Treatment of renal cell carcinoma with interferons

Renal cell carcinoma (RCC) is considered to be an immunogenic cancer. RCC is refractory to chemotherapy and radiation. Immunotherapy including interferon (IFN)-alpha, gamma and interleukin-2 are the treatment of choice for metastatic RCC. IFN-alpha is most widely used in Japan. The response rate of IFN-alpha is 10-20 %. Lung lesions and lymphnodes are the usual effective sites. The survival benefit of IFN-alpha in patients with metastatic RCC has been shown in prospective randomized studies. Nephrectomy is recommended before interferon therapy if the patients have good performance status. Adjuvant interferon therapy failed to show any survival benefit after curative excision of primary RCC. The place of IFN-alpha is going to be changed due to the recent use of molecular targeting drugs.     

奥沙利铂与顺铂化疗方案治疗进展期胃癌的Meta分析

目的探讨奥沙利铂与顺铂治疗进展期胃癌的疗效、预后及不良反应的优劣。 方法检索中国知网（CNKI）、万方、PubMed/ Medline、Embase/Ovid、Cochrane Library、历年美国临床肿瘤学会（ASCO）和欧洲肿瘤内科学会（EMSO）年会文献汇编及北美临床试验注册网。评价指标为总体生存期（OS）、无进展生存期（FPS）、客观缓解率（ORR）及严重不良反应。 结果纳入32篇文献,共3994位患者参与(奥沙利铂组1992例,顺铂组2002例）。采用含奥沙利铂方案的总生存期（HR=0.90, 95%CI 0.81~0.99）、无进展生存期（HR=0.89, 95%CI 0.81~0.98）、有效率（OR=1.33, 95%CI 1.17~1.51）明显优于顺铂组。白人亚组和亚洲人种亚组均受益于含奥沙利铂的化疗方案（OR=1.55, 95%CI 1.05~2.01）。严重不良反应方面奥沙利铂方案较少发生的贫血(OR=0.49, 95%CI 0.38~0.62）、白细胞减少（OR=0.37, 95%CI 0.27~0.51）、中性粒细胞减少（OR=0.49, 95%CI 0.40~0.59）等骨髓抑制,易发生严重的恶心/呕吐（OR=0.37, 95%CI 0.21~0.61）和周围神经病变（OR=7.16, 95%CI 4.06~12.64）,差异有统计学意义。 结论与顺铂方案相比,奥沙利铂方案具有较好的疗效与预后,不良反应相对较少,可被推荐和替代顺铂用于治疗进展期胃癌。未来需要大样本高质量的研究提供更多信息进一步探讨不同因素对两种方案的影响。       

Meta-analysis of randomized controlled trials of vancomycin for the treatment of patients with gram-positive infections: focus on the study design

ObjectiveTo study the effectiveness and safety of vancomycin compared with that of other antibiotics for the treatment of gram-positive infections.MethodsMajor electronic databases were searched. Data from published randomized controlled trials (January 1, 1950, to September 15, 2011) were pooled using a meta-analytic method.ResultsFifty-three trials comparing vancomycin with linezolid, daptomycin, quinupristin-dalfopristin, tigecycline, ceftaroline, ceftobiprole, telavancin, teicoplanin, iclaprim, and dalbavancin were included in the meta-analysis. Individual antibiotics were as effective as vancomycin, except for linezolid, which was more effective than vancomycin for the treatment of skin and soft tissue infections (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.07-2.43). Comparators were as effective as vancomycin in the intent-to-treat population (OR, 1.08; 95% CI, 0.98-1.18) but were more effective in the clinically evaluable population (OR, 1.14; 95% CI, 1.02-1.27) when all infections were pooled. When available data from all trials were pooled, no differences were noted when patients with febrile neutropenia (OR, 1.07; 95% CI, 0.82-1.39), pneumonia (OR, 1.10; 95% CI, 0.87-1.37), bacteremia (OR, 1.05; 95% CI, 0.76-1.45), and skin and soft tissue infections (OR, 1.11; 95% CI, 0.89-1.39) were studied. Comparators were more effective in open-label (OR, 1.28; 95% CI, 1.08-1.50) but not in double-blind trials (OR, 1.04; 95% CI, 0.90-1.20). Total adverse events attributed to studied antibiotics (OR, 1.07; 95% CI, 0.90-1.28) and patients withdrawn from trials (OR, 0.86; 95% CI, 0.68-1.09) were similar in the compared groups. Mortality was not different between vancomycin and comparator antibiotics when all trials were included in the analysis (OR, 1.09; 95% CI, 0.96-1.23). Comparators were associated with higher mortality in open-label (OR, 1.27; 95% CI, 1.05-1.54) but not double-blind trials (OR, 0.96; 95% CI, 0.80-1.14).ConclusionOn the basis mainly of data from open-label trials, vancomycin is a treatment choice that is as effective as other available antibiotics for patients with gram-positive infections. Study design seems to make a major contribution to the outcome.     

