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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 -
Journal of Clinical Medicine Jun 2023Emerging evidence suggests that neuroinflammation may play a potential role in aneurysmal subarachnoid hemorrhage (aSAH). We aim to analyze the influence of... (Review)
Review
Emerging evidence suggests that neuroinflammation may play a potential role in aneurysmal subarachnoid hemorrhage (aSAH). We aim to analyze the influence of anti-inflammatory therapy on survival and outcome in aSAH. Eligible randomized placebo-controlled prospective trials (RCTs) were searched in PubMed until March 2023. After screening the available studies for inclusion and exclusion criteria, we strictly extracted the main outcome measures. Dichotomous data were determined and extracted by odds ratio (OR) with 95% confidence intervals (CIs). Neurological outcome was graded using the modified Rankin Scale (mRS). We created funnel plots to analyze publication bias. From 967 articles identified during the initial screening, we included 14 RCTs in our meta-analysis. Our results illustrate that anti-inflammatory therapy yields an equivalent probability of survival compared to placebo or conventional management (OR: 0.81, 95% CI: 0.55-1.19, = 0.28). Generally, anti-inflammatory therapy trended to be associated with a better neurologic outcome (mRS ≤ 2) compared to placebo or conventional treatment (OR: 1.48, 95% CI: 0.95-2.32, = 0.08). Our meta-analysis showed no increased mortality form anti-inflammatory therapy. Anti-inflammatory therapy in aSAH patients tends to improve the neurological outcome. However, multicenter, rigorous, designed, prospective randomized studies are still needed to investigate the effect of fighting inflammation in improving neurological functioning after aSAH.
PubMed: 37373858
DOI: 10.3390/jcm12124165 -
The Cochrane Database of Systematic... 2000Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers have been used in an attempt to prevent cerebral vasospasm after injury,... (Review)
Review
BACKGROUND
Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers have been used in an attempt to prevent cerebral vasospasm after injury, maintain blood flow to the brain and so prevent further damage.
OBJECTIVES
To estimate the effects of calcium channel blockers in patients with acute traumatic brain injury and in a subgroup of brain injury patients with traumatic subarachnoid haemorrhage.
SEARCH STRATEGY
Hand searching and electronic searching for randomized controlled trials available by October 1997.
SELECTION CRITERIA
Randomized controlled trials in patients with all levels of severity of clinically diagnosed acute traumatic brain injury.
DATA COLLECTION AND ANALYSIS
Two reviewers (JL and CG) independently assessed the identified studies for eligibility and extracted data from each study. Summary odds ratios were calculated using the Mantel-Haenszel method.
MAIN RESULTS
Four RCTs were identified as eligible for inclusion in the systematic review. The effect of calcium channel blockers on the risk of death was reported in all RCTs. The pooled odds ratio for the four studies was 0.91 (95% confidence interval 0. 70 to 1.17). For the three RCTs that reported death and severe disability the pooled odds ratio was 0.85 (95% CI 0.68 to 1.07). In the two RCTs which reported the risk of death in a sub group of traumatic subarachnoid haemorrhage patients, the pooled odds ratio was 0.59 (95% CI 0.37 to 0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled odds ratio was 0.67 (95% CI 0.46 to 0.98).
REVIEWER'S CONCLUSIONS
This systematic review of randomized controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.
Topics: Brain Injuries; Calcium Channel Blockers; Humans; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 10796727
DOI: 10.1002/14651858.CD000565 -
Translational Stroke Research Feb 2024Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal... (Meta-Analysis)
Meta-Analysis Review
Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databases PubMed, Embase, and Web of Science for articles describing in vivo experiments using the SAH perforation mouse model and measuring mortality, SAH grade, and/or vasospasm. After screening, 42 articles (total of 1964 mice) were included into systematic review and meta-analysis. Certain model characteristics were insufficiently reported, e.g., perforation location (not reported in six articles), filament (material (n = 15) and tip texture (n = 25)), mouse age (n = 14), and weight (n = 10). Used injective anesthetics and location of perforation showed large variation. In a random-effects meta-analysis, the overall animal mortality following SAH was 21.3% [95% CI: 17.5%, 25.7%] and increased with longer observational periods. Filament material significantly correlated with animal mortality (p = 0.024) after exclusion of hyperacute studies (time after SAH induction < 24 h). Reported mean SAH grade was 10.7 [9.6, 11.7] on the scale of Sugawara (J Neurosci Methods 167:327-34, 2008). Furthermore, mean diameter of large cerebral arteries after SAH was reduced by 27.6% compared to sham-operated non-SAH mice. Uniforming standards of experimental procedures and their reporting are indispensable to increase overall comparability.
