Pharmacotherapy in obesity: a systematic review and meta-analysis of randomized controlled trials of anti-obesity drugs

ABSTRACT

Introduction: Obesity poses a significant increase in morbidity and mortality and thus five anti-obesity drugs have been approved currently by US FDA. Several phase 3 trials have shown a significant improvement in cardio-metabolic profile including significant weight reduction with these agents compared to placebo.

Areas covered: We systematically searched the database of PubMed, Embase, The Cochrane Library and The ClinicalTrials.gov up to 30 September 2019 and retrieved all the randomized controlled trials (RCTs) that were conducted with these five drugs for ≥1 year and explicitly reported their efficacy versus placebo. Subsequently, we have conducted the meta-analysis to primarily study the effect of these anti-obesity drugs on weight reduction. We additionally reviewed the effect of these drugs on other cardio-metabolic parameters including key adverse events.

Expert opinion: This meta-analysis finds a significant reduction in body weight with orlistat (N = 10,435; ? ?3.07 Kg, 95% CI, ?3.76 to ?2.37), phentermine plus topiramate (N = 2985; ? ?9.77 Kg; 95% CI, ?11.73 to ?7.81), lorcaserin (N = 16,856; ? ?3.08 Kg; 95% CI, –3.49 to –2.66), naltrexone plus bupropion (N = 3239; ? ?4.39 Kg; 95% CI, ?5.05 to ?3.72) and liraglutide (N = 4978; ? ?5.25 Kg; 95% CI, ?6.17 to ?4.32), compared to placebo (all p < 0.00001).     

针刺治疗偏头痛的系统评价和Meta分析

目的:应用Meta分析方法,系统评价针刺治疗偏头痛的疗效和分析国内外评价疗效差异的原因。方法:检索Pubmed、Cochrane Library、中国生物医学文献数据库(CBM)等数据库,筛选针刺治疗偏头痛的随机对照临床试验(randomized controlled trials,RCT),应用Cochrane协作网提供的Rev Man 5.0软件进行统计分析。结果:本研究共纳入12篇高质量的、以假针刺组为对照的RCT。Meta分析结果显示:针刺治疗结束时,真针刺和假针刺组的有效率分别为49.5%和43.3%,两组之间有统计学差异(OR=1.28,95%CI:1.02~1.61,P=0.03);随访结束时,两组的有效率分别为47.7%和38.5%,两组间无统计学差异(OR=1.33,95%CI:0.70~2.51,P=0.39)。对国内及国外临床试验进行亚组分析发现,在治疗结束及随访结束时,国内试验针刺组的有效率均显著高于假针刺组(P<0.05),而国外临床试验均显示两组间无统计学意义(P>0.05)。结论:上述结果提示在治疗期间针刺对偏头痛具有一定疗效,但治疗停止的随访期间针刺的疗效不显著。国内外临床试验在设计及执行等方面差异较大,今后尚需更多科学严谨的、符合中医特点的高质量RCT来验证针刺治疗偏头痛的疗效。     

Efficacy of indirect dopamine agonists for psychostimulant dependence: a systematic review and meta-analysis of randomized controlled trials

Psychostimulant dependence is characterized by dopamine deficit, which could be reversed with indirect dopamine agonists (IDAs). A systematic review and meta-analysis of randomized, parallel-group, placebo-controlled clinical trials assessing the efficacy of IDAs in psychostimulant-dependent individuals were conducted. The study outcomes were psychostimulant abstinence, assessed by means of urinalysis, and retention in treatment. Risk of bias was determined using a Cochrane Collaboration instrument. Twenty-nine studies fulfilled the inclusion criteria, involving 2,467 participants. Compared with placebo, IDAs increased psychostimulant abstinence (standardized mean difference = 0.20; 95% confidence interval, 0.06-0.35; p = .005) but did not increase retention in treatment. Efficacy was larger in comorbid heroin-dependent individuals and was positively related with treatment length. No study was considered fully free of bias. IDAs appear to be efficacious for reducing psychostimulant use but did not improve retention. Efforts should be undertaken to reduce the risk of bias of clinical trials with psychostimulant-dependent individuals.     

