Assessing short-term risk of ischemic stroke in relation to all prescribed medications.
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ABSTRACT:
SUBMITTER: Janszky I
PROVIDER: S-EPMC8568938 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Assessing short-term risk of ischemic stroke in relation to all prescribed medications.
Janszky Imre I Vardaxis Ioannis I Lindqvist Bo Henry BH Horn Jens Wilhelm JW Brumpton Ben Michael BM Strand Linn Beate LB Bakken Inger Johanne IJ Alsnes Ingvild Vatten IV Romundstad Pål Richard PR Ljung Rickard R Mukamal Kenneth Jay KJ Sen Abhijit A
Scientific reports 20211104 1
We examined the short-term risk of stroke associated with drugs prescribed in Norway or Sweden in a comprehensive, hypothesis-free manner using comprehensive nation-wide data. We identified 27,680 and 92,561 cases with a first ischemic stroke via the patient- and the cause-of-death registers in Norway (2004-2014) and Sweden (2005-2014), respectively, and linked these data to prescription databases. A case-crossover design was used that compares the drugs dispensed within 1 to 14 days before the ...[more]
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Project description:ObjectiveWe aimed to evaluate the safety and effectiveness of short-term remote ischemic postconditioning (RIPC) in acute stroke monkey models.MethodsAcute stroke monkeys were allocated to four groups based on the number of limbs exposed to RIPC. RIPC was initiated by 5-min cuff inflation/deflation cycles of the target limb(s) for 5-10 bouts. Vital signs, skin integrity, brain MRI, and serum levels of cardiac enzymes (myoglobin, creatine kinase [CK], CK-muscle/brain [CK-MB]), one inflammatory marker (high-sensitivity C-reactive protein [hsCRP], and one endothelial injury marker (von Willebrand factor [vWF]) were assessed. Spetzler scores were used to assess neurological function.ResultsNo significant differences in vital signs or local skin integrity were found. Short-term RIPC did not reduce infarct volume under any condition at the 24th hour after stroke. However, neurological function improved in multi-limb RIPC compared with sham and single-limb RIPC at the 30th day follow-up after stroke. Myoglobin, CK, and CK-MB levels were reduced after multi-limb RIPC, regardless of the number of bouts. Moreover, multi-limb RIPC produced a greater diminution in CK-MB levels, whereas two-limb RIPC was more effective in reducing serum CK levels at the 24th hour after stroke. hsCRP increased after 5 bouts of multi-limb RIPC before decreasing below baseline and single-limb RIPC levels. Serum vWF was decreased at later time points after RIPC in all RIPC groups.ConclusionsStroke monkeys in hyperacute stage may benefit from short-term RIPC; however, whether this intervention can be translated into clinical use in patients with acute ischemic stroke warrants further study.
| S-EPMC6389742 | biostudies-literature
Project description:Wholesale, unbiased assessment of Scandinavian electronic health-care databases offer a unique opportunity to reveal potentially important undiscovered drug side effects. We examined the short-term risk of acute myocardial infarction (AMI) associated with drugs prescribed in Norway or Sweden. We identified 24,584 and 97,068 AMI patients via the patient- and the cause-of-death registers and linked to prescription databases in Norway (2004-2014) and Sweden (2005-2014), respectively. A case-crossover design was used to compare the drugs dispensed 1-7 days before the date of AMI diagnosis with 15-21 days' time -window for all the drug individually while controlling the receipt of other drugs. A BOLASSO approach was used to select drugs that acutely either increase or decrease the apparent risk of AMI. We found 48 drugs to be associated with AMI in both countries. Some antithrombotics, antibiotics, opioid analgesics, adrenergics, proton-pump inhibitors, nitroglycerin, diazepam, metoclopramide, acetylcysteine were associated with higher risk for AMI; whereas angiotensin-II-antagonists, calcium-channel blockers, angiotensin-converting-enzyme inhibitors, serotonin-specific reuptake inhibitors, allopurinol, mometasone, metformin, simvastatin, levothyroxine were inversely associated. The results were generally robust in different sensitivity analyses. This study confirms previous findings for certain drugs. Based on the known effects or indications, some other associations could be anticipated. However, inverse associations of hydroxocobalamin, levothyroxine and mometasone were unexpected and needs further investigation. This pharmacopeia-wide association study demonstrates the feasibility of a systematic, unbiased approach to pharmacological triggers of AMI and other diseases with acute, identifiable onsets.