Topics: Mice; Animals; Subarachnoid Hemorrhage; Disease Models, Animal; Autonomic Nervous System Diseases; Vasospasm, Intracranial
PubMed: 36422813
DOI: 10.1007/s12975-022-01106-4 -
The Cochrane Database of Systematic... 2000To assess the effects and toxicity of Cyclofenil versus placebo for the treatment of Raynaud's phenomenon (RP) in scleroderma. (Review)
Review
OBJECTIVES
To assess the effects and toxicity of Cyclofenil versus placebo for the treatment of Raynaud's phenomenon (RP) in scleroderma.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or Vasospasm, Scleroderma or Progressive Systematic Sclerosis or Connective Tissue Disease or Autoimmune Disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA
All randomized trials comparing cyclofenil versus placebo were eligible if they reported any clinical outcomes within the trial.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratio (OR) was calculated for all dichotomous outcomes, and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous respectively.
MAIN RESULTS
One trial with 38 patients was included. There was a trend for Cyclofenil to demonstrate more improvement and more dropouts compared to placebo, but there were no statistically significant differences.
REVIEWER'S CONCLUSIONS
Cyclofenil is not effective in the treatment of Raynaud's phenomenon secondary to scleroderma.
Topics: Cyclofenil; Humans; Raynaud Disease; Scleroderma, Systemic
PubMed: 10796397
DOI: 10.1002/14651858.CD000955 -
Neurosurgical Review Apr 2022Neurosurgical clipping and endovascular coiling are both standard therapies to prevent rebleeding after aneurysmal subarachnoid hemorrhage (aSAH). However, controversy... (Meta-Analysis)
Meta-Analysis Review
Neurosurgical clipping and endovascular coiling are both standard therapies to prevent rebleeding after aneurysmal subarachnoid hemorrhage (aSAH). However, controversy still exists about which is the optimal treatment. This meta-analysis aims to assess the effectiveness and safety of two treatments with high-quality evidence. Web of Science, Cochrane Library, EMBASE, Pubmed, Sinomed, China National Knowledge Infrastructure, and Wanfang Data databases were systematically searched on August 5, 2021. Randomized controlled trials (RCTs) and prospective cohort studies that evaluated the effectiveness and safety of clipping versus coiling in aSAH patients at discharge or within 1-year follow-up period were eligible. No restriction was set on the publication date. Meta-analyses were conducted to calculate the pooled estimates and 95% confidence intervals (CI) of relative risk (RR). Eight RCTs and 20 prospective cohort studies were identified. Compared to coiling, clipping was associated with a lower rebleeding rate at discharge (RR: 0.52, 95% CI: 0.29--0.94) and a higher aneurysmal occlusion rate (RR: 1.33, 95% CI: 1.19-1.48) at 1-year follow-up. In contrast, coiling reduced the vasospasm rate at discharge (RR: 1.45, 95% CI: 1.23-1.71) and 1-year poor outcome rate (RR: 1.27, 95% CI: 1.16-1.39). Subgroup analyses presented that among patients with a poor neurological condition at admission, no statistically significant outcome difference existed between the two treatments. The overall prognosis was better among patients who received coiling, but this advantage was not significant among patients with a poor neurological condition at admission. Therefore, the selection of treatment modality for aSAH patients should be considered comprehensively.
