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Journal of Stroke and Cerebrovascular... Apr 2021To compare outcomes between two models of acute ischemic stroke care. Namely 1) "drip-and-stay", i.e. IV tissue plasminogen activator (tPA) administered at a spoke... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To compare outcomes between two models of acute ischemic stroke care. Namely 1) "drip-and-stay", i.e. IV tissue plasminogen activator (tPA) administered at a spoke hospital in a telestroke network, with the patient remaining at the spoke, versus 2) "drip-and-ship", i.e. tPA administered at a spoke hospital with subsequent patient transfer to a hub hospital, and 3) "hub", i.e. tPA and subsequent treatment at a hub hospital.
MATERIALS AND METHODS
We performed a systematic review and meta-analysis according to PRISMA guidelines. Literature searches of MEDLINE, Embase, and Cochrane from inception-October 2019 included randomized control trials and observational cohort studies comparing the drip-and-stay model to hub and drip-and-ship models. Outcomes of interest were functional independence (modified Rankin Scale ≤ 1), symptomatic intracranial hemorrhage (sICH), mortality, and length of stay. Pooled effect estimates were calculated using a fixed-effects meta-analysis and random-effects Bayesian meta-analysis. Non-inferiority was calculated using a fixed-margin method.
RESULTS
Of 2806 unique records identified, 10 studies, totaling 4,164 patients, fulfilled the eligibility criteria. Meta-analysis found no significant difference in functional outcomes (mRS0-1) (6 studies, RR=1.09, 95%CI 0.98-1.22, p=0.123), sICH (8 studies, RR=0.98, 95%CI 0.64-1.51, p=0.942), or 90-day mortality (5 studies, RR=0.98, 95%CI 0.73-1.32, p=0.911, respectively) between patients treated in a drip-and-stay model compared to patients treated in drip-and-ship or hub models. There was no significant heterogeneity in these outcomes. Drip-and-stay outcomes (mRS 0-1, sICH) were non-inferior when compared to the combined group.
CONCLUSIONS
Our findings indicate that drip-and-stay is non-inferior to current models of drip-and-ship or hub stroke care, and may be as safe and as effective as either.
Topics: Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Humans; Infusions, Intravenous; Intracranial Hemorrhages; Ischemic Stroke; Length of Stay; Male; Middle Aged; Observational Studies as Topic; Patient Transfer; Randomized Controlled Trials as Topic; Recovery of Function; Risk Assessment; Risk Factors; Telemedicine; Thrombolytic Therapy; Time Factors; Time-to-Treatment; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 33540336
DOI: 10.1016/j.jstrokecerebrovasdis.2021.105638 -
Journal of Gastrointestinal and Liver... Jun 2022Several studies have investigated the role of multiple proteins in nonalcoholic fatty liver disease (NAFLD); one that has recently gained attention is plasminogen... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Several studies have investigated the role of multiple proteins in nonalcoholic fatty liver disease (NAFLD); one that has recently gained attention is plasminogen activator inhibitor-1 (PAI-1). However, studies evaluating PAI-1 levels in NAFLD demonstrated conflicting results. Our objective was to understand the role of PAI-1 in NAFLD more clearly by carrying out a systematic review and meta-analysis.
METHODS
We gathered evidence by performing a systematic search on PubMed, EMBASE, and Cochrane Library, through using a predefined search string. The included studies diagnosed NAFLD through either liver biopsy, ultrasonography, computed tomography (CT), magnetic resonance spectroscopy, or using one of the latter methods with blood parameters. Studies had to fulfill predefined inclusion and exclusion criteria. To assess the quality of the studies included, we used the NHLBI quality assessment tools. The main summary outcome was the mean difference (MD) in serum PAI-1 levels reported as ng/mL Results: 33 articles involving 10,840 subjects fulfilled our inclusion criteria and were systematically reviewed. 11 studies were included in our meta-analyses. We found a significant MD in PAI-1 levels in NAFLD patients vs. controls [17.147 (95%CI: 7.720-26.574)]. Moreover, subgroup analysis evaluating PAI-1 levels in biopsy- proven NAFLD vs. controls remained significant [24.086 (95%CI: 3.812-44.361)], as well as in CT-diagnosed NAFLD [15.523 (95%CI: 7.163-23.883)]. However, no significant MD in PAI-1 levels was found in ultrasound- diagnosed NAFLD patients vs. controls [10.394 (95%CI: -13.335-34.123)]. No significant MD in PAI-1 levels in NASH patients vs. controls was observed [26.835 (95%CI: -0.879-54.549)].
