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Lowered Dependence on What about anesthesia ? during Ultra-Fast Cranial MRI inside Children: One-Year Conclusion.
We observed a gradient of decreasing risk of hospitalisation from EAF to RAF/non-flood wet season to dry season. Adaptation measures should be strengthened to prepare for the increased probability of more frequent extreme floods in the future, driven by climate change.
We observed a gradient of decreasing risk of hospitalisation from EAF to RAF/non-flood wet season to dry season. Adaptation measures should be strengthened to prepare for the increased probability of more frequent extreme floods in the future, driven by climate change.
To evaluate the safety and effectiveness of the Flow Redirection Endoluminal Device (FRED) flow diverter in support of an application for Food and Drug Administration approval in the USA.

145 patients were enrolled in a prospective, single-arm multicenter trial. Patients with aneurysms of unfavorable morphology for traditional endovascular therapies (large, wide-necked, fusiform, etc) were included. The trial was designed to demonstrate non-inferiority in both safety and effectiveness, comparing trial results with performance goals (PGs) established from peer-reviewed published literature. The primary safety endpoint was death or major stroke (National Institutes of Health Stroke Scale score ≥4 points) within 30 days of the procedure, or any major ipsilateral stroke or neurological death within the first year. The primary effectiveness endpoint was complete occlusion of the target aneurysm with ≤50% stenosis of the parent artery at 12 months after treatment, and in which an alternative treatment of the target intracranial aneurysm had not been performed.

145 patients underwent attempted placement of a FRED device, and one or more devices were placed in all 145 patients. 135/145 (93%) had a single device placed. Core laboratory adjudication deemed 106 (73.1%) of the aneurysms large or giant. A safety endpoint was experienced by 9/145 (6.2%) patients, successfully achieving the safety PG of <15%. The effectiveness PG of >46% aneurysm occlusion was also achieved, with the effectiveness endpoint being met in 80/139 (57.6%) CONCLUSION As compared with historically derived performance benchmarks, the FRED flow diverter is both safe and effective for the treatment of appropriately selected intracranial aneurysms.

NCT01801007.
NCT01801007.Nitrosamines have gained unexpected attention again, triggered by their discovery at significant concentrations in some active pharmaceutical ingredients (APIs) excipients. Regulatory agencies not only expect the marketing authorization holders to include a nitrosamine risk assessment in their drug development process but to also apply it retrospectively on the marketed drug product. As part of this risk assessment, all possible sources of nitrosamines need to be evaluated. This review provides the chemical background of nitrosamines and elastomeric formulations, the current regulatory status in the pharmaceutical and other industries and discusses analytical challenges of nitrosamine measurement. This evaluation of elastomeric components as a potential nitrosamine source proposes how this information can be used in a drug product risk assessment. Lay abstract Nitrosamines are a group of chemical substances that in many cases have been shown to be carcinogenic. They can form in many ways, from acidic conditions in the human stomach to high temperatures during food preparation. They are also known to be generated during beer brewing and smoking of cigarettes, and naturally exist in the air, soil and our water supply. In the past years, they have also been discovered as impurities in drug products. Extensive investigations have been initiated to find the root causes, whereby all possible sources are included. One of these sources are elastomers, since they are used as primary packaging components in syringe, cartridge and vial systems. This review provides the chemical background of nitrosamines and elastomeric formulations, the current regulatory status in the pharmaceutical and other industries and discusses analytical challenges of nitrosamine measurement. This evaluation of elastomeric components as a potential nitrosamine source proposes how this information can be used in a drug product risk assessment.The fill-finish process of highly concentrated protein formulations poses several technical challenges and in particular the filling process is critical to ensure filling accuracy. As highly concentrated formulations comprise a significant non-volatile fraction, drying of drug product at the filling nozzle may occur during line interruptions. In many cases, this is a result of dripping at the filling nozzle and dependent on environmental factors. The dried product may be picked up by the units after filling interruption and although in small quantities, the effect of drying on the quality of the drug product is currently unclear. selleckchem We investigated the drying phenomenon of a highly concentrated monoclonal antibody formulation (120 mg/mL) and studied drying kinetics and associated aggregation propensity. To this regard, we established a robust method simulating the drying process dependent on environmental conditions such as relative humidity and air flow. We revealed that drying kinetics were characterized by an initial fast evaporation phase, which was shorter for lower relative humidity and air flow, followed by a plateau phase. Protein aggregation particularly increased during the plateau phase and was positively correlated with relative humidity. Drying kinetics and aggregate formation were modeled using Hill's equation. We highlight that drying phenomena are relevant for small-volume drug products (magnitude of 100-200 μL) in particular for dosing accuracy, but less critical for larger fill volumes in the milliliter range. Especially for the latter, they might be negligible if the dried product can fully dissolve in the first units after filling interruption and in case of consistent drug product quality because of adequate formulation choice. Ultimately, we summarize technical options to avoid drying phenomena of highly concentrated protein formulations and emphasize the importance of adequate pump parameter setting.
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