 and August 2018, 255 patients (171 intestinal BD, 49 NBD, and 51 VBD; including 16 with two disease types) were enrolled from 133 medical centers and treated with infliximab. Adverse events, ADRs, and serious ADRs occurred in 100 (39.2%), 72 (28.2%), and 38 (14.9%) patients, respectively; incidences were generally similar across intestinal BD, NBD, and VBD groups. No new safety concerns were identified. At the final evaluation, 68.8% of patients with intestinal BD showed improvement, most patients with chronic progressive NBD and VBD had not worsened (100% and 91.7%, respectively), and 93.3% of patients with acute NBD had no new acute attacks during the observation period. These results confirmed the safety and effectiveness of infliximab in clinical practice in 255 patients with intestinal BD, NBD, and VBD. There were no new safety concerns.

Unveiling New Horizons: Advancing Technologies in Cosmeceuticals for Anti-Aging Solutions.

In the last years, the landscape of anti-aging cosmetics has been marked by significant advances in cosmeceutical delivery systems. This study aimed to conduct a systematic review of these technological innovations, with a focus on anti-aging effects, from 2018 to 2023. The methodology included a thorough search on PubMed and through gray literature, applying rigorous exclusion criteria. The descriptors were selected based on the Medical Subject Headings (MeSH). A total of 265 articles were found. Exclusion criteria were applied, and 90 of them were selected for full reading. After reading the full 90 articles, 52 were excluded, leaving 38 articles for final evaluation composing this review. The key findings highlighted a clear prevalence of studies exploring nanotechnology, including nanoparticles, niosomes, and liposomes. Most of the formulations analyzed in this review emphasize antioxidant activities, which play a crucial role in preventing premature aging caused by free radicals. The reviewed studies revealed specific activities, such as the reduction in melanin synthesis, the inhibition of enzymes involved in the skin aging process, and the prevention of morphological changes typical of aging.