Efficacy and safety of canagliflozin in type 2 diabetes mellitus: systematic review of randomized controlled trials

Background: Currently available antihyperglycemic agents (AHAs), despite being effective, do not provide adequate glycemic control in some cases and are associated with side effects. A sodium glucose co-transporter 2 inhibitor, canagliflozin, is a newer AHA, which acts by decreasing the reabsorption of filtered glucose thereby elevating the urinary glucose excretion in diabetics.

Areas covered: This systematic review was completed to assess the clinical effectiveness and safety of canagliflozin in T2DM. A literature search in PubMed, MEDLINE, Cochrane and ClinicalTrials.gov was conducted for randomized clinical trials of canagliflozin as an AHA by applying predetermined inclusion and exclusion criteria. Total 13 studies were included in the systematic review. The main outcomes assessed were change in HbA1c and fasting plasma glucose.

Expert opinion: Canagliflozin monotherapy or combination therapy has the potential to decrease inadequately controlled hyperglycemia in T2DM. It acts by a novel insulin independent mechanism which complements the action of the existing AHA and improves glycemic control and decreases the body weight. Safety profile of canagliflozin indicates lower number of hypoglycemic episodes. Some manageable adverse events include genital mycotic infections, urinary tract infections, osmotic diuresis-related events etc. These findings affirm the utility of canagliflozin in T2DM; however, data on long-term safety and efficacy are needed.     

Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials

The objective of this review was to determine the effectiveness, adverse effects and acceptability of folate in the treatment of depression. Electronic databases (Cochrane Controlled Trials Register and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register) and reference lists were searched, and authors, experts and pharmaceutical companies contacted to identify randomized controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, for patients with a diagnosis of depressive disorder. Three randomized trials (247 participants) were included. Two studies assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale (HDRS) scores on average by a further 2.65 points [95% confidence interval (CI) 0.38-4.93]. Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at 10 weeks (relative risk 0.47, 95% CI 0.24-0.92). The remaining study found no statistically significant difference when folate alone was compared with trazodone. The identified trials did not find evidence of any problems with the acceptability or safety of folate. The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.     

司美格鲁肽周制剂治疗成人超重和肥胖有效性与安全性的系统评价和Meta分析

目的：系统评价司美格鲁肽周制剂治疗成人超重和肥胖的有效性与安全性。方法：计算机检索PubMed、Embase、Cochrane Library、The ClinicalTrials.gov、中国知网、万方数据库、维普数据库,查找关于司美格鲁肽周制剂治疗成人超重和肥胖的随机对照试验（randomised controlled trials,RCTs）。由2名研究员独立筛选文献、提取资料,并进行方法学质量评价,应用RevMan 5.3软件进行Meta分析。结果：最终纳入7项RCTs,共计4 711例患者。Meta分析结果显示,与安慰剂组相比,司美格鲁肽可有效降低受试者体质量[MD=-10.75,95% CI （-13.22,-8.28）,P<0.001];提高减重>5%、10%和15%的患者分别占总体的比例[RR=2.29,95% CI （1.73,3.04）,P<0.001]、[RR=4.54,95% CI （2.94,7.02）,P<0.001]、[RR=6.91,95% CI （4.32,11.05）,P<0.001];降低身体质量指数[MD=-3.85,95% CI （-5.51,-2.19）,P<0.001];减小腰围[MD=-8.01,95% CI （-10.05,-5.97）,P<0.001];降低收缩压[MD=-3.88,95% CI （-4.93,-2.82）,P<0.001]和舒张压[MD=-1.79,95% CI （-2.95,-0.62）,P=0.003],差异均有统计学意义。司美格鲁肽总不良反应发生率与安慰剂组接近[RR=1.05,95% CI （1.00,1.10）,P=0.040];严重不良反应发生率高于安慰剂组,但差异无统计学意义[RR=1.49,95% CI （0.87,2.56）,P=0.150];胃肠道不良反应发生率显著高于安慰剂组,差异有统计学意义[RR=1.58,95% CI （1.41,1.78）,P<0.001]。结论：司美格鲁肽周制剂在成人超重和肥胖患者中的减重效果较好,但应警惕其胃肠道不良反应。     

