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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 Vascular Surgery Feb 2020The initial treatment of patients with acute limb ischemia (ALI) remains undefined. The aim of this article was to compare the safety and effectiveness of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The initial treatment of patients with acute limb ischemia (ALI) remains undefined. The aim of this article was to compare the safety and effectiveness of catheter-driven thrombolysis (CDT) with surgical revascularization and evaluate the various fibrinolytic agents, endovascular, and pharmacochemical approaches that aim for thrombectomy.
METHODS
PubMed, Embase, and the Cochrane Library were searched for studies on the management of ALI by means of surgical or endovascular recanalization, returning 520 studies. All randomized, controlled trials, nonrandomized prospective, and retrospective studies were included comparing treatment of ALI.
RESULTS
Twenty-five studies, investigating a total of 4689 patients, were included for meta-analysis spread across nine different comparisons. No differences were found in limb salvage between thrombectomy and thrombolysis. More major vascular events were seen in the thrombolysis group (6.5% compared with 4.4% in the surgically treated group; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13-0.87; P = .02; I = 20%). Comparable limb salvage was found for high- and low-dose recombinant tissue plasminogen activator (r-tPA). No significant differences were found in major vascular event between low r-tPA (14%) and high r-tPA (10.5%; P = .13). The 30-day limb salvage rate was 79.7% for r-tPA treatment and 60.4% for streptokinase (OR, 3.14; 95% CI, 1.26-7.85; P = .01; I = 0%). AngioJet showed more limb salvage at 6 months compared with r-tPa (OR, 2.21; 95% CI, 1.17-4.18; P = .01; I = 0%).
CONCLUSIONS
Both CDT and surgery have comparable limb salvage rates in patients with ALI; however, CDT is associated with a higher risk of hemorrhagic complications. No conclusions can be drawn regarding the risk of hemorrhagic complications regarding thrombolytic therapy by means of r-tPA, streptokinase, or urokinase. Insufficient data are available to conclude the preference of using a hybrid approach, ultrasound-accelerated CDT, heated r-tPA. or novel endovascular (rheolytical) thrombectomy systems. Future trials regarding ALI need to be constructed carefully, ensuring comparable study groups, and should follow standardized practices of outcome reporting.
Topics: Acute Disease; Endovascular Procedures; Fibrinolytic Agents; Humans; Ischemia; Limb Salvage; Lower Extremity; Tissue Plasminogen Activator; Vascular Surgical Procedures
PubMed: 31353270
DOI: 10.1016/j.jvs.2019.05.031 -
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 Orthopaedic Surgery and... Jul 2023Calcaneal fractures are a common orthopedic disease, account for approximately 2% of all bone fractures, and represent 60% of fractures of tarsal bones. Tranexamic acid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Calcaneal fractures are a common orthopedic disease, account for approximately 2% of all bone fractures, and represent 60% of fractures of tarsal bones. Tranexamic acid (TXA) is a synthetic antifibrinolytic drug that competitively blocks the lysine-binding sites of plasminogen, plasmin, and tissue plasminogen activator, delaying fibrinolysis and blood clot degradation. However, the effect of TXA on patients with calcaneal surgery remains controversial. Our objective was to evaluate the effectiveness of TXA in calcaneal fractures surgeries.
METHODS
The electronic literature databases of Pubmed, Embase, and Cochrane library were searched in December 2022. The data on blood loss, the stay in the hospital, the duration of surgery, hemoglobin, hematocrit, platelet count, prothrombin time, activated partial thromboplastin time, and wound complication were extracted. The Stata 22.0 software was used for the meta-analysis.
RESULTS
Four randomized controlled studies met our inclusion criteria. This meta-analysis showed that TXA significantly reduced postoperative blood loss during the first 24 h (p < 0.001), improved the level of hemoglobin (p < 0.001) and hematocrit (p = 0.03), and reduced the risk of wound complications (p = 0.04). There was no significant difference between the two groups regarding total and intraoperative blood loss, hospital stay, duration of surgery, platelet count, activated partial thromboplastin time, and prothrombin time.
CONCLUSION
TXA significantly reduced blood loss during the first 24 h postoperatively, improved the level of hemoglobin and hematocrit, and reduced the risk of wound complications. Given the evidence, TXA can be used in patients with calcaneal fractures and had the potential benefit of blood reduction.
PROTOCOL REGISTRATION
The protocol was registered in PROSPERO (registration No. CRD42023391211).
Topics: Humans; Tranexamic Acid; Tissue Plasminogen Activator; Randomized Controlled Trials as Topic; Calcaneus; Tarsal Bones; Ankle Injuries
PubMed: 37438798
DOI: 10.1186/s13018-023-03924-0 -
Journal of Diabetes and Metabolic... Dec 2020The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the... (Review)
Review
BACKGROUND
The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the findings are conflicting. Herein, we conducted a case-control and meta-analysis study to explore the association of PAI-1 4G5G polymorphism with risk of DNR.
METHODS
We retrieved PubMed, EMBASE, Web of Knowledge, and CNKI databases and screened eligible studies up to August 15, 2020. The strength of associations was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI).
RESULTS
A total of 27 case-control studies including 16 studies with 1,825 cases case and 1,731 controls on DN and eleven studies with 1,397 cases and 1,545 controls on DR were selected. Pooled data showed that the PAI-1 4G5G polymorphism was significantly associated with DN (allele model: OR = 0.674, 95% CI 0.524-0.865, p = 0.002; homozygote model: OR = 0.536, 95% CI 0.351-0.817, p = 0.004; heterozygote model: OR = 0.621, 95% CI 0.427-0.903, p = 0.013; dominant model: OR = 0.575, 95% CI 0.399-0.831, p = 0.003; and recessive model: OR = 0.711, 95% CI 0.515-0.981, p = 0.038) and DR (homozygote model: OR = 0.770, 95% CI 0.621-0.955, p = 0.0.017) risk. Stratified analyses by ethnicity indicated that PAI-1 4G5G polymorphism was associated with DN and DR risk in Asians and Caucasians, respectively.