Efficacy of magnesium sulfate in acute adult asthma: a meta-analysis of randomized trials

The purpose of this article was to review of the literature to determine whether MgSO4 provides an additive improvement in adults with acute asthma in the emergency department (ED). English-language published and unpublished studies (1968-1998) were retrieved using MEDLINE, SCIENCE CITATION INDEX, CURRENT CONTENTS, bibliographic reviews of primary research, review articles, consultation with experts, and the register of Medical Editors' Trial Amnesty. Meta-analysis of randomized, placebo controlled trials. The five selected trials included 374 patients with acute asthma (mean age 38.3 +/- 13.4 years, 30% men, 70% women). The main outcome measure was pulmonary function; admission rate was evaluated as a secondary goal. Individual and pooled effect sizes (ES) were determined for pulmonary function data. Binary outcome (admission rate) was combined and reported as odds ratio (OR). The overall summary ES (95% confidence interval [CI]) of the five trials satisfying all inclusion criteria, weighted by sample size was nonsignificant (ES = 0.02, -0.20 to 0.24, P = .84). This pooled ES was equivalent to 1.7%, 95% CI: -9.8 to 13.1%) greater in pulmonary function the MgSO4 compared with the control group. On the other hand, four studies addressed the effect of MgSO4 administration on hospital admissions. Pooled results revealed that MgSO4 did not decrease significantly admission rates (OR = 0.68, 95% CI: 0.41 to 1.15). The existing evidence reveals that the addition of MgSO4 to ED patients with moderate to severe asthmatic exacerbations does not alter treatment outcomes. Nevertheless, the number and size of studies being pooled remain small.     

氟尿嘧啶联合紫杉类或铂类药物治疗进展期胃癌的心脏毒性研究

目的分析接受氟尿嘧啶类药物为基础方案化疗的胃癌患者心脏毒性的发生情况,并探讨其可能的危险因素以及联合或者不联合紫杉类药物对其的影响。 方法回顾2011年1月至2016年10月北京大学第一医院肿瘤化疗科连续收治的进展期胃癌患者中接受氟尿嘧啶类药物为基础方案化疗的患者,分析其心脏毒性发生情况以及联合或不联合紫杉类药物时心脏毒性事件发生率的差异。将出现严重心脏毒性的患者采用1:2的比例运用倾向性评分匹配（PSM）方法与无严重心脏毒性者进行匹配,匹配因素为年龄,采用Logistic后退法回归分析,探寻严重心脏事件的可能独立危险因素。 结果研究共纳入128例患者,接受化疗1~18周期,中位接受化疗6周期。共38例（29.7%）患者发生心脏毒性事件,12例（9.4%）发生严重心脏事件,2例（1.6%）死于心脏毒性。氟尿嘧啶类药物联合紫杉类与联合铂类的两种方案间,各级别心脏毒性及严重心脏事件的发生率比较,差异均无统计学意义（P>0.05）。经PSM法匹配年龄后进行多因素分析,结果显示严重心脏事件的独立危险因素为美国东部肿瘤协作组体力状态评分（ECOG PS）≥2分（OR=9.795,95%CI：1.283~74.772,P=0.028）和≥3度中性粒细胞减少（OR=8.374,95%CI：1.183~59.279,P=0.033）。 结论ECOG PS≥2分和≥3度中性粒细胞减少是进展期胃癌患者发生化疗相关严重心脏毒性的独立危险因素。本研究未发现紫杉类药物与铂类药物在心脏毒性发生率上的差异。     