| S-EPMC6547702 | biostudies-literature
Project description:ImportanceCause of ischemic stroke in young people is highly variable; however, the risk of recurrence is often presented with all subtypes of stroke grouped together in classification systems such as the Trial of ORG (danaparoid sodium [Orgaran]) 10172 in Acute Stroke Treatment (TOAST) criteria, which limits the ability to individually inform young patients with stroke about their risk of recurrence.ObjectiveTo determine the short-term and long-term risk of recurrent vascular events after ischemic stroke at a young age by stroke cause and to identify factors associated with recurrence.Design, setting, and participantsThis cohort study used data from the Observational Dutch Young Symptomatic Stroke Study, a prospective, multicenter, hospital-based cohort study, conducted at 17 hospitals in the Netherlands between 2013 and 2021. Eligible participants included 30-day survivors of an initial, neuroimaging-proven ischemic stroke (aged 18-49 years). Data analysis was conducted from June to July 2023.ExposureDiagnosis of a first-ever, ischemic stroke via neuroimaging.Main outcome and measuresThe primary outcome was short-term (within 6 months) and long-term (within 5 years) recurrence risk of any vascular event, defined as fatal or nonfatal recurrent ischemic stroke, transient ischemic attack, myocardial infarction, and revascularization procedure. Predefined characteristics were chosen to identify factors associated with risk of recurrence (cause of stroke, age, sex, stroke severity, and cardiovascular health factors).ResultsA total of 1216 patients (median [IQR] age, 44.2 [38.4-47.7] years; 632 male [52.0%]; 584 female [48.0%]) were included, with a median (IQR) follow-up of 4.3 (2.6-6.0) years. The 6-month risk of any recurrent ischemic event was 6.7% (95% CI, 5.3%-8.1%), and the 5-year risk was 12.2% (95% CI, 10.2%-14.2%)The short-term risk was highest for patients with cervical artery dissections (13.2%; 95% CI, 7.6%-18.7%). Other factors associated with a recurrent short-term event were atherothrombotic stroke, rare causes of stroke, and hypertension. The long-term cumulative risk was highest for patients with atherothrombotic stroke (22.7%; 95% CI, 10.6%-34.7%) and lowest for patients with cryptogenic stroke (5.8%; 95% CI, 3.0%-8.5%). Cardioembolic stroke was associated with a recurrent long-term event, as were diabetes and alcohol abuse.Conclusions and relevanceThe findings of this cohort study of 1216 patients with an ischemic stroke at a young age suggest that the risk of recurrent vascular events was high and varied by cause of stroke both for short-term and long-term follow-up, including causes that remained concealed when combined into 1 category in the routinely used TOAST criteria. This knowledge will allow for more personalized counseling of young patients with stroke.
