The Effect of Statins on Mortality in Septic Patients: A Meta-Analysis of Randomized Controlled Trials

Objective

Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay.

Data sources and study selection

Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients.

Data extraction and synthesis

Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found.

Conclusions

Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic.     

Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials

Background

Obesity is associated with increased mortality, and weight loss trials show rapid improvement in many mortality risk factors. Yet, observational studies typically associate weight loss with higher mortality risk. The purpose of this meta-analysis of randomized controlled trials (RCTs) of weight loss was to clarify the effects of intentional weight loss on mortality.

Methods

2,484 abstracts were identified and reviewed in PUBMED, yielding 15 RCTs reporting (1) randomization to weight loss or non-weight loss arms, (2) duration of ≥18 months, and (3) deaths by intervention arm. Weight loss interventions were all lifestyle-based. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated for each trial. For trials reporting at least one death (n = 12), a summary estimate was calculated using the Mantel-Haenszel method. Sensitivity analysis using sparse data methods included remaining trials.

Results

Trials enrolled 17,186 participants (53% female, mean age at randomization = 52 years). Mean body mass indices ranged from 30–46 kg/m², follow-up times ranged from 18 months to 12.6 years (mean: 27 months), and average weight loss in reported trials was 5.5±4.0 kg. A total of 264 deaths were reported in weight loss groups and 310 in non-weight loss groups. The weight loss groups experienced a 15% lower all-cause mortality risk (RR = 0.85; 95% CI: 0.73–1.00). There was no evidence for heterogeneity of effect (Cochran’s Q = 5.59 (11 d.f.; p = 0.90); I² = 0). Results were similar in trials with a mean age at randomization ≥55 years (RR = 0.84; 95% CI 0.71–0.99) and a follow-up time of ≥4 years (RR = 0.85; 95% CI 0.72–1.00).

Conclusions

In obese adults, intentional weight loss may be associated with approximately a 15% reduction in all-cause mortality.     

Incidence and Risk of Treatment-Related Mortality with Anti-Epidermal Growth Factor Receptor Monoclonal Antibody in Cancer Patients: A Meta-Analysis of 21 Randomized Controlled Trials

Background

Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) cetuximab and panitumumab have emerged as an effective targeted therapy in the treatment of cancer patients, but the overall incidence and risk of fatal adverse events (FAEs) associated with these agents is still unclear.

Methods

Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating MoAbs in cancer patients with adequate data on FAEs. Statistical analyses were conducted to calculate the summary incidence, odds ratio and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies.

Results

A total of 14,776 patients with a variety of solid tumors from 21 clinical trials were included in our analysis. The overall incidence of MoAbs associated FAEs was 1.7% (95%CI: 1.1–2.5%), and the incidence of cetuximab-related FAEs was higher than that of panitumumab (2.0% versus 0.9%). Compared with the controls, the use of MoAbs was associated with a significantly increased risk of FAEs, with an OR of 1.37 (95%CI: 1.04–1.81, p=0.024). Subgroup analysis based on EGFR-MoAbs drugs, phase of trials and tumor types demonstrated a tendency to increase the risk of FAEs, but the risk did not increase in breast cancer, esophagus cancer and phase II trials.

Conclusions

With present evidence, the use of EGFR-MoAbs is associated with an increased risk of FAEs in patients with advanced solid tumors.     

Dezocine for Preventing Postoperative Pain: A Meta-Analysis of Randomized Controlled Trials

Background

Dezocine is considered to be an alternative medication for managing postoperative pain. The aim of this study was to assess the efficacy and safety of this drug in this regard.

Methods

Medline, EMBASE and the Cochrane Central Register of Control Trials (CENTRAL) were searched to identify all randomized controlled trials (RCTs) that compare dezocine with placebo or dezocine with morphine on postoperative pain. The data were extracted and pooled using Mantel-Haenszel random effects model. Heterogeneity was tested using the I ² statistic with values >50% and Chi² test with P ≤ 0.05 indicating obvious heterogeneity between the studies.