The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials

BACKGROUND: Low-molecular-weight heparins (LMWH) have an antitumor effect in vitro and in experimental animal models of malignancy. Retrospective data suggest that it might improve survival in cancer patients. OBJECTIVES: To evaluate the effect of LMWH compared to placebo or no anticoagulant intervention on the survival of cancer patients. METHODS: We conducted a systematic review of randomized trials specifically evaluating the impact of LMWH on the survival of cancer patients. DATA SOURCES WERE: MEDLINE, EMBASE, HealthSTAR, Cochrane library, gray literature and cross-referencing from reference lists. Data extraction was performed by one reviewer, and accuracy was independently verified by a second reviewer. Meta-analysis was conducted using: (i) odds ratio (OR) and relative risk (RR); (ii) survival rates using censored endpoints; and (iii) hazard ratios (HR). RESULTS: The pooled HR in all patients was 0.83 (95% CI 0.70-0.99; P = 0.03), and in patients with advanced disease it was 0.86 (95% CI 0.74-0.99; P = 0.04), both in favor of the LMWH group. The results of the OR, RR and survival meta-analysis consistently favored the LMWH group. Sensitivity analyses according to tumor type were not conducted, because of a lack of information. CONCLUSIONS: LMWH improves overall survival in cancer patients, even in those with advanced disease. Additional trials are required to define the tumor types, disease stages and dosing schedules most likely to provide the greatest survival benefit.     

Meta-Analysis to Assess the Efficacy and Toxicity of Docetaxel-Based Doublet Compared with Docetaxel Alone for Patients with Advanced NSCLC who Failed First-Line Treatment

PurposeThe benefit of docetaxel-based therapy in the second-line treatment of advanced non–small cell lung cancer (NSCLC) is still unclear. The goal of this meta-analysis was to assess the efficacy and toxicity of docetaxel-based doublet compared with docetaxel alone for patients with advanced NSCLC who failed to improve with first-line treatment.MethodsSeveral databases were searched, including PubMed, Embase, and the Cochrane databases. The end points were overall survival, progression-free survival (PFS), objective response rate, disease control rate, and grade 3 or 4 adverse events. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by using Review Manager version 5.2. The pooled hazard ratio (HR) or odds ratio (OR) and 95% CIs were calculated by using fixed or random effects models depending on the heterogeneity of the included trials.FindingsTwelve eligible trials involving 2680 patients were identified. The intention-to-treatment analysis found that docetaxel-based therapy significantly improved overall survival (HR, 0.89 [95% CI, 0.83–0.96]; P < 0.01), PFS (HR, 0.79 [95% CI, 0.71–0.89]; P < 0.01), objective response rate (OR, 1.73 [95% CI, 1.37–2.18; P < 0.01), and disease control rate (OR, 1.30 [95% CI, 1.09–1.55]; P < 0.01). In addition, a subgroup analysis based on type of combined drug showed that there were significant improvement in PFS and overall survival in combining docetaxel with targeted therapy. In addition, a higher incidence of grade 3 or 4 diarrhea and thrombocytopenia was observed in docetaxel-based doublet therapy.ImplicationsBased on the available evidence, docetaxel-based doublet therapy seems superior to docetaxel monotherapy as a second-line treatment for advanced NSCLC. More studies should focus on combining docetaxel with targeted therapy to identify patients who will most likely benefit from the appropriate combination targeted therapy.     

Effectiveness of acupuncture-type interventions versus expectant management to correct breech presentation: a systematic review

OBJECTIVE: A systematic review of studies assessing the effectiveness of acupuncture-type interventions (moxibustion, acupuncture, or electro-acupuncture) on acupuncture point BL 67 to correct breech presentation compared to expectant management, based on controlled trials. DATA SOURCES: Articles published from 1980 to May 2007 in databases of Medline, EMBASE, the Cochrane Central Register of Controlled Trials, AMED, NCCAM, Midirs and reference lists. STUDY SELECTION: Studies included were original articles; randomised controlled trials (RCT) or controlled cohort studies; acupuncture-type intervention on BL 67 compared with expectant management; ultrasound confirmed breech presentation and position of the fetus after treatment confirmed with ultrasound, position at delivery, and/or the proportion of caesarean sections reported. DATA EXTRACTION: Three reviewers independently extracted data. Disagreements were resolved by consensus. DATA SYNTHESIS: Of 65 retrieved citations, six RCT's and three cohort studies fulfilled the inclusion criteria. Data were pooled using random-effects models. In the RCT's the pooled proportion of breech presentations was 34% (95% CI: 20-49%) following treatment versus 66% (95% CI: 55-77%) in the control group (OR 0.25 95% CI: 0.11-0.58). The pooled proportion in the cohort studies was 15% (95% CI: 1-28%) versus 36% (95% CI: 14-58%), (OR 0.29, 95% CI: 0.19-0.43). Including all studies the pooled proportion was 28% (95% CI: 16-40%) versus 56% (95% CI: 43-70%) (OR 0.27, 95% CI: 0.15-0.46). CONCLUSIONS: Our results suggest that acupuncture-type interventions on BL 67 are effective in correcting breech presentation compared to expectant management. Some studies were of inferior quality to others and further RCT's of improved quality are necessary to adequately answer the research question.     