Efficacy and safety of telavancin: a systematic review and meta-analysis

The emergence and rapid spread of multidrug-resistant gram-positive bacteria has become a vital and serious medical problem. A literature search was conducted in PubMed, EMBASE, and Elsevier databases to identify relevant publications. To calculate the risk ratios (RRs) with 95% confidential intervals (CIs), a fixed- or random-effects model was applied based on the heterogeneity across studies. Five studies containing seven RCTs were included in this meta-analysis. Regarding cSSTIs, HAP, SAB, there was no statistically significant difference in the rate of clinical cure between telavancin and vancomycin or standard therapy in intention-to-treat population (ITT) (RR 1.01, 95% CI 0.97–1.05, P = 0.72; FEM) and clinically evaluable population (CE) (RR 1.01, 95% CI 0.98–1.04, P = 0.41; FEM). However, telavancin was more effective than vancomycin or standard therapy in MRSA eradication rate (RR 1.08, 95% CI 1.02–1.14, P = 0.009; FEM). Regarding the safety profile, no statistically significant differences were found in all-cause mortality (9.0% vs. 8.4%; RR 1.07, 95% CI 0.88–1.31, P = 0.49; FEM) and overall adverse events (77.0% vs. 72.3%; RR 1.08, 95% CI 0.98–1.20, P = 0.12; FEM) between telavancin and vancomycin or standard therapy. Pooled data from cSSTIs, HAP and SAB studies on telavancin indicated higher rates of adverse-event related withdrawals (7.7% vs. 5.4%; RR 1.43, 95% CI 1.12–1.83, P = 0.05; FEM) and creatinine elevation (10.0% vs. 5.1%; RR 1.95, 95% CI 1.53–2.48, P<0.00001; FEM)than vancomycin or standard therapy.Telavancin and vancomycin or standard therapy are equally effective for the treatment of cSSTIs, HAP and SAB, and telavancin might be an option for the treatment of difficult-to-treat serious infections caused by MRSA. However, telavancin is associated a higher incidence of creatinine elevation and adverse-event related withdrawals.     

Efficacy and safety of dronedarone: a review of randomized trials

Importance of the field: Dronedarone is developed for treatment of atrial fibrillation (AF) or flutter (AFL). It is a noniodinized amiodarone analogue and believed to be without the adverse effects of amiodarone. However, long-term adverse effects are not yet well investigated.

Areas covered in this review: This is a review of seven studies on dronedarone.

What the reader will gain: DAFNE established an effective dose to be 400 mg b.i.d. ADONIS and EURIDIS showed significant prevention of AF/AFL recurrence hazard ratio (HR 0.78 and 0.73) compared to placebo. In ATHENA, cardiovascular death/hospitalization was significantly reduced (HR 0.76) in patients with AF and additional risk factors. ANDROMEDA was stopped because dronedarone increased early mortality (HR 2.13) in advanced heart failure (HF). ERATO found that dronedarone significantly reduced heart rate compared to placebo in patients with AF. DIONYSOS showed that amiodarone was superior to dronedarone to maintain sinus rhythm in patients with AF/AFL.

Take home message: Dronedarone is superior to placebo but less efficient than amiodarone in maintaining sinus rhythm in patients with a history of AF. In patients with AF and risk factors dronedarone reduces cardiovascular mortality and morbidity, but in patients with severe HF dronedarone significantly increases mortality.     

