Effects of Coffee Consumption on Insulin Resistance and Sensitivity: A Meta-Analysis

Coffee is widely consumed worldwide and impacts glucose metabolism. After a previous meta-analysis that evaluated the effects of coffee consumption on insulin resistance and sensitivity, additional randomized controlled trials (RCTs) were conducted. This meta-analysis aimed to evaluate the effects of coffee consumption on insulin resistance or sensitivity. We selected RCTs that evaluated the effects of coffee consumption for seven days or more on insulin sensitivity or resistance using surrogate indices (homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda index). The fixed-effects or random-effects model was used according to heterogeneity. Four studies with 268 participants were analyzed in this meta-analysis. Coffee consumption significantly decreased HOMA-IR compared to control (mean difference (MD) = −0.13; 95% CI = −0.24–−0.03; p-value = 0.01). However, the significance was not maintained in the sensitivity analysis (MD = −0.04; 95% CI = −0.18–0.10; p-value = 0.55) after excluding data from the healthy, young, normal-weight group. Matsuda index was not significantly different between coffee and control groups (standardized mean difference (SMD) = −0.33; 95% CI = −0.70–0.03; p-value = 0.08). In conclusion, long-term coffee consumption has a nonsignificant effect on insulin resistance and sensitivity. More studies evaluating the effects of coffee consumption in the healthy, young, and normal-weight individuals are needed.

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Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis

Journal of International Medical Research ◽

10.1177/03000605211031758 ◽

2021 ◽

Vol 49 (7) ◽

pp. 030006052110317

Author(s):

Chenyun Miao ◽

Qingge Guo ◽

Xiaojie Fang ◽

Yun Chen ◽

Ying Zhao ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Confidence Interval ◽

Polycystic Ovary ◽

Serum Insulin ◽

Meta Analysis ◽

Mean Difference ◽

Model Assessment ◽

Ovary Syndrome ◽

Synbiotic Supplementation

Objective This meta-analysis evaluated the effect of probiotics and synbiotics on insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods A systematic search was performed to identify all relevant publications listed on the electronic databases (PubMed®, Web of Science, Embase® and China National Knowledge Infrastructure) between inception and 30 October 2020. All statistical analyses were performed on randomized controlled trials (RCTs) using RevMan version 5.3 software provided by the Cochrane Collaboration. Results A total of 486 patients from seven RCTs were included in the meta-analysis. Probiotic and synbiotic supplementation appeared to improve levels of homeostatic model assessment of insulin resistance (mean difference = –0.37; 95% confidence interval –0.69, –0.05) and serum insulin (standardized mean difference = –0.66; 95% confidence interval –1.19, –0.12). The results failed to show any influence of probiotic and synbiotic supplementation on body mass index, waist circumference, hip circumference and fasting blood sugar. Conclusions Probiotics and synbiotics appear to have a partially beneficial effect on indices of insulin resistance in patients with PCOS.

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The effect comparisons of different exercise interventions on blood glucose and insulin resistance relative indicators for prediabetes: a network meta-analysis

10.21203/rs.2.10396/v1 ◽

2019 ◽

Author(s):

