Tianyi Zhang

Body mass index and mortality in chronic obstructive pulmonary disease: A dose-response meta-analysis.

Abstract The aim of this study is to summarize the evidence on the dose–response relationship between body mass index (BMI) and mortality in patients with chronic obstructive pulmonary disease (COPD). We performed a systemic literature search in PubMed, Embase, and Web of Science for relevant studies that were published until June 2015. A random effects meta-analysis was used to estimate the pooled relative risks (RRs) of all-cause mortality in COPD patients with normal weight compared with those who were underweight, overweight, or obese. In addition, a dose–response meta-analysis was conducted to explore the dose–response relationship between BMI and all-cause mortality in COPD patients. A total of 17 observational studies involving 30,182 COPD patients among 285,960 participants were included. Compared with the reference category, the RRs of underweight, overweight, and obese individuals were 1.40 (95% confidence interval (CI), 1.20–1.63), 0.80 (95% CI, 0.67–0.96), and 0.77 (95% CI, 0.62–0.95), respectively. A significant nonlinear relationship between BMI and mortality of COPD patients was found by using a random effects model. COPD patients with BMI of <21.75 kg/m2 had a higher risk of death. Moreover, an increase in the BMI resulted in a decrease in the risk of death. The risk of death was lowest when BMI was 30 kg/m2 (RR = 0.69; 95% CI, 0.53–0.89). The BMI was not associated with all-cause mortality when BMI was >32 kg/m2. Our findings indicate that overweight is associated with a lower risk of all-cause mortality among patients with COPD whereas underweight is associated with a higher risk of all-cause mortality in these patients. However, there is limited evidence to support the association between obesity and the risk of all-cause mortality in patients with COPD.

Effects of three injectable antidiabetic agents on glycaemic control, weight change and drop-out in type 2 diabetes suboptimally controlled with metformin and/or a sulfonylurea: A network meta-analysis

AIMS The objective of this review was to assess glucagon-like peptide-1 receptor agonists (GLP-1 RAs), basal insulin, and premixed insulin among participants with type 2 diabetes inadequately controlled with metformin and/or a sulfonylurea. METHODS We searched PubMed, EmBase, and the Cochrane Library to identify eligible randomized controlled trials (RCTs) for a network meta-analysis. RESULTS A total of 17 RCTs involving 5874 adult individuals were included. Compared with placebo, all three therapies showed a significant effect on achieving target glycated hemoglobin (HbA1c) (GLP-1 RAs: 31.7%, 95% CI, 24.7-38.6%; premixed insulin: 31.1%, 95% CI, 20.4-41.8%; basal insulin: 26.0%, 95% CI, 16.4-35.7%). However, there was no significant difference between the three therapies. A similar result was found in HbA1c reduction. The use of GLP-1 RAs resulted in significant body weight loss (-3.73 kg, 95% CI, -4.52 to -2.95 kg vs. basal insulin and -5.27 kg, 95% CI, -6.17 to -4.36 kg vs. premixed insulin) but there was a higher drop-out rate of participants. Premixed insulin seemed associated with more severe hypoglycemic episodes. CONCLUSIONS The three injectables had similar impact on glycemic control but other differentiating features relevant to the management of type 2 diabetes with GLP-1 RAs having the most favorable profile.

Reporting patterns of adverse drug reactions over recent years in China: analysis from publications

Purpose: The goal of this study was to clarify the reporting patterns of self-reported adverse drug reactions (ADRs) in China. Methods: A variety of sources were searched, including the official website of China FDA, the national center for ADR monitoring center, publications from PubMed, and so on. We retrieved the relevant information and made descriptive and comparative analysis from the year 2009 to 2013. Results: The ADR reporting numbers were 638,996, 692,904, 852,799, 1,200,000 and 1,317,000 from 2009 to 2013, respectively. Healthcare professionals contributed significantly, and their proportion always exceeded 80% before 2012. The average report per million inhabitants has increased from 479 to 983 from 2009 to 2013. However, the proportion of new or serious report was always below 25%. The reports mainly concern anti-infective agents and traditional Chinese medicine (TCM), especially TCM injection. The proportion of ADR reports in geriatric patients has increased for 4 consecutive years. Conclusions: ADR report numbers and reporting rates in China are on the rise. However, the proportion of new or serious reports as well as the proportion of reports contributed by consumers and pharmaceutical companies are still quite low. More attention should be paid to the elderly, anti-infective agents and TCM, especially TCM injections.

