Background
The impact of COVID-19 on clinical outcomes in acute ischemic stroke patients receiving reperfusion therapy remains unclear. We therefore aimed to synthesize the available evidence to ...investigate the safety and short-term efficacy of reperfusion therapy in this patient population.
Methods
We searched the electronic databases MEDLINE, Embase and Cochrane Library Reviews for randomized controlled trials and observational studies that investigated the use of intravenous thrombolysis, endovascular therapy, or a combination of both in acute ischemic stroke patients with laboratory-confirmed COVID-19, compared to controls. Our primary safety outcomes included any intracerebral hemorrhage (ICH), symptomatic ICH and all-cause in-hospital mortality. Short-term favorable functional outcomes were assessed at discharge and at 3 months. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using DerSimonian and Laird random-effects model. Heterogeneity was evaluated using Cochran’s Q test and
I
2
statistics.
Results
We included 11 studies with a total of 477 COVID-19 positive and 8,092 COVID-19 negative ischemic stroke patients who underwent reperfusion therapy. COVID-19 positive patients exhibited a significantly higher risk of experiencing any ICH (RR 1.54, 95% CI 1.16–2.05,
p
< 0.001), while the nominally increased risk of symptomatic ICH in these patients did not reach statistical significance (RR 2.04, 95% CI 0.97–4.31;
p
= 0.06). COVID-19 positive stroke patients also had a significantly higher in-hospital mortality compared to COVID-19 negative stroke patients (RR 2.78, 95% CI 2.15–3.59,
p
< 0.001). Moreover, COVID-19 positive stroke patients were less likely to achieve a favorable functional outcome at discharge (RR 0.66, 95% CI 0.51–0.86,
p
< 0.001) compared to COVID-19 negative patients, but this difference was not observed at 3-month follow-up (RR 0.64, 95% CI 0.14–2.91,
p
= 0.56).
Conclusion
COVID-19 appears to have an adverse impact on acute ischemic stroke patients who undergo reperfusion therapy, leading to an elevated risk of any ICH, higher mortality and lower likelihood of favorable functional outcome.
Systematic review registration
PROSPERO
, identifier CRD42022309785.
Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has ...been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain.
Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis.
Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval 1.31; 12.82) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects.
Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients' comorbidities and co-medication.
Ischemic stroke is one of the leading causes for death and disability worldwide. In patients with large space-occupying infarction, the subsequent edema complicated by transtentorial herniation poses ...a lethal threat. Especially in patients with malignant middle cerebral artery infarction, brain swelling secondary to the vessel occlusion is associated with high mortality. By decompressive craniectomy, a significant proportion of the skull is surgically removed, allowing the ischemic tissue to shift through the surgical defect rather than to the unaffected regions of the brain, thus avoiding secondary damage due to increased intracranial pressure. Several studies have shown that decompressive craniectomy reduces the mortality rate in patients with malignant cerebral artery infarction. However, this is done for the cost of a higher proportion of patients who survive with severe disability. In this review, we will describe the clinical and radiological features of malignant middle cerebral artery infarction and the role of decompressive craniectomy and additional therapies in this condition. We will also discuss large cerebellar stroke and the possibilities of suboccipital craniectomy.
Objective
To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19).
Methods
In a retrospective multicenter study, we retrieved ...individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis.
Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran’s
Q
and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity.
Results
Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without RR 2.07, 95% confidence interval (CI) 1.52–2.81;
p
< 0.0001. This association was also observed in clusters of studies that defined severe manifestation of the disease by clinical parameters (RR 1.44, 95% CI 1.22–1.71;
p
< 0.0001), necessity of intensive care (RR 2.79, 95% CI 1.83–4.24;
p
< 0.0001) and in-hospital death (RR 2.18, 95% CI 1.75–2.7;
p
< 0.0001).
Conclusion
A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19 suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.
Recent exploratory analysis suggested comparable outcomes among stroke patients undergoing endovascular therapy (EVT) for anterior circulation large vessel occlusion, whether selected via the ...telestroke network or admitted directly to an EVT-capable centre. We further studied the role of telemedicine in selection of ischaemic stroke patients potentially eligible for EVT.
We prospectively included consecutive ischaemic stroke patients with anterior circulation large vessel occlusion who underwent EVT at our neurovascular centre (January 2016 to March 2018). We compared safety and efficacy including symptomatic intracerebral haemorrhage (sICH), successful reperfusion (mTICI 2b/3), 90-day favourable outcome (mRS ≤ 2) and 90-day survival between patients transferred from telestroke hospitals and patients directly admitted.
