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1.
Comput Methods Programs Biomed ; 196: 105613, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32593974

ABSTRACT

BACKGROUND AND OBJECTIVE: Health care costs represent a substantial an increasing percentage of global expenditures. One key component is treatment of respiratory diseases, which account for one in twelve deaths in Europe. Computational simulations of lung airflow have potential to provide considerable cost reduction and improved outcomes. Such simulations require accurate in silico modeling of the lung airway. The geometry of the lung is extremely complex and for this reason very simple morphologies have primarily been used to date. The objective of this work is to develop an effective methodology for the creation of hybrid pulmonary geometries combining patient-specific models obtained from CT images and idealized pulmonary models, for the purpose of carrying out experimental and numerical studies on aerosol/particle transport and deposition in inhaled drug delivery. METHODS: For the construction of the hybrid numerical model, lung images obtained from computed tomography were exported to the DICOM format to be treated with a commercial software to build the patient-specific part of the model. At the distal terminus of each airway of this portion of the model, an idealization of a single airway path is connected, extending to the sixteenth generation. Because these two parts have different endings, it is necessary to create an intermediate solid to link them together. Physically realistic treatment of truncated airway boundaries in the model was accomplished by mapping of the flow velocity distribution from corresponding conducting airway segments. RESULTS: The model was verified using two sets of simulations, steady inspiration/expiration and transient simulation of forced spirometry. The results showed that the hybrid model is capable of providing a realistic description of air flow dynamics in the lung while substantially reducing computational costs relative to models of the full airway tree. CONCLUSIONS: The model development outlined here represents an important step toward computational simulation of lung dynamics for patient-specific applications. Further research work may consist of investigating specific diseases, such as chronic bronchitis and pulmonary emphysema, as well as the study of the deposition of pollutants or drugs in the airways.


Subject(s)
Hydrodynamics , Lung , Computer Simulation , Europe , Humans , Lung/diagnostic imaging , Models, Biological , Particle Size , Trachea
2.
Sci Adv ; 6(20): eaaz4880, 2020 05.
Article in English | MEDLINE | ID: mdl-32440546

ABSTRACT

Mercury (Hg) biomagnification in aquatic food webs is a global concern; yet, the ways species traits and interactions mediate these fluxes remain poorly understood. Few pathways dominated Hg flux in the Colorado River despite large spatial differences in food web complexity, and fluxes were mediated by one functional trait, predation resistance. New Zealand mudsnails are predator resistant and a trophic dead end for Hg in food webs we studied. Fishes preferred blackflies, which accounted for 56 to 80% of Hg flux to fishes, even where blackflies were rare. Food web properties, i.e., match/mismatch between insect production and fish consumption, governed amounts of Hg retained in the river versus exported to land. An experimental flood redistributed Hg fluxes in the simplified tailwater food web, but not in complex downstream food webs. Recognizing that species traits, species interactions, and disturbance mediate contaminant exposure can improve risk management of linked aquatic-terrestrial ecosystems.


Subject(s)
Mercury , Animals , Colorado , Ecosystem , Environmental Monitoring , Fishes/metabolism , Food Chain , Rivers
3.
J Med Chem ; 63(4): 1526-1527, 2020 02 27.
Article in English | MEDLINE | ID: mdl-32073265

ABSTRACT

Orexin receptors are G protein coupled receptors that may be useful targets for sleep disorders, eating disorders, or addictive behavior. Recent work shows that binding of antagonists to these receptors is complex, with strong dependence on hydrophobic hot spots and networks of water-mediated hydrogen bonds. Despite the minimal structural differences between receptor types, selectivity can be achieved in a number of different ways.


