Chemotherapy with or without irinotecan in patients with advanced or recurrent gastric cancer: a meta-analysis of randomized controlled trials

Background Studies have shown that irinotecan can improve survival in patients with advanced or recurrent gastric cancer,but the overall benefit of irinotecan in the treatment of advanced or recurrent gastric cancer remains controversial.The aim of this study was to evaluate the benefits and risks of irinotecan for survival in patients with advanced or recurrent gastric cancer.Method We searched PubMed,EmBase,the Cochrane Central Register of Controlled Trials,reference lists of articles,and proceedings of major conferences for relevant clinical trials.We included randomized controlled trials that reported on the efficacy and safety of irinotecan in patients with advanced or recurrent gastric cancer.Outcomes were analyzed by survival rate,objective response rate （ORR）,and toxicity.Furthermore,the analysis was further stratified by factors that could affect the treatment effects.Results Eight trials recruiting 1 546 patients with advanced or recurrent gastric cancer were included in the analysis.Overall,irinotecan therapy was associated with a 6％ improvement in survival rate,but this difference was not statistically significant （odds ratio （OR） 0.94; 95％ confidence interval （95％ CI） 0.70-1.27; P=-0.69）.However,irinotecan therapy had more frequent ORR than irinotecan-free arm （OR 1.70; 95％ CI 1.34-2.17; P ＜0.001）.Furthermore,irinotecan therapy was associated with a clinically and statistically significant increase in the risk for declined hemoglobin,hyponatremia,and diarrhea,but it also protected against thrombocytopenia risk when compared with irinotecan-free therapy.Conclusions There is no evidence to support the use of irinotecan therapy in patients with advanced or recurrent gastric cancer; however,given the significant advantage in ORR irinotecan therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment.     

Efficacy and safety of micafungin for invasive candida infections: a meta-analysis of randomized controlled trials

Background  Invasive fungal infections such as candidiasis and mold infections cause significant morbidity and mortality in seriously ill patients. Micafungin is an echinocandin antifungal agent with potent activity against most species of Candida and Aspergillus. We did this meta-analysis to clarify whether micafungin offers superior efficacy and safety compared with other antifungal agent for treating infections associated with invasive candidiasis.

Methods  We did a meta-analysis of randomized controlled trials to examine whether micafungin has superior efficacy and safety compared with other antifungal agents recommended by the treatment guidelines for fungal infection. Seven trials involving 2913 patients were included in this analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.

Results  Micafungin was associated with significantly better treatment success compared with the comparator antifungal agents (modified intention to treat, 2851 patients; random-effects model, OR 1.20, 95% CI 1.00–1.45, P=0.0487). In addition, micafungin was more effective than the comparators for antifungal prophylaxis of neutropenic patients undergoing hematopoietic stem cell transplantation (OR 1.47, 95% CI 1.08–2.00, P=0.01). Although there was no significant difference between the compared regimens in terms of the incidence of adverse drug effects (OR 0.94, 95% CI 0.77–1.11), fewer patients treated with micafungin withdrew from the studies because of adverse events (OR 0.64, 95% CI 0.44–0.94).

Conclusions  Micafungin has a good safety and tolerability profile, with an efficacy at least comparable to the other antifungal agents. Micafungin offers advantages over other agents for antifungal prophylaxis. Micafungin offers an appropriate alternative for antifungal prophylaxis rather than the treatment of invasive candida infections.

     

参附注射液治疗缓慢性心律失常的有效性和安全性研究：随机对照试验的系统评价和Meta分析

目的评价参附注射液治疗缓慢性心律失常的有效性及安全性。方法计算机检索中国期刊全文数据库、万方数据库、中文科技期刊数据库、中国生物医学数据库、Medline、EMbase、ClinicalTrials.gov,筛选出参附注射液治疗缓慢性心律失常的随机对照试验;用Cochrane协作网评价偏倚风险工具对纳入研究进行质量评价,Rev Man5.3软件进行Meta分析。结果共收集参附注射液治疗缓慢性心律失常文献99篇,经过初筛和严格评价,纳入13个研究,共978例,纳入文献质量普遍偏低,除一项研究为C级外,其他文献质量级别均为B级。总体疗效(临床症状或心率改善)方面,参附注射液优于阿托品(RR=1.27,95%CI 1.09~1.48,P=0.002),参附注射液联合阿托品较阿托品单用无统计学差异(RR=0.84,95%CI 0.73~0.97,P=0.30),参附注射液与极化液对比,可以更好改善临床症状(RR=0.52,95%CI 0.40~0.67,P=0.01);在心率改善方面无明显差异(RR=0.57,95%CI 0.32~1.20,P=0.06)。有4个研究报道了不良反应的发生,主要表现为口干舌燥等。结论鉴于目前的研究质量较低,尚不能肯定参附注射液在治疗缓慢性心律失常中的疗效,今后需更多高质量的研究以证实其疗效。     

