Statins and the Risk of Lung Cancer: A Meta-Analysis

Purpose

Several epidemiologic studies have evaluated the association between statins and lung cancer risk, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. We conducted a meta-analysis of all relevant studies to examine this association.

Methods

A systematic literature search up to March 2012 was performed in PubMed database. Study-specific risk estimates were pooled using a random-effects model.

Results

Nineteen studies (5 RCTs and 14 observational studies) involving 38,013 lung cancer cases contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of lung cancer either among RCTs (relative risk [RR] 0.91, 95% confidence interval [CI] 0.76–1.09), among cohort studies (RR 0.94, 95% CI 0.82–1.07), or among case-control studies (RR 0.82, 95% CI 0.57–1.16). Low evidence of publication bias was found. However, statistically significant heterogeneity was found among cohort studies and among case-control studies. After excluding the studies contributing most to the heterogeneity, summary estimates were essentially unchanged.

Conclusion

The results of our meta-analysis suggest that there is no association between statin use and the risk of lung cancer.     

Effect of Stem Cell Therapy on Bone Mineral Density: A Meta-Analysis of Preclinical Studies in Animal Models of Osteoporosis

Background

Preclinical studies of the therapeutic role of stem cell based therapy in animal models of osteoporosis have largely yielded inconsistent results. We performed a meta-analysis to provide an overview of the currently available evidence.

Methods

Pubmed, Embase and Cochrane Library databases were systematically searched for relevant controlled studies. A random-effect model was used for pooled analysis of the effect of stem cell based therapy on bone mineral density (BMD). Stratified analyses were performed to explore the effect of study characteristics on the outcomes.

Results

Pooled results from 12 preclinical studies (110 animals in stem cell treatment groups, and 106 animals in control groups) indicated that stem cell based treatment was associated with significantly improved BMD (standardized mean difference [SMD] = 1.29, 95% Confidence Interval [CI]: 0.84–1.74, P < 0.001) with moderate heterogeneity (Cochrane’s Q test: P = 0.02, I² = 45%) among the constituent studies. Implantation of bone marrow cells, bone marrow mesenchymal stem cells, adipose-derived stem cells, and human umbilical cord blood-derived CD34+ cells, were all associated with improved BMD as compared to that in the controls (P < 0.05 for all); the only exception being the use of embryonic stem cell transplantation (P > 0.05). Egger’s test detected potential publication bias (P = 0.055); however, ‘trim and fill’ analysis yielded similar results after statistically incorporating the hypothetical studies in the analysis (SMD = 1.24, 95% CI: 0.32–2.16, P < 0.001).

Conclusions

Stem cell transplantation may improve BMD in animal models of osteoporosis. Our meta-analysis indicates a potential therapeutic role of stem cell based therapy for osteoporosis, and serves to augment the rationale for clinical studies.     

The Efficacy of Hyperbaric Oxygen Therapy on Middle Cerebral Artery Occlusion in Animal Studies: A Meta-Analysis

Background

Inconsistent results have been reported for hyperbaric oxygen therapy (HBO) for acute stroke. We conducted a systematic review and meta-analysis to evaluate the benefit of HBO in animal studies of middle cerebral artery occlusion (MCAO).

Methods

A systematic search of the literature published prior to September 2015 was performed using Embase, Medline (OvidSP), Web of Science and PubMed. Keywords included “hyperoxia” OR “hyperbaric oxygen” OR “HBO” AND “isch(a)emia” OR “focal cerebral ischemia” OR “stroke” OR “infarct” OR “middle cerebral artery occlusion (MCAO).” The primary endpoints were the infarct size and/or neurological outcome score evaluated after HBO treatment in MCAO. Heterogeneity was analyzed using Cochrane Library’s RevMan 5.3.5.

Results

Fifty-one studies that met the inclusion criteria were identified among the 1198 studies examined. When compared with control group data, HBO therapy resulted in infarct size reduction or improved neurological function (32% decrease in infarct size; 95% confidence interval (CI), range 28%–37%; p < 0.00001). Mortality was 18.4% in the HBO group and 26.7% in the control group (RR 0.72, 95% CI, 0.54–0.98; p = 0.03). Subgroup analysis showed that a maximal neuro-protective effect was reached when HBO was administered immediately after MCAO with an absolute atmospheric pressure (ATA) of 2.0 (50% decrease; 95% CI, 43% -57% decrease; p < 0.0001) and more than 6 hours HBO treatment (53% decrease; 95% CI, 41% -64% decrease; p = 0.0005).

