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2.
J Clin Med ; 12(18)2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37762789

ABSTRACT

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April-30 July 2020 and 21 January-19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0-1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40-60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude.

3.
Gates Open Res ; 7: 3, 2023.
Article in English | MEDLINE | ID: mdl-37601311

ABSTRACT

BACKGROUND: Tranexamic acid (TXA) reduces the risk of death and is recommended as a treatment for women with severe postpartum bleeding. There is hope that giving TXA shortly before or immediately after birth could prevent postpartum bleeding. Extending the use of TXA to prevent harmful postpartum bleeding could improve outcomes for millions of women; however we must carefully consider the balance of benefits and potential harms. This article describes the protocol for a systematic review and individual patient data (IPD) meta-analysis to assess the effectiveness and safety of TXA for preventing postpartum bleeding in all women giving birth, and to explore how the effects vary by underlying risk and other patient characteristics.   Methods: We will search for prospectively registered, randomised controlled trials involving 500 patients or more assessing the effects of TXA in women giving birth. Two authors will extract data and assess risk of bias. IPD data will be sought from eligible trials. Primary outcomes will be life-threatening bleeding and thromboembolic events. We will use a one-stage model to analyse the data. Subgroup analyses will be conducted to explore whether the effectiveness and safety of TXA varies by underlying risk, type birth, maternal haemoglobin (Hb), and timing of TXA. This protocol is registered on PROSPERO (CRD42022345775).  Conclusions: This systematic review and IPD meta-analysis will address important clinical questions about the effectiveness and safety of the use of TXA for the prevention of postpartum bleeding that cannot be answered reliably using aggregate data and will inform the decision of who to treat.   PROSPERO registration: CRD42022345775  Keywords   Anti-fibrinolytics; Tranexamic acid; childbirth; postpartum haemorrhage; meta-analysis.

4.
Respirol Case Rep ; 11(9): e01202, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37577412

ABSTRACT

Alteplase as a fibrinolytic can be used to break up fibrin to encourage clot breakdown for clinical use. In the pleural space, it is used for symptomatic loculated malignant pleural effusions and pleural infections and can potentially avoid the need for surgical intervention. The optimal dose and dosing regimen of intrapleural fibrinolytics is still unknown. Although generally considered safe, bleeding is a serious potential complication and studies are ongoing to try and determine the lowest effective dose of alteplase to successfully treat pleural infections. This case highlighted the safe use of very low doses of alteplase ranging from 0.25 to 0.5 mg following pleural bleeding after the use of alteplase to treat a patient with symptomatic malignant loculated effusion. It demonstrates once pleural bleeding has stopped, there is a role for carefully titrated intrapleural alteplase use to avoid surgery.

5.
Chest ; 164(5): 1125-1138, 2023 11.
Article in English | MEDLINE | ID: mdl-37463660

ABSTRACT

BACKGROUND: The optimal treatment for community-acquired childhood pneumonia complicated by empyema remains unclear. RESEARCH QUESTION: In children with parapneumonic effusion or empyema, do hospital length of stay and other key clinical outcomes differ according to the treatment modality used? STUDY DESIGN AND METHODS: A living systematic review of randomized controlled trials (RCTs) was conducted by searching the Cochrane Central Register of Controlled Trials, Embase, Latin American and Caribbean Health Sciences Literature, Ovid MEDLINE, and Web of Science Core Collection databases. Eligible RCTs included patients aged < 18 years and compared two of the following treatment modalities: antibiotics alone, chest tube insertion with or without fibrinolytics, video-assisted thoracoscopic surgery (VATS), and decortication via thoracotomy. A network meta-analysis was performed to evaluate treatment effects on hospital length of stay (LOS), the primary outcome. RESULTS: Eleven trials including a total of 590 patients were selected for the network meta-analysis. Compared with a chest tube alone, a chest tube with fibrinolytics, thoracotomy, and VATS were all associated with shorter LOS, with a mean difference of 5.05 days (95% CI, 2.46-7.64), 6.33 days (95% CI, 3.17-9.50), and 5.86 days (95% CI, 3.38-8.35), respectively. No substantial differences in LOS were observed between the latter three interventions. None of the 11 RCTs compared antibiotics alone vs other types of treatment. Most trials reported peri-procedural complications and the need for reintervention, but the descriptions differed significantly between trials, preventing meta-analysis. In trials reporting health care-associated costs, fibrinolytics had cost advantages compared with VATS. Short- and long-term morbidity and mortality were very low, regardless of the treatment modality. INTERPRETATION: The results of this network meta-analysis showed that a chest tube alone was associated with a longer LOS compared with other treatment modalities. The lower cost associated with a chest tube plus fibrinolytics warrants consideration when choosing between treatment options, given similar LOS and clinical outcomes compared with the other modalities.


