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Iranian Journal of Pharmaceutical... 2021Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator... (Review)
Review
Efficacy and Safety of Different Dosage of Recombinant Tissue-type Plasminogen Activator (rt-PA) in the Treatment of Acute Pulmonary Embolism: A Systematic Review and Meta-analysis.
Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator (rt-PA) could be considered to improve bleeding complications. The aim of this study was to evaluate the efficacy and safety of a reduced dose of rt-PA for the treatment of acute PE, compared with anticoagulation and standard dose. PubMed Central, Scopus, Web of Science and Embase were searched for all relevant randomized studies and prospective observational studies that compared reduced dose of rt-PA with anticoagulation alone or standard dose of rt-PA in patients with acute PE. The risk ratios (RR, with 95% CI) were calculated according to the value of I2. Outcomes were described as bleeding events, all-cause death, and recurrence of PE. Thirteen articles, including four observational studies (4223 patients) and nine RCTs (780 patients), were included. In comparing reduced dose of rt-PA with anticoagulant, a greater incidence of total bleeding events in low dose was showed (RR, 5.08 (95% CI, (1.39-18.6), I2 = 0.0%). In the standard dose rt-PA reduced dose, there was a greater incidence of total bleeding events in the standard dose of rt-PA, RR 1.48 (95% CI, (1.00-2.19), I2 = 0.0%) was shown. There were no statistical differences in recurrent PE or all-cause mortality. It concluded that in the absence of the benefit of a standard dose of rt-PA in comparison with dose reduction, a reduced dose of rt-PA showed a lower rate of total bleeding events and similar efficacy regarding mortality and PE recurrence rate.
PubMed: 34567173
DOI: 10.22037/ijpr.2021.114142.14688 -
Journal of Neurology Feb 2023Hemorrhagic transformation (HT) is a common complication of alteplase treatment. However, the prevalence rate, risk factors, and clinical outcomes of remote... (Meta-Analysis)
Meta-Analysis Review
Prevalence, risk factors, and clinical outcomes of remote intracerebral hemorrhage after intravenous thrombolysis in acute ischemic stroke: a systematic review and meta-analysis.
BACKGROUND
Hemorrhagic transformation (HT) is a common complication of alteplase treatment. However, the prevalence rate, risk factors, and clinical outcomes of remote intracerebral hemorrhage (rICH) after intravenous thrombolysis in acute ischemic stroke are not well understood.
METHODS
Following a previously registered protocol, the PubMed, Web of Science, and Embase databases were systematically searched to identify relevant literature up to June 2022. Cohort studies reporting thrombolysis-related rICH in patients with acute ischemic stroke were included. Random effects models were used to calculate pooled prevalence rate, mean difference (MD) or odds ratio (OR) with corresponding 95% confidence interval (CI).
RESULTS
Fourteen studies with 52,610 patients were included in this meta-analysis. The pooled rICH prevalence was 3.2% (95% CI 3.1-3.4%). Compared to patients without intracerebral hemorrhage (ICH), those with rICH were older, more likely to be female, and had a higher proportion of prior stroke, chronic heart failure and cardioembolism, and higher diastolic blood pressure. Small vessel disease markers (e.g., white matter hyperintensities and cerebral microbleeds) were strongly associated with rICH. The presence of rICH decreased the likelihood of favorable outcomes (OR 0.36, 95% CI 0.31-0.41) and increased the risk of mortality (OR 4.37, 95% CI 2.86-6.67).
CONCLUSIONS
Although rICH is uncommon after intravenous thrombolysis, its presence can lead to worse functional outcomes and higher mortality in acute ischemic stroke. Patients at high risk of rICH must be identified based on potential risk factors.
Topics: Female; Humans; Male; Brain Ischemia; Cerebral Hemorrhage; Fibrinolytic Agents; Ischemic Stroke; Prevalence; Risk Factors; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 36198828
DOI: 10.1007/s00415-022-11414-2 -
Neurology May 2023The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs.
METHODS
We first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK.
RESULTS
Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44-5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03-0.20) and an sICH rate of 0.07 (95% CI 0.02-0.17) in TNK-treated patients, no significant difference was observed.
