Search

A limited number of studies have directly examined the effects of liposomal encapsulated phytochemicals and their anti-obesity effects in adults. This study aimed to summarize the evidence on the effect of liposomal encapsulated phytochemicals and their role in regulating major pathways involved in the anti-obesity mechanism. A systematic search was performed using several search engines like Science Direct, Google Scholar, and other online journals, focusing on laboratory research, systematic reviews, clinical trials, and meta-analysis that focused on liposomal encapsulated phytochemicals with anti-obesity properties, and followed the preferred reporting terms for this systematic review. An initial search provided a result of 1810 articles, and 93 papers were selected after the inclusion and exclusion criteria. Very few studies have been conducted on the liposomal encapsulation of phytochemicals or its synergistic study to combat obesity; hence this review paves the way for future obesity research and is mainly helpful for the pediatric obesity population. Liposomal encapsulation of phytochemicals has improved the efficiency of freely administered phytochemicals. Targeted delivery improved drug utilization and regulated the anti-obesity pathways. PPARƔ is a major therapeutic target for obesity as it inhibits adipocyte differentiation and maintains energy homeostasis. [ABSTRACT FROM AUTHOR]

The number of rheumatology journals, and papers related to this specialty, is expanding every day. Careful consideration for ethical aspects of such published work is mandatory for authors, readers, reviewers, editors, and all stakeholders. Recent instances of lack of appropriate research ethics committee overview, or participant consent for inclusion in the research study, or a case report, resulting in retractions, emphasize the need for greater awareness regarding these ethical aspects. Authors should strive to avoid redundancy, especially for review articles, both systematic and narrative. Clinical trial registration before commencing enrolment is mandatory as per contemporary norms. Transparent declaration of authorship contributions as well as appropriate attribution of authorship are recommended, since these may help avoid subsequent authorship conflicts. Authors, reviewers, and editors should disclose conflicts of interest, both financial and non-financial. Unbiased peer review is a critical part of editorial decision making; recent instances of peer review fraud have resulted in numerous retractions of scientific papers. Any reproduction of text, figures, or tables should be with due attribution to source, and after seeking permission of the copyright holder. Citations to published work should be relevant and diverse. Research assessment should rely on the assessment of quality of published work, rather than mere citation analyses. Authors should beware predatory, low-quality journals, and utilize social media channels to ethically promote their research with due consideration to privacy and copyright. Rheumatology societies should collaborate to develop guidelines for ethical research reporting, and educate young scientists regarding these principles. [ABSTRACT FROM AUTHOR]

Purpose: Rural community-based organizations (CBOs) serving immigrant communities are critical settings for implementing evidence-based interventions (EBIs). The Implementation Studio is a training and consultation program focused on facilitating the selection, adaptation, and implementation of cancer prevention and control EBIs. This paper describes implementation and evaluation of the Implementation Studio on CBO's capacity to implement EBIs and their clients' knowledge of colorectal cancer (CRC) screening and intention to screen. Methods: Thirteen community health educators (CHEs) from two CBOs participated in the Implementation Studio. Both CBOs selected CRC EBIs during the Studio. The evaluation included two steps. The first step assessed the CHEs' capacity to select, adapt, and implement an EBI. The second step assessed the effect of the CHEs-delivered EBIs on clients' knowledge of CRC and intention to screen (n = 44). Results: All CHEs were Hispanic and women. Pre/post-evaluation of the Studio showed an increase on CHEs knowledge about EBIs (pre: 23% to post: 75%; p < 0.001). CHEs' ability to select, adapt, and implement EBIs also increased, respectively: select EBI (pre: 21% to post: 92%; p < 0.001), adapt EBI (pre: 21% to post: 92%; p < 0.001), and implement EBI (pre: 29% to post: 75%; p = 0.003). Pre/post-evaluation of the CHE-delivered EBI showed an increase on CRC screening knowledge (p < 0.5) and intention to screen for CRC by their clients. Conclusion: Implementation Studio can address unique needs of low resource rural CBOs. An implementation support program with training and consultation has potential to build the capacity of rural CBOs serving immigrant communities to implementation of cancer prevention and control EBIs. Clinical Trials Registration Number: NCT04208724 registered. [ABSTRACT FROM AUTHOR]

Thanks to advances in care, most children with congenital heart disease nowadays survive into adulthood. The majority of patients remain at high risk for future complications. Hence, life-long follow-up is mandatory. Care needs of patients evolve, especially when reaching adulthood. A structured transition period to adult care is advocated. Currently, a fully detailed and structured transition program is not available for patients with congenital heart disease. The aim is to describe the development and design of a multicomponent transition program for adolescents with congenital heart disease, called "Transition with a heart." Transition with a heart was developed based on the Dutch program "On your own feet," starting at the age of 12 years and continuing after transfer. The most vital core components include a general and individualized flowchart, adolescent-centered communication, a joined transfer consultation, and an appointed transition coordinator. Adolescents are gradually informed about their condition and potential late consequences in adult life and stimulated to take medical care in their own hands.Conclusion: Transition with a heart is a practical, multicomponent, comprehensive transition program developed to cover the essential aspects of transitional care for adolescents with congenital heart disease (i.e., continuity of care, disease knowledge, and self-management skills). Interventions were selected from the highest sources of scientific evidence currently available.Clinical trial registration: Not applicableWhat is Known:• Transition towards adult life and health care is a complex process, requiring careful patients' guidance. Various task forces have described the need and potential benefits of transition programs in young people with chronic conditions. Details about the practical development and content of such programs in congenital heart disease are, however, currently lacking.What is New:• This method paper presents the development and design of a person-centered multicomponent transition program for adolescents with congenital heart disease comprising interventional components covering the most important aspects of transitional care: promoting autonomy, disease knowledge, and continuity of care. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is a common concern following laparoscopic sleeve gastrectomy (LSG). This paper aimed to assess the incidence of reflux disease following these bariatric procedures. A literature search was conducted to identify observational studies and clinical trials reporting patients developed GERD disease after LSG. Twenty-two studies included in the analysis, involve 20,495 participants, indicated that the estimated proportion of patients who developed post-surgery GERD was 0.35 (95% CI 0.30–0.41). Subgroup analysis revealed a proportion of 0.33 (95% CI 0.27–0.38) in observational studies and 0.58 (95% CI 0.39–0.75) in clinical trials. High heterogeneity was noted across studies (I2 = 98%). Sensitivity analyses and publication bias assessments were performed to enhance the robustness of the results. Our findings highlight a moderate to high risk of developing GERD following LSG surgery. [ABSTRACT FROM AUTHOR]

Introduction: Fibroblast activation protein (FAP) is highly overexpressed in stromal tissue of various cancers. While FAP has been recognized as a potential diagnostic or therapeutic cancer target for decades, the surge of radiolabeled FAP-targeting molecules has the potential to revolutionize its perspective. It is presently hypothesized that FAP targeted radioligand therapy (TRT) may become a novel treatment for various types of cancer. To date, several preclinical and case series have been reported on FAP TRT using varying compounds and showing effective and tolerant results in advanced cancer patients. Here, we review the current (pre)clinical data on FAP TRT and discuss its perspective towards broader clinical implementation. Methods: A PubMed search was performed to identify all FAP tracers used for TRT. Both preclinical and clinical studies were included if they reported on dosimetry, treatment response or adverse events. The last search was performed on July 22 2022. In addition, a database search was performed on clinical trial registries (date 15th of July 2022) to search for prospective trials on FAP TRT. Results: In total, 35 papers were identified that were related to FAP TRT. This resulted in the inclusion of the following tracers for review: FAPI-04, FAPI-46, FAP-2286, SA.FAP, ND-bisFAPI, PNT6555, TEFAPI-06/07, FAPI-C12/C16, and FSDD. Conclusion: To date, data was reported on more than 100 patients that were treated with different FAP targeted radionuclide therapies such as [177Lu]Lu-FAPI-04, [90Y]Y-FAPI-46, [177Lu]Lu-FAP-2286, [177Lu]Lu-DOTA.SA.FAPI and [177Lu]Lu-DOTAGA.(SA.FAPi)2. In these studies, FAP targeted radionuclide therapy has resulted in objective responses in difficult to treat end stage cancer patients with manageable adverse events. Although no prospective data is yet available, these early data encourages further research. [ABSTRACT FROM AUTHOR]