Subject(s)
Community-Acquired Infections , Empyema, Pleural , Pleural Effusion , Pneumonia , Child , Humans , Anti-Bacterial Agents/therapeutic use , Chest Tubes , Community-Acquired Infections/drug therapy , Drainage/methods , Empyema, Pleural/surgery , Empyema, Pleural/drug therapy , Network Meta-Analysis , Pleural Effusion/surgery , Pneumonia/drug therapy , Thoracic Surgery, Video-Assisted
6.
Open Access Emerg Med ; 15: 217-225, 2023.
Article in English | MEDLINE | ID: mdl-37292453

ABSTRACT

Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism are limited. Despite a lack of compelling evidence in some practices, clinical practice guidelines focus on the management of these patients. We present the case of a 24-year-old patient at 36 weeks of pregnancy in whom pulmonary thromboembolism (PTE) was diagnosed in a timely manner also with hemodynamic instability and echocardiographic images with clear involvement of the right cavities. She received thrombolytic therapy with alteplase 100 mg intravenously over 2 hours, which resulted in excellent outcomes for both the pregnant woman and fetus. Understanding the acute approach and management of these patients will improve our clinical practice; therefore, we reviewed a case report of a pregnant patient with high-risk PTE and compared it with current evidence. In conclusion, PE is a common disease with a high mortality rate during pregnancy. Therefore, having made a timely diagnosis using the relevant diagnostic aids and performing thrombolysis with rtPA increase the probability of survival in our patient, leading to successful results for both her and the fetus.

7.
J Am Coll Emerg Physicians Open ; 4(1): e12896, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36817082

ABSTRACT

Primary literature detailing updated management principles of acute ischemic stroke outpaces current guidelines, resulting in heterogenous practices. Recent advancements in neuroimaging have shifted treatment from a time-based approach to an individualized, image-guided appraisal directed by the presence or absence of salvageable brain tissue. In addition, tenecteplase appears to be a safe and effective for the treatment of acute ischemic stroke and is becoming an attractive agent due to its practical administration. Several factors must be accounted for when implementing tenecteplase into the health-system including cost, education, and changes in clinician workflows. Larger studies with broad patient populations are needed to more definitively evaluate whether intravenous thrombolytics should be used in combination with endovascular thrombectomy in patients with anterior large-vessel occlusions. Although debate regarding the safety and efficacy of various endovascular therapies, delays encountered in the identification, triage, and care of acute ischemic stroke patients increase the likelihood of necrotic core lesion development and loss of salvageable penumbra.

8.
Ann Pharmacother ; 57(10): 1147-1153, 2023 10.
Article in English | MEDLINE | ID: mdl-36688289

ABSTRACT

BACKGROUND: Recent evidence suggests tenecteplase at an intravenous dose of 0.25 mg/kg is as safe and efficacious as intravenous alteplase standard dose and demonstrates a more favorable pharmacokinetic profile for treatment of acute ischemic stroke. OBJECTIVE: The purpose was to compare the safety and efficacy of alteplase versus tenecteplase for the treatment of acute ischemic stroke at a large community hospital health system following conversion in the preferred formulary thrombolytic. METHODS: Prior to converting, medication safety and operationalization analyses were conducted. A multicenter, retrospective medical record review was performed for patients who received alteplase 6 months prior to formulary thrombolytic conversion and for tenecteplase 6 months post-conversion for the treatment of acute ischemic stroke. Primary outcomes included the rate of symptomatic intracranial and extracranial hemorrhage complications. Secondary outcomes included door-to-needle time, reduction in National Institute Health Stroke Scale at 24 hours and at discharge, order-to-administration time, and thrombolytic errors. The rates of hemorrhage were compared using binomial regression. RESULTS: Of the 287 patients reviewed, 115 received alteplase and 172 received tenecteplase. Symptomatic intracranial hemorrhagic complications occurred in 1 patient (1%) who received alteplase compared with 3 patients (2%) who received tenecteplase (P = 0.9). There was no statistical difference in rates of symptomatic intracranial or extracranial hemorrhagic complications. CONCLUSION AND RELEVANCE: Conversion from alteplase to tenecteplase can be safely and effectively achieved at a large community hospital health system with differing levels of stroke certification. There were also additional cost savings and practical advantages including workflow benefits.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Tissue Plasminogen Activator/adverse effects , Tenecteplase , Ischemic Stroke/drug therapy , Hospitals, Community , Retrospective Studies , Brain Ischemia/drug therapy , Fibrinolytic Agents/adverse effects , Stroke/drug therapy , Intracranial Hemorrhages/drug therapy , Treatment Outcome
9.
Pediatr Int ; 64(1): e15386, 2022 Jan.
Article in English | MEDLINE | ID: mdl-36225107

