Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials

OBJECTIVES: The aim of this research was to estimate the efficacy and safety of current high-density lipoprotein cholesterol (HDL-C)-increasing drugs. BACKGROUND: Epidemiologic evidence has shown that HDL-C is inversely related to coronary heart disease (CHD) risk. However, the evidence for reducing CHD risk by raising HDL-C is thin, predominantly due to the paucity of effective and safe HDL-increasing drugs. METHODS: Randomized controlled trials with fibrates and niacin, published between 1966 through February 2004 (MEDLINE), were retrieved. Information on treatment, baseline characteristics, serum lipids, end points, and side-effects were independently abstracted by two authors using a standardized protocol. RESULTS: Data from 53 trials (16,802 subjects) using fibrates and 30 trials (4,749 subjects) using niacin were included. Random-effects model showed 11% versus 10% reduction in total cholesterol, 36% versus 20% reduction in triglycerides, 8% versus 14% reduction in low-density lipoprotein cholesterol, and 10% versus 16% increase in HDL-C for fibrates and niacin, respectively. Apart from flushes in the niacin group, both fibrates and niacin were shown to be well-tolerated and safe. Fibrates reduced the risk for major coronary events by 25% (95% confidence interval 10% to 38%), whereas current available data for niacin indicate a 27% reduction. CONCLUSIONS: Fibrates reduce major coronary events and increase HDL-C levels without significant toxicity. Niacin has a more potent effect on HDL-C levels, whereas data on cardiovascular event rate reduction are limited. Future studies need to evaluate whether additional HDL increase by fibrates or particularly newer niacin formulations on top of statin therapy translates into further event reduction in high-risk subjects, without significant toxicity.     

Efficacy and safety of benralizumab for eosinophilic asthma: A systematic review and meta-analysis of randomized controlled trials

Context: Benralizumab is a humanized monoclonal antibody that targets the α chain of the IL-5 receptor (IL-5Rα) and is currently being assessed in clinical trials for asthma control. Objective: Our systematic review and meta-analysis intends to evaluate the therapeutic efficacy and safety of benralizumab in patients with eosinophilic asthma. Data sources and extraction: Literature searches of PubMed, Embase, and the Cochrane Library were performed to identify randomized controlled trials of benralizumab and clinic outcomes in asthmatics. Results: In total, 7 articles with 2,321 subjects met our inclusion criteria. From this pooled analysis, we found that benralizumab significantly reduces exacerbations (RR: 0.63, 95% CI: 0.52–0.76, p < 0.00001; I² = 52%, p = 0.06) compared to placebo in eosinophilic asthma. There was no statistical trend for improvement in forced expiratory volume in 1 second or asthma control indices such as Quality of Life Assessment (AQLQ) and Asthma Control Questionnaire score in benralizumab-treated patients. In addition, safety data indicated that benralizumab administration resulted no increasing incidence of adverse events and was well tolerated (RR: 1.00, 95% CI: 0.95–1.05, p = 0.96; I² = 40%, p = 0.13). Conclusion: These results demonstrate the efficacy and safety of benralizumab for asthma patients with severe or uncontrolled symptoms and elevated eosinophils and provide support for benralizumab as an ideal option to treat asthma in this patient population.     

Efficacy and safety of Lianhuaqingwen for mild or moderate coronavirus disease 2019: A meta-analysis of randomized controlled trials