Results

Seven trials evaluating 665 patients were included. The number of patients with at least 50% pain relief was increased (N = 234; RR 3.04, 95% CI 2.27 to 4.08) and physician (N = 465; RR 2.84, 95% CI 1.66 to 4.84) and patient satisfaction (N = 390; RR 2.81, 95% CI 1.85 to 4.26) were improved following the administration of dezocine compared with the placebo. The effects of dezocine were similar to those of morphine in terms of the number of patients reporting at least 50% pain relief within 2–6 h after surgery (N = 235; RR 1.29, 95% CI 1.15 to 1.46) and physician (N = 234; RR 1.18, 95% CI 0.93 to 1.49) and patient (N = 158; RR 1.33, 95% CI 0.93 to 1.92) satisfaction. While, the number of patients with at least 50% pain relief within 0–1 h after surgery increased following dezocine compared with morphine treatment (N = 79; RR 1.45, 95% CI 1.18 to 1.77). There was no difference in the incidence of postoperative nausea and vomiting (PONV) following dezocine treatment compared with the placebo (N = 391; RR 1.06, 95% CI 0.42 to 2.68) or morphine treatment (N = 235; RR 0.65, 95% CI 0.14 to 2.93).

Conclusion

Dezocine is a promising analgesic for preventing postoperative pain, but further studies are required to evaluate its safety.     

Association between B Vitamins Supplementation and Risk of Cardiovascular Outcomes: A Cumulative Meta-Analysis of Randomized Controlled Trials

Background

Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base.

Methodology and Principal Findings

In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93–1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97–1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90–1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93–1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85–1.03; P = 0.18).

Conclusion/Significance

B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.     

Effects of Zinc Supplementation on the Incidence of Mortality in Preschool Children: A Meta-Analysis of Randomized Controlled Trials

Background

Previous trials have shown that zinc supplementation can decrease the risk of diarrhea, pneumonia, and malaria in children; however, the effects of zinc supplementation on mortality remain unclear. This study aimed at evaluating the benefits and risks of zinc supplementation on both total mortality and cause-specific mortality.

Methodology and Principal Findings

We searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in preschool children reporting total mortality or cause-specific mortality. Relative risk (RR) was used as a measure of the effect of zinc supplementation on the risk of mortality using a random effect model. Of the 1,520 identified articles, we included 8 trials reporting data on 87,854 children. Overall, zinc supplementation had no effect on total mortality (RR, 0.76; 95% CI: 0.56–1.04; P = 0.084), diarrhea-related mortality (RR, 0.80; 95% CI: 0.53–1.20; P = 0.276), pneumonia-related mortality (RR, 0.52; 95% CI: 0.11–2.39; P = 0.399), malaria-related mortality (RR, 0.90; 95% CI: 0.77–1.06; P = 0.196), or other causes of mortality (RR, 0.98; 95% CI: 0.67–1.44; P = 0.917). Subgroup analysis indicated that zinc supplementation was associated with a reduction in total mortality risk if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.

Conclusions/Significance

Zinc supplementation does not have an effect on total mortality, diarrhea-related mortality, pneumonia-related mortality, malaria-related mortality, or other causes of mortality. Subgroup analysis suggested that zinc supplementation can effectively reduce the risk of total mortality if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.     

Pharmacogenetics-Based versus Conventional Dosing of Warfarin: A Meta-Analysis of Randomized Controlled Trials

Background

Recently, using the patient’s genotype to guide warfarin dosing has gained interest; however, whether pharmacogenetics-based dosing (PD) improves clinical outcomes compared to conventional dosing (CD) remains unclear. Thus, we performed a meta-analysis to evaluate these two strategies.

Methods

The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese VIP and Chinese Wan-fang databases were searched. The Cochrane Collaboration’s tool was used to assess the risk of bias in randomized controlled trials (RCTs). The primary outcome was time within the therapeutic range (TTR); the secondary end points were the time to maintenance dose and time to first therapeutic international normalized ratio (INR), an INR greater than 4, adverse events, major bleeding, thromboembolism and death from any cause.