CONCLUSIONS
The present meta-analysis revealed that the PAI-1 4G5G polymorphism was associated with increased risk of DN and DR risk. However, well-designed large-scale clinical studies are required to further validate our results.
PubMed: 33520873
DOI: 10.1007/s40200-020-00675-1 -
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 -
Shock (Augusta, Ga.) Apr 2020Soluble urokinase-type plasminogen activator receptor (suPAR) has the potential to diagnose infectious diseases. Due to the lack of reliable biomarkers and the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Soluble urokinase-type plasminogen activator receptor (suPAR) has the potential to diagnose infectious diseases. Due to the lack of reliable biomarkers and the importance of timely diagnosis for sepsis treatment, we conducted this systematic review and meta-analysis to evaluate the value of suPAR diagnosis and prognosis for sepsis.
METHODS
PubMed, Embase, Web of Science, and Cochrane Library databases were searched for studies, which reported the value of suPAR diagnosis and/or prognosis in patients with sepsis.
RESULTS
A total of 30 studies involving 6,906 patients were included. Sensitivity and specificity of suPAR for diagnosing sepsis were 0.76 [95% confidence interval (CI), 0.63-0.86] and 0.78 (95% CI, 0.72-0.83), respectively. The area under the summary receiver-operating characteristic curve (AUC) was 0.83 (95% CI, 0.80-0.86). Pooled sensitivity and specificity for predicting mortality were 0.74 (95% CI, 0.67-0.80) and 0.70 (95% CI, 0.63-0.76), respectively, with AUC of 0.78 (95% CI, 0.74-0.82). In addition, AUC for differentiating sepsis from systemic inflammatory response syndrome (SIRS) was 0.81 (95% CI, 0.77-0.84), and the sensitivity and specificity were 0.67 (95% CI, 0.58-0.76) and 0.82 (95% CI, 0.73-0.88), respectively.
CONCLUSION
suPAR is a feasible biomarker for timely diagnosis and prognosis of sepsis. Compared with effective value of procalcitonin (PCT) identified by previous meta-analysis, suPAR has similar clinical guiding value, whereas suPAR exhibits higher specificity, which can facilitate the deficiencies of PCT. suPAR also shows a diagnostic value in differentiating sepsis from SIRS. Considering the lack of biomarkers for sepsis and the similar clinical value of suPAR and PCT, suPAR should be considered as a biomarker in clinical practice for sepsis.
Topics: Biomarkers; Humans; Predictive Value of Tests; Prognosis; Receptors, Urokinase Plasminogen Activator; Sepsis
PubMed: 31490358
DOI: 10.1097/SHK.0000000000001434 -
Frontiers in Neurology 2022This study aims to assess the efficacy and safety of different doses of intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) by adopting a...
BACKGROUND
This study aims to assess the efficacy and safety of different doses of intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) by adopting a network meta-analysis (NMA).
METHODS
Studies comparing different doses of tPA in AIS were identified by retrieving electronic databases. NMAs of outcome measures included favorable functional outcome with a modified Rankin scale score (mRS) of 0 or 1 at 3 months after treatment (3M-FF), the functional independence with a mRS of 0, 1, or 2 at 3 months (3M-FI), symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M). Symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M) were assessed. Probability-based ranking and surface under cumulative ranking (SUCRA) were performed to identify the best dose of tPA. Inconsistency was evaluated by node-splitting analysis and a loop-specific approach. Publication bias was analyzed by funnel plots.
RESULTS
A total of 14 studies were included in the quantitative synthesis. The NMA results revealed no difference among low (<0.7 mg/kg), moderate (0.8 mg/kg), and standard (0.9 mg/kg) doses of tPA with regard to efficacy and safety. The SUCRAs of 3M-FF and 3M-FI showed that the standard dose ranked first, the moderate dose ranked second, and the low dose ranked third. The SUCRA of sICH showed that the standard dose ranked first (78.1%), the low dose ranked second (61.0%), and the moderate dose ranked third (11.0%). The SUCRAs of 3-month mortality showed that the standard dose ranked first (73.2%), the moderate dose ranked second (40.8%), and the low dose ranked third (36.1%). No significant inconsistency was shown by node-splitting analysis and no publication bias was shown in funnel plots.
CONCLUSION
Lower dose tPA was comparable to the standard dose with regard to efficacy and safety. Based on the SUCRA results and American Heart Association/American Stroke Association (AHA/ASA) guidelines, the standard dose was still the optimal selection for AIS.
PubMed: 35812086
DOI: 10.3389/fneur.2022.884267 -
Journal of Thrombosis and Haemostasis :... Dec 2020Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear.
OBJECTIVES
This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature.
PATIENTS/METHODS
PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated.
RESULTS
Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in <2%. The MTHFR C677T and PAI 4G homozygous polymorphism were observed in 13% (95% CI: 10-17) and 23% (95% CI: 16-31) of RVO, respectively; 8% presented APL antibodies. Similar findings were observed in individuals with RAO.
CONCLUSIONS
Compared with healthy subjects, patients with retinal vascular occlusion showed similar prevalences of inherited and acquired thrombophilias. These findings do not support routine thrombophilia screening in individuals with RAO or RVO.
Topics: Adult; Factor V; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Prothrombin; Retinal Vein Occlusion; Risk Factors; Thrombophilia
PubMed: 32805772
DOI: 10.1111/jth.15068 -
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