| S-EPMC10879951 | biostudies-literature
Project description:BackgroundBiological age (BA), an integrated measure of physiological aging, has a clear link to stroke. There is a paucity of long-term longitudinal studies about the association between accelerated biological age and stroke prognosis in patients with previous strokes, and the differences in the predictive ability of various BA indicators calculated from clinical biochemistry biomarkers for future stroke outcomes are still unknown. To evaluate the role of three accelerated BA indicators for short- and long-term prognosis of patients with ischemic stroke or transient ischemic attack (TIA), and to identify the most appropriate predictor.MethodsThis study included 7396 patients from the Third China National Stroke Registry (CNSR-III), a prospective national registry of patients with acute ischemic stroke or TIA between August 2015 and March 2018 in China. We constructed accelerated BA using three widely recognized algorithms: PhenoAge, Klemera-Doubal, and HD method. To ascertain the association of accelerated BA with the risk of short- and long-term stroke outcomes, a Cox or logistic regression model was conducted for the analysis. The net reclassification index and integrated discrimination improvement were used to evaluate the added model improvement ability of BA acceleration.FindingsCompared to those with the lowest of PhenoAge acceleration, patients with the highest were more likely to have a higher risk of stroke (HR 1.98, 95% CI 1.49-2.63, P < 0.001), ischemic stroke (HR 1.88, 95% CI 1.41-2.53, P < 0.001), composite vascular events (HR 2.03, 95% CI 1.53-2.68, P < 0.001), all-cause death (HR 7.02, 95% CI 3.41-14.47, P < 0.001) and the modified Rankin scale of 3-6 (OR 2.55, 95% CI 2.05-3.16, P < 0.001) at three months, and the association observed within one year and five years was similar to that within three months. The risk of all stroke outcomes for HDAge was consistent with PhenoAge acceleration, but KDMAge acceleration was the same, except for stroke within one year (HR 1.24, 95% CI 1.00-1.53, P = 0.053). PhenoAge acceleration provided a better improvement in the model's predictive ability for stroke prognosis, compared to BA determined by other algorithms.InterpretationIn this prospective cohort study, BA acceleration, particularly PhenoAge, may help identify stroke patients with risks of short- and long-term poor outcomes, potentially enabling subclinical prevention and early intervention.FundingThis work was supported by grants from Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-029), the National Natural Science Foundation of China (U20A20358), Beijing Hospitals Authority Clinical Medicine Development of special funding support (ZLRK202312), the National Key R&D Program of China (No. 2022YFC3602500, 2022YFC3602505), Outstanding Young Talents Project of Capital Medical University (A2105), and Beijing High-Level Public Health Technical Personnel Construction Project (Discipline leader -03-12).
| S-EPMC11697706 | biostudies-literature
Project description:IntroductionAtrial fibrillation (AF) and cancer are each associated with worse outcomes in patients with acute ischemic stroke (AIS). Few studies have evaluated the impact of AF on outcomes of cancer-related stroke.Patients and methodsWe conducted a retrospective cross-sectional study using the 2016-2019 National Inpatient Sample, identifying all hospitalizations with diagnosis codes for cancer and AIS. The primary exposure was a diagnosis of AF. The primary outcome was in-hospital mortality. The secondary outcomes were length-of-stay and discharge to non-home locations. We used multiple logistic and linear regression models, adjusted for age, gender, race-ethnicity, and the Charlson Comorbidity Index, to examine the association between AF and study outcomes.ResultsAmong 150,200 hospitalizations with diagnoses of cancer and AIS (mean age 72 years, 53% male), 40,084 (26.7%) included comorbid AF. Compared to hospitalizations without AF, hospitalizations with AF had higher rates of in-hospital mortality (14.8% [95% CI, 14.0%-15.6%] vs 12.1% [95% CI, 11.6%-12.5%]) and non-home discharge disposition (83.5% [95% CI, 82.7%-84.3%] vs 75.1% [95% CI, 74.5%-75.7%]) as well as longer mean length-of-stay (8.4 days [95% CI, 8.2-8.6 days] vs 8.2 days [95% CI, 8.0-8.3 days]). In multivariable analyses, AF remained independently associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR], 1.34; 95% CI, 1.24-1.46), non-home discharge disposition (aOR, 1.32; 95% CI, 1.23-1.42), and longer length-of-stay (adjusted mean difference, 13.7%; 95% CI, 10.9%-16.7%).Discussion and conclusionIn cancer-related AIS, comorbid AF is associated with worse short-term outcomes, including higher odds for in-hospital mortality, poor discharge disposition, and longer hospital stays.
