Increased risk of acute stroke among patients with severe COVID‐19: a multicenter study and meta‐analysis

Introduction: Recent studies linked coronavirus disease 2019 (COVID-19) to thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment. Objective: We aimed to assess the risk of acute stroke in patients with COVID-19 related to clinical severity of the disease. Methods: We conducted an observational multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we performed a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified articles following PRISMA guidelines including data from observational studies of acute stroke in COVID-19 patients. Data was extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RR) and 95% confidence intervals (95%CIs) for acute stroke related to COVID-19 severity using random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I 2 -statistics. PROSPERO identifier : CRD42020187194. Results: Of 165 patients hospitalized for COVID-19 (49.1% males, median age 67 [57-79], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95%CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Among 741 pooled COVID-19 patients overall stroke rate was 2.9% (95%CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR 4.12, 95%CI 1.7-10.25; p=0.002) with no evidence of heterogeneity (I 2 =0%, p=0.82). Conclusions: Synthesized analysis of data from our multicenter study and previously published cohorts demonstrate that severity of COVID-19 is associated with an increased risk of acute stroke, underscoring the necessity of neurological monitoring in patients infected with SARS-CoV-2.

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A Systematic Review and Meta-Analysis of Molecular Biomarkers Associated with Early Neurological Deterioration Following Acute Stroke

Cerebrovascular Diseases ◽

10.1159/000495572 ◽

2018 ◽

Vol 46 (5-6) ◽

pp. 230-241 ◽

Cited By ~ 10

Author(s):

Alexander J. Martin ◽

Christopher I. Price

Keyword(s):

Ischaemic Stroke ◽

Acute Stroke ◽

Fixed Effects ◽

Meta Analysis ◽

Density Lipoprotein ◽

High Sensitivity ◽

Neurological Status ◽

Neurological Deterioration ◽

Increased Risk ◽

Early Neurological Deterioration

Background: Early neurological deterioration (END) following acute stroke is associated with poorer long-term outcomes. Identification of patients at risk could assist early monitoring and treatment decisions. This review summarised the evidence describing non-radiological biomarkers for END. Summary: Electronic searches from January 1990 to March 2017 identified studies reporting a blood/cerebrospinal fluid (CSF)/urine biomarker measurement within 24 h of acute stroke and at least 2 serial assessments of clinical neurological status (< 24 h and < 7 days). Out of 12,895 citations, 82 studies were included, mostly focusing on ischaemic stroke. Using higher neurological thresholds, the n-weighted END incidence for ischaemic stroke was 11.9% (95% CI 11.4–12.4%) and 18.6% (17.9–19.2%) for lower thresholds. Incidence decreased with advancing study publication year (Pearson r-squared 0.23 and 0.15 for higher and lower threshold studies). After classification into 3 broad categories, meta-analysis showed that biomarkers associated with increased END risk (n; fixed-effects mean difference; 95% CI) were “metabolic” (glucose [n = 9,481; 0.90 mmol/L; 0.74–1.06], glycosylated haemoglobin [n = 3,146; 0.33%; 0.19–0.46], low-density lipoprotein [n = 4,839; 0.13 mmol/L; 0.06–0.21], total cholesterol [n = 4,762; 0.21 mmol/L; 0.11–0.31], triglycerides [n = 4,820; 0.11 mmol/L; 0.06–0.17], urea [n = 1,351; 0.55 mmol/L; 0.14–0.96], decreasing albumin [n = 513; 0.33 g/dL; 0.05–0.61]); “inflammatory and excitotoxic” (plasma glutamate [n = 688; 60.13 µmol/L; 50.04–70.22], CSF glutamate [n = 369; 7.50 µmol/L; 6.76–8.23], homocysteine [n = 824; 2.15 µmol/L; 0.68–3.61], leucocytes [n = 3,766; 0.54 × 109/L; 0.34–0.74], high-sensitivity C-reactive protein [n = 1,707; 3.79 mg/L; 1.23–6.35]); and “coagulation/haematological” (fibrinogen [n = 3,132; 0.32 g/L; 0.25–0.40]; decreasing haemoglobin [n = 3,586; 2.38 g/L; 0.15–4.60]). Key Messages: Declining incidence of END may represent improving care standards; however, it remains a frequent occurrence. Although statistical associations exist between biomarkers and an increased risk of END, the most promising still need prospective evaluation to determine their additional value relative to baseline radiological and clinical characteristics.

