Efficacy and Safety of Antifibrinolytic Agents in Reducing Perioperative Blood Loss and Transfusion Requirements in Scoliosis Surgery: A Systematic Review and Meta-Analysis

Background

Routine use of antifibrinolytic agents in spine surgery is still an issue of debate.

Objective

To gather scientific evidence for the efficacy and safety of antifibrinolytic agents including aprotinin, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA, traditionally known as Amicar) in reducing perioperative blood loss and transfusion requirements in scoliosis surgery.

Methods

We conducted a systematic review and meta-analysis for randomized controlled trials (RCTs), retrospective case-control studies, and retrospective cohort studies on the use of antifibrinolytic agents in scoliosis surgery by searching in the MEDLINE and EMBASE databases and the Cochrane Database of Systematic Reviews and Controlled Trials of papers published from January 1980 through July 2014. Safety of the antifibrinolytic agents was evaluated in all included studies, while efficacy was evaluated in RCTs.

Results

Eighteen papers with a total of 1,158 patients were eligible for inclusion in this study. Among them, 8 RCTs with 450 patients were included for evaluation of pharmacologic efficacy (1 RCT was excluded because of a lack of standard deviation data). Mean blood loss was reduced in patients with perioperative use of antifibrinolytic agents by 409.25 ml intraoperatively (95% confidence interval [CI], 196.57–621.94 ml), 250.30 ml postoperatively (95% CI, 35.31–465.30), and 601.40 ml overall (95% CI, 306.64–896.16 ml). The mean volume of blood transfusion was reduced by 474.98 ml (95% CI, 195.30–754.67 ml). The transfusion rate was 44.6% (108/242) in the patients with antifibrinolytic agents and 68.3% (142/208) in the patients with placebo. (OR 0.38; 95% CI; 0.25–0.58; P<0.00001, I² = 9%). All studies were included for evaluation of safety, with a total of 8 adverse events reported overall (4 in the experimental group and 4 in the control group).

Conclusion

The systematic review and meta-analysis indicated that aprotinin, TXA, and EACA all significantly reduced perioperative blood loss and transfusion requirements in scoliosis surgery. There was no evidence that the use of antifibrinolytic agents was a risk factor for adverse events, especially thromboembolism, in scoliosis surgery.     

The Safety and Efficacy of Antifibrinolytic Therapy in Neonatal Cardiac Surgery

BackgroundNeonates undergoing open-heart surgery are particularly at risk of postoperative bleeding requiring blood transfusion. Aprotinin has attained high efficacy in reducing the requirement for a blood transfusion following a cardiopulmonary bypass, but is seldom studied in the neonatal age group. The aim of this study was to compare the efficacy and adverse effects of aprotinin and tranexamic acid in neonates undergoing open-heart surgery at a single centre.MethodsBetween October 2003 and March 2008, perioperative data of 552 consecutive neonatal patients undergoing open-heart surgery in Children’s Hospital Boston were reviewed. Among them, 177 did not receive antifibrinolytic therapy (Group A); 100 were treated with tranexamic acid only (Group B); and 275 patients received aprotinin with or without tranexamic acid (Group C). Except for antifibrinolytic therapy, the anaesthesiological and surgical protocols remained identical. Postoperative complications and in-hospital mortality were the primary study endpoints.ResultsBody weight and Risk Adjustment for Congenital Heart Surgery (RACHS-1) scores were statistically comparable among the three groups. No statistically significant differences were observed between the duration of hospitalization, chest tube drainage, reexploration for bleeding, and kidney function impairment. In Group C, less blood was transfused within 24 hours than in GroupB. Operative mortality was similar among the three groups.ConclusionNo further risk and kidney injury were observed in the use of aprotinin in neonatal cardiac surgery, aprotinin demonstrated a reduced requirement for blood transfusion compared with tranexamic acid. Our data provide reasonable evidence that aprotinin and tranexamic acid are safe and efficacious as antifibrinolytic modalities in neonatal patients undergoing cardiac surgery.     

