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Translational Stroke Research Dec 2020As a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists... (Meta-Analysis)
Meta-Analysis
As a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists and guidelines were developed over the past decades. This systematic review assesses the overall methodological quality of preclinical SAH research. An electronic search for preclinical studies on SAH revealed 3415 potential articles. Of these, 765 original research papers conducted in vivo in mice, rats, rabbits, cats, dogs, pigs, goats, and non-human primates with a focus on brain damage related to delayed cerebral vasospasm and early brain injury met the inclusion criteria. We found methodological shortcomings still to prevail in preclinical SAH research. In addition, basic animal characteristics were typically well described but important technical parameters of SAH induction were often underreported. None of the species, models, or techniques used in preclinical SAH research was methodologically superior to the others. Methodological quality of preclinical SAH research was independent of the number of citations or impact factor of a publication. Consequently, we suggest the SAH research community should consider strategies to improve preclinical research quality in their field, such as public platforms to (pre)register preclinical experiments, consequent support of open science policies, stricter editorial (and reviewer) control of (pre)existing guidelines, and increased efforts in education and training of good laboratory practice for the next generation of researchers.
Topics: Animals; Disease Models, Animal; Subarachnoid Hemorrhage
PubMed: 32172515
DOI: 10.1007/s12975-020-00801-4 -
Circulation Journal : Official Journal... Oct 2019We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing...
BACKGROUND
We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database.
METHODS AND RESULTS
We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics.
CONCLUSIONS
We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.
Topics: Administrative Claims, Healthcare; Aged; Aged, 80 and over; Comprehensive Health Care; Databases, Factual; Delivery of Health Care, Integrated; Delphi Technique; Feasibility Studies; Female; Guideline Adherence; Healthcare Disparities; Humans; Japan; Male; Middle Aged; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quality Improvement; Quality Indicators, Health Care; Risk Factors; Stroke; Time Factors; Treatment Outcome
PubMed: 31554766
DOI: 10.1253/circj.CJ-19-0089 -
Acta Neurochirurgica Oct 2019In patients with spontaneous subarachnoid haemorrhage (SAH), a vascular cause for the bleed is not always found on initial investigations. This study aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In patients with spontaneous subarachnoid haemorrhage (SAH), a vascular cause for the bleed is not always found on initial investigations. This study aimed to systematically evaluate the delayed investigation strategies and clinical outcomes in these cases, often described as "non-aneurysmal" SAH (naSAH).
METHODS
A systematic review was performed in concordance with the PRISMA checklist. Pooled proportions of primary outcome measures were estimated using a random-effects model.
RESULTS
Fifty-eight studies were included (4473 patients). The cohort was split into perimesencephalic naSAH (PnaSAH) (49.9%), non-PnaSAH (44.7%) and radiologically negative SAH identified on lumbar puncture (5.4%). The commonest initial vascular imaging modality was digital subtraction angiography. A vascular abnormality was identified during delayed investigation in 3.9% [95% CI 1.9-6.6]. There was no uniform strategy for the timing or modality of delayed investigations. The pooled proportion of a favourable modified Rankin scale outcome (0-2) at 3-6 months following diagnosis was 92.0% [95% CI 86.0-96.5]. Complications included re-bleeding (3.1% [95% CI 1.5-5.2]), hydrocephalus (16.0% [95% CI 11.2-21.4]), vasospasm (9.6% [95% CI 6.5-13.3]) and seizure (3.5% [95% CI 1.7-5.8]). Stratified by bleeding pattern, we demonstrate a higher rate of delayed diagnoses (13.6% [95% CI 7.4-21.3]), lower proportion of favourable functional outcome (87.2% [95% CI 80.1-92.9]) and higher risk of complications for non-PnaSAH patients.
CONCLUSION
This study highlights the heterogeneity in delayed investigations and outcomes for patients with naSAH, which may be influenced by the initial pattern of bleeding. Further multi-centre prospective studies are required to clarify optimal tailored management strategies for this heterogeneous group of patients.
Topics: Angiography, Digital Subtraction; Female; Humans; Hydrocephalus; Male; Middle Aged; Subarachnoid Hemorrhage; Tomography, X-Ray Computed
PubMed: 31410556
DOI: 10.1007/s00701-019-04025-w -
Ophthalmic Research 2019To compare the choroidal thickness (CT) measured by enhanced depth imaging optical coherence tomography (EDI-OCT) in preeclamptic, healthy pregnant, and healthy... (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the choroidal thickness (CT) measured by enhanced depth imaging optical coherence tomography (EDI-OCT) in preeclamptic, healthy pregnant, and healthy nonpregnant women.
METHODS
Studies that focused on the CT evaluation of pregnant women were retrieved by searching PubMed, Embase, Ovid, Cochrane, and Web of Science. We used Stata 14.0 SE for the meta-analysis and presented the results as the weighted mean difference (WMD) with a corresponding 95% CI.