Background: Digital health technologies (DHTs) can facilitate the execution of de-centralized trials that can offer opportunities to reduce the burden on participants, collect outcome data in a real-world setting, and potentially make trial populations more diverse and inclusive. However, DHTs can also be a significant source of electronic waste (e-waste). In recognition of the potential health and environmental impact from DHT use in trials, private and public institutions have recently launched initiatives to help measure and manage this e-waste. But in order to develop sound e-waste management policies, it will be necessary to first estimate the current volume of e-waste that results from the use of DHTs in trials. Materials and Methods: A Web Ontology Language (OWL)-compliant ontology of DHTs was created using a list of 500 DHT device names derived from a mixture of public and private sources. The U.S. clinical trials registry, ClinicalTrials.gov, was then queried to identify and classify trials using any of the devices in the ontology. The ClinicalTrials.gov records from this search were then analyzed to characterize the volume and properties of trials using DHTs, as well as estimating the total volume of individual DHT units that have been provisioned (or are planned to be provisioned) for clinical research. Results: Our ontology-driven search identified 2326 unique clinical trials with a reported "actual" enrollment of 200,947 participants and a "planned" enrollment of an additional 4,094,748 participants. The most-used class of DHTs in our ontology was "wearables," (1852 trials), largely driven by the use of smart watches and other wrist-worn sensors (estimated to involve 149,391 provisioned devices). The most-used subtype of DHTs in trials was "subcutaneous" devices (367 trials), driven by the prevalent use and testing of glucose monitors (estimated to involve 17,666 provisioned devices). Conclusion: Thousands of trials, involving hundreds of thousands of devices, have already been completed, and many more trials (potentially involving millions more devices) are planned. Despite the great opportunities that are afforded by DHTs to the clinical trial enterprise, if the industry lacks the ability to track DHT use with sufficient resolution, the result is likely to be a great deal of e-waste. A new ontology of DHTs, combined with rigorous data science methods like those described in this paper, can be used to provide better information across the industry, and in turn, help create a more sustainable and equitable clinical trials enterprise. [ABSTRACT FROM AUTHOR]

This paper provides a thorough analysis of the storage structure of hive files and then proposes a new method for processing hive files independently of the Windows registry API and for achieving direct access. The method has the advantages of high priority and of preserving the computing environment. In particular, it is suitable for occasions when the hive files of the target operating system cannot be copied or directly loaded. This paper also presents a set of algorithms for key operations associated with hive files such as access, deletion, creation, and expansion. These operations are designed to be independent of the Windows API. Third-party developers can develop other specialized applications on the basis of this set of algorithms. A complete hivedit program to carry out the operations described above has been implemented. This program can be executed before loading the operating system with the assistance of the ECM-XDP3 emulator, and the correctness of all the algorithms has been verified. [ABSTRACT FROM AUTHOR]

Background: Juvenile drug treatment courts (JDTC) have struggled to define themselves since their inception in 1995. Early courts followed a format similar to adult drug courts, but these did not address the unique needs of juveniles, which led to the creation of 16 Strategies by a consensus panel of practitioners and researchers. But, like the first JDTCs, research with courts following these strategies failed to provide convincing evidence that this "model" was associated with significant reductions in recidivism or drug use. More recently, a new set of evidence-based guidelines were developed through meta-analyses commissioned by the Office of Juvenile Justice and Delinquency Prevention (OJJDP, 2016). Method: OJJDP provided funding for a rigorous multi-site evaluation of the guidelines. This study protocol paper for the Juvenile Drug Treatment Court (JDTC) Guidelines Cross-Site Evaluation presents research designs for the comparison of youth outcomes from 10 JDTCs compared with 10 Traditional Juvenile Courts (TJCs) in the same jurisdictions. Two sites opted into a randomized controlled trial (RCT) and eight sites chose to follow a regression discontinuity design (RDD). Youth data are captured at baseline, and at 6- and 12-month follow-ups using an interview comprised of several standardized assessments. The youths' official records also are abstracted for recidivism and substance use information. The degree to which the evidence-based guidelines are implemented at each site is assessed via an in-depth court self-assessment collected at baseline and again 2 years later and via structured site visits conducted once during implementation. Discussion: As a field-based trial, using both RCT and RDD designs, findings will provide important, policy-relevant information regarding the implementation of the OJJDP evidence-based guidelines, including the degree to which JDTCs adopted and/or modified these practices, their relative impact on recidivism and substance use, as well as the degree to which JDTCs differ from TJCs. Specific inferences may be drawn about whether following or not following specific guidelines differentially impact youth outcomes, yielding recommendations about the translation of this information from research-to-practice for potentiating the broader adoption of these guidelines by JDTCs nationwide. Clinical trials registration: This was not an NIH supported trial. The funder, OJJDP/NIJ, instead required publishing the design with even more information at https://www.ojp.gov/ncjrs/virtual-library/abstracts/juvenile-drug-treatment-court-jdtc-guidelines-cross-site-evaluation. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is not uncommon among adolescents and young adults (AYAs). Left untreated, transition to adulthood might be especially challenging and/or prolonged for AYAs. However, it is unclear whether AYAs are adequately represented in current PTSD treatment research and whether they benefit to the same degree as younger or older individuals. In the first part of the paper, we reflect on developmental considerations in the treatment of AYAs and give an overview of current age-specific results in PTSD treatment research. Furthermore, we review individual trauma-focused evidence-based treatments that were examined in AYAs over the last 10 years. In the second part, we present data from an uncontrolled feasibility trial evaluating cognitive processing therapy (CPT) with some age-adapted modifications and an exposure component (written accounts). We treated 17 AYAs (aged 14 to 21) suffering from posttraumatic stress symptoms (PTSS). At posttreatment, participants had improved significantly with respect to clinician-rated PTSS severity (d = 1.32). Treatment gains were maintained throughout the 6-week and 6-month follow-ups. Results indicated that CPT, with only minor adaptations, was feasible and safe in AYAs. The recommendations for future research focus on the inclusion of young adults in trials with adolescents, more refined age reporting in clinical trials, and the encouragement of dismantling studies in youth. To conclude, clinical recommendations for caregiver involvement and the addressing of developmental tasks, motivational issues and emotion regulation problems are discussed. [ABSTRACT FROM AUTHOR]

StudyPortal was implemented as the first multilingual search platform for geographic visualization of clinical trials and scientific articles. The platform queries information from ClinicalTrials.gov, PubMed, a geodatabase and geographic maps to enable geospatial study search and real-time rendering of study locations or research networks on a map. Thus, disease-specific clinical studies or whole research networks can be shown in a geographic proximity. Moreover, a semantic layer enables multilingual disease input and autosuggestion of medical terms based on the Unified Medical Language System. The portal is accessible on https://studyportal.uni-muenster.de. This paper presents details on implementation of the novel search platform, its search evaluation and future work. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depressed patients. This study (a secondary analysis of a completed randomized controlled trial) aimed to examine whether higher levels of IL-8 mitigate increases in depressed mood in response to an experimental model of inflammation induced depression. Given epidemiologic relationships identified between IL-6, tumor necrosis factor (TNF)- α, and subsequent depression, levels of these pro-inflammatory cytokines were also explored as potential moderators of depressed mood response to endotoxin. Secondary analyses were completed on data from healthy adults (n = 114) who completed a double-blind, placebo-controlled randomized trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). IL-8, as well as IL-6 and TNF- α, were measured at baseline prior to infusion, and depressed mood and feelings of social disconnection were assessed approximately hourly. Baseline levels of IL-8, but not IL-6 or TNF-α, moderated depressed mood (β = − 0.274, p =.03) and feelings of social disconnection (β = − 0.307, p =.01) responses, such that higher baseline IL-8 was associated with less increase in depressed mood and feelings of social disconnection in the endotoxin, but not placebo, condition. IL-8 had threshold effects, in which highest quartile IL-8 (≥ 2.7 pg/mL) attenuated increases in depressed mood in response to endotoxin as compared to lower IL-8 quartiles (p =.02). These findings suggest that IL-8 may be a biological factor that mitigates risk of inflammation-associated depression. Clinical trials registration: ClinicalTrials.gov NCT01671150, registration date 23/08/2012. [ABSTRACT FROM AUTHOR]