ABSTRACT

BACKGROUND: Community-acquired pneumonia (CAP) in children continues to be one of the prominent causes of pediatric morbidity and mortality worldwide. By determining the risk factors associated with the development of complicated CAP (CCAP), new approaches for early diagnosis and effective treatment can be identified. METHODS: This retrospective cohort study enrolled patients with CAP and CCAP who visited the pediatric ward of the study hospital between January 1, 2017 and December 31, 2017. For patients with CCAP, data regarding medical procedures performed, surgical intervention, and hospitalization duration were collected. RESULTS: A total of 111 patients, 93 (83.7%) with CAP and 18 (16.3%) with CCAP, aged between 3 months and 18 years were hospitalized because of severe pneumonia. The mean age of the patients was 3.6 ± 1.2 years and 60 (54%) of them were female. The mean age of patients with CCAP was higher than that of patients with CAP (4.2 ± 3.3 vs. 2.8 ± 2.1 years respectively); however, the difference was not significant (p = 0.012). Patients with CCAP exhibited a significantly higher C-reactive protein level than those with CAP (10.06 ± 7.55 vs. 4.43 ± 3.37 g/L respectively; p = 0.007). Hypoxia upon admission was noted more commonly in the CCAP group than in the CAP group (p < 0.001). CONCLUSION: Findings related to hypoxia, respiratory distress, and pleural effusion on imaging are important distinguishing factors associated with the development of complications in patients hospitalized with CAP. Therefore, CCAP etiology, diagnosis, and treatment approaches should be established and protective measures adopted.


Subject(s)
Community-Acquired Infections , Pleural Effusion , Pneumonia , Child , Humans , Female , Infant , Child, Preschool , Male , Retrospective Studies , Pneumonia/diagnosis , Pneumonia/epidemiology , Pneumonia/complications , Risk Factors , Hospitalization , Pleural Effusion/etiology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/epidemiology , Community-Acquired Infections/therapy
10.
Ann Thorac Med ; 17(3): 145-150, 2022.
Article in English | MEDLINE | ID: mdl-35968395

ABSTRACT

OBJECTIVE: The objective of this study is to compare the outcome of treatment with drainage and urokinase (UK) versus thoracoscopy (TS) in pleural empyema secondary to complicated pneumonia. METHODS: This was a retrospective study of patients with complicated parapneumonic effusions between 2008 and 2019 treated with UK or TS. Epidemiological and evolutionary data compared days of fever, antibiotic, pre- and postprocedure stay, time to radiological resolution, and complications. The results were expressed as medians and the comparisons were made by the Mann-Whitney U-test. RESULTS: Of 143 patients with NC, 46 were empyemas (26 men), 25 were treated with TS, and 10 were treated with UK. The remaining 11 received combined treatment, being excluded from the study. There were no significant differences between TS versus UK in age (median 4 vs. 3 years), days of fever before the procedure (4 vs. 2) and after (2 vs. 2), days of antibiotic treatment before the procedure (4 vs. 4), overall hospital stay (15 vs. 13 days), and months until radiological normalization (2 vs. 2). The complications related to the therapy were scarce in both groups and had no impact on evolution. Patients with TS had a longer preprocedural stay (4 vs. 1; P < 0.001) and required fewer days of subsequent antibiotic after procedure (8 vs. 11; P = 0.03), and a shorter overall antibiotic treatment time (11 vs. 16; P = 0.03). They also had a shorter post-TS stay (9 vs. 12 days), although this difference did not become significant (P = 0.09). CONCLUSIONS: In our experience, the results obtained with both procedures are quite similar, although patients undergoing TS had a better evolution (fewer days of antibiotic and a tendency to less hospitalization), despite having been performed a priori in more evolved patients.

