Phase III

Childhood cancer survivors have a higher risk of developing cardiomyopathy than members of the general population. Screening echocardiograms can facilitate early detection and treatment of cardiomyopathy. Furthermore, motivational interviewing can increase uptake of cardiac screening. However, such approaches are time- and resource-intensive, which limits their reach to the survivors who need them. We describe how we utilized a user-centered design process to translate an in-person motivational interviewing intervention into an eHealth tool to improve cardiac screening among childhood cancer survivors...

Wastewater treatment recycling is critical to ensure safe water supply or to overcome water shortage. Herein, we developed metallic Co integration onto MnO nanorods (MON) resulting in a phase-separated synergetic catalyst by creating more Mn(III) via the Jahn-Teller effect and oxygen vacancies and improving the redox capability of Co nanoparticles mediated by a thin carbon layer. Additionally, the N-doped surface carbon network on MON contributes to polar sites, facilitating the enrichment of contaminants around reactive sites, thereby shortening the migration of reactive oxidative species (ROS) toward contaminants...

The accessibility of multiple valence states of americium (Am) inspired redox-based protocols aimed at efficient separation of trivalent Am (Am3+ ) from trivalent lanthanides (Ln3+ ) alternative to the traditional liquid-liquid extraction. This requires an extensive understanding of the coordination chemistry of Am in its various accessible valence states in the aqueous phase. In this work, by means of DFT calculations, the coordination of AmIII-VI with five typical N-donor ligands, i.e., terpyridine (tpy), bispyrazinylpyridine (dpp), bistriazinylpyridine (BTP), bistriazinyl bipyridine (BTBP), and bistrazinyl phenanthroline (BTPhen), was studied in terms of energy and topological analysis...

AIMS: Lethal arrhythmias in hypertrophic cardiomyopathy (HCM) are widely attributed to myocardial ischaemia and fibrosis. How these factors modulate arrhythmic risk remains largely unknown, especially as invasive mapping protocols are not routinely used in these patients. By leveraging multiscale digital-twin technologies, we aim to investigate ischaemic mechanisms of increased arrhythmic risk in HCM. METHODS AND RESULTS: Computational models of human HCM cardiomyocytes, tissue and ventricles were used to simulate outcomes of phase 1A acute myocardial ischaemia...

Background: Clinical trial is a crucial step in the development of a new therapy (e.g., medication) and is remarkably expensive and time-consuming. Forecasting the approval of clinical trials accurately would enable us to circumvent trials destined to fail, thereby allowing us to allocate more resources to therapies with better chances. However, existing approval prediction algorithms did not quantify the uncertainty and provide interpretability, limiting their usage in real-world clinical trial management...

BACKGROUND: Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials. OBJECTIVES: The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making. DESIGN: Systematic review and network meta-analysis...

OBJECTIVES: The inJectable Antiretroviral feasiBility Study (JABS) aimed to evaluate the implementation of long-acting regimens in a 'real world' Australian setting, with inclusion of participants with complex medical needs, social vulnerability and/or historical non-adherence. METHODS: JABS was a 12-month, single-centre, single-arm, open-label phase IV study of long-acting cabotegravir 600 mg plus rilpivirine 900 mg administered intramuscularly every 2 months to adults with treated HIV-1 infection...

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups...

Objective: To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer. Methods: This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected...

OBJECTIVE: Dravet syndrome is a rare developmental epilepsy syndrome associated with severe, treatment-resistant seizures. Since seizures and seizure clusters are linked to morbidity, reduced quality of life, and premature mortality, a greater understanding of these outcomes could improve trial designs. This analysis explored seizure types, seizure clusters, and factors affecting seizure cluster variability in Dravet syndrome patients. METHODS: Pooled post-hoc analyses were performed on data from placebo-treated patients in GWPCARE 1B and GWPCARE 2 randomized controlled phase III trials comparing cannabidiol and placebo in Dravet syndrome patients aged 2-18 years...

Metal-organic frameworks (MOFs) are good adsorbents for targeted chemicals with their adjustable properties. Herein, we prepared a zirconium based MOF (MOF-808(Zr)) and functionalized it employing 2-mercapto-4-methyl-5-thiazolacetic acid (MOF-808(Zr)-Tz). The prepared MOFs were characterized by XRD, FTIR, SEM-EDX, TGA, N2 sorption, zeta potential measurements, and elemental analysis. The surface area of MOF-808(Zr)-Tz was 1348 m2 /g. Dispersive solid-phase micro-extraction (D-SPµE) method based on MOF-808(Zr)-Tz was firstly developed and applied to the extraction of chromium, silver, and rhodium in waters...

