Opioid Antagonist in the Treatment of Ischemic Stroke

Stroke is a leading cause of death and disability, and novel treatments need to be found, particularly drugs with neuroprotective and restorative effects. Lately, there has been an increased interest in the relationship between opioids and ischemic stroke. To further appreciate this association between opioids and stroke, we conducted a systematic review to investigate anti-opioid medication’s effectiveness in treating ischemic stroke. We used PubMed advanced-strategy and Google Scholar searches and only included full-text clinical trials on humans and written in the English language. After applying the inclusion/exclusion criteria, seven clinical trials were reviewed. Only one of the naloxone and nalmefene clinical trials showed statistically favorable results. Overall, the nalmefene clinical trials used more updated measures (NIHSS, GOS) to evaluate recovery and functional status in ischemic stroke patients than the naloxone clinical trials. There was less bias in the nalmefene clinical trials. Animal and in vitro studies have showed promising results. Additional research should be conducted with new clinical trials of both drugs with larger samples in patients less than 70 years old and moderate to severe infarcts.

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Adverse Effects of Natural Products: A Brief Pre-Systematic Review

Current Nutraceuticals ◽

10.2174/2665978601999200702163914 ◽

2020 ◽

Vol 01 ◽

Author(s):

Carla Pires ◽

Ana Fernandes

Keyword(s):

Systematic Review ◽

Adverse Event ◽

Natural Products ◽

Adverse Events ◽

In Vitro Study ◽

Google Scholar ◽

Inclusion Criteria ◽

Exclusion Criteria ◽

Meta Analyses

Background: Natural products are commonly used for treating health problems. These products may be associated with adverse events, which are defined as "noxious and unintended response to a medicinal product" by the European Medicine Agency. Objectives: To identify studies describing at least one adverse event (or with potential to promote an adverse event) related to the use of natural products, as well as to describe the involved product(s) and adverse event(s). Methods: A pre-systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Keywords: "natural product(s)" and ["adverse drug reaction(s)" or "adverse effect(s)"]. Screened databases: PubMed, SciELO, DOAJ and Google Scholar. Inclusion criteria: papers describing at least one adverse event associated with the use of natural products and published between 2017 and 2019. Exclusion criteria: Repeated studies, reviews and papers written in other languages than English, Portuguese, French or Spanish. Results: 104 studies were identified (20 PubMed; 0 SciELO; 2 DOAJ; 82 Google Scholar), but only 10 were selected (4 PubMed and 6 Google Scholar): 1 in-vitro study; 2 non-clinical studies, 1 study reporting in-vitro and clinical data and 5 studies were cases reports. Globally, 997 reports of adverse drug reactions with natural products were identified, mainly non-severe cases. Conclusion: Since a limited number of studies was found, we conclude that adverse events due to natural products may be underreported, or natural products may have a good safety profile. This review contributes for assuring the safety of natural products consumers, by evaluating the knowledge/information on the potential adverse events and interactions of these products.

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Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

Biomolecules ◽

10.3390/biom11030347 ◽

2021 ◽

Vol 11 (3) ◽

pp. 347

Author(s):

Zsuzsa Bagoly ◽

Barbara Baráth ◽

Rita Orbán-Kálmándi ◽

István Szegedi ◽

Réka Bogáti ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Intravenous Thrombolysis ◽

Fibrin Clot ◽

Clot Lysis ◽

Stroke Patients ◽

Plasmin Inhibitor ◽

Fibrin Clots

Cross-linking of α2-plasmin inhibitor (α2-PI) to fibrin by activated factor XIII (FXIIIa) is essential for the inhibition of fibrinolysis. Little is known about the factors modifying α2-PI incorporation into the fibrin clot and whether the extent of incorporation has clinical consequences. Herein we calculated the extent of α2-PI incorporation by measuring α2-PI antigen levels from plasma and serum obtained after clotting the plasma by thrombin and Ca2+. The modifying effect of FXIII was studied by spiking of FXIII-A-deficient plasma with purified plasma FXIII. Fibrinogen, FXIII, α2-PI incorporation, in vitro clot-lysis, soluble fibroblast activation protein and α2-PI p.Arg6Trp polymorphism were measured from samples of 57 acute ischemic stroke patients obtained before thrombolysis and of 26 healthy controls. Increasing FXIII levels even at levels above the upper limit of normal increased α2-PI incorporation into the fibrin clot. α2-PI incorporation of controls and patients with good outcomes did not differ significantly (49.4 ± 4.6% vs. 47.4 ± 6.7%, p = 1.000), however it was significantly lower in patients suffering post-lysis intracranial hemorrhage (37.3 ± 14.0%, p = 0.004). In conclusion, increased FXIII levels resulted in elevated incorporation of α2-PI into fibrin clots. In stroke patients undergoing intravenous thrombolysis treatment, α2-PI incorporation shows an association with the outcome of therapy, particularly with thrombolysis-associated intracranial hemorrhage.

