scholarly journals When positive studies of novel therapies are subsequently nullified: cumulative meta-analyses in preeclampsia

2015 ◽  
Vol 38 (5) ◽  
pp. 274 ◽  
Author(s):  
Fatma Etwel ◽  
Gideon Koren
Keyword(s):  
Protective Effect ◽  
Impact Factor ◽  
Sample Size ◽  
Null Hypothesis ◽  
Low Dose ◽  
Protective Effects ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Study Results ◽  
Meta Analyses

Purpose: The purpose of this study was to examine changes over time in the pooled effect size of randomized, double-blinded, placebo-controlled trials (RCTs) published on the protective effects of antioxidants and low dose aspirin against preeclampsia, and to identify determinants that may affect such changes. Methods: Two recently published meta-analyses of RCTs examining the effects of antioxidant treatment or low dose aspirin on the rates of preeclampsia and its adverse effects were used. Chronological, cumulative meta-analyses were conducted to investigate the possibility of a time-dependent effect. The journal’s impact factor, citation numbers of each paper, and their sample size, were correlated with the risk ratio (RR) of the study. Results: The median sample size of positive antioxidant trials (i.e., showing protective effect) was tenfold smaller (median 267) than that of the negative trials (median 2120) (P = 0.017). A similar trend was seen for low dose aspirin studies. There was a significant correlation between study size and RR for the effects of antioxidants and low dose aspirin on intrauterine growth restriction (IUGR). There was no correlation between RR and citation number, or between RR and the journal’s impact factor for the two therapeutic modalities. For both modalities, the journal’s impact factor correlated significantly with the number of citations per year. Cumulative meta-analyses revealed that during the first few years and studies, there was a seeming significant protective effect of antioxidant or aspirin against preeclampsia. For both treatment, the initial protective effects gradually disappeared and nullified by larger, later studies. Conclusions: Initial studies, often published in high impact factor journals, are cited significantly more times but do not exhibit a higher likelihood of predicting a correct long term answer. Studies with smaller sample sizes are more likely to be biased against the null hypothesis. As such, cumulative meta-analysis is an effective tool in predicting potential bias against the null hypothesis and the need for additional studies.

Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

2008 ◽  
Vol 294 (4) ◽  
pp. H1562-H1570 ◽  
Author(s):  
Hélène Bulckaen ◽  
Gaétan Prévost ◽  
Eric Boulanger ◽  
Géraldine Robitaille ◽  
Valérie Roquet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Protective Effect ◽  
Structural Changes ◽  
Low Dose ◽  
Age Groups ◽  
Dose Aspirin ◽  
Age Related ◽  
Low Dose Aspirin ◽  
Old Mice

The age-related impairment of endothelium-dependent vasodilatation contributes to increased cardiovascular risk in the elderly. For primary and secondary prevention, aspirin can reduce the incidence of cardiovascular events in this patient population. The present work evaluated the effect of low-dose aspirin on age-related endothelial dysfunction in C57B/J6 aging mice and investigated its protective antioxidative effect. Age-related endothelial dysfunction was assessed by the response to acetylcholine of phenylephrine-induced precontracted aortic segments isolated from 12-, 36-, 60-, and 84-wk-old mice. The effect of low-dose aspirin was examined in mice presenting a decrease in endothelial-dependent relaxation (EDR). The effects of age and aspirin treatment on structural changes were determined in mouse aortic sections. The effect of aspirin on the oxidative stress markers malondialdehyde and 8-hydroxy-2′-deoxyguanosine (8-OhdG) was also quantified. Compared with that of 12-wk-old mice, the EDR was significantly reduced in 60- and 84-wk-old mice ( P < 0.05); 68-wk-old mice treated with aspirin displayed a higher EDR compared with control mice of the same age (83.9 ± 4 vs. 66.3 ± 5%; P < 0.05). Aspirin treatment decreased 8-OHdG levels ( P < 0.05), but no significant effect on intima/media thickness ratio was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 wk of age). It was found that low-dose aspirin is able to prevent age-related endothelial dysfunction in aging mice. However, the absence of this effect in the older age groups demonstrates that treatment should be initiated early on. The underlying mechanism may involve the protective effect of aspirin against oxidative stress.

scholarly journals Low-dose aspirin protective effects are correlated with deregulation of HNF factor expression in the preeclamptic placentas from mice and humans