Administration of antimicrobials via the respiratory tract for the treatment of patients with nosocomial pneumonia: a meta-analysis

BACKGROUND: Aerosolized antibiotics are a widely recognized treatment for patients with cystic fibrosis (CF). We sought to clarify their role in the treatment of non-CF patients with nosocomial pneumonia by performing a meta-analysis of randomized controlled trials (RCTs) that compared administration of antimicrobials via the respiratory tract (with or without concurrent usage of systemic antibiotics) with control treatment. METHODS: An extensive search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, Current Contents and bibliographies from retrieved publications was made. RESULTS: Five RCTs were included in the meta-analysis. Administration of antimicrobials via respiratory tract (either inhaled or endotracheally instilled) as opposed to control was associated with better treatment success in intention-to-treat [fixed effect model: odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.29-4.44; random effects model: OR = 2.75, 95% CI 1.06-7.17] and in clinically evaluable patients (fixed effect model: OR = 3.14, 95% CI 1.48-6.70; random effects model: OR = 3.07, 95% CI 1.15-8.19). There were no statistically significant differences between therapeutic regimens regarding all-cause mortality (fixed effect model: OR = 0.84, 95% CI 0.43-1.64; random effects model: OR = 0.71, 95% CI 0.27-1.88), microbiological success (fixed effect model: OR = 2.06, 95% CI 0.91-4.68; random effects model: OR = 2.23, 95% CI 0.64-7.71) and toxicity (fixed effect model: OR = 0.34, 95% CI 0.04-2.53; random effects model: OR = 0.36, 95% CI 0.04-3.16). CONCLUSIONS: The limited available evidence seems not to preclude a benefit from the administration of antimicrobial agents via the respiratory tract for treating nosocomial pneumonia.     

The Relative Efficacy of Phenothiazines for the Treatment of Acute Migraine: A Meta-Analysis

Objective and Background.— Ranges of agents are used in the emergency departments to treat migraine headache. Some experts suggest that phenothiazines are among the most effective; clinical trials have been small with varied results. We performed a systematic review and meta-analysis to determine the relative effectiveness of phenothiazines compared with placebo and other active agents for the treatment of acute migraine.
Methods.— We searched MEDLINE, EMBASE, CINAHL, Cochrane database, and international clinical trial registers for randomized controlled trials comparing parenteral phenothiazines with placebo or another active parenteral agent for treatment of acute migraine in adults. The primary outcome was relief of headache, and secondary outcome was clinical success. Analysis was for phenothiazines vs placebo, pooled other active agents, and metoclopramide for each outcome. Odds ratios (ORs) were calculated and pooled by using a random effects model (RevMan v5).
Results.— Thirteen trials were appropriate and had available data. Phenothiazines were compared with placebo in 5 trials and to another active agent in 10 (metoclopramide 4). Phenothiazine was more effective than placebo for headache relief (OR 15.02, 95% confidence interval [CI] 7.57-29.82) and clinical success (OR 8.92, 95% CI 4.08-19.51). Phenothiazines were more effective than other agents combined (OR 2.04, 95% CI 1.25-3.31) and the metoclopramide subgroup (OR 2.25, 95% CI 1.29-3.92) for clinical success, but no differences were found for headache relief. The clinical success rate of phenothiazines was 78% (95% CI 74-82).
Conclusion.— Phenothiazines are more effective than placebo for the treatment of migraine headache and have higher rates of clinical success than other agents against which they have been compared.     