Background: Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus treatments. Traditional Chinese Medicine (TCM) has been widely used to treat COVID-19 in China, and the most used one is Lianhuaqingwen (LH). This study aimed to assess the efficacy and safety of LH combined with usual treatment vs usual treatment alone in treating mild or moderate COVID-19 by a meta-analysis of randomized controlled trials (RCTs).Methods and analysis: We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the efficacy and safety of LH in combination with usual treatment vs usual treatment for mild or moderate COVID-19. A meta-analysis was performed to calculate the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes and mean difference (MD) for continuous outcomes.Results: A total of 5 RCTs with 824 individuals with mild or moderate COVID 19 were included. Compared with the usual treatment alone, LH in combination with usual treatment significantly improved the overall clinical efficacy (RR = 2.39, 95% CI 1.61–3.55), increased the rate of recovery of chest computed tomographic manifestations (RR = 1.80, 95% CI 1.08–3.01), reduced the rate of conversion to severe cases (RR = 0.47, 95% CI 0.29–0.74), shorten the duration of fever (MD = −1.00, 95% CI −1.17 to −0.84). Moreover, LH in combination with usual treatment did not increase the occurrence of the adverse event compared to usual treatment alone.Conclusion: Our meta-analysis of RCTs indicated that LH in combination with usual treatment may improve the clinical efficacy in patients with mild or moderate COVID-19 without increasing adverse events. However, given the limitations and poor quality of included trials in this study, further large-sample RCTs or high-quality real-world studies are needed to confirm our conclusions.     

Efficacy and safety of adalimumab in hidradenitis suppurativa: A systematic review and meta-analysis of randomized controlled trials

Background:Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to evaluate the efficacy and safety of adalimumab in patients with moderate-to-severe HS.Methods:We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Pooled estimates, namely standardized mean difference (SMD) and relative risk (RR), were calculated using random-effect model with trial sequential analysis. Small study effects were examined using the Doi plot. Certainty of evidence (CoE) was assessed using “The Grading of Recommendations Assessment, Development, and Evaluation” approach, and number-needed-to-treat (NNT) was calculated.Results:Five randomized controlled trials, involving 1014 patients, were included. We performed subgroup analysis of adalimumab administered subcutaneously both weekly and every other week. Adalimumab administered weekly was associated with better clinical response achievement (RR 1.76, 95% confidence interval [95% CI] 1.35–2.29; trial sequential analysis TSA-adjusted CI 1.01–3.08; CoE: low; NNT = 5) and a significant improvement in modified Sartorius score (SMD = −0.45, 95% CI = −0.76 to −0.13; CoE: very low; NNT = 10) and dermatology life quality index (DLQI) (SMD −0.47, 95% CI −0.61 to −0.32; CoE: low; NNT = 10). Nevertheless, adalimumab administered every other week showed an improvement only in modified Sartorius score. The pooled RRs of adverse events in both groups revealed no statistical significance when compared with the placebo.Conclusions:Adalimumab administered weekly resulted in not only better clinical responses than placebo but also significantly improved disease severity and quality of life of patients with moderate-to-severe HS. Our study provides supporting evidence to the current guidelines and aids decision-making in the application of adalimumab in HS management.     

Efficacy and safety of meditative movement therapies in fibromyalgia syndrome: a systematic review and meta-analysis of randomized controlled trials

A systematic review with meta-analysis of the efficacy and safety of meditative movement therapies (Qigong, Tai Chi and Yoga) in fibromyalgia syndrome (FMS) was carried out. We screened Clinicaltrials.Gov, Cochrane Library, PsycINFO, PubMed and Scopus (through December 2010) and the reference sections of original studies for meditative movement therapies (MMT) in FMS. Randomized controlled trials (RCT) comparing MMT to controls were analysed. Outcomes of efficacy were pain, sleep, fatigue, depression and health-related quality of life (HRQOL). Effects were summarized using standardized mean differences (SMD [95% confidence interval]). Outcomes of safety were drop out because of adverse events and serious adverse events. A total of 7 out of 117 studies with 362 subjects and a median of 12 sessions (range 8–24) were included. MMT reduced sleep disturbances (?0.61 [?0.95, ?0.27]; 0.0004), fatigue (?0.66 [?0.99, ?0.34]; <0.0001), depression (?0.49 [?0.76, ?0.22]; 0.0004) and limitations of HRQOL (?0.59 [?0.93, ?0.24]; 0.0009), but not pain (?0.35 [?0.80, 0.11]; 0.14) compared to controls at final treatment. The significant effects on sleep disturbances (?0.52 [?0.97, ?0.07]; 0.02) and HRQOL (?0.66 [?1.31, ?0.01]; 0.05) could be maintained after a median of 4.5 (range 3–6) months. In subgroup analyses, only Yoga yielded significant effects on pain, fatigue, depression and HRQOL at final treatment. Drop out rate because of adverse events was 3.1%. No serious adverse events were reported. MMT are safe. Yoga had short-term beneficial effects on some key domains of FMS. There is a need for high-quality studies with larger sample sizes to confirm the results.     