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Pre-Admission CHADS2 and CHA2DS2-VASc Scores on Early Neurological Worsening

Cerebrovascular Diseases ◽

10.1159/000513396 ◽

2021 ◽

pp. 1-8

Author(s):

Ki-Woong Nam ◽

Chi Kyung Kim ◽

Sungwook Yu ◽

Jong-Won Chung ◽

Oh Young Bang ◽

...

Keyword(s):

Ischemic Stroke ◽

Stroke Risk ◽

Multivariable Analysis ◽

National Institutes Of Health ◽

Risk Scores ◽

Stroke Patients ◽

Nihss Score ◽

Early Neurological Deterioration ◽

Close Relationship ◽

The Relationship

Background: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. Objective: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. Methods: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. Results: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04–1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04–1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01–1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. Conclusions: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.

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Abstract P683: Thrombin Generation in Plasma of Stroke Patients With Atrial Fibrillation

Stroke ◽

10.1161/str.52.suppl_1.p683 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Sarina Falcione ◽

Gina Sykes ◽

Joseph Kamtchum Tatuene ◽

Danielle Munsterman ◽

Twinkle Joy ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Thrombin Generation ◽

Thrombus Formation ◽

Lag Time ◽

Thrombin Time ◽

Stroke Patients ◽

Time To Peak ◽

Generation Capacity

Background and Purpose: Thrombus formation is central to pathophysiology of stroke in patients with atrial fibrillation. Whether factors in plasma contribute to thrombus generation in patients with atrial fibrillation remains unclear. In this study we sought to determine whether plasma contributes to thrombin generation in patients with atrial fibrillation. Methods: There were 78 acute ischemic strokes with atrial fibrillation and 37 non-stroke controls. Plasma thrombin generation was measured by thrombin generation assay, resulting lag time, peak thrombin, time to peak and area under the curve was assessed. Thrombin generation capacity was compared in stroke patients with atrial fibrillation to non-stroke controls. The relationship to anticoagulation was assessed. In vitro, the effect of anticoagulation on plasma thrombin generation was determined. Results: Thrombin generation capacity was increased (shorter lag time and time to peak) in ischemic stroke patients with atrial fibrillation compared to non-stroke atrial-fibrillation controls (p<0.05 and p<0.01, respectively). Anticoagulation decreased plasma induced thrombin generation. Ischemic stroke patients with atrial fibrillation treated with anticoagulation (DOAC or warfarin) had lower plasma induced thrombin generation compared to atrial-fibrillation patients not on anticoagulation (p<0.05). Thrombin generation by plasma could be further reduced by DOAC in an in-vitro assay. Conclusions: Stroke patients with atrial fibrillation have a higher plasma induced thrombin generation compared to atrial fibrillation controls. Factors in plasma such as leukocyte derived tissue factor likely contribute to thrombus formation in patients with atrial fibrillation. As such, components in plasma may represent new targets to reduce thrombus formation and stroke risk in patients with atrial fibrillation.

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Abstract 90: Socioeconomic Status Is Associated With Disability Following Acute Ischemic Stroke: Findings From The Adherence eValuation After Ischemic stroke-Longitudinal (AVAIL) Registry

Stroke ◽

10.1161/str.43.suppl_1.a90 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Janet Prvu Bettger ◽

Xin Zhao ◽

Cheryl Bushnell ◽

Louise Zimmer ◽

Ying Xian ◽

...