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Project description:Stroke is one of the leading causes of death and long-term disability worldwide. Mitochondrial DNA (mtDNA) is a potential contributor for the sex differences of ischemic stroke heritability. Although mtDNA haplogroups were associated with stroke onset, their impacts on stroke outcomes remain unclear. This study aimed to evaluate the impacts of mtDNA haplogroups on short-term outcomes of neurological functions in patients with ischemic stroke. A total of 303 patients were included, and their clinical data and mtDNA sequences were analyzed. Based on the changes between baseline and 14-day follow-up stroke severity, our results showed that haplogroup N9 was an independent protective factor against neurological worsening in acute ischemic stroke patients. These findings supported that mtDNA variants play a role in post-stroke neurological recovery, thus providing evidences for future pharmacological intervention in mitochondrial function.
| S-EPMC4438613 | biostudies-literature
Project description:The Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence trial raised concern that loading doses of clopidogrel may increase hemorrhagic complications. We investigated if similar rates of hemorrhage occur in patients with acute ischemic stroke (AIS) of varying severity.Patients meeting inclusion criteria were divided into 2 groups: the LOAD group and non-LOAD group. The LOAD group was defined as patients who were administered a loading dose of 300 mg or more of clopidogrel with or without aspirin within 24 hours of admission. The non-LOAD group was devised using propensity score (PS): 55 patients who received a loading dose of clopidogrel of 300 mg or more were matched on PS to 55 patients who did not receive loading doses. These patients were taken from a pool of 341 consecutive ischemic patients ineligible for intravenous or intra-arterial fibrinolysis, 162 of whom received a clopidogrel loading dose and the remainder of whom did not. The frequency of hemorrhage was compared between the 2 groups using Student t test and chi-square. Logistic regression was used to assess the relationship between loading dose and serious bleeding events (symptomatic intracerebral hemorrhage [sICH] or transfusion for systemic bleeding).AIS patients (N = 596) were screened during the 31-month period of this retrospective study. Of this sample, 170 patients were excluded: 149 patients were excluded because they were treated with intravenous tissue plasminogen activator (IV t-PA) alone, 11 were excluded because they were treated with IV t-PA combined with intra-arterial therapy (IAT), and 10 were excluded for treatment with IAT alone. An additional 85 patients were excluded because they were not admitted to the stroke service or because they had an in-hospital stroke. Baseline characteristics of the groups were well matched. There were no significant differences in the rates of sICH, transfusion, hemorrhagic transformation, or systemic bleeding. Clopidogrel loading was not associated with increased odds of serious bleeding events in the crude model (odds ratio [OR] .92, 95% confidence interval [CI] .27-3.13) or after adjusting for covariates and confounders of interest (OR 1.06, 95% CI .28-4.04).Contrary to our original hypothesis, patients with AIS receiving clopidogrel loading doses within 24 hours of symptom onset did not appear to experience a higher rate of new serious bleeding events during acute hospitalization when compared with patients who did not receive loading doses. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke trial is expected to provide insight into the safety of clopidogrel loading as an acute intervention after cerebral ischemia.
| S-EPMC4447207 | biostudies-other
Project description:ObjectiveDespite improvements in treatment, stroke remains a leading cause of mortality and long-term disability. In this study, we leveraged administrative data to build predictive models of short- and long-term post-stroke all-cause-mortality.MethodsThe study was conducted and reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guideline. We used patient-level data from electronic health records, three algorithms, and six prediction windows to develop models for post-stroke mortality.ResultsWe included 7144 patients from which 5347 had survived their ischemic stroke after two years. The proportion of mortality was between 8%(605/7144) within 1-month, to 25%(1797/7144) for the 2-years window. The three most common comorbidities were hypertension, dyslipidemia, and diabetes. The best Area Under the ROC curve(AUROC) was reached with the Random Forest model at 0.82 for the 1-month prediction window. The negative predictive value (NPV) was highest for the shorter prediction windows - 0.91 for the 1-month - and the best positive predictive value (PPV) was reached for the 6-months prediction window at 0.92. Age, hemoglobin levels, and body mass index were the top associated factors. Laboratory variables had higher importance when compared to past medical history and comorbidities. Hypercoagulation state, smoking, and end-stage renal disease were more strongly associated with long-term mortality.ConclusionAll the selected algorithms could be trained to predict the short and long-term mortality after stroke. The factors associated with mortality differed depending on the prediction window. Our classifier highlighted the importance of controlling risk factors, as indicated by laboratory measures.