Results

A total of 11 trials involving 2,678 patients were included in our meta-analysis. The results showed that PD did not improve the TTR compared to CD, although PD significantly shortened the time to maintenance dose (MD = -8.80; 95% CI: -11.99 to -5.60; P<0.00001) and the time to first therapeutic INR (MD = -2.80; 95% CI: -3.45 to -2.15; P<0.00001). Additionally, PD significantly reduced the risk of adverse events (RR = 0.86; 95% CI: 0.75 to 0.99; P = 0.03) and major bleeding (RR = 0.36; 95% CI: 0.15 to 0.89, P = 0.03), although it did not reduce the percentage of INR greater than 4, the risk of thromboembolic events and death from any cause. Subgroup analysis showed that PD resulted in a better improvement in the endpoints of TTR and over-anticoagulation at a fixed initial dosage rather than a non-fixed initial dosage.

Conclusions

The use of genotype testing in the management of warfarin anticoagulation was associated with significant improvements in INR-related and clinical outcomes. Thus, genotype-based regimens can be considered a reliable and accurate method to determine warfarin dosing and may be preferred over fixed-dose regimens.

Trial Registration PROSPERO

Database registration: CRD42015024127.     

Merocel versus Nasopore for Nasal Packing: A Meta-Analysis of Randomized Controlled Trials

Objective

To compare the clinical outcomes, including efficacy and complications, of Merocel versus Nasopore as a nasal packing material after nasal surgery.

Methods

Relevant randomized controlled trials were identified from electronic databases (The Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure and Chinese Biomedical Database). Conference proceedings and references from identified trials and review articles were also searched. Outcome measures were pain during nasal packing, pain and bleeding upon packing removal, pressure sensation, nasal blockage, formation of synechiae, mucosal healing, and patients'' general satisfaction.

Results

Seven randomized controlled trials met criteria for analysis. Compared with Merocel, Nasopore significantly reduced patients'' subjective symptoms including in situ pain (pain experienced while packing is in place), nasal pressure, pain and bleeding during packing removal, and increased patients'' general satisfaction with nasal packing. There were no significant differences in nasal obstruction, adhesion and mucosal healing between the Merocel and Nasopore groups.

Conclusions

Preliminary evidence suggests that Nasopore may be superior to Merocel as a nasal packing material with regard to in situ pain, pain and bleeding upon removal, pressure, and general satisfaction and does not differ from Merocel in terms of nasal obstruction, tissue adhesion, and long-term mucosal healing.     

Statin Use and Risk of Lung Cancer: a Meta-Analysis of Observational Studies and Randomized Controlled Trials

Clinical studies have shown that statin use may alter the risk of lung cancer. However, these studies yielded different results. To quantify the association between statin use and risk of lung cancer, we performed a detailed meta-analysis. A literature search was carried out using MEDLINE, EMBASE and COCHRANE database between January 1966 and November 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to calculate the pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. A total of 20 (five randomized controlled trials, eight cohorts, and seven case–control) studies contributed to the analysis. Pooled results indicated a non-significant decrease of total lung cancer risk among all statin users (RR = 0.89, 95% CI [0.78, 1.02]). Further, long-term statin use did not significantly decrease the risk of total lung cancer (RR = 0.80, 95% CI [0.39 , 1.64]). In our subgroup analyses, the results were not substantially affected by study design, participant ethnicity, or confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of results. The findings of this meta-analysis suggested that there was no significant association between statin use and risk of lung cancer. More studies, especially randomized controlled trials and high quality cohort studies are warranted to confirm this association.     

Effect of Flexible Sigmoidoscopy-Based Screening on Incidence and Mortality of Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Randomized controlled trials (RCTs) have yielded varying estimates of the benefit of flexible sigmoidoscopy (FS) screening for colorectal cancer (CRC). Our objective was to more precisely estimate the effect of FS-based screening on the incidence and mortality of CRC by performing a meta-analysis of published RCTs.