Efficacy and Safety of HER2-Targeted Agents for Breast Cancer with HER2-Overexpression: A Network Meta-Analysis

BackgroundClinical trials of human epidermal growth factor receptor 2 (HER2)-targeted agents added to standard treatment have been efficacious for HER2-positive (HER2+) advanced breast cancer. To our knowledge, no meta-analysis has evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We performed a network meta-analysis of both direct and indirect comparisons to evaluate the effect of adding HER2-targeted agents to standard treatment and examined side effects.MethodsWe performed a Bayesian-framework network meta-analysis of randomized controlled trials to compare 6 HER2-targeted treatment regimens and 1 naïve standard treatment (NST, without any-targeted drugs) in targeted treatment of HER2+ breast cancer in adults. These treatment regimens were T-DM1, LC (lapatinib), HC (trastuzumab), PEC (pertuzumab), LHC (lapatinib and trastuzumab), and PEHC (pertuzumab and trastuzumab). The main outcomes were overall survival and response rates. We also examined side effects of rash, LVEF (left ventricular ejection fraction), fatigue, and gastrointestinal disorders, and performed subgroup analysis for the different treatment regimens in metastatic or advanced breast cancer.ResultsWe identified 25 articles of 21 trials, with data for 11,276 participants. T-DM1 and PEHC were more efficient drug regimens with regard to overall survival as compared with LHC, LC, HC and PEC. The incidence of treatment-related rash occurs more frequently in the patients who received LC treatment regimen than PEHC and T-DM1 and HC. In subgroup analysis, T-DM1 was associated with increased overall survival as compared with LC and HC. PEHC was associated with increased overall response as compared with LC, HC, and NST.ConclusionsOverall, the regimen of T-DM1 as well as pertuzumab in combination with trastuzumab and docetaxel is efficacious with fewer side effects as compared with other regimens, especially for advanced HER2+ breast cancer.ImpactThis study suggests that both T-DM1 and PEHC therapy are potentially and equally useful treatments for HER2+ breast cancer.     

Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials

BackgroundMethotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse.ObjectiveIn order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods).ResultsIn terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1–60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5–5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1–14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time.LimitationsMeta-analyses for efficacy and safety, respectively, employed non-identical selection criteria.ConclusionsThese meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes.     

Efficacy and Safety of Talc Pleurodesis for Malignant Pleural Effusion: A Meta-Analysis

Background

Talc pleurodesis has been widely used to control malignant pleural effusion; however, it is still not clear whether talc pleurodesis is more effective than other local therapies. We performed a meta-analysis to evaluate the efficacy and safety of talc pleurodesis in the management of malignant pleural effusion.

Methods

PubMed, Embase, and Web of Science were searched for English-language studies of clinical controlled trials comparing talc pleurodesis with control therapies until August 8, 2013. Success rate and incidence of adverse events were evaluated. Relative risks were estimated using random- or fixed- effects model and statistical heterogeneity was assessed using I² test.

Results

Twenty trials involving 1,525 patients with malignant pleural effusion were included. The success rate of talc pleurodesis was significantly higher than that of control therapies (relative risk, 1.21; 95% confidence interval, 1.01–1.45; p = 0.035) with similar adverse events. In addition, thoracoscopic talc poudrage was more effective than bedside talc slurry (relative risk, 1.12; 95% confidence interval, 1.01–1.23; p = 0.026).

Conclusions

The current evidences suggested the benefit for talc pleurodesis in the treatment of malignant pleural effusion. Talc pleurodesis, especially thoracoscopic talc poudrage pleurodesis, should be performed in patients with malignant pleural effusion, especially those with life-expectancy longer than one month.     

Efficacy and Safety Assessment of the Addition of Bevacizumab to Adjuvant Therapy Agents in Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Aim

To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients.

