Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor.
使用 P2Y12 抑制剂普拉格雷或替格瑞洛双联抗血小板治疗眼内出血的荟萃分析。
- 作者列表："Sun MT","Huang S","Wiviott SD","Antman EM","Roe MT","Ohman EM","Neely M","Wallentin L","Wong CX
:Intraocular bleeding is a devastating clinical event due to its potentially blinding nature. It is not known if determine if dual antiplatelet therapy using aspirin and potent P2Y12 inhibitors increases this risk. We searched MEDLINE and ClinicalTrials.gov for randomized controlled trials that were phase III, randomly assigned patients to dual antiplatelet therapy with either aspirin and a potent P2Y12 inhibitor or aspirin and clopidogrel, had follow-up of 6 months, and at least 200 patients. Corresponding authors were contacted for intraocular bleeding data. Inverse-variance, weighted, fixed-effects meta-analysis was undertaken, with random-effects meta-analysis performed as a sensitivity analysis. Four trials enrolling 42,850 patients were included. The median follow-up ranged from 12 to 14 months. There was overall low risk of bias. Pooled analysis demonstrated no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (risk ratio 0.89, 95% confidence interval 0.58 to 1.36). There was no significant heterogeneity observed across trials (I2 statistic 0%, p = 0.98). The use of random-effects meta-analysis did not change the effect estimate or confidence intervals, and the results appeared similar when stratified by potent P2Y12 inhibitor (p = 0.97). In conclusion, this collaborative meta-analysis of dual antiplatelet trials does not suggest that the risk of intraocular bleeding is increased with the use of potent P2Y12 inhibitors compared with clopidogrel. Our results suggest that these potent P2Y12 inhibitors may continue to be used cautiously where indicated as part of dual antiplatelet therapy, even in those at high risk of spontaneous intraocular bleeding.
: 眼内出血是一个毁灭性的临床事件，由于其潜在的致盲性。不知道是否使用阿司匹林和有效的 P2Y12 抑制剂的双重抗血小板治疗会增加这种风险。我们检索了 MEDLINE 和 ClinicalTrials.gov 的随机对照试验，这些试验是 III 期的，随机分配患者接受阿司匹林和有效的 P2Y12 抑制剂或阿司匹林和氯吡格雷的双重抗血小板治疗。随访 6 个月，至少有 200 例患者。联系相应作者了解眼内出血数据。进行反方差、加权、固定效应 meta 分析，随机效应 meta 分析作为敏感性分析。纳入了 4 项试验，招募了 42,850 例患者。中位随访时间 12 ~ 14 个月。总体偏倚风险较低。合并分析显示，与氯吡格雷相比，使用强效 P2Y12 抑制剂的双联抗血小板治疗的眼内出血风险无统计学显著增加 (风险比 0.89，95% 置信区间 0.58 至 1.36)。各试验均未观察到显著的异质性 (I2 统计量 0%，p = 0.98)。使用随机效应荟萃分析没有改变效应估计值或置信区间，当采用强效 P2Y12 抑制剂分层时，结果看起来相似 (p = 0.97)。总之，这项双联抗血小板试验的协作荟萃分析并不表明与氯吡格雷相比，使用强效 P2Y12 抑制剂会增加眼内出血的风险。我们的结果表明，这些强效的 P2Y12 抑制剂在作为双联抗血小板治疗的一部分时，即使在自发性眼内出血的高危人群中，也可以继续谨慎使用。
METHODS:BACKGROUND:People with stroke are not meeting recommended levels of physical activity. The modifiable factors associated with post-stroke physical activity levels need to be identified to develop targeted interventions. OBJECTIVE:The objective of this study was to investigate the factors at discharge from inpatient rehabilitation that are associated with physical activity levels at 3 months following discharge. DESIGN:This was a prospective cohort study. METHODS:Sixty-four people with stroke completed baseline assessments at discharge from inpatient rehabilitation and 55 completed the follow-up 3 months later. The candidate factors (i.e. gait speed, balance, strength, cognition, mood and motivation) were measured at discharge. The primary outcome measure at follow-up was walking related activity (measured by wrist-worn accelerometer). Secondary outcome measures were physical activity participation (Activity Card Sort) and intensity of physical activity (International Physical Activity Questionnaire - Short 7 days). Adjusted separate multivariable linear regression models or proportional odds regression models were used to evaluate the associations between candidate factors and physical activity. RESULTS:Gait speed and balance were associated with all aspects of physical activity. Higher level of intrinsic motivation was also associated with higher physical activity participation. Anxiety demonstrated a significant non-linear relationship with physical activity participation. LIMITATIONS:Inclusion of fatigue and individual muscle strength could have provided further insights into associations with steps per day. CONCLUSION:The results demonstrated that better physical function at discharge from inpatient rehabilitation was associated with future increased levels of physical activity. Additionally, higher levels of motivation impacted on increased physical activity participation. The influence of anxiety on physical activity participation requires further exploration. Mixed-method study designs can be utilized to further understand the factors associated with post-stroke physical activity.