Methods and Findings

Medline and Embase databases were searched for eligible articles published between 1966 and 28 May 2012. After screening 3,319 citations and 29 potentially relevant articles, two reviewers identified five RCTs evaluating the effect of FS screening on the incidence and mortality of CRC. The reviewers independently extracted relevant data; discrepancies were resolved by consensus. The quality of included studies was assessed using criteria set out by the Evidence-Based Gastroenterology Steering Group. Random effects meta-analysis was performed.The five RCTs meeting eligibility criteria were determined to be of high methodologic quality and enrolled 416,159 total subjects. Four European studies compared FS to no screening and one study from the United States compared FS to usual care. By intention to treat analysis, FS-based screening was associated with an 18% relative risk reduction in the incidence of CRC (0.82, 95% CI 0.73–0.91, p<0.001, number needed to screen [NNS] to prevent one case of CRC = 361), a 33% reduction in the incidence of left-sided CRC (RR 0.67, 95% CI 0.59–0.76, p<0.001, NNS = 332), and a 28% reduction in the mortality of CRC (relative risk [RR] 0.72, 95% CI 0.65–0.80, p<0.001, NNS = 850). The efficacy estimate, the amount of benefit for those who actually adhered to the recommended treatment, suggested that FS screening reduced CRC incidence by 32% (p<0.001), and CRC-related mortality by 50% (p<0.001).Limitations of this meta-analysis include heterogeneity in the design of the included trials, absence of studies from Africa, Asia, or South America, and lack of studies comparing FS with colonoscopy or stool-based testing.

Conclusions

This meta-analysis of randomized controlled trials demonstrates that FS-based screening significantly reduces the incidence and mortality of colorectal cancer in average-risk patients. Please see later in the article for the Editors'' Summary     

Endoscopic Vascular Harvest in Coronary Artery Bypass Grafting Surgery: A Meta-Analysis of Randomized Trials and Controlled Trials

OBJECTIVE:: This meta-analysis sought to determine whether endoscopic vascular graft harvesting (EVH) improves clinical and resource outcomes compared with conventional open graft harvesting (OVH) in adults undergoing coronary artery bypass surgery. METHODS:: A comprehensive search was undertaken to identify all randomized and nonrandomized trials of EVH versus OVH up to April 2005. The primary outcome was wound complications. Secondary outcomes included any other clinical morbidity and resource utilization. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences (SMD) and their 95% confidence intervals (95% CI) were analyzed. RESULTS:: Thirty-six trials of 9,632 patients undergoing saphenous vein harvest met the inclusion criteria (13 randomized; 23 nonrandomized). Risk of wound complications was significantly reduced by EVH compared with OVH (OR 0.31, 95% CI 0.23-0.41). Similarly, the risk of wound infections was significantly reduced (OR 0.23, 95% CI 0.20-0.53; P < 0.0001). Need for surgical wound intervention was also significantly reduced (OR 0.16, 95% CI 0.08-0.29). The incidence of pain, neuralgia, and patient satisfaction was improved with EVH compared with OVH. Postoperative myocardial infarction, stroke, reintervention for ischemia or angina recurrence, and mortality were not significantly different. Operative time was significantly increased (WMD 15.26 minutes; 95% CI 0.01, 30.51), hospital length of stay was reduced (WMD -0.85 days; 95% CI -1.55, -0.15), and readmissions were reduced (OR 0.53, 95% CI 0.29-0.98). Costs were insufficiently reported to allow for aggregate analysis. CONCLUSIONS:: Endoscopic vascular graft harvesting of the saphenous vein reduces wound complications and improves patient satisfaction and resource utilization. Further research is required to determine the incremental cost-effectiveness of EVH versus OVH.     

Effect of Grape Polyphenols on Blood Pressure: A Meta-Analysis of Randomized Controlled Trials

Background

The effect of grape polyphenols on blood pressure remains unclear, which we aimed to address via a meta-analysis study.

Methods

We conducted study trial searches in PubMed, Embase, and the Cochrane Library databases. Summary estimates of weighted mean differences and 95% confidence intervals were obtained by using fixed-effects models. Subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the international database of prospectively registered systematic reviews (registration number CRD42015019196).

