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Y Gary C Lee - One of the best experts on this subject based on the ideXlab platform.
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successful management of pleural infection with very low dose Intrapleural tissue plasminogen activator deoxyribonuclease regime
Respirology case reports, 2019Co-Authors: Jodi Andrea Hart, Y Gary C Lee, Arash BadieiAbstract:Pleural infection managed with Intrapleural therapy using a combination of 10 mg of tissue plasminogen activator (tPA) and 5 mg of deoxyribonuclease (DNase) has been shown in randomized and open-label studies to successfully treat >90% of patients without resorting to surgery. Potential bleeding risks, although low, and costs associated with tPA remain important concerns. No phase I studies exist for Intrapleural tPA therapy and the lowest effective dose has not been established. In patients with high bleeding risks, lower doses may present a safer alternative. We report a case of a complex parapneumonic effusion in a patient with coagulopathy that was successfully treated with a very low dose tPA (1 mg) and DNase (5 mg) regime.
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tissue plasminogen activator potently stimulates pleural effusion via a monocyte chemotactic protein 1 dependent mechanism
American Journal of Respiratory Cell and Molecular Biology, 2014Co-Authors: Sally M Lansley, Y Gary C Lee, Hui Min Cheah, Julius Varano F Della Vergiliana, Aron ChakeraAbstract:Pleural infection is common. Evacuation of infected pleural fluid is essential for successful treatment, but it is often difficult because of adhesions/loculations within the effusion and the viscosity of the fluid. Intrapleural delivery of tissue plasminogen activator (tPA) (to break the adhesions) and deoxyribonuclease (DNase) (to reduce fluid viscosity) has recently been shown to improve clinical outcomes in a large randomized study of pleural infection. Clinical studies of Intrapleural fibrinolytic therapy have consistently shown subsequent production of large effusions, the mechanism(s) of which are unknown. We aimed to determine the mechanism by which tPA induces exudative fluid formation. Intrapleural tPA, with or without DNase, significantly induced pleural fluid accumulation in CD1 mice (tPA alone: median [interquartile range], 53.5 [30–355] μl) compared with DNase alone or vehicle controls (both, 0.0 [0.0–0.0] μl) after 6 hours. Fluid induction was reproduced after Intrapleural delivery of strep...
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two sequential tpa dnase courses for noncommunicating loculated collections in pleural infection
Respirology case reports, 2014Co-Authors: Y Gary C Lee, Natalia Popowicz, Francesco Piccolo, Ranjan ShresthaAbstract:Intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy is being increasingly employed as an alternative to surgical intervention for the treatment of complicated parapneumonic effusions and empyema. Published cases are limited to one randomized control trial and few case reports. No data exist on employing sequential or repeated courses of Intrapleural tPA/DNase to aid evacuation of separate collections in patients' with a multiloculated pleural infection. This is the first report of successful use of sequential delivery of separate courses of Intrapleural tPA/DNase to two noncommunicating infected pleural fluid collections within the same hemithorax of a patient. Our case confirms that prior treatment with tPA/DNase therapy does not preclude subsequent effective and safe use of this Intrapleural treatment.
Nick A Maskell - One of the best experts on this subject based on the ideXlab platform.
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Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.
Annals of the American Thoracic Society, 2017Co-Authors: Natalia Popowicz, Duneesha De Fonseka, Oliver J Bintcliffe, Kevin G. Blyth, Nicola A. Smith, Francesco Piccolo, Geoffrey Martin, Donny Wong, Anthony Edey, Nick A MaskellAbstract:Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with Intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for Intrapleural tPA. The first of several planned studies is presented here.Objectives: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered Intrapleurally for pleural infection.Methods: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice ...
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u k controlled trial of Intrapleural streptokinase for pleural infection
The New England Journal of Medicine, 2005Co-Authors: Nick A Maskell, A J Nunn, Christopher W H Davies, Fergus V. Gleeson, Emma L. Hedley, R F Miller, Rhian Gabe, Glyn L Rees, T E A Peto, Mark A WoodheadAbstract:Background Intrapleural fibrinolytic agents are used in the drainage of infected pleural-fluid collections. This use is based on small trials that did not have the statistical power to evaluate accurately important clinical outcomes, including safety. We conducted a trial to clarify the therapeutic role of Intrapleural streptokinase. Methods In this double-blind trial, 454 patients with pleural infection (defined by the presence of purulent pleural fluid or pleural fluid with a pH below 7.2 with signs of infection or by proven bacterial invasion of the pleural space) were randomly assigned to receive either Intrapleural streptokinase (250,000 IU twice daily for three days) or placebo. Patients received antibiotics and underwent chest-tube drainage, surgery, and other treatment as part of routine care. The number of patients in the two groups who had died or needed surgical drainage at three months was compared (the primary end point); secondary end points were the rates of death and of surgery (analyzed s...
Michael H Livingston - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of Intrapleural tissue plasminogen activator and dornase alfa vs tissue plasminogen activator alone in children with pleural empyema a randomized clinical trial
JAMA Pediatrics, 2020Co-Authors: Michael H Livingston, Sanjay Mahant, Bairbre Connolly, Ian Maclusky, Sophie Laberge, Lucia Giglia, Connie L Yang, Ashley Roberts, Anna C ShawyerAbstract:Importance Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and Intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children. Objective To determine if Intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema. Design, Setting, and Participants This multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children’s hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017. Interventions Participants underwent chest tube insertion and 3 daily administrations of Intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation. Main Outcomes and Measures The primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost. Results Of the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, −0.1 days; 95% CI, −2.0 to 2.1;P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths. Conclusions and Relevance The addition of DNase to Intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and Intrapleural fibrinolytics alone as first-line treatment for pediatric empyema. Trial Registration ClinicalTrials.gov identifier:NCT01717742
Sophia Karandashova - One of the best experts on this subject based on the ideXlab platform.
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dose dependency of outcomes of Intrapleural fibrinolytic therapy in new rabbit empyema models
American Journal of Physiology-lung Cellular and Molecular Physiology, 2016Co-Authors: Andrey A Komissarov, Jake Boren, Mignote Chamiso, Galina Florova, Kathleen Koenig, Timothy Craig Allen, Ali Azghani, Ann Buchanan, Sophia KarandashovaAbstract:The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with Intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing Intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive Intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of pl...
Namrata Banga - One of the best experts on this subject based on the ideXlab platform.
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a study of empyema thoracis and role of Intrapleural streptokinase in its management
BMC Infectious Diseases, 2004Co-Authors: Amit Banga, G C Khilnani, Sanjeev Sharma, A Dey, Naveet Wig, Namrata BangaAbstract:Background Clinical spectrum, microbiology and outcome of empyema thoracis are changing. Intrapleural instillation of fibrinolytic agents is being increasingly used for management of empyema thoracis. The present study was carried out to describe the clinical profile and outcome of patients with empyema thoracis including those with chronic empyema and to study the efficacy and safety of Intrapleural streptokinase in its management.