Impact of Thrombophilia On Arterial Ischemic Stroke or Cerebral Venous Sinus Thromboses in Children: A Systematic Review & Meta-Analysis of Observational Studies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3993-3993
Author(s):  
Lisa K Lütkhoff ◽  
Manuela Albisetti ◽  
Timothy J. Bernard ◽  
Mariana Bonduel ◽  
Leonardo R. Brandao ◽  
...  

Abstract Abstract 3993 Poster Board III-929 Background The incidence of stroke in children is estimated at about 2.6 per 100,000 per year. Risk factors include congenital heart malformations, trauma, hemolytic anemias, collagen tissue diseases, inborn metabolic disorders, and infectious diseases. Apart from acquired thrombophilic risk factors, such as the presence of antiphospholipid antibodies, inherited thrombophilias (IT) have been found to be associated with stroke in infants and children. However, results of single studies on the risk of stroke onset associated with IT have been contradictory or inconclusive, mainly due to lack of statistical power. The aim of this study was to estimate the impact of thrombophilia (IT) on risk of childhood stroke via meta-analysis of published observational studies. Methods and Results A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted using key words in combination both as MeSH terms and text words. Citations were independently screened by two authors and those meeting the a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, stroke type (arterial ischemic stroke [AIS]; cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed-effects and random-effects models. Twenty-one of 185 references found met inclusion criteria. 1698 patients (AIS: 1291; CSVT: 407) and 2913 controls aged neonate to 18 years were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with stroke onset was demonstrated for each IT trait evaluated, with no difference found between AIS (table) and CSVT. Summary ORs/CIs (random-effects model) for AIS & CSVT cohorts were as follows: Protein C-deficiency (8.76/4.53-16.96), FV G1691A (3.34/2.66-4.26), FII G20210A (2.50/1.67-3.74), MTHFR T677T (1.61/1.21-2.14), antiphospholipid antibodies (5.84/3.06-11.18), elevated lipoprotein (a) (6.24/4.51-8.64), and combined ITs (8.85/3.32-23.57). Carrier rates reported for antithrombin- or protein S deficiency among patients were 1.5% and 1.6% as compared with 0.06% (p<0.001) and 0.4% (p=0.003) in healthy controls. Conclusions The present meta-analysis indicates that IT serve as risk factors for incident stroke. However, the impact of IT upon outcome and recurrence risk needs to be further investigated. Disclosures: Manco-Johnson: Baxter BioScience: Honoraria; Bayer HealthCare: Honoraria; CSL Behring: Honoraria; NovoNordisk: Honoraria; Octapharma: Honoraria. Off Label Use: Enoxaparin (LMWH) is used off-label in children to prevent symptomatic thromboembolism.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3169-3169
Author(s):  
Gili Kenet ◽  
Mariana Bonduel ◽  
Anthony Chan ◽  
Neil Goldenberg ◽  
Suzzane Holtzhauer ◽  
...  

Abstract Abstract 3169 Background: Adapted from the adult definition, pediatric antiphospholipid syndrome [APS] has been defined as one or more arterial or venous thrombosis associated with persistent antiphospholipid antibodies, i.e. IgM or IgG anticardiolipin antibodies [ACL: cut-off > 99th age-dependent percentile] or the presence of lupus anticoagulants confirmed in at least one follow-up visit more than 8 to 12 weeks apart. Antiphospholipid antibodies play an important role in the development of pediatric thromboembolism [TE] with arterial TE or stroke being more often associated with primary APS compared to deep venous thrombosis [DVT], which is observed predominantly in children with secondary APS. However, results of single studies on the risk thromboembolism onset associated with APS have been contradictory or inconclusive, mainly due to lack of statistical power. The aim of this study was to estimate the impact of APS on risk of childhood arterial and venous TE via meta-analysis of published observational studies. Methods: A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2010 was conducted using key words in combination both as MeSH terms and text words. Citations were independently screened by two authors and those meeting the a priori defined inclusion criteria were retained. Data on year of publication, study design, laboratory methodologies, country of origin, number of patients/controls, ethnicity, type and location of TE were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed-effects and random-effects models. Results: Eight of 319 (DVT) and seven out of 185 (arterial TE) references found met inclusion criteria: In total 1403 patients and 1904 population-based controls aged neonate to 18 years were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. In addition, regression analysis did not reveal statistical significant differences between locations of TE, age at first disease onset, study country, or publication year. Thus, data from arterial and venous TE were analyzed together. A statistically significant association with a first TE onset was demonstrated with a cumulative summary ORs/CIs (fixed-effects model) of 5.9/3.6-9.7. Conclusions: The present meta-analysis indicates that APS serves as a clinical meaningful risk factor for a first symptomatic TE in children. However, the impact of APS upon outcome and recurrence risk needs to be further investigated. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
F Bala ◽  
B Beland ◽  
A Ganesh