Antithrombotic Treatment for Recurrent Miscarriage: Bayesian Network Meta-Analysis and Systematic Review.

AbstractCombined use of heparin and aspirin is frequently prescribed for treatment of recurrent miscarriage (RM) in patients with antiphospholipid syndrome (APS), or in those without apparent cause of RM other than thrombophilia; however, this strategy is largely based on expert opinion and has not been well studied. The option for the use of different antithrombotic therapies to improve live birth remains unclear. In this network meta-analysis, we incorporated direct and indirect evidence to evaluate effects of different antithrombotic treatments on prevention of pregnancy losses.We searched PubMed and Embase for randomized clinical trials comparing effects of at least 2 antithrombotic treatments on live birth in RM patients published from 1965 through the early of May 2015. Potential risk bias of eligible trials was evaluated according to the Cochrane Collaboration guidelines. Bayesian network meta-analysis was used to estimate relative effects on live birth.A total of 19 trials involving 2391 RM patients with or without thrombophilia and 543 with APS were included. No beneficial effect of antithrombotic treatment was observed either in RM patients with or without thrombophilia or in patients with APS; however, for patients with or without thrombophilia, low molecular weight heparin therapy had the greatest probability (61.48%) of being the best option in terms of live birth; for patients with APS, unfractionated heparin plus aspirin was the superior treatment for RM with the highest possibility (75.15%) of being top 2 places for reducing pregnancy losses. Aspirin was inferior in both groups.Our results do not support the use of combined low molecular weight heparin and aspirin for RM treatment, and suggested aspirin may have negative effects for lowering the risk of pregnancy loss.

Adult weight gain and risk of prostate cancer: A dose–response meta-analysis of observational studies

The association between adult weight gain and risk of prostate cancer has not been widely studied and the findings are inconsistent. Therefore, our study aimed to investigate the association between adult weight gain and risk of prostate cancer. PubMed, Embase and Web of Science databases were searched for relevant studies published before September 2014 using terms related to weight gain and prostate cancer. Summary estimates were obtained using the random‐effects model. Dose–response meta‐analysis, sensitivity analysis and publication bias tests were performed. Nine studies involving 497,634 participants and 22,338 cancer cases were included. For total prostate cancer, a positive relationship with adult weight gain was observed until weight gain increased to >30 kg. For low‐intermediate‐risk prostate cancer, a positive relationship with adult weight gain was observed until weight gain increased to >15 kg. For high‐risk prostate cancer, we observed a positive linear relationship with adult weight gain with a relative risk (RR) of 1.02 [95% confidence interval (CI) 1.00–1.04] for every 5‐kg increase. For fatal prostate cancer, we observed a positive linear relationship with adult weight gain with an RR of 1.12 (95% CI: 1.05–1.19) for every 5‐kg increase. There is evidence that adult weight gain is associated with an increased risk of high‐risk and fatal prostate cancer, but only low weight gain is positively associated with low‐intermediate‐risk prostate cancer.

Association Between Alcohol Consumption and the Risk of Barrett's Esophagus: A Meta-Analysis of Observational Studies.