Efficient resource identification and discovery is the primary requirements for cloud computing services, as it assists in scheduling and managing of cloud applications. Cloud computing is a revolution of the economic model rather than technological. It takes advantage of several technologies that were tested and modified by replacing the local use of computers with centralized shared resources that are managed and stored by Cloud Service Providers (CSPs) in a transparent manner for Cloud Consumers (CCs). With this new use, various cloud services have appeared and it is mainly classified into three broad categories i.e., Infrastructure as a service (IaaS), Software as a service (SaaS) and Platform as a service (PaaS). Each of these cloud services provides several benefits to the CCs through their respective Quality of Service (QoS) metric. Among the cloud service models, most of the QoS attribute and metric are identical and some are different. The vendors of cloud have focused their objectives on the development of scalability, resource consumption and performance, other characteristics of cloud have been ignored. While CSPs face challenging difficulties in publishing cloud services that displays their cloud resources, at the same time CCs do not have standard mechanism for cloud resource discovery, automated cloud services selection, and easy use of cloud services. In this frame, this paper puts forward a set of QoS metric for SaaS, IaaS, PaaS services and propose (i) An efficient algorithm for identifying the cloud services based on the QoS metric given by the cloud consumer using decision tree classification algorithm (ii) An efficient algorithm for Cloud service resource registry which aims to enable CSPs to register their services with its QoS attributes and (iii) A Cloud service resource discovery that search for the suitable cloud service and their attributes in the cloud service registry that meets the CCs application requirements using Split and Cache (SAC) algorithm. Our new approach makes the provisioning of cloud service possible by ease of resource identification, publication, discovery based on dynamic QoS attributes via web GUI interface backed by series of test that has validated and the proposed approach is feasible and sound. The recommended solution is important: instead of putting effort in locating, learning about the services and evaluating them, CCs can easily identify, discover the services, select and use the required cloud resources. The efficiency of our algorithms was assessed through experiments using CloudSim, which primarily decreases the response time, CPU utilization and memory consumption for identifying and searching the cloud services and increases the accuracy of the CSPs list retrieved along with their QoS attributes. [ABSTRACT FROM AUTHOR]

Objective: A systematic review and meta-analysis was conducted to investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents. Data Sources: Major databases (PubMED, EMBASE, Cochrane Central Register of Controlled Trials), systematic snowballing, and trial registries were screened from the inception dates until September 2017. Methods and Study Selection: Comparative studies involving reproductive-aged women undergoing chemotherapy with or without coadministration of GnRHa were included. Spontaneous menstrual resumption was assessed as a main outcome. Statistical analyses were performed with STATA 14.2 statistical software. Effect estimates were presented as risk ratios (RR) with 95% confidence intervals (CIs). Results: The literature search yielded 25 436 citations and 84 papers were assessed in full text. Eighteen studies (11 randomized controlled trials [RCTs] and 7 cohort studies) published between 1987 and 2015 were included in the analysis, revealing a significant protective effect of GnRHa (n = 1043; RR:1.38; 95% CI: 1.18-1.63) although with high heterogeneity (I2 = 83.3%). Subgroup analyses revealed a significant benefit of GnRHa cotreatment both in RCTs and in cohort studies. Statistical significance was found in all subgroups by the underlying disease, that is, hematological malignancies, autoimmune diseases, and breast cancer. Sensitivity analyses in GnRH agonist-treated patients, in patients younger than 40 years old, and in patients without supradiaphragmatic radiotherapy also revealed a significant benefit of GnRHa cotreatment. Conclusion: Our results indicate that concurrent GnRHa administration is an effective method to decrease gonadotoxicity of alkylating agents. The presence of low-quality evidence favoring gonadoprotective effect requires a strong recommendation for offering GnRHa coadministration to young women who are to undergo gonadotoxic chemotherapy. Capsule: The present systematic review and meta-analysis shows a significant gonadoprotective effect of gonadotropin-releasing hormone analogs in women treated with alkylating agents. [ABSTRACT FROM AUTHOR]

This paper reviews past and current progress in developing pharmacologic agents for the treatment of individuals with bulimia nervosa (BN). We searched the literature and clinical trial registries for compounds studied in BN, the related condition, binge eating disorder (BED), and preclinical models of binge-eating behavior. Drug classes evaluated included antidepressants, antiepileptic drugs, stimulants and other medications for attention-deficit/hyperactivity disorder, opioid antagonists, and weight loss agents, among others. The only available drugs with established efficacy in BN at this time include antidepressants (especially selective serotonin reuptake inhibitors [SSRIs]) and the antiepileptic topiramate, though the efficacy of these compounds is modest at best. The only medications we found currently receiving empirical study in people with BN were fluoxetine, other serotonergic antidepressants, intranasal naloxone, lisdexamfetamine dimesylate, phentermine-topiramate combination, the antiandrogenic oral contraceptive ethinyl estradiol plus drospirenone, and prazosin. Preclinical models suggest that nociceptin receptor antagonists, the selective serotonin 5-HT2C receptor agonist lorcaserin, monoamine stabilizers, and selective orexin-1 receptor antagonists might be helpful. We found no evidence of a drug developed specifically for the treatment of individuals with BN. Future areas for research in the pharmacotherapy of BN are suggested. Importantly, until drugs are developed specifically for eating disorders, drugs developed for other conditions that are centrally acting and associated with beneficial psychotropic effects and/or reduced appetite or weight loss might be considered for repurposing in BN. [ABSTRACT FROM AUTHOR]

The author discusses the ways in avoiding missteps in clinical research reporting by statisticians. He is critical of the importance of several reporting guidelines including the standards for reporting of diagnostic accuracy (STARD), strengthening the reporting of observational studies in epidemiology (STROBE), and preferred reporting items for systematic reviews and meta-analyses (PRISMA). Also mentioned is the essence of using tables in presenting data results.

Due to growing interest in the investigation of exercise induced sweat biomarkers to assess an individual's health and the increasing prevalence of tattoos in the world's population, investigators sought to determine whether local sweat concentrations and excretion rates of epidermal growth factor (EGF), interleukin (IL) -1α, IL-6, IL-8, cortisol, glucose, blood urea nitrogen (BUN), and lactate differ between tattooed and contralateral non-tattooed skin during exercise. Sixteen recreational exercisers [female (50%)] (age = 25–48 years) with ≥ 1 unilateral permanent tattoo [median tattoo age = 6 years, IQR = 5] on the arm/torso completed an outdoor group fitness session. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate concentrations. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate excretion rate. Findings suggest that permanent tattoos older than 1 year may not impact local sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, and lactate concentrations or excretion rates during exercise. Clinical trial identifier NCT04920266 was registered on June 9, 2021. [ABSTRACT FROM AUTHOR]

The aim of this split-mouth randomized clinical trial was to evaluate the clinical outcomes (operative time, edema, trismus, and pain), the immediate histological effects, the alveolar repair (2 and 4 months), and the quality of life after the extraction of impacted third molars using high-speed pneumatic and electrical rotation. Sixteen patients underwent extraction of the two mandibular third molars with a minimum interval of 15 days. On one side of the participant's mouth, high-speed pneumatic rotation was used (Control Group—CG) while for the other side, high-speed electrical rotation was used (Study Group—SG). Statistical analysis included ANOVA repeated measures and Pearson correlations. SG group showed: shorter operative time (p = 0.019), less pain (p = 0.034), swelling (p < 0.001) and trismus (p = 0.025) on the 1st postoperative day; less pain (p = 0.034) and trismus (p = 0.010) on the 3rd postoperative day; less trismus (p = 0.032) on the 7th postoperative day; and better quality of life (p = 0.007). No differences were observed for peripheral bone damage or bone density of alveolar repair at 2 and 4 months between groups. Electric high-speed rotation provided better postoperative clinical parameters of pain, edema and trismus when compared with pneumatic high-speed rotation for mandibular third molar surgery. Trial registration: Brazilian Registry of Clinical Trials registration number RBR-4xyqhqm (https://ensaiosclinicos.gov.br/rg/RBR-4xyqhqm). [ABSTRACT FROM AUTHOR]

Background: To assess the effectiveness, safety, and tolerability of anti-Alzheimer agents (memantine, galantamine, rivastigmine, and donepezil) in controlling ADHD symptoms in children, adolescents, and adults. Methods: Following the PRISMA guideline, clinical trials assessing the potency of anti-Alzheimer medications in managing ADHD symptoms were imported from PubMed, Web of Science, and Scopus (until February 2023). Screening stages were conducted by two independent researchers. Two independent researchers also extracted data from clinical trials reporting the outcomes as the reduction in scores of ADHD questionnaires. The risk of bias within the included studies was assessed using the Cochrane Collaboration tool, while the certainty of outcomes was evaluated based on the GRADE criteria. Results: Of the initial 1597 studies, 11 studies were included. No studies were available for rivastigmine, and only a single study was conducted for galantamine. The results of the other two medications had a slight inconsistency. While both memantine and donepezil were reported to be effective in several studies, they were reported to be ineffective in some other studies. Side effects were mostly reduced appetite and headache. The tolerability of memantine, donepezil, and galantamine was all convincing. Conclusions: While galantamine did not demonstrate a promising efficacy in ADHD, memantine and donepezil showed effectiveness. However, future studies are needed to confirm their efficacy in ADHD since there was some inconsistency. [ABSTRACT FROM AUTHOR]