Lijun Tang ◽

Yingjie Fang ◽

Jianchun Yin

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Glycaemic Control ◽

Fixed Effects ◽

Meta Analysis ◽

Fasting Blood Glucose ◽

The Body ◽

Model Assessment ◽

Curative Effect ◽

Exercise Interventions

Abstract Background: In order to recommend the optimum type of exercise for type 2 diabetes prevention, the effect of different exercise interventions on glycaemic control and insulin resistance relative indicators were compared. Methods: The studies involving the curative effect of aerobic exercise trailing (AET) or resistance trailing (RT) for prediabetes were searched with pre-established strategy . The Body Mass Index (BMI), fasting blood glucose (FBG), glycated haemoglobin (HbA1c), Insulin and homeostasis model assessment-insulin resistance index (HOMAIR) were used as outcomes indictors. Q statistic was calculated to evaluate the heterogeneity within studies. A fixed effects model was chosen for pooling data with p > 0.05, otherwise, a random effects model was chosen. The consistency test in this network meta-analysis was conducted by Node-splitting analysis. Results: A total of 12 eligible studies were included into this network meta-analysis. According to p score values, prediabetes individuals in AET group had better curative effect in BMI (p score = 0.7525), Insulin (p score = 0.6411) and HOMAIR (p score = 0.6411) value controls than in other groups, while the curative effect of RT on FBG (p score = 0.8465) and HbA1c (p score = 0.8550) values were optimum. The rank of P-scores for each indicator under above two effect models was basically consistent, indicating that our results of network meta-analysis were stable. Conclusions: AET might be a better intervene method for improving insulin resistance to prediabetes, while RT was more effective than AET, AET+RT or CT for glycaemic control in prediabetes.

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Effect of interventions based on educational technologies on the prevention of sexually transmitted infections in incarcerated women: protocol of a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-043373 ◽

2021 ◽

Vol 11 (4) ◽

pp. e043373

Author(s):

Isaiane da Silva Carvalho ◽

Ryanne Carolynne Marques Gomes Mendes ◽

Priscila de Oliveira Cabral Melo ◽

Caroline Ferraz Simões ◽

Luciana Pedrosa Leal ◽

...

Keyword(s):

Systematic Review ◽

Health Education ◽

Sexually Transmitted Infections ◽

Fixed Effects ◽

Meta Analysis ◽

Incarcerated Women ◽

Mean Difference ◽

World Health ◽

Educational Technologies ◽

Sexually Transmitted

IntroductionPrisons are places with high vulnerability and high risk for the development of sexually transmitted infections. World Health Agencies recommend establishing intervention measures, such as information and education, on the prevention of diseases. Thus, technologies as tools for health education have been used to reduce sexually transmitted infections. However, no systematic review has investigated the effectiveness of these interventions. Therefore, this review’s objective is to examine the effect of educational technologies used for preventing sexually transmitted infections in incarcerated women.Methods and analysisPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be strictly followed. The following electronic databases will be searched: Scopus; Cumulative Index of Nursing and Allied Health, Education Resources Information Center, Embase, PsycINFO, PubMed/Medline, Web of Science and Google Scholar. Randomised clinical trials of interventions that used educational technologies to prevent sexually transmitted infections in incarcerated women will be searched in the databases from the beginning of 2020 until December by two researchers independently. A narrative synthesis will be constructed for all included studies, and if there are sufficient data, a meta-analysis will be performed using the Review Manager software (V.5.3). Continuous results will be presented as the weighted mean difference or the standardised mean difference with 95% CIs. Under the heterogeneity of the included studies, a random-effects or fixed-effects model will be used. The studies’ heterogeneity will be assessed by the I2 method. The sensitivity analysis will be carried out to examine the magnitude of each study’s influence on the general results. A significance level of p≤0.05 will be adopted.Ethics and disclosureEthical approval is not required because no primary data will be collected. The results will be published in journals reviewed by peers.PROSPERO registration numberCRD42020163820.

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SAT0111 THE RELATIONSHIP BETWEEN THE ADMINISTRATION OF IL-6 INHIBITORS AND INSULIN RESISTANCE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6509 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 989.3-989

Author(s):

A. Jitaru ◽

C. Pomirleanu ◽

M. M. Leon-Constantin ◽

F. Mitu ◽

C. Ancuta

Keyword(s):

Rheumatoid Arthritis ◽

Insulin Resistance ◽

Insulin Sensitivity ◽

Beneficial Effect ◽

Disease Activity ◽

Interleukin 6 ◽

Normal Weight ◽

Diabetic Patients ◽

Model Assessment ◽

Inflammatory Status

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly

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Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study

Cadernos de Saúde Pública ◽

10.1590/0102-311x00072120 ◽

2020 ◽

Vol 36 (8) ◽

Author(s):

Maria de Fátima Haueisen Sander Diniz ◽

Alline Maria Rezende Beleigoli ◽

Maria Inês Schmidt ◽

Bruce B. Duncan ◽

Antônio Luiz P. Ribeiro ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Normal Weight ◽

