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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 -
Mayo Clinic Proceedings Oct 2013To consolidate the evidence from randomized trials for the use of endovascular therapy (ET) in patients with acute ischemic stroke. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To consolidate the evidence from randomized trials for the use of endovascular therapy (ET) in patients with acute ischemic stroke.
METHODS
We searched major databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus) from their inception to February 12, 2013, for randomized trials evaluating the efficacy of ET compared with standard of care for acute ischemic stroke. Pooled absolute and relative risk estimates were synthesized by using a random-effects model. Heterogeneity was assessed by using Q statistic and I(2) statistic. Subset analysis was performed for patients with severe stroke (National Institutes of Health Stroke Scale score ≥20). The study was conducted from January 15, 2013 to April 30, 2013.
RESULTS
Of the 1252 retrieved articles, 5 randomized trials enrolling 1197 patients with acute ischemic stroke were included. Seven hundred eleven patients received ET, and 486 received intravenous (IV) tissue plasminogen activator. There was no significant improvement in any of the outcomes in patients receiving ET compared with those receiving IV thrombolysis. On subgroup analysis, ET was found to have better outcomes in patients with severe stroke (National Institutes of Health Stroke Scale score ≥20), showing a dose-response gradient and improving excellent, good, and fair outcomes by an additional 4%, 7%, and 13%, respectively, compared with IV thrombolysis.
CONCLUSION
Overall, ET is not superior to IV thrombolysis for acute ischemic strokes (level B recommendation). However, ET showed promise and improved outcomes in patients with severe strokes, but the evidence is limited due to sample size. There is a need for further trials evaluating the role of ET in this high-risk group.
Topics: Databases, Bibliographic; Endovascular Procedures; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke; Thrombolytic Therapy
PubMed: 24079677
DOI: 10.1016/j.mayocp.2013.07.015 -
The Canadian Journal of Cardiology Mar 2015Atrial fibrillation (AF) increases the risk of stroke and thromboembolic events. Recently, biomarkers have been proposed as a practical tool to predict adverse outcomes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atrial fibrillation (AF) increases the risk of stroke and thromboembolic events. Recently, biomarkers have been proposed as a practical tool to predict adverse outcomes in patients with AF. The prognostic value of inflammatory and hemostatic markers in AF has been widely studied; however, the results of previous studies have been inconclusive.
METHODS
We conducted a systematic review and meta-analysis to evaluate the association of inflammatory and hemostatic markers with stroke and thromboembolic events in patients with AF.
RESULTS
A total of 27 studies including 22,176 participants met our inclusion criteria for the systematic review. Our meta-analysis determined that elevated circulating plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin (TAT) were significantly associated with increased risk of stroke in patients with AF (standardized mean difference [SMD], 0.89; 95% confidence interval [CI], 0.20-1.59 and 1.43; 95% CI, 0.40-2.47, respectively). Higher levels of D-dimer were associated with increased subsequent thromboembolic event risk with a pooled hazard ratio of 2.90 (95% CI, 1.22-6.90) for cohort studies and an SMD of 0.93 (95% CI, 0.36-1.50) for case-control studies. There was also very limited evidence indicating that other biomarkers-such as interleukin-6, von Willebrand factor, P-selectin, and mean platelet volume-could predict adverse outcomes in AF.
CONCLUSIONS
In conclusion, increased circulating PAI-1 and TAT levels were significantly associated with subsequent stroke in patients with AF, and high levels of D-dimer were associated with thromboembolic events in AF. Further epidemiologic studies are needed to accumulate more evidence on the prognostic role of inflammatory and hemostatic markers in AF.
Topics: Anticoagulants; Antifibrinolytic Agents; Antithrombin III; Atrial Fibrillation; Biomarkers; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Mean Platelet Volume; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prognosis; Selectins; Sensitivity and Specificity; Serine Proteinase Inhibitors; Stroke; Thromboembolism; von Willebrand Factor
PubMed: 25746020
DOI: 10.1016/j.cjca.2014.12.002 -
Medicine May 2017Pending results from double-blind, multicenter, parallel-group, randomized trials, the benefit and safety of the novel plasminogen activator, desmoteplase remain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pending results from double-blind, multicenter, parallel-group, randomized trials, the benefit and safety of the novel plasminogen activator, desmoteplase remain undetermined. The aim of this meta-analysis was to help evaluate desmoteplase's efficacy and safety.