Objectives: Digital breast tomosynthesis (DBT) can improve diagnostic accuracy compared to 2D mammography, but DBT reporting is time-consuming and potentially more fatiguing. Changes in diagnostic accuracy and subjective and objective fatigue were evaluated over a DBT reporting session, and the impact of taking a reporting break was assessed. Materials and methods: Forty-five National Health Service (NHS) mammography readers from 6 hospitals read a cancer-enriched set of 40 DBT cases whilst eye tracked in this prospective cohort study, from December 2020 to April 2022. Eye-blink metrics were assessed as objective fatigue measures. Twenty-one readers had a reporting break, 24 did not. Subjective fatigue questionnaires were completed before and after the session. Diagnostic accuracy and subjective and objective fatigue measures were compared between the cohorts using parametric and non-parametric significance testing. Results: Readers had on average 10 years post-training breast screening experience and took just under 2 h (105.8 min) to report all cases. Readers without a break reported greater levels of subjective fatigue (44% vs. 33%, p = 0.04), which related to greater objective fatigue: an increased average blink duration (296 ms vs. 286 ms, p < 0.001) and a reduced eye-opening velocity (76 mm/s vs. 82 mm/s, p < 0.001). Objective fatigue increased as the trial progressed for the no break cohort only (ps < 0.001). No difference was identified in diagnostic accuracy between the groups (accuracy: 87% vs. 87%, p = 0.92). Conclusions: Implementing a break during a 2-h DBT reporting session resulted in lower levels of subjective and objective fatigue. Breaks did not impact diagnostic accuracy, which may be related to the extensive experience of the readers. Clinical relevance statement: DBT is being incorporated into many mammography screening programmes. Recognising that reporting breaks are required when reading large volumes of DBT studies ensures this can be factored in when setting up reading sessions. Trial registration: Clinical trials registration number: NCT03733106 Key Points: • Use of digital breast tomosynthesis (DBT) in breast screening programmes can cause significant reader fatigue. • The effectiveness of incorporating reading breaks into DBT reporting sessions, to reduce mammography reader fatigue, was investigated using eye tracking. • Integrating breaks into DBT reporting sessions reduced reader fatigue; however, diagnostic accuracy was unaffected. [ABSTRACT FROM AUTHOR]

I read with interest the paper published by Robert et al. [[1]], reporting a randomized clinical trial comparing the outcomes of One-Anastomosis Gastric Bypass (OAGB) with Roux-en-Y gastric bypass (RYGB) at 2-year follow-up (YOMEGA trial). The authors describe that patients were recruited from nine high-volume bariatric institutions in France, but they required nearly 2 years to enroll 261 patients. Finally, it is surprising that 3% of patients after RYGB have esophagitis at endoscopy and 8% at esophageal biopsy, 2 years after RYGB, when this technique is considered the gold standard anti-reflux surgery for obese patients. [Extracted from the article]

Dupilumab, a monoclonal antibody that inhibits both interleukin (IL)-4 and IL-13 signaling, is an effective treatment option in moderate-to-severe atopic dermatitis (AD). Patients with AD are already at increased risk of developing conjunctivitis, and clinical trials and case reports have shown a greater incidence of conjunctivitis in individuals with AD treated with dupilumab. As this is one of the more commonly reported side effects of this biologic agent, it is important that clinicians are aware of this association and advise patients receiving dupilumab to report signs of conjunctivitis. This review summarizes the risk factors, clinical features, and management options for patients with AD presenting with conjunctivitis after receiving dupilumab therapy. [ABSTRACT FROM AUTHOR]

With increasing numbers of older prisoners, effective strategies for preventing and treating age-associated diseases, such as cognitive disorders, are needed. As pharmacological therapies are limited, non-pharmacological interventions are increasingly recognized as potential treatment strategies. One approach is cognitive training (CT). However, no study has investigated CT in the prison setting. Thus, this one-arm feasibility trial aims to analyze the feasibility of (i) the study protocol and (ii) the implementation of multimodal CT for older prisoners. Eighteen older male prisoners from two specific divisions for older prisoner participated in 12 weekly CT sessions using the NEUROvitalis program. The feasibility analysis included recruitment, dropout, and CT participation rates, and motivation for and satisfaction with CT (using 6-point Likert-scales). The study protocol demonstrated sufficient feasibility with high recruitment rates between 46 and 50%. Therefore, the CT implementation was successful: Only one prisoner ceased participation; all others completed the CT sessions (i.e., attended > 75% of the sessions). Prisoners reported high CT motivation and satisfaction, and would recommend CT. This is the first study to demonstrate CT feasibility in older prisoners. Although more research is needed, these results are a starting point for expanding services to include cognitively enhancing activities for older prisoners. This one-arm feasibility study was pre-registered in the German Clinical Trials Register (DRKS; ID: DRKS00020227).), Registered 11 Mai 2021 https://drks.de/search/de/trial/DRKS00020227. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the effect pegcetacoplan, a C3 and C3b inhibitor, on the rate of progression of geographic atrophy (GA) as assessed by spectral domain optical coherence tomography (SD-OCT) using a split-person study design and deep-learning quantification. Methods: A post hoc analysis of phase 2 FILLY trial data comparing study (treated monthly, treated every other month and sham-treated) and fellow (untreated) eyes in a split-person study design was performed. This analysis included 288 eyes from 144 patients with bilateral GA from the FILLY phase 2 trial (Clinical Trials identifier: NCT02503332). Only patients with bilateral GA and without evidence of choroidal neovascularisation in either eye were included. Patient study eyes were treated with sham injections or with pegcetacoplan monthly (PM) or every other month (PEOM) for 12 months. SD-OCT scans of study and fellow eyes taken at baseline and 12 months were used for the analysis. The main outcomes were the annual change in the area of retinal pigment epithelial and outer retinal atrophy (RORA), its constituent features (photoreceptor degeneration [PRD], retinal pigment epithelium [RPE] loss, hypertransmission) and intact macula as compared to the untreated fellow eye. Results: Annual GA growth was reduced in eyes treated with PM versus untreated fellow eyes for OCT features, including RORA (study eye 0.792 vs. fellow eye 1.13 mm2; P = 0.003), PRD (0.739 vs. 1.23 mm2; P = 0.015), RPE-loss (0.789 vs. 1.17 mm2; P = 0.007) and intact macula (− 0.735 vs. − 1.29 mm2; P = 0.011). Similar (but not statistically significant) trends were observed with the PEOM treatment or when GA was quantified with fundus autofluorescence (FAF). The sham treatment demonstrated no effect. Pearson correlation coefficients showed concordance in the enlargement rate of GA between the study and fellow eyes in the sham (R = 0.64) and PEOM (R = 0.68) groups, but not in the PM group (R = 0.21). Conclusions: Pegcetacoplan-treated eyes demonstrated a reduction in spatial GA progression compared to their untreated counterparts. This effect was more evident on OCT than with FAF. Trial Registration: Clinical Trials identifier: NCT02503332. [ABSTRACT FROM AUTHOR]

The aim of this study is to profile academic institutions (n = 127) based on publications, citations in the top 10% of journals, patent citations in Food and Drug Administration (FDA) approvals, clinical trials with uploaded results, contributions to clinical practice guidelines, awarded patents, start-ups, and licenses generating income in response to the Association of University Technology Managers (AUTM) Licensing Activity Survey: Fiscal Years 2011–2015. Latent variable modeling (LVM) was conducted in Mplus v.8.1, specifically latent profile analysis (LPA) was utilized to predict institutional profiles of research, which were compared with the 2015 Carnegie Classification System ranks. Multivariate regression of profile assignment on research expenditure and income generated by licensure was used to show concurrent validity. The LPA resulted in three profiles as the most parsimonious model. Mantel-Haenszel test of trend to the Carnegie Classification found a positive and significant association among institution rankings (r = 0.492, χ2(1) = 26.69, p < 0.001). Profile assignment significantly predicted differences in research expenditure and income generated by licensure. By classifying academic institutions into improving, mobilizing and thriving translational research profiles allows for a universal metric of translation of science from basic or bench to practice or policy. [ABSTRACT FROM AUTHOR]

