Subject(s)
Acetamides/adverse effects , Amino Alcohols/adverse effects , COVID-19 Vaccines/adverse effects , Decanoates/adverse effects , Drug Hypersensitivity/etiology , Fatty Alcohols/adverse effects , Hypersensitivity, Immediate/chemically induced , Polyethylene Glycols/adverse effects , BNT162 Vaccine , COVID-19 Vaccines/chemistry , Drug Compounding , Drug Hypersensitivity/immunology , Humans , Hypersensitivity, Immediate/immunology , Nanoparticles , Risk Assessment , Risk FactorsSubject(s)
Anaphylaxis/chemically induced , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Liposomes/adverse effects , Nanoparticles/adverse effects , Vaccines, Synthetic/adverse effects , 2019-nCoV Vaccine mRNA-1273 , Amino Alcohols/adverse effects , Amino Alcohols/chemistry , Anaphylaxis/diagnosis , Anaphylaxis/pathology , BNT162 Vaccine , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/chemistry , Decanoates/adverse effects , Decanoates/chemistry , Excipients/adverse effects , Excipients/chemistry , Humans , Liposomes/administration & dosage , Liposomes/immunology , Mass Vaccination/statistics & numerical data , Nanoparticles/administration & dosage , Polyethylene Glycols/adverse effects , Polyethylene Glycols/chemistry , SARS-CoV-2/pathogenicity , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/chemistry , mRNA VaccinesABSTRACT
BACKGROUND: Synthetic vascular material use, particularly polytetrafluoroethylene- (PTFE) -based, can be associated with bleeding, which may increase operative time and blood loss. None of the commercially available sealants designed to ensure hemostasis combine bioresorption, high viscosity, hydrophobicity, and compliance with the underlying tissue and on-demand activation. METHODS: A study was designed to assess the biocompatibility and in-vivo performance and bioresorption of a new synthetic on-demand light-activated poly(glycerol-sebacate) acrylate- (PGSA) -based SETALIUM™ Vascular Sealant (TISSIUM, Paris, France) in three large animal studies of open vascular carotid and aortic surgery. The pre-clinical results were then translated into a clinical setting in a prospective, single-arm multicenter study in patients requiring carotid endarterectomy using an ePTFE patch. RESULTS: The biocompatibility testing showed that the PGSA-based SETALIUM™ Vascular Sealant did not induce any significant toxic reaction at a standard clinical dose nor at doses up to 40 times the equivalent intended clinical dose. The PGSA-based sealant was shown to be non-pyrogenic, non-sensitizing, non-irritant, non-clastogenic, and non-mutagenic. The animal studies showed excellent performance and safety results, with clinically significant hemostasis achieved in 100% of the animals in both carotid and aorta studies and excellent local tolerance. Histopathology and morphometric analyses showed surface-based gradual and sustained bioresorption of the PGSA-based sealant up to 86% at 12 months. In the clinical study, the application of the PGSA-based sealant resulted in good performance and safety, with immediate hemostasis achieved in 84% of the cases and no adverse event related to the sealant reported through the one-year follow-up. CONCLUSIONS: The new synthetic on-demand light activated PGSA-based SETALIUM™ Vascular Sealant investigated in our studies demonstrated good biocompatibility, sustained and gradual surface based bioresorption, and acceptable safety profile in animal studies. In addition, the first in-human use showed that the sealant is a safe and effective alternative to achieve fast and controlled hemostasis in vascular carotid reconstructions. A larger randomized controlled study will allow further validation of these encouraging preliminary results.
Subject(s)
Acrylates/administration & dosage , Angioplasty/adverse effects , Aorta, Thoracic/surgery , Carotid Arteries/surgery , Decanoates/administration & dosage , Endarterectomy, Carotid/adverse effects , Glycerol/analogs & derivatives , Hemorrhage/prevention & control , Hemostatic Techniques , Polymers/administration & dosage , Tissue Adhesives/administration & dosage , Acrylates/adverse effects , Aged , Aged, 80 and over , Angioplasty/instrumentation , Animals , Decanoates/adverse effects , Endarterectomy, Carotid/instrumentation , Female , Glycerol/administration & dosage , Glycerol/adverse effects , Hemostatic Techniques/adverse effects , Humans , Male , Materials Testing , Middle Aged , Models, Animal , Polymers/adverse effects , Prospective Studies , Sheep, Domestic , Time Factors , Tissue Adhesives/adverse effects , Treatment OutcomeSubject(s)
Decanoates/adverse effects , Decanoic Acids/adverse effects , Fluphenazine/adverse effects , Heptanoates/adverse effects , Heptanoic Acids/adverse effects , Autonomic Nervous System/drug effects , Clinical Trials as Topic , Decanoates/administration & dosage , Double-Blind Method , Heptanoates/administration & dosage , Humans , Movement Disorders/chemically induced , Sleep Stages/drug effects , Time FactorsABSTRACT
Forty-nine schizophrenic outpatients stabilized on oral antipsychotic medication and procyclidine received 12.5 mg or 18.75 mg of fluphenazine enanthate or fluphenazine decanoate and were examined for extrapyramidal side effects one and two weeks later. Extrapyramidal side effects were present in 30 patients (61%) but were clinically significant in only 11 (22%). Fluphenazine enanthate produced more clinically significant extrapyramidal symptoms, particularly akathisia, than did fluphenazine decanoate.
Subject(s)
Basal Ganglia Diseases/chemically induced , Fluphenazine/adverse effects , Adolescent , Adult , Akathisia, Drug-Induced , Ambulatory Care , Decanoates/adverse effects , Delayed-Action Preparations/adverse effects , Female , Heptanoates/adverse effects , Humans , Male , Middle Aged , Schizophrenia/drug therapyABSTRACT
The author examined the incidence and severity of extrapyramidal symptoms (EPS) in 19 male psychotic outpatients receiving fluphenazine decanoate. Ten patients developed an EPS; only 3 had symptoms of the highest severity. The data suggest that neither prophylactic nor long-term use of antiparkinsonian agents is necessary for most patients receiving fluphenazine decanoate. On the basis of a comparison to a study of fluphenazine enanthate patients, the author concludes that fluphenazine decanoate is the drug of choice in terms of incidence and severity of EPS.