METHODS
A thorough search was performed of the Cochrane Library, PubMed, and Embase from the inception of electronic data to March 2017, and double-blind, multicenter, parallel-group, randomized trials were chosen. We conducted a meta-analysis of studies investigating intravenous desmoteplase treatment of acute ischemic stroke patients 3 to 9 hours after symptom onset. Asymptomatic intracerebral hemorrhage, good clinical outcome at 90 days, and reperfusion 4 to 8 hours posttreatment were variables assessing efficacy; symptomatic intracerebral hemorrhage and death rates were measures of safety.
RESULTS
Six trials involving 1071 patients thrombolyzed >3 hours postonset were included (600 received intravenous desmoteplase, 471 placebo). Desmoteplase was associated with increased reperfusion (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.10-2.24; P = .01 vs control) and showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.97-1.62; P = .09 vs control), whereas there was no increase in symptomatic intracerebral hemorrhage and death rate with desmoteplase. However, there was no difference in the clinical response at 90 days (OR 1.14; 95% CI, 0.88-1.49; P = .31 vs control). Subgroup analysis showed that desmoteplase 90 μg/kg (OR 1.53; 95% CI, 1.07-2.21; P = .02 vs control) and 125 μg/kg (OR 4.07; 95% CI, 1.16-14.24; P = .03 vs control) were associated with an increase in reperfusion. Also, we found desmoteplase 90 μg/kg showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.95-1.63; P = .11 vs control).
CONCLUSION
Intravenous desmoteplase is associated with a favorable reperfusion efficacy and acceptable safety in ischemic stroke treatment >3 hours after symptom onset. Well-designed randomized controlled trials with larger patient cohorts and a moderate dose of drugs are needed to further evaluate the true efficacy of desmoteplase in stroke patients.
TRIAL REGISTRATION
URL: http://www.crd.york.ac.uk/PROSPERO; PROSPERO registration number: CRD42016037667).
Topics: Administration, Intravenous; Brain Ischemia; Fibrinolytic Agents; Humans; Plasminogen Activators; Randomized Controlled Trials as Topic; Stroke
PubMed: 28471961
DOI: 10.1097/MD.0000000000006667 -
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 -
Interventional Neuroradiology : Journal... Dec 2015To date only a few studies have compared the effectiveness and functional outcomes of stent retrievers versus intravenous thrombolysis in acute ischaemic stoke. Our aim... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To date only a few studies have compared the effectiveness and functional outcomes of stent retrievers versus intravenous thrombolysis in acute ischaemic stoke. Our aim was to identify and collate all the available data and to assess for statistical differences in patient outcomes between the two treatments.
MATERIALS AND METHODS
We performed a systematic review and meta-analysis of studies with a randomised controlled design which utilised stentrievers and intravenous thrombolysis in acute ischaemic stroke.
RESULTS
Five randomised controlled studies published in 2015 were identified. Second-generation thrombectomy devices constituted at least 80% of thrombectomy devices in the included studies, namely MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME and REVASCAT. No significant heterogeneity was seen in the included studies and the five trials were therefore included in the meta-analysis.A total of 46.10% of patients treated with stentrievers achieved an independent functional outcome (mRS < 2) at 90 days compared with 26.46% of those treated with intravenous thrombolysis with an odds ratio of 2.40 (p < 0.001). The weighted recanalisation mean in the thrombectomy arms was 76.02%.A lower mortality rate was observed with stentrievers compared to intravenous thrombolysis (15.33% vs 18.74%; OR 0.81, p = 0.15). Stentrievers were also associated with a lower risk of symptomatic intracranial haemorrhage (7.86% vs 8.64%; OR 1.02, p = 0.93). The differences in the secondary/safety outcomes were not statistically significant.
CONCLUSION
Stentrievers can achieve a high rate of recanalisation and functional independence in acute ischaemic stroke and have a relatively good safety profile. Our meta-analysis demonstrates a clear benefit of an intra-arterial mechanical approach vs standard treatment.
Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Stents; Stroke; Thrombectomy; Tissue Plasminogen Activator
PubMed: 26490828
DOI: 10.1177/1591019915609133 -
Journal of Clinical Medicine Jun 2020We aimed to systematically review the effectiveness of probiotic/synbiotic formulations to counteract cardiometabolic risk (CMR) in healthy people not receiving... (Review)
Review
The Effect of Probiotics and Synbiotics on Risk Factors Associated with Cardiometabolic Diseases in Healthy People-A Systematic Review and Meta-Analysis with Meta-Regression of Randomized Controlled Trials.