Efficacy and safety of gemcitabine-capecitabine combination therapy for pancreatic cancer: A systematic review and meta-analysis of randomized controlled trials

Background:Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime shows promising efficacy in pancreatic cancer patients. Here, we conducted a meta-analysis to compare the efficacy and safety of gemcitabine (Gem) with GemCap for pancreatic cancer.Methods:The database of MEDLINE (PubMed), EMBASE, Cochrane Central Controster of Controlled Trials, Web of Science was searched for relevant randomized controlled trials before 8 April, 2020. The outcomes were overall survival (OS), 12-month survival rate, progress free survival (PFS), partial response rate (PRR), objective response rate (ORR), and Grade 3/4 toxicities.Results:Five randomized controlled trials involving 1879 patients were included in this study. The results showed that GemCap significantly improves the OS (hazard ratio = 1.15, 95% CI: 1.037-1.276, P = .008), PFS (hazard ratio = 1.211, 95% CI 1.09-1.344, P = 0), PRR (relative risk (RR) = 0.649, 95% CI 0.488-0.862, P = .003), ORR (RR = 0.605, 95% CI 0.458-0.799, P = 0), and the overall toxicity (RR = 0.708, 95% CI 0.620-0.808, P = .000) compared to Gem alone. However, no significant difference was found in 12-month survival.Conclusions:Despite a higher incidence of Grade 3/4 toxicity, GemCap was associated with better outcomes of OS, PFS, PRR, ORR, as compared with Gem, which is likely to become a promising therapy for pancreatic cancer.     

Efficacy and safety of drug-eluting stents in patients with acute ST-segment-elevation myocardial infarction: a meta-analysis of randomized controlled trials

We compared the efficacy and safety of drug-eluting stents with that of bare-metal stents in patients who experienced acute ST-segment-elevation myocardial infarction (STEMI) and underwent primary percutaneous coronary intervention. To do this, we performed a meta-analysis of 13 randomized controlled trials in which drug-eluting stents were compared with bare-metal stents in STEMI patients. The trials involved 6,769 patients (4,246 received drug-eluting stents and 2,523 received bare-metal stents) and follow-up periods of 6 to 48 months. In comparison with bare-metal stents, drug-eluting stents significantly reduced the incidence of major adverse cardiac events, with a risk ratio (RR) of 0.59 (95% confidence interval [CI], 0.47-0.73; P < 0.00001). Drug-eluting stents were not associated with a significant reduction in overall death (RR = 0.94; 95% CI, 0.74-1.20; P = 0.64), but were associated with significant reductions in recurrent myocardial infarction (RR = 0.76; 95% CI, 0.58-0.98; P = 0.03), target-vessel revascularization (RR = 0.47; 95% CI, 0.39-0.56; P <0.00001), and in-stent restenosis (RR = 0.32; 95% CI, 0.25-0.39; P < 0.00001). Moreover, no significant difference was found in the comparative risk of stent thrombosis (RR = 0.85; 95% CI, 0.63-1.14; P = 0.27).On the basis of risk ratio, we conclude that using drug-eluting stents in STEMI patients who undergo primary percutaneous coronary intervention is safe with regard to stent thrombosis within 48 months, and that drug-eluting stents improve clinical outcomes by reducing the risks of major adverse cardiac events, recurrent myocardial infarction, reintervention, and in-stent restenosis, compared with bare-metal stents. However, in order to investigate possible very late stent thrombosis, follow-up of these trials beyond 48 months is warranted.     