Background: Practice-changing trials of endovascular thrombectomy (EVT) for acute stroke excluded patients with pre-morbid disability. Observational studies may inform the role of EVT in this population. We performed a meta-analysis to estimate the effect of EVT in patients with pre-morbid disability. Methods: We adhered to PRISMA guidelines and searched Medline and Embase for studies describing EVT in adults with and without pre-morbid disability with stroke. Random-effects meta-analysis was used to pool outcomes, including favorable outcomes (mRS=0-2 or return to baseline), no increase in disability at 90 days, symptomatic ICH (sICH) and 90-day mortality. Results: We included 8 studies with 5570 patients (mRS 3-5=863, mRS 0-2=4,707). Patients with pre-morbid disability were more likely to return to their baseline mRS (aOR 2.53, 95% CI=1.47-4.36), although they had higher 90-day mortality (aOR=2.21, 95% CI=1.66-2.93). aOR for favorable outcome (aOR=0.83, 95% CI=0.67-1.03) or sICH (aOR=1.07, 95% CI=0.74-1.54) was not significantly different between groups. Conclusions: Observational studies suggest that EVT is safe in patients with pre-stroke disability and may result in comparable return to pre-stroke status as in patients without such disability. These findings argue against the routine exclusion of patients with pre-morbid disability from EVT and merit validation with randomized controlled trials.


2020 ◽  
pp. jim-2020-001588
Author(s):  
Ziba Majidi ◽  
Shaghayegh Hosseinkhani ◽  
Nasrin Amiri-Dashatan ◽  
Solaleh Emamgholipour ◽  
Sara Tutunchi ◽  
...  

Patients with type 2 diabetes have high levels of malondialdehyde (MDA), and clinical data suggest a reducing effect of rosiglitazone (RSG) on the level of MDA in these patients. However, the results of available studies on the level of MDA in RSG-treated patients are not univocal. This meta-analysis aimed to assess the impact of RSG on the level of MDA. We performed a comprehensive search of PubMed, the Institute for Scientific Information Web of Science, Embase, Scopus, and Cochrane Library for related controlled trials until July 2020. Eligible studies were selected based on the inclusion criteria. Extracted data from each study were combined using a random-effects model. Sensitivity and subgroup analyses were conducted to explore potential heterogeneity. Eight trials with 456 subjects met the inclusion criteria. The results significantly showed the reducing effect of RSG on circulating MDA level (−0.47 μmol/mL; 95% CI −0.93 to −0.01; p=0.04; I2=82.1%; p heterogeneity=0.00) in individuals with T2D. No publication bias was observed with Begg’s rank correlation (p=0.71) and Egger’s linear regression (p=0.52) tests. Subgroup analyses showed that an intervention dose of 8 mg/day in serum samples was found to have a reducing effect on the level of MDA (−0.56 μmol/mL; 95% CI −0.98 to −0.14; p=0.008; I2=11.4%; p heterogeneity=0.32). Random-effects meta-regression did not show any significant association between the level of MDA and potential confounders including RSG dose, treatment duration, and sex. In conclusion, we found a significant reduction in MDA concentration in subjects with T2D who received a dose of 8 mg of RSG daily.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3189-3189 ◽  
Author(s):  
Guy Young ◽  
Frauke Friedrichs ◽  
Anthony Chan ◽  
Gili Kenet ◽  
Paolo Simioni ◽  
...  