We aimed to systematically review the effectiveness of probiotic/synbiotic formulations to counteract cardiometabolic risk (CMR) in healthy people not receiving adjunctive medication. The systematic search (PubMed/MEDLINE/Embase) until 1 August 2019 was performed for randomized controlled trials in >20 adult patients. Random-effect meta-analysis subgroup and meta-regression analysis of co-primary (haemoglobin A1c (HbA1C), glucose, insulin, body weight, waist circumference (WC), body mass index (BMI), cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and blood pressure) and secondary outcomes (uric acid, plasminogen activator inhibitor-1-PAI-1, fibrinogen, and any variable related to inflammation/endothelial dysfunction). We included 61 trials (5422 persons). The mean time of probiotic administration was 67.01 ± 38.72 days. Most of probiotic strains were of and genera. The other strains were , , and . The daily probiotic dose varied between 10 and 10 colony-forming units (CFU)/gram. Probiotics/synbiotics counteracted CMR factors (endpoint data on BMI: standardized mean difference (SMD) = -0.156, = 0.006 and difference in means (DM) = -0.45, = 0.00 and on WC: SMD = -0.147, = 0.05 and DM = -1.21, = 0.02; change scores on WC: SMD = -0.166, = 0.04 and DM = -1.35, = 0.03) in healthy persons. Overweight/obese healthy people might additionally benefit from reducing total cholesterol concentration (change scores on WC in overweight/obese: SMD: -0.178, = 0.049). Poor quality of probiotic-related trials make systematic reviews and meta-analyses difficult to conduct and draw definite conclusions. "Gold standard" methodology in probiotic studies awaits further development.
PubMed: 32521799
DOI: 10.3390/jcm9061788 -
Frontiers in Neurology 2023Capsular warning syndrome (CWS) is characterized by recurrent stereotyped episodes of unilateral transient motor and/or sensory symptoms affecting the face and upper and...
INTRODUCTION
Capsular warning syndrome (CWS) is characterized by recurrent stereotyped episodes of unilateral transient motor and/or sensory symptoms affecting the face and upper and lower limbs, without cortical signs in 24 h and with a high risk of developing stroke. Among the possible underlying mechanisms, small perforating artery disease is the most common. The aim was to assess the most common risk factors, the therapeutic alternatives, and the different outcomes in patients with CWS, along with the presentation of two cases treated in our Emergency Department.
METHODS
Stroke Code, launched at our institution in January 2017, was triggered 400 times, and by December 2022, 312 patients were admitted as having an acute ischemic stroke. Among them, two of them fulfilled the criteria of CWS. A systematic search was carried out in PubMed, Scopus, and Web of Science databases to seek demography and therapeutic approaches in CWS.
RESULTS
Of 312 cases, two with acute ischemic stroke exhibited CWS. The first patient had six events of right hemiparesis with recovery in 10-30 min; after MRI and digital subtraction angiography (DSA), he received apixaban and clopidogrel; however, a day after admission, he developed ischemic infarction with partial recovery. The second patient presented five transient events of right hemiparesis. After MRI and DSA with an intra-arterial infusion of nimodipine, oral aspirin, and ticagrelor, he presented another event-developing stroke and was discharged with partial recovery. A systematic review found 190 cases of CWS in 39 articles from 1993 to 2022. Most were male subjects (66.4%), and hypertension (60%), smoking (36%), diabetes (18%), and dyslipidemia (55%) were the most common risk factors. Over 50% of the cases were secondary to small perforating artery disease. The most commonly used treatments were dual antiplatelet therapy (DAT), recombinant tissue plasminogen activator, and anticoagulant therapy (ACT), where the combination of DAT plus ACT was linked to the most positive functional outcomes (82.6%).
CONCLUSION
Our cases fit with the description of patients with partial recovery and risk factors (hypertension, diabetes, and smoking) in male patients. There is a lack of evidence regarding the best treatment option; dual antiplatelet therapy and anticoagulation therapy are strong contenders for a favorable result.
PubMed: 37260605
DOI: 10.3389/fneur.2023.1177660 -
Journal of Neurosurgery. Pediatrics Nov 2014The objective of this systematic review and analysis was to answer the following question: What are the optimal treatment strategies for posthemorrhagic hydrocephalus... (Review)
Review
OBJECT
The objective of this systematic review and analysis was to answer the following question: What are the optimal treatment strategies for posthemorrhagic hydrocephalus (PHH) in premature infants?
METHODS
Both the US National Library of Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to PHH. Two hundred thirteen abstracts were reviewed, after which 98 full-text publications that met inclusion criteria that had been determined a priori were selected and reviewed.
RESULTS
Following a review process and an evidentiary analysis, 68 full-text articles were accepted for the evidentiary table and 30 publications were rejected. The evidentiary table was assembled linking recommendations to strength of evidence (Classes I-III).