Conclusions

HBO had a neuro-protective effect and improved survival in animal models of MCAO, especially in animals given more than 6 hours of HBO and when given immediately after MCAO with 2.0 ATA.     

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.     

Peripapillary Retinal Nerve Fiber Layer Changes in Preclinical Diabetic Retinopathy: A Meta-Analysis

BackgroundDiabetic retinopathy is a microvascular neurodegenerative disorder in diabetic patients. Peripapillary retinal nerve fiber layer changes have been described in patients with preclinical diabetic retinopathy, but study results have been inconsistent.ObjectiveTo assess changes in peripapillary retinal nerve fiber layer thickness in diabetic patients with preclinical diabetic retinopathy.MethodsA literature search was conducted through PubMed, EMBASE, Web of Science and Cochrane Library. Case-control studies on RNFL thickness in preclinical diabetic retinopathy patients and healthy controls were retrieved. A meta-analysis of weighted mean difference and a sensitivity analysis were performed using RevMan 5.2 software.ResultsThirteen case-control studies containing 668 diabetic patients and 556 healthy controls were selected. Peripapillary RNFL thickness was significantly reduced in patients with preclinical diabetic retinopathy compared to healthy controls in studies applying Optical Coherence Tomography (-2.88μm, 95%CI: -4.44 to -1.32, P = 0.0003) and in studies applying Scanning Laser Polarimeter (-4.21μm, 95%CI: -6.45 to -1.97, P = 0.0002). Reduction of RNFL thickness was significant in the superior quadrant (-3.79μm, 95%CI: -7.08 to -0.50, P = 0.02), the inferior quadrant (-2.99μm, 95%CI: -5.44 to -0.54, P = 0.02) and the nasal quadrant (-2.88μm, 95%CI: -4.93 to -0.82, P = 0.006), but was not significant in the temporal quadrant (-1.22μm, 95%CI: -3.21 to 0.76, P = 0.23), in diabetic patients.ConclusionPeripapillary RNFL thickness was significantly decreased in preclinical diabetic retinopathy patients compared to healthy control. Neurodegenerative changes due to preclinical diabetic retinopathy need more attention.     

Determinants of the Efficacy of Cardiac Ischemic Preconditioning: A Systematic Review and Meta-Analysis of Animal Studies

Background

Ischemic preconditioning (IPC) of the heart is a protective strategy in which a brief ischemic stimulus immediately before a lethal ischemic episode potently limits infarct size. Although very promising in animal models of myocardial infarction, IPC has not yet been successfully translated to benefit for patients.

Objective

To appraise all preclinical evidence on IPC for myocardial infarction and identify factors hampering translation.

Methods and results

Using systematic review and meta-analysis, we identified 503 animal studies reporting infarct size data from 785 comparisons between IPC-treated and control animals. Overall, IPC reduced myocardial infarction by 24.6% [95%CI 23.5, 25.6]. Subgroup analysis showed that IPC efficacy was reduced in comorbid animals and non-rodents. Efficacy was highest in studies using 2–3 IPC cycles applied <45 minutes before myocardial infarction. Local and remote IPC were equally effective. Reporting of study quality indicators was low: randomization, blinding and a sample size calculation were reported in 49%, 11% and 2% of publications, respectively.

Conclusions

Translation of IPC to the clinical setting may be hampered by the observed differences between the animals used in preclinical IPC studies and the patient population, regarding comorbidity, sex and age. Furthermore, the IPC protocols currently used in clinical trials could be optimized in terms of timing and the number of ischemic cycles applied. In order to inform future clinical trials successfully, future preclinical studies on IPC should aim to maximize both internal and external validity, since poor methodological quality may limit the value of the preclinical evidence.     

Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury,a Systematic Review and Meta-Analysis

Background

Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies.

Method

We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy.

Results

We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported.

Conclusion

High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials.     