CONCLUSIONS
In summary, elevated serum PAI-1 levels are associated with adult NAFLD (biopsy-proven and CT-diagnosed). However, no significant difference was found in ultrasound-diagnosed NAFLD and NASH patients. Nonetheless, the included studies have methodological variance, dictating that the obtained results should be carefully interpreted.
Topics: Adult; Biopsy; Humans; Non-alcoholic Fatty Liver Disease; Plasminogen Activator Inhibitor 1
PubMed: 35574617
DOI: 10.15403/jgld-4091 -
Neurological Sciences : Official... Sep 2023We aimed to evaluate the available evidence on the efficacy and safety outcomes of intravenous tenecteplase (TNK) compared with intravenous alteplase(ALT) for patients... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We aimed to evaluate the available evidence on the efficacy and safety outcomes of intravenous tenecteplase (TNK) compared with intravenous alteplase(ALT) for patients with acute ischemic stroke (AIS) in randomized controlled trials (RCTs).
METHODS
The MEDLINE/PubMed, Embase, Springer, Web of Science, Cochrane Collaboration database, China National Knowledge Infrastructure (CNKI) database, and Wanfang database were comprehensively searched for RCTs regarding the effects of TNK versus ALT among AIS patients in these English and Chinese electronic databases from inception dates to August 1, 2022. This meta-analysis followed PRISMA guidelines. Two reviewers independently retrieved RCTs and extracted relevant information. The methodological quality of the included trials was estimated using the Cochrane risk of bias tool. The pooled analyses were performed using RevMan 5.3 software. The primary outcome was functional outcome on the modified Rankin Scale (mRS) (range 0 to 5) and mortality at 90 days. The secondary outcomes included successful recanalization, early neurologic improvement < 48 h, any intracranial hemorrhage (ICH), and symptomatic ICH. The follow-up time of all studies was at least 3 months.
RESULTS
A total of nine RCTs involving 1958 patients in TNK group and 1731 patients in ALT group were finally included. For the efficacy outcomes, there were no significant differences between the two groups in terms of mRS score 0 ~ 2 (RR 1.00; 95% CI 0.88-1.13; P = 0.96), mRS score 0 ~ 1 (RR 1.03; 95% CI 0.96-1.10; P = 0.36), successful recanalization (RR 1.25; 95% CI 0.88-1.76; P = 0.21), and early neurologic improvement < 48 h (RR 1.08; 95% CI 0.92-1.26; P = 0.37). Similar results were seen for the safety outcomes, which have no statistical differences in terms of any ICH (RR 1.01; 95% CI 0.72-1.41; P = 0.96), symptomatic ICH (RR 1.19; 95% CI 0.81-1.76; P = 0.37), and mortality at 90 days (RR 0.99; 95% CI 0.83-1.19; P = 0.94).
CONCLUSION
Overall, the efficacy and safety outcomes of intravenous thrombolysis with TNK versus ALT for AIS were not statistically different. However, TNK at a dose of 0.25 mg/kg may be a reasonable alternative to ALT for thrombolysis.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Stroke; Intracranial Hemorrhages; Ischemic Stroke; Thrombolytic Therapy; Treatment Outcome; Brain Ischemia
PubMed: 37061572
DOI: 10.1007/s10072-023-06801-0 -
American Journal of Reproductive... Apr 2015Human plasminogen activator inhibitor-1 (PAI-1) is closely related to embryonic development and pregnancy success. The association between PAI-1 gene polymorphisms... (Meta-Analysis)
Meta-Analysis Review
Human plasminogen activator inhibitor-1 (PAI-1) is closely related to embryonic development and pregnancy success. The association between PAI-1 gene polymorphisms (PAI-1-844G/A and PAI-1-675G/A) and the risk of recurrent pregnancy loss (RPL) is controversial. Therefore, we perform this review to clarify the association between PAI-1 gene polymorphisms and RPL risk. We performed a systematic search for studies that described the effect of PAI-1 polymorphisms on RPL risk. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were considered under recessive genetic models. Furthermore, we conducted a subgroup analysis based on the studies' geographic regions of origin. Data were analyzed using Stata 11.2 software. Eighteen studies were included, and a high degree of statistical heterogeneity existed among the studies. In this study, we found a significant association between the PAI-1-675G/A polymorphism and the risk of RPL under the recessive model (OR = 1.70, 95% CI = 1.21-2.38). However, no significant association between the PAI-1-844G/A polymorphism and RPL was noted. PAI-1-675G/A (4G/5G) polymorphisms play a potential role in RPL. The screening of PAI-1 (4G/5G) gene mutations should be included during an RPL diagnostic workup, and patients should be treated using anticoagulant therapy during pregnancy if necessary.