Results

Ten studies were included in the present meta-analysis. Our results showed daily grape polyphenol intake could significantly reduce systolic blood pressure by 1.48 mmHg when compared to control subjects (12 comparisons; -1.48 [-2.79 to -0.16] mmHg; P = 0.03). Subgroup analyses indicated larger reduction was identified in the intake of low-dose of grape polyphenols (< 733 mg/day, median level of the included studies) or patients with metabolic syndrome. Contrarily, diastolic blood pressure was not significantly decreased in the grape polyphenols group as compared to controls. No significant heterogeneity or publication bias was detected in the meta-analysis of either systolic or diastolic blood pressure.

Conclusions

Daily grape polyphenol intake can significantly reduce the systolic blood pressure in humans, although the reduction is modest when compared with anti-hypertensive medications. Larger, better designed trials, that specifically include hypertensive subjects, are required to verify our results in the future.     

Single Incision versus Conventional Laparoscopic Cholecystectomy Outcomes: A Meta-Analysis of Randomized Controlled Trials

Background

Previous meta-analyses that compared the outcome of SILC and CLC have not presented consistent conclusions. This meta-analysis was performed after adding many recent RCTs, to clarify this issue.

Methods

Relevant articles published in English were identified by searching PubMed, Embase, Web of Knowledge, and the Cochrane Controlled Trial Register from January 1997 to February 2013. Reference lists of the retrieved articles were reviewed to identify additional articles. Primary outcomes (postoperative pain scores, cosmetic score, and length of incision) and secondary outcomes (operating time, blood loss, conversion rates, postoperative complications, postoperative hospital stay, time to initial oral intake, and time to resume work) were pooled. Quantitative variables were calculated using the weighted mean difference (WMD), and qualitative variables were pooled using odds ratios (OR).

Results

25 appropriate RCTs were identified from 2128 published articles. 1841 patients were treated, 944 with SILC and 897 with CLC. SILC was superior to CLC in cosmetic score (WMD = 1.155, P<0.001), shorter length of incision (WMD = -3.285, P = 0.029), and postoperative pain within 12 h (VAS in 3-4 h, WMD = -0.704, P = 0.026; VAS in 6-8 h, WMD = -0.613, P = 0.010). CLC was superior to SILC in operating time (OT) (WMD = 13.613, P<0.001) and need of additional instruments (OR = 7.448, P<0.001). Other secondary outcomes were similar.

Conclusions

SILC offered a better cosmetic result and less postoperative pain for patients with uncomplicated cholelithiasis or polypoid lesions of the gallbladder. However, SILC was associated with a longer OT and required additional instruments.     

Aerobic Exercise for Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Although some trials assessed the effectiveness of aerobic exercise for Parkinson''s disease (PD), the role of aerobic exercise in the management of PD remained controversial.

Objective

The purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD.

Methods

Seven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I² statistic.

Results

18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, −0.57; 95% CI −0.94 to −0.19; p = 0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p = 0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p<0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI −0.23 to 0.46; p = 0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD.

Conclusion

Aerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings.     

Effect of Antioxidant Vitamin Supplementation on Cardiovascular Outcomes: A Meta-Analysis of Randomized Controlled Trials

Background

Antioxidant vitamin (vitamin E, beta-carotene, and vitamin C) are widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamin on cardiovascular events remains unclear.

Methodology and Principal Findings

We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant literature. Eligible studies were randomized controlled trials that reported on the effects of antioxidant vitamin on cardiovascular outcomes as compared to placebo. Outcomes analyzed were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any possible adverse events. We used the I² statistic to measure heterogeneity between trials and calculated risk estimates for cardiovascular outcomes with random-effect meta-analysis. Independent extraction was performed by two reviewers and consensus was reached. Of 293 identified studies, we included 15 trials reporting data on 188209 participants. These studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation as compared to placebo had no effect on major cardiovascular events (RR, 1.00; 95%CI, 0.96–1.03), myocardial infarction (RR, 0.98; 95%CI, 0.92–1.04), stroke (RR, 0.99; 95%CI, 0.93–1.05), total death (RR, 1.03; 95%CI, 0.98–1.07), cardiac death (RR, 1.02; 95%CI, 0.97–1.07), revascularization (RR, 1.00; 95%CI, 0.95–1.05), total CHD (RR, 0.96; 95%CI, 0.87–1.05), angina (RR, 0.98; 95%CI, 0.90–1.07), and congestive heart failure (RR, 1.07; 95%CI, 0.96 to 1.19).