Paclitaxel-based versus docetaxel-based regimens in metastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials

Abstract

Objectives:

Docetaxel and paclitaxel show significant clinical activity in metastatic breast cancer (MBC) and have been approved for MBC by the U.S. Food and Drug Administration, but it is still unclear whether a paclitaxel-based regimen improves outcomes over a docetaxel-based regimen in patients with MBC. We therefore performed a meta-analysis of randomized controlled trials to compare the safety and efficacy of these two regimens in MBC.     

Antihypertensive effects and safety of eprosartan: a meta-analysis of randomized controlled trials

Purpose  

The benefits of reducing blood pressure (BP) have been well established, but uncertainty remains about the comparative effects of different BP-lowering regimens. We aimed to estimate the efficacy and the tolerability of eprosartan compared with other agents as monotherapy.     

Efficacy and safety of tumor necrosis factor-α blockers for ulcerative colitis: A systematic review and meta-analysis of published randomized controlled trials

To evaluate the efficacy and safety of TNF-α blockers for ulcerative colitis. A systematic search for randomized controlled trials (RCTs) of TNF-α blockers for treatment of ulcerative colitis (UC) were performed in PubMed, Web of Science, Embase and cochrane clinical trial. We estimated Pooled estimates of the odds ratio (OR) and relevant 95% confidence interval (CI) using fixed effects model or random effects model as appropriate. Heterogeneity, publication bias, and subgroup analyses were conducted. Nine randomized controlled studies met the selection criteria with a total of 2518 patients. Five studies compared Infliximab with placebo. Two studies compared Infliximab to corticosteroids. Two studies compared Adalimumab to placebo. One study compared subcutaneous golimumab to placebo. Short-term response, short-term remission, long-term remission and mucosal healing were better in the TNF-α blocker group than in the control group (p < 0.05). TNF-α blockers decreased the colectomy rate and serious adverse reactions (p < 0.05). The TNF-α blockers were superior to controls in achieving short-term clinical response/remission, long-term remission and mucosal healing and decreased the colectomy rate and serious adverse reactions.     

Efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

As a new oral hypoglycemic agent, saxagliptin belongs to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. However, it remains inconclusive whether saxagliptin is associated with increased risk of adverse events (AE) and efficacy as add-on treatment. Therefore, we performed an up-to-date meta-analysis to compare the efficacy and safety of saxagliptin with placebo and other oral hypoglycemic agents in adult patients with type 2 diabetes mellitus (T₂DM). Randomized clinical trials (RCTs) comparing saxagliptin with comparators were retrieved by selecting articles from Pubmed, Embase, Cochrane Library and Clinical Trials Registry Platform up to Oct. 2013. Weighted mean difference (WMD) was used to analyze the effect of hypoglycemic agents on HbA1c, weight and fasting plasma glucose (FPG). While the patients who achieved HbA1c<7.0% and had AE were analyzed as relative risks (RR).A total of 18 articles from 16 RCTs and one clinic trial from the WHO International Clinical Trials Registry Platform met the included criterion. Clinically significant decrease from baseline HbA1c compared with placebo was certified for 2.5 mg/day saxagliptin (WMD = –0.45%, 95%CI, –0.48% to –0.42%) and 5 mg/d saxagliptin (WMD = –0.52%, 95%CI, –0.60% to –0.44%). Saxagliptin as add-on therapy was superior to thiazolidinediones, up-titrated glyburide, up-titrated metformin or metformin monotherapy in achieving HbA1c<7.0%. Treatment with saxagliptin had negligible effect on weight, and it was considered weight neutral. Saxagliptin treatment did not increase the risk of hypoglycemia (RR = 1.28, 95% CI 0.72 to 2.27, P = 0.40) and serious adverse experiences (RR = 1.25, 95% CI 0.94 to 1.66, P = 0.13). No statistically significant differences were observed between saxagliptin and comparators in terms of the risk of infections.The present study showed that saxagliptinwas effective in improving glycaemic control in T₂DM with a low risk of hypoglycaemia and incidence of infections in either monotherapy or add-on treatment. This founding should be further certified by large-sample size and good-designed RCT.     