Methods & Design/ Results

PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials comparing bevacizumab and adjuvant therapy with adjuvant therapy alone published from January 1966 to 7^th of May 2014. Progression free survival, overall survival, overall response rate, safety and quality of life were analyzed using random- or fixed-effects models according to the PRISMA guidelines. We obtained data from 44 randomized controlled trials (30,828 patients). Combining bevacizumab with different adjuvant therapies resulted in significant improvement of progression free survival (log hazard ratio, 0.87; 95% confidence interval (CI), 0.84–0.89), overall survival (log hazard ratio, 0.96; 95% CI, 0.94–0.98) and overall response rate (relative risk, 1.46; 95% CI: 1.33–1.59) compared to adjuvant therapy alone in all studied tumor types. In subgroup analyses, there were no interactions of bevacizumab with baseline characteristics on progression free survival and overall survival, while overall response rate was influenced by tumor type and bevacizumab dose (p-value: 0.02). Although bevacizumab use resulted in additional expected adverse drug reactions except anemia and fatigue, it was not associated with a significant decline in quality of life. There was a trend towards a higher risk of several side effects in patients treated by high-dose bevacizumab compared to the low-dose e.g. all grade proteinuria (9.24; 95% CI: 6.60–12.94 vs. 2.64; 95% CI: 1.29–5.40).

Conclusions

Combining bevacizumab with different adjuvant therapies provides a survival benefit across all major subsets of patients, including by tumor type, type of adjuvant therapy, and duration and dose of bevacizumab therapy. Though bevacizumab was associated with increased risks of some adverse drug reactions such as hypertension and bleeding, anemia and fatigue were improved by the addition of bevacizumab.     

脊柱微创手术对骨质疏松性椎体骨折的疗效及安全性分析

目的：探究脊柱微创手术对骨质疏松性椎体骨折的疗效及安全性。方法：选取我院骨科于2008年3月-2011年3月收治的72例骨质疏松性椎体压缩骨折进行分组治疗,观察组（n=36）接受脊柱微创手术,对照组（n=36）接受传统保守治疗,对比两组患者术后生活情况、疗效及观察组术后并发症。结果：两组患者治疗前压缩椎体高度/病椎上下椎体高度和之半、椎体后凸Cobb角及骨块侵占椎管比率无明显统计学差异（P〉0.05）,治疗后上述指标均显著改善,观察组改善程度较对照组更为明显（P〈0.05）;观察组治疗优良率91.7%,对照组为58.3%,其中6例患者因症状加重转为手术治疗,观察组治疗效果明显优于对照组（P〈0.05）;观察组患者术后未出现内植物松动、断裂、形成假关节、截瘫等并发症,钉棒内固定系统坚强可靠;两组患者均获得有效随访,平均随访时间（9.7±2.5）个月,观察组平均下地时间（4.1±1.7）d,肌力恢复时间（3.7±0.8）周,Frankel神经功能均恢复E级;对照组平均下地时间（7.4±3.0）d,肌力恢复时间（5.9±1.4）周,Frankel神经功能评分：D级6例,E级30例。结论：脊柱微创手术能够有效改善骨质疏松性椎体骨折患者骨骼力学变化,可有效保证其术后恢复情况,疗效较好,且不会引发严重并发症,值得临床广泛推广。     

Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis

Aim

The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome.

Methods

We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis.

Results

Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score ≥4). Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77). In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71), while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28). The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99). The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17). In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37). Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups.

Conclusions

TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS.     

Comparison of Clinical Efficacy and Safety between Indacaterol and Tiotropium in COPD: Meta-Analysis of Randomized Controlled Trials

Two once-daily inhaled bronchodilators, indacaterol and tiotropium, are widely used as first-line therapy in stable COPD patients. This study was performed to compare the clinical efficacy and safety between indacaterol and tiotropium in patients with moderate-to-severe COPD. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched to identify all published randomized controlled trials (RCTs). The primary outcome was trough forced expiratory volume in 1 second (FEV₁) at week 12. Four RCTs were eligible for inclusion (three RCTs with moderate-to-severe COPD patients and one RCT with only severe COPD patients). Trough FEV₁ at weeks 12 and 26 were not significantly different between indacaterol and tiotropium by the standardized mean difference with 0.014 (95% CI, -0.036, 0.063, I²= 23.5%) and with 0.037 (95% CI, -0.059 to 0.133, I²= 0%) along with differences in means of 0.003L and 0.014L, respectively. Indacaterol and tiotropium also showed similar St. George`s Respiratory Questionnaire (SGRQ) total scores and percentages of patients with SGRQ improvement (≥ 4 units) at week 26. The incidences of nasopharyngitis, serious cardiovascular events, and serious adverse events were not different between indacaterol and tiotropium, while those of cough (OR = 1.68, P < 0.001, and RR = 1.63) and COPD worsening (OR = 1.18, P = 0.003, and RR = 1.12) were higher for indacaterol than tiotropium. However, when one study with only severe COPD patients was removed from the meta-analysis, the difference in the incidence of COPD worsening between indacaterol and tiotropium became non-significant (OR = 1.13, P = 0.204, and RR = 1.09). The clinical efficacy and serious adverse events between indacaterol and tiotropium were equivocal in patients with moderate-to-severe COPD. Cough is a common complaint associated with indacaterol, and COPD worsening needs to be carefully monitored in severe COPD patients when treated with indacaterol.     