Efficacy and safety of vitamin D3 in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials

Background Several studies found that vitamin D3 might alter glucose metabolism,protect kidney from injury and even proposed the mechanisms.But results from previous studies have been conflicting.The aim of this study was to evaluate the efficacy and safety of vitamin D3 in patients with diabetic nephropathy.The underlying mechanism of vitamin D3 decreasing proteinuria is also discussed.Methods We conducted a search of English and Chinese articles using database of Pubmed,Embase,Sinomed,CNKI,Wanfang and clinical trial register centers,for randomized controlled trials of vitamin D3 in diabetic nephropathy patients.Two reviewers performed independently.Meta-analysis was used when studies were homogeneous enough.Results Twenty studies,including 1 497 patients with diabetic nephropathy,were involved in this systemic review.Vitamin D3-treated patients with diabetic nephropathy had a statistically significant reduction in 24-hour proteinuria （weighted mean difference-0.44,95% CI-0.54 to-0.34,Z=8.80,P 〈0.000 01） and urine albumin/creatine ratio （standardized mean difference-0.29,95% CI-0.48 to-0.10,Z=2.96,P=0.003）.But vitamin D3 supplementation did not significantly reduce blood pressure and hemoglobin A1c compared with control group.The potential mechanisms about the renal protection of vitamin D3,including the inhibition of rennin-angiotensin system,the protection of kidney from inflammation,fibrosis and the structure change of kidney are discussed.In addition,vitamin D3 did not significantly increase the incidence of adverse effects,including total adverse effects,gastrointestinal adverse effects and fluctuation of blood pressure.Conclusions Vitamin D3 can ameliorate proteinuria and protect kidney from injury in patients with diabetic nephropathy.This renoprotective effect is independent of blood pressure and glucose reduction.And it does not increase any adverse effects than control,even in combination therapy with angiotensin converting enzyme inhibitors/angiotensin receptor blockers.But due to the limite     

Intravitreal bevacizumab with or without triamcinolone acetonide for diabetic macular edema: a meta-analysis of randomized controlled trials

Background Intravitreal anti-vascular endothelial growth factor （anti-VEGF） drugs and corticosteroids are being widely used to treat diabetic macular edema （DME）. The purpose of this study was to evaluate further the efficacy and safety of intravitreal bevacizumab （IVB） alone in comparison with intravitreal bevacizumab combined with triamcinolone acetonide （IVB/IVT） in the treatment of DME. Methods Pertinent publications were identified through CNKI, PubMed, Medline, EMBASE, and the Cochrane Controlled Trials Register up to November 30, 2013. Two investigators independently assessed the quality of the trials, and changes in central macular thickness （CMT） and best-corrected visual acuity （BCVA） were extracted at 6 weeks and 3, 6, 12, and 24 months after the initial treatment. A meta-analysis was carried out to compare the results between the groups receiving IVB and IVB/IVT using the software RevMan 5.0. Results A total of six randomized controlled trials （RCTs） were identified and included. The meta-analysis revealed that a significant reduction of the CMT was observed at 3 months after the initial treatment in the IVB/IVT group compared to the IVB group （P=-0.001）. Also, changes in CMT at 6 weeks and 6, 12, and 24 months did not vary significantly between the IVB and IVB/IVT groups （P=0.53, 0.76, 0.34, and 0.09, respectively）. Similarly, changes in BCVA at 6 weeks and 3, 6, 12, and 24 months also did not vary significantly between the two groups （P=-0.66, 0.98, 0.81, 0.07, and 0.80, respectively）. The results were robust to sensitivity analyses. However, the rate of intraocular pressure （IOP） rise after intravitreal injections varied significantly between the IVB and IVB/IV＇r groups （P 〈0.01）. A publication bias was not detected by funnel plots, the Egger method, or the Begg method. Conclusions Results of this meta-analysis showed that the treatments with IVB alone and combined IVB/IVT were similarly effective in improving the visual acuity, and, to some degre     