Keyword(s):

Socioeconomic Status ◽

Ischemic Stroke ◽

Household Income ◽

Work Status ◽

Stroke Patients ◽

Level Of Education ◽

Post Stroke ◽

Relationship Of ◽

The Relationship ◽

Education Work

Background: Socioeconomic status (SES) is widely recognized as an area of inequity that affects health outcomes. However, social determinants of health are less frequently measured in longitudinal studies of acute stroke patients. The relationship of SES on disability 3-months post-stroke is unknown. Methods: We analyzed ischemic stroke patients in the AVAIL registry who were enrolled at 98 hospitals participating in Get With The Guidelines-Stroke. Patients who died (n=64) or did not complete a modified Rankin Scale (mRS) at 3-months (n=154) were excluded. Multivariable logistic regression was used to examine the relationship of SES (defined by level of education, work status, and perceived adequacy of household income to meet needs) and disability (mRS scores 3-5). Results: Among the 2092 stroke patients who met eligibility criteria, the mean age was 65.5 ± 13.7, 44.2% were female, and 82.7% were White. Fifty seven percent had a high school or less education, 11.4% were not working post-stroke and were home not by choice, and 25.7% were without an adequate household income. A third of the sample had some level of disability at 3-months (34.6% mRS 3-5). Those with disability were more likely to be older, non-White, female, single, less educated, have inadequate income, and were home not by choice. In the multivariable analysis, lower education, inadequate income, and being home but not by choice (compared with those who returned to work) were independently associated with disability (p<0.01; Table ). Conclusion: In this national cohort of stroke survivors, socioeconomic status as measured by level of education, work status, and income were independently associated with post-stroke disability.

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The relationship between aortic stiffness and changes in retinal microvessels among Asian ischemic stroke patients

Journal of Human Hypertension ◽

10.1038/jhh.2011.88 ◽

2011 ◽

Vol 26 (12) ◽

pp. 716-722 ◽

Cited By ~ 13

Author(s):

D A De Silva ◽

◽

F-P Woon ◽

J J F Manzano ◽

E Y Liu ◽

...

Keyword(s):

Ischemic Stroke ◽

Aortic Stiffness ◽

Stroke Patients ◽

The Relationship

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HUBUNGAN PERDARAHAN GASTROINTESTINAL DENGAN LUARAN PASIEN STROKE ISKEMIK AKUT

Majalah Kedokteran Neurosains Perhimpunan Dokter Spesialis Saraf Indonesia ◽

10.52386/neurona.v36i2.58 ◽

2020 ◽

Vol 36 (2) ◽

Author(s):

Rico Defryantho ◽

Lisda Amalia ◽

Ahmad Rizal ◽

Suryani Gunadharma ◽

Siti Aminah ◽

...

Keyword(s):