The Quantum Yield of Photoinactivation of Photosystem II in Pea Leaves is Greater at Low Than High Photon Exposure

The quantum yield of PSII photoinactivation in pea leaves atlow photon exposure was 3 x 10^-7 mol PSII per mol photons absorbedby PSII and 2.5 x 10^-8 at high photon exposures (mol photonsm^-2), regardless of photomodulation of chloroplasts. We postulatethat the doseresponse behaviour of PSII photoinactivation, whichdepends on the number of photons absorbed, results from thebalance of light consumption with supply. (Received July 18, 1995; Accepted August 8, 1995)     

Calibration of ADHD Assessments Across Studies: A Meta-Analysis Tool

When analyzed separately, data from small studies provide only limited information with limited clinical generalizability, due to small sample size, differing assessments, and limited scope. In this methodological paper we outline a theoretical framework for performing meta-analysis of data obtained from disparate studies using disparate tests, based on calibration of the data from such studies and tests into a unified probability scale. We apply this method to combine the data from five studies examining the diagnostic abilities of different assessments of Attention Deficit/Hyperactivity Disorder (ADHD), including behavioral rating scales and EEG assessments. The studies enrolled a total of 111 subjects, 56 ADHD and 55 controls. Each individual study had a small sample focused on a specific age/gender group, for example 8 boys ages 6–10, and generally had insufficient power to detect statistically significant differences. No gender, or age comparisons were possible within any single study. However, when calibrated and combined, the data resulted in a clear separation between ADHD versus non-ADHD groups in males below the age of 16 (p < 0.001), males above the age of 16, (p = 0.015), females below the age of 16, (p = 0.0014), and females above the age of 16, (p = 0.0022).We conclude that if data from various studies using various tests are made comparable, the resulting combined sample size and the increased diversity of the combined sample lead to increased significance of the statistical tests and allow for cross-sectional comparisons, which are not possible within each individual study.     

A Comprehensive Review on the Anticancer Potential of Bacteriocin: Preclinical and Clinical Studies

International Journal of Peptide Research and Therapeutics - Chikungunya virus is a major arbovirus of great public health concern in the whole world, but no vaccine is yet available, still advance...     

Treatment Efficacy for Non-Cardiovascular Chest Pain: A Systematic Review and Meta-Analysis

Background

Non-cardiovascular chest pain (NCCP) leads to impaired quality of life and is associated with a high disease burden. Upon ruling out cardiovascular disease, only vague recommendations exist for further treatment.

Objectives

To summarize treatment efficacy for patients presenting with NCCP.

Methods

Systematic review and meta-analysis. In July 2013, Medline, Web of Knowledge, Embase, EBSCOhost, Cochrane Reviews and Trials, and Scopus were searched. Hand and bibliography searches were also conducted. Randomized controlled trials (RCTs) evaluating non-surgical treatments in patients with NCCP were included. Exclusion criteria were poor study quality and small sample size (<10 patients per group).

Results

Thirty eligible RCT’s were included. Most studies assessed PPI efficacy for gastroesophageal reflux disorders (GERD, n = 10). Two RCTs included musculoskeletal chest pain, seven psychotropic drugs, and eleven various psychological interventions. Study quality was high in five RCTs and acceptable in 25. PPI treatment in patients with GERD (5 RCTs, 192 patients) was more effective than placebo [pooled OR 11.7 (95% CI 5.5 to 25.0, heterogeneity I² = 6.1%)]. The pooled OR in GERD negative patients (4 RCTs, 156 patients) was 0.8 (95% CI 0.2 to 2.8, heterogeneity I² = 50.4%). In musculoskeletal NCCP (2 RCTs, 229 patients) manual therapy was more effective than usual care but not than home exercise [pooled mean difference 0.5 (95% CI −0.3 to 1.3, heterogeneity I² = 46.2%)]. The findings for cognitive behavioral treatment, serotonin reuptake inhibitors, tricyclic antidepressants were mixed. Most evidence was available for cognitive behavioral treatment interventions.

Limitations

Only a small number of studies were available.

Conclusions

Timely diagnostic evaluation and treatment of the disease underlying NCCP is important. For patients with suspected GERD, high-dose treatment with PPI is effective. Only limited evidence was available for most prevalent diseases manifesting with chest pain. In patients with idiopathic NCCP, treatments based on cognitive behavioral principles might be considered.     

Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis

BackgroundStem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM.ConclusionsStem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34⁺ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy.     

Association between Herpesviruses and Chronic Periodontitis: A Meta-Analysis Based on Case-Control Studies

Objective

Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis.

Methods

A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger''s funnel plot.

Results

Ten eligible studies were included to investigate the association between Epstein–Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53–13.00, P<0.001). The association between human cytomegalovirus (HCMV) and chronic periodontitis was analyzed in 10 studies. The pooled result showed that HCMV also has a significant association with chronic periodontitis (OR = 3.59, 95% CI = 1.41–9.16, P = 0.007). Similar results were found in the sensitivity analyses. No significant publication bias was observed. Two eligible studies were included to investigate the association between herpes simplex virus (HSV) and chronic periodontitis risk. The association between HSV and chronic periodontitis was inconclusive (OR = 2.81 95% CI = 0.95–8.27, P = 0.06). Only one included study investigated the association between human herpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0.21–4.86).