BACKGROUND: An ambitious reform of the early access (EA) process was set up in July 2021 in France, aiming to simplify procedures and accelerate access to innovative drugs. OBJECTIVE: This study analyzes the characteristics of oncology drug approvals through the EA process and its impact on real-life data for oncology patients. METHODS: The number and characteristics of EA demands concerning oncology drugs submitted to the National Health Authority (HAS, Haute Autorité de Santé) were reviewed until 31 December 2022...

BACKGROUND: To analyze the relationship between lipid metabolism, coagulation function, and bone metabolism and the contributing factor and staging of non-traumatic femoral head necrosis, and to further investigate the factors influencing the blood indicators related to the staging of non-traumatic femoral head necrosis. METHODS: The medical records of patients with femoral head necrosis were retrieved from the inpatient medical record management system, and the lipid metabolism, bone metabolism, and coagulation indices of non-traumatic femoral head necrosis (including alcoholic, hormonal, and idiopathic group) were obtained according to the inclusion and exclusion criteria, including Low-Density Lipoprotein Cholesterol, Triglycerides, Non-High-Density Lipoprotein Cholesterol, Apolipoprotein A1, Apolipoprotein (B), Apolipoprotein (E), Uric Acid, Alkaline Phosphatase, Bone-specific Alkaline Phosphatase, Activated Partial Thromboplastin Time, Prothrombin Time, D-dimer, Platelet count...

The α-Proteobacteria belonging to Bradyrhizobium genus are microorganisms of extreme slow growth. Despite their extended use as inoculants in soybean production, their physiology remains poorly characterized. In this work, we produced quantitative data on four different isolates: B. diazoefficens USDA110, B. diazoefficiens USDA122, B. japonicum E109 and B. japonicum USDA6 which are representative of specific genomic profiles. Notably, we found conserved physiological traits conserved in all the studied isolates: (i) the lag and initial exponential growth phases display cell aggregation; (ii) the increase in specific nutrient concentration such as yeast extract and gluconate hinders growth; (iii) cell size does not correlate with culture age; and (iv) cell cycle presents polar growth...

OBJECTIVE: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting. Therefore, to complement existing approaches, we set out here to design a longitudinal multivariate analytical framework that accepts as input an entire clinical trial database, comprising all measurements, patients, and time points across multiple trials...

BACKGROUND: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score...

In 2019, the European Society of Radiotherapy and Oncology (ESTRO) published its 2030 Vision "Radiation Oncology, Optimal Health, For All, Together". However, in 2020, the global pandemic, coinciding with the Society's 40th anniversary, had long-term consequences on global behaviours and on the financial environment for scientific associations worldwide. In 2022, ESTRO conducted a survey among its members, revealing their strong appreciation for networking opportunities and the creation of high-quality interdisciplinary scientific content...

The Fe(II)/Fe(III) cycle is an important driving force for dissolution and transformation of jarosite. Divalent heavy metals usually coexist with jarosite; however, their effects on Fe(II)-induced jarosite transformation and different repartitioning behavior during mineral dissolution-recrystallization are still unclear. Here, we investigated Fe(II)-induced (1 mM Fe(II)) jarosite conversion in the presence of Cd(II), Mn(II), Co(II), Ni(II) and Pb(II) (denoted as Me(II), 1 mM), respectively, under anaerobic condition at neutral pH...

BACKGROUND: Most studies focus on the risk factors associated with the development of pressure ulcers (PUs) during acute phase or community care for individuals with spinal cord injury (SCI). OBJECTIVES: This study aimed to i) compare clinical and demographic characteristics of inpatients after SCI with PUs acquired during rehabilitation vs inpatients without PUs and ii) evaluate an existing PU risk assessment tool iii) identify first PU predictors. METHODS: Individuals (n = 1,135) admitted between 2008 and 2022 to a rehabilitation institution within 60 days after SCI were included...

BACKGROUND: Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments. OBJECTIVES: To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population. DESIGN: Ongoing, multicenter, phase III open-label extension (OLE) study...