RESULTS
A total of 14 studies with 1,227 participants were included in our meta-analysis. The CT of the healthy pregnancies (μm, WMD = 34.19, 95% CI: 20.63-47.76) was significantly higher than that of the nonpregnancies (Test of WMD = 0: z = 4.94, p = 0.000), but the CT of the preeclampsia (μm, WMD = 54.30, 95% CI: -13.40 to 122.01) was not significantly different from the nonpregnancies (Test of WMD = 0: z = 1.57, p = 0.116). In the preeclampsia versus healthy pregnancy group, 3 studies found that the choroid was thinner with preeclampsia, only one study found the CT increased.
CONCLUSIONS
This meta-analysis suggested that the CT of the healthy pregnant women was significantly higher than that of the nonpregnant women. The presence of preeclampsia might complicate this situation. Most studies found that the CT decreased in the preeclamptic patients because of the increases in the systemic vasospasm and the blood pressure, which led to no significant difference compared with the nonpregnant women.
Topics: Blood Pressure; Case-Control Studies; Choroid; Female; Humans; Intraocular Pressure; Pre-Eclampsia; Pregnancy; Tomography, Optical Coherence
PubMed: 31141806
DOI: 10.1159/000499916 -
Neurocritical Care Feb 2020Delayed cerebral ischemia (DCI) is among the most dreaded complications following aneurysmal subarachnoid hemorrhage (SAH). Despite advances in neurocritical care, DCI...
BACKGROUND
Delayed cerebral ischemia (DCI) is among the most dreaded complications following aneurysmal subarachnoid hemorrhage (SAH). Despite advances in neurocritical care, DCI remains a significant cause of morbidity and mortality, prolonged intensive care unit and hospital stay, and high healthcare costs. Large artery vasospasm has classically been thought to lead to DCI. However, recent failure of clinical trials targeting vasospasm to improve outcomes has underscored the disconnect between large artery vasospasm and DCI. Therefore, interest has shifted onto other potential mechanisms such as microvascular dysfunction and spreading depolarizations. Animal models can be instrumental in dissecting pathophysiology, but clinical relevance can be difficult to establish.
METHODS
Here, we performed a systematic review of the literature on animal models of SAH, focusing specifically on DCI and neurological deficits.
RESULTS
We find that dog, rabbit and rodent models do not consistently lead to DCI, although some degree of delayed vascular dysfunction is common. Primate models reliably recapitulate delayed neurological deficits and ischemic brain injury; however, ethical issues and cost limit their translational utility.
CONCLUSIONS
To facilitate translation, clinically relevant animal models that reproduce the pathophysiology and cardinal features of DCI after SAH are urgently needed.
Topics: Animals; Brain Ischemia; Disease Models, Animal; Dogs; Injections; Mice; Rabbits; Rats; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 30671784
DOI: 10.1007/s12028-018-0650-5 -
Translational Stroke Research Sep 2018In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To... (Review)
Review
In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To analyze how parameter choice affects the relevance and comparability of findings, we systematically reviewed 765 experimental studies of in vivo animal SAH models (2000-2014). During the last decade, we found marked increases in publications using smaller species and models for simulating acute events after SAH. Overall, the fewer types of species and models used did not correlate with an increased standardization in the experimental characteristics and procedures. However, by species, commonly applied, reliable parameters for each experimental SAH technique were identified in mouse, rat, rabbit, and dog models. Our findings can serve as a starting point for discussion toward a more uniform performance of SAH experiments, development of preclinical SAH common data elements, and establishment of standardized protocols for multicenter preclinical trials.
PubMed: 30209798
DOI: 10.1007/s12975-018-0657-4 -
Emergency Medicine Journal : EMJ Sep 2018Beta blockers (β-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, β-blocker therapy in patients with cocaine-associated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Beta blockers (β-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, β-blocker therapy in patients with cocaine-associated chest pain (CACP) continues to be an area of debate due to the potential risk of unopposed α-adrenergic stimulation and coronary vasospasm. Therefore, we performed a systematic review and meta-analysis of available studies to compare outcomes of β-blocker versus no β-blocker use among patients with CACP.
METHODS
We searched the MEDLINE and EMBASE databases through September 2016 using the keywords 'beta blocker', 'cocaine' and commonly used β-blockers ('atenolol', 'bisoprolol', 'carvedilol', 'esmolol', 'metoprolol' and 'propranolol') to identify studies evaluating β-blocker use among patients with CACP. We specifically focused on studies comparing outcomes between β-blocker versus no β-blocker usage in patients with CACP. Studies without a comparison between β-blocker and no β-blocker use were excluded. Outcomes of interest included non-fatal myocardial infarction (MI) and all-cause mortality. Quantitative data synthesis was performed using a random-effects model and heterogeneity was assessed using Q and Istatistics.