腹腔镜手术治疗粘连性肠梗阻的疗效及安全性研究

目的：探讨腹腔镜粘连松解术治疗粘连性肠梗阻（AIO）的疗效,减少再梗阻率。方法：将120 例AIO 患者随机分为两组,每组60 例,开腹组实施开腹手术,腹腔镜组实施腹腔镜粘连松解术,观察两组术后恢复及并发症发生情况,对再梗阻危险因素进行Logistic 回归分析。结果：腹腔镜组术中失血量（73.48± 9.32）mL,少于开腹组的（207.45± 33.21）mL（P<0.05）;腹腔镜组手术、术后镇痛、下床活动、肠恢复蠕动、肛门恢复排气、拔除尿管及住院时间分别为（69.15± 10.13）min、（14.67± 7.23）h、（27.14± 7.04）h、（3.11± 0.96）d、（3.24± 1.02）d、（3.37± 1.23）d、（7.95± 3.05）d,均短于开腹组的（83.84± 9.24）min、（27.38± 8.02）h、（36.23± 5.87）h、（4.05± 1.35）d、（4.35± 1.74）d、（5.02± 2.13）d、（10.35± 3.71）d（P<0.05);腹腔镜组并发症发生率、再梗阻率分别为10.00%、10.00%,均低于开腹组的33.33%、40.00%（P<0.05);多因素Logistic 回归分析显示开腹手术、手术时间≥ 60 min 是再梗阻发生的独立危险因素。结论：腹腔镜手术治疗AIO 疗效优于开腹手术,而且并发症与再梗阻率低。     

Comparative Efficacy and Safety of Different Antiplatelet Agents for Prevention of Major Cardiovascular Events and Leg Amputations in Patients with Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis

There is a lack of consensus regarding which type of antiplatelet agent should be used in patients with peripheral arterial disease (PAD) and little is known on the advantages and disadvantages of dual antiplatelet therapy. We conducted a systematic review and network meta-analysis of available randomized controlled trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine, Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or in combination with aspirin) in PAD patients (PROSPERO public database; CRD42014010299).We collated evidence from previous relevant meta-analyses and searched online databases. Primary efficacy endpoints were: (1) the composite rate of major adverse cardiovascular events (MACE; including vascular deaths, non-fatal myocardial infarction and non-fatal stroke), and (2) the rate of major leg amputations. The primary safety endpoint was the rate of severe bleeding events. Bayesian models were employed for multiple treatment comparisons and risk-stratified hierarchies of comparative efficacy were produced to aid medical decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are reported in case of significant results. We analyzed 49 RCTs comprising 34,518 patients with 88,358 person-years of follow-up with placebo as reference treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in reducing MACE. A significant MACE reduction was noted with Ticagrelor plus aspirin (RR: 0.67; 95%CrI: 0.46–0.96, NNT = 66), Clopidogrel (RR: 0.72; 95%CrI: 0.58–0.91, NNT = 80), Ticlopidine (RR: 0.75; 95%CrI: 0.58–0.96, NNT = 87), and Clopidogrel plus aspirin (RR: 0.78; 95%CrI: 0.61–0.99, NNT = 98). Dual antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46–0.99 compared to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with Ticlopidine (RR: 5.03; 95%CrI: 1.23–39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI: 1.22–2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05–2.10, NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm profile (79% cumulative rank probability best and 77% cumulative rank probability safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce the rate of major leg amputations following revascularization, but carries a slightly higher risk of severe bleeding.     

Efficacy and Safety of Biodegradable Polymer Biolimus-Eluting Stents versus Durable Polymer Drug-Eluting Stents: A Meta-Analysis

Backgrounds

Drug-eluting stents (DES) with biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation DES. We aimed to determine the efficacy and safety of biodegradable polymer biolimus-eluting stents (BES) versus durable polymer DES.