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Aurélien Ducat ◽  
Alexandra Vargas ◽  
Ludivine Doridot ◽  
Alessia Bagattin ◽  
Jonathan Lerner ◽  
...  
Keyword(s):  
Low Dose ◽  
Protective Effects ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Factor Expression

scholarly journals Effect of low‐dose aspirin on health outcomes: An umbrella review of systematic reviews and meta‐analyses

2020 ◽  
Vol 86 (8) ◽  
pp. 1465-1475 ◽  
Author(s):  
Nicola Veronese ◽  
Jacopo Demurtas ◽  
Trevor Thompson ◽  
Marco Solmi ◽  
Gabriella Pesolillo ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Systematic Reviews ◽  
Low Dose ◽  
Umbrella Review ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Meta Analyses

scholarly journals Aspirin to Prevent Preeclampsia

2020 ◽  
Vol 32 (2) ◽  
pp. 106-116
Author(s):  
Ferdousi Begum ◽  
TA Chowdhury
Keyword(s):  
Preterm Birth ◽  
High Risk ◽  
Low Dose ◽  
Growth Restriction ◽  
Mortality And Morbidity ◽  
Pregnancy And Childbirth ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Adverse Pregnancy ◽  
Meta Analyses

Background: Pre-eclampsia is a major cause of mortality and morbidity during pregnancy and childbirth. There are recommendations on use of medications to prevent preeclampsia, including low dose aspirin. Objective: The objective of this review is to discuss role of aspirin in reducing the incidence and maternal mortality and morbidity due to preeclampsia including its dose and duration of use. Methods: Review of available literature in internet and from libraries. Results: Four large randomized trials have demonstrated a reduction in the incidence of preeclampsia in patients treated with low-dose aspirin prophylaxis compared with placebo/ no treatment (15 versus 19 percent, 18 versus 20 percent, 6.7 versus 7.6 percent, and 1.6 versus 4.3 percent); however, the results were statistically significant in only the last trial. When data from these and other trials were pooled, meta-analyses supported the significance of the trend observed in individual trials. When begun early in the second trimester, use of low-dose aspirin (75-150 mg) reduced the incidence of preeclampsia by at least 10 percent, with the greatest absolute benefit in women at moderate to high risk of developing the disease. Serious sequelae of early onset preeclampsia, such as preterm birth and fetal growth restriction, were also reduced. Conclusion: Low-dose aspirin reduces the frequency of preeclampsia, as well as related adverse pregnancy outcomes (preterm birth, growth restriction), by about 10 to 20 percent when given to women at moderate to high risk of the disease. It has an excellent maternal/ fetal safety profile in pregnancy. WHO recommends Low-dose acetylsalicylic acid (aspirin, 75 mg) for the prevention of preeclampsia in women at high risk of developing the condition; should be initiated before 20 weeks of pregnancy. It should be taken preferably from 13th week of pregnancy, daily, regularly and may be discontinued 5 to 10 days before delivery. Bangladesh J Obstet Gynaecol, 2017; Vol. 32(2) : 106-116

scholarly journals Recent Advances in NSAIDs-Induced Enteropathy Therapeutics: New Options, New Challenges

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yun Jeong Lim ◽  
Hoon Jai Chun
Keyword(s):  
Small Intestine ◽  
Low Dose ◽  
Gram Negative Bacteria ◽  
Protective Effects ◽  
Promising Strategy ◽  
Dose Aspirin ◽  
Nsaid Enteropathy ◽  
Low Dose Aspirin ◽  
Small Intestinal ◽  
Cox 2 Inhibitors

The injurious effects of NSAIDs on the small intestine were not fully appreciated until the widespread use of capsule endoscopy. It is estimated that over two-thirds of regular NSAID users develop injury in the small intestinal injuries and that these injuries are more common than gastroduodenal mucosal injuries. Recently, chronic low-dose aspirin consumption was found to be associated with injury to the lower gut and to be a significant contributing factor in small bowel ulceration, hemorrhage, and strictures. The ability of aspirin and NSAIDs to inhibit the activities of cyclooxygenase (COX) contributes to the cytotoxicity of these drugs in the gastrointestinal tract. However, many studies found that, in the small intestine, COX-independent mechanisms are the main contributors to NSAID cytotoxicity. Bile and Gram-negative bacteria are important factors in the pathogenesis of NSAID enteropathy. Here, we focus on a promising strategy to prevent NSAID-induced small intestine injury. Selective COX-2 inhibitors, prostaglandin derivatives, mucoprotective drugs, phosphatidylcholine-NSAIDs, and probiotics have potential protective effects on NSAID enteropathy.

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