| S-EPMC8480306 | biostudies-literature
Project description:OBJECTIVES:Presence of sleep-disordered breathing (SDB) affects negatively recovery from stroke. The aim of this study is to evaluate the relationships between sleep-disordered breathing (SDB) and outcome measures in Finnish stroke unit cohort: mRS, need of rehabilitation and hospitalization time. MATERIAL AND METHODS:An observational longitudinal study consisted of 95 patients referred to the Stroke Unit of Satakunta Hospital District over a period of November 2013 to March 2016. Patients were tested for SDB within 72 hr from the hospital admission because of ischemic stroke or TIA. The patients underwent polysomnography with NOX T3 wireless recorder. RESULTS:There are 37% (n = 35) non-OSA patients, 20% (n = 19) of patients have mild obstructive sleep apnea (OSA) and 39% (n = 37) have moderate/severe OSA and 4% (n = 4) have CSA. Patients with OSA have higher proportion of disability scores of mRS 3-5 (38%) compared to non-OSA (11%) and mild OSA (5%) patients on registration day (mRS0), and the same trend is seen at hospital discharge 35% versus 9% and 5%. (p = .009). Proportion of patients with OSA who needed rehabilitation is 65% (n = 19) versus non-OSA patients 17.5% (n = 4) and mild OSA patients 17.5% (n = 4; p = .039). We observed longer duration of hospitalization (5-15 days) in 29% of OSA patients compared to mild OSA patients 47% and OSA patients 54%. (p = .045). CONCLUSION:Ischemic stroke patients with OSA have higher disability, higher need of rehabilitation, and longer hospitalization length. Prescreening tools for recognizing these stroke patients in acute phase could be valuable. That could result in earlier initiation of treatment and might prevent worse recovery from stroke.
| S-EPMC7559619 | biostudies-literature
Project description:BackgroundThe short and long-term health effects of JUUL electronic cigarette (e-Cig) are largely unknown and warrant extensive research. We hypothesized that JUUL exposure could cause cerebrovascular toxicities impacting the progression and outcome of ischemic stroke comparable to tobacco smoke (TS) exposure.MethodsWe exposed male C57 mice to TS/JUUL vapor for 14 days. LCMS/MS was used to measure brain and plasma nicotine and cotinine level. Transient middle cerebral artery occlusion (tMCAO) followed by reperfusion was used to mimic ischemic stroke. Plasma levels of IL-6 and thrombomodulin were assessed by enzyme-linked immunosorbent assay. At the same time, western blotting was used to study blood-brain barrier (BBB) tight junction (TJ) proteins expression and key inflammatory and oxidative stress markers.ResultstMCAO upregulated IL-6 and decreased plasma thrombomodulin levels. Post-ischemic brain injury following tMCAO was significantly worsened by JUUL/TS pre-exposure. TJ proteins expression was also downregulated by JUUL/TS pre-exposure after tMCAO. Like TS, exposure to JUUL downregulated the expression of the antioxidant Nrf2. ICAM-1 was upregulated in mice subjected to tMCAO following pre-exposure to TS or JUUL, with a greater effect of TS than JUUL.ConclusionsThese results suggest that JUUL exposure could negatively impact the cerebrovascular system, although to a lesser extent than TS exposure.
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