AbstractThe association between alcohol consumption and Barretts esophagus (BE) remained uncertain and controversial in the previous studies. We performed a meta-analysis of observational studies to clarify the association.We searched PubMed, Web of Science, and Embase for studies on alcohol consumption and risk of BE published before February 2015. A total of 20 studies reporting the association between alcohol consumption and the risk of BE were identified. Subgroup analyses, meta-regression analyses, sensitivity analyses, and publication bias tests were also performed. Several results from individual studies were pooled using a dose–response meta-analysis.A total of 20 studies involving 45,181 participants and 4432 patients of BE were included in the meta-analysis. No association was found between alcohol consumption and BE (relative risk [RR] = 1.10, 95% confidence interval [CI] 0.96–1.27, I2 = 48.60%) in our study. In subgroup analysis, alcohol consumption was associated with an increased risk of BE in men (RR = 1.35, 95% CI 1.13–1.61, I2 = 0.00%) and Asian population (RR = 1.60, 95% CI 1.03–2.49, I2 = 60.60%). In beverage-specific consumption analysis, liquor was associated with an increased risk of BE (RR = 1.16, 95% CI 1.02–1.32, I2 = 0.00%). Multivariate meta-regression analysis suggested that geographic area, and adjusted age, sex, body mass index, and smoke, might explain 70.75% of the heterogeneity between the studies. We also found the inverse association (RR = 0.84, 95% CI 0.72–0.98, I2 = 0.00%) between alcohol consumption and BE among subjects when compared with population controls.Overall, there was no significant association between alcohol consumption and BE. Alcohol consumption may be a risk factor of BE in men and Asian population, and liquor consumption may also increase the risk of BE. Significant inverse association was observed between alcohol consumption and BE, for comparisons with population controls.

Risk of treatment-related mortality with sorafenib in patients with cancer.

BACKGROUND Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. METHODS Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. RESULTS 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). CONCLUSIONS It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry

Objective Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. Methods A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. Results A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Conclusions Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task.

Blood glucose concentration and risk of liver cancer: systematic review and meta-analysis of prospective studies

The question of whether elevated blood glucose is a risk factor for liver cancer has been intensively studied, yet with inconsistent results. To explore the relationship between blood glucose concentration and risk of liver cancer, we conduct a meta-analysis of prospective studies. Literature search was comprehensively performed using database of PubMed, EMBASE and the Cochrane Library through October 2016. Random-effect models were used to combine the effect estimations. Eight articles containing ten studies with a total of 1975 liver cancer cases were included. The pooled RRs demonstrated that elevated fasting blood glucose was associated with increased risk of liver cancer (combined RRs: 1.77; 95% CI: 1.46, 2.13) with mild heterogeneity (I2 = 30.40%, P = 0.17). In sensitivity analysis, the pooled result remained significant (combined RRs: 1.33; 95% CI: 1.12, 1.59; I2 = 33.90%, P = 0.16) when we restricted blood glucose categories in the range of nondiabetic subjects. We also detected a J-shaped non-linear dose-response relationship between blood glucose concentration and risk of liver cancer. There is evidence that elevated blood glucose increases risk of liver cancer across the range of prediabetes and diabetes. Considering the rapidly increasing prevalence of prediabetes and diabetes, controlling blood glucose may lower the risk of liver cancer.

Effect and safety of dual anti-human epidermal growth factor receptor 2 therapy compared to monotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer: a systematic review

BackgroundDual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients. We undertook a systematic review to compare treatment outcomes for patients who received single or combined anti-HER2 therapies.MethodsWe identified randomized control trials that compared dual anti-HER2 therapy and anti-HER2 monotherapy in patients with HER2-positive breast cancer. Outcomes included pathologic complete response (pCR), overall survival (OS), progression-free survival (PFS), and adverse events. Included in the analysis were seven trials that recruited 2,609 patients.ResultsIn the neoadjuvant setting, the pooled pCR rate in the dual anti-HER2 therapy and monotherapy groups in combination with chemotherapy was 54.8% and 36%, respectively. This difference was statistically significant (relative risk, 1.56; 95% confidence interval (CI), 1.23–1.97; p < 0.001). In the metastatic setting, dual anti-HER2 therapy demonstrated significant benefits in both PFS (hazard ratio (HR), 0.71; 95% CI, 0.62–0.81; p < 0.001) and OS (HR, 0.68; 95% CI, 0.57–0.82; p < 0.001). Subgroup analyses indicated that the addition of chemotherapy to dual anti-HER2 therapy could greatly improve pCR in the neoadjuvant settings. However, in the metastatic setting, similar PFS and OS were found in patients receiving dual anti-HER2 therapy with or without chemotherapy. Dual anti-HER2 therapy was associated with more frequent adverse events than monotherapy, but no statistical differences were observed in cardiac toxicity.ConclusionsThis systematic review provides a summary of all the data currently available, and confirms the benefits and risks of dual anti-HER2 therapy for HER2-positive breast cancer.