Conclusion/Significance

Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.     

Intravenous N-Acetylcysteine for Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of Randomized,Controlled Trials

Background

Contrast-induced nephropathy (CIN) is one of the common causes of acute renal insufficiency after contrast procedures. Whether intravenous N-acetylcysteine (NAC) is beneficial for the prevention of contrast-induced nephropathy is uncertain. In this meta-analysis of randomized controlled trials, we aimed to assess the efficacy of intravenous NAC for preventing CIN after administration of intravenous contrast media.

Study Design

Relevant studies published up to September 2012 that investigated the efficacy of intravenous N-acetylcysteine for preventing CIN were collected from MEDLINE, OVID, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and the conference proceedings from major cardiology and nephrology meetings. The primary outcome was CIN. Secondary outcomes included renal failure requiring dialysis, mortality, and length of hospitalization. Data were combined using random-effects models with the performance of standard tests to assess for heterogeneity and publication bias. Meta-regression analyses were also performed.

Results

Ten trials involving 1916 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-induced nephropathy was 0.68 (95% CI, 0.46 to 1.02), a nonsignificant trend towards benefit in patients treated with intravenous NAC. There was evidence of significant heterogeneity in NAC effect across studies (Q = 17.42, P = 0.04; I² = 48%). Meta-regression revealed no significant relation between the relative risk of CIN and identified differences in participant or study characteristics.

Conclusion

This meta-analysis showed that research on intravenous N-acetylcysteine and the incidence of CIN is too inconsistent at present to warrant a conclusion on efficacy. A large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for intravenous NAC in CIN prevention.     

Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Low levels of 25-OH vitamin D are associated with respiratory tract infection (RTI). However, results from randomized controlled trials are inconclusive. Therefore, we performed a systematic review and meta-analysis to assess the preventive effect of vitamin D supplementation on RTI.

Methods

Randomized, controlled trials of vitamin D for prevention of RTI were used for the analysis. The risks of within-trial and publication bias were assessed. Odds ratios of RTI were pooled using a random-effects model. Heterogeneity was assessed using Cochran''s Q and I². Meta-regressions and subgroup analyses were used to assess the influence of various factors on trial outcome. The pre-defined review protocol was registered at the PROSPERO international prospective register of systematic reviews, registration number CRD42013003530.

Findings

Of 1137 citations retrieved, 11 placebo-controlled studies of 5660 patients were included in the meta-analysis. Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). There was significant heterogeneity among studies (Cohran''s Q p<0.0001, I² = 72%). The protective effect was larger in studies using once-daily dosing compared to bolus doses (OR = 0.51 vs OR = 0.86, p = 0.01). There was some evidence that results may have been influenced by publication bias.

Interpretation

Results indicate that vitamin D has a protective effect against RTI, and dosing once-daily seems most effective. Due to heterogeneity of included studies and possible publication bias in the field, these results should be interpreted with caution.     

Cinacalcet in Patients with Chronic Kidney Disease: A Cumulative Meta-Analysis of Randomized Controlled Trials

Background

Calcimimetic agents lower serum parathyroid hormone levels in people with chronic kidney disease (CKD), but treatment effects on patient-relevant outcomes are uncertain. We conducted a systematic review and meta-analysis to summarize the benefits and harms of calcimimetic therapy in adults with CKD and used cumulative meta-analysis to identify how evidence for calcimimetic treatment has developed in this clinical setting.