The efficacy and safety of topical tranexamic acid: A systematic review and meta-analysis

Tranexamic acid (TXA) is an effective hemostatic agent used for the reduction of blood loss and transfusion. However, the safety profile of TXA remains in question due to a potential increased risk of venous thromboembolism. By applying TXA topically as opposed to intravenously, systemic absorption may be reduced and unwanted side-effects mitigated. The objective of our review is to investigate the efficacy and safety of topically applied tranexamic acid compared to both placebo, and the intravenous administration. Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ISI Web of Science, PubMed, and Clinicaltrials.gov were searched from inception to November, 2016. We included randomized controlled trials that compared topical tranexamic acid to either placebo (or standard care) or intravenous administration, in adult patients. Surgical and non-surgical trials were included. Abstract, full-text selection, data extraction and risk of bias assessment were all performed in duplicate. In total, 67 studies involving 6,034 patients met inclusion criteria. The majority of trials evaluated orthopedic procedures. Compared to placebo, the administration of topical TXA significantly reduced the odds of receiving a blood transfusion (pooled OR 0.28, 95% CI 0.20 to 0.38; P < 0.001) and significantly reduced mean blood loss (WMD -276.6, 95% CI -327.8 to -225.4; P < 0.0001). When compared to the intravenous administration, there was no difference between the two groups in terms of transfusion requirements (pooled OR 1.03, 95% CI 0.72 to 1.46; P=0.88) or blood loss (WMD -21.95, 95% CI -66.61 to 27.71; P=0.34). There was no difference in the odds of developing a venous thromboembolic complication between the topical TXA and control groups (pooled OR=0.78, 95% CI 0.47 to 1.29; P=0.33) or the topical and intravenous groups (pooled OR=0.75, 95% CI 0.39 to 1.46; P=0.40). The topical application of TXA effectively reduces both transfusion risk and blood loss compared to placebo, without increasing thromboembolic risks. There were no major differences between topical and intravenous tranexamic acid with respect to safety and efficacy, and both were superior to placebo with regards to blood loss and transfusion requirements. Further study of the topical application is required outside of the field of orthopedics.     

Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta‐analysis

Summary. Introduction: The incidence of venous thromboembolism (VTE) in patients with multiple myeloma (MM) treated with thalidomide‐ and lenalidomide‐based regimens is high. Recent observational studies have suggested that thromboprophylaxis might be efficacious in decreasing the risk of VTE in this population. Purpose: To determine the absolute rates of VTE with and without different thromboprophylactic agents in patients with newly diagnosed or previously treated MM receiving thalidomide‐ or lenalidomide‐based regimens. Results: Patients with newly diagnosed MM treated with thalidomide in combination with dexamethasone have a VTE risk of 4.1 (95% CI, 2.8–5.9) per 100 patient‐cycles. Therapeutic doses of anticoagulants seem to provide the largest absolute risk reduction of VTE. The rate of VTE in patients with previously treated MM receiving thalidomide in combination with dexamethasone is 0.8 (95% CI, 0.1–2.1) per 100 patient‐months. A combination of lenalidomide and dexamethasone is associated with of risk of VTE of 0.8 (95% CI, 0.07–2.0) per 100 patient‐cycles and 0.7 (95% CI, 0.4–0.9) per 100 patient‐cycles in patients with newly diagnosed and previously treated MM, respectively. Similarly, the rates of VTE in patients also receiving thromboprophylaxis with aspirin were 0.9 (95% CI, 0.5–1.5) and 0.6 (95% CI, 0.01–2.1), respectively. Conclusion: Patients with newly diagnosed or previously treated MM receiving thalidomide‐ or lenalidomide‐based regimens in combination with dexamethasone are at high risk of VTE. The benefit of various types of thromboprophylaxis is difficult to quantify in patients with MM receiving immunomodulatory therapy, especially in those receiving lenalidomide‐based therapy or who have previously treated MM. Randomized controlled trials are needed to address this important clinical need.     