Purpose: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship. Methods: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed. Results: The across studies results show that aspirin use associated with lower incidence of PCa (RR: 0.96, 95% CI: 0.95–0.98), and reduced mortality (RR: 0.88, 95% CI: 0.82–0.95). The results of the subgroup analysis indicated that both cohort and population studies in the Americas showed a reduction in PCa incidence and mortality with aspirin use. A linear correlation was observed between dosage/duration of aspirin use and its protective effect. Additionally, post-diagnosis aspirin use was associated with decreased risk of PCa mortality. Conclusions: This meta-analysis revealed an independent correlation between the use of aspirin and reductions in both the incidence and mortality rates of PCa. However, randomized controlled trials did not find any association between aspirin use and PCa. Furthermore, the impact of aspirin on PCa occurrence was found to be dependent on both dosage and duration. [ABSTRACT FROM AUTHOR]

Background and Objectives: Vericiguat is a soluble guanylate cyclase stimulator indicated to reduce the risk of cardiovascular death and hospitalization due to heart failure. A dedicated QTc study in patients with chronic coronary syndromes demonstrated no clinically relevant QTc effect of vericiguat for exposures across the therapeutic dose range (2.5–10 mg). Interval prolongation concentration-QTc (C-QTc) modeling was performed to complement the statistical evaluations of QTc in the dedicated QTc study. Methods: Individual time-matched, baseline- and placebo-corrected Fridericia-corrected QT interval values (ΔΔQTcF) were derived. Two approaches for ΔΔQTcF calculation were investigated: (1) ΔΔQTcF correction with data from a single baseline (as in the primary statistical analysis); and (2) ΔΔQTcF correction with a modeled baseline (considering all available individual non-treatment baselines). The ΔΔQTcF values were related to observed vericiguat concentrations with linear mixed-effects modeling. Results: For both modeling approaches, a positive relationship was found between ΔΔQTcF and vericiguat concentration; however, the slope for the single-baseline approach was not statistically significant, whereas the slope from the modeled-baseline approach was statistically significant. The upper bound of the two-sided 90% confidence interval for model-derived QTc was < 10 ms at the highest observed exposure (745 μg/L; investigated dose range 2.5–10 mg). Conclusion: By applying a single-baseline approach and a modeled-baseline approach that integrated all available QTc data across doses to characterize the QTc prolongation potential, this study showed that vericiguat 2.5–10 mg is not associated with clinically relevant QTc effects, in line with the conclusion from the primary statistical analysis. Clinical Trials Registration Number: ClinicalTrials.gov NCT03504982. [ABSTRACT FROM AUTHOR]

With increasing numbers of older prisoners, effective strategies for preventing and treating age-associated diseases, such as cognitive disorders, are needed. As pharmacological therapies are limited, non-pharmacological interventions are increasingly recognized as potential treatment strategies. One approach is cognitive training (CT). However, no study has investigated CT in the prison setting. Thus, this one-arm feasibility trial aims to analyze the feasibility of (i) the study protocol and (ii) the implementation of multimodal CT for older prisoners. Eighteen older male prisoners from two specific divisions for older prisoner participated in 12 weekly CT sessions using the NEUROvitalis program. The feasibility analysis included recruitment, dropout, and CT participation rates, and motivation for and satisfaction with CT (using 6-point Likert-scales). The study protocol demonstrated sufficient feasibility with high recruitment rates between 46 and 50%. Therefore, the CT implementation was successful: Only one prisoner ceased participation; all others completed the CT sessions (i.e., attended > 75% of the sessions). Prisoners reported high CT motivation and satisfaction, and would recommend CT. This is the first study to demonstrate CT feasibility in older prisoners. Although more research is needed, these results are a starting point for expanding services to include cognitively enhancing activities for older prisoners. This one-arm feasibility study was pre-registered in the German Clinical Trials Register (DRKS; ID: DRKS00020227).), Registered 11 Mai 2021 https://drks.de/search/de/trial/DRKS00020227. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the treatment efficacy of fluoride toothpaste alone and those of adjunctive use of resin infiltration, sodium fluoride varnish, and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on white spot lesions (WSLs). Materials and methods: Seventy-nine patients (356 teeth) with WSLs after orthodontic treatment were randomly allocated into four groups. The WSLs of the participants received resin infiltration only at baseline, and the other groups received fluoride varnish, CPP-ACP mousse, and placebo treatment every 6 months, respectively. A toothpaste containing 1400 ppm fluoride and toothbrushes were distributed to all participants, and oral hygiene instructions were provided. Photos of the teeth with WSL were taken to compare the change between groups which was measured by ImageJ software. Results: Twelve months later, different degrees of reduction in the area of WSLs were observed in all groups. The percentage of lesion area reduction in WSLs in the resin infiltration group was 46.6%, which was significantly higher than that in fluoride varnish group (26.6%), CPP-ACP group (28.6%), and control group (29.8%), and the differences were statistically significant (p < 0.001). Conclusions: This study shows that after 1-year follow-up, the use of fluoride toothpaste, with or without the use of fluoride varnish or CPP-ACP, can reduce the area of WSLs. While resin infiltration can immediately improve dental aesthetics and continuously improved in 12 months, resin infiltration group showed much better results than other groups. Trial registration: Clinical Trials Registration Number: ChiCTR2000032516. Clinical significance: The use of fluoride toothpaste, with or without adjunctive use of fluoride varnish and CPP-ACP, can reduce the area of WSLs, while resin infiltration treatment has additional effect and can immediately improve dental aesthetics. [ABSTRACT FROM AUTHOR]

#1 Patient: Unavailable iPTH measurement due to the lack of reagents for the assay STAT-IntraOperative-Intact-PTH Chemiluminescence Immunoassay for the intraoperative quantitative determination of iPTH levels in EDTA plasma. #5 Patient: Patient who received a subtotal bilateral thyroidectomy and not total thyroidectomy. There is no overlap between the patient populations of the two studies, since patients participating in other competing research protocols were excluded as indicated in the protocols [[1], [7]]. Again, this is proved by the fact that an eventual randomized addition of 17 patients would occur with a very strange distribution (+13 patients in the PRECISE group vs +4 in the FOCUS group) [[1], [7]]. [Extracted from the article]

In recent years, median regression models have been shown to be useful for analyzing a variety of censored survival data in clinical trials. For inference on the regression parameter, there have been a variety of semiparametric procedures. However, the accuracy of such procedures in terms of coverage probability can be quite low when the censoring rate is heavy. In this paper, based on weighted empirical hazard functions, we apply an empirical likelihood (EL) ratio method to the median regression model with censoring data and derive the limiting distribution of EL ratio. Confidence region for the regression parameter can then be obtained accordingly. Furthermore, we compared the proposed method with the standard method through extensive simulation studies. The proposed method almost always outperformed the existing method. [ABSTRACT FROM AUTHOR]

Schizophrenia is a serious mental illness that imposes huge burden of illness on the society. We aimed to conduct a meta-analytic and systematic review of literature on the effectiveness of community-based rehabilitation interventions on symptoms and functioning for people with schizophrenia. The PubMed, Embase, the Cochrane Library, Web of Science, and CINAHL databases were searched through April 16 and 17, 2021, including clinical trial registries and previous Cochrane reviews. We included 24 randomized controlled trials in this review. The content of interventions varied from single-faceted rehabilitation intervention or cognitive retraining, to multi-component rehabilitation interventions or case management. Among 20 studies that reported effects of community-based rehabilitation interventions on symptoms, the pooled SMDs across all interventions was 0.94 (95% CI = 0.11, 1.76; P < 0.001; I2 = 99.1%; n = 3694), representing a strong effect. 21 included studies showed that community-based rehabilitation interventions also had beneficial impacts on functioning (SMD = 1.65; 95% CI = 0.88, 2.43; P < 0.001; I2 = 98.9%; n = 3734). Overall quality of evidence was moderate with a high level of heterogeneity. Community-based rehabilitation interventions have positive effectiveness in improving patients' symptoms and functioning. Community-based rehabilitation interventions should therefore be provided as an adjuvant service in addition to facility-based care for people with schizophrenia. [ABSTRACT FROM AUTHOR]