Of 280 potentially EVT-eligible patients, 72/129 (56%) telestroke and 91/151 (60%) direct admissions eventually underwent EVT (age 76 (66-82) years, median (interquartile range), 46% men, NIHSS score 17 (13-20)). Telestroke patients had larger pre-EVT infarct cores (ASPECTS: 7 (6-8)
. 8 (7-9);
< 0.0001) and shorter door-to-groin puncture times (71 (56-84)
. 101 (79-133) min;
< 0.0001) than directly admitted patients. sICH (2.8%
. 1.1%;
= 0.58), successful reperfusion (81%
. 77%;
= 0.56), 90-day favourable outcome (25%
. 29%;
= 0.65) and 90-day survival (73%
. 67%;
= 0.39) rates were comparable among telestroke and direct admissions.
Our data underpins the important role of telemedicine in identifying acute ischaemic stroke patients lacking immediate access to EVT-capable stroke centres. Stroke patients selected via telemedicine and those directly admitted had comparable chances of favourable outcomes after EVT for large vessel occlusion.
A systematic review and meta-analysis was conducted to investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents.
Major ...databases (PubMED, EMBASE, Cochrane Central Register of Controlled Trials), systematic snowballing, and trial registries were screened from the inception dates until September 2017.
Comparative studies involving reproductive-aged women undergoing chemotherapy with or without coadministration of GnRHa were included. Spontaneous menstrual resumption was assessed as a main outcome. Statistical analyses were performed with STATA 14.2 statistical software. Effect estimates were presented as risk ratios (RR) with 95% confidence intervals (CIs).
The literature search yielded 25 436 citations and 84 papers were assessed in full text. Eighteen studies (11 randomized controlled trials RCTs and 7 cohort studies) published between 1987 and 2015 were included in the analysis, revealing a significant protective effect of GnRHa (n = 1043; RR:1.38; 95% CI: 1.18-1.63) although with high heterogeneity (I
= 83.3%). Subgroup analyses revealed a significant benefit of GnRHa cotreatment both in RCTs and in cohort studies. Statistical significance was found in all subgroups by the underlying disease, that is, hematological malignancies, autoimmune diseases, and breast cancer. Sensitivity analyses in GnRH agonist-treated patients, in patients younger than 40 years old, and in patients without supradiaphragmatic radiotherapy also revealed a significant benefit of GnRHa cotreatment.
Our results indicate that concurrent GnRHa administration is an effective method to decrease gonadotoxicity of alkylating agents. The presence of low-quality evidence favoring gonadoprotective effect requires a strong recommendation for offering GnRHa coadministration to young women who are to undergo gonadotoxic chemotherapy.
The present systematic review and meta-analysis shows a significant gonadoprotective effect of gonadotropin-releasing hormone analogs in women treated with alkylating agents.
To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for ...nonvalvular atrial fibrillation (NVAF).
We evaluated consecutive patients with NVAF with nontraumatic, anticoagulant-related ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA- or DOAC-related ICH.
We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.6 ± 9.8 years, 57.8% men, median admission NIH Stroke Scale NIHSS
score 13 points, interquartile range 6-21). DOAC-related (n = 47) and VKA-related (n = 114) ICH did not differ in demographics, vascular risk factors, HAS-BLED and CHA
DS
-VASc scores, and antiplatelet pretreatment except for a higher prevalence of chronic kidney disease in VKA-related ICH. Patients with DOAC-related ICH had lower median NIHSS
scores (8 3-14 vs 15 7-25 points,
= 0.003), median baseline hematoma volume (12.8 4-40 vs 24.3 11-58.8 cm
,
= 0.007), and median ICH score (1 0-2 vs 2 1-3 points,
= 0.049). Severe ICH (>2 points) was less prevalent in DOAC-related ICH (17.0% vs 36.8%,
= 0.013). In multivariable analyses, DOAC-related ICH was independently associated with lower baseline hematoma volume (
= 0.006), lower NIHSS
scores (
= 0.022), and lower likelihood of severe ICH (odds ratio OR 0.34, 95% confidence interval CI 0.13-0.87,
= 0.025). In meta-analysis of eligible studies, DOAC-related ICH was associated with lower baseline hematoma volumes on admission CT (standardized mean difference = -0.57, 95% CI -1.02 to -0.12,
= 0.010) and lower in-hospital mortality rates (OR = 0.44, 95% CI 0.21-0.91,
= 0.030).