Subject(s)
Receptors, G-Protein-Coupled , Orexin Receptors , Orexins
4.
Bioorg Med Chem Lett ; 29(18): 2565-2570, 2019 09 15.
Article in English | MEDLINE | ID: mdl-31416666

ABSTRACT

We describe the design, synthesis, and biological evaluation of novel HIV-1 protease inhibitors containing a squaramide-derived scaffold as the P2 ligand in combination with a (R)-hydroxyethylamine sulfonamide isostere. Inhibitor 3h with an N-methyl-3-(R)-aminotetrahydrofuranyl squaramide P2-ligand displayed an HIV-1 protease inhibitory Ki value of 0.51 nM. An energy minimized model of 3h revealed the major molecular interactions between HIV-1 protease active site and the tetrahydrofuranyl squaramide scaffold that may be responsible for its potent activity.


Subject(s)
Drug Design , Ethers, Cyclic/pharmacology , HIV Protease Inhibitors/pharmacology , HIV Protease/metabolism , Quinine/analogs & derivatives , Dose-Response Relationship, Drug , Ethers, Cyclic/chemical synthesis , Ethers, Cyclic/chemistry , HIV Protease Inhibitors/chemical synthesis , HIV Protease Inhibitors/chemistry , Humans , Ligands , Molecular Structure , Quinine/chemical synthesis , Quinine/chemistry , Quinine/pharmacology , Structure-Activity Relationship
5.
Comput Methods Biomech Biomed Engin ; 20(8): 915-917, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28387524

ABSTRACT

The innovation presented is a method for adaptive time-stepping that allows clustering of time steps in portions of the cycle for which flow variables are rapidly changing, based on the concept of using a uniform step in a relevant dependent variable rather than a uniform step in the independent variable time. A user-defined function was developed to adapt the magnitude of the time step (adaptive time step) to a defined rate of change in inlet velocity. Quantitative comparison indicates that the new adaptive time stepping method significantly improves accuracy for simulations using an equivalent number of time steps per cycle.


Subject(s)
Computer Simulation , Lung/physiology , Rheology , Humans , Numerical Analysis, Computer-Assisted , Spirometry , Time Factors
7.
Article in English | MEDLINE | ID: mdl-27595502

ABSTRACT

BACKGROUND: The need for a better understanding of pulmonary diseases has led to increased interest in the development of realistic computational models of the human lung. METHODS: To minimize computational cost, a reduced geometry model is used for a model lung airway geometry up to generation 16. Truncated airway branches require physiologically realistic boundary conditions to accurately represent the effect of the removed airway sections. A user-defined function has been developed, which applies velocities mapped from similar locations in fully resolved airway sections. The methodology can be applied in any general purpose computational fluid dynamics code, with the only limitation that the lung model must be symmetrical in each truncated branch. RESULTS: Unsteady simulations have been performed to verify the operation of the model. The test case simulates a spirometry because the lung is obliged to rapidly perform both inspiration and expiration. Once the simulation was completed, the obtained pressure in the lower level of the lung was used as a boundary condition. The output velocity, which is a numerical spirometry, was compared with the experimental spirometry for validation purposes. CONCLUSIONS: This model can be applied for a wide range of patient-specific resolution levels. If the upper airway generations have been constructed from a computed tomography scan, it would be possible to quickly obtain a complete reconstruction of the lung specific to a specific person, which would allow individualized therapies.


Subject(s)
Computer Simulation , Lung/anatomy & histology , Lung/physiology , Humans , Hydrodynamics , Lung/physiopathology , Tomography, X-Ray Computed
8.
Bioorg Med Chem Lett ; 26(22): 5476-5480, 2016 11 15.
Article in English | MEDLINE | ID: mdl-27777011

ABSTRACT

The inflammatory caspases (caspase-1, -4 and -5) are potential therapeutic targets for autoimmune and inflammatory diseases due to their involvement in the immune response upon inflammasome formation. A series of small molecules based on the 4-(piperazin-1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold were synthesized with varying substituents on the piperazine ring. Several compounds were pan-selective inhibitors of the inflammatory caspases, caspase-1, -4 and -5, with the ethylbenzene derivative CK-1-41 displaying low nanomolar Ki values across this family of caspases. Three analogs were nearly 10 fold selective for caspase-5 over caspase-1 and -4. The compounds display non-competitive, time dependent inhibition profiles. To our knowledge, this series is the first example of small molecule inhibitors of all three inflammatory caspases.