Study aims were to (I) transfer the measurement of the approach bias (Apb) related to alcoholic stimuli via the Approach Avoidance Task (AAT) into Virtual Reality (VR), (II) check whether measuring Apb in VR leads to similar or different results compared to the classical PC-based version, (III) check the validity of VR versus PC-based bias scores in terms of relatedness to clinical variables. Different 'grasping-conditions' were tested and contrasted in VR concerning (Ia) feasibility (performance): (1) never grasp, (2) always grasp, (3) grasp when PULLing stimuli towards oneself. (Ib) Differences in the bias scores between patients with alcohol use disorder (AUD) and healthy controls (HC) were examined for each grasping-condition. (II) PC-based bias scores were computed and contrasted for AUD versus HC. (III) Correlations of the different VR- versus PC-based bias scores with AUD symptom severity and impulsivity were checked to evaluate validity. (Ia) Grasping-condition 1, followed by 3, showed acceptable (> 50%) and good (> 80%) rates of correct performances allowing for robust median estimation. (Ib) Significant differences in the resulting bias scores emerged between AUD and HC only for grasping-condition 1 (p = 0.034) and 3 at trend-level (p = 0.093). For grasping-condition 1 the Apb Median for AUD was different from zero at a non-significant trend-level (p = 0.064). (II) The PC-based bias scores did not discriminate between AUD versus HC groups. (III) Grasping-condition 1 and 3 VR-based bias scores correlated significantly with impulsivity. In sum, transferring the AAT into VR is feasible, valid, and best implemented without an additional grasping-component when using the VR-controller. This way of Apb assessment represents a viable, perhaps even superior, alternative to PC-based assessments. Trial registration The trial was pre-registered at AsPredicted #76854: 'Transferring the approach avoidance task into virtual reality', 10/13/2021; prior to any analyses being undertaken. [ABSTRACT FROM AUTHOR]

Agitation is common in the early recovery period following traumatic brain injury (TBI), known as post-traumatic amnesia (PTA). Non-pharmacological interventions are frequently used to manage agitation, yet their efficacy is largely unknown. This systematic review aims to synthesize current evidence on the effectiveness of non-pharmacological interventions for agitation during PTA in adults with TBI. Key databases searched included MEDLINE Ovid SP interface, PubMed, CINAHL, Excerpta Medica Database, PsycINFO and CENTRAL, with additional online reviewing of key journals and clinical trial registries to identify published or unpublished studies up to May 2020. Eligible studies included participants aged 16 years and older, showing agitated behaviours during PTA. Any non-pharmacological interventions for reducing agitation were considered, with any comparator accepted. Eligible studies were critically appraised for methodological quality using Joanna Briggs Institute Critical Appraisal Instruments and findings were reported in narrative form. Twelve studies were included in the review: two randomized cross-over trials, three quasi-experimental studies, four cases series and three case reports. Non-pharmacological interventions were music therapy, behavioural strategies and environmental modifications, physical restraints and electroconvulsive therapy. Key methodological concerns included absence of a control group, a lack of formalised agitation measurement and inconsistent concomitant use of pharmacology. Interventions involving music therapy had the highest level of evidence, although study quality was generally low to moderate. Further research is needed to evaluate non-pharmacological interventions for reducing agitation during PTA after TBI. Systematic review registration number: PROSPERO (CRD42020186802), registered May 2020. [ABSTRACT FROM AUTHOR]

Background: Hip resurfacing arthroplasty (HRA) is associated with excellent functional outcomes and return to pre-disease level of activity. The time for return to sport (RTS) following HRA remains unknown. The aim of this meta-analysis was to establish the time for RTS following HRA. Methods: A search was performed on PUBMED, MEDLINE, EMBASE, and the Cochrane Library for trials on HRA and RTS, in the English language, published from the inception of the database to October 2020. In addition, a manual search was performed of relevant sports medicine and orthopaedic journals, and the bibliographies reviewed for eligible trials. All clinical trials reporting on time to RTS following HRA were included. Data relating to patient demographics, methodological quality, operation type, RTS, clinical outcomes, and complications were recorded by two independent reviewers. The PRISMA guidelines for reporting meta-analyses was used to undertake this study. Results: The initial literature search identified 1559 studies and nine further studies were found. Of these, 11 studies with a total of 659 patients matched the inclusion criteria. Two studies involving a total of 94 patients demonstrated an overall pooled proportion of 91.8% (95% CI 71.8–100) of patients RTS by three months post-operatively. Four studies including a total of 265 patients determined a pooled proportion of 96.8% (95% CI 91.0–99.7) of patients able to RTS by the 6-month post-operative stage. Pooled proportion analysis from all 11 studies comprising 659 patients showed 90.9% (95% CI 82.2–96.9) of patients were able to RTS by final follow up of 3 years. Conclusion: Pooled proportion analysis showed an increasing number of patients were able to RTS after HRA over the first one year after surgery. There remains marked inter and intra-study variations in time for RTS but the pooled analysis shows that over 80% of patients were able to RTS at 6 to 12 months after HRA. The findings of this meta-analysis will enable more informed discussions between patients and healthcare professionals about time for RTS following HRA. [ABSTRACT FROM AUTHOR]

Purpose: In Australia and elsewhere, suicide rates among construction workers remain high. Construction workplaces are thus an important setting for targeted suicide prevention programs. This study aimed to compare suicide prevention literacy and help-seeking intentions among participants receiving face-to-face suicide prevention training, with those receiving face-to-face training augmented by a smartphone application. Methods: A two-arm randomised controlled trial of a smartphone suicide prevention intervention was conducted among construction workers in four Australian states (trial registration number: ACTRN12619000625178). All participants received face-to-face training and were randomised to the control condition (face-to-face only, n = 575), or MATESmobile condition (face-to-face + smartphone application,n = 509). Surveys administered at baseline and 3-month follow-up measured suicide prevention literacy and help-seeking intentions for personal/emotional problems and suicidal thoughts. A mixed-model repeated measures (MMRM) analysis included all 1084 randomised participants. Results: Outcomes did not differ significantly for suicide prevention literacy, nor help-seeking intentions from formal sources, informal sources outside the workplace, or no one (did not intend to seek help from anyone). However, relative to those in the control condition, those in the MATESmobile group showed greater increase in help-seeking intentions for emotional problems from a MATES worker/Connector (mean difference 0.54, 95% CI 0.22–0.87) and help-seeking intentions for suicidal thoughts from a workmate (mean difference 0.47, 95% CI 0.10–0.83) or MATES worker/Connector (mean difference 0.47, 95% CI 0.09–0.85). Conclusion: Results indicate that the MATESmobile application, together with face-to-face training, is beneficial in enhancing help-seeking intentions from MATES workers/Connectors and workmates to a greater extent than face-to-face training only. While this research provides some evidence that smartphone applications may support suicide prevention training, further research is needed. [ABSTRACT FROM AUTHOR]

Background: With the advance of subthalamic nucleus (STN) deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD), it is desired to identify objective criteria for the monitoring of the therapy outcome. This paper explores the feasibility of metabolic network derived from positron emission tomography (PET) with 18F-fluorodeoxyglucose in monitoring the STN DBS treatment for PD. Methods: Age-matched 33 PD patients, 33 healthy controls (HCs), 9 PD patients with bilateral DBS surgery and 9 controls underwent 18F-FDG PET scans. The DBS patients were followed longitudinally to investigate the alternations of the PD-related metabolic covariance pattern (PDRP) expressions. Results: The PDRP expression was abnormally elevated in PD patients compared with HCs (P < 0.001). For DBS patients, a significant decrease in the Unified Parkinson's Disease Rating Scale (UPDRS, P = 0.001) and PDRP expression (P = 0.004) was observed 3 months after STN DBS treatment, while a rollback was observed in both UPDRS and PDRP expressions (both P < 0.01) 12 months after treatment. The changes in PDRP expression mediated by STN DBS were generally in line with UPDRS improvement. The graphical network analysis shows increased connections at 3 months and a return at 12 months confirmed by small-worldness coefficient. Conclusions: The preliminary results demonstrate the potential of metabolic network expression as complimentary objective biomarker for the assessment and monitoring of STN DBS treatment in PD patients. Clinical Trial Registration ChiCTR-DOC-16008645. http://www.chictr.org.cn/showproj.aspx?proj=13865. [ABSTRACT FROM AUTHOR]