Conclusion

The findings of this meta-analysis suggest that two members of the herpesvirus family, EBV and HCMV, are significantly associated with chronic periodontitis. There is insufficient evidence to support associations between HSV, HHV-7 and chronic periodontitis.     

The Role of Statins in Prevention and Treatment of Community Acquired Pneumonia: A Systematic Review and Meta-Analysis

Background

Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications.

Purpose

Performed a systematic review to address the role of statins in the prevention or treatment of CAP.

Data Source

Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies.

Study Selection

Two authors independently reviewed studies that examined the role of statins in CAP.

Data Extraction

Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted.

Data Synthesis

Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74–0.95), I² = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59–0.78), I² = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77–0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder.

Conclusions

Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias.     

Relationship Between the Use of Statins and Patient Survival in Colorectal Cancer: A Systematic Review and Meta-Analysis

Background

Studies have indicated that statins influence the risks and mortality rates of several types of solid tumors. However, the association between statin use and survival in patients with colorectal cancer (CRC) remains unclear.

Methods

We searched the PubMed and Embase databases for relevant studies published up to September 2014 that assessed statin use and CRC prognosis. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). The secondary outcomes were disease-free survival (DFS) and recurrence-free survival (RFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled with Mantel–Haenszel random-effect modeling. All statistical tests were two-sided.

Results

Four studies on post-diagnosis statin therapy and five studies on pre-diagnosis statin use were included in our meta-analysis of 70,608 patients. Compared with the non-users, the patients with post-diagnosis statin use gained survival benefits for OS (HR 0.76; 95% CI: 0.68 to 0.85, P<0.001) and CSS (HR 0.70; 95% CI: 0.60 to 0.81, P<0.001). In addition, we observed that pre-diagnosis statin use prolonged the survival of patients with CRC for OS (HR 0.70; 95% CI: 0.54 to 0.91, P=0.007) and CSS (HR 0.80; 95% CI: 0.74 to 0.86, P<0.001). However, we did not observe a survival benefit for DFS (HR 1.13; 95% CI: 0.78 to 1.62, P=0.514) or RFS (HR 0.98; 95% CI: 0.36 to 2.70, P=0.975) in the CRC patients with post-diagnosis statin use.

Conclusions

Statin use before or after cancer diagnosis is related to reductions in overall and cancer-specific mortality in colorectal cancer survivors.     

Sedentary Behavior and Incident Cancer: A Meta-Analysis of Prospective Studies

Background

Sedentary behavior is ubiquitous in modern adults'' daily lives and it has been suggested to be associated with incident cancer. However, the results have been inconsistent. In this study, we performed a systematic review and meta-analysis of prospective cohort studies to clarify the association between sedentary behavior and incident cancer.

Method

PubMed and Embase databases were searched up to March 2014. All prospective cohort studies on the association between sedentary behavior and incident cancer were included. The summary relative risks (RRs) with 95% confidence intervals (CIs) were estimated using random effect model.

Results

A total of 17 prospective studies from 14 articles, including a total of 857,581 participants and 18,553 cases, were included in the analysis for sedentary behavior and risk of incident cancer. The overall meta-analysis suggested that sedentary behavior increased risk of cancer (RR = 1.20, 95%CI = 1.12–1.28), with no evidence of heterogeneity between studies (I ² = 7.3%, P = 0.368). Subgroup analyses demonstrated that there were statistical associations between sedentary behavior and some cancer types (endometrial cancer: RR = 1.28, 95% CI = 1.08–1.53; colorectal cancer: RR = 1.30, 95%CI = 1.12–1.49; breast cancer: RR = 1.17, 95%CI = 1.03–1.33; lung cancer: RR = 1.27, 95%CI = 1.06–1.52). However, there was no association of sedentary behavior with ovarian cancer (RR = 1.26, 95%CI = 0.87–1.82), renal cell carcinoma (RR = 1.11, 95%CI = 0.87–1.41) or non-Hodgkin lymphoid neoplasms (RR = 1.09, 95%CI = 0.82–1.43).

Conclusion

The present meta-analysis suggested that prolonged sedentary behavior was independently associated with an increased risk of incident endometrial, colorectal, breast, and lung cancers, but not with ovarian cancer, renal cell carcinoma or non-Hodgkin lymphoid neoplasms.