Ischemic Stroke ◽

Length Of Stay ◽

Clinical Outcome ◽

Gastrointestinal Bleeding ◽

Acute Ischemic Stroke ◽

Stroke Patients ◽

Exclusion Criteria ◽

Risk Of Death ◽

History Of ◽

Gcs Score

ASSOCIATION BETWEEN GASTROINTESTINAL BLEEDING WITH CLINICAL OUTCOME ACUTE ISCHEMIC STROKE PATIENTABSTRACTIntroduction: Gastrointestinal bleeding associated by the delay in the administration of antiplatelet and anticoagulant, thus affected the clinical outcome and patient treatment.Aims: To find the association between gastrointestinal bleeding and clinical outcome in acute ischemic stroke patient.Methods: This study was a prospective observational, conducted at Hasan Sadikin Hospital Bandung in November 2017 to February 2018. Acute ischemic stroke patients that fulfill the inclusion and exclusion criteria were observed while being treated in the ward and the survival rate and length of stay were studied. This study used univariate, bivariate, multivariate, and stratification analysis.Results: In the study period, 100 acute ischemic stroke patients were found and 24 patients had gastrointestinal bleeding. A history of previous peptic ulcer/gastrointestinal bleeding was found in patient with gastrointestinal bleeding (20.8%). Median NIHSS score was higher (16 vs 7) and GCS score was lower (12 vs 15) in patients with bleeding. Multivariate analysis showed that gastrointestinal bleeding were significantly associated with survival and length of stay. The analysis of stratification showed subjects with infections who later experienced gastrointestinal bleeding had a lower risk of death and length of stay than subjects without infection who experienced gastrointestinal bleeding (1.7 vs 22.5 times and 1.5 vs 2 times).Discussion: Ischemic stroke with gastrointestinal bleeding had higher mortality and length of stay than without gastrointestinal bleeding in acute ischemic stroke patient.Keyword: Acute ischemic stroke, gastrointestinal bleeding, length of stay, mortalityABSTRAKPendahuluan: Perdarahan gastrointestinal berhubungan dengan penundaan terapi antiplatelet atau antikoagulan, sehingga berpengaruh terhadap luaran dan tata laksana pasien.Tujuan: Mengetahui hubungan perdarahan gastrointestinal dengan luaran pasien stroke iskemik akut.Metode: Penelitian prospektif observasional terhadap pasien stroke iskemik akut di RSUP Dr. Hasan Sadikin, Bandung pada bulan November 2017 hingga Februari 2018. Pasien stroke iskemik akut yang memenuhi kriteria inklusi dan eksklusi diobservasi selama perawatan untuk mengetahui survival dan lama perawatan di rumah sakit. Analisis statistik yang digunakan adalah univariat, bivariat, multivariat, dan stratifikasi.Hasil: Selama periode penelitian didapatkan 100 subjek stroke iskemik akut dengan 24 subjek mengalami perdarahan gastrointestinal. Riwayat ulkus peptikum/perdarahan gastrointestinal sebelumnya sebanyak 20,8% pada perdarahan gastrointestinal. Median skor NIHSS lebih tinggi (16 vs 7) dan skor GCS lebih rendah (12 vs 15) pada perdarahan. Analisis multivariat didapatkan perdarahan gastrointestinal memiliki hubungan signifikan dengan survival dan lama perawatan. Berdasarkan analisis stratifikasi subjek dengan infeksi yang kemudian mengalami perdarahan gastrointestinal memiliki risiko mortalitas dan lama perawatan lebih rendah dibandingkan subjek tanpa infeksi kemudian mengalami perdarahan gastrointestinal (1,7 vs 22,5 kali dan 1,5 vs 2 kali).Diskusi: Stroke iskemik akut yang mengalami perdarahan gastrointestinal memiliki risiko mortalitas dan lama perawatan lebih tinggi dibandingkan tanpa perdarahan gastrointestinal.Kata kunci: Lama perawatan, mortalitas, perdarahan gastrointestinal, stroke iskemik akut

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High serum non-high-density lipoprotein and the risk of ischemic stroke: A systematic review

Romanian Journal of Neurology ◽

10.37897/rjn.2021.1.2 ◽

2021 ◽

Vol 20 (1) ◽

pp. 15-20

Author(s):

Nyoman Tyas Apsari ◽

◽

Kumara Tini ◽

I Putu Eka Widyadharma ◽

◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

High Density Lipoprotein ◽

Large Population ◽

Density Lipoprotein ◽

High Serum ◽

High Density ◽

Inclusion Criteria ◽

Increased Risk ◽

The Relationship

Objectives. High levels of non high density lipoprotein cholesterol (non-HDL-C) are known to contribute to an increased risk of ischemic stroke. This systematic review was conducted to identify the relationship between high non-HDL-C levels and the risk of ischemic stroke. Material and methods. This systematic review using PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement guideline, with a pre-determined search strategy. The search was conducted in Pubmed Central (PMC) and Pubmed from 2009 until 2020 with inclusion criteria, patients with a diagnosis of ischemic stroke, age >18 years, with non-HDL-C levels. The title and abstract of these articles were reviewed for relevance, based on inclusion criteria. This systematic review using STROBE to evaluate the quality in individual study which consists of 22 domains. Results. In the final stage, this systematic review identifies six cohort study consisting 166.720 participants. Overall, the quality in individual studies based on STROBE is good. We reported that there are two studies report that high non-HDL-C levels can significantly increase the risk of ischemic stroke. Meanwhile, there are four studies that report there was no significant relationship between high non-HDL-C levels and the risk of ischemic stroke. Conclusions. Overall, this systematic review provides the result about relationship between high levels of nonHDL-C and the risk of ischemic stroke, there are two studies with a larger population support that high levels of non-HDL-C can increase the risk of ischemic stroke. However, further studies is needed with a large population that specifically identify the relationship between non-HDL-C levels and risk of ischemic stroke and makes a better adjustments for confounding variables.