3 种喹诺酮类药治疗尿路感染效果的Meta 分析

目的 系统评价莫西沙星与左氧氟沙星、加替沙星治疗尿路感染的临床疗效。方法 利用Cochrane Library、Pubmed、Embase、中国生物医学文献数据库、中国知网及万方数据库（自建库至2017 年2 月28 日） 检索符合要求的随机对照试验研究,按照Cochrane 风险偏倚评估工具评价纳入研究的方法学质量。运用Rev Man 5.3 软件计算合并效应及95%CI,并按照不同药物种类和给药方式进行分层分析。结果 共纳入8 篇符合标 准的文献（包括1 039 例研究对象）,入选病例的治疗药物有莫西沙星、左氧氟沙星及加替沙星。Meta 分析显示, 莫西沙星治疗尿路感染的总有效率低于左氧氟沙星和加替沙星（P <0.05）,但两组不良反应发生率比较,差异 无统计学意义（P >0.05）;分层分析显示,莫西沙星治疗尿路感染总有效率低于左氧氟沙星（P <0.05）,而与 加替沙星比较,差异无统计学意义（P >0.05）。莫西沙星与左氧氟沙星、加替沙星通过口服给药治疗尿路感 染总有效率比较,差异有统计学意义（P <0.05）。结论 与左氧氟沙星、加替沙星相比,莫西沙星治疗尿路感 染的临床疗效并无优势。     

托瑞米芬与他莫昔芬治疗进展期乳腺癌的系统评价

目的：评价托瑞米芬（TOR）与他莫昔芬（TAM）治疗进展期乳腺癌的有效性和安全性．方法：计算机检索PubMed,CBMdisc,Cochrane Library,中国生物医学文献数据库,中国期刊全文数据库,中文科技期刊全文数据库等,并辅以手工检索和其他检索．按纳入标准全面搜集有关TOR对比TAM治疗进展期乳腺癌的随机对照试验,检索截至2008-06．按照Cochrane系统评价手册4．2．6质量评价标准,由2位研究者独立对纳入研究进行方法学质量评价,并进行资料提取,采用RevMan4．2．10软件进行Meta分析,计数资料采用相对危险度（RR）为疗效分析统计量;计量资料采用加权均数差（WMD）．结果：纳入10个随机对照试验（3680例患者）．Meta分析结果显示：TOR组与TAM组相比,1,3a总生存率差异无统计学意义,5a总生存率差异有统计学意义,其RR和95％可信区间（CI）分别为1．00（0．97,1．03）,1．04（0．98,1．09）,1．06（1．01,1．12）;1,3a无病生存率差异无统计学意义,5a无病生存率差异有统计学意义,其RR（95％CI）分别为1．00（0．98,1．02）,1．05（1．00,1．10）,1．08（1．02,1．15）;完全缓解率、部分缓解率及客观缓解率差异均无统计学意义,其RR（95％CI）分别为1．41（0．90,2．22）,0．91（0．71,1．17）,0．97（0．82,1．14）．TOR组不良事件发生率低于TAM组,生存质量与TAM组相似．结论：TOR在提高进展期乳腺癌患者的远期生存率和安全性方面均优于TAM．     