Topics: Embryo Loss; Female; Genetic Predisposition to Disease; Humans; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Pregnancy; Risk Factors
PubMed: 25250948
DOI: 10.1111/aji.12321 -
Molecular Neurobiology Jan 2017The plasminogen activator inhibitor-1 (PAI-1) is a candidate gene for stroke based on PAI-1's crucial role in fibrinolytic system. However, association studies have... (Meta-Analysis)
Meta-Analysis Review
The plasminogen activator inhibitor-1 (PAI-1) is a candidate gene for stroke based on PAI-1's crucial role in fibrinolytic system. However, association studies have yielded conflicting results regarding the association between PAI-1 polymorphisms and stroke susceptibility. To further elucidate the putative association, we performed a systematic review and meta-analysis to provide a complete picture of the loci investigated for association of PAI-1 polymorphism with stroke risk and to derive a precise estimation. PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched until June 2015 to identify eligible studies. Forty data sets from 39 studies with a total of 8336 cases and 14,403 controls were included. The most commonly investigated polymorphism was -675 4G/5G, followed by -844 G/A, 11053 T>G, HindIII C/G, and (CA)n. Overall, our meta-analysis provided evidence for the significant association of PAI-1 4G/5G polymorphism with an increased risk of adult but not pediatric ischemic stroke (adult: 4G/4G vs. 4G/5G + 5G/5G, OR = 1.21, 95 % CI = 1.04-1.42). In the subgroup analysis, significant association was detected in Asians (4G/4G vs. 4G/5G + 5G/5G, OR = 1.45, 95 % CI = 1.14-1.85) but not Caucasians. Moreover, we found that -844 G/A but not 11053 T>G polymorphism was associated with an increased risk of ischemic stroke (-844G/A: A/A vs. G/G: OR = 1.32, 95 % CI = 1.01-1.73). A tendency of PAI-1 4G/5G polymorphism towards a decreased risk of hemorrhagic stroke was observed (4G/4G + 4G/5G vs. 5G/5G, OR = 0.77, 95 % CI = 0.59-1.02, P = 0.066). Future well-designed studies in large well-characterized sample size and presenting results stratified by gender, age, and stroke subtype are warranted.
Topics: Case-Control Studies; Genetic Predisposition to Disease; Humans; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Risk Factors; Stroke
PubMed: 26742513
DOI: 10.1007/s12035-015-9549-8 -
Journal of Stroke and Cerebrovascular... Feb 2018Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However, it brings financial burden to patients and is associated with symptomatic intracranial hemorrhage (SICH). Whether low-dose tPA can effectively reduce SICH and has the same efficacy as standard-dose tPA is still controversial.
METHODS
We searched for English clinical trials published before March, 2017on the comparison of the efficacy and safety between low and standard dose of tPA in the treatment of AIS using MEDLINE, Embase, and Cochrane Library. The modified Rankin scale (mRS) score was used as the primary efficacy outcome. The mRS1 corresponded to 0-1, whereas mRS2 corresponded to 0-2. The SICH and mortality were adopted as primary safety outcomes.
RESULTS
Twelve high-quality studies were selected, including 7686 patients (low-dose: 2888, standard-dose: 4798). With no statistical heterogeneity, the fixed effects model was adopted in the analysis. Similarly to standard doses, low-dose tPA improved the mRS scores (mRS1: odds ratio [OR] = .92, 95% confidence interval [CI] .84-1.02; P = .12; mRS2: OR = .97, 95% CI .88-1.08; P = .57). Compared with standard-dose tPA, low-dose tPA reduced the incidence of SICH (by National Institute of Neurological Disorders and Stroke [NINDS] definition: OR = .71, 95% CI .57-0.89; P = .003; by Safe Implementation of Thrombolysis in Stroke Monitoring Study [SITS-MOST] definition: OR = .64, 95% CI .42-0.99; P = .04), while both reduced mortality (OR = .87, 95% CI .74-1.02; P = .08).