11.
Exp Physiol ; 107(7): 749-758, 2022 07.
Article in English | MEDLINE | ID: mdl-35733235

ABSTRACT

NEW FINDINGS: What is the topic of this review? Overview of the coagulation abnormalities, including elevated D-dimers widely reported with COVID-19, often labelled as COVID coagulopathy. What advances does it highlight? The review highlights the changes in bronchoalveolar haemostasis due to apoptosis of alveolar cells, which contributes to acute lung injury and acute respiratory distress syndrome; the pathophysiological mechanisms, including endothelial dysfunction and damage responsible for thrombosis of pulmonary microcirculation and potential contribution to the hypoxaemia of COVID-19 acute lung injury; and changes in coagulation proteins responsible for the hypercoagulability and increased risk of thrombosis in other venous and arterial beds. The rationale for anticoagulation and fibrinolytic therapies is detailed, and potential confounders that might have led to less than expected improvement in the various randomised controlled trials are considered. ABSTRACT: Coronavirus disease 19 (COVID-19) causes acute lung injury with diffuse alveolar damage, alveolar-capillary barrier disruption, thrombin generation and alveolar fibrin deposition. Clinically, hypoxaemia is associated with preserved lung compliance early in the disease, suggesting the lack of excessive fluid accumulation typical of other lung injuries. Notably, autopsy studies demonstrate infection of the endothelium with extensive capillary thrombosis distinct from the embolic thrombi in pulmonary arteries. The inflammatory thrombosis in pulmonary vasculature secondary to endothelial infection and dysfunction appears to contribute to hypoxaemia. This is associated with elevated D-dimers and acquired hypercoagulability with an increased risk of deep vein thrombosis. Hypercoagulability is secondary to elevated plasma tissue factor levels, von Willebrand factor, fibrinogen, reduced ADAMTS-13 with platelet activation and inhibition of fibrinolysis. Multi-platform randomised controlled studies of systemic therapeutic anticoagulation with unfractionated and low molecular mass heparins demonstrated a survival benefit over standard care with full-dose anticoagulation in patients with non-severe disease who require supplemental oxygen, but not in severe disease requiring ventilatory support. Late intervention and the heterogeneous nature of enrolled patients can potentially explain the apparent lack of benefit in severe disease. Improvement in oxygenation has been demonstrated with intravenous fibrinolytics in small studies. Inhaled anticoagulants, thrombolytic agents and non-specific proteolytic drugs in clinical trials for decreasing alveolar fibrin deposition might benefit early disease. Essentially, COVID-19 is a multi-system disorder with pulmonary vascular inflammatory thrombosis that requires an interdisciplinary approach to combination therapies addressing both inflammation and intravascular thrombosis or alveolar fibrin deposits to improve outcomes.


Subject(s)
Acute Lung Injury , COVID-19 , Thrombophilia , Thrombosis , Acute Lung Injury/drug therapy , Anticoagulants/therapeutic use , Fibrin/metabolism , Humans , Hypoxia/drug therapy , SARS-CoV-2 , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombosis/drug therapy
12.
Future Cardiol ; 18(3): 191-206, 2022 03.
Article in English | MEDLINE | ID: mdl-35133192

ABSTRACT

As the third most common cardiovascular disease, pulmonary embolism (PE) has an uptrending incidence and mortality, resulting in significant healthcare expenditure. Risk stratification of acute PE guides management. Although anticoagulation remains the cornerstone management, systemic fibrinolysis and targeted therapeutic approaches, catheter-directed thrombolysis and catheter-based embolectomy are available for high-risk patients. Life-threatening bleeding complications associated with systemic fibrinolysis have restricted its widespread implementation. Catheter-based techniques for intermediate high-risk categories were devised to reduce bleeding complications and improve outcomes. Catheter-directed thrombolysis helps minimize bleeding by way of direct drug delivery. Catheter-based embolectomy mechanically retrieves thrombi without using fibrinolytics. This focused review of medical and interventional management of acute PE provides a highlight of ongoing trials expected to add value to current practice.


