scholarly journals The effect of rapamycin treatment on cerebral ischemia: A systematic review and meta-analysis of animal model studies

2018 ◽  
Vol 14 (2) ◽  
pp. 137-145 ◽  
Author(s):  
Daniel J Beard ◽  
Gina Hadley ◽  
Neal Thurley ◽  
David W Howells ◽  
Brad A Sutherland ◽  
...  

Background Amplifying endogenous neuroprotective mechanisms is a promising avenue for stroke therapy. One target is mammalian target of rapamycin (mTOR), a serine/threonine kinase regulating cell proliferation, cell survival, protein synthesis, and autophagy. Animal studies investigating the effect of rapamycin on mTOR inhibition following cerebral ischemia have shown conflicting results. Aim To conduct a systematic review and meta-analysis evaluating the effectiveness of rapamycin in reducing infarct volume in animal models of ischemic stroke. Summary of review Our search identified 328 publications. Seventeen publications met inclusion criteria (52 comparisons: 30 reported infarct size and 22 reported neurobehavioral score). Study quality was modest (median 4 of 9) with no evidence of publication bias. The point estimate for the effect of rapamycin was a 21.6% (95% CI, 7.6%–35.7% p < 0.01) improvement in infarct volume and 30.5% (95% CI 17.2%–43.8%, p < 0.0001) improvement in neuroscores. Effect sizes were greatest in studies using lower doses of rapamycin. Conclusion Low-dose rapamycin treatment may be an effective therapeutic option for stroke. Modest study quality means there is a potential risk of bias. We recommend further high-quality preclinical studies on rapamycin in stroke before progressing to clinical trials.

2005 ◽  
Vol 25 (6) ◽  
pp. 713-721 ◽  
Author(s):  
Malcolm R. Macleod ◽  
Tori O'Collins ◽  
Laura L. Horky ◽  
David W. Howells ◽  
Geoffrey A. Donnan

FK506 is a candidate drug for acute stroke. For such drugs, any decision to proceed to clinical trial should be based on a full and unbiased assessment of the animal data, and consideration should be given to the limitations of those data. Such an assessment should include not only the efficacy of a drug but also the in vivo characteristics and limits to that efficacy. Here we use systematic review and meta-analysis to assess the evidence for a protective effect of FK506 in animal models of stroke. In all, 29 studies were identified describing procedures involving 1759 animals. The point estimate for the effect of FK506 was a 31.3% (95% confidence interval 27.2% to 35.4%) improvement in outcome. Efficacy was higher with ketamine anaesthesia and temporary ischaemia and was lower in rats, in animals with comorbidities, and where outcome was measured as infarct size alone. Reported study quality was modest by clinical trial standards, and efficacy was lower in high-quality studies. These findings show a substantial efficacy for FK506 in experimental stroke, but raise concerns that our estimate of effect size might be too high because of factors such as study quality and possible publication bias.


2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Angeline Jeyakumar ◽  
Vidhya Shinde ◽  
Reshma Ravindran

Abstract Background Vitamin D deficiency among pregnant women is a public health concern globally. In India, individual studies report high prevalence. However, lack of national data masks the true burden. This work determined the pooled prevalence of vitamin D deficiency among pregnant women in India through a systematic review of literature and meta-analysis. Methods Three different search engines yielded 15 eligible articles. Study quality was assessed by 10 different criteria and summary of study quality was categorized as per Cochrane standards. Meta-analysis was performed to estimate pooled prevalence of vitamin D deficiency among healthy pregnant women and heterogeneity among selected studies. A sample of n = 4088 was used to study the pooled prevalence among pregnant women. Results The random effects combined estimate was 32.35% (95% CI, (12.58–117.48). High heterogeneity (tau2 = 0.39, I2 = 100%) and high risk of bias was observed among the selected studies. The test for overall effect was observed to be z = 2.54(P = 0.01). Conclusion Pooled estimate > 30% emphasizes the need for screening through antenatal care services and initiate preventive measures to address the deficiency.


2014 ◽  
Vol 45 (2) ◽  
pp. 231-246 ◽  
Author(s):  
A. van Straten ◽  
J. Hill ◽  
D. A. Richards ◽  
P. Cuijpers

BackgroundIn stepped care models patients typically start with a low-intensity evidence-based treatment. Progress is monitored systematically and those patients who do not respond adequately step up to a subsequent treatment of higher intensity. Despite the fact that many guidelines have endorsed this stepped care principle it is not clear if stepped care really delivers similar or better patient outcomes against lower costs compared with other systems. We performed a systematic review and meta-analysis of all randomized trials on stepped care for depression.MethodWe carried out a comprehensive literature search. Selection of studies, evaluation of study quality and extraction of data were performed independently by two authors.ResultsA total of 14 studies were included and 10 were used in the meta-analyses (4580 patients). All studies used screening to identify possible patients and care as usual as a comparator. Study quality was relatively high. Stepped care had a moderate effect on depression (pooled 6-month between-group effect size Cohen'sdwas 0.34; 95% confidence interval 0.20–0.48). The stepped care interventions varied greatly in number and duration of treatment steps, treatments offered, professionals involved, and criteria to step up.ConclusionsThere is currently only limited evidence to suggest that stepped care should be the dominant model of treatment organization. Evidence on (cost-) effectiveness compared with high-intensity psychological therapy alone, as well as with matched care, is required.


Author(s):  
Andressa Rodrigues de Souza ◽  
Thulssa Auxiliadora Gomes Medeiros dos Santos ◽  
Camila Bomfim Von Jakitsch ◽  
Ana Lúcia Gargione Galvão de Sant'Anna ◽  
João Carlos Marchiori de Claudio ◽  
...  