RESULTS
A total of five studies evaluating 1794 subjects were included. Overall, there was no significant difference on MI in patients with CACP on β-blocker versus no β-blocker (OR 1.36, 95% CI 0.68 to 2.75; p=0.39). Similarly, there was no significant difference in all-cause mortality in patients on β-blocker versus no β-blocker (OR 0.68, 95% CI 0.26 to 1.79; p=0.43).
CONCLUSIONS
In patients presenting with acute chest pain and underlying cocaine, β-blocker use does not appear to be associated with an increased risk of MI or all-cause mortality.
Topics: Humans; Acute Coronary Syndrome; Adrenergic beta-Antagonists; Atenolol; Bisoprolol; Carvedilol; Cocaine; Metoprolol; Propanolamines; Propranolol
PubMed: 29921621
DOI: 10.1136/emermed-2017-207065 -
Frontiers in Physiology 2018While cannabis is perceived as a relatively safe drug by the public, accumulating clinical data suggest detrimental cardiovascular effects of cannabinoids. Cannabis has... (Review)
Review
While cannabis is perceived as a relatively safe drug by the public, accumulating clinical data suggest detrimental cardiovascular effects of cannabinoids. Cannabis has been legalized in several countries and jurisdictions recently. Experimental studies specifically targeting cannabinoids' effects on the cerebral vasculature are rare. There is evidence for transient vasoconstrictive effects of cannabinoids in the peripheral and cerebral vasculature in a complex interplay of vasodilation and vasoconstriction. Vasoreactivity to cannabinoids is dependent on the specific molecules, their metabolites and dose, baseline vascular tone, and vessel characteristics as well as experimental conditions and animal species. We systematically review the currently available literature of experimental results in and animal studies, examining cannabinoids' effects on circulation and reactive vasodilation or vasoconstriction, with a particular focus on the cerebral vascular bed.
PubMed: 29896112
DOI: 10.3389/fphys.2018.00622 -
Neurologia Medico-chirurgica Nov 2017The number of elderly patients with an aneurysmal subarachnoid hemorrhage (aSAH) has been increasing in aging- or aged societies in many countries. A treatment strategy... (Review)
Review
The number of elderly patients with an aneurysmal subarachnoid hemorrhage (aSAH) has been increasing in aging- or aged societies in many countries. A treatment strategy for the elderly with aSAH has not been established, although many studies have been published emphasizing poor outcome for aSAH. The aim of this study was to analyze the factors and treatments affecting outcome in aSAH in the elderly in a systematic review of the literature by investigating patients over age 75. A literature search was done for "elderly aSAH" in PubMed and Embase. Literature with a clear description of treatment measures for aneurysmal occlusion and outcome was selected. Twelve studies, consisted of 816 cases, met the eligibility criteria. Patient characteristics included 83.2% female, 33.8% poor clinical grade on admission, 57.1% Fischer group 3, and 41% internal carotid artery aneurysm. As complications, symptomatic vasospasm was seen in 25.5% of patients, hydrocephalus in 31.1%, and medical complication in 38.4%. Favorable outcome was 35.0% in total, 45.3% for clipping, 36.3% for coiling, and 9.0% for conservative treatment. Several studies by multivariate analysis indicated that poor clinical grade on admission could be a risk factor for neurological outcome and mortality. Advanced age and selection of conservative treatment without aneurysmal occlusion could be a risk factor for mortality. Patients under age 85 with good clinical grade on admission can be candidates for treatment of aneurysm repair. However, treatment for patients over age 85 or with poor clinical grade should be carefully determined.
Topics: Age Factors; Aged, 80 and over; Humans; Subarachnoid Hemorrhage
PubMed: 28835583
DOI: 10.2176/nmc.ra.2017-0057 -
Frontiers in Neurology 2017Delayed cerebral ischemia (DCI) is a life-threatening complication after subarachnoid hemorrhage. There is a strong association between cerebral vessel narrowing and... (Review)
Review
Delayed cerebral ischemia (DCI) is a life-threatening complication after subarachnoid hemorrhage. There is a strong association between cerebral vessel narrowing and DCI. Alpha calcitonin gene-related peptide (αCGRP) is a potent vasodilator, which may be effective at reducing cerebral vessel narrowing after subarachnoid hemorrhage (SAH). Here, we report a meta-analysis of data from nine animal studies identified in a systematic review in which αCGRP was administered in SAH models. Our primary outcome was change in cerebral vessel diameter and the secondary outcome was change in neurobehavioral scores. There was a 40.8 ± 8.2% increase in cerebral vessel diameter in those animals treated with αCGRP compared with controls ( < 0.0005, 95% CI 23.7-57.9). Neurobehavioral scores were reported in four publications and showed a standardized mean difference of 1.31 in favor of αCGRP (CI -0.49 to 3.12). We conclude that αCGRP reduces cerebral vessel narrowing seen after SAH in animal studies but note that there is insufficient evidence to determine its effect on functional outcomes.
PubMed: 28790969
DOI: 10.3389/fneur.2017.00357