急性缺血性卒中后阿司匹林联合缓释型双嘧达莫预防脑血管缺血事件的临床观察

目的：比较阿司匹林联合缓释型双嘧达莫和阿司匹林预防急性缺血性卒中后预防脑血管缺血事件的疗效。方法：60例发病48小时内急性缺血性卒患者随机分为联合组（n=30）和阿司匹林组（n=30）,分别采用联合应用阿司匹林和缓释型双嘧达莫（50mg,2次／d;双嘧达莫100mg,2次／d）和单独应用阿司匹林（50mg,2次／d）进行抗血小板治疗。随访6个月,比较2组脑血管缺血事件发生率和NIHSS评分降低值,并记录药物不良反应。结果：治疗组3例失访和1例终止实验,对照组5例失访,进入结果分析的例数为51例。联合组的患者6个月内脑血管缺血事件发生率明显低于单独应用阿司匹林组（11．5％VS．20．O％,P〈0．05）。而且,联合组NIHSS评分比单独应用阿司匹林降低更明显（4．52±1．8 vs．3．62±3.3,P〈0．05）。结论：联合应用阿司匹林和双嘧达莫在急性缺血性卒中后预防脑血管缺血事件的疗效明显优于单独应用阿司匹林。     

Efficacy and Safety of Adding Clopidogrel to Aspirin on Stroke Prevention among High Vascular Risk Patients: A Meta-Analysis of Randomized Controlled Trials

Objectives

Whether clopidogrel should be added to aspirin for stroke prevention remained controversial for the risk of hemorrhagic complications. This meta-analysis was aimed to assess the efficacy and safety of adding clopidogrel to aspirin on stroke prevention in high vascular risk patients, and to provide evidence for a suitable duration of dual antiplatelet therapy.

Methods

We searched PubMed, EMBase, OVID and Cochrane Central Register of Controlled Trials (up to June, 2013) for randomized controlled trials evaluating the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in high vascular risk patients. Comparisons of stroke and hemorrhagic complications between treatment groups were expressed by the pooled Relative Risks (RRs) with 95% Confidence Intervals (CIs).

Results

Fifteen trials with a total of 97692 intention-to-treat participants were included with duration of follow-up ranging from 7 days to 3.6 years. Dual antiplatelet therapy reduced all stroke by 21% (RR: 0.79, 95% CI: 0.73–0.85) with no evidence of heterogeneity across the trials (P = 0.27, I ² = 17%).The effects were consistent between short-term subgroup (≤1 month, RR: 0.76, 95% CI: 0.67–0.85) and long-term subgroup (≥3 months, RR: 0.81, 95% CI: 0.73–0.89). The risk of major bleeding was not significantly increased by dual antiplatelet therapy in short-term subgroup (RR: 1.11, 95% CI: 0.91–1.36), while significantly increased in long-term subgroup (RR: 1.52, 95% CI: 1.36–1.69). Long-term dual antiplatelet therapy substantially increased the risk of intracranial bleeding (RR: 1.76, 95% CI: 1.22–2.54).

Conclusions

This meta-analysis demonstrates that short-term combination of clopidogrel and aspirin is effective and safe for stroke prevention in high vascular risk patients. Long-term combination therapy substantially increases the risk of major bleeding and intracranial bleeding.     

The Efficacy and Adverse Reaction of Bleeding of Clopidogrel plus Aspirin as Compared to Aspirin Alone after Stroke or TIA: A Systematic Review

Background and Purpose

Given the high risk of stroke after TIA (transient ischemia attack) or stroke and the adverse reaction of bleeding of antiplatelets, we undertook a meta-analysis, reviewed randomized controlled trials (RCTs) comparing aspirin plus clopidogrel with aspirin alone to determine the efficacy and adverse reaction of bleeding of the two protocols in the prevention of stroke.

Methods

We analyzed the incidences of stroke, bleeding and severe bleeding by using fixed-effect model or random-effect model on the basis of the result of heterogeneity test.