METHODS:Cerebral ischemia-reperfusion (I/R) is characterized by initial transient cerebral ischemia followed by reperfusion. Various pathophysiological processes are involved in brain injury and functional recovery during cerebral I/R. There are few studies on dynamic metabolic process after cerebral I/R. The present study was to observe dynamic alteration of brain injury, functional recovery, and metabolites after cerebral I/R in rats and discover potential metabolic markers. The cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 90 min, following reperfusion in rats. The results of cerebral infarction area, cerebral edema, and behavior test showed that there were dynamic changes in brain injury and functional recovery at different periods after cerebral I/R. Further analysis showed that the brain injury was severe on the first day of cerebral I/R, and there was a significant functional recovery from the 7th day of cerebral I/R, followed by an aggravation trend of brain injury from the days 7 to 28. Furthermore, Matrix-assisted laser desorption ionization mass spectrometry imaging analysis showed that the expression of ATP, glucose, and citric acid on 7th day was the highest during cerebral I/R, which indicated that energy metabolism and oxidative phosphorylation played important roles during cerebral I/R. In addition, the untargeted metabolomic results showed that the level of isocitric acid, the ratio of oxyglutaric acid/glutamic acid, and the level of pyruvic acid associated with the TCA cycle were also the highest on the 7th day during cerebral I/R, which indicated that the transient spontaneous recovery of ischemic brain on the 7th day after ischemia-reperfusion might be related to oxidative phosphorylation and energy metabolism in the brain in this period. In conclusion, the results suggest that some small molecule metabolites participate in the brain injury and functional recovery during cerebral I/R, which is of great significance to the development of therapeutic drugs and diagnostic markers.
METHODS:The aims of this study were to study the effects of miR-2 on cerebral ischemia–reperfusion rats and to explore its further mechanism. Rats were assigned into sham, model, miR-22 control and miR-22 groups. Observation of neurological behaviors at 24 h after operation found that neurological functions were severely damaged in the model and miR-22 control groups and these damages were improved by miR-22. RT-PCR indicated that miR-22 mRNA level in the brain tissue was significantly decreased in the model and miR-22 control groups, but increased in the miR-22 group. TTC staining showed increased percentage of cerebral infarction volume in the model and miR-22 control groups and this increase was reduced by miR-22. Immunohistochemistry showed increased densities of CD34^+ and VEGF^+ microvessels in the cortex in the model and miR-22 control groups, which were further increased in the miR-22 group. ELISA showed increased serum VEGF and Ang-1 levels in the model and miR-22 control groups, which were also further increased in the miR-22 group. Western blot analysis showed increased phosphorylation level of PI3K and Akt in brain tissue in the model and miR-22 control groups, which were further increased in the miR-22 group. Administration of LY294002, a specific PI3K pathway inhibitor, significantly reversed all the effects of miR-22 on rats in the model group. miR-22 exerts its neuroprotective and angiogenic functions via the PI3K/Akt signaling pathway, at least partly, in rats under cerebral ischemia–reperfusion.