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Stroke Sep 2015The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography-based planimetry (CTP).
METHODS
In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression.
RESULTS
In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC (r(2)=0.93) than with site-ABC (r(2)=0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm(3); CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P<0.001). This was consistent with overestimation of ICH volume in 6 of 8 previous studies. Agreement with CTP was greater for RC-ABC (84% within 5 mL; 48% of scans within 20%) than for site-ABC (81% within 5 mL; 41% within 20%). RC-ABC had moderate accuracy for detecting ≥5 mL change in CTP volume between consecutive scans (sensitivity, 0.76; specificity, 0.86) and was more accurate with smaller ICH, thalamic hemorrhage, and homogeneous clots.
CONCLUSIONS
ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: MISTIE-II NCT00224770; CLEAR-III NCT00784134.
Topics: Cerebral Hemorrhage; Humans; Severity of Illness Index
PubMed: 26243227
DOI: 10.1161/STROKEAHA.114.007343 -
World Neurosurgery Nov 2017The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to evaluate whether there are differences between recombinant tissue-plasminogen activator (rt-PA) and urokinase according to subgroup analyses.
METHODS
A meta-analysis was undertaken of randomized controlled trials in patients with IVH that compared the administration of rt-PA or urokinase through extraventricular drainage (EVD) with normal saline through EVD or EVD placement alone.
RESULTS
Six randomized controlled trials involving 607 patients with IVH were included; 2 trials investigated urokinase and 4 rt-PA. IVF reduced death from any cause at the end of follow-up (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47-0.83), which was driven mostly by rt-PA (RR 0.65, 95% CI 0.48-0.86). Urokinase did not reduce mortality (RR 0.30, 95% CI 0.06-1.53). However, rt-PA did not reduce the proportion of survivors with poor functional outcome (RR 1.36, 95% CI 1.04-1.77), or the composite endpoint of death and poor functional outcome (RR 0.96, 95% CI 0.83-1.11). IVF neither reduced the need for shunt placement (RR 1.06, 95% CI 0.75-1.49) nor increased ventriculitis (RR 0.57, 95% CI 0.35-0.93) and rebleeding (RR 1.65, 95% CI 0.79-3.45).
CONCLUSIONS
Although the use of IVF in patients with IVH appears generally safe, its benefit is limited to a reduction in mortality at the expense of an increased number of survivors with moderately-severe to severe disability. Subgroup analyses do not suggest an advantage of IVF with urokinase over rt-PA.
Topics: Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Injections, Intraventricular; Randomized Controlled Trials as Topic; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 28778779
DOI: 10.1016/j.wneu.2017.07.135 -
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 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2021Arterial catheterization is frequently performed in neonatal intensive care units with an inherent risk of peripheral ischemic injury, especially in preterm infants. The... (Review)
Review
BACKGROUND
Arterial catheterization is frequently performed in neonatal intensive care units with an inherent risk of peripheral ischemic injury, especially in preterm infants. The treatment options following vascular damage involve invasive and non-invasive modalities. The primary objective of this systematic review was to evaluate the evidence of the use of topical nitroglycerine (TNG) either alone or as adjunctive therapy. The secondary aim was to develop an approach to the treatment of catheter induced ischemia in infants based on the available evidence.
METHODS
A comprehensive search was conducted of available databases for relevant articles that involved the treatment of peripheral tissue ischemia in neonates with the use of TNG. Citations were restricted to human subjects.
RESULTS
Six hundred and eighty-nine articles were identified, and twenty-seven case reports and case series were compatible with the inclusion and exclusion criteria. Sixty-eight infants out of the 76 published cases (89%) experienced a favorable outcome and 79% (n = 60) demonstrated complete recovery with the topical application of TNG to the ischemic site.
CONCLUSION
The available evidence demonstrates that TNG is effective for the treatment of peripheral ischemia in neonates after standard conservative measures have failed. However, due to the absence of robust evidence for this therapeutic modality, there are no uniform guidelines regarding the frequency, duration, and safety of TNG use. Planning the management of peripheral ischemia in neonates with TNG should be a multidisciplinary decision that includes close surveillance of blood pressure, methemoglobin levels, and follow up cranial ultrasound.