Topics: Databases, Factual; Endovascular Procedures; Humans; Intracranial Aneurysm; Neurosurgical Procedures; Prospective Studies; Subarachnoid Hemorrhage; Treatment Outcome
PubMed: 34870768
DOI: 10.1007/s10143-021-01704-0 -
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 -
The Cochrane Database of Systematic... 2000To assess the effects and toxicity of the following agent: ketanserin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. (Review)
Review
OBJECTIVES
To assess the effects and toxicity of the following agent: ketanserin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systematic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA
All randomized controlled trials comparing ketanserin versus placebo were eligible if they reported clinical outcomes of interest. Trials with dropout rates greater than 35% were excluded.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios (OR) were calculated for all dichotomous outcomes, and a weighted mean difference (WMD) was carried out on all continuous outcomes. A fixed effects or random effects model were used if the data was homogeneous or heterogeneous, respectively.
MAIN RESULTS
Three trials and 66 patients were included. The proportion improved was significantly better in the group on ketanserin with an odds ratio (OR) of 4.80 (95% CI 1.33, 17.37). However, when comparing ketanserin to placebo, the decrease in severity of RP attacks favoured placebo but this was not statistically significant. Side effects were significantly more common in the group using active treatment with an OR of 5.96 (95% CI 1.61, 22.06). Frequency of attacks did not change, but the duration of attacks decreased significantly in the ketanserin group.
REVIEWER'S CONCLUSIONS
Ketanserin may have some efficacy in the treatment of Raynaud's phenomenon secondary to scleroderma. Overall, ketanserin is not significantly different from placebo for the treatment of Raynaud's phenomenon except for some decrease in the duration of attacks and more subjects improved on ketanserin compared to placebo. However, there were more side effects. It can be concluded that ketanserin treatment in Raynaud's phenomenon secondary to scleroderma is not clinically beneficial.
Topics: Humans; Ketanserin; Raynaud Disease; Scleroderma, Systemic; Serotonin Antagonists
PubMed: 10796396
DOI: 10.1002/14651858.CD000954 -
The Cochrane Database of Systematic... 2000To determine the effects and toxicity of prazosin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. (Review)
Review
OBJECTIVES
To determine the effects and toxicity of prazosin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, and Medline up to December 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages.
SELECTION CRITERIA
Randomized controlled trials comparing prazosin versus placebo were eligible if they reported clinical outcomes from the start of therapy. Trials with a greater than 35% dropout were excluded. Trials were included if patients with diffuse or limited scleroderma were the subjects. If patients with other connective tissue diseases or primary Raynaud's were included, the trial was used if the data on the scleroderma patients could be extracted from the paper.
DATA COLLECTION AND ANALYSIS
All data were abstracted by two independent and trained reviewers (DF, AT), and verified by a third reviewer (JP). Each trial was assessed independently by the same two reviewers for its quality using a validated quality assessment tool (Jadad 1996). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was carried out on all continuous outcomes. Fixed effects and random effects model were used if the data was homogeneous or heterogeneous, respectively.
MAIN RESULTS
Two trials with a total of 40 patients were included. Prazosin has been found in two randomized controlled cross-over trials to be more effective than placebo in the treatment of Raynaud's secondary to scleroderma. However, the positive response is modest and side effects are not rare in those taking prazosin.
REVIEWER'S CONCLUSIONS
Prazosin is modestly effective in the treatment of Raynaud's phenomenon secondary to scleroderma.
Topics: Adrenergic alpha-Antagonists; Humans; Prazosin; Raynaud Disease; Scleroderma, Systemic
PubMed: 10796398
DOI: 10.1002/14651858.CD000956 -
Neurosurgical Review Apr 2024Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after... (Review)
Review
Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.
Topics: Humans; Subarachnoid Hemorrhage; DNA Methylation; Cerebral Infarction; Brain Ischemia; Biomarkers; Vasospasm, Intracranial; Cadherin Related Proteins
PubMed: 38594575
DOI: 10.1007/s10143-024-02381-5