Results

Five qualified RCTs satisfied the inclusion criteria. We found that treatment with aspirin plus clopidogrel was associated with lower incidence of stroke (Risk Ratio (RR), 0.66, 95% confidence interval (CI), 0.47 to 0.93), higher incidence of bleeding (RR, 1.75, 95% CI, 1.48 to 2.05) as compared with aspirin-alone treatment. In terms of severe bleeding, no statistical difference existed between them (RR, 2.21, 95% CI, 0.25 to 19.52).

Conclusion

The combined use of aspirin and clopidogrel is more effective than aspirin alone for patients with previous TIA or stroke for the prevention of stroke, with risk of bleeding being higher. No statistical difference was found in severe bleeding between the two treatment protocols.     

Multimodal Secondary Prevention Behavioral Interventions for TIA and Stroke: A Systematic Review and Meta-Analysis

Background

Guidelines recommend implementation of multimodal interventions to help prevent recurrent TIA/stroke. We undertook a systematic review to assess the effectiveness of behavioral secondary prevention interventions.

Strategy

Searches were conducted in 14 databases, including MEDLINE (1980-January 2014). We included randomized controlled trials (RCTs) testing multimodal interventions against usual care/modified usual care. All review processes were conducted in accordance with Cochrane guidelines.

Results

Twenty-three papers reporting 20 RCTs (6,373 participants) of a range of multimodal behavioral interventions were included. Methodological quality was generally low. Meta-analyses were possible for physiological, lifestyle, psychosocial and mortality/recurrence outcomes. Note: all reported confidence intervals are 95%. Systolic blood pressure was reduced by 4.21 mmHg (mean) (−6.24 to −2.18, P = 0.01 I² = 58%, 1,407 participants); diastolic blood pressure by 2.03 mmHg (mean) (−3.19 to −0.87, P = 0.004, I² = 52%, 1,407 participants). No significant changes were found for HDL, LDL, total cholesterol, fasting blood glucose, high sensitivity-CR, BMI, weight or waist:hip ratio, although there was a significant reduction in waist circumference (−6.69 cm, −11.44 to −1.93, P = 0.006, I² = 0%, 96 participants). There was no significant difference in smoking continuance, or improved fruit and vegetable consumption. There was a significant difference in compliance with antithrombotic medication (OR 1.45, 1.21 to 1.75, P<0.0001, I² = 0%, 2,792 participants) and with statins (OR 2.53, 2.15 to 2.97, P< 0.00001, I² = 0%, 2,636 participants); however, there was no significant difference in compliance with antihypertensives. There was a significant reduction in anxiety (−1.20, −1.77 to −0.63, P<0.0001, I² = 85%, 143 participants). Although there was no significant difference in odds of death or recurrent TIA/stroke, there was a significant reduction in the odds of cardiac events (OR 0.38, 0.16 to 0.88, P = 0.02, I² = 0%, 4,053 participants).

Conclusions

There are benefits to be derived from multimodal secondary prevention interventions. However, the findings are complex and should be interpreted with caution. Further, high quality trials providing comprehensive detail of interventions and outcomes, are required.

Review Registration

PROSPERO CRD42012002538.     

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis

Objective

We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT) combined with temozolomide (TMZ) versus RT alone as first-line treatment for brain metastases (BM).

Methods

Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs). Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and adverse events.

Results

Seven studies were selected from the literature search. RT plus TMZ produced significant improvement in ORR with odds ratio (OR) of 2.27 (95% CI, 1.29 to 4.00; P = 0.005) compared with RT alone. OS and PFS were not significantly different between the two arms (OS: HR, 1.00; P = 0.959; PFS: HR, 0.73; P = 0.232). However, the RT plus TMZ arm was associated with significantly more grade 3 to 4 nausea and thrombocytopenia.

Conclusion

Concomitant RT and TMZ, compared to RT alone, significantly increases ORR in patients with BM, but yields increased toxicity and fails to demonstrate a survival advantage.     

Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis

Background

Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.

Objective

A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.

Data Sources

MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.

Study Selection

Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.

Data Extraction

Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.

Data Synthesis

Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11–0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69–3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40–1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.

Conclusions

VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients’ risk for recurrent PE as well as the patients’ values and preferences.     

Dacarbazine Combined Targeted Therapy versus Dacarbazine Alone in Patients with Malignant Melanoma: A Meta-Analysis

Background

Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma.

Methods

We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events.