As the third most common disease affecting the heart and blood circulation, clot(s) in a blood vessel in the lungs lead to an increased likelihood of death. Using medication that prevents the blood from clotting is the cornerstone treatment. Medications that break the clot are also available but life-threatening bleeding can occur. Treatment approaches such as using a flexible tube to break the clot or retrieving it are used in severe disease. These approaches were developed to reduce bleeding and improve outcomes by delivering clot-breaking medication directly at the site of the clot. This is a review of managing clots in the blood vessel in the lungs that also provides a highlight of ongoing studies expected to improve current practice.


Subject(s)
Fibrinolytic Agents , Pulmonary Embolism , Acute Disease , Embolectomy/methods , Fibrinolytic Agents/therapeutic use , Humans , Pulmonary Embolism/etiology , Pulmonary Embolism/therapy , Thrombolytic Therapy/methods , Treatment Outcome
13.
Cureus ; 13(8): e16893, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34513466

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 is the virus responsible for the 2019 global pandemic. Pulmonary complications of COVID-19 are well established in the literature. However, the virus causes numerous extrapulmonary manifestations, notably acute aortic occlusion (AAO). COVID-19 creates a hypercoagulable state via the upregulation of numerous procoagulant cytokines in endothelial cells of blood vessels. We present a case of a 63-year-old patient without a previous history of prothrombotic disorders who developed AAO in the distal abdominal aorta and bilateral common iliac arteries after contracting COVID-19. The patient was a poor surgical candidate and was treated with fibrinolytics that were administered via an EkoSonic™ Endovascular System (EKOS) catheter using a bilateral transfemoral approach. This case highlights a unique treatment option for non-surgical candidates with AAO.

14.
Niger J Clin Pract ; 24(9): 1326-1331, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34531345

ABSTRACT

AIMS: We aimed to investigate of intrapleural use of ecballium elaterium (EE) in a rabbit model empyema. METHODS: An empyema was induced in 21 rabbits after inoculation of Staphylococcus aureus. Glucose levels, pH, lactate dehydrogenase levels, and amounts of pleural drainage were evaluated in addition to pleural and empyema scores. The rabbits were divided into three groups, each 7, the isotonic solution, the streptokinase, and the ecballium group. RESULTS: At autopsy, there was no difference in pH, glucose, and LDH levels in three groups. The mean pleural drainage was greater in the ecballium group. A significant difference was detected between groups in terms of drainage amounts and pleural and empyema scores (P < 0.05). A significant difference in pleural and empyema scores was detected in the ecballium and streptokinase groups (P < 0.05). EE group had significant differences in drainage amounts and plural and empyema scores regard to the control group (P < 0.05). No significance was found between streptokinase and EE groups. CONCLUSION: We conclude that intrapleural use of EE is at least as effective as streptokinase for the treatment of empyema.


Subject(s)
Empyema, Pleural , Animals , Drainage , Empyema, Pleural/drug therapy , Fibrinolytic Agents/therapeutic use , Rabbits , Streptokinase/therapeutic use , Thrombolytic Therapy
15.
J Cardiothorac Surg ; 16(1): 236, 2021 Aug 21.
Article in English | MEDLINE | ID: mdl-34419110

ABSTRACT

The use of intrapleural fibrinolytics for complicated parapneumonic effusion has been shown to be an effective and safe alternative to surgery. However, there is limited evidence about its use during pregnancy. We present a case and a review of the literature of pregnant women who had successful treatment of their complicated parapneumonic effusion with intrapleural fibrinolytics. To our knowledge this is the first review of cases of pregnant women with parapneumonic effusion managed with intrapleural fibrinolytic.


Subject(s)
Empyema, Pleural , Pleural Effusion , Empyema, Pleural/drug therapy , Female , Fibrinolytic Agents/therapeutic use , Humans , Pleural Effusion/drug therapy , Pregnancy , Thrombolytic Therapy
16.
Molecules ; 26(9)2021 Apr 29.
Article in English | MEDLINE | ID: mdl-33947107