Methods

Systematic database searches of MEDLINE (1950 to June 2013), EMBASE (1966 to June 2013), the Cochrane Central Register of Controlled Trials (Issue 6 of 12, June 2013), and a review of related literature were conducted. All randomized controlled trials comparing biodegradable polymer BES versus durable polymer DES were included.

Results

Eight randomized controlled trials investigating 11,015 patients undergoing percutaneous coronary interventions were included in the meta-analysis. The risk of major adverse cardiac events did not differ significantly between the patients treated with the biodegradable polymer BES and the durable polymer DES (Relative risk [RR], 0.970; 95% CI, 0.848–1.111; p = 0.662). However, biodegradable polymer BES was associated with reduced risk of very late ST compared with the durable polymer DES, while the risk of early or late ST was similar (RR for early or late ST, 1.167; 95% CI 0.755–1.802; p = 0.487; RR 0.273; 95% CI 0.115–0.652; p = 0.003; p for interaction = 0.003).

Conclusions

In this meta-analysis of randomized controlled trials, treatments with biodegradable polymer BES did not significantly reduce the risk of major adverse cardiac events, but demonstrated a significantly lower risk of very late ST when compared to durable polymer DES. This conclusion requires confirmation by further studies with long-term follow-up.

PROSPERO register number

http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004364#.UnM2lfmsj6J     

Clinical Efficacy and Safety of Nerve-Sparing Radical Hysterectomy for Cervical Cancer: A Systematic Review and Meta-Analysis

Backgroud and Objective

Nerve-sparing radical hysterectomy (NSRH) may be associated with lower postoperative morbidity than radical hysterectomy (RH). We aimed to compare the clinical efficacy and safety of abdominal or laparoscopic NSRH and RH for treating cervical cancer through systematic review and meta-analysis.

Methods

PubMed, EMBASE, The Cochrane Library and the Chinese National Knowledge Infrastructure databases were systematically searched for all relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to compare intra- and postoperative outcomes for the two techniques.

Results

A total of 17 clinical trials were identified. Meta-analysis showed that although operating time was significantly longer for abdominal or laparoscopic NSRH than for RH, NSRH based on laparotomy or laparoscopy proved more effective for postoperative recovery of bladder function. NSRH was also associated with lower bladder dysfunction morbidity and fewer postoperative complications. Two abdominal trials and one laparoscopic study further suggested that NSRH was associated with shorter time to recovery of anal/rectal function. In contrast, RH and NSRH based on laparotomy or laparoscopy were similar in terms of extent of resection, recurrence rate, survival rate, blood loss and frequency of intraoperative complications. The meta-analysis showed that abdominal NSRH was not significantly different from RH in length of hospital stay, while one trial suggested that length of hospital stay was shorter after laparoscopic NSRH than after the corresponding RH.

Conclusion

NSRH may be a reliable technique for treating early cervical cancer. Available evidence suggests that it is better than RH for postoperative recovery of pelvic organ function and postoperative morbidity, while the two techniques involve similar clinical safety and extent of resection. These results should be considered preliminary since they are based on a relatively small number of controlled trials, most of which were non-randomized. The findings should be verified in larger, well-designed studies.     

Comparison of the Efficacy and Safety of S-1-Based and Capecitabine-Based Regimens in Gastrointestinal Cancer: A Meta-Analysis

Purpose

Oral fluoropyrimidine (S-1, capecitabine) has been considered as an important part of various regimens. We aimed to evaluate the efficacy and safety of S-1-based therapy versus capecitabine -based therapy in gastrointestinal cancers.

Methods

Eligible studies were identified from Pubmed, EMBASE. Additionally, abstracts presented at American Society of Clinical Oncology (ASCO) conferences held between 2000 and 2013 were searched to identify relevant clinical trials. The outcome included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and advent events.