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Abstract TP24: Trends in Iv r-tpa and Thrombectomy Treatment Rates Before and After the LVO RCT’s in a Regional Tele-stroke Network

Stroke ◽

10.1161/str.48.suppl_1.tp24 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Naregnia Pierre Louis ◽

Suman Nalluri ◽

Benny Kim ◽

Aashish Anand ◽

Tanzila Shams ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Statistical Test ◽

Stroke Therapy ◽

Stroke Patients ◽

Chi Square ◽

The Third ◽

Before And After ◽

Acute Stroke Therapy

The presentation of endovascular stroke trials at international stroke conference was a land mark event in acute stroke therapy. This study aims to analyze the rates of utilization of IV r-tPA, with or without mechanical thrombectomy before and after the 2015 International Stroke Conference (ISC) in a large regional tele-stroke network. Methods: A systematic review of prospective telestroke and procedure database was performed for 18 months prior and 18 months post conference. There were three groups included in the analysis. The first group consisted ischemic stroke patients presented within 12 hours of onset including inpatient events, transfers from primary centers and rural clinics. The second group consisted of patients who received IV r-tPA, and the third group consisted of patients who received IV r-tPA and/or underwent mechanical thrombectomy for a demonstrated LVO. Results: A total of 2628 consecutive ischemic stroke events presented within 12 hours of onset were evaluated. In the pre-ISC conference group, there were 1135 ischemic stroke patients. IV r-tPA was given 535 times(47.1%) and mechanical thrombectomy was utilized in addition to IV r-tPA or alone 42 times(3.7%). In the post-ISC conference group, there were 1493 ischemic stroke patients. IV r-tPA was given 642 times(43%) and mechanical thrombectomy was utilized in addition to IV r-tPA or alone 132 times(8.84%). The Chi Square statistical test was performed comparing these groups. When comparing the rate of IV r-tPA usage, there was a significant decrease from the pre-ISC conference group to the post-ISC conference group (P= 0.04). When comparing the rate of mechanical thrombectomy performed, there was a significant increase of greater than double the percentage of thrombectomy procedures performed in the post conference group compared to the preconference group (p< 0.001). Conclusion: There was a significant decrease in IV r-tPA usage but a greater than double the increase in the thrombectomy rate . This may be secondary to increased awareness of benefit of thrombectomy at referral centers. Slightly lower rates of IV r-tPA usage may be secondary to an increase in transfers of patients outside of the 0-4.5 hr window but were deemed candidates for thrombectomy.

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Abstract WP190: Excessive Daytime Sleepiness and Depression in Stroke Survivors

Stroke ◽

10.1161/str.48.suppl_1.wp190 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Quynh Huong Pham ◽

Anjail Sharrief ◽

Sean Savitz ◽

Amrou Sarraj ◽

Lauren Fournier ◽

...

Keyword(s):

Ischemic Stroke ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Severe Depression ◽

Stroke Survivors ◽

Stroke Patients ◽

Patient Health ◽

Post Stroke Depression ◽

The Relationship ◽

Concentration Table

Introduction: Excessive daytime sleepiness (EDS) and post-stroke depression (PSD) are risk factors for stroke morbidity and mortality. EDS is commonly seen after stroke, but is not routinely assessed after stroke. EDS may be related to sleep disordered breathing (SDB) including obstructive and central sleep apneas, but can also occur in the absence of SDB. The relationship between EDS and PSD is not well understood. Hypothesis: We sought to assess the association between EDS and PSD. We hypothesized that patients with EDS are more likely to demonstrate symptoms of moderate to severe depression compared to patients without EDS. Methods: We identified ischemic stroke patients from the outpatient clinic registry (06/2014 - 10/2015). We screened for depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9; range 0-27, higher worse), and for EDS using the Epworth Sleepiness Scale (ESS; range 0-24, higher worse). Univariate and multivariate analyses were used to evaluate association between EDS and PHQ-9 (moderate to severe depression = PHQ-9 > 9). Regression analysis was also used to evaluate association between EDS and symptoms included in the PHQ-9. Results: Among 200 ischemic stroke patients, 166 completed ESS and PHQ-9 within 90 days of stroke occurrence. Mean age was 61.5 and 54.8% were male. EDS (ESS>9) and moderate to severe depression were each present in 28.9% of patients. Patients with EDS had 3.5 times odds of moderate to severe depression compared to patients without EDS (table 1). Moreover, EDS was associated with higher odds of anhedonia, impaired mood, sleep disturbance, low energy, poor appetite, and impaired concentration (table 1). Conclusion: The presence of EDS is associated with moderate to severe depression in stroke survivors. This is not related solely to SDB symptoms. Patients with fatigue and EDS should be screened for depression. Future studies are also needed to explore the role that SDB plays in this relationship.

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