CONCLUSIONS
There are 7 recommendations for the management of PHH in infants. Three recommendations reached Level I strength, which represents the highest degree of clinical certainty. There were two Level II and two Level III recommendations for the management of PHH. Recommendation Concerning Surgical Temporizing Measures: I. Ventricular access devices (VADs), external ventricular drains (EVDs), ventriculosubgaleal (VSG) shunts, or lumbar punctures (LPs) are treatment options in the management of PHH. Clinical judgment is required.
STRENGTH OF RECOMMENDATION
Level II, moderate degree of clinical certainty. Recommendation Concerning Surgical Temporizing Measures: II. The evidence demonstrates that VSG shunts reduce the need for daily CSF aspiration compared with VADs.
STRENGTH OF RECOMMENDATION
Level II, moderate degree of clinical certainty. Recommendation Concerning Routine Use of Serial Lumbar Puncture: The routine use of serial lumbar puncture is not recommended to reduce the need for shunt placement or to avoid the progression of hydrocephalus in premature infants.
STRENGTH OF RECOMMENDATION
Level I, high clinical certainty. Recommendation Concerning Nonsurgical Temporizing Agents: I. Intraventricular thrombolytic agents including tissue plasminogen activator (tPA), urokinase, or streptokinase are not recommended as methods to reduce the need for shunt placement in premature infants with PHH.
STRENGTH OF RECOMMENDATION
Level I, high clinical certainty. Recommendation Concerning Nonsurgical Temporizing Agents. II. Acetazolamide and furosemide are not recommended as methods to reduce the need for shunt placement in premature infants with PHH.
STRENGTH OF RECOMMENDATION
Level I, high clinical certainty. Recommendation Concerning Timing of Shunt Placement: There is insufficient evidence to recommend a specific weight or CSF parameter to direct the timing of shunt placement in premature infants with PHH. Clinical judgment is required.
STRENGTH OF RECOMMENDATION
Level III, unclear clinical certainty. Recommendation Concerning Endoscopic Third Ventriculostomy: There is insufficient evidence to recommend the use of endoscopic third ventriculostomy (ETV) in premature infants with posthemorrhagic hydrocephalus.
STRENGTH OF RECOMMENDATION
Level III, unclear clinical certainty.
Topics: Cerebral Hemorrhage; Cerebrospinal Fluid Shunts; Contraindications; Drainage; Evidence-Based Medicine; Fibrinolytic Agents; Humans; Hydrocephalus; Infant; Infant, Newborn; Infant, Premature, Diseases; Neuroendoscopy; Spinal Puncture; Third Ventricle; United States; Ventriculostomy
PubMed: 25988778
DOI: 10.3171/2014.7.PEDS14322 -
Stroke Nov 2015Stroke affects ≈700,000 patients annually. Recent randomized controlled trials comparing endovascular thrombectomy (ET) with medical therapy, including intravenous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Stroke affects ≈700,000 patients annually. Recent randomized controlled trials comparing endovascular thrombectomy (ET) with medical therapy, including intravenous thrombolysis (IVT) with tissue-type plasminogen activator, have shown effectiveness of ET for some stroke patients. The study objective is to evaluate the effect of ET on good outcome in stroke patients.
METHODS
We searched PubMed, Embase, Web of Science, SCOPUS, ClinicalTrials.gov, and Cochrane databases to identify original research publications between 1996 and 2015 that (1) reported clinical outcomes in patients for stroke at 90 days with the modified Rankin Scale; (2) included at least 10 patients per group; (3) compared outcome with a control arm, and (4) included anterior circulation strokes in each arm. Two authors reviewed articles for inclusion independently.
RESULTS
Nine of 23 809 studies met inclusion criteria. In primary analysis, ET was associated with increased odds for good outcome (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.20-2.54). In secondary analysis, younger patients (OR, 1.85; 95% CI, 1.50-2.28), older patients (OR, 1.93; 95% CI, 1.10-3.37), patients receiving intravenous thrombolysis (OR, 1.83; 95% CI, 1.46-2.31), patients with worse strokes (OR, 2.23; 95% CI, 1.56-3.18), and patients with more moderate strokes (OR, 1.72; 95% CI, 1.36-2.18) had increased odds for good outcome. Symptomatic intracranial hemorrhage and mortality were similar between ET and control patients. No evidence of publication bias was seen.
CONCLUSIONS
ET improves good outcomes after anterior circulation stroke. ET should be strongly considered for all patients presenting within 6 hours of onset with a stroke affecting a proximal, anterior circulation vessel without a contraindication to ET.
Topics: Brain Ischemia; Combined Modality Therapy; Endovascular Procedures; Humans; Stroke; Thrombectomy; Thrombolytic Therapy; Treatment Outcome
PubMed: 26396032
DOI: 10.1161/STROKEAHA.115.009847