DISCUSSION
Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/ct2/show/NCT02388061; clinicaltrials.gov/ct2/show/NCT03340493.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Treatment Outcome; Stroke; Intracranial Hemorrhages; Brain Ischemia
PubMed: 36878701
DOI: 10.1212/WNL.0000000000207138 -
Endocrine Practice : Official Journal... Jun 2023The impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the... (Review)
Review
OBJECTIVE
The impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT.
METHODS
A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included.
RESULTS
From 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration.
CONCLUSIONS
The results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42022323757.
Topics: Male; Female; Humans; Transgender Persons; Tissue Plasminogen Activator; Ankle Brachial Index; Cross-Sectional Studies; Pulse Wave Analysis; Atherosclerosis; Hormones
PubMed: 36603652
DOI: 10.1016/j.eprac.2022.12.017 -
Journal of the Neurological Sciences Sep 2020Accumulating clinical evidence has indicated that sonothrombolysis can aid in the treatment of ischemic stroke; however, these findings remain controversial. The purpose... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Accumulating clinical evidence has indicated that sonothrombolysis can aid in the treatment of ischemic stroke; however, these findings remain controversial. The purpose of the present meta-analysis was to assess randomized clinical studies concerning the effects of sonothrombolysis on ischemic stroke to evaluate its safety and efficacy.
METHODS
We systematically searched the Cochrane Library, PubMed, and EMBASE databases for literature published between the inception of electronic data and May 2019 regarding sonothrombolysis for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on patient characteristics, ultrasound variables (any duration or frequency, without microbubble), and outcome variables (safety and efficacy).
RESULTS
Five trials were included in the present study. Clinical functional recovery was evaluated at different time points (several days or 3 months), and heterogeneity was low. Sonothrombolysis did not lead to an increase in symptomatic intracranial hemorrhagic complications or death. Our results demonstrated that patients treated with sonothrombolysis had significantly higher rates of recanalization and asymptomatic intracerebral hemorrhage than patients treated with intravenous thrombolysis alone. In the subgroup of middle cerebral artery (MCA) occlusion patients, sonothrombolysis was found to greatly increase the efficacy outcomes compared to intravenous thrombolysis.
CONCLUSIONS
Evidence suggests that sonothrombolysis is a technically feasible and potentially effective treatment that has beneficial effects on recanalization and increases the rate of asymptomatic intracerebral hemorrhage in stroke patients. Additionally, short- and long-term clinical outcome analyses were improved in the MCA occlusion sonothrombolysis subgroup. Larger clinical trials of MCA occlusion patients are necessary to verify these findings.
Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Ischemic Stroke; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 32623143
DOI: 10.1016/j.jns.2020.116998 -
European Journal of Medical Research Feb 2023At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the treatment of COVID-19 patients with elevated soluble urokinase plasminogen activator receptor (suPAR). However, the role of Anakinra in COVID-19 remains unanswered, especially in patients receiving different forms of respiratory support. Therefore, the objective of this systematic review is to assess the safety and effects of Anakinra compared to placebo or standard care alone on clinical outcomes in adult hospitalized patients with SARS-CoV-2 infection.
METHODS
We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, medRxiv, and the Cochrane Central Register of Controlled Trials (CCSR)) and the WHO COVID-19 Global literature on coronavirus disease database to identify completed and ongoing studies from inception of each database to December 13, 2021. Since then, we monitored new published studies weekly up to June 30, 2022 using the CCSR. We included RCTs comparing treatment with Anakinra to placebo or standard care alone in adult hospitalized patients with SARS-CoV-2 infection.
RESULTS
We included five RCTs with 1,627 patients (n = 888, n = 739, mean age 59.63 years, 64% male). Random-effects meta-analysis was used to pool data. We found that Anakinra makes little or no difference to all-cause mortality at up to day 28 compared to placebo or standard care alone (RR 0.96, 95% CI 0.64-1.45; RD 9 fewer per 1000, 95% CI 84 fewer to 104 more; 4 studies, 1593 participants; I = 49%; low certainty of evidence).