Results

A total of 6 studies (4 RCTs and 2 retrospective analysis studies) containing 790 participants were included in this meta-analysis, including 401 patients in the S-1-based group and 389 patients in the capecitabine-based group. Results of our meta-analysis indicated that S-1-based and capecitabine-based regimens showed very similar efficacy in terms of PFS (HR 0.92, 95% CI 0.78–1.09, P = 0.360), OS (HR 1.01, 95% CI 0.84–1.21, P = 0.949), ORR (HR 1.04, 95% CI 0.87–1.25, P = 0.683) and DCR (HR 1.02, 95% CI 0.94–1.10, P = 0.639). There was also no significant difference in toxicity between regimens other than mild more hand–foot syndrome in capecitabine-based regimens.

Conclusion

Both the S-1-based and capecitabine-based regimens are equally active and well tolerated, and have the potential of backbone chemotherapy regimen in further studies of gastrointestinal cancers.     

An Updated Meta-Analysis of the Efficacy and Safety of Acupuncture Treatment for Cerebral Infarction

Background

Ischemic stroke is the second most common cause of death and the primary cause of disability throughout the world. Acupuncture is frequently advocated as an adjunct treatment during stroke rehabilitation. The aim of this study was to update the clinical efficacy and safety of acupuncture for cerebral infarction.

Methods

Randomized controlled trials (RCT) on acupuncture treating cerebral infarction were searched from the following databases: PubMed, EMBASE, Cochrane Library, CNKI, CMB and VIP from inception to October 2013. The data of RCTs meeting the inclusive criteria were extracted according to Cochrane methods. The meta-analyses were conducted using Rev Man 5.0 software.

Results

A total of 25 trials involving 2224 patients were included. The results of this meta-analysis showed that the groups receiving acupuncture (observation group) were superior to the comparison groups (control group), with significant differences in the Clinical Efficacy Rates [OR = 4.04, 95%CI (2.93, 5.57), P<0.001], Fugl-Meyer Assessment [MD = 11.22, 95%CI (7.62, 14.82), P<0.001], Barthel Index Score [MD = 12.84, 95%CI (9.85, 15.82), P<0.001], and Neurological Deficit Score [MD = −2.71, 95% CI (−3.84, −1.94), P<0.001]. Three trials reported minor adverse events.

Conclusion

Current evidence provisionally demonstrates that acupuncture treatment is superior to either non-acupuncture or conventional therapy for cerebral infarction. Despite this conclusion, given the often low quality of the available trials, further large scale RCTs of better quality are still needed.     

Efficacy and Safety of Oral Antidiabetic Drugs in Comparison to Insulin in Treating Gestational Diabetes Mellitus: A Meta-Analysis

Objective

To assess the efficacy and safety of oral antidiabetic drugs (OADs) in gestational diabetes mellitus (GDM) in comparison to insulin.

Methods

A meta-analysis of randomized controlled trials was conducted. The efficacy and safety of OADs in comparison to insulin in GDM patients were explored. Studies were identified by conducting a literature search using the electronic databases of Medline, CENTRAL, CINAHL, LILACS, Scopus and Web of Science in addition to conducting hand search of relevant journals from inception until October 2013.

Results

Thirteen studies involving 2,151 patients met the inclusion criteria. These studies were randomized controlled trials of metformin and glyburide in comparison to insulin therapy. Our results indicated a significant increase in the risk for preterm births (RR, 1.51; 95% CI, 1.04–2.19, p = 0.03) with metformin compared to insulin. However, a significant decrease in the risk for gestational hypertension (RR, 0.54; 95% CI, 0.31–0.91, p = 0.02) was found. Postprandial glucose levels also decreased significantly in patients receiving metformin (MD, −2.47 mg/dL; 95% CI, −4.00, −0.94, p = 0.002). There was no significant difference between the two groups for the remaining outcomes. There were significant increases in the risks of macrosomia (RR, 2.34; 95% CI, 1.18–4.63, p = 0.03) and neonatal hypoglycemia (RR, 2.06; 95% CI, 1.27–3.34, p = 0.005) in the glyburide group compared to insulin whereas results for the other analyzed outcomes remained non-significant.

Conclusion

The available evidence suggests favorable effects of metformin in treating GDM patients. Metformin seems to be an efficacious alternative to insulin and a better choice than glyburide especially those with mild form of disease.     