ABSTRACT

Hemostasis disorders play an important role in the pathogenesis, clinical manifestations, and outcome of COVID-19. First of all, the hemostasis system suffers due to a complicated and severe course of COVID-19. A significant number of COVID-19 patients develop signs of hypercoagulability, thrombocytopenia, and hyperfibrinolysis. Patients with severe COVID-19 have a tendency toward thrombotic complications in the venous and arterial systems, which is the leading cause of death in this disease. Despite the success achieved in the treatment of SARS-CoV-2, the search for new effective anticoagulants, thrombolytics, and fibrinolytics, as well as their optimal dose strategies, continues to be relevant. The wide therapeutic potential of seaweed sulfated polysaccharides (PSs), including anticoagulant, thrombolytic, and fibrinolytic activities, opens up new possibilities for their study in experimental and clinical trials. These natural compounds can be important complementary drugs for the recovery from hemostasis disorders due to their natural origin, safety, and low cost compared to synthetic drugs. In this review, the authors analyze possible pathophysiological mechanisms involved in the hemostasis disorders observed in the pathological progression of COVID-19, and also focus the attention of researchers on seaweed PSs as potential drugs aimed to correction these disorders in COVID-19 patients. Modern literature data on the anticoagulant, antithrombotic, and fibrinolytic activities of seaweed PSs are presented, depending on their structural features (content and position of sulfate groups on the main chain of PSs, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on the hemostasis system and the issues of oral bioavailability of PSs, important for their clinical use as oral anticoagulant and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, and fibrinolytic properties, along with low toxicity and relative cheapness of production, open up prospects for the clinical use of PSs as alternative sources of new anticoagulant and antithrombotic compounds. However, further investigation and clinical trials are needed to confirm their efficacy.


Subject(s)
Anticoagulants/pharmacology , COVID-19/complications , Hemostasis/drug effects , Polysaccharides/pharmacology , Seaweed , Sulfates/pharmacology , Thrombosis/complications , Animals , Anticoagulants/chemistry , Anticoagulants/pharmacokinetics , Anticoagulants/therapeutic use , COVID-19/blood , Drug Discovery , Humans , Polysaccharides/chemistry , Polysaccharides/pharmacokinetics , Polysaccharides/therapeutic use , Seaweed/chemistry , Sulfates/chemistry , Sulfates/pharmacokinetics , Sulfates/therapeutic use , Thrombosis/blood , Thrombosis/drug therapy , COVID-19 Drug Treatment
17.
Contemp Clin Trials Commun ; 22: 100777, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33997464

ABSTRACT

BACKGROUND: Empyema is a common thoracic surgery presentation, defined as pus in the pleural space. Despite the commonality of empyema, consensus on initial management remains ambiguous. Two standard of care treatment options include inserting a chest tube (thoracostomy) and the administration of intrapleural fibrinolytics, or an initial surgical approach, surgical decortication. Due to the complexity of this pleural space infection, often repeat interventions are required after initial management in order to achieve source control and resolution of clinical symptoms. This study aims to identify the most effective initial management option for empyema. STUDY DESIGN: We present a study protocol for a randomized control trial (RCT) comparing adult individuals with empyema to one of two standard of care initial management options. Participants will be randomized into either interventional radiology guided chest tube insertion with intrapleural fibrinolytics (Dornase 5 mg and Alteplase 10 mg intrapleural twice daily for three days) or video-assisted thoracoscopic surgery (VATS) decortication. METHODS: All adults with empyema meeting inclusion criteria will be invited to participate. They will be randomized into one of two intervention groups; interventional radiology guided chest tube insertion with fibrinolytics or initial VATS decortication. Each intervention will take place within 48 hours of randomization. The primary outcome will be the rate of re-intervention within 30 days. Re-intervention is defined as repeat chest tube insertion, VATS decortication, or decortication via thoracotomy. Secondary outcomes include a change in the size of empyema, length of stay, morbidity, as well as 30-day and 90-day mortality, as well as quality of life measurements. ANTICIPATED IMPACT: This study is aimed at identifying the most effective initial management option for individuals with empyema.