Alpha-lipoic acid effect on leptin and adiponectin concentrations: a systematic review and meta-analysis of randomized controlled trials

New evidence suggests that dysregulation of adipocytokines caused by excess adiposity plays an important role in the pathogenesis of various obesity comorbidities. Our aim in this meta-analysis was to determine the effect of alpha-lipoic acid (ALA) supplementation on serum levels of leptin and adiponectin. We searched Scopus, PubMed, Google Scholar, and ISI Web of Science from inception up to July 2019. Mean difference for leptin and adiponectin were calculated by subtracting the change from baseline in each study group. Summary estimates for the overall effect of ALA on serum leptin and adiponectin concentrations were calculated using random effects model. Results were presented as weighted mean difference (WMD) and their 95% confidence intervals (CI). Between-study heterogeneity was examined using the I2 statistics. Eight studies were included in systematic review and seven studies in meta-analysis. The overall effect suggested a significant decrement in serum leptin concentrations (WMD = − 3.63; 95% CI, − 5.63, − 1.64 μg/ml; I2 = 80.7%) and a significant increase in serum levels of adiponectin (WMD = 1.98 μg/ml; 95% CI, 0.92, 3.04; I2 = 95.7%). Subgroup analyses based on age showed a significant reduction in leptin levels only in younger adults, and subgroup analysis based on duration indicated in studies with a duration of more than 8 weeks adiponectin levels increased significantly and leptin levels decreased significantly. Our results revealed ALA decreased leptin and increased adiponectin especially in studies lasted more than 8 weeks. We still need more studies with different ALA dose, intervention duration, and separately on male and female.     

Compound glycyrrhizin plus conventional therapy for psoriasis vulgaris: a systematic review and meta-analysis of randomized controlled trials

Background: Psoriasis vulgaris is a chronic skin condition affecting patients’ quality of life. Long-term use of conventional therapy increases risk of unwanted side effects. Compound glycyrrhizin in conjunction with conventional therapy has been used in clinical practice, but the evidence for such practice has not been evaluated systematically.

Objective: This review aims to evaluate the efficacy and safety of compound glycyrrhizin in combination with conventional therapy for psoriasis vulgaris.

Methods: PubMed, Excerpta Medica dataBASE (Embase), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database (AMED), CiNii, Chinese Biomedical Literature, China National Knowledge Infrastructure, Chinese Scientific Journals Full Text Database and Wanfang Data were searched from their respective inceptions to July 2015. Randomized controlled trials comparing compound glycyrrhizin plus conventional therapy to conventional therapy alone for psoriasis vulgaris were included. Data analysis was performed using Review Manager 5.3.

Results: Eleven randomized controlled trials were included in this review. Meta-analysis of the 11 randomized controlled trials indicated that the addition of compound glycyrrhizin increased the number of patients achieving Psoriasis Area and Severity Index (PASI) 60 (RR: 1.30 [1.21, 1.40], I² = 6%), when compared with conventional therapy alone. Comparable numbers of patients experienced adverse events in the two groups.

Conclusions: Compound glycyrrhizin in conjunction with conventional therapy enhances clinical response, and compound glycyrrhizin as add-on therapy does not appear to pose any additional risk in the treatment of psoriasis vulgaris. However, the findings should be interpreted with caution of methodological flaws in the included studies.

PROSPERO registration number: CRD42015027763.     