Subject(s)
Caspase 1/metabolism , Caspase Inhibitors/chemistry , Caspase Inhibitors/pharmacology , Caspases, Initiator/metabolism , Caspases/metabolism , Piperazines/chemistry , Piperazines/pharmacology , Caspase 1/chemistry , Caspases/chemistry , Caspases, Initiator/chemistry , Humans , Inflammation/drug therapy , Inflammation/enzymology , Molecular Docking Simulation , Pyrimidines/chemistry , Pyrimidines/pharmacology , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology
9.
Intern Med J ; 46(8): 992-3, 2016 08.
Article in English | MEDLINE | ID: mdl-27554006
10.
Environ Sci Technol ; 50(9): 4650-8, 2016 05 03.
Article in English | MEDLINE | ID: mdl-27014905

ABSTRACT

Production of organic chemicals (OCs) is increasing exponentially, and some OCs biomagnify through food webs to potentially toxic levels. Biomagnification under field conditions is best described by trophic magnification factors (TMFs; per trophic level change in log-concentration of a chemical) which have been measured for more than two decades. Syntheses of TMF behavior relative to chemical traits and ecosystem properties are lacking. We analyzed >1500 TMFs to identify OCs predisposed to biomagnify and to assess ecosystem vulnerability. The highest TMFs were for OCs that are slowly metabolized by animals (metabolic rate kM < 0.01 day(-1)) and are moderately hydrophobic (log KOW 6-8). TMFs were more variable in marine than freshwaters, unrelated to latitude, and highest in food webs containing endotherms. We modeled the probability that any OC would biomagnify as a combined function of KOW and kM. Probability is greatest (∼100%) for slowly metabolized compounds, regardless of KOW, and lowest for chemicals with rapid transformation rates (kM > 0.2 day(-1)). This probabilistic model provides a new global tool for screening existing and new OCs for their biomagnification potential.


Subject(s)
Ecosystem , Food Chain , Animals , Fresh Water , Organic Chemicals , Polychlorinated Biphenyls , Water Pollutants, Chemical
11.
Soft Matter ; 12(13): 3265-70, 2016 Apr 07.
Article in English | MEDLINE | ID: mdl-26922903

ABSTRACT

Vapor-deposited glasses can be anisotropic and molecular orientation is important for organic electronics applications. In organic light emitting diodes (OLEDs), for example, the orientation of dye molecules in two-component emitting layers significantly influences emission efficiency. Here we investigate how substrate temperature during vapor deposition influences the orientation of dye molecules in a model two-component system. We determine the average orientation of a linear blue light emitter 1,4-di-[4-(N,N-diphenyl)amino]styryl-benzene (DSA-Ph) in mixtures with aluminum-tris(8-hydroxyquinoline) (Alq3) by spectroscopic ellipsometry and IR dichroism. We find that molecular orientation is controlled by the ratio of the substrate temperature during deposition and the glass transition temperature of the mixture. These findings extend recent results for single component vapor-deposited glasses and suggest that, during vapor deposition, surface mobility allows partial equilibration towards orientations preferred at the free surface of the equilibrium liquid.

12.
Intern Med J ; 46(1): 29-34, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26813899

ABSTRACT

Coronary artery disease (CAD) is the leading single cause of death in Australia affecting around 1.4 million people. Coronary computed tomography angiography has an established role in the assessment of patients with low to intermediate pretest probability for CAD who have chest pain and is typically used with the aim to rule out significant coronary artery stenosis. Use was initially limited because of concerns over radiation exposure, a Medicare rebate restricted to specialist referrals and an absence of data supporting its use as an alternative to functional testing in patients with chest pain. Recent advances in scanner technology and image sequencing, along with data from randomised control trials, have addressed these issues and indicate that coronary computed tomography angiography will play a greater role in the assessment of CAD in the coming years.