The efficacy of Chinese herbal medicine as an adjunctive therapy for colorectal cancer: a systematic review and meta-analysis

Although Chinese herbal medicine (CHM) has been widely used as an adjunctive therapy for colorectal cancer in Asia, its efficacy is not well defined. The purpose of this systematic review is to assess the efficacy of CHM as an adjunctive therapy to chemotherapy for the patients with colorectal cancer. Randomized controlled trials with CHM to treat colorectal cancer were extensively searched in seven databases. Two researchers independently assessed the quality and validity of included trials and extracted outcome data for synthesis. 20 trials were included for analysis. Compared to using chemotherapy alone, CHM combined with chemotherapy significantly increased 1- and 3-year survival rate [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.32-4.41; OR 2.40, 95% CI 1.49-3.87]. The combined therapy significantly slowed colorectal cancer progression (OR 0.50, 95% CI 0.32-0.77) and improved quality of life (OR 3.43, 95% CI 2.35-5.02). It had positive effects in immunoregulation. CHM as an adjunctive therapy also had significant advantages in reducing the adverse effects of chemotherapy. This systematic review suggests that CHM as an adjunctive therapy with chemotherapy versus chemotherapy alone has significant efficacy in terms of prolonging survival, enhancement of tumor response, improvement of quality of life, immunoregulation, and alleviation of acute adverse effects. However, a firm conclusion could not be reached because of the poor quality of the included trials. Further trials with higher quality are required and the efficacy in other forms of advantages remains to be further determined.     

食管癌新辅助化疗后手术和单纯手术生存比较的Meta分析

目的评价新辅助化疗(CS组)与单纯手术(S组)治疗食管癌的疗效与安全性。方法检索PubMed、万方等数据库的关于食管癌的英文和中文随机对照试验(RCT)文献,按入选标准纳入研究。数据分析采用stata v.10.0软件,检验异质性,选择相应效应模型合并统计量。通过漏斗图等评定有无发表偏倚。结果共10项RCT(2 080例食管癌患者)入选。与S组比较,CS组未明显延长食管癌生存期,合并HR为0.95(95%CI 0.86-1.04),其中新辅助化疗有效的患者较单纯手术者生存期有改善,HR为0.58(95%CI 0.47-0.72);CS组术后并发症与S组相比较无明显差异,OR为1.05(95%CI 0.87-1.27)。结论与单纯手术相比较,新辅助化疗未增加术后并发症的发生率,且有效的新辅助化疗能延长食管癌患者的生存期。     

Effects of Telestroke on Thrombolysis Times and Outcomes: A Meta-analysis

Objective: Telestroke systems are tools, used to provide an advanced stroke care in regions without sufficient neurologic services. We performed this meta-analysis to assess the effects of telemedicine on treatment times and clinical outcomes of acute stroke care. Methods: A literature search of PubMed, SCOPUS, and Cochrane CENTRAL was conducted for original studies investigating telemedicine applications in acute stroke care. Dichotomous data on treatment outcomes were pooled as odds ratios (ORs), while continuous data on thrombolysis times were pooled as mean differences (MDs) with 95% confidence interval (CI), using RevMan software (version 5.3). Results: Pooling data from 26 studies (6605 thrombolysed patients) showed no significant differences between the telestroke and control groups in terms of in-hospital mortality (OR = 1.21, 95% CI [0.98, 1.49]), 90-day mortality (OR = 1.08, 95% CI [0.85, 1.37]), symptomatic intracranial hemorrhage (sICH) (OR = 1.10, 95% CI [0.79, 1.53]), and favorable clinical outcome at discharge (OR = 1.03, 95% CI [0.69, 1.53]) and 90 days later (OR = 0.99, 95% CI [0.82, 1.18]). The onset-to-door (OTD) duration (MD = ?10.4 minutes, 95% CI [?14.79, ?.01]) and length of hospital stay (MD = ?0.55 days, 95% CI [?1.02, ?0.07]) were significantly shorter in the telestroke group, compared to the control group. Although the overall effect estimate (under the fixed-effect model) showed a significant decrease in the onset-to-treatment (OTT) duration in the telestroke group (MD = ?5.83 minutes, 95% CI [?8.57, ?3.09]), employing the random-effects model for between-study heterogeneity abolished this significance (MD = ?5.90 minutes, 95% CI [?13.23, 1.42]). Conclusion: Telestroke significantly reduced OTD and hospital stay durations in stroke patients without increasing the risk of mortality or sICH. Therefore, telemedicine can improve stroke care in regional areas with minor experience in thrombolysis. Further randomized controlled trials are needed to assess the benefits of telestroke systems, especially in terms of cost-effectiveness and quality of life outcomes.     