A systematic review and meta-analysis of randomized controlled trials of cardiovascular toxicity of medical cannabinoids

BackgroundSeveral systematic reviews (SRs) have summarized the potential effectiveness of medical cannabinoids, but it is unclear to what extent safety-related outcomes were incorporated.ObjectiveThe objective of this study was to evaluate the cardiovascular toxicity associated with medical use of cannabinoids.MethodsA 2-stage systematic review (SR) approach was undertaken to assess the current evidence on cannabinoid-associated cardiovascular events reported among randomized controlled trials (RCTs). First, we searched for SRs in multiple sources until June 2019. Second, RCTs identified from the SRs were included if they assessed medical cannabis and reported cardiovascular events. The outcomes of interest were all types of cardiovascular events. Data were extracted by 2 independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios (RRs) and 95% CIs were calculated using a random-effects model.ResultsA total of 47 studies involving 2800 patients were included. The median duration of cannabinoid use was 15.8 days (range 1 to 322), and 45% of the studies excluded patients with underlying cardiovascular diseases. Cannabinoid use was significantly associated with increased risks of orthostatic hypotension (RR 3.16 [95% CI 2.27–4.40], I² = 2.3%) and hypotension (3.55 [1.45–8.71], I² = 31.8%), with a trend of increased risk of tachycardia (1.94 [0.81–4.64], I² = 48.6%). No study reported serious cardiovascular events.ConclusionsCannabinoid use was associated with tachycardia, hypotension, and orthostatic hypotension. There is a paucity of data for other cardiovascular events among medical cannabis users. More data, especially regarding long-term effects among patients with existing cardiovascular diseases, are needed.     

The efficacy and safety of cilnidipine on mild to moderate essential hypertension: a systematic review and meta-analysis of randomized controlled trials in Chinese patients

The purpose of this study was to evaluate the efficacy and safety of Cilnidipine tablets to treat Chinese patients with mild to moderate essential hypertension, and to examine the ability of Cilnidipine to lower blood pressure without eliciting unfavorable side effects. Medical databases and review articles were screened for randomized controlled trials that reported the effects of and adverse reactions to Cilnidipine and Amlodipine in treating Chinese patients with mild to moderate essential hypertension. The quality of the included studies was critically evaluated. A total of 547 articles were found, from which 11 articles met the inclusion criteria. The heterogeneity test, the efficacy analysis (Q statistic = 4.62, p = 0.91, I(2) = 0%) and safety analysis (Q statistic = 3.73, p = 0.93, I(2) = 0%) showed that Cilnidipine was equally effective and safe compared to Amlodipine. The funnel-plot displayed a symmetrical figure, indicating there was no publication bias, and all articles included described high quality trials. In conclusion, Cilnidipine is a useful agent to treat mild to moderate essential hypertension in China.     

Assessment of pharmacist-led patient counseling in randomized controlled trials: a systematic review

Background Pharmacists’ counseling has improved health-related outcomes in many acute and chronic conditions. Several studies have shown how pharmacists have been contributing to reduce morbidity and mortality related to drug-therapy (MMRDT). However, there still is a lack of reviews that assemble evidence-based clinical pharmacists’ counseling. Equally, there is also a need to understand structure characteristics, processes and technical contents of these clinical services. Aim of the review To review the structure, processes and technical contents of pharmacist counseling or education reported in randomized controlled trials (RCT) that had positive health-related outcomes. Methods We performed a systematic search in specialized databases to identify RCT published between 1990 and 2013 that have evaluated pharmacists’ counseling or educational interventions to patients. Methodological quality of the trials was assessed using the Jadad scale. Pharmacists’ interventions with positive clinical outcomes (p < 0.05) were evaluated according to patients’ characteristics, setting and timing of intervention, reported written and verbal counseling. Results 753 studies were found and 101 RCT matched inclusion criteria. Most of the included RCTs showed a Jadad score between two (37 studies) and three (32 studies). Pharmacists were more likely to provide counseling at ambulatories (60 %) and hospital discharge (25 %); on the other hand pharmacists intervention were less likely to happen when dispensing a medication. Teaching back and explanations about the drug therapy purposes and precautions related to its use were often reported in RCT, whereas few studies used reminder charts, diaries, group or electronic counseling. Most of studies reported the provision of a printed material (letter, leaflet or medication record card), regarding accessible contents and cultural-concerned informations about drug therapy and disease. Conclusion Pharmacist counseling is an intervention directed to patients’ health-related needs that improve inter-professional and inter-institutional communication, by collaborating to integrate health services. In spite of reducing MMRDT, we found that pharmacists’ counseling reported in RCT should be better explored and described in details, hence collaborating to improve medication-counseling practice among other countries and settings.     