Efficacy and safety of corticosteroid in the treatment of hand osteoarthritis: a systematic review and meta-analysis of randomized controlled trials

Clinical Rheumatology - To assess the efficacy and safety of corticosteroid therapy including oral corticosteroid and intra-articular corticosteroid in patients with hand osteoarthritis (OA), to...     

Antibiotics for vascular diseases: a meta-analysis of randomized controlled trials

BACKGROUND: Trials of antibiotic treatment of vascular diseases, in attempts to eradicate possible microbial initiators, have had mixed results. We sought to evaluate the efficacy of antibiotics in treating patients with atherosclerotic vascular diseases, using a meta-analysis. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials and also used cross-references. Randomized controlled trials of antibiotic treatment of vascular diseases were included. Two independent raters assessed the trials for quality. We performed summary estimates, subgroup analyses and tests for homogeneity. RESULTS: Twelve trials, with a total of 12,236 patients, were included. Antibiotic treatment resulted in a non-significant reduction in the risk of new vascular events or death (odds ratio (OR), 0.84; 95% confidence interval (CI), 0.67-1.05). There was significant heterogeneity between the sub-groups in type of vascular disease (coronary heart disease, CHD versus non-CHD (p=0.01)). Among the 72 non-CHD patients, a trend appears for treatment benefit in reducing recurrent events or death (OR, 0.22; 95% CI, 0.07-0.66). CONCLUSIONS: Overall, antibiotic treatment did not significantly reduce occurrence of new vascular events or death. However, further trials are needed to confirm the benefit demonstrated in non-CHD patients.     

Efficacy and safety of standard and anti-reflux self-expanding metal stent: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND Self-expanding metal stents are the main palliative treatment modality for unresectable esophageal cancer. Gastroesophageal reflux is a common adverse outcome after placement of esophageal stent for cancer involving the gastroesophageal junction and the gastric cardia. Anti-reflux stents with valve have been designed to prevent the acid reflux. The superiority of anti-reflux stent over standard stent in preventing gastroesophageal reflux has not been established well. This study compares the anti-reflux stent and the standard stent in terms of their efficacy to prevent acid reflux.AIM To compare the standard and the anti-reflux stents in terms of their efficacy,safety, and complications.METHODS The meta-analysis included 8 randomized clinical trials(RCTs) to compare pooled outcomes of total 395 patients. Primary outcomes include improvement in reflux symptoms and dysphagia score. Secondary outcomes include complications of stent migration, occlusion, and bleeding.RESULTS A total of eight RCTs were included in the meta-analysis. Compared to the standard stent, the anti-reflux stent showed a trend towards reduction in the dysphagia score without reaching a statistical significance [Standardized mean difference(SMD):-0.33(-0.71, 0.05); P = 0.09, I2: 37%]. There was no statistical difference in the gastrointestinal reflux(GER) scores between the two types of stents [SMD:-0.17(-0.78, 0.45); P = 0.008, I2: 74%]. Compared to standard stent,anti-reflux stent showed no difference in the risk of stent migration [OR: 1.37(0.66, 2.83); P = 0.40, I2: 0 %], bleeding [OR: 1.43(0.40, 5.13); P = 0.59, I2: 0 %], and obstruction [OR: 1.66(0.60, 4.60); P = 0.33, I2: 0 %].CONCLUSION Traditional self-expanding standard esophageal stent and anti-reflux stent with valve are similar in terms of outcomes and complications.     

Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: a meta-analysis of multicenter randomized controlled trials

Journal of Thrombosis and Thrombolysis - Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the...     

Efficacy and safety of abciximab on acute myocardial infarction treated with percutaneous coronary interventions: a meta-analysis of randomized, controlled trials

Objective

To evaluate the efficacy and safety of abciximab following acute myocardial infarction (AMI) treated with percutaneous coronary interventions.