Methods and Findings

Cochrane and Embase databases (through February 7, 2013) were electronically searched to identify randomized trials evaluating effects of calcimimetic therapy on mortality and adverse events in adults with CKD. Two independent reviewers identified trials, extracted data, and assessed risk of bias.Eighteen trials comprising 7,446 participants compared cinacalcet plus conventional therapy with placebo or no treatment plus conventional therapy in adults with CKD. In moderate- to high-quality evidence (based on Grading of Recommendations Assessment, Development, and Evaluation criteria) in adults with CKD stage 5D (dialysis), cinacalcet had little or no effect on all-cause mortality (relative risk, 0.97 [95% confidence interval, 0.89–1.05]), had imprecise effect on cardiovascular mortality (0.67 [0.16–2.87]), and prevented parathyroidectomy (0.49 [0.40–0.59]) and hypercalcemia (0.23 [0.05–0.97]), but increased hypocalcemia (6.98 [5.10–9.53]), nausea (2.02 [1.45–2.81]), and vomiting (1.97 [1.73–2.24]). Data for clinical outcomes were sparse in adults with CKD stages 3–5. On average, treating 1,000 people with CKD stage 5D for 1 y had no effect on survival and prevented about three patients from experiencing parathyroidectomy, whilst 60 experienced hypocalcemia and 150 experienced nausea. Analyses were limited by insufficient data in CKD stages 3–5 and kidney transplant recipients.

Conclusions

Cinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D, but does not appear to improve all-cause or cardiovascular mortality. Additional trials in CKD stage 5D are unlikely to change our confidence in the treatment effects of cinacalcet in this population. Please see later in the article for the Editors'' Summary     

Post-Operative Auto-Transfusion in Total Hip or Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials

Background

Total hip or knee arthroplasty is an elective procedure that is usually accompanied by substantial blood loss, which may lead to acute anemia. As a result, almost half of total joint arthroplasty patients receive allogeneic blood transfusions (ABT). Many studies have shown that post-operative auto-transfusion (PAT) significantly reduces the need for ABT, but other studies have questioned the efficacy of this method.

Methods

The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Checklist S1. To evaluate the efficacy of PAT, we conducted a Cochrane systematic review that combined all available data from randomized controlled trials. Data from the six included trials were pooled for analysis. We then calculated relative risks with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes.

Findings and Conclusion

To our knowledge, this is the first meta-analysis to compare the clinical results between PAT and a control in joint replacement patients. This meta-analysis has proven that the use of a PAT reinfusion system reduced significantly the demand for ABT, the number of patients who require ABT and the cost of hospitalization after total knee and hip arthroplasty. This study, together with other previously published data, suggests that PAT drains are beneficial. Larger, sufficiently powered studies are necessary to evaluate the presumed reduction in the incidence of infection as well as DVT after joint arthroplasty with the use of PAT.     

Stereotactic Aspiration versus Craniotomy for Primary Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

Background

A wealth of evidence based on the randomized controlled trials (RCTs) has indicated that surgery may be a better choice in the management of primary intracerebral hemorrhage (ICH) compared to conservative treatment. However, there is considerable controversy over selecting appropriate surgical procedures for ICH. Thus, this meta-analysis was performed to assess the effects of stereotactic aspiration compared to craniotomy in patients with ICH.

Methods

According to the study strategy, we searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials. Other sources such as the internet-based clinical trial registries, relevant journals and the lists of references were also searched. After literature searching, two investigators independently performed literature screening, assessment of quality of the included trials and data extraction. The outcome measures included death or dependence, total risk of complication, and the risk of rebleeding, gastrointestinal hemorrhage and systematic infection.

Results

Four RCTs with 2996 participants were included. The quality of the included trials was acceptable. Stereotactic aspiration significantly decreased the odds of death or dependence at the final follow-up (odds ratio (OR): 0.80, 95% confidence interval (CI): 0.69–0.93; P = 0.004) and the risk of intracerebral rebleeding (OR: 0.44, 95% CI: 0.26–0.74; P = 0.002) compared to craniotomy with no significant heterogeneity among the study results.

Conclusions

The present meta-analysis provides evidence that the stereotactic aspiration may be associated with a reduction in the odds of being dead or dependent in primary ICH, which should be interpreted with caution. Further trials are needed to identify those patients most likely to benefit from the stereotactic aspiration.