Efficacy and Safety of Deep Anterior Lamellar Keratoplasty vs. Penetrating Keratoplasty for Keratoconus: A Meta-Analysis

Purpose

To evaluate difference in therapeutic outcomes between deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PKP) for the clinical treatment of keratoconus.

Methods

A comprehensive search was conducted in Pubmed, EMBASE, Cochrane Library, and Web of science. Eligible studies should include at least one of the following factors: best corrected visual acuity (BCVA), postoperative spherical equivalent (SE), postoperative astigmatism and endothelial cell count (ECC), central corneal thickness (CCT), graft rejection and graft failure, of which BCVA, graft rejection and graft failure were used as the primary outcome measures, and postoperative SE, astigmatism, CCT and ECC as the secondary outcome measures. Given the lack of randomized clinical trials (RCTs), cohort studies and prospective studies were considered eligible.

Results

Sixteen clinical trials involving 6625 eyes were included in this review, including 1185 eyes in DALK group, and 5440 eyes in PKP group. The outcomes were analyzed using Cochrane Review Manager (RevMan) version 5.0 software. The postoperative BCVA in DALK group was significantly better than that in PKP group (OR = 0.48; 95%CI 0.39 to 0.60; p<0.001). There were fewer cases of graft rejection in DALK group than those in PKP group (OR = 0.28; 95%CI 0.15 to 0.50; p<0.001). Nevertheless the rate of graft failure was similar between DALK and PKP groups (OR = 1.05; 95%CI 0.81 to 1.36; p = 0.73). There were no significant differences in the secondary outcomes of SE (p = 0.70), astigmatism (p = 0.14) and CCT (p = 0.58) between DALK and PKP groups. And ECC in DALK group was significantly higher than PKP group (p<0.001). The postoperative complications, high intraocular pressure (high-IOP) and cataract were analyzed, fewer cases of complications occurred in DALK group than those in PKP group (high-IOP, OR 0.22, 95% CI 0.11–0.44, P<0.001) (cataract, OR 0.22; 95% CI 0.08–0.61, P = 0.004). And no cases of expulsive hemorrhage and endophthalmitis were reported.

Conclusion

The visual outcomes for DALK were not equivalent to PKP. The rate of graft failure was similar between DALK and PKP. Fewer postoperative complications occurred in DALK group, indicating that compared with PKP, DALK has lower efficacy but higher safety.     

Efficacy and Safety of Radiotherapy Plus EGFR-TKIs in NSCLC Patients with Brain Metastases: A Meta-Analysis of Published Data

Background: The role of radiotherapy (RT) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains controversial. Therefore, we conducted a meta-analysis to comprehensively evaluate the efficacy and safety of RT plus EGFR-TKIs in those patients. Materials and Methods: Relevant literatures published between 2012 and 2017 were searched. Objective response rate(ORR), disease control rate (DCR), overall survival (OS), intracranial progression-free survival (I-PFS) and adverse events (AEs) were extracted. The combined hazard ratios (HRs) and relative risks (RRs) were calculated using random effects models. Results: Twenty-four studies (2810 patients) were included in the analysis. Overall, RT plus EGFR-TKIs had higher ORR (RR?=?1.32, 95%CI: 1.13–1.55), DCR (RR?=?1.12, 95%CI: 1.04–1.22), and longer OS (HR?=?0.72, 95%CI: 0.59–0.89), I-PFS (HR?=?0.64, 95%CI: 0.50–0.82) than monotherapy, although with higher overall AEs (20.2% vs 11.8%, RR?=?1.34, 95% CI: 1.11–1.62). Furthermore, subgroup analyses found concurrent RT plus EGFR-TKIs could prolong OS (HR?=?0.69, 95%CI: 0.55–0.86) and I-PFS (HR?=?0.57, 95%CI: 0.44–0.75). Asian ethnicity and lung adenocarcinoma (LAC) patients predicted a more favorable prognosis (HR?=?0.69,95%CI: 0.54–0.88, HR?=?0.66, 95%CI: 0.53–0.83, respectively). Conclusion: RT plus EGFR-TKIs had higher response rate, longer OS and I-PFS than monotherapy in NSCLC patients with BM. Asian LAC patients with EGFR mutation had a better prognosis with concurrent treatment. The AEs of RT plus EGFR-TKIs were tolerated.