Methods

A meta-analysis of randomized controlled trials of platelet glycoprotein IIb/IIIa inhibitor abciximab as adjunctive therapy to percutaneous coronary interventions for AMI was performed. Main outcomes measured were: (1) mortality, (2) reinfarction, (3) target vessel revascularization (TVR), (4) major cardiac events (MACE) that were a composite endpoint of death, reinfarction, and TVR, and (5) major bleeding.

Results

Six trials randomized 3755 patients who were followed for a mean of 5.5 months. Compared with the control, abciximab significantly reduced mortality (OR 0.70, 95% CI 0.50-0.97), TVR (0.79, 95% CI 0.65-0.96) and MACE (0.76, 95% CI 0.65-0.90). Reduction on TVR and MACE was confirmed in stent patients, but not in balloon angioplasty patients. Abciximab was associated with an increased risk of major bleeding (OR 1.39, 95% CI 1.03-1.87), but bleeding was observed only with a 100U/kg heparin bolus followed by a maintenance infusion (OR 1.89, 95% CI 1.10-3.28) and not with a bolus of 70U/kg (OR 1.22, 95% CI 0.85-1.73).

Conclusions

Abciximab, as adjunctive therapy to percutaneous coronary interventions, reduces mortality, TVR and MACE following AMI. The reduction of clinical outcomes occurs with stent implantation but not with balloon angioplasty. A 70U/kg heparin bolus must be used to avoid major bleeding.     

Techniques for liver parenchymal transection: a meta-analysis of randomized controlled trials

Background:

Different techniques of liver parenchymal transection have been described, including the finger fracture, sharp dissection, clamp–crush methods and, more recently, the Cavitron ultrasonic surgical aspirator (CUSA), the hydrojet and the radiofrequency dissection sealer (RFDS). This review assesses the benefits and risks associated with the various techniques.

Methods:

Randomized clinical trials were identified from the Cochrane Library Trials Register, MEDLINE, EMBASE, Science Citation Index Expanded and reference lists. Odds ratio (ORs), mean difference (MDs) and standardized mean differences (SMDs) were calculated with 95% confidence intervals based on intention-to-treat analysis or available-case analysis.

Results:

We identified seven trials including a total of 556 patients. Blood transfusion requirements were lower with the clamp–crush technique than with the CUSA or hydrojet. The clamp–crush technique was quicker than the CUSA, hydrojet or RFDS. Infective complications and transection blood loss were greater with the RFDS than with the clamp–crush method. There was no significant difference between techniques in mortality, morbidity, liver dysfunction or intensive therapy unit and hospital stay.

Conclusions:

The clamp–crush technique is more rapid and is associated with lower rates of blood loss and otherwise similar outcomes when compared with other methods of parenchymal transection. It represents the reference standard against which new methods may be compared.     

Psychological interventions for rheumatoid arthritis: a meta-analysis of randomized controlled trials

OBJECTIVE: To carry out a systematic review of the literature examining the efficacy of psychological interventions (e.g., relaxation, biofeedback, cognitive-behavioral therapy) in the treatment of rheumatoid arthritis (RA).METHODS: Studies that met the following criteria were included: random assignment, wait-list or usual care control condition; publication in peer-reviewed journals; treatment that included some psychological component beyond simply providing education information; and separate data provided for patients with RA if subjects with conditions other than RA were included. Two investigators independently extracted data on study design, sample size and characteristics, type of intervention, type of control, direction and nature of the outcome(s).RESULTS: Twenty-five trials met the inclusion criteria. Methodologic quality was assessed, and effect sizes were calculated for 6 outcomes. Significant pooled effect sizes were found postintervention for pain (0.22), functional disability (0.27), psychological status (0.15), coping (0.46), and self efficacy (0.35). At followup (averaging 8.5 months), significant pooled effect sizes were observed for tender joints (0.33), psychological status (0.30), and coping (0.52). No clear or consistent patterns emerged when effect sizes for different types of treatment and control conditions were compared, or when higher quality trials were compared to lower quality ones. Findings do, however, suggest that these psychological interventions may be more effective for patients who have had the illness for shorter duration.CONCLUSIONS: Despite some methodologic flaws in the literature, psychological interventions may be important adjunctive therapies in the medical management of RA.     