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Micro-Embolic Signals and Dissection: Association or Causation for Stroke? A Systematic Review and Meta-Analysis

Cerebrovascular Diseases ◽

10.1159/000519553 ◽

2021 ◽

pp. 1-8

Author(s):

Pachipala Sudheer ◽

Deepti Vibha

Keyword(s):

Systematic Review ◽

Acute Stroke ◽

Meta Analysis ◽

Small Population ◽

Cochrane Library ◽

Artery Dissection ◽

Cervical Artery Dissection ◽

Pooled Prevalence ◽

Increased Risk ◽

Embolic Signals

Background and Objective: Although the mechanism of stroke in cervical artery dissection (CAD) has been hypothesized to be embolization rather than hemodynamic compromise, there are a limited number of studies supporting this hypothesis. Detection of micro-embolic signals (MESs) using transcranial Doppler (TCD) helps in understanding the mechanism in these patients. A systematic review and meta-analysis were performed to estimate the prevalence of MES and its association with stroke outcomes in patients with acute stroke/TIA secondary to dissection. Methods: A comprehensive literature search was conducted for studies before January 26, 2021, in PubMed, Embase, Google Scholar, Cochrane Library, and ClinicalTrials.gov. Studies were identified that used TCD to detect MES in stroke/TIA patients secondary to CAD. Pooled prevalence was calculated. Entire statistical analysis was conducted in R version 3.6.2. Results: Eleven studies involving 112 patients (50 MES+, 62 MES−) were included in our meta-analysis. The pooled prevalence of MES among acute stroke/TIA patients secondary to dissection was 46.0% (95% CI 26.0–67.0%). The presence of MES was associated with an increased risk of early ischemic recurrence in patients with CAD. We could not estimate the functional outcome and mortality associated with the presence of MES due to the scarcity of data. Conclusions: Our meta-analysis showed 46% prevalence of MES in the studies which looked at acute stroke/TIA secondary to CAD using TCD. This finding supports the assumption that embolism may be a major cause of stroke in patients with dissection although this could be determined only in a small population.

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Impact of Dysphagia Assessment and Management on Risk of Stroke-Associated Pneumonia: A Systematic Review

Cerebrovascular Diseases ◽

10.1159/000492730 ◽

2018 ◽

Vol 46 (3-4) ◽

pp. 97-105 ◽

Cited By ~ 10

Author(s):

Sabrina A. Eltringham ◽

Karen Kilner ◽

Melanie Gee ◽

Karen Sage ◽

Benjamin D. Bray ◽

...

Keyword(s):

Acute Stroke ◽

Acute Phase ◽

Primary Outcome ◽

Meta Analysis ◽

Limited Information ◽

Increased Risk ◽

Screening Protocol ◽

Screening Assessment ◽

Management Of Dysphagia ◽

Alternative Feeding

Background: Patients with dysphagia are at an increased risk of stroke-associated pneumonia. There is wide variation in the way patients are screened and assessed during the acute phase. The aim of this review was to identify the methods of assessment and management in acute stroke that influence the risk of stroke-associated pneumonia. Studies of stroke patients that reported dysphagia screening, assessment or management and occurrence of pneumonia during acute phase stroke were screened for inclusion after electronic searches of multiple databases from inception to November 2016. The primary outcome was association with stroke-associated pneumonia. Summary: Twelve studies of 87,824 patients were included. The type of dysphagia screening protocol varied widely across and within studies. There was limited information on what comprised a specialist swallow assessment and alternative feeding was the only management strategy, which was reported for association with stroke-associated pneumonia. Use of a formal screening protocol and early dysphagia screening (EDS) and assessment by a speech and language pathologist (SLP) were associated with a reduced risk of stroke-associated pneumonia. There was marked heterogeneity between the included studies, which precluded meta-analysis. Key Messages: There is variation in the assessment and management of dysphagia in acute stroke. There is increasing evidence that EDS and specialist swallow assessment by an SLP may reduce the odds of stroke-associated pneumonia. There is the potential for other factors to influence the incidence of stroke-associated pneumonia during the acute phase.

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European Stroke Organisation (ESO) guidelines on glycaemia management in acute stroke

European Stroke Journal ◽

10.1177/2396987317742065 ◽

2017 ◽

Vol 3 (1) ◽

pp. 5-21 ◽

Cited By ~ 4

Author(s):

Blanca Fuentes ◽

George Ntaios ◽

Jukka Putaala ◽

Brenda Thomas ◽

Guillaume Turc ◽

...

Keyword(s):

Glycaemic Control ◽

Acute Stroke ◽

Meta Analysis ◽

Standard Operating Procedure ◽

Haemorrhagic Stroke ◽

Tight Glycaemic Control ◽

Stroke Patients ◽

Intravenous Insulin ◽

Increased Risk ◽

Guideline Document

Background Hyperglycaemia is a frequent complication in acute stroke that has been shown to be independently associated with larger infarct size, haematoma growth, poor clinical outcome and mortality. This Guideline Document presents the European Stroke Organisation (ESO) Guidelines for the management of blood glucose levels in patients with acute ischemic or haemorrhagic stroke. Methods The working group identified related questions and developed its recommendations based on evidence from randomised controlled trials following the standard operating procedure of the ESO. This Guideline Document was reviewed and approved by the European Stroke Organisation Guidelines Committee and the European Stroke Organisation Executive Committee. Results We found low-quality evidence from clinical trials in ischemic or haemorrhagic stroke exploring the use of intravenous insulin aimed to achieve a tight glycaemic control with different glucose level targets and several other sources of heterogeneity. None of these trials neither the meta-analysis of them have demonstrated any significant benefit of tight glycaemic control with intravenous insulin in acute ischemic or haemorrhagic stroke patients on functional outcome or in survival and they have shown an increased risk for hypoglycaemia. Conclusions We suggest against the routine use of tight glycaemic control with intravenous insulin as a means to improve outcomes. The currently available data about the management of glycaemia in patients with acute stroke are limited and the strengths of the recommendations are therefore weak. Nevertheless, this does not prevent that hyperglycaemia in acute stroke patients could be treated as any other hospitalised patient.