复方甘草酸苷治疗慢性乙型肝炎的效果及安全性的meta分析

目的系统评价复方甘草酸苷（SNMC）治疗慢性乙型肝炎的疗效和安全性。方法计算机检索EMBASE、MEDLINE、
CNKI、CBM,从建库至2012年12月,纳入SNMC治疗慢性乙肝的随机对照试验（RCT）。两名评价者独立筛选试验;提取资料
和按照Cochrane评价者手册评价偏倚风险。Meta-分析采用RevMan 5.1软件。结果纳入31篇RCT,共2753例患者。Meta 分
析显示：SNMC可改善患者肝功能ALT（MD=-31.63,95% CI：-51.57,-11.70）、AST（MD=-18.70,95% CI：-25.10,-12.30）、TBIL
（MD=-12.17,95% CI：-17.63,-6.71）和肝纤维化HA（MD=-94.89,95% CI：-125.19,-64.60）、LN（MD=-40.08,95%
CI：-52.38,-27.78）、IV-C（MD=-50.61,95% CI：-63.40,-37.81）;PC-Ⅲ（MD=-49.71,95% CI ：-71.72,-27.69）情况,组间差异有统
计学意义。试验组HBeAg（OR=2.23,95% CI：1.70,2.94）、HBV-DNA（OR=2.20,95% CI：1.70,2.84）、HBsAg（OR=2.25,95% CI：
1.24,4.07）的阴转率,总有效率（OR=4.37,95% CI：2.62,7.28）和ALT复常率（OR=3.77,95% CI：2.46,5.79）均高于对照组,差异
有统计学意义。结论SNMC治疗慢性乙型肝炎在肝功能恢复、肝纤维化指标改善、乙肝标志物阴转率等方面均优于对照组,且
无严重不良反应。但受纳入文献质量限制,以上结论尚需高质量临床试验进一步证实。
     

Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial

CONTEXT: Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration. OBJECTIVE: To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy. DESIGN: Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING: Thirty-three US HIV treatment centers. PARTICIPANTS: Of 1171 patients screened, 442 patients infected with HIV receiving stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater than 2500 copies/mL and CD4+ cell count above 0.20 x 10(9)/L were randomized. INTERVENTION: Patients were randomized to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after 24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES: Changes in HIV RNA from baseline, based on area under the curve and CD4+ cell levels, adverse events, and effect of baseline genotypic resistance on response to adefovir. RESULTS: Patients assigned to adefovir demonstrated a 0.4-log10 decline from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated hepatic enzyme levels (P<.001), gastrointestinal tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between 24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients, usually returning to baseline after discontinuation of adefovir. Patients with lamivudine or lamivudine and zidovudine resistance mutations demonstrated anti-HIV effects with adefovir (P< or =.01 vs placebo group). CONCLUSIONS: This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine. Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.     

VEGF pathway-targeted therapy for advanced renal cell carcinoma: A meta-analysis of randomized controlled trials

Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma (mRCC).Anti-angiogenesis-targeted therapy has recently been identif...     

放、化疗治疗局部晚期鼻咽癌的Meta分析

目的 比较放、化疗综合治疗与单纯放疗在局部晚期鼻咽癌(nasopharyngeal carcinoma,NPC)患者中的疗效,分析两者在死亡率(mortality rate,MR)、无事件生存率(event-free survival,EFS)、局部复发率(10cal recurrence rate,LRR)及远处转移率(distant metastasis rate,DMR)的差别,以进一步明确放、化疗综合治疗在局部晚期NPC中的作用. 方法 根据制定的文献纳入标准,选择已发表的临床随机对照研究进行Meta分析.结果本研究共纳入16项临床研究,累计3 768例患者.同期放化疗组患者的2、3、5年MR、EFR、LRR及DMR均较单纯放疗组显著改善(P<0.01).与单纯放疗组相比,诱导化疗组的LRR及DMR亦较低(P<0.05).而辅助化疗组与单纯放疗组相比,OS、EFR、LRR和DMR都没有统计学差异(P>0.05). 结论 放、化疗综合治疗(尤其是同期放、化疗)与单纯放疗相比,能更好的改善NPC患者的生存率,并降低其LRR和DMR,是治疗局部晚期NPC的有效方法.     

Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial

Context  Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. Objective  To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia. Design  Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years. Setting and Participants  Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands. Intervention  After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108). Main Outcome Measures  The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels. Results  Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], –0.010 [0.048] mm; P = .049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P = .28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P = .02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (–24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. Conclusion  Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.      

Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a meta-analysis

Background What benefits and toxicities patients acquire from the use of bevacizumab combined with first-line chemotherapy remains controversial.This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer （mCRC）.Methods Several databases,including PubMed,Embase,and Cochrane Library,were searched up to April 30,2013.Eligible studies were only randomized,controlled trials （RCTs） with a direct comparison between mCRC patients treated with and without bevacizumab.Overall risk ratio （RR）,hazard ratio （HR）,odds ratio （OR）,and 95％ confidence intervals （CO were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials.Results Six RCTs,including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group,were included.Overall,the addition of bevacizumab to first-line chemotherapy increased overall response rate （ORR） by 4.5％,prolonged both progression-free survival （PFS） and overall survival （OS）,and increased the rate of total Grades 3 or 4 adverse events （G3/4AEs） by 6.9％.Significant differences were found in ORR （RR=1.22 （95％ CI 1.01-1.46）,P=0.03）,PFS （HR=0.60 （95％ Cl 0.47-0.77）,P ＜0.0001）,OS （HR=0.83 （95％ Cl 0.70-0.97）,P=0.02）,and any G3/4AEs （OR=1.56 （95％ Cl 1.29-1.89）,P ＜0.00001）.Conclusion Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC,because of conferring a significant improvement in ORR,PFS,and OS,even though it increased adverse events.     

Efficacy and tolerability of one-site versus two-site phaco- trabeculectomy: a meta-analysis of randomized controlled clinical trials

Background Phacotrabeculectomy can be performed using one-site or two-site incisions.This meta-analysis evaluated the efficacy and tolerability of one-site versus two-site phacotrabecuiectomy in the treatment of patients with coexisting cataract and glaucoma.Methods A comprehensive literature search was performed according to the Cochrane Collaboration methodology toidentify randomized controlled clinical trials comparing one-site with two-site phacotrabeculectomy.Studies meeting our predefined criteria were included in the meta-analysis.Efficacy estimates were measured by weighted mean difference （WMD） for the percentage intraocular pressure （IOP） reduction from baseline to end point, relative risk （RR） for the proportion of patients with a best-corrected visual acuity （BCVA） of 0.5 or better after surgery and complete success rates.Tolerability estimates were measured by RR for adverse events.All of outcomes were reported with 95% confidence interval （95% CI）.Data were synthesised by Stata 10.1 for Windows.Results Two-site phacotrabeculectomy was associated with greater reductions in IOP than the one-site procedure （WMD： -5.99, 95% CI： -10.74-1.24, P=0.01）.A greater proportion of patients also achieved a BCVA of 0.5 or better （RR：0.91, 95% CI： 0.74-1.12, P=0.36） and the target IOP without anti-glaucoma medication at the study end point （RR： 0.94,95% CI： 0.83-1.07, P=0.34） after two-site than one-site phacotrabeculectomy, but the differences were not significant.There were no significant differences in adverse events between two surgical procedures.Conclusions Two-site phacotrabeculectomy is superior to one-site phacotrabeculectomy in reducing IOP, but other post-operative effects are similar.One-site and two-site phacotrabeculectomies have similar adverse event rates.     

Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of pentoxifylline therapy in improving the walking capacity of patients with moderate intermittent claudication. DATA SOURCES: A search of MEDLINE for trials published between 1976 and 1994 inclusive, and a bibliographic review of all articles retrieved. STUDY SELECTION: Randomized, placebo-controlled, double-blind clinical trials were selected that evaluated the pain-free walking distance (the distanced walked on a treadmill before the onset of calf pain) and the absolute claudication distance (the maximum distance walked on a treadmill) among patients with moderate intermittent claudication. Twelve study groups in 11 trials were included in the analysis. DATA EXTRACTION: In addition to information regarding the trial design, patient characteristics, dosages and treatment periods, the means and standard deviations were collected for both the pain-free walking and absolute claudication distances. Trial quality was also assessed. DATA SYNTHESIS: Overall, there was a statistically significant improvement in the pain-free walking distance after pentoxifylline therapy (weighted mean difference 29.4 m [95% confidence interval (CI) 13.0 to 45.9 m]); this finding was based on a total sample of 612 patients (308 in the treatment groups and 304 in the control groups). A significant improvement was also noted in the absolute claudication distance (weighted mean difference 48.4 m [95% CI 18.3 to 78.6 m]); this was based on a total sample of 511 patients (258 in the treatment group and 253 in the control group). In a sensitivity analysis of the pain-free walking distance, significant treatment effects and no statistically significant heterogeneity were found when only trials were included that were "medically eligible" (involved patients with stage II disease and a pain-free walking distance of 50 to 200 m). In a similar sensitivity analysis of the absolute claudication distance, the two conditions resulting in a significant treatment effect and no significant heterogeneity were the inclusion of "medically eligible" trials and those with a shorter treatment duration (13 weeks or less). CONCLUSION: Pentoxifylline therapy may be efficacious in improving the walking capacity of patients with moderate intermittent claudication. However, properly conducted clinical trials are required to provide a true estimate of the benefit.     

Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial

Context  Echinacea is a widely used herbal remedy for treatment of upper respiratory tract infections (URIs). However, there are few data on the efficacy and safety of echinacea in treating URIs in children. Objectives  To determine if Echinacea purpurea is effective in reducing the duration and/or severity of URI symptoms in children and to assess its safety in this population. Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial of healthy children 2 to 11 years old recruited from a regional practice-based network and an alternative medical center in 4-month periods from 2000 through 2002. Interventions  Study patients were randomized to receive either echinacea or placebo for up to 3 URIs over a 4-month period. Study medication was begun at the onset of symptoms and continued throughout the URI, for a maximum of 10 days. Main Outcome Measures  Primary outcomes were duration and severity of symptoms and adverse events recorded by parents; secondary outcomes included peak severity of symptoms, number of days of peak severity, number of days of fever, and a global assessment of severity of symptoms by parents of study children. Results  Data were analyzed on 707 URIs that occurred in 407 children, including 337 URIs treated with echinacea and 370 with placebo. There were 79 children who completed their study period without having a URI. The median duration of URIs was 9 days (95% confidence interval, 8-10 days); there was no difference in duration between URIs treated with echinacea or placebo (P = .89). There was also no difference in the overall estimate of severity of URI symptoms between the 2 treatment groups (median, 33 in both groups; P = .69). In addition, there were no statistically significant differences between the 2 groups for peak severity of symptoms (P = .68), number of days of peak symptoms (1.60 in the echinacea group and 1.64 in the placebo group; P = .97), number of days of fever (0.81 in the echinacea group vs 0.64 in the placebo group; P = .09), or parental global assessment of severity of the URI (P = .67). Overall, there was no difference in the rate of adverse events reported in the 2 treatment groups; however, rash occurred during 7.1% of the URIs treated with echinacea and 2.7% of those treated with placebo (P = .008). Conclusions  Echinacea purpurea, as dosed in this study, was not effective in treating URI symptoms in patients 2 to 11 years old, and its use was associated with an increased risk of rash.      

Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials

Context  The role and dose of oral vitamin D supplementation in nonvertebral fracture prevention have not been well established. Objective  To estimate the effectiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older persons. Data Sources  A systematic review of English and non-English articles using MEDLINE and the Cochrane Controlled Trials Register (1960-2005), and EMBASE (1991-2005). Additional studies were identified by contacting clinical experts and searching bibliographies and abstracts presented at the American Society for Bone and Mineral Research (1995-2004). Search terms included randomized controlled trial (RCT), controlled clinical trial, random allocation, double-blind method, cholecalciferol, ergocalciferol, 25-hydroxyvitamin D, fractures, humans, elderly, falls, and bone density. Study Selection  Only double-blind RCTs of oral vitamin D supplementation (cholecalciferol, ergocalciferol) with or without calcium supplementation vs calcium supplementation or placebo in older persons (60 years) that examined hip or nonvertebral fractures were included. Data Extraction  Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators. Data Synthesis  All pooled analyses were based on random-effects models. Five RCTs for hip fracture (n = 9294) and 7 RCTs for nonvertebral fracture risk (n = 9820) met our inclusion criteria. All trials used cholecalciferol. Heterogeneity among studies for both hip and nonvertebral fracture prevention was observed, which disappeared after pooling RCTs with low-dose (400 IU/d) and higher-dose vitamin D (700-800 IU/d), separately. A vitamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% (3 RCTs with 5572 persons; pooled RR, 0.74; 95% confidence interval [CI], 0.61-0.88) and any nonvertebral fracture by 23% (5 RCTs with 6098 persons; pooled RR, 0.77; 95% CI, 0.68-0.87) vs calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons; pooled RR for hip fracture, 1.15; 95% CI, 0.88-1.50; and pooled RR for any nonvertebral fracture, 1.03; 95% CI, 0.86-1.24). Conclusions  Oral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized elderly persons. An oral vitamin D dose of 400 IU/d is not sufficient for fracture prevention.