Overweight And Obesity ◽

Model Assessment ◽

Adult Health ◽

Homeostasis Model Assessment ◽

The Metabolic Syndrome ◽

Brazilian Cohort ◽

Overweight Or Obesity

Abstract: Homeostasis model assessment of insulin resistance (HOMA-IR) is a method to measure insulin resistance. HOMA-IR cut-offs for identifying metabolic syndrome might vary across populations and body mass index (BMI) levels. We aimed to investigate HOMA-insulin resistance cut-offs that best discriminate individuals with insulin resistance and with metabolic syndrome for each BMI category in a large sample of adults without diabetes in the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among the 12,313 participants with mean age of 51.2 (SD 8.9) years, the prevalence of metabolic syndrome was 34.6%, and 60.1% had overweight or obesity. The prevalence of metabolic syndrome among normal weight, overweight and obesity categories were, respectively, 13%, 43.2% and 60.7%. The point of maximum combined sensitivity and specificity of HOMA-IR to discriminate the metabolic syndrome was 2.35 in the whole sample, with increasing values at higher BMI categories. This investigation contributes to better understanding HOMA-IR values associated with insulin resistance and metabolic syndrome in a large Brazilian adult sample, and that use of cut-off points according to ROC curve may be the better strategy. It also suggests that different values might be appropriate across BMI categories.

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Serum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women

Journal of the Endocrine Society ◽

10.1210/jendso/bvab158 ◽

2021 ◽

Author(s):

Daniel A Dumesic ◽

Ayli Tulberg ◽

Megan McNamara ◽

Tristan R Grogan ◽

David H Abbott ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Elevated Serum ◽

Normal Weight ◽

Model Assessment ◽

Metabolic Function ◽

Ovary Syndrome ◽

Intravenous Glucose

Abstract Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective To examine whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women. Design Prospective cohort study. Setting Academic center. Patients Nineteen normal-weight PCOS women; 21 age- and body mass index-matched controls. Intervention(s) Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy. Main Outcome Measure(s) Serum T/A4 ratios, hormone/metabolic measures and AKR1C3 expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si). Results Increased serum T/A4 ratios (P=0.040) and log adipose-IR values (P=0.002) in PCOS women versus controls were accompanied by AKR1C3 mRNA overexpression of PCOS adipocytes matured in vitro (P=0.016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TG: R=-0.65, P=0.002) and the TG index (R=-0.57, P=0.011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R=-0.57, P=0.013) and TG index (R=-0.50, P=0.036), respectively, without significant relationships with other metabolic measures. Conclusion An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.

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PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

BMC Endocrine Disorders ◽

10.1186/s12902-019-0486-9 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Jiayu Huang ◽

Lin Liu ◽

Chunyan Chen ◽

Ying Gao

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary ◽

Predictive Biomarker ◽

Normal Weight ◽

Inflammatory Factors ◽

Low Grade ◽

Model Assessment ◽

Increased Risk ◽

Homeostatic Model Assessment ◽

Low Grade Inflammation

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR. Methods A total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed. Results First, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS. Conclusions Elevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

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Insulin resistance and lung function in obese asthmatic pre-pubertal children

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0182 ◽

2018 ◽

Vol 31 (1) ◽

pp. 45-51 ◽

Cited By ~ 4

Author(s):

Paola Di Filippo ◽

Alessandra Scaparrotta ◽

Daniele Rapino ◽

Tommaso de Giorgis ◽

Marianna Immacolata Petrosino ◽

...

Keyword(s):