CONCLUSIONS
Low-dose tPA is comparable to standard-dose tPA in improving the neurologic function and reducing mortality in AIS patients. Moreover, low-dose tPA can reduce the incidence of SICH compared with standard-dose tPA. Therefore, low-dose tPA is highly recommended in AIS patients.
Topics: Brain Ischemia; Chi-Square Distribution; Disability Evaluation; Fibrinolytic Agents; Humans; Infusions, Intravenous; Intracranial Hemorrhages; Odds Ratio; Recovery of Function; Risk Factors; Stroke; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 29111341
DOI: 10.1016/j.jstrokecerebrovasdis.2017.09.014 -
Frontiers in Endocrinology 2022Despite patients with thyroid dysfunction show obvious abnormal hemostatic indicators in the peripheral blood, the current research on whether and how subclinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite patients with thyroid dysfunction show obvious abnormal hemostatic indicators in the peripheral blood, the current research on whether and how subclinical hypothyroidism (SCH) influence hemostatic function (the coagulation and fibrinolytic system) still remains controversial.
OBJECTIVE
We conducted this study to evaluate how SCH influence on the coagulation and fibrinolytic system in human body.
METHODS
Prior to March 2022, Web of Science, Embase, PubMed, WanFang, CNKI data and reference lists were searched to identify eligible researches. Two of us independently extracted the data and evaluated study quality. The effect size is represented by standard mean difference (SMD). Both fixed and random-effects models were used where appropriate. Review Manager 5.3 and STATA 16.0 were used to analyze the eligible data.
RESULTS
1325 patients from twelve observational studies were involved in our research. Our study revealed that SCH changed the heamostatic balance towards hypercoagulable and hypofibrinolytic conditions accompanied by an increase in tissue fibrinogen, plasminogen activator and plasminogen activator inhibitor-1. By contrast, there was no statistically difference in acivated partial thromboplastin time (APTT) and D-Dimer in SCH group compared with that in control subjects.
CONCLUSIONS
Our study confirmed that SCH is related with a prothrombotic state, as reflected by changes in both coagulation and fibrinolysis. It is highly recommended for screening cardiovascular risk factors in combination with an adequate evaluation of SCH state.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/#recordDetails] PROSPERO [CRD42021275313].
Topics: Blood Coagulation; Fibrinolysis; Hemostatics; Humans; Hypothyroidism; Thyroid Diseases
PubMed: 35574019
DOI: 10.3389/fendo.2022.861746 -
OncoTargets and Therapy 2015Although the urokinase plasminogen activator receptor (uPAR) is expressed in gastric cancer (GC) and colorectal cancer (CRC), its evaluation as a prognostic biomarker... (Review)
Review
PURPOSE
Although the urokinase plasminogen activator receptor (uPAR) is expressed in gastric cancer (GC) and colorectal cancer (CRC), its evaluation as a prognostic biomarker remains controversial. In this study, we performed a literature review and meta-analysis to evaluate the association of uPAR expression with the prognosis of patients with GC and CRC.
METHOD
The PubMed database was searched for material published in English, and data were then extracted and assessed by two reviewers independently. Correlations between uPAR expression and clinicopathological features and overall survival (OS) of patients with GC or CRC were analyzed.
RESULTS
A total of 2,082 patients with GC and CRC from ten studies were included. The results of the meta-analysis showed that the uPAR expression rate in GC and CRC tissues was higher than that in normal tissues (odds ratio [OR] =3.385; 95% confidence interval [CI] 2.605-4.400; P=0.000). Our meta-analysis also revealed a significant association between uPAR expression and lymph node metastasis (OR =1.366; 95% CI =1.086-1.718; P=0.008) and tumor stage (OR =3.076; 95% CI =2.330-4.061; P=0.000). Furthermore, we found that high uPAR expression correlated with poor OS (OR =1.937; 95% CI =1.570-2.930; P=0.000).
CONCLUSION
The uPAR expression may serve as a novel disease marker in GC and CRC, as well as a therapeutic target.
PubMed: 26150727
DOI: 10.2147/OTT.S80634 -
Neurological Research Jul 2014Post-intravenous recombinant tissue plasminogen activator (r-tPA) orolingual angioedema (PIROLA), including the life-threatening form, is an underappreciated... (Review)
Review
RATIONALE
Post-intravenous recombinant tissue plasminogen activator (r-tPA) orolingual angioedema (PIROLA), including the life-threatening form, is an underappreciated complication of ischaemic stroke treatment.