PubMed: 34400871
DOI: 10.1016/j.jsps.2021.05.008 -
Medicine Dec 2014Renal dysfunction is a prevalent comorbidity in acute ischemic stroke patients requiring thrombolytic therapy. However, the effect of renal dysfunction on the clinical... (Meta-Analysis)
Meta-Analysis Review
Renal dysfunction is a prevalent comorbidity in acute ischemic stroke patients requiring thrombolytic therapy. However, the effect of renal dysfunction on the clinical outcome of this population remains controversial. This study aimed to evaluate the safety and effectiveness of thrombolytic therapy in acute stroke patients with renal dysfunction using a meta-analysis. We systematically searched PubMed and EMBASE for studies that evaluated the relationship between renal dysfunction and intravenous tissue plasminogen activator (tPA) in patients with acute ischemic stroke. Poor outcome (modified Rankin Scale≥2), mortality, and symptomatic intracranial hemorrhage (ICH) and any ICH were analyzed. Fourteen studies were included (N=53,553 patients). The mean age ranged from 66 to 75 years. The proportion of male participants was 49% to 74%. The proportion of renal dysfunction varied from 21.9% to 83% according to different definitions. Based on 9 studies with a total of 7796 patients, the meta-analysis did not identify a significant difference in the odds of poor outcome (odds ratio [OR]=1.06; 95% confidence interval [CI]: 0.96-1.16; I=44.5) between patients with renal dysfunction and those without renal dysfunction. Patients with renal dysfunction were more likely to die after intravenous thrombolysis (OR=1.13; 95% CI: 1.05-1.21; I=70.3). No association was observed between symptomatic ICH (OR=1.02; 95% CI: 0.94-1.10; I=0) and any ICH (OR=1.07; 95% CI: 0.96-1.18; I=25.8). Renal dysfunction does not increase the risk of poor outcome and ICH after stroke thrombolysis. Renal dysfunction should not be a contraindication for administration of intravenous thrombolysis to eligible patients.
Topics: Acute Disease; Brain Ischemia; Fibrinolytic Agents; Global Health; Glomerular Filtration Rate; Humans; Incidence; Renal Insufficiency; Thrombolytic Therapy
PubMed: 25526464
DOI: 10.1097/MD.0000000000000286 -
The Cochrane Database of Systematic... Aug 2018About one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have traditionally been considered ineligible for thrombolytic treatment...
BACKGROUND
About one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have traditionally been considered ineligible for thrombolytic treatment because the time of stroke onset is unknown. However, some studies suggest that these people may benefit from recanalisation therapies.
OBJECTIVES
To assess the effects of intravenous thrombolysis and other recanalisation therapies versus control in people with acute ischaemic stroke presenting on awakening.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (last search: 9 January 2018). In addition, we searched the following electronic databases in December 2017: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11) in the Cochrane Library, MEDLINE, Embase, US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the ISRCTN registry, and Stroke Trials Registry. We also screened references lists of relevant trials, contacted trialists, undertook forward tracking of relevant references, and contacted manufacturers of relevant devices and equipment.
SELECTION CRITERIA
Randomised controlled trials of intravenous thrombolytic drugs or intra-arterial therapies in people with acute ischaemic stroke presenting upon awakening.
DATA COLLECTION AND ANALYSIS
Two review authors applied the inclusion criteria, extracted data, and assessed trial quality and risk of bias using the GRADE approach. We obtained both published and unpublished data.
MAIN RESULTS
We included one pilot trial with nine participants. The trial was a feasibility trial that included participants with an unknown onset of stroke and signs on perfusion computed tomography of ischaemic tissue at risk of infarction, who were randomised to alteplase (0.9 mg/kg) or placebo. One trial was prematurely terminated due to signs of efficacy of the intervention arm; we did not include this trial because we were not able to obtain data for the portion of the participants with wake-up stroke after requesting this information from the trial authors. We identified six ongoing trials.
AUTHORS' CONCLUSIONS
There is insufficient evidence from randomised controlled trials for recommendations concerning recanalisation therapies for wake-up stroke. Results from ongoing trials will hopefully establish the efficacy and safety of such therapies.
Topics: Feasibility Studies; Fibrinolytic Agents; Humans; Mechanical Thrombolysis; Pilot Projects; Randomized Controlled Trials as Topic; Sleep; Stroke; Time Factors; Tissue Plasminogen Activator; Wakefulness
PubMed: 30129656
DOI: 10.1002/14651858.CD010995.pub2 -
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 -
Journal of Ayurveda and Integrative... 2023Adipokines have an important role in the pathophysiology of overweight and obesity and associated inflammatory diseases. (Review)
Review
BACKGROUND
Adipokines have an important role in the pathophysiology of overweight and obesity and associated inflammatory diseases.
OBJECTIVE
The present review aims to evaluate the role of Yoga on adipokines among people with overweight and obesity.
METHODS
Authors performed a systematic search for relevant research studies as per the PRISMA guidelines in Google Scholar, Medline/Pubmed, Scopus, Web of Science, PsychInfo electronic databases. Two independent authors conducted the selection of articles, data extraction, assessment of the risk of bias for individual studies. Any disagreements were resolved by discussion with the third author.