Introduction: Colchicine, thought to exert its effect via reduction of inflammation, has recently been studied in patients following acute coronary syndromes (ACS). We performed a meta-analysis of all available randomized controlled trials (RCTs) in this high-risk cohort, evaluating efficacy and safety. Methods: MEDLINE, PubMed, EMBASE, clinical trial registries, and select conference proceedings were searched for RCTs comparing colchicine to placebo in patients following ACS. The primary outcome was trial-defined major adverse cardiovascular events (MACE). Secondary endpoints included stroke, myocardial infarction (MI), all-cause and cardiovascular death, and urgent revascularization. Analysis was performed at the longest available clinical follow-up. Results: Two RCTs with a pooled sample size of 5540 patients with 2778 (50.1%) receiving colchicine and 2762 (49.9%) placebo were included. In order to maximize consistency, composite efficacy endpoints between trials were modified. Compared to placebo, patients receiving colchicine had reduction in study-defined composite endpoint (5.5% vs. 7.6%) OR 0.67 (95% CI 0.46–0.98, p = 0.04, I2 = 46%). Similarly, there was a significant reduction in cerebrovascular accidents (OR 0.31, 95% CI 0.14–0.69, p = 0.004, I2 = 0%) and repeat revascularization OR 0.36 (95% CI 0.14–0.90, p = 0.03, I2 = 54%). There was no difference between cardiovascular death (OR 0.92, 95% CI 0.52–1.62, p = 0.78, I2 = 0%), non-cardiovascular death OR 1.27 (95% CI 0.72–2.24, p = 0.41, I2 = 0%), MI at longest available follow-up OR 0.89 (95% CI 0.67–1.17, p = 0.39, I2 = 0%) or resuscitated cardiac arrest OR 0.88 (95% CI 0.32–2.43, p = 0.81, I2 = 0%) in those receiving colchicine. Conclusions: These data suggest colchicine, in addition to guideline-directed medical therapy following acute coronary syndrome reduces MACE, cerebrovascular accidents, and rates of urgent revascularization at 2 years of follow-up. [ABSTRACT FROM AUTHOR]

Aims: Surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. Multiple risk scores aim to stratify HCC risk, potentially allowing individualized surveillance strategies. We sought to validate four risk scores and quantify the consequences of surveillance via the calculation of numbers needed to benefit (NNB) and harm (NNH) according to classification by risk score strata.Methods: Data were collected on 482 patients with cirrhosis during 2013-2014, with follow-up until 31/12/2019. Risk scores (aMAP, Toronto risk index, ADRESS HCC, HCC risk score) were derived from index clinic results. The area under the receiving operating characteristic curve (AUC) was calculated for each. Additionally, per-risk strata, NNB was calculated as total surveillance ultrasounds per surveillance diagnosed early HCC (stage 0/A) and NNH as total ultrasounds performed per false positive (abnormal surveillance with normal follow-up imaging).Results: 22 (4.6%) patients developed HCC. 77% (17/22) were diagnosed through surveillance, of which 13/17 (76%) were early stage. There were 88 false positives and no false negatives (normal surveillance result however subsequent HCC detection). Overall NNB and NNH were 241 and 36, respectively. No score was significantly superior using AUC. Patients classified as low risk demonstrated no surveillance benefit (AMAP, THRI) or had a high NNB of > 300/900 (ADRESS HCC, HCC risk score), with low NNH (24-38).Conclusion: Given the lack of benefit and increased harm through false positives in low-risk groups, a risk-based surveillance strategy may have the potential to reduce patient harm and increase benefit from HCC surveillance.Clinical Trials Registration: This was not a clinical trial and the study was not pre-registered. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score (39.5%). Frailty status was categorized with 3 levels as (frail, intermediate fit, or fit) in 51.2% of the studies and dichotomized (frail, non-frail) in 18.6% of studies. Frailty prevalence greatly varied across trials ranging from 17.2% to 73.6% of the cohort. Of the included studies, 72.0% conducted subgroup analysis (planned or post-hoc) based on frailty status. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes. [ABSTRACT FROM AUTHOR]

Latent tuberculosis infection (LTBI) prevalence among adults with chronic hepatitis B (CHB) is two times higher than LTBI prevalence in the general adult population. Although newer CHB treatments evaluated in clinical trials modulate the immune system and potentially increase LTBI reactivation risk, it is unknown whether CHB clinical trials are screening for LTBI. We describe LTBI screening practices in CHB clinical trials. We utilized the ClinicalTrials.gov website to identify clinical trials that evaluated CHB treatments. CHB treatments were categorized according to LTBI reactivation risk as unknown, low, moderate, and high-risk. Tuberculosis burden among countries in which CHB clinical trials were conducted were defined using World Health Organization definitions. Of 651 CHB clinical trials identified, 452 (69%) were included in the final cohort, among which 337 (75%), 108 (24%), and 7 (1%) evaluated CHB medications with a low, unknown, and moderate LTBI reactivation risk, respectively. A total of 330 (73.0%) CHB clinical trials reviewed were conducted in high TB burden countries. Three (0.6%) CHB trials reviewed screened for LTBI; one each among CHB treatments with low, moderate, and high LTBI reactivation risk. Although nearly 75% of all CHB clinical trials were conducted in high TB burden countries and 25% of trials evaluated CHB treatments with an unknown LTBI reactivation risk, less than 1% of trials screened for LTBI. Consideration should be given to screen for LTBI among CHB clinical trials given high prevalence of co-infection and potential for increased LTBI reactivation risk with CHB treatments evaluated. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that coronavirus disease-2019 (COVID-19) may lead to a wide range of post-acute sequelae outcomes, including new onset of diabetes. The aim of this meta-analysis was to estimate the incidence of newly diagnosed diabetes in survivors of COVID-19. We searched MEDLINE, Scopus, Cochrane Central Register of Controlled Trials and the World Health Organization Global Literature on Coronavirus Disease and clinical trial registries for studies reporting the association of COVID-19 and diabetes. Search dates were December 2019–October 16, 2022. Two investigators independently assessed studies for inclusion. Risk of bias was assessed using the Newcastle–Ottawa Scale. We estimated the effect of COVID-19 on incident diabetes by random-effects meta-analyses using the generic inverse variance method. We identified 8 eligible studies consisting of 4,270,747 COVID-19 patients and 43,203,759 controls. Median age was 43 years (interquartile range, IQR 35–49), and 50% were female. COVID-19 was associated with a 66% higher risk of incident diabetes (risk ratio, 1.66; 95% CI 1.38; 2.00). The risk was not modified by age, sex, or study quality. The median risk of bias assessment was 7. In this systematic review and meta-analysis, COVID-19 was associated with higher risk for developing new onset diabetes among survivors. Active monitoring of glucose dysregulation after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is warranted. [ABSTRACT FROM AUTHOR]

Background: Traumatic facet dislocations in the subaxial cervical spine, also known as locked facets, are commonly associated with neurological deficits. The fear of the presence of an associated traumatic disc herniation and consequent neurological worsening usually causes a delay in the spinal realignment. This study's aim is an analysis of safety and efficacy when treating acute cervical traumatic facet dislocations using cranial-cervical traction or posterior open reduction and fixation in the presence of disc herniations. Methods: Inclusion criteria addressed the following patient groups: (1) MRI diagnosis of traumatic cervical facet dislocations with disc herniation, (2) intervention: either cranial-cervical traction or posterior open reduction and fixation, (4) neurological outcomes after treatment, (5) adult 18 plus years of age, (6) sample sizes greater than 20 patients, (7) English language publication. The following databases and search tools were analyzed: MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and the clinical trial registries (ClinicalTrials.gov), October 2021. Results: Six studies were found, 2 with posterior open reduction and fixation and 4 with cranial-cervical traction, totalizing 197 patients. Neurological worsening was reported only in 1 case (0.5%). Conclusions: Traumatic disc herniation in cervical facet dislocations is not an absolute contraindication of cranial-cervical traction or posterior open reduction. Early realignment of the spine could bring more neurological benefits than waiting for an MRI or surgical discectomy. However, caution is needed in this review's data interpretation until prospective and well-designed studies are performed. [ABSTRACT FROM AUTHOR]

Anticoagulant rodenticides (ARs) are used worldwide for the control of rodent pests and are the main method of control of rat pest populations in agricultural areas. The main aim of this review is to discuss the risk of ARs to non-target wildlife in oil palm areas in Southeast Asia, mainly Indonesia and Malaysia. We discussed AR use in oil palm areas and toxicities of ARs on target and non-target animals. We also reviewed published literature on wildlife species reported in oil palm areas in Southeast Asia and utilizing this information, we assessed the hazard risk of ARs to non-target wildlife in oil palm plantations. ARs are a secondary exposure hazard to rodent-consuming mammalian carnivores, such as leopard cats and civets, and rodent-consuming raptors, such as barn owls. Consumption of dead poisoned prey puts scavengers, such as water monitors, at high risk for AR exposure. Domestic livestock and granivorous birds are at high risk for AR exposure via primary exposure to toxic bait, while omnivores such as macaques and wild pigs are at moderate risk for both primary and secondary exposure to ARs. The effects of ARs on barn owls have been well studied in the field and in laboratory secondary toxicity studies. Thus, the nest-box occupancy and reproductive parameters of local barn owl populations can be monitored as an indicator of the AR exposure level in the area. Clinical Trials Registration: No clinical trials were involved in this study. [ABSTRACT FROM AUTHOR]