Subject(s)
Cardiology/trends , Coronary Angiography/trends , Coronary Artery Disease/diagnostic imaging , Tomography, X-Ray Computed/trends , Cardiology/methods , Chest Pain/diagnostic imaging , Chest Pain/therapy , Coronary Angiography/methods , Coronary Artery Disease/therapy , Follow-Up Studies , Humans , Multicenter Studies as Topic/methods , Tomography, X-Ray Computed/methods
13.
Clin Exp Immunol ; 183(1): 50-6, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26332693

ABSTRACT

B cells undergo a number of different developmental stages, from initial formation of their B cell receptor (BCR) genes to differentiation into antibody-secreting plasma cells. Because the BCR is vital in these differentiation steps, autoreactive and exogenous antigen binding to the BCR exert critical selection pressures to shape the B cell repertoire. Older people are more prone to infectious disease, less able to respond well to vaccination and more likely to have autoreactive antibodies. Here we review evidence of changes in B cell repertoires in older people, which may be a reflection of age-related changes in B cell selection processes.


Subject(s)
Aging/immunology , B-Lymphocytes/immunology , Clonal Selection, Antigen-Mediated , Immunity, Humoral , Receptors, Antigen, B-Cell/metabolism , Animals , Antibody Diversity , Autoantibodies/immunology , Cell Differentiation , Humans , Receptors, Antigen, B-Cell/genetics
14.
Intern Med J ; 46(1): 42-51, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26482426

ABSTRACT

BACKGROUND: Degenerative aortic stenosis is the most common valvular heart disease in the elderly, and many patients are not suitable for aortic valve replacement surgery. Transcatheter aortic valve implantation (TAVI) is a new therapeutic option for selected patients at high risk for surgery. AIM: To evaluate the safety and efficacy of TAVI in Australian patients. METHODS: This is a prospective study of patients undergoing TAVI for severe symptomatic aortic stenosis at The Prince Charles Hospital, Brisbane, Australia between August 2008 and July 2013. Patients were at high risk of surgical aortic valve replacement, or inoperable, as deemed by a multidisciplinary 'heart team'. Outcomes include procedural success and complications, 30-day and 1-year mortality and stroke, combined end-points as outlined by the Valve Academic Research Consortium 2 consensus document. RESULTS: Two hundred and nine patients underwent TAVI during the study period. The mean age was 83.7 ± 6.7 years, and 101 (48%) were men. The valve systems utilised were as follows: Edwards-SAPIEN valve in 104 (49.5%), Medtronic CoreValve in 86 (41.2%) and Boston Scientific Lotus valve in 19 (9.3%) patients. Thirty-day and 1-year mortality rates were 5.7% and 11.5% respectively. Thirty-day and 1-year stroke rates were 4.3% and 6.2% respectively. The composite end-points of device success, early safety and clinical efficacy occurred in 80.4%, 27.3% and 68.4%. CONCLUSIONS: TAVI with various valve systems, delivered through several approaches, is feasible in high surgical risk and inoperable patients with severe aortic stenosis, with acceptable outcomes at short-term and intermediate-term follow up.


Subject(s)
Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/surgery , Transcatheter Aortic Valve Replacement/mortality , Transcatheter Aortic Valve Replacement/trends , Aged , Aged, 80 and over , Aortic Valve Stenosis/diagnosis , Australia/epidemiology , Cohort Studies , Female , Follow-Up Studies , Heart Valve Prosthesis Implantation/mortality , Heart Valve Prosthesis Implantation/trends , Humans , Male , Mortality/trends , Patient Selection , Prospective Studies , Risk Factors , Treatment Outcome
15.
Eur J Med Chem ; 106: 120-31, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26536532

ABSTRACT

Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5'-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity.