Results

Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR]  = 1.60, 95% confidence interval [CI]: 1.27–2.01) and 1-year survival (combined RR = 1.26, 95% CI: 1.14–1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR = 1.23, 95% CI: 1.10–1.36), vomiting (combined RR = 1.73, 95% CI: 1.41–2.12) and neutropenia (combined RR = 1.75, 95% CI: 1.42–2.16) compared to the group for DTIC alone.

Conclusion

These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion.     

A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

Objectives

The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery.

Methods

Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software.

Results

Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone.

Conclusion

The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone.

Level of Evidence

Level I, meta-analysis of Level I studies.     

Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials

Objective

The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted.

Methods

A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I² tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg’s funnel plots and Egger’s linear regression test were used to detect any publication bias.

Results

This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = −1.0 min, 95% CI −1.5 to −0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001).

Conclusion

Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus.     

Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials

Background

Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke.

Methods

A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions.

Results

B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12.

Conclusions

B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.     

Aspirin Use and Risk of Age-Related Macular Degeneration: A Meta-Analysis

Background

Age-related macular degeneration (AMD) is the main cause of blindness and the curative options are limited. The objective of this meta-analysis was to determine the association between aspirin use and risk of AMD.

Methods

A comprehensive literature search was performed in PubMed, Embase, Web of Science, and reference lists. A meta-analysis was performed by STATA software.

Results

Ten studies involving 171729 individuals examining the association between aspirin use and risk of AMD were included. Among the included studies, 2 were randomized-controlled trials (RCTs), 4 were case-control studies and 4 were cohort studies. The relative risks (RRs) were pooled using a random-effects model. Relative risks with 95% confidence intervals (CIs) of aspirin use as a risk for AMD. The pooled RR of 10 included studies between the use of aspirin and risk of AMD was 1.09 (95% CI, 0.96–1.24). The same result was detected in early and late stage AMD subgroup analysis. In the subgroup analyses, the pooled RR of RCTs, case-control studies and cohort studies were 0.81 (95% CI, 0.64–1.02), 1.02 (95% CI, 0.92–1.14) and 1.08 (95% CI, 0.91–1.28), respectively.

Conclusions

The use of aspirin was not associated with the risk of AMD.     

Efficacy and Safety of Endovascular Treatment versus Intravenous Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Background and Purpose

Although endovascular therapy (ET) is increasingly used in patients with moderate to severe acute ischemic stroke, its efficacy and safety remains controversial. We performed a meta-analysis aiming to compare the benefits and safety of endovascular treatment and intravenous thrombolysis in the treatment of acute ischemic stroke.

Methods

We systematically searched PubMed, Embase, Science direct and Springer unitil July, 2013. The primary outcomes included good outcome (mRS ≤ 2) and excellent outcome (mRS ≤ 1) at 90 days or at trial end point. Secondary outcomes were occurrence of symptomatic hemorrhage and all-cause mortality.

Results

Using a prespecified search strategy, 5 RCTs with 1106 patients comparing ET and intravenous thrombolysis (IVT) were included in the meta-analysis. ET and IVT were associated with similar good (43.06% vs 41.78%; OR=1.14; 95% CI, 0.77 to 1.69; P=0.52;) and excellent (30.43% vs 30.42%; OR=1.05; 95% CI, 0.80 to 1.38; P=0.72;) outcome. For additional end points, ET was not associated with increased occurrence of symptomatic hemorrhage (6.25% vs. 6.22%; OR=1.03; 95% CI, 0.62 to 1.69; P=0.91;), or all-cause mortality (18.45% vs. 17.35%; OR=1.00; 95% CI, 0.73 to 1.39; P=0.99;).

Conclusions

Formal meta-analysis indicates that there are similar safety outcomes and functional independence with endovascular therapy and intravenous thrombolysis for acute ischemic stroke.     

Neoadjuvant Bevacizumab plus Chemotherapy versus Chemotherapy Alone to Treat Non-Metastatic Breast Cancer: A Meta-Analysis of Randomised Controlled Trials

Purpose

Results from previous randomised controlled trials (RCTs) investigating whether the addition of bevacizumab to neoadjuvant chemotherapy (NAC) could statistically significantly increase the pathological complete response (pCR) and to identify which subgroup would benefit most from such regimens have produced conflicting results. This meta-analysis was designed to assess the efficacy and safety of bevacizumab plus chemotherapy compared with chemotherapy alone in the neoadjuvant setting.