AIMS
We present an audit report and a systematic review of published observational studies on PIROLA occurrence in acute ischaemic stroke patients.
METHODS
Clinical files of patients treated in the stroke unit of Bourg-en-Bresse General Hospital (France) from January 2010 to December 2012 were reviewed, and MEDLINE (inception to May 2013) were searched and bibliographies/citations of retrieved articles examined for evidence of PIROLA.
RESULTS
Of the 129 acute ischaemic stroke patients treated at Bourg-en-Bresse between 2010 and 2012, four patients, all receiving angiotensin converting enzyme inhibitor (ACEI), developed a PIROLA (cumulative incidence rate: 32‰). The complication started within an hour of receiving r-tPA and integrally resolved within 3-24 hours, with antihistamines/steroid treatment in two patients. The systematic review identified 27 studies, totalising with ours, over 9050 acute ischaemic stroke patients from 12 countries, among whom 100 (cumulative incidence rate: 17‰; 95% confidence intervals: 8-26), developed a PIROLA within 6-240 minutes of receiving r-tPA, 0-100% of them occurring among patients on ACEI. The complication was contralateral to the stroke location in 47% cases, ipsilateral in 14%, and bilateral in 39%; and resolved within 24 hours with treatment in 90%. No related death was recorded.
CONCLUSIONS
About 17‰ acute ischaemic stroke patients receiving r-tPA develop PIROLA, occurring essentially among those on concomitant ACEI. PIROLA occurrence should be actively monitored, particularly within the first few hours as some may require urgent lifesaving procedures.
Topics: Angioedema; Brain Ischemia; Fibrinolytic Agents; France; Hospitals, General; Humans; Incidence; Medical Audit; Mouth Diseases; Observational Studies as Topic; Recombinant Proteins; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 24620962
DOI: 10.1179/1743132813Y.0000000302 -
Journal of Vascular Surgery Mar 2014Limited data exist regarding the development of abdominal compartment syndrome (ACS) after endovascular repair of ruptured abdominal aortic aneurysms (RAAAs). We aimed... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Limited data exist regarding the development of abdominal compartment syndrome (ACS) after endovascular repair of ruptured abdominal aortic aneurysms (RAAAs). We aimed to record the incidence, management, and outcome of this complication.
METHODS
A systematic review and meta-analysis of the English language literature was undertaken through June 2012. Articles reporting data on outcome after endovascular repair of RAAAs were identified, and information regarding ACS was sought.
RESULTS
Included were 39 eligible studies reporting 1134 patients. The pooled perioperative mortality was 21% (95% confidence interval [CI], 18%-24%). A total of 109 cases of ACS were recorded. There was significant within-study heterogeneity (Cochran Q = 94.1; P < .0001), and the pooled ACS rate was 8% (95% CI, 5.6%-10.8%). Only six studies accurately defined ACS, and four focused specifically on ACS. When the meta-analysis was repeated after including only studies with a definition and those focusing on ACS, the pooled rate increased to 17% (95% CI, 10%-26%) and 21% (95% CI, 13%-30%), respectively. A random-effects meta-regression analysis investigating the effect of ACS and other risk factors on mortality revealed a significant linear correlation between hemodynamic instability and death (r = 0.303) and a nonlinear (second degree polynomial) association between bifurcated endograft approach and death (R(2) = 0.348; P = .0027). However, no statistically significant association could be found between ACS and death. A further meta-regression analysis failed to identify any statistically significant predictors of ACS. Treatment included open decompression in 86 patients, percutaneous drainage in 18 (catheter only in five, combined with tissue plasminogen activator infusion in 13), and conservative measures in five. Data on outcome of ACS were only available for 76 patients; 35 of these died, for a mortality rate of 47%.
CONCLUSIONS
The pooled ACS rate was calculated at 8%, but this figure may be >20% with improved awareness and vigilant monitoring. Although no statistically significant association could be found between ACS and death, almost half the patients who developed ACS after endovascular repair of RAAAs were likely to die.
Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Vessel Prosthesis Implantation; Decompression, Surgical; Drainage; Endovascular Procedures; Hemodynamics; Humans; Incidence; Intra-Abdominal Hypertension; Nonlinear Dynamics; Reoperation; Risk Factors; Treatment Outcome
PubMed: 24439324
DOI: 10.1016/j.jvs.2013.11.085