Octreotide for advanced hepatocellular carcinoma: a meta-analysis of randomized controlled trials

Purpose

To evaluate the effectiveness of octreotide in advanced hepatocellular carcinoma participants on the basis of randomized controlled trials.

Methods

We searched the Cochrane Center Register of Controlled Trials in The Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database, China Journal Full-text Database, Chinese Scientific Journals Database up to June 2008 in any language. Randomized controlled trials of octreotide for advanced hepatocellular carcinoma were selected and evaluated by two investigators. Any disagreement was solved by discussion. Analyses were performed using Review Manager 4.2.

Results

Six randomized controlled trials totaling 352 participants were included. The median survival time was reported in four randomized controlled trials. The results between the octreotide group and the control group (the placebo or best supportive care group) were as follows: 13.0 versus 4.0 months, 1.93 versus 1.97 months, 4.7 versus 5.3 months, and 7.0 versus 2.5 months. Three randomized controlled trials reported 6-month survival rates and 12-month survival rates and meta-analysis results in these two outcomes [(RR 1.35, 95% CI 0.92–1.97); (RR 1.35, 95% CI 0.66–11.16) respectively] were not found to be statistically significant by random-effects model. When we analyzed 6-month survival rates by fixed-effect model (RR 1.30, 95% CI 1.02–1.66), meta-analysis result reached statistical significance.

Conclusions

As for the limitations of the included trials, the result may not demonstrate a significant superiority of octreotide administration in participants with advanced hepatocellular carcinoma from the available evidence.     

Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials

The objective of this study was to evaluate the efficacy and safety of topical diclofenac therapy for osteoarthritis (OA). A meta-analysis of randomized controlled trials was conducted. A comprehensive literature search, covering the databases of Medline, the Cochrane Central Register of Controlled Trials, and EMBASE, was conducted in September 2014 to identify the randomized controlled trials which adopted the topical diclofenac therapy for OA. A total of nine papers were included in this meta-analysis. Topical diclofenac appears to be effective in both pain relief (standard mean differences (SMD)?=?0.40; 95 % confidence interval (CI) 0.19 to 0.62; P?=?0.0003) and function improvement (SMD?=?0.23; 95 % CI 0.03 to 0.43; P?=?0.03) when compared with the control group. The sensitivity analysis and subgroup analysis showed that the result of pain intensity was stable and reliable, while the result of physical function improvement was vague. With respect to safety, topical diclofenac demonstrated a higher incidence of adverse events such as dry skin, rash, dermatitis, neck pain, and withdrawal. Topical diclofenac is effective in pain relief as a treatment of OA. It may also have a potential effect in function improvement, which needs further studies to be explored. Although, some adverse effects were observed in the application of topical diclofenac, none of them was serious.     

Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials

To evaluate the efficacy and tolerability of oxycodone in cancer-related pain, we conducted a systematic review of randomized controlled trials. Four studies, comparing oral oxycodone with either oral morphine (n = 3) or oral hydromorphone (n = 1), were suitable for meta-analysis. Standardized mean differences in pain scores comparing oxycodone with control groups were pooled using random-effects models. Overall, there was no evidence that mean pain scores differed between oxycodone and control drugs (pooled standardized mean difference, 0.04; 95% confidence interval [CI], -0.29 to 0.36; P = .8; I(2) = 62%). In meta-regression analyses, pain scores were higher for oxycodone compared with morphine (0.20; 95% CI, -0.04 to 0.44) and lower compared with hydromorphone (-0.36; 95% CI, -0.71 to 0.00), although these effect sizes were small. The efficacy and tolerability of oxycodone are similar to morphine, supporting its use as an opioid for cancer-related pain.