Additive effect of α-ketoacids in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials

α-Ketoacids (KAs) are widely used in chronic kidney disease (CKD), but their efficacy is not clear. Therefore, we conducted a systematic review of the benefits of KAs. Two reviewers independently searched MEDLINE, EMBASE, the Cochrane library (http://www.cochrane.org), CNKI, and Wan Fang databases from inception to May 31, 2016 for randomized controlled trials (RCTs) comparing KAs plus low protein diet (LPD) with LPD only on CKD patients. Statistical analyses were performed using both a random effects model and a fixed effects model with Rev Man 5.3, followed by sensitivity analysis. We identified 21 randomized controlled trials that enrolled a total of 1448 patients. 726 had received LPD plus KAs and 722 had received only LPD. Compared with simply using of LPD, combining with KAs could decrease serum creatinine (95% CI, 0.46–0.96; P<0.00001), serum cholesterol (95% CI, 0.24–0.77; P = 0.02), serum LDL cholesterol (95% CI, 0.12–0.54; P = 0.31), and serum triglyceride (95% CI, 0.28–0.83; P = 0.02) while increasing serum HDL cholesterol (95% CI, -1.73–0.07; P<0.00001). Likewise, a decrease in P^3– (95% CI, 0.90–1.26; P<0.00001) and PTH (95% CI, 0.70–1.21; P = 0.007) were observed. No hypercalcemia and other ARD or toxicity was reported, which indicated the safety of KAs. Nevertheless, the studies were pooled with considerable heterogeneity. In patients with CKD, there was low-quality evidence suggesting that KAs may perform an additive effect on the improvement of renal function, lipid profile, as well as the correction of calcium-phosphate metabolism disorders. On account of the considerable heterogeneity of the meta-analysis and the costly price and adherence of KAs administration, KAs’ roles in the management of mild or moderate CKD patients may need more RCTs of large scale and high quality to confirm.     

Efficacy and safety of dendritic cell vaccines for patients with glioblastoma: A meta-analysis of randomized controlled trials

BackgroundDendritic cell (DC)-based vaccination has been suggested to be promising for glioblastoma. However, the evidence in randomized controlled trials (RCTs) is inconsistent. We aimed to systematically evaluate the efficacy and safety of DC vaccine for glioblastoma via a meta-analysis of RCTs.MethodsRelated randomized controlled trials (RCTs) were identified via a search of PubMed, Embase, and Cochrane’s Library. We used a random-effect model to pool the results.ResultsSix phase II RCTs with 347 patients with newly diagnosed or recurrent glioblastoma that underwent conventional treatments were included. Compared to the control group with placebo or blank treatment, DC vaccine was associated with significantly improved overall survival in patients with glioblastoma (hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.49 to 0.97, p = 0.03) with moderate heterogeneity (p for Cochrane’s Q test = 0.07, I² = 51%). A trend of improved progression-free survival was also detected in patients allocated to the DC vaccine group compared to those in the control group (HR: 0.76, 95% CI: 0.56 to 1.02, p = 0.07), with no significant heterogeneity (I² = 0%). Moreover, the incidence of adverse events was not significant between patients treated with DC vaccine or control (odds ratio = 1.52, 95% CI: 0.88 to 2.62, p = 0.14; I² = 0%).ConclusionsEvidence based on phase II RCTs suggests that DC vaccine may improve the survival of patients with glioblastoma. Large-scale RCTs are needed to validate the findings and determine the optimal regimens for DC vaccine.