Weekly cyclophosphamide and alternate-day prednisone: an effective, convenient, and well-tolerated oral treatment for relapsed multiple myeloma after autologous stem cell transplantation

OBJECTIVE: To assess the efficacy and tolerability of weekly oral cyclophosphamide in combination with alternate-day prednisone (CP) as salvage therapy for patients with relapsed multiple myeloma (MM) after autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: We retrospectively reviewed the medical records of all patients identified in our clinical database as having received CP as treatment for relapsed MM after ASCT at Princess Margaret Hospital between July 1998 and May 2004. The CP regimen consisted of oral cyclophosphamide at 500 mg once weekly and oral prednisone at 100 mg on alternate days. RESULTS: A total of 66 patients received the CP regimen, with a median of 2.0 prior therapies (range, 1.0-5.0) from time of diagnosis to initiation of CP. The median time from relapse after ASCT to start of CP therapy was 1.5 months (range, 0.0-23.5 months). Because of nonsecretory disease in 7 patients, only 59 patients were evaluable for response. The median duration of CP treatment was estimated at 5.8 months (95% confidence interval [CI], 4.6-7.8 months). With a median follow-up of 15.9 months (range, 1.4-67.2 months), 36 patients (61%) responded to treatment, 24 (41%) of whom had a partial response. The 1-year progression-free survival of all evaluable patients was estimated at 66% (95% CI, 54%-80%), with a median progression-free survival of 18.6 months (95% CI, 13.9-29.9 months). The median overall survival from time of initiation of CP was estimated at 28.6 months (95% CI, 22.1-not available months). CONCLUSION: Our data show that CP is an effective, well-tolerated, and convenient regimen as salvage therapy for MM after ASCT.     

西妥昔单抗联合含奥沙利铂化疗方案对转移性结直肠癌作用的系统评价和Meta分析

目的:系统评价西妥昔单抗联合含奥沙利铂化疗方案对转移性结直肠癌(metastatic colorectal cancer,mCRC)的有效性及安全性。方法:检索Pubmed、SCI-EX-PANDED、EMBASE、Cochrane图书馆、CBM及CNKI数据库,同时检索会议文献、正在进行的研究,并追踪已获文献的参考文献。根据设定的标准,2名作者独立对文献进行筛选及数据提取。采用RevMan5.2软件进行文献质量评估、数据综合。根据异质性的大小采用固定或随机效应模型。结果:共有7项研究(3291例)符合纳入标准。纳入研究的KRAS(v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog)基因野生型及总人群无进展生存期(progression free survival,PFS)的危险比(hazard ratio,HR)分别为0.89(95%CI:0.71~1.12,P=0.31)、0.98(95%CI:0.86~1.12,P=0.81)。两组人群总生存期(overall survival,OS)的HR值分别为1.00(95%CI:0.92~1.09,P=0.97)、1.02(95%CI:0.94~1.11,P=0.64)。两组人群临床有效率的风险比(risk ratio,RR)分别为1.20(95%CI:1.02~1.41,P=0.01)、1.25(95%CI:1.03~1.52,P=0.03)。试验组不良反应(尤其是皮疹及腹泻等)的发生率较对照组高。结论:西妥昔单抗联合含奥沙利铂化疗方案较单纯化疗并未明显延长mCRC患者的PFS和OS,即使在KRAS野生型的患者中也是如此,且增加了不良反应发生率;但是,该方案明显提高了治疗有效率。     

Fluoroquinolones vs beta-lactams for empirical treatment of immunocompetent patients with skin and soft tissue infections: a meta-analysis of randomized controlled trials

OBJECTIVE: To compare the effectiveness and safety of fluoroquinolones with beta-lactams in the treatment of patients with skin and soft tissue infections (SSTIs). METHODS: We searched the PubMed database, Cochrane Database of Controlled Trials, and references of relevant articles for study reports published between January 1980 and February 2006. RESULTS: Twenty randomized controlled trials that enrolled 4817 patients were included in the analysis. Fluoroquinolones as empirical treatment of patients with SSTIs were more effective than beta-lactams for the clinically evaluable patients (90.4% vs 88.2%; odds ratio [OR], 1.29; 95% confidence interval [CI], 1.00-1.66). This was also true in subset analyses of randomized controlled trials that studied ciprofloxacin (OR, 2.49; 95% CI, 1.45-4.26) and for patients with mild to moderate infections (OR, 1.83; 95% CI, 1.13-2.96). In contrast, no difference was found between the compared regimens for patients with moderate to severe infections (OR, 1.12; 95% CI, 0.80-1.55), for patients who did not receive third-generation cephalosporins as the comparator antibiotic (OR, 0.99; 95% CI, 0.73-1.34), or for the microbiologically evaluable patients (OR, 1.19; 95% CI, 0.89-1.59). Fluoroquinolones were also associated with more adverse effects (19.2% vs 15.2%; OR, 1.33; 95% CI, 1.13-1.57). CONCLUSION: The high proportion of successfully treated patients in the compared groups of antibiotics and the development of more adverse effects associated with fluoroquinolone use suggest that these antibiotics do not have substantial advantages compared with beta-lactams for empirical treatment of patients with SSTIs.     