Insulin Resistance ◽

Lung Function ◽

Statistical Significance ◽

Serum Levels ◽

Forced Expiratory Volume ◽

Normal Weight ◽

Model Assessment ◽

Obese Children ◽

Asthmatic Children ◽

Insulin Resistant

AbstractBackground:Recent findings have supposed that the underlying association between the increased prevalence of both asthma and obesity may be insulin resistance (IR).Methods:Insulin and glucose serum levels were analyzed to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) for IR in 98 pre-pubertal children. Lung function and allergy status evaluation were performed. The study population was divided into four groups: (1) obese asthmatic children (ObA); (2) normal-weight asthmatic children (NwA); (3) normal-weight non-asthmatic children (Nw) and (4) obese non-asthmatic children (Ob).Results:Forced expiratory volume in 1 s (FEV1) was slightly lower in obese subjects compared with normal-weight subjects and forced vital capacity (FVC) appeared lower in asthmatics, whereas between non-asthmatics subjects, it was lower in the obese group than in the normal-weight one. The post hoc analysis revealed a statistically significant reduction in FEV1, peak expiratory flow (PEF), forced expiratory flows (FEF) between 50% and 25% of the FVC (FEF50and FEF25) between ObA and Nw and in FEV1, FVC, PEF, FEF50and FEF25between NwA and Nw, but no statistically significant differences of lung function parameters were observed between ObA and NwA. We found an inverse relationship between HOMA-IR and all spirometric parameters, although without any statistical significance. We also observed a significantly lower FVC in insulin-resistant children (HOMA-IR>95th percentile) (p=0.03).Conclusions:This study suggests that lung function could be early altered in obese children, already in pre-pubertal age. Although IR should not manifest its effects on lungs in pre-pubertal obese children, the prevention or treatment of obesity in the pre-pubertal period may prevent definitive negative effects on lungs.

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The Relationship between Circulating Acetate and Human Insulin Resistance before and after Weight Loss in the DiOGenes Study

Nutrients ◽

10.3390/nu12020339 ◽

2020 ◽

Vol 12 (2) ◽

pp. 339

Author(s):

Manuel A. González Hernández ◽

Emanuel E. Canfora ◽

Kenneth Pasmans ◽

A. Astrup ◽

W. H. M. Saris ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Insulin Sensitivity ◽

Positive Association ◽

Fat Free Mass ◽

Model Assessment ◽

Random Factor ◽

Before And After ◽

Homeostatic Model Assessment ◽

Matsuda Index

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index >27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (stdβ 0.130, p = 0.033) in women, but not in men (stdβ −0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

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Hand–foot skin reaction, an anticipated dermatologic toxicity to pazopanib, with an unexpected low incidence: A systematic review of literature and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.365 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 365-365 ◽

Cited By ~ 2

Author(s):

Y. Balagula ◽

S. Wu ◽

X. Su ◽

M. E. Lacouture

Keyword(s):

Clinical Trials ◽

Tyrosine Kinases ◽

Fixed Effects ◽

Meta Analysis ◽

Statistical Significance ◽

P Value ◽

High Grade ◽

Multikinase Inhibitor ◽

Systematic Analysis ◽

Dermatologic Toxicity

365 Background: Pazopanib is a novel multikinase inhibitor that has been approved for the treatment of advanced renal cell carcinoma (RCC). It shares a similar spectrum of target receptors with sorafenib and sunitinib, including VEGFR, PDGFR, and c-kit tyrosine kinases. We have performed a systematic analysis to investigate the risk of HFSR to pazopanib. Exploring the differences in the incidence of HFSR between sorafenib, sunitinib, and pazopanib may offer additional insights into underlying mechanisms of this toxicity. Methods: Relevant studies were identified from PubMed (1998-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. Eligible studies were limited to prospective phase II-III clinical trials in which cancer patients were treated with pazopanib 800 mg orally once daily. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 942 patients from 10 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 4.5% (95% CI: 2.5-7.9%) and 1.5% (95% CI: 0.7-3.1 %), respectively. The relative risks of all-grade and high-grade HFSR to pazopanib monotherapy in comparison with controls were increased, reaching statistical significance for all-grade (RR=6.05, 95% CI: 1.11-33.12, p=0.038), but not for high-grade (RR=2.51, 95% CI: 0.12-51.9, p=0.55). The incidence of all-grade HFSR was significantly higher in patients with RCC as compared to patients with non-RCC malignancies (7.8% vs. 2.4%, p value=0.015). Conclusions: Despite sharing the same spectrum of target receptors with sorafenib and sunitinib, pazopanib is associated with an unexpectedly low risk of HFSR. Further investigations are needed to elucidate HFSR pathogenesis. [Table: see text]

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