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Acupuncture Efficacy on Acute Stroke Patients: A Meta-analysis

Rehabilitation Medicine ◽

10.3724/sp.j.1329.2018.03062 ◽

2018 ◽

Vol 28 (3) ◽

pp. 62

Author(s):

Jiaqing LIU ◽

Tongyan LIU ◽

Yun XIANG ◽

Ning ZHAO ◽

Hong ZHANG

Keyword(s):

Acute Stroke ◽

Meta Analysis ◽

Stroke Patients

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Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis

Current Pharmaceutical Design ◽

10.2174/1381612826666200625110349 ◽

2020 ◽

Vol 26 (44) ◽

pp. 5739-5745

Author(s):

Jieqiong Guan ◽

Wenjing Song ◽

Pan He ◽

Siyu Fan ◽

Hong Zhi ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Major Bleeding ◽

Dual Antiplatelet Therapy ◽

Meta Analysis ◽

Cochrane Library ◽

Drug Eluting Stent ◽

Efficacy And Safety ◽

Risk Of Bleeding ◽

Increased Risk ◽

Drug Eluting

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

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The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis

Current Diabetes Reviews ◽

10.2174/1573399814666171215120228 ◽

2018 ◽

Vol 15 (1) ◽

pp. 31-43 ◽

Cited By ~ 6

Author(s):

Sayantan Nath ◽

Sambuddha Das ◽

Aditi Bhowmik ◽

Sankar Kumar Ghosh ◽

Yashmin Choudhury

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Meta Analysis ◽

Subsequent Development ◽

Asian Population ◽

Gstm1 Null Genotype ◽

Increased Risk

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.

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ctDNA as a prognostic factor in operable colon cancer patients: a systematic review and meta-analysis

Future Oncology ◽

10.2217/fon-2020-0671 ◽

2020 ◽

Author(s):

Emre Yekedüz ◽

Elif Berna Köksoy ◽

Hakan Akbulut ◽

Yüksel Ürün ◽

Güngör Utkan

Keyword(s):

Colon Cancer ◽

Prognostic Factor ◽

Cancer Patients ◽

Meta Analysis ◽

Circulating Tumor Dna ◽

Random Effects Model ◽

Inverse Variance ◽

Increased Risk ◽

Significant Step ◽

Tumor Dna

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on March 31, 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.

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Psychological interventions as an alternative and add-on to antidepressant medication to prevent depressive relapse: systematic review and meta-analysis

The British Journal of Psychiatry ◽

10.1192/bjp.2020.198 ◽

2020 ◽

pp. 1-8

Author(s):

Josefien Johanna Froukje Breedvelt ◽

Maria Elisabeth Brouwer ◽

Mathias Harrer ◽

Maria Semkovska ◽

David Daniel Ebert ◽

...

Keyword(s):

Psychological Intervention ◽

Meta Analysis ◽

Antidepressant Medication ◽

Cochrane Library ◽

Psychological Interventions ◽

Relapse Risk ◽

Increased Risk ◽

Antidepressant Use ◽

Randomised Controlled ◽

Risk Of Relapse

Background After remission, antidepressants are often taken long term to prevent depressive relapse or recurrence. Whether psychological interventions can be a viable alternative or addition to antidepressants remains unclear. Aims To compare the effectiveness of psychological interventions as an alternative (including delivered when tapering antidepressants) or addition to antidepressants alone for preventing depressive relapse. Method Embase, PubMed, the Cochrane Library and PsycINFO were searched from inception until 13 October 2019. Randomised controlled trials (RCTs) with previously depressed patients in (partial) remission where preventive psychological interventions with or without antidepressants (including tapering) were compared with antidepressant control were included. Data were extracted independently from published trials. A random-effects meta-analysis on time to relapse (hazard ratio, HR) and risk of relapse (risk ratio, RR) at the last point of follow-up was conducted. PROSPERO ID: CRD42017055301. Results Among 11 included trials (n = 1559), we did not observe an increased risk of relapse for participants receiving a psychological intervention while tapering antidepressants versus antidepressants alone (RR = 1.02, 95% CI 0.84–1.25; P = 0.85). Psychological interventions added to antidepressants significantly reduced the risk of relapse (RR = 0.85, 95% CI 0.74–0.97; P = 0.01) compared with antidepressants alone. Conclusions This study found no evidence to suggest that adding a psychological intervention to tapering increases the risk of relapse when compared with antidepressants alone. Adding a psychological intervention to antidepressant use reduces relapse risk significantly versus antidepressants alone. As neither strategy is routinely implemented these findings are relevant for patients, clinicians and guideline developers.

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