Methods

A literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane library was performed to identify eligible studies. The primary endpoint of interest was pCR. The secondary endpoints were clinical complete rate (cCR), surgery rate, breast-conserving surgery (BCS) rate, and toxicity. The meta-analysis was performed using Review Manager software version 5.3.

Results

Nine RCTs matched the selection criteria, yielding a total of 4967 patients (bevacizumab plus chemotherapy: 50.1%, chemotherapy alone: 49.9%). The results of this meta-analysis demonstrated that the addition of bevacizumab to NAC significantly increased the pCR rate (odds ratio [OR] = 1.34 [1.18–1.54]; P < 0.0001) compared with chemotherapy alone. Subgroup analysis showed that the effect of bevacizumab was more pronounced in patients with HER2-negative cancer (OR = 1.34 [1.17–1.54]; P < 0.0001) compared with HER2-positive cancer (OR = 1.69 [0.90–3.20]; P = 0.11). Similarly, in patients with HER2-negative cancer, the effect of bevacizumab was also more pronounced in patients with HR-negative cancer (OR = 1.38 [1.09–1.74]; P = 0.007) compared with HR-positive cancer (OR = 1.36 [0.78–2.35]; P = 0.27). No significant differences were observed between the groups with respect to cCR, surgery rate, or BCS rate. Additionally bevacizumab was associated with a higher incidence of neutropenia, febrile neutropenia, and hand–foot syndrome.

Conclusions

Higher proportions of patients achieved pCR when bevacizumab was added to NAC compared with when they received chemotherapy alone; acceptable toxicities were also found. Subgroup analysis demonstrated that patients with histologically confirmed HER2-negative and HR-negative breast cancer benefited the most.     

Neoadjuvant Chemotherapy Followed by Surgery versus Surgery Alone for Gastric Carcinoma: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

The effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC.

Methods

We systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed.

Results

A total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65–1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20–3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment.

Conclusions

NAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with chemotherapy-related adverse effects as a drawback. This level 1a evidence doesn''t support NAC to outweigh SA in terms of survival and surgical benefits when dealing with GC.     

Regional versus General Anesthesia for Percutaneous Nephrolithotomy: A Meta-Analysis

ObjectiveTo compare the effectiveness and safety of regional anesthesia (RA) and general anesthesia (GA) for percutaneous nephrolithotomy (PNL).ResultsEight randomized controlled trials (RCTs) and six non-randomized controlled trials (nRCTs) involving 2270 patients were included. Patients receiving RA were associated with shorter operative time (−6.22 min; 95%CI, −9.70 to −2.75; p = 0.0005), lower visual analgesic score on the first and third postoperative day (WMD, −2.62; 95%CI, −3.04 to −2.19; p < 0.00001 WMD, −0.38; 95%CI, −0.58 to −0.18; p = 0.0002), less analgesic requirements (WMD, −59.40 mg; 95%CI, −78.39 to −40.40; p<0.00001), shorter hospitalization (WMD, −0.36d; 95%CI, −0.66 to −0.05; p = 0.02), less blood transfusion (RR, 0.61; 95%CI, 0.41 to 0.93; p = 0.02), fewer modified Clavion-Dindo Grade II (RR, 0.56; 95%CI, 0.37 to 0.83; p = 0.005), Grade III or above postoperative complications (RR, 0.51; 95%CI, 0.33 to 0.77; p = 0.001), and potential benefits of less fever (RR, 0.79; 95%CI, 0.61 to 1.02; p = 0.07), nausea or vomiting (RR, 0.54; 95%CI, 0.20 to 1.46; p = 0.23), whereas more intraoperative hypotension (RR, 3.13; 95%CI, 1.76 to 5.59; p = 0.0001) when compared with patients receiving GA. When nRCTs were excluded, most of the results were stable but the significant differences were no longer detectable in blood transfusion, Grade II and more severe complications. No significant difference in the total postoperative complications and stone-free rate were found.ConclusionsCurrent evidence suggests that both RA and GA can provide safe and effective anesthesia for PNL in carefully evaluated and selected patients. Each anesthesia technique has its own advantages but some aspects still remain unclear and need to be explored in future studies.     