Subject(s)
Hydroxamic Acids/pharmacology , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase/metabolism , Oxazolidinones/pharmacology , Dose-Response Relationship, Drug , Humans , Hydroxamic Acids/chemical synthesis , Hydroxamic Acids/chemistry , Models, Molecular , Molecular Structure , Monoamine Oxidase Inhibitors/chemical synthesis , Monoamine Oxidase Inhibitors/chemistry , Oxazolidinones/chemical synthesis , Oxazolidinones/chemistry , Structure-Activity Relationship
16.
FEBS Open Bio ; 5: 335-40, 2015.
Article in English | MEDLINE | ID: mdl-25941630

ABSTRACT

The antipsychotic drug olanzapine is widely prescribed to treat schizophrenia and other psychotic disorders. However, it often causes unwanted side effects, including diabetes, due to disruption of insulin-dependant glucose metabolism through a mechanism yet to be elucidated. To determine if olanzapine can affect the first step in glucose metabolism - glucose transport inside cells - we investigated the effect of this drug on the transport activity of a model glucose transporter. The glucose transporter from Staphylococcus epidermidis (GlcPSe) is specific for glucose, inhibited by various human glucose transporter (GLUT) inhibitors, has high sequence and structure homology to GLUTs, and is readily amenable to transport assay, mutagenesis, and computational modeling. We found that olanzapine inhibits glucose transport of GlcPSe with an IC50 0.9 ± 0.1 mM. Computational docking of olanzapine to the GlcPSe structure revealed potential binding sites that were further examined through mutagenesis and transport assay to identify residues important for olanzapine inhibition. These investigations suggest that olanzapine binds in a polar region of the cytosolic part of the transporter, and interacts with residues R129, strictly conserved in all GLUTs, and N136, conserved in only a few GLUTs, including the insulin-responsive GLUT4. We propose that olanzapine inhibits GlcPSe by impeding the alternating opening and closing of the substrate cavity necessary for glucose transport. It accomplishes this by disrupting a key salt bridge formed by conserved residues R129 and E362, that stabilizes the outward-facing conformation of the transporter.

17.
Minerva Cardioangiol ; 63(4): 343-57, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25952129

ABSTRACT

Transcatheter aortic valve implantation (TAVI) is the new standard of care for selected patients with severe symptomatic aortic stenosis who are at high risk for surgical aortic valve replacement (AVR), or are inoperable. Multicentre randomised controlled trials have demonstrated equivalent or superior clinical outcomes for TAVI compared to AVR in carefully selected patient cohorts. A number of important limitations were observed with early generation TAVI valves and their delivery systems, and rapid evolution of the technology continues. The Lotus Valve System aims to address a number of these limitations - it is repositionable and retrievable, and has an adaptive seal to prevent paravalvular aortic regurgitation. Early clinical outcomes for the Lotus Valve System have recently been published with promising results in terms of paravalvular regurgitation and repositionability.


Subject(s)
Aortic Valve Insufficiency/prevention & control , Aortic Valve Stenosis/surgery , Transcatheter Aortic Valve Replacement/methods , Aortic Valve Stenosis/physiopathology , Heart Valve Prosthesis , Heart Valve Prosthesis Implantation/methods , Humans , Patient Selection , Prosthesis Design , Randomized Controlled Trials as Topic , Transcatheter Aortic Valve Replacement/instrumentation
18.
Environ Sci Technol ; 48(17): 10415-22, 2014 Sep 02.
Article in English | MEDLINE | ID: mdl-25093980

ABSTRACT

The response of larval aquatic insects to stressors such as metals is used to assess the ecological condition of streams worldwide. However, nearly all larval insects metamorphose from aquatic larvae to winged adults, and recent surveys indicate that adults may be a more sensitive indicator of stream metal toxicity than larvae. One hypothesis to explain this pattern is that insects exposed to elevated metal in their larval stages have a reduced ability to successfully complete metamorphosis. To test this hypothesis we exposed late-instar larvae of the mayfly, Centroptilum triangulifer, to an aqueous Zn gradient (32-476 µg/L) in the laboratory. After 6 days of exposure, when metamorphosis began, larval survival was unaffected by zinc. However, Zn reduced wingpad development at concentrations above 139 µg/L. In contrast, emergence of subimagos and imagos tended to decline with any increase in Zn. At Zn concentrations below 105 µg/L (hardness-adjusted aquatic life criterion), survival between the wingpad and subimago stages declined 5-fold across the Zn gradient. These results support the hypothesis that metamorphosis may be a survival bottleneck, particularly in contaminated streams. Thus, death during metamorphosis may be a key mechanism explaining how stream metal contamination can impact terrestrial communities by reducing aquatic insect emergence.