CONCLUSIONS
Anakinra has no effect on adult hospitalized patients with SARS-CoV-2 infection regarding mortality, clinical improvement and worsening as well as on safety outcomes compared to placebo or standard care alone.
TRIAL REGISTRATION
PROSPERO Registration Number: CRD42021257552.
Topics: Adult; Humans; Male; Middle Aged; Female; COVID-19; Interleukin 1 Receptor Antagonist Protein; SARS-CoV-2
PubMed: 36841793
DOI: 10.1186/s40001-023-01072-z -
Journal of Stroke and Cerebrovascular... Jul 2022The benefit and risk of administration of tissue plasminogen activator (tPA) before endovascular mechanical thrombectomy (E-MT) in acute stroke has been actively... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The benefit and risk of administration of tissue plasminogen activator (tPA) before endovascular mechanical thrombectomy (E-MT) in acute stroke has been actively debated. We therefore aimed to investigate the efficacy and safety of three therapeutic strategies for acute stroke: direct E-MT, E-MT with pre-administration of tPA, and tPA alone with a network meta-analysis.
MATERIALS AND METHODS
PUBMED and EMBASE were searched from September to November 2021 for randomized control trials that compared direct E-MT, E-MT with tPA, and tPA alone therapies in acute stroke. The primary outcome was functional independence, defined as modified Rankin Scale score of 0-2, at 90 days. All-cause mortality, symptomatic intracranial hemorrhage, and successful revascularization were also evaluated.
RESULTS
We identified 11 randomized controlled trials with a total of 3,640 patients with acute stroke. Compared to E-MT with tPA, direct E-MT provided comparable outcomes regarding functional independence (relative risk (RR): 1.02; 95% confidence interval (CI): 0.88-1.19, I = 36.6%) and all-cause mortality (RR: 1.05; 95% CI: 0.85-1.31, I = 0%). The incidence of symptomatic intracranial hemorrhage was not significantly different between direct E-MT and E-MT with tPA (RR: 0.83; 95% CI: 0.57-1.20, I = 0%). Direct E-MT had favorable functional independence (RR: 1.41; 95% CI: 1.15-1.74, I = 36.6%) and higher successful revascularization rate (RR: 1.60; 95% CI: 1.33-1.93, I = 61.2%) than tPA alone.
CONCLUSIONS
Direct E-MT alone led to acceptable outcomes even in comparison to E-MT with tPA, whereas additional tPA did not cause higher risk of symptomatic intracranial hemorrhage.
Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Mechanical Thrombolysis; Network Meta-Analysis; Stroke; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 35468495
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106491 -
Annals of Agricultural and... Jun 2023The global impact of acute kidney injury (AKI) has not been thoroughly investigated. With the development of new techniques, soluble urokinase plasminogen activator... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVE
The global impact of acute kidney injury (AKI) has not been thoroughly investigated. With the development of new techniques, soluble urokinase plasminogen activator receptor (suPAR) has become increasingly important in the diagnosis of AKI. Therefore, a systematic review and meta-analysis was carried out to evaluate the predictive value of suPAR for AKI.
MATERIAL AND METHODS
The review and meta-analysis investigated the relationship between suPAR levels and acute kidney injury. Pubmed, Scopus, Cochrane Controlled Register of Trials, and Embase were searched for relevant studies from inception to 10 January 2023. Stata (Ver. 16 StataCorp, College Station, TX, USA) was used for all statistical analyses. A random effects model using the Mantel-Haenszel approach was employed, and odds ratios (OR) and standard mean differences (SMD) with 95% confidence intervals (CI) were calculated for binary and continuous outcomes, respectively.
RESULTS
Nine studies reported suPAR levels among patients with and without AKI. Pooled analysis showed that suPAR levels in patients with and without AKI varied and amounted to 5.23 ± 4.07 vs. 3.23 ±0.67 ng/mL (SMD = 3.19; 95%CI: 2.73 to 3.65; p<0.001). The results from the sensitivity analysis did not alter the direction.