Late-term fetal demise including fetal death in utero, late miscarriage and late termination of pregnancy are relatively frequent occurrences. Post-traumatic stress disorder (PTSD) is a pathology that finds its roots in exposure to a life-threatening event or an event related to death. Exposure to fetal death during a late-term fetal demise is, therefore, a situation at risk of trauma. The objective of this study was to assess the prevalence of PTSD symptoms in the short term among patients faced with late fetal demise, and to identify potential risk factors. All women were assessed at 15 days, one month, and three months after late fetal demise using the Impact of Event Scale-Revised (IES-R) and the Peritraumatic Dissociative Experiences Questionnaire (PDEQ). At 15 days, 44.2% of patients presented a pathological score on the IES-R (≥ 33). At one month and three months, this figure was 34.1% and 9.1% respectively. Factor associated with PTSD symptoms were: peritraumatic dissociation (p = 0.014), seeing the fetus during hospitalization (p = 0.035), holding the fetus in one's arms (p = 0.046), and the organization of a funeral service (p = 0.025). Patients experiencing late fetal demise are at significant risk of trauma. Care providers should remain vigilant to identify high-risk situations to offer appropriate care. Clinical trials registration number: NCT03433989. [ABSTRACT FROM AUTHOR]

Ribosomal protein dysfunction causes diverse human diseases, including Diamond–Blackfan anemia (DBA). Despite the universal need for ribosomes in all cell types, the mechanisms underlying ribosomopathies, which are characterized by tissue-specific defects, are still poorly understood. In the present study, we analyzed the transcriptomes of single purified erythroid progenitors isolated from the bone marrow of DBA patients. These patients were categorized into untreated, glucocorticoid (GC)-responsive and GC-non-responsive groups. We found that erythroid progenitors from untreated DBA patients entered S-phase of the cell cycle under considerable duress, resulting in replication stress and the activation of P53 signaling. In contrast, cell cycle progression was inhibited through induction of the type 1 interferon pathway in treated, GC-responsive patients, but not in GC-non-responsive patients. Notably, a low dose of interferon alpha treatment stimulated the production of erythrocytes derived from DBA patients. By linking the innately shorter cell cycle of erythroid progenitors to DBA pathogenesis, we demonstrated that interferon-mediated cell cycle control underlies the clinical efficacy of glucocorticoids. Our study suggests that interferon administration may constitute a new alternative therapeutic strategy for the treatment of DBA. The trial was registered at www.chictr.org.cn as ChiCTR2000038510. [ABSTRACT FROM AUTHOR]

Chloride (Cl−) influences the bioavailability and toxicity of metals in fish, but the mechanisms by which it influences these processes is poorly understood. Here, we investigated the effect of chloride on the cytotoxicity, bioavailability (i.e., accumulation) and bioreactivity (i.e., induction of mRNA levels of metal responsive genes) of copper (Cu) and silver (Ag) in the rainbow trout gut cell line (RTgutGC). Cells were exposed to metals in media with varying Cl− concentrations (0, 1, 5 and 146 mM). Metal speciation in exposure medium was analyzed using Visual MINTEQ software. Cytotoxicity of AgNO3 and CuSO4 was measured based on two endpoints: metabolic activity and membrane integrity. Cells were exposed to 500 nM of AgNO3 and CuSO4 for 24 h in respective media to determine metal bioavailability and bioreactivity. Ag speciation changes from free ionic (Ag+) to neutral (AgCl), to negatively charged chloride complexes (AgCl2−, AgCl3−) with increasing Cl− concentration in exposure media whereas Cu speciation remains in two forms (Cu2+ and CuHPO4) across all media. Chloride does not affect Ag bioavailability but decreases metal toxicity and bioreactivity. Cells exposed to Ag expressed significantly higher metallothionein mRNA levels in low Cl− media (0, 1, and 5 mM) than in high Cl− medium (146 mM). This suggests that chloride complexation reduces silver bioreactivity and toxicity. Conversely, Cu bioavailability and toxicity were higher in the high chloride medium (146 mM) than in the low Cl− (0, 1, and 5 mM) media, supporting the hypothesis that Cu uptake may occur via a chloride dependent mechanism. Clinical trials registration: This study did not require clinical trial registration. [ABSTRACT FROM AUTHOR]

Outcome reporting bias is one of the fundamental forms of publication bias. It implies publishing only outcomes that have positive results. The aim of this observational study was to explore primary outcome discrepancies between registry of clinical trials and their corresponding publications, since these can indicate outcome reporting bias in child mental health. Data were extracted from completed interventional clinical trials from ClinicalTrial.gov registry and its Archive site. Trials were registered under "Behaviours and Mental Disorders" category, and conducted on underage participants (0–17 years). Their primary outcomes were compared to those published in publication which had a corresponding NCT number stated in the text. Sixteen percent of trials did not have the minimum information on primary outcome stated in the registry—neither the measure used nor the measurement time points; 38.9% of trials had the minimum information stated to describe primary outcome, while only 3.3% of trials had all the necessary elements stated in the registry. Most of the publication in our sample had positive results (66.4%). Half of the trials registered before completion had non-matching primary outcomes in the registry and publication; 85.4% of trials with non-matching outcomes indicated possible outcome reporting bias for some of the primary outcome. Middle-sized trials and industry-funded trials were related with higher quality of primary outcome registration. Industry funding was related with positive findings in publication. Non-industry funding proved to be the only significant predictor of discrepancy between registered and published primary outcomes, and possible outcome reporting bias. Journal impact factor was not related with any of the outcome measures. The main limitation of the study is that it primarily offers an insight into discrepancy of registered and published outcomes. The methodology does not imply an access to results of unpublished outcomes — therefore, it was not possible to determine the presence of the bias with sufficient certainty in large number of trials. Further research should be done with improved methodology and additional data. [ABSTRACT FROM AUTHOR]

Aim This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to compare the efficacy of different caries removal techniques: complete caries removal (CCR), selective caries removal (SCR) and stepwise caries removal (SWR) for deep carious lesions in vital primary teeth. Data sources The design of this review followed the PRISMA guidance (http://www.prisma-statement.org/). Relevant studies were identified using electronic databases (PubMed [Medline], Cochrane Library, EMBASE) and finally reference lists were screened. The US National Institutes of Health Trials Register (NIHTR; http://clinicaltrials.gov) and World Health Organisation International Clinical Trials Registry Platform (WHO ICTRP; http://apps.who.int/trialsearch) were used to help assess publication bias, as it was not possible to test funnel plot asymmetry. Duplicates were located and eliminated using EndNote X7 programme. Study selection To be included, studies had to be published RCTs comparing SCR or SWR with CCR as caries removal strategies for deep carious lesions in vital primary teeth. The outcomes were pulp exposure, pulpo-periodontal complications (clinical and radiological failures) and/or restorative failures. RCTs applying these caries removal techniques were excluded if one of the other trial arms did not involve caries removal (that is, Hall Technique, therapeutic sealing of cavity lesions). Initially, 1,374 potentially eligible articles were identified, out of which 15 (English or French language only) were selected for full-text screening, which included ten relevant references corresponding to eight studies. Data extraction and synthesis Two authors independently extracted data using a piloted data extraction sheet, with a third reviewer resolving any disagreements. The authors performed conventional intention-to-treat and per-protocol meta-analyses, and calculated odds ratios (ORs) as effect estimates in the random-effects model, using Revman5. Results The eight included RCTs were conducted between 1977 and 2018. They include 669 patients and 824 teeth, with follow-up ranging from four weeks to 24 months. Collective results showed reduced risk of pulp exposure after SCR (OR: 0.10, 95% CI [0.04, 0.25]) or SWR (OR: 0.20, 95% CI [0.09, 0.44]), compared with CCR. There was a higher risk of composite restorative failure (OR: 2.61, 95% CI [1.05, 6.49]) using United States Public Health Service (USPHS) criteria, after SCR was compared with CCR only in intention-to-treat analysis. However, when comparing the risk of clinical or radiographic failure of pulpo-periodontal complications, no difference was found between SCR, CCR or SWR. Conclusion The conclusions of the paper are that there is a significant decrease in pulp exposure risk with SCR and SWR in comparison with CCR. However, there is a need for further studies with less risk of bias powered to report on the long-term outcomes of pulpo-periodontal health and restoration longevity. [ABSTRACT FROM AUTHOR]