Subject(s)
Environmental Exposure , Insecta/drug effects , Insecta/growth & development , Metamorphosis, Biological/drug effects , Zinc/toxicity , Animals , Electric Conductivity , Hardness , Hydrogen-Ion Concentration , Larva/drug effects , Life Cycle Stages/drug effects , Linear Models , Oxygen/analysis , Solubility , Temperature , Wings, Animal/anatomy & histology , Wings, Animal/drug effects
19.
Org Biomol Chem ; 12(35): 6842-54, 2014 Sep 21.
Article in English | MEDLINE | ID: mdl-25050776

ABSTRACT

A series of potent macrocyclic HIV-1 protease inhibitors have been designed and synthesized. The compounds incorporated 16- to 19-membered macrocyclic rings between a nelfinavir-like P2 ligand and a tyrosine side chain containing a hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent than their corresponding acyclic counterparts. Saturated derivatives showed slight reduction of potency compared to the respective unsaturated derivatives. Compound containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity.


Subject(s)
HIV Protease Inhibitors/chemistry , Nelfinavir/chemistry , Sulfonamides/chemistry , Antiviral Agents/chemical synthesis , Catalytic Domain , Cell Line , Darunavir , Drug Design , Drug Evaluation, Preclinical , HIV-1/drug effects , Humans , Hydrogen Bonding , Inhibitory Concentration 50 , Kinetics , Ligands , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Structure-Activity Relationship , Tyrosine/chemistry
20.
Int J Cardiol ; 170(3): 406-12, 2014 Jan 01.
Article in English | MEDLINE | ID: mdl-24309083

ABSTRACT

BACKGROUND: We report the findings of the SOURCE-ANZ registry of the clinical outcomes of the Edwards SAPIEN™ Transcatheter Heart Valve (THV) in the Australian and New Zealand (ANZ) clinical environment. METHODS: This single arm registry of select patients treated in eight centres, represent the initial experience within ANZ with the balloon expandable Edwards SAPIEN THV delivered by transfemoral (TF) and transapical (TA) access. RESULTS: The total enrolment for the study was 132 patients, 63 patients treated by TF, 56 by TA, and 2 patients were withdrawn from the study. The mean ages: 83.7 (TF) and 81.7 (TA), female: 34.3% (TF) and 61.3% (TA), logistic EuroSCORE: 26.8% (TF) and 28.8% (TA), and with procedural success (successful implant without conversion to surgery or death): 92.4% (TF) and 87.1% (TA) (p=0.32). Outcomes were not significantly different between TF and TA implants. These included one year mortality of 13.6% (TF) and 21.7% (TA) (p=0.24), MACCE: 16.7% (TF) and 28.3% (TA) (p=0.12), pacemaker: 4.6% (TF) and 8.3% (TA) (p=0.39), and VARC major vascular complication of 4.6% (TF) and 5.0% (TA) (p=0.91). CONCLUSION: TAVI in the ANZ clinical environment has demonstrated excellent outcomes for both the TA and TF approaches in highly selected patients. These results are consistent with those demonstrated in European, Canadian registries and the pivotal US clinical trials. ACTRN12611001026910.


Subject(s)
Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/surgery , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis/statistics & numerical data , Aged, 80 and over , Aortic Valve Stenosis/diagnostic imaging , Female , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Humans , Kaplan-Meier Estimate , Male , Postoperative Complications/diagnostic imaging , Postoperative Complications/mortality , Prevalence , Prospective Studies , Registries/statistics & numerical data , Risk Factors , Treatment Outcome , Ultrasonography
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