CONCLUSIONS
This results show that increasing suPAR levels are associated with the occurrence of AKI. SuPAR might act as a novel biomarker for CI-AKI in clinical practice.
Topics: Humans; Receptors, Urokinase Plasminogen Activator; Acute Kidney Injury; Odds Ratio; Universities
PubMed: 37387388
DOI: 10.26444/aaem/167464 -
Pulmonary Pharmacology & Therapeutics Dec 2021Multiple studies describing the benefits of intrapleural fibrinolytic over placebo and DNase therapy have been published, but few have been published on intrapleural... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Multiple studies describing the benefits of intrapleural fibrinolytic over placebo and DNase therapy have been published, but few have been published on intrapleural fibrinolytic and DNase therapy.
OBJECTIVE
Our meta-analysis aims to compare the outcomes of surgical intervention, mortality, and hospital length of stay between intrapleural fibrinolytic and DNase therapy with either intrapleural fibrinolytic or DNase therapy alone in patients with pleural space infections.
METHODS
We searched Pubmed, EMBASE, Web of Science, and Cochrane library databases for observational studies and randomized controlled trials (RCTs) containing comparative data for hospitalized adults and children with pleural infections receiving intrapleural therapy of fibrinolytic and DNase versus those receiving intrapleural fibrinolytic or DNase alone. Meta-analysis was performed using the Review Manager software, and heterogeneity was tested using I statistics.
RESULTS
A total of 2 cohorts and 2 RCTs involving 362 adult and children was included. There was significant reduction in surgical intervention requirement among patients who received intrapleural fibrinolytic and DNase (OR 0.30; 95% CI 0.11-0.83; I = 31%; P = 0.02) than those receiving either intrapleural fibrinolytic or DNase alone. No difference was observed for mortality (OR 0.72; 95% CI 0.31-1.71; I = 0%; P = 0.46) and complication rates (OR 3.09; 95% CI 0.75-12,74; I = 54%; P = 0.12). The hospital length of stay (mean 13.70 vs. 16.67 days; P = 0.19) and duration of chest tube drainage (mean 6.47 vs. 6.30 days; P = 0.58) was similar between the two groups.
CONCLUSION
Combination of intrapleural fibrinolytic and DNase, compared to single-agent intrapleural therapy alone, is associated with a lesser need for surgical interventions. However, no difference was found in mortality, hospital length of stay, and chest tube drainage duration.
Topics: Adult; Child; Deoxyribonucleases; Empyema, Pleural; Fibrinolytic Agents; Humans; Pleural Effusion; Thrombolytic Therapy
PubMed: 34571093
DOI: 10.1016/j.pupt.2021.102081 -
Trends in Psychiatry and Psychotherapy 2023Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its development. Previous studies have reported elevated plasminogen activator inhibitor-1 (PAI-1) levels in patients with depression, suggesting that PAI-1 levels might be linked to the etiology of MDD.
METHODS
We systematically searched the following online databases: MEDLINE, Scopus, and Web of Science up to September 10, 2020, to identify studies in which PAI-1 levels were reported in subjects with MDD. Subsequently we used RevMan 5.3 to perform a meta-analysis of data extracted from the included studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO criteria for the search and analysis.
RESULTS
Six studies that reported mean ± standard deviation (SD) were included in the analysis, with a total of 507 MDD patients and 3,453 controls. The overall standardized mean difference (SMD) was 0.27 (95% confidence interval [95% CI] 0.01-0.53). PAI-1 serum levels were 0.27 SDs higher in MDD patients than in controls. The test for overall effect was significant (z = 2.04, p = 0.04). Substantial heterogeneity was detected among the studies, demonstrated by the inconsistency test (I² = 72%) and the chi-square test (χ² = 18.32; p = 0.003).
CONCLUSIONS
This systematic review and meta-analysis showed that MDD might be related to elevated PAI-1 levels. We propose larger prospective clinical studies to further investigate this clinical correlation and validate the clinical significance of these observations.
Topics: Humans; Depressive Disorder, Major; Plasminogen Activator Inhibitor 1; Prospective Studies
PubMed: 34798692
DOI: 10.47626/2237-6089-2021-0338