DOAC-related ICH is associated with smaller baseline hematoma volume and lesser neurologic deficit at hospital admission compared to VKA-related ICH.
We studied the association of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large-vessel occlusion and functional outcome and scrutinized its dependence on ...grade of reperfusion and distal thrombus migration.
We included consecutive patients with anterior circulation large-vessel occlusion from our prospective registry of thrombectomy-eligible patients treated from January 1, 2017 to January 1, 2023 at a tertiary stroke center in Germany in this retrospective cohort study. To evaluate the association of bridging IVT and functional outcome quantified via modified Rankin Scale score at 90 days we used multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset-to-recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching. In our study population of 1000 thrombectomy-eligible patients (513 women; median age, 77 years interquartile range, 67-84), IVT emerged as a predictor of favorable functional outcome (modified Rankin Scale score, 0-2) independent of modified mTICI score (adjusted odds ratio, 0.49 95% CI, 0.32-0.75;
=0.001). In those who underwent thrombectomy (n=812), the association of IVT and favorable functional outcome was reproduced (adjusted odds ratio, 0.49 95% CI, 0.31-0.74;
=0.001) and was further confirmed on propensity score analysis, where IVT led to a 0.35-point decrease in 90-day modified Rankin Scale score (ß=-0.35 95 CI%, -0.68 to 0.01;
=0.04). The additive benefit of IVT remained independent of modified mTICI score (ß=-1.79 95% CI, -3.43 to -0.15;
=0.03) and distal thrombus migration (ß=-0.41 95% CI, -0.69 to -0.13;
=0.004) on interaction analysis. Consequently, IVT showed an additive association with functional outcome in the subpopulation of patients undergoing thrombectomy who achieved successful reperfusion (mTICI ≥2b; ß=-0.46 95% CI, -0.74 to -0.17;
=0.002) and remained beneficial in those with unsuccessful reperfusion (mTICI ≤2a; ß=-0.47 95% CI, -0.96 to 0.01;
=0.05).
In thrombectomy-eligible patients with anterior circulation large-vessel occlusion, IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.
Background:
Neuroprotective and neurorestorative effects have been postulated for selective serotonin-reuptake inhibitors (SSRI). We hypothesized that sertraline, which is characterized by less ...severe adverse effects and more stable pharmacokinetics than classic SSRI, is associated with improved functional recovery in acute ischemic stroke patients with motor deficits.
Methods:
Prospective observational study of consecutive acute ischemic stroke patients who received sertraline for clinically suspected post-stroke depression (PSD) or at high risk for PSD. Eligibility comprised acute motor deficit caused by ischemic stroke (≥2 points on NIHSS motor items) and functional independence pre-stroke (mRS ≤1). Decision to initiate treatment with SSRI during hospital stay was at the discretion of the treating stroke physician. Patients not receiving sertraline served as control group. Favorable functional recovery defined as mRS ≤2 was prospectively assessed at 3 months. Multivariable logistic regression analysis was used to explore the effects of sertraline on 3-months functional recovery. Secondary outcomes were frequency of any and incident PSD (defined by BDI ≥10) at 3 months.
Results:
During the study period (03/2017–12/2018), 114 patients were assigned to sertraline (
n
= 72, 62.6%) or control group (
n
= 42, 37.4%). At study entry, patients in sertraline group were more severely neurologically affected than patients in the control group (NIHSS: 8 IQR, 5–11 vs. 5 IQR, 4–7;
p
= 0.002). Also, motor NIHSS scores were more pronounced in sertraline than in control group (4 IQR 2–7 vs. 2 IQR 2–4,
p
= 0.001). After adjusting for age and baseline NIHSS, multivariable regression analysis revealed a significant association between sertraline intake and favorable functional outcome at 3 months (OR 3.10, 95% CI 1.02–9.41;
p
= 0.045). There was no difference between both groups regarding the frequency of any depression at 3 months (26/53 49.1% vs. 14/28 50.0% patients,
p
= 0.643, BDI ≥10). However, fewer incident depressions were observed in sertraline group patients compared to patients in control group (0/53 0% vs. 5/28 17.9% patients,
p
= 0.004).
Conclusions:
In this non-randomized comparison, early treatment with sertraline tended to favor functional recovery in patients with acute ischemic stroke. While exploratory in nature, this hypothesis needs further investigation in a clinical trial.
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