Abstract Background: Inherited thrombophilia (IT) has been described as a risk factor for venous thromboembolism (VTE) in children. So far the majority of studies performed in the field were either retrospective or prospective on small numbers of patients. Thus, the results are contradictory or inconclusive mainly due to lack of statistical power. The aim of this study was to better estimate the impact of IT on early VTE onset and recurrence in children as a prerequisite to develop primary and secondary treatment options. Methods: A systematic search of publications listed in the electronic databases (Pubmed, Medline, EMBASE, Web of Science, The Cochrane Library) up to August 2007 using key words in combination both as MeSH terms and text words, was conducted. Citations were screened by two independent group members and those meeting the inclusion criteria were retained. Articles were included if published after 1990, when pediatric VTE was started to be systematically investigated. Findings: Twenty case-control and 17 cohort studies from 13 countries met the inclusion criteria. In these studies > 70% of patients had at least one clinical risk factor. The summary odds ratios (OR) and 95% confidence intervals (CI) of included studies under a fixed-effects and random-effects model showed statistically significant associations between the IT traits investigated and VTE onset (table). For the rare event of VTE recurrence, 1227 patients (eight studies) were evaluated: at the present state due to high heterogeneity, a trend towards association with recurrent VTE was found for ≥2 IT traits in the fixed-effects model (0R/CI: 2.8/1.6–4.8). Interpretation: The present meta-analysis gives evidence that the detection of inherited thrombophilia is clincially meaningful in children with VTE and underlines the importance of a pediatric thrombophilia screening program. Summary of Data Risk Factors OR/CI:fixed model OR/CI:random model patients/controls 2470/4119 N/A FV G1691A 3.5/2.9–4.2 3.2/2.3–4.4 FII G20210A 2.2/1.5–3.3 2.2/1.5–3.4 Protein C defiiciency 9.8/5.9–16 9.9/6.1–16.1 Protein S deficiency 7.1/3.9–13.2 6.8/3.7–12.7 Antithrombin deficiency 7.9/3.8–16.6 7.3/3.4–15.3 Lipoprotein(a) 4.4/3,2–5.9 4/2.4–6.6 ≥ 2 risk factors 12.6/7.3–21.8 11.6/6.2–20.2


2022 ◽  
Author(s):  
Miao He ◽  
◽  
Zhaoqiong Zhu ◽  
Min Jiang ◽  
Xingxing Liu ◽  
...  

Review question / Objective: Patientor population: patients with emergence delirium; Exposure: anaesthesia and surgery; Control: patients with no emergence delirium; Outcome: risk factors; Study design: meta-analysis. Eligibility criteria: To ensure the quality of this meta-analysis, inclusion criteria was decided before we carried out the search. These criteria were: (a) Original researches that carried out in observational studies. (b)Adult patients who were extubated and recovered at PACU, operation room, or intensive care unit (ICU) after surgeries and anesthesia (including general and neuraxial anesthesia, peripheral nerve blocks and sedation). (c) Risk factors for delirium must be assessed with odds ratio (OR) with 95% confidence interval (CI). Researches must present the results of multivariate regression to be considered eligible for inclusion, since multivariate analysis results shall be used to identify variables eligible for meta-analysis. (d) Full-text available literatures.


2019 ◽  
Vol 25 ◽  
pp. 107602961986950 ◽  
Author(s):  
Beata Sarecka-Hujar ◽  
Ilona Kopyta ◽  
Michał Skrzypek

The role of genetic risk factors for ischemic stroke seems to be in particular significance in pediatric patients. Numerous polymorphic variants of genes encoding proteins, that is, plasminogen activator inhibitor as well as coagulation factors, involved in the coagulation cascade may be related to arterial ischemic stroke (AIS) both in adults and children. We performed systematic review and 2 meta-analyses to assess possible correlations between common plasminogen activator inhibitor ( PAI-1) and FXIII polymorphisms and ischemic stroke in children. We searched PubMed to identify available data published before October 2018 using appropriate keywords and inclusion criteria. Finally, 12 case–control studies were included: 8 analyzing PAI-1 polymorphism (600 children with stroke and 2152 controls) and 4— FXIII polymorphism (358 children with stroke and 451 controls). R and Comprehensive Meta-Analysis software were used to analyze the impact of the particular polymorphism in the following models: dominant, recessive, additive, and allelic. No publication bias was observed in both meta-analyses. In case of PAI-1 polymorphism, we observed no relation between 4G4G genotype of 4G allele and ischemic stroke in children. We also demonstrated lack of association between FXIII polymorphism and childhood ischemic stroke. In children with AIS, the PAI-1 and FXIII polymorphisms are not risk factors for the disease.