18.
Am J Emerg Med ; 47: 339.e1-339.e3, 2021 09.
Article in English | MEDLINE | ID: mdl-33750664

ABSTRACT

INTRODUCTION: Management of massive pulmonary embolism in patients with hemodynamic instability encompasses the use of fibrinolytics. Use of fibrinolytic therapy is currently recommended in this patient population by ACCP, AHA, and EHA if treatment benefit outweighs the risk of bleeding. There is currently no data challenging or exploring the risk of using fibrinolytic therapy for the management of massive PE in patients with a history of intracranial hemorrhage. CASE PRESENTATION: A 38-year old female with suspected massive pulmonary embolism was admitted with a chief complaint of chest pain and right leg pain. Shortly after a confirmatory CT of bilateral PE, the patient had multiple cardiac arrests along with severe shock that led to a general agreement among the team to proceed with IV and then catheter-directed TPA as well as thrombectomy. Following fibrinolytic therapy, the patient was started on a heparin drip along with epinephrine for hemodynamic support. CT chest angiography showed the resolution of emboli following treatment with the fibrinolytic agent. CT of the head taken approximately 24 h post tPA initiation was used to rule out intracranial hemorrhage or other complications resulting from tPA administration. CONCLUSION: In patients with a history of intracranial hemorrhage, catheter guided fibrinolytic and thrombectomy may be effective treatment options of massive pulmonary embolism.


Subject(s)
Fibrinolytic Agents/administration & dosage , Pulmonary Embolism/drug therapy , Tissue Plasminogen Activator/administration & dosage , Adult , Catheterization, Peripheral , Female , Heart Arrest/etiology , Hematoma, Subdural/complications , Humans , Pulmonary Embolism/etiology
19.
Pediatr Surg Int ; 37(7): 897-902, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33751198

ABSTRACT

PURPOSE: To define the spectrum of management for thoracic empyema in children in Australia and New Zealand. METHODS: Online survey of members of the Australian and New Zealand Association of Paediatric Surgeons (ANZAPS), limited to consultant/attending paediatric surgeons. RESULTS: A total of 54/80 (67.5%) members, from 16 paediatric surgical centres, responded. The majority (33/54, 61%) preferred chest drain with fibrinolytics, whilst 21/54 (39%) preferred video-assisted thoracoscopic surgery (VATS) with drain insertion. Urokinase was the most commonly used fibrinolytic (64%). There were no significant differences in management preferences between practising surgeons in Australia and New Zealand (p = 0.54), nor between consultants who had been practising a shorter (< 5 years) or longer (> 20 years) amount of time (p = 0.21). The practices described by the surveyed ANZAPS members were in line with the Thoracic Society of Australia and New Zealand recommendations for the management of paediatric empyema. CONCLUSION: Across Australia and New Zealand there exists significant variation surrounding the intra- and post-intervention management of thoracic empyema in children. The surveyed paediatric surgeons demonstrated a preference for fibrinolytics over the use of VATS. All management regimens were within published local guidelines.


Subject(s)
Disease Management , Empyema, Pleural/surgery , Thoracic Surgery, Video-Assisted/methods , Adolescent , Australia/epidemiology , Chest Tubes , Child , Child, Preschool , Empyema, Pleural/epidemiology , Female , Humans , Incidence , Male , New Zealand/epidemiology , Surveys and Questionnaires , Young Adult
20.
Expert Rev Cardiovasc Ther ; 19(4): 357-362, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33567924

ABSTRACT

The impact of diabetes mellitus (DM) on clinical outcomes of acute ST-segment elevation myocardial infarction (STEMI) following fibrinolytic therapy remains uncertain. We queried the National Inpatient Sample (NIS) for STEMI patients who received fibrinolytic therapy. Categorical and continuous variables were compared using the unadjusted odds ratio (uOR) and t-test analysis, respectively. A binary logistic regression model was used to control the outcomes for patient demographics, procedural characteristics, and baseline comorbidities. A total of 111,155 (no-DM 84,146, DM 27,009) were included. The unadjusted odds of in-hospital mortality (8.4% vs. 6.8%, uOR 1.25, 95% CI 1.19-1.31, P = <0.0001) and cardiogenic shock (7.7% vs. 6.2%, uOR 1.26, 95% CI 1.20-1.33, P = <0.0001) were significantly higher in patients with DM compared to those with no DM, respectively. The odds for major bleeding and cardiopulmonary arrest were significantly lower for in diabetes. The adjusted pooled estimates mirrored the unadjusted findings. Diabetic patients receiving fibrinolytic therapy for STEMI might have higher odds of all-cause mortality and cardiogenic shock compared to non-diabetic patients.


Subject(s)
Diabetes Mellitus/epidemiology , ST Elevation Myocardial Infarction/therapy , Thrombolytic Therapy/methods , Aged , Comorbidity , Female , Heart Arrest/epidemiology , Hemorrhage/epidemiology , Hospital Mortality , Humans , Inpatients , Male , Middle Aged , Shock, Cardiogenic/epidemiology
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