Author(s):  
Yanjie Zhang ◽  
Chunxiao Li ◽  
Liye Zou ◽  
Xiaolei Liu ◽  
Wook Song

Background: As the situation of cognitive aging is getting worse, preventing or treating cognitive decline through effective strategies is highly important. This systematic review aims to investigate whether mind-body exercise is an effective approach for treating cognition decline. Methods: Searches for the potential studies were performed on the eight electronic databases (MEDLINE, Scopus, Web of Science, SPORTDiscus, CINAHL, PsycArtilces, CNKI, and Wanfang). Randomized controlled trials (RCTs) examining the effect of mind-body exercise on cognitive performance in older adults were included. Data were extracted and effect sizes were pooled with 95% confidence intervals (95% CI) using random-effects models. The Physiotherapy Evidence Database Scale was employed to examine the study quality. Results: Nineteen RCTs including 2539 elders (67.3% female) with fair to good study quality were identified. Mind-body exercise, relative to control intervention, showed significant benefits on cognitive performance, global cognition (Hedges’g = 0.23), executive functions (Hedges’g = 0.25 to 0.65), learning and memory (Hedges’g = 0.37 to 0.49), and language (Hedges’g = 0.35). In addition, no significant adverse events were reported. Conclusion: Mind-body exercise may be a safe and effective intervention for enhancing cognitive function among people aged 60 years or older. Further research evidence is still needed to make a more conclusive statement.


2018 ◽  
Vol 62 (4) ◽  
pp. 244-252 ◽  
Author(s):  
Lauren Pearson ◽  
Rachel E. Factor ◽  
Sandra K. White ◽  
Brandon S. Walker ◽  
Lester J. Layfield ◽  
...  

Objective: Rapid on-site evaluation (ROSE) has been shown to improve adequacy rates and reduce needle passes. ROSE is often performed by cytopathologists who have limited availability and may be costlier than alternatives. Several recent studies examined the use of alternative evaluators (AEs) for ROSE. A summary of this information could help inform guidelines regarding the use of AEs. The objective was to assess the accuracy of AEs compared to cytopathologists in assessing the adequacy of specimens during ROSE. Study Design: This was a systematic review and meta-analysis. Reporting and study quality were assessed using the STARD guidelines and QUADAS-2. All steps were performed independently by two evaluators. Summary estimates were obtained using the hierarchal method in Stata v14. Heterogeneity was evaluated using Higgins’ I2 statistic. Results: The systematic review identified 13 studies that were included in the meta-analysis. Summary estimates of sensitivity and specificity for AEs were 97% (95% CI: 92–99%) and 83% (95% CI: 68–92%). There was wide variation in accuracy statistics between studies (I2 = 0.99). Conclusions: AEs sometimes have accuracy that is close to cytopathologists. However, there is wide variability between studies, so it is not possible to provide a broad guideline regarding the use of AEs.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Ruth E Taylor-Piliae ◽  
Brooke A Finley

Background: Regular exercise is beneficial for adults with chronic heart failure (CHF). Tai Chi is popular among older adults and may offer additional exercise options for those with CHF. Objectives: A systematic review and meta-analysis was conducted to examine the benefits of Tai Chi exercise among adults with CHF. Methods: An electronic literature search of ten databases (AMED, CINAHL, Embase, OpenGrey, PsycARTICLES, PsycINFO, PubMed, Scopus, SPORTDiscus, and Web of Science) was conducted from January 1, 2004 to August 1, 2019. Clinical trials that examined Tai Chi exercise, were published in English or German languages, among participants with CHF were included. Study quality was assessed independently by two reviewers, using the modified Downs and Black Quality Index checklist (low quality = score ≤14, moderate quality = score 15-23, high quality = score ≥ 24). Comprehensive Meta-Analysis version 2.0 software (Biostat, Inc.) was used to calculate the effect sizes (i.e., Hedges’ g) and the 95% confidence intervals using random effects models. Results: A total of six studies met the inclusion criteria (five RCTs and one quasi-experimental study with a comparison group), enrolling 229 participants (mean age=68 years old, 28% women, mean ejection fraction=37%). The Yang style of Tai Chi was most commonly practiced in these studies (n=5, 83%), with usual care the most common control condition. Study quality was moderate (mean score=23). At least three studies reported outcomes for exercise capacity, quality of life (QOL), depression, and b-type natriuretic peptide (BNP), allowing for meta-analysis. Compared to controls, Tai Chi participants had significantly better exercise capacity (Hedge’s g=0.353; p=0.026, I 2 =32.72%), improved QOL (Hedge’s g=0.617; p=0.000, I 2 =0%), with less depression (Hedge’s g=0.627; p=0.000, I 2 =0%), and decreased BNP expression (Hedge’s g=0.333; p=0.016, I 2 =0%). Conclusion: Among adults with CHF, Tai Chi was effective in improving exercise capacity and quality of life, with less depression and BNP levels observed, when compared to controls. Tai Chi is popular and safe form of exercise among older adults, yet few studies have been conducted during the past 15 years examining the benefits of Tai Chi among adults with CHF. Tai Chi can be easily integrated into existing cardiac rehabilitation programs. Further research is needed with more rigorous study designs and larger samples, before widespread recommendations can be made.


2020 ◽  
Vol 11 ◽  
Author(s):  
Zhi-Ze Xiao ◽  
Ze-Fen Wang ◽  
Tian Lan ◽  
Wen-Hong Huang ◽  
Yu-Hang Zhao ◽  
...  

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