Meta-analysis of adjuvant immunochemotherapy using OK-432 in patients with resected non-small-cell lung cancer

The benefits of immunochemotherapy with a penicillin-treated, lyophilized preparation of Streptococcus pyogenes, OK-432 (Picibanil), were reassessed in patients with resected non-small-cell lung cancer through a meta-analysis based on data from 1,520 patients enrolled in 11 randomized clinical trials. All 11 trials were started before 1991, and the subjects had been followed up for at least 5 years after surgery and randomization. In these trials, standard chemotherapy was compared with the same therapy plus OK-432. The endpoint of interest was overall survival, and analysis was based on intent-to-treat population without patient exclusion. Data were analyzed using the Mantel-Haenszel method. The 5-year survival rate for all eligible patients in the 11 trials was 51.2% in the immunochemotherapy group versus 43.7% in the chemotherapy group. The odds ratio (OR) for overall survival was 0.70 (95% CI = 0.56-0.87, p = 0.0010). Analysis of four trials in which central randomization was performed also reconfirmed a significantly longer survival time for the immunochemotherapy group (OR = 0.66, 95% CI = 0.44-1.00, p = 0.049). Based on these results of meta-analysis, it is postulated that postoperative adjuvant immunochemotherapy using OK-432 might improve the survival of patients after resection of non-small-cell lung cancer.     

The Effects of Lysine Analogs During Pelvic Surgery: A Systematic Review and Meta-Analysis

Pelvic vasculature is complex and inconsistent while pelvic bones impede access to pelvic organs. These anatomical characteristics render pelvic surgery inherently difficult, and some of these procedures are frequently associated with blood loss that necessitates blood transfusion. The aim of this study was to review the literature on the use of lysine analogs to prevent bleeding and blood transfusion during pelvic surgery. The objective of this study was to assess the safety and efficacy of lysine analogs during pelvic surgery. A systematic literature search was performed using Medline, Cochrane Register of Clinical Trials, Embase, and the reference lists of relevant articles. Randomized controlled trials or observational cohort studies comparing a lysine analog to placebo or standard care were included. Outcomes collected were blood transfusion, blood loss, thromboembolic adverse events (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism), nonthromboembolic adverse events, and death. There were no language limitations. Fifty-six articles reported on 68 comparisons between a lysine analog and an inactive comparator, involving a total of 7244 patients published between 1961 and 2013. Thirty-nine studies evaluated urologic procedures, and 21 evaluated gynecologic procedures. Thirty-six studies (60%) were published before 1980. Of the 43 randomized comparisons, only 30 (44%) had a score of 3 or higher on Jadad's 5-point scale of methodological quality. Among randomized trials, lysine analogs reduced the risk of blood transfusion (pooled odds ratio [OR], 0.47; 95% confidence interval [CI], 0.35-0.64) and blood loss (pooled OR, 0.22; 95% CI, 0.18-0.27). There was a small statistically insignificant increased risk of thromboembolic events (pooled OR, 1.07; 95% CI, 0.72-1.59) and no-thrombotic serious adverse events (pooled OR, 1.11; 95% CI, 0.67-1.83). In the 17 randomized trials published since the year 2000, only 6 thrombotic events were reported, 4 of which occurred in the placebo arm. Lysine analogs did not increase risk of death (pooled OR, 0.91; 95% CI, 0.34-2.48). These results are significant as they indicate that lysine analogs significantly reduce blood loss and blood transfusion during pelvic surgery. Although there does not appear to be a large increase in the risk of thromboembolic and nonthrombotic adverse events, more data are required to definitively assess these outcomes. Based on this review, lysine analogs during pelvic surgery seem to reduce bleeding and blood transfusion requirements. Although there does not seem to be a significant risk of adverse effects, larger studies would help clarify risks, if any, associated with lysine analog use.