RESULTS
Eight randomized trials and four uncontrolled trials involving a total of 1054 participants were included. Yoga with varying frequencies was administered for different durations. The studied adipokines among overweight and obese were leptin, adiponectin, interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-α), chemerin, visfatin, plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta (TGF-β). The methodological quality of the included studies was low to moderate on the Cochrane risk of bias tool and Newcastle-Ottawa Quality Assessment Scale. The higher the frequency and duration of Yoga practice, the more significant changes in the adipokine levels were seen.
CONCLUSION
The present review indicates that Yoga practices positively impacts adipokines among people with overweight and obesity. However, the present study precludes the generalizability of results due to the methodological heterogeneity, the type of Yoga intervention, and settings.
PubMed: 38041935
DOI: 10.1016/j.jaim.2023.100813 -
The Cochrane Database of Systematic... May 2013Stroke is a leading cause of death and disability world wide. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is licensed for treatment of acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stroke is a leading cause of death and disability world wide. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is licensed for treatment of acute ischaemic stroke in the early hours after symptom onset. It has been shown in randomised controlled trials (RCTs) and the 2009 Cochrane review of thrombolysis for acute ischaemic stroke to reduce dependency but at the increased risk of intracranial haemorrhage. Methods to reduce the risk of haemorrhage while retaining or enhancing the benefit could increase the use of thrombolytic treatment. While most available information comes from RCTs of intravenous rt-PA at 0.9 mg/kg, it is possible that other doses, drugs and other routes of administration might increase benefit and reduce the hazard.
OBJECTIVES
To assess the risks and benefits of different thrombolytic agents, doses and routes of administration for the treatment of acute ischaemic stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (May 2012), MEDLINE (1966 to May 2012) and EMBASE (1980 to May 2012). We handsearched journals and conference proceedings, searched ongoing trials registers and contacted pharmaceutical companies and researchers.
SELECTION CRITERIA
Unconfounded randomised and quasi-randomised trials of different doses of a thrombolytic agent, or different agents, or the same agent given by different routes, in people with confirmed acute ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility and quality, and extracted the data using a structured proforma. We cross-checked and resolved discrepancies by discussion to reach consensus. We obtained translations and additional information from study authors where required.
MAIN RESULTS
We included 20 trials involving 2527 patients. Concealment of allocation was poorly described. Different doses (of tissue plasminogen activator, urokinase, desmoteplase or tenecteplase) were compared in 13 trials (N = 1433 patients). Different agents (tissue plasminogen activator versus urokinase, tissue-cultured urokinase versus conventional urokinase, tenecteplase versus tissue plasminogen activator) were compared in five trials (N = 875 patients). Five trials (N = 485) compared different routes of administration. As some trials compared different agents and different doses, some patients contributed to two analyses. There was an approximately three-fold increase in fatal intracranial haemorrhages in patients allocated to higher than to lower doses of the same thrombolytic drug (odds ratio (OR) 2.71, 95% confidence interval (CI) 1.22 to 6.04). There was no difference in the number of patients who were dead or dependent at the end of follow-up between those allocated higher or lower doses of thrombolytic drug (OR 0.86, 95% CI 0.62 to 1.19). Higher versus lower doses of desmoteplase were associated with more deaths at the end of follow-up (OR 3.21, 95% CI 1.23 to 8.39). There was no evidence of any benefit for intra-arterial over intravenous treatment.
AUTHORS' CONCLUSIONS
These limited data suggest that higher doses of thrombolytic agents may lead to higher rates of bleeding. However, the evidence is inadequate to conclude whether lower doses of thrombolytic agents are more effective than higher doses, or whether one agent is better than another, or which route of administration is the best, for acute ischaemic stroke. At present, intravenous rt-PA at 0.9mg/kg as licensed in many countries appears to represent best practice and other drugs, doses or routes of administration should only be used in randomised controlled trials.
Topics: Acute Disease; Brain Ischemia; Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Stroke; Tenecteplase; Thrombolytic Therapy; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator
PubMed: 23728633
DOI: 10.1002/14651858.CD000514.pub3 -
British Journal of Clinical Pharmacology Jul 2017Statins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
Statins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an add-on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear, the aim of the present study was to investigate this through a meta-analysis of controlled trials.
METHODS
A systematic review was performed, followed by a bibliographic search in PubMed, Medline, SCOPUS, Web of Science and Google Scholar databases. Quantitative data synthesis was performed using a fixed- or random-effects model (based on the level of interstudy heterogeneity) and the generic inverse variance weighting method. Effect sizes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI).
RESULTS
Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124). However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF-α) (SMD -0.48, 95% CI -0.87, -0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy.
CONCLUSIONS
The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect.
Topics: Adiponectin; Anticholesteremic Agents; Atherosclerosis; Drug Therapy, Combination; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Leptin; Plasminogen Activator Inhibitor 1; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha
PubMed: 28166606
DOI: 10.1111/bcp.13250