2021 ◽  
Author(s):  
Sitian Ma ◽  
Xiaoxuan Fan ◽  
Xiaoping Zhao ◽  
Kai Wang ◽  
Huan Wang ◽  
...  

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e039358
Author(s):  
Suhairul Sazali ◽  
Salziyan Badrin ◽  
Mohd Noor Norhayati ◽  
Nur Suhaila Idris

ObjectiveTo determine the effects of coenzyme Q10 (CoQ10) for reduction in the severity, frequency of migraine attacks and duration of headache in adult patients with migraine.DesignSystematic review and meta-analysis.Data sourcesCochrane Central Register of Controlled Trials, CENTRAL, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Psychological Information Database (PsycINFO) from inception till December 2019.Study selectionAll randomised control trials comparing CoQ10 with placebo or used as an adjunct treatment included in this meta-analysis. Cross-over designs and controlled clinical trials were excluded.Data synthesisHeterogeneity at face value by comparing populations, settings, interventions and outcomes were measured and statistical heterogeneity was assessed by means of the I2 statistic. The treatment effect for dichotomous outcomes were using risk ratios and risk difference, and for continuous outcomes, mean differences (MDs) or standardised mean difference; both with 95% CIs were used. Subgroup analyses were carried out for dosage of CoQ10 and if CoQ10 combined with another supplementation. Sensitivity analysis was used to investigate the impact risk of bias for sequence generation and allocation concealment of included studies.ResultsSix studies with a total of 371 participants were included in the meta-analysis. There is no statistically significant reduction in severity of migraine headache with CoQ10 supplementation. CoQ10 supplementation reduced the duration of headache attacks compared with the control group (MD: −0.19; 95% CI: −0.27 to −0.11; random effects; I2 statistic=0%; p<0.00001). CoQ10 usage reduced the frequency of migraine headache compared with the control group (MD: −1.52; 95% CI: −2.40 to −0.65; random effects; I2 statistic=0%; p<0.001).ConclusionCoQ10 appears to have beneficial effects in reducing duration and frequency of migraine attack.PROSPERO registration numberCRD42019126127.


Heart ◽  
2020 ◽  
pp. heartjnl-2020-317901
Author(s):  
SungA Bae ◽  
So Ree Kim ◽  
Mi-Na Kim ◽  
Wan Joo Shim ◽  
Seong-Mi Park

ObjectivePrevious studies that evaluated cardiovascular risk factors considered age as a potential confounder. We aimed to investigate the impact of cardiovascular disease (CVD) and its risk factors on fatal outcomes according to age in patients with COVID-19.MethodsA systematic literature review and meta-analysis was performed on data collected from PubMed and Embase databases up to 11 June 2020. All observational studies (case series or cohort studies) that assessed in-hospital patients were included, except those involving the paediatric population. Prevalence rates of comorbid diseases and clinical outcomes were stratified by mean patient age in each study (ranges: <50 years, 50–60 years and ≥60 years). The primary outcome measure was a composite fatal outcome of severe COVID-19 or death.ResultsWe included 51 studies with a total of 48 317 patients with confirmed COVID-19 infection. Overall, the relative risk of developing severe COVID-19 or death was significantly higher in patients with risk factors for CVD (hypertension: OR 2.50, 95% CI 2.15 to 2.90; diabetes: 2.25, 95% CI 1.89 to 2.69) and CVD (3.11, 95% 2.55 to 3.79). Younger patients had a lower prevalence of hypertension, diabetes and CVD compared with older patients; however, the relative risk of fatal outcomes was higher among the former.ConclusionsThe results of the meta-analysis suggest that CVD and its risk factors (hypertension and diabetes) were closely related to fatal outcomes in COVID-19 for patients across all ages. Although young patients had lower prevalence rates of cardiovascular comorbidities than elderly patients, relative risk of fatal outcome in young patients with hypertension, diabetes and CVD was higher than in elderly patients.Prospero registration numberCRD42020198152.


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