Robotic versus Open Gastrectomy for Gastric Cancer: A Meta-Analysis

Aim

To evaluate the safety and efficacy of robotic gastrectomy versus open gastrectomy for gastric cancer.

Methods

A comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Knowledge was performed. Systematic review was carried out to identify studies comparing robotic gastrectomy and open gastrectomy in gastric cancer. Intraoperative and postoperative outcomes were also analyzed to evaluate the safety and efficacy of the surgery. A fixed effects model or a random effects model was utilized according to the heterogeneity.

Results

Four studies involving 5780 patients with 520 (9.00%) cases of robotic gastrectomy and 5260 (91.00%) cases of open gastrectomy were included in this meta-analysis. Compared to open gastrectomy, robotic gastrectomy has a significantly longer operation time (weighted mean differences (WMD) =92.37, 95% confidence interval (CI): 55.63 to 129.12, P<0.00001), lower blood loss (WMD: -126.08, 95% CI: -189.02 to -63.13, P<0.0001), and shorter hospital stay (WMD = -2.87; 95% CI: -4.17 to -1.56; P<0.0001). No statistical difference was noted based on the rate of overall postoperative complication, wound infection, bleeding, number of harvested lymph nodes, anastomotic leakage and postoperative mortality rate.

Conclusions

The results of this meta-analysis suggest that robotic gastrectomy is a better alternative technique to open gastrectomy for gastric cancer. However, more prospective, well-designed, multicenter, randomized controlled trials are necessary to further evaluate the safety and efficacy as well as the long-term outcome.     

High-Maintenance-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background

Despite routine use of clopidogrel, adverse cardiovascular events recur among some patients undergoing percutaneous coronary intervention (PCI). To optimize antiplatelet therapies, we performed a meta-analysis to quantify the efficacy of high versus standard-maintenance-dose clopidogrel in these patients.

Methods

Randomized controlled trials (RCTs) comparing high (>75 mg) and standard maintenance doses of clopidogrel in patients undergoing PCI were included. The primary efficacy and safety end-points were major adverse cardiovascular/cerebrovascular events (MACE/MACCE) and major bleeding. The secondary end-points were other ischemic and bleeding adverse effects. The pooled odds ratio (OR) for each outcome was estimated.

Results

14 RCTs with 4424 patients were included. Compared with standard-maintenance-dose clopidogrel, high-maintenance-dose clopidogrel significantly reduced the incidence of MACE/MACCE (OR 0.60; 95% CI 0.43 to 0.83), stent thrombosis (OR 0.56; 95% CI 0.32 to 0.99) and target vessel revascularization (OR 0.38; 95% CI 0.20 to 0.74), without significant decrease of the risk of cardiovascular death (OR 0.92; 95% CI 0.74 to 1.13) and myocardial infarction (OR 0.83; 95% CI 0.51 to 1.33). For safety outcomes, it did not significantly increase the risk of major bleeding (OR 0.73; 95% CI 0.41 to 1.32), minor bleeding (OR 1.29; 95% CI 1.00 to 1.66) and any bleeding (OR 1.14; 95% CI 0.91 to 1.43).

Conclusion

High-maintenance-dose clopidogrel reduces the recurrence of most ischemic events in patients post-PCI without increasing the risk of bleeding complications.     

Aspirin for Primary Prevention of Cardiovascular Events: Meta-Analysis of Randomized Controlled Trials and Subgroup Analysis by Sex and Diabetes Status

Objective

To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status.

Methods

We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12.

Results

Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85–0.95), myocardial infarction (0.86; 0.75–0.93), ischemic stroke (0.86; 0.75–0.98) and all-cause mortality (0.94; 0.89–0.99). There were also increases in hemorrhagic stroke (1.34; 1.01–1.79) and major bleeding (1.55; 1.35–1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59–0.85) and ischemic stroke among women (0.77; 0.63–0.93). Aspirin use was associated with a